You are on page 1of 34

For the week of April 26, 2004

BioCentury 100 Indicators
Week ended 4/23/04
PRICES VOLUME

TM

VOLUME 12, NUMBER 19

BioCentury
THE BERNSTEIN REPORT

1649.29 up 4%

540.9M shrs up 37% P AGE A1 OF 20

ON

B IOBUSINESS

Regulation

Tag team wrestling
BioCentury This Week
Cover Story
As SEC intensifies its scrutiny of biotech with the help of FDA, there is widespread agreement that companies need to rethink old assumptions that the two agencies can be handled independently. development in response to investor deBy Kathryn Calkins mand. That, in turn, is prompting more & Steve Usdin questions, according to Jeffrey Riedler, diSenior Writers Increased collaboration between FDA rector of SEC’s corporate finance division, and SEC, fallout from the ImClone Systems who described the agency’s activity at a Inc. case, and investor demands for more recent meeting of the Food and Drug Law Institute in Washington. information about Elizabeth Gray, a early-stage drug develpartner at Foley & opment, are contrib‘The assumption Lardner LLP in Washuting to an intensificaington and a former tion of SEC’s scrutiny of secrecy at FDA assistant director at of public disclosures by SEC’s division of enb i o p h a r m a c e u t i c a l has been dashed forcement, told BioCencompanies. Biotech explicitly.’ tury that initiatives like companies are receiv— Alan Goldberg of the FDA-SEC MOU ofing more queries from Goulston & Storrs ten result from several SEC, and the questions forces that together creare far more technical, ate the need for faster, according to attorneys who specialize in handling securities is- more informed enforcement. “Complexity in the filings could have been a trigger, and sues for biotech companies. The vigilance includes a more rigorous it could have been one reason for the scrutiny for consistency of statements made FDA-SEC agreement,” she said Some securities lawyers suggest there to both FDA and the public, as well as the use of trading suspensions in a handful of are other reasons for SEC’s increased cases related to allegations of misleading surveillance. John Kamp, an attorney at Wiley Rein & Fielding LLP in Washington, disclosures. As a result, corporate attorneys are told the FDLI meeting that biotech and warning that it’s no longer possible to deal pharma companies are experiencing the fallout from corporate scandals. He sugwith each regulatory agency separately. In February, the agencies exchanged gested SEC is trying to demonstrate that it memos formalizing a route for FDA offi- is aggressively regulating the biotech seccials to report suspected false and mis- tor in response to the media storm created leading statements from companies to SEC, by the trials of former IMCL CEO Samuel and streamlining SEC access to non-pub- Waksal and especially Martha Stewart. Both Gray and Terri Garland, a seculic information from FDA. But while the increased scrutiny might appear to be the rities litigator and partner at Morrison & direct result of the MOU, senior officials at Foerster LLP in San Francisco, also pointed both agencies say that’s just coincidence to the IMCL scandal in 2001-2002 as a probable touchstone for SEC’s apparent (see “ABCs of the FDA-SEC MOU,” A4). In part, what appears to be happening is interest in biotech. That scandal, Garland that companies are proactively disclosing noted, was rooted in FDA-sponsor comSee next page more information about early-stage drug

Strategy
BioMarin’s head start/Page A6 ID BioMedical heading south/Page A7

Product Development
Alteon: More or less/Page A8 Anadys: Five is not a crowd/Page A9

Technology Briefing
Mass Listeria/Page A10

Emerging Company Profile
Cancer trifecta: Hudson; Cougar & Gloucester/Page A11

Washington
CMS rationing wars/Page A13 Patents vs. research/Page A14

Ebb & Flow
MEDI’s R&D; IPO queue; earnings week; EPO sales, et al./Page A15 Online this week/Page A10 Stock charts & tables/Page A20 Company index/Page A9

BioEquity Europe Update
Europe’s clinical bellwethers. Please see announcement following A20.

BioCentury,
Regulation, from previous page

THE BERNSTEIN REPORT

ON

BIOBUSINESS

APRIL 26, 2004

P AGE A2 OF 20

clinical trial, for example, “the investing public should know whether or not there ‘FDA and the sponsor has been statistical analysis done and the munications. Gray said that the prosecu- might be more guarded, results” of the analysis, Reidler said. “We tion history in that case probably revealed would like the company to disclose what a need for better coordination between and the interchange the trial is designed to show,” he added. FDA and SEC. It also may have sharpened might be less productive “Another area of concern is how comSEC’s awareness of the inherent complexpanies describe their role in the drug develif meetings were ity of biotech filings. opment process,” Reidler noted. “We would Garland also noted that the sector like companies to be clear and transparent recorded.’ enjoyed a huge increase in investment about their role. For example, if a company about three years ago, which is resulting — Frank Sasinowski primarily licenses intellectual property, we in projects now coming to fruition in the of Hyman, Phelps would like it to say not that it has filed an industry. Investor complaints to SEC probIND with the FDA, but that its collaborator ably have increased as investment has has filed an IND.” grown, which she said also can focus the commission’s attention. Reidler also cautioned companies about the way they charWhile there is some disagreement about SEC’s motivation, acterize clinical trials. SEC might question whether a company is there is widespread agreement that companies need to rethink stretching the truth when it says a trial is Phase I/II, he said. Such old assumptions that interactions with SEC and FDA can be questions would go to the FDA. handled independently. Securities filings and press releases must The bottom line is that companies must be consistent in their be crafted with the expectation that FDA officials with access to communications with FDA, SEC and the public, said John INDs and NDAs may review the documents for accuracy, Manthei, a partner at Latham & Watkins LLP in Washington. “If, according to senior SEC officials. And FDA filings, as well as in all the communications to FDA, investigators describe a trial public statements about the interactions with the agency, may be as Phase I, even if it has some efficacy endpoints, don’t turn the subject of discussion between FDA and SEC, according to around and call it a Phase I/II trial” in a press release, Manthei attorneys at both agencies. advised the FDLI audience.

More, and more detailed, questions
The MOU notwithstanding, SEC has a longstanding policy of routinely querying FDA about statements in securities filings on topics such as the status of a company’s NDA, and when it has concerns about press releases or other public statements. “FDA has provided technical support for SEC enforcement of federal securities law for years,” Coleen Klasmeier, special assistant to the FDA Chief Counsel, said at the FDLI meeting. “Typically we assess the accuracy of statements in registration and other securities filings with regard to the status of FDA’s review of a product or other issues within our purview.” SEC’s Riedler agreed. “The SEC and FDA have been talking to each other and sharing information for many, many years,” he noted. “This agreement is merely a refinement, a modernization of the procedures that we engage in, in order to share information. We hope it will make the process a lot more efficient.” Riedler added that the number of such queries has increased in recent months as companies have included more data about FDA-related topics in prospectuses and other documents. Indeed, companies’ apparent efforts to be proactive on this score seem to have backfired. Instead of decreasing regulatory scrutiny, Riedler said, the trend to increasingly detailed disclosures has led SEC to question whether drug companies are providing sufficient context to allow investors to make informed decisions. “We have concerns with regard to several areas of disclosure that drug companies make. We have noticed of late that drug companies are making more disclosures about the drug development process, particularly the preliminary results of drug trials,” he said. “There certainly is no requirement under federal securities law that companies disclose preliminary results of drug trials, but if they choose to make those disclosures, we feel they should be in the proper context so investors don’t make erroneous conclusions.” If a company chooses to disclose interim results from a

A different take
While government attorneys are downplaying the scope and novelty of the SEC-FDA MOU, several attorneys told BioCentury that they do see more coordination between FDA and SEC, saying that they have seen increasing numbers of questions from SEC on biotech filings, and that the questions betray specific knowledge about products and the drug approval process that only FDA possesses. They maintain that the playing field thus has changed perceptibly in recent months. “In the last four to five months, there has been a real up-tick in IPOs,” Manthei said. “The quality, the depth and amount of disclosures going into securities statements are much more than a few years ago.” At the same time, “comments from the SEC have been significantly better and much more specific, leading industry to wonder if they were formulated by someone at FDA.” SEC may be seeing a shift in complexity and detail of filings because the companies going public are more mature, and thus have more advanced products, than those that went public in the past, suggested Alan Mendelson, a partner at Latham & Watkins in Palo Alto. The companies that Mendelson has helped to file IPOs this year — Corgentech Inc. (South San Francisco, Calif.), Dynavax Technologies Corp. (DVAX, Berkeley, Calif.) and Renovis Inc. (RNVS, South San Francisco, Calif.) — have wanted to include detailed data from their clinical trials. To take a company public, “bankers say they want a Phase II or Phase III product and good data, so companies are laying that out,” he told BioCentury. The level of company maturity demanded by the market also shows the sophistication of investors now, Mendelson added. Corgentech’s CGT003 E2F Decoy is in Phase III testing to prevent peripheral bypass graft failure, DVAX’s AIC is in Phase II/III studies in allergy, and RNVS’s Ceravive is in Phase III trials
See next page

BioCentury,
Regulation, from previous page

THE BERNSTEIN REPORT

ON

BIOBUSINESS

APRIL 26, 2004

P AGE A3 OF 20

the FDA-sponsor discussion. “I imagine that this could lead to a less robust ex“It would be ill-advised change,” he said. “Part of the dialog in for stroke. meetings permits a work-through of opto disclose less.’ While questions from SEC are not tions. FDA and the sponsor might be more necessarily burdensome, lawyers say the — Laura Berezin of guarded, and the interchange might be increasing frequency of such consultaCooley Godward less productive if meetings were recorded.” tions makes it more challenging to meet However sponsors handle meetings and the agency’s requirement for explaining other interactions with FDA in the future, the risks of a biotech business to investors in plain English. All they will be aware that even if an SEC liaison isn’t in the room, this adds to the rising cost of completing public offerings. securities regulators may be made aware of the content of Laura Berezin, a partner at Cooley Godward LLP in Palo Alto, discussions and documents. “What you say now has to be noted that her primary concern is not with FDA reviewing analyzed in terms of both agencies. The assumption of secrecy clients’ disclosures — which she said the agency has done for at FDA has been dashed explicitly. What you say to FDA can some time — but with the change in the nature and extent of the travel to the SEC,” Alan Goldberg, a director at Goulston & comments she sees from SEC. Specifically, Berezin noted that Storrs in Washington, said at the FDLI meeting. disclosures in SEC filings are required to be complete and written in “plain English.” “Theoretically, these are not mutually exclusive,” Berezin Enforcement said. One should be able to disclose information completely to SEC enforcement actions against biotech companies have satisfy SEC while making the disclosure understable to the been on the rise since mid-2003, Garland said. She added, average investor. The reality, she noted, is different. however, that it is too early to judge whether this will translate According to Berezin, SEC staff has begun requiring extensive to a greater cost to biotechs in defending such actions. Garland disclaimer language about the preliminary nature of clinical and Gray also noted an increased interest in the sector by the results, potentially in response to comments from FDA. Berezin Private Plaintiffs’ Bar, attorneys who bring class action lawsuits. said while companies don’t have a problem stating that their Recent securities trading suspensions leveled at small cap results are preliminary, SEC has been asking for the same companies also signal a level of scrutiny by SEC that has not been disclosure information to be repeated every time clinical infor- seen before, Gray noted. In separate cases in April, SEC suspended mation is discussed, making language repetitive, cumbersome trading for 10 days in BioCurex Inc. (BOCX, Richmond, B.C.) and and awkward. Vaso Active Pharmaceuticals Inc. (VAPH, Danvers, Mass.). In both “In my view, that absolutely violates the principle of plain cases, SEC referred to statements of questionable accuracy made English,” Berezin said. Instead of clarity, “we’re getting more in relation to FDA approval of the companies’ products and/or boilerplate, which confuses the issue. It doesn’t help investors in relation to studies intended to demonstrate efficacy. understand the risks better.” BOCX develops cancer detection tests and tools. VAPH She suggested that FDA’s zeal for caution and lack of concern develops compounds targeted at the OTC market that are about plain English is producing documents not intended for a formulated with transdermal technology from VAPH’s parent Wall Street audience. company, BioChemics Inc. (Danvers, Mass.). SEC’s response to increased disclosure by biotech companies However, the two suspensions did not necessarily result from is not resulting in improved communication to investors, accord- information provided by FDA. ing to Berezin. “In my experience, the filings are not different in In the BOCX case, trading volume spiked to 25.8 million substance now, but there is a heightened concern among shares on April 5 from low background volumes. On the same companies about what to disclose,” she said. day, the price of BOCX stock increased more than 400%, to $2.38. On April 8, SEC temporarily suspended trading “because of questions regarding the accuracy of assertions by BioCurex FDA relations and by others, in press releases and emails to investors concernSome attorneys also worry that the situation will damage ing, among other things, (1) a study confirming the effectiveness relations between companies and FDA. of its primary product and (2) approval of its main product by To illustrate, Frank Sasinowski, a partner at Hyman, Phelps & the Food and Drug Administration.” McNamara PC in Washington, noted that an SEC liaison from In a press release, BOCX said it did not send and was not FDA’s chief counsel’s office sat in on a meeting he attended with a responsible for emails touting its stock. client. Both companies released statements saying they would coopAlthough Sasinowski said that SEC liaisons do not attend all erate with SEC to remedy misinformation. Indeed, on April 19, FDA-sponsor meetings, he now advises his clients to document BOCX released a statement “clarifying” that its Histo-Recaf carefully any discrepancies between their own meeting minutes cancer detection product has been classified by FDA as a Class and those drawn up separately by FDA. Standard procedure is I device exempt from the premarket notification process. “The for each party to write its own minutes of meetings. FDA has not ‘approved’ the Histo-Recaf product for the diagnoWhile Sasinowski previously had not worried about small sis of cancer,” the company said. differences, he now believes clients should send letters about BOCX’s stock has changed to the Pink Sheets and resumed them to the agency to create a written record of the differences. trading on Friday, when the stock closed at $1.27, down $0.65 Meetings are recorded on rare occasions, Sasinowski said, from the trading halt. but he does not advocate this approach to solving the problem On April 1, SEC announced suspension of trading in VAPH, of discrepancies in minutes, warning that recording could chill See next page

Gray said. nor should we. there has been only one referral from FDA since the MOU was exchanged in Regulation. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. Big pharma. SEC argued that the circumstances affected the larger program in a negative way. VAPH also ceased marketing its three OTC products. costs of public offerings generally have risen by one-third to one-half in the last three to five years. and does not need to raise money. 5). Training of SEC and FDA staff to better understand food and drug and securities law is another aspect of the MOU.” A10). The law. extending the process and making it more expensive. Those people. “We continue to have great respect for all of the statutory restrictions on the disclosure of non-public information. so companies should take care to ensure that they are accurate and consistent with information they have communicated to both agencies. which decides whether any report should be referred to the SEC.BioCentury. BPUR had not disclosed that FDA had not agreed to a portion of a proposed clinical trial for its lead product. contact FDA’s chief counsel’s office. according to spokesperson Matt Carter. but now they frequently wait through the third set of comments to assure themselves that no major changes will require them to reprint their documents. adding that one potential stumbling block for biotechs in terms of adequate disclosure is the big company partner. 2004 P AGE A4 OF 20 Tag Team Wrestling ABCs of the FDA-SEC MOU By Steve Usdin & Kathryn Calkins Senior Writers The FDA-SEC memorandum of understanding (MOU) primarily involves referrals from FDA of possible criminal misconduct. Mass. believes that companies will respond by putting less detail in their prospectuses to avoid detailed questioning from the agencies. Mendelson agreed.” VAPH’s stock was delisted from NASDAQ on April 8 at the company’s request. Feb. A few years ago. There has been no increase in criminal referrals since the memorandum was signed. Neither she nor Mendelson. does not like to disclose more information than is legally required. Cambridge.” Securities attorneys have differing views on whether the FDASEC relationship will clarify which communications with FDA that companies should consider material. “It would be illadvised to disclose less. Berezin said she thinks clients have heightened concerns about being second-guessed by FDA after the fact as a result of the inter-agency collaboration. companies would wait for a single set of SEC comments to come back before printing. In this case.” Berezin said. especially European and Asian partners.” As an example. but she does not expect companies to clam up. Press releases “appear to receive the most scrutiny from FDA and SEC. Her best advice to companies is that “any disclosure must be put into the context of your entire development program. . according to senior FDA officials. led to changes in the filing process. Jan. The MOU is an incremental step that is intended to remove some of the red tape that made FDA-SEC communications cumbersome. Klasmeier added that the MOU does not modify restrictions on the disclosure of proprietary information. Hemopure hemoglobin glutamer. (BPUR. such companies often are unsympathetic to the disclosure needs of their smaller partners. Gray cited a Wells Notice received recently by BioPure Corp. The cost While apparent shifts in SEC’s attention toward biotech have resulted in incremental increases in the time required to complete SEC filings — and thus the costs to companies employing securities lawyers — such increases are dwarfed by the impact of Sarbanes-Oxley. Therefore. according to officials at both agencies. special assistant to the FDA Chief Counsel. passed in 2002 to combat corporate and accounting fraud as a result of the Enron and Arthur Andersen scandals. BPUR said it has cooperated with SEC and is waiting for further information from the agency. 9). in turn. A Wells Notice alerts a company that an SEC team is going to recommend an enforcement action to the commission and allows the company time to develop a defense. Former SEC attorney Gray said she believes the SEC-FDA communications will change disclosures. FDA employees have been informed of the appropriate people within the agency to contact if they come upon statements of potential interest to SEC. adding that companies are waiting until later in the SEC comment process to print their prospectuses and go on the road. What’s material A core problem posed by all of these changes — or perceived changes — is the definition of what is “material. and is unrelated to routine inquiries from SEC about the truthfulness of corporate filings and press releases. however. as the health SEC. which included one for athlete’s foot and two for pain relief.) (see BioCentury. although last December the commission did release a document advising companies on how to improve the language in the Management’s Discussion and Analysis (MD&A) section of filings (see “Online Links. According to Mendelson. “We do not view ourselves. but it does not reflect a major change in policy.” she said. according to Coleen Klasmeier. Indeed.” she said. from previous page February (see BioCentury. A BLA for Hemopure is under review by FDA. “I am particularly looking forward to the mutual training our two See next page citing concerns related to “(1) FDA approval of certain key products and (2) the regulatory consequences of the future application of their primary product.” Manthei suggested. However. Although the trial was under a separate IND from the primary trial and was never initiated. Gray said. Berezin agreed. SEC regulations covering what is material have not changed.

increased training. No part of this publication may be copied. business. San Carlos CA 94070-1246 650-595-5333. Fax: 312-755-0658 Washington D. Fax: +44 (0)1865-311195 Corporate KAREN BERNSTEIN. more sharing of confidential information. BioCentury is pleased to acknowledge its conference partners and sponsors through promotional announcements in its publications and on its Web site. reader interest. Main Offices PO Box 1246. “No rogue reviewer can now go straight to SEC with a statement” because of this vetting procedure.C. business. reproduced. while FDA “will train us in what the FDA’s requirements are and the FDA’s examination process. Europe AIMEE R. Unsolicited manuscripts may not be acknowledged or returned. BEN AMIWERO. BioCentury does NOT sell advertising in any of its publications. completeness. retransmitted. Outside contributors are subject to editing for space and other factors. KEITH HAAN.” he said. Information Services.com Newsroom: pressreleases@biocentury. and other criteria established at BioCentury's sole discretion. “I can’t help but look at what they are doing and think that a year or two from now it will lead to a much greater level of activity by FDA in this area. nor should we. circulated.: 202-462-9582. Tag Team. ALL RIGHTS RESERVED. .com. and The Clear Route to ROI are trademarks of BIOCENTURY PUBLICATIONS INC. SYLVIA D'HAENENS ZIMMERLI/Marketing Manager. sold. He suggested sponsors may become more circumspect and formal in communicating with FDA as they try to create a paper trail that avoids potential legal liabilities. Fax: 650-595-5589 Website: www. tax or legal opinions cited in the publication.” On the other hand. CHARLEY LU/Editor. BIOCENTURY PUBLICATIONS INC. Europe KATHRYN CALKINS./Senior Editor. SEC will train FDA staff in terms of the SEC examination procedures and disclosure regulations. TRACY CORRAL/ Associate Production Managers Subscriber & Business Services TIM TULLOCH/Senior Director. the new relationship is damaging to company-FDA relations.D. the MOU’s creation of formal channels for FDA officials to refer potential violations of securities laws to the SEC is likely to protect companies. Subscriber Services. Phelps & McNamara PC in Washington. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. Outside contributions may be accepted based on timeliness. tax or legal advice. commercially exploited or used to create derivative works without the written consent of BioCentury. or timeliness of the information. from previous page BioCentury® THE BERNSTEIN REPORT ON BIOBUSINESS® BioCentury®. published. CEO & Publisher KRIS HALL/Administrative Assistant Editorial ERIC PIERCE/Senior Editor. WALTER YANG/ Staff Writers Information Services JULIA KULIKOVA/Director. The contents of this publication are not intended as investment. and the streamlining of communications under the new inter-agency initiative is likely to lead to greater coordination and involvement in the future. The Bernstein Report on BioBusiness®. SUSAN SCHAEFFER.biocentury. however. Germany: +49 (40)41-35-77-60.” said Jeffrey Riedler. disseminated. But Sasinowski believes that. CHRISTOPHER MAGGOS/Senior Writers STEVE EDELSON/News Editor. Fax: +49 (40)41-35-77-62 Oxford. JARROD KLEIN/ Marketing & Sales Associates. JOSEPHINE ASCIUTTO/Manager. UK: +44 (0)1865-512155. Conferences & Special Projects Business Administration BRENDA GEORG/Business Manager Privacy & Advertising BioCentury does NOT sell or rent its customer information or usage data to third parties. Ph.BioCentury. JULIANA BALESTRIERI. “You should be relieved by part of this. ROSY ROGERS/Senior Director. News STEVE USDIN/Senior Editor. and BioCentury is not responsible for any investment. broadcast.com Chicago: 312-755-0798. 2004 P AGE A5 OF 20 BIOCENTURY PUBLICATIONS INC . Ph.’ — Coleen Klasmeier of FDA BioCentury International Hamburg. so we can better understand it and understand drug companies. and that the two agencies may begin to collaborate more closely in the future.” he said. a partner at Latham & Watkins LLP in Washington. DINGWELL.. WILLIAM WEYENETH/ Manager./Chairman & Editor-in-Chief DAVID FLORES/President. Information Services JENNY NICHOLS/Production Manager. director of SEC’s corporate finance division. agencies will do. but such announcements do not constitute paid advertising. All contents Copyright © 2004.D. Fax: 202-667-2922 ‘We do not view ourselves. Information provided by this publication is gathered from sources that BioCentury believes are reliable. overall. Ph. SHAUN BROWN/News Editor.” he told an audience of biotech executives and attorneys attending a recent meeting in Palo Alto. Referrals will be vetted by FDA attorneys who are familiar with securities laws. CONRAD SEELYE/Manager. according to Frank Sasinowski. said John Manthei. The BioCentury 100. “The identification of inter-agency liaisons. Joint training and streamlined communications suggest that the MOU is only the starting point. MICHELLE ORTEGA/Subscriber Services Associate. Letters & Outside Contributors Letters to the Editor and inquiries about Guest Commentary may be submitted to biocentury@biocentury. as the health SEC. ePublishing. distributed. BioCentury does not guarantee the accuracy. Customer Service.D. MICHAEL FLANAGAN. a partner with FDA specialty firm Hyman. nor does BioCentury make any warranties of any kind regarding the information. Conferences & Special Projects. Washington LUDGER WESS.

” said VI) within the next 18 months.” Orapred is a liquid corticosteroid. Cambridge.000 of the 25. sales have been slow for BMRN’s first enzyme its non-pediatric products. which is expected to start clinical trials for severe PKU next year.) up to $175 million you can imagine the logistical and emotional effects.3 million. Phoenix. is going to cost $150.000 a year — therapy for burn deridement. Calif. two. Most are treated phenylketonuria (PKU). Ariz. three years before “If you buy a sales force with a to increase that number to about 19. “that gives us said that commercializing compounds 18 months to not only educate physifor genetic diseases. BMRN (Novato. Parents of children with the disease often first notice Phenoptin. has been best known for its focus on enzyme replacement therapies for genetic diseases. by the way. and. BMRN plans two. MPS-VI is caused by a deficiency of the N-acetylgalac. and pediatricians one. will refocus to become a pediatrics company and partner out And we can’t afford to do that.).S. but to get the field force comin children. For an extremely rare disease like the U.000 profitable. Price said product. requires “significant groundwork” prior to launch not only to educate physicians pletely comfortable with the drug. and a ‘If you don’t start going that acquiring Ascent now hedges some 73-person sales and marketing team. The deal provides BMRN with Genzyme (GENZ. Chairman and CEO Fredric Price — BioMarin’s Fredric Price October 2005.’ Assuming Aryplase is approved in sary. ability: immediate and growing reveIn addition to providing a foot in the nues from the sale of Ascent’s main door at pediatricians’ offices.launched.person sales force and 7 regional managers to market its toms. BMRN expects the typically are very rare. the logistical on how to identify and properly diagnose diseases that issues surrounding treatment. an oral form of the enzyme cofactor tetrahydrocloudy eyes.” said Price. Mass. The company also plans to file this year for regulatory awareness exists. At the end of 2003. or a slight sway in the back. GENZ provided 2004 sales guidance of $40-$44 million. although some younger patients receive bone nia lyase.000-30. Vibrilase is in Phase Ib trials. coarse facial features. then if there by the time it launches its Aryplase treat. in nearly nonexistent.” Indeed. “This can’t be rectified by an ad in one of the journals.S. three years before so it came as a surprise last week when the company said it launch. Price. The transformation is pegged to BMRN’s acquisition of replacement therapy. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26.BioCentury. BMRN will pay MRX (Phoenix.) hopes to eventually use the 66MPS-VI. he argued. timely diagnosis also can be hindered by vague symp. .000 to $200. Ariz. It results in a variety of neurological complications. Price said. the Ascent Pediatrics Inc. 2004 P AGE A6 OF 20 Strategy BioMarin’s head start You can’t just mention this once and think that there will be By Aimee Dingwell a common understanding. it is not the end of the world and it doesn’t cost you anything. in cash and stock over the next five years for Ascent (see B2). seizures and tremors. and parental knowledge is approval of a non-refrigerated version of the drug. but also to prepare for logistical issues drug to have net sales of about $42 million this year. and Phenylase phenylalanine ammosymptomatically. Aldurazyme laronidase to treat MPS-I.stumble when the drug is are delays.launch. by early 2006. which hopefully is not too far away. asthma drug Orapred.). “if you don’t start going to medical BioMarin Pharmaceutical Inc. particularly those cians. you are going to stumble when the drug is launched. “Explaining to parents that the treatment is a two to three tion and brain damage. geneticists and pediatricians one. for which diagnostics are readily available and public market. to file for approval in the fourth quarter.” Staff Writer Thus.100 patients in the western world. Corp (MRX. a quick-dissolve tablet formulation. physicians then must describe the treatment to ties of phenylalanine hydroxylase. including severe mental retardaparents. BMRN plans to out-license its Vibrilase topical enzyme geneticist’s office.000 III testing in MPS-VI and BMRN expects board-certified pediatricians in the U. hour infusion that will need to be administered in a medical and cognitive problems.Price said is more than 50% of the liquid oral prednisolone tions. Price said physicians spend little time learning about genetic disorders. the diseases. Unlike more common diseases such as bacterial infec. First quarter sales were two key elements that it sees as essential to reaching profit.$7. BMRN also plans to launch OraPred in markets outside tosamine 4-sulfate enzyme. PKU is a pediatric disease caused by insufficient quantiOnce diagnosis of a lysosomal storage disorder like MPSVI is made. marrow transplants. and to launch OraPred 2. Aryplase has completed Phase about 14. BMRN says the head start is neces. of the risk inherent in timing drug apThe sales force currently calls on to medical geneticists provals.2005. growing product. who have an active practice. which affects about 1. mental illness. business of Medicis Pharmaceutical even though the drug is sold by an experienced partner. which related to treatment administration and costs. biopterin that is in Phase I testing to treat mild to moderate Most patients are diagnosed by age five. you are going to ment for mucopolysaccharidosis VI (MPS.

But. The deal includes one marketed vaccine. Gaithersburg. the flu business itself was. Emeryville. IDB inherits an agreement worth an estimated C$60 million (US$44. one or more of its preclinical vaccine candidates.K. said Holler. which is an intranasal vaccine in nonpivotal Phase III testing.6 million) with Technology Partnerships Canada. SHP. B.S. according to IDB CEO Anthony Holler. “our main goal is to bring both Fluviral and FluInsure to market in the U. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26.S. ID Biomedical (TSE:IDB. Fluviral. . The company also will look to out-license.BioCentury. Madison. IDB would be the fourth entrant into the U. nonliving vaccine sold to the Canadian government.9 million. We previously had to purchase small amounts of antigen from a number of suppliers. ‘It’s the BioCentury’TM Authoritative. IDB also acquires three research and manufacturing facilities in the U. These will complement IDB’s FluInsure. France). which are in Phase II and III trials.” If successful.). (MEDI. flu vaccine market IDB’s bigger pipeline ID Biomedical’s acquisition of Shire’s vaccine business adds a marketed flu vaccine and a Phase I compound to IDB’s two clinical candidates. Vancouver.K. a subunit. The U. IDB plans to keep Canadian rights for all of its products. development and sustainability of life science ventures into 2005 and beyond. of which Holler said $70 million will be written off. SHPGY. Based in St. and its StreptAvax group A streptococcus vaccine.) and Wyeth (WYE. IDB expects to sell 7 million doses of Fluviral to the Canadian government this year. the fifth largest flu vaccine manufacturer. Strasbourg. Quebec. which is an intramuscular influenza prophylactic marketed in Canada. U. The company solved that problem last week — and positioned itself to enter the U. Chiron Corp. in 2001 contracted with the Canadian government to supply up to C$300 million (US$222. Foy.C. he said.S. SHP also will provide IDB with a $100 million loan facility. IDBE. and partners MedImmune Inc. and Canada. as well as some 400 employees. N. or possibly co-develop. which is in Phase I/II studies.) also gets 10 vaccine candidates that are in or near preclinical development (see “IDB’s Bigger Pipeline”). while the remainder will be repaid by a percentage of sales of Fluviral outside Canada and any products resulting from SHP’s preclinical pipeline.S. company also receives rights to acquire 5. has two vaccines in development but has lacked an adequate antigen supply. “it is important to note that while Shire’s vaccine business as a whole was not profitable. The leading perspective on the strategic issues essential to the formation. a government agency that promotes Canadian technology and will help offset some R&D expenses. as well as a streptococcal pneumonia vaccine that has finished Phase I testing.8 million) in flu vaccine over the next several years.). SHP’s vaccine business generated C$36 million (US$26. Europe and Asia.” Indeed. 2004 P AGE A7 OF 20 Strategy Coming to America By Michael Flanagan Staff Writer ID Biomedical Corp. Along with SHP’s vaccine unit. Having our own antigen supply means we don’t have to deal with a third party. plus another $30 million on the first anniversary of closing. Basingstoke.). of which C$30 million came from sales of Fluviral. by 2007. vaccine market — by announcing that it would buy the vaccine business of Shire Pharmaceuticals Group plc (LSE:SHP. Product Fluviral (intramuscular) FluInsure (intranasal) StreptAvax Pneumococcal vaccine NA NA NA NA NA Indication Influenza Influenza Group A streptococcus Streptococcus pneumoniae Allergy Plague RSV Group B streptococcus Neisseria meningitidis Status Mkt (Canada) Non-pivotal Ph III Ph II Ph I complete Preclin Preclin Preclin Preclin Preclin Originator SHP IDB IDB SHP IDB IDB IDB SHP SHP occupied by Aventis SA (AVE. (CHIR. most of whom are involved in manufacturing — a significant jump from IDB’s headcount of 150. SHP’s vaccine business posted a 2003 net operating loss of $21. Calif.7 milion) in 2003 sales. and to find partners for StreptAvax in North America. “the most important aspect of the deal is the flexibility the antigen supply allows us with our flu vaccines. providing us with the flexibility to negotiate our own marketing and distribution deals.” Now.4 million IDB shares worth another $60 million. Globally focused. SHP will receive $30 million in cash at closing.J. Md.

N.mass (p=0. Results are expected in change was about 4 mmHg.S. while high dose alagebrium could be efficacious for to the company’s two failed Phase IIb trials. which was done in patients with normal ejection primary endpoint of exercise tolerance were not reportable fractions. The company is now hypothesizing that the two patient Moch said. Data on the DIAMOND. and both missed the primary endpoint of an improve. 27. . trial in diastolic PEDESTAL is enrolling a different patient population than heart failure patients with normal ejection fractions. 210 mg of alagebrium twice daily showed signifiSenior Writer cance on the secondary endpoint of reduction in left ventricular Last year. Phase II trial in 20 endpoint.heart’s ability to pump is diminished. Editorial announcements emailed to the Editor-in-Chief and/or the Publisher may not receive immediate attention and potential stories will be delayed. “We saw a good p-value 2005. ALT also saw a trend toward improved Alagebrium is an oral thiazolium comleft ventricular diastolic filling in DIApound that breaks advanced glycation MOND. Moch said the company also wants to study of measurement (see BioCentury. patients with abnormal ejection fraction. Jan. VEGF and growth hormones. BioCentury. If you have two separate mechanisms of action.com. it could raise blood pressure in hypertension SILVER. 2004 P AGE A8 OF 20 Product Development Getting it right. each of which may be give a blood pressure drug. Usually it takes years. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. Doses tested were in the range of 35-210 mg per day (see month. for heart failure. because it allows the heart to pump more blood. the heart changes from populations need different dose levels because alagebrium may a cylindrical volume pump to a spherical pressure pump. To understand why. and the compound significantly endproduct (AGE) crosslinks. Conversely. Phase IIb SPECTRA trial in about 390 BioCentury. 2003). VEGF high doses of alagebrium may be what ease by altering cell signaling. news announcements and story inquiries should be submitted to our News Room at pressreleases@biocentury.S. March 15).” said President and CEO Kenneth Moch.01) (see harden tissues such as artery walls. stiffness by breaking glucose cross-links ALT (Ramsey. alagebrium reduces the At higher doses. it is necessary to go back Hence. more or less By Christopher Maggos However. Last dose. SAPPHIRE and heart failure. a hypertension patients with or without left ventricular hypertro.” failure. a U. where the phy (LVF). “What we saw in SAPPHIRE/SILVER was that the best result Patients will receive 10. But that was not a prospectively defined Last week. over the course of years patients can triggered at a different dose.J. which published showing that (MLHF) questionnaire (p=0. 2003). July 21.higher dose would be better in heart failure patients.) thinks a lower dose and decrease mass by reducing the signalcould work for hypertension while a higher dose may be effective ing that causes the heart muscle to bulk up.’s alagebrium (ALT-711) failed in sepa. “In DIAMOND we saw that alagebrium could rate Phase II trials in systolic hypertension and diastolic heart remodel the heart in a matter of months. ALT thinks alagebrium may be actthe Minnesota Living with Heart Failure ing to break glucose cross-links. DIAMOND was a 16-week. open-label U. 50 or 150 mg of alagebrium or placebo was actually at the lower dose of about 35 mg/day and that the for 12 weeks (see BioCentury. ment in systolic blood pressure of at least 5 mmHg at the highest More data should come in the next year and a half. mg twice daily (see B10). patients with a systolic blood pressure of at least 140 mmHg. At all dose ‘Data have been improved quality of life as measured by levels. Results are expected in the second half. Patients will receive 35 mg/day or 210 the American Society of Hypertension meeting in New York.’ mass seen in DIAMOND.04). alagebrium also may ALT hypothesizes that the down regube acting to alleviate some of the anatomic expression of cytokines lation of cytokines and growth factors by and functional manifestations of heart dis. April 7.” Moch said. Although ALT saw an effect in patients with normal because of variability attributed to both methods and execution ejection fraction.05. “As blood pressure increases.” new Phase II trials. 2003). ALT began the U. that was less than 0. Alteon Inc.S. ALT expects reduces the expression of cytokines such this would make the hypertrophied heart — Alteon’s Kenneth Moch a better pump because it would lessen as TGF beta.BioCentury.such as TGF beta.” patients with diastolic dysfunction in diastolic heart failure and More analyses of the low dose data will be released in May at impaired ejection fraction. All press releases. as well as to the Phase IIa DIAMOND trial. “Data have facilitated the reduction in left ventricle been published showing that alagebrium and growth hormones. ALT is testing that hypothesis in two get back to a cylindrical volume pump. Thus. ALT began PEDESTAL. a lower SAPPHIRE and SILVER both enrolled uncontrolled systolic dose would be desirable in hypertension patients.

In addition to Epivir lamivudine. Korea) has commercialization rights in China. B13 Anadys (ANDS) A9.) has restarted development of its entecavir. Interferon alpha also is indicated to treat HBV but does not directly inhibit viral replication.6 log for telbivudine.) and GlaxoSmithKline plc (LSE:GSK. Xanthopoulos estimated that there are 8-10 million cases of HBV in the territories licensed by ANDS. which leads to a trade-off in potency. 2. in combination with animal toxicology studies. Korea and Southeast Asia. 2004 P AGE A9 OF 20 Product Development In HBV. Calif. ANA380 reduced mean HBV DNA by 4. president and CEO of ANDS (San Diego.). a nucleoside analog also in Phase III. (GILD. he said it has demonstrated high potency.). that figure increases to 65%. AXCA) A10 Barbeau Pharma B5 Beckman Coulter (BEC) B4 Benitec (ASX:BLT) B8 Bertek A10. Although the company has not yet identified how ANA380 produces a different result. A18. The partners plan to develop the compound for chronic HBV infection as front-line therapy and salvage therapy for lamivudine-resistant patients. Lamivudine’s primary drawback is viral resistance. AAA) B5 Alteon (ALT) A8. (BMY. ANDS plans to start a Phase II trial of ANA380 in lamivudine-resistant HBV patients within the next six months. Although ANA380 and adefovir are in the same chemical class – both are nucleotide analogs – ANDS said ANA380 showed a 20-fold differential in indicators of nephrotoxicity in head-to-head in vitro studies. AZN) A10. B2 Anika (ANIK) B10 Antigenics (AGEN) A17. he said this compares to a reduction of 1. Citing data extracted from published sources. Mass. senior vice president of drug development. B6 BioChemics A3 BioCurex (BOCX) A3 Bioenvision (BIV) B8 BioGeneriX B5 Biogen Idec )BIIB) A13 BioInvent (SSE:BINV) B2 BioMarin (BMRN. But the dose must be kept low to avoid nephrotoxicity. B5 Axcan (TSE:AXP. Japan and the rest of the world.BioCentury. But Anadys Pharmaceuticals Inc. Idenix Pharmaceuticals Inc.” In humans. suggests that we’ll have a very high safety margin.” said Devron Averett. In a head-to-head Phase IIb trial in 104 patients. a nucleoside analog in Phase III testing. five is not a crowd By Susan Schaeffer Staff Writer With two polymerase inhibitors on the market and two more in Phase III trials. high toxicity and lack of activity against resistant strains. “Such a large difference in vitro. ANDS reckons ANA380 is about 12-18 months behind telbivudine in development. B10 Amgen (AMGN) A13. that is in Phase II trials. U. low toxicity and activity against lamivudine-resistant HBV strains in preclinical and early clinical studies. Foster City. after the first four weeks of treatment.9 log for entecavir. Under the deal. Basingstoke. B13 Antisoma (LSE:ASM) B2 Applied Biosystems (ABI) B6 Array (ARRY) B12 . the compound has shown no renal or other toxicity in animal models. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. LG Life Sciences (Seoul. In addition. the marketed HBV polymerase inhibitors include Hepsera adefovir dipivoxil. in about 25% of HBV patients treated with lamivudine. the virus develops resistance within one year. a polymerase inhibitor from LG Life Sciences Ltd. ANDS expects final data from the trial within the next couple of quarters. B2 AtheroGenics (AGIX) A16 Auxilium A15.). the company said interim results from a Phase IIa trial of ANA380 in 28 patients showed potency greater than lamivudine. According to Xanthopoulos.J.2 log for lamivudine. According to Kleanthis Xanthopoulos. ANDS last week exercised its option to co-develop ANA380 (LB80380). U. and 2. B2 See page A12 BioCentury Company Index April 26. SHPGY. Princeton. GSK. Averett said that an in vitro assessment of ANA380’s potency in lamivudine-resistant strains showed “about a two-fold difference in one direction for one mutation. adefovir and entecavir and comparable to telbivudine. within four years. Idenix said telbivudine has not been tested in lamivudine-resistant patients. According to Xanthopoulos. Calif. SWX:BMRN) A6. B12 Avant (AVAN) B2 Avecia B7 Aventis (AVE) A7. N. is betting that the shortcomings of all four leave room for it to work on a better mousetrap. (Cambridge. shortcomings of other polymerase inhibitors include low potency. London.9 log for adefovir. a nucleotide analog from Gilead Sciences Inc. 2004 Actlion (SWX:ATLN) A13 Adprotech B2 Advanced Biotherapy (ADVB) B9 Advanced Viral Research (ADVR) B7 Agencourt B7 Agrobiogen B11 Alexion (ALXN) B8 Alkermes (ALKS) A17.) is developing telbivudine. In addition. Of the up-and-comers. and a two-fold difference in the other direction for another mutation — what you see is very similar to adefovir. and ANDS has rights in North America. India. telbivudine demonstrated superior antiviral activity compared with lamivudine. a nucleoside analog from Shire Pharmaceuticals Group plc (LSE:SHP. Idenix said telbivudine has a favorable safety profile and that it is focusing on developing the compound as a first-line therapy because untreated patients represent the greater unmet medical need.1 log. B5. Adefovir has a very low resistance profile. and Bristol-Myers Squibb Co.K. Europe. Indeed. B9 Altana (FSE:ALT.K. A18. at single-digit percentages within the first year. the market for hepatitis B therapeutics is getting crowded. Ascent A6 Astex B2 AstraZeneca (LSE:AZN. 3.

Calif. vice president of R&D at CERS. CERS (Concord. you’d expect to get antigen presentation. Stephen Isaacs. Transparency Summary of actions taken at the April meeting of the EMEA’s Committee for Orphan Medicinal Products (COMP). added that Listeria is easy to manufacture and scale up. MEDI is responsible for clinical development. Thus. from AstraZeneca plc (LSE:AZN.” said Jim Young. manufacturing and commercialization. More recently. Although the deal was officially announced last week. Patents CPMP executive recommendations for improving transparency of information provided to patients. Md.’s Listeria technology. Young told BioCentury that a main reason MEDI opted for this technology is the broad immune stimulation elicited by Listeria.) said the data showed that the technology elicited Class I and II immune responses and stimulated cytokine production from the innate immune system. U.). “Following this. Orphan drugs of Financial Condition and Results of Operations (MD&A) sections of SEC filings (see Cover Story). As a vaccine delivery vehicle for its antigen. and will receive an upfront payment and development funding and is eligible for milestones and royalties. showing that the vaccine significantly improved survival times compared with control in a mouse model of lung cancer. over time. In March. (TSE:AXP. The company did not disclose a timeline for getting the vaccine into the clinic. Fla. AXCA).” said Michael Kinch. MEDI chose CERS’s Listeria technology. which uses strains of the bacteria that have been engineered to have reduced toxicity. CERS will participate in development. London. they presented data at the American Association for Cancer Research meeting in Orlando. the human immune system is able to.” MEDI said further research could include studies on the combination of EphA2 antibodies and vaccines. — PhotoBarr: EPAR for PhotoBarr porfimer sodium to treat high-grade dysplasia associated with Barrett’s esophagus. the company decided to add a complementary approach by developing EphA2 cancer vaccines. In addition. and set about looking for a platform with which to deliver the antigen.. Last week. and metastatic melanoma. It lives inside host cells and eventually is encapsulated into a vesicle where antigens are processed and presented for CD4 cells. which the partners hope will provide a broad immune response and straightforward manufacturing. from Axcan Pharma Inc. the company’s first order of business was to develop antibodies against the cancer target.” he said. “You don’t have any subsequent purification steps because the bacterium itself is the product.” Last year. prostate and colon cancer. — Paxil: Summary of the CPMP’s safety review of Paxil paroxetine to treat depression.com. director of biology. MEDI published in Cancer Research that 6 mg/kg of its anti-EphA2 antibodies inhibited tumor growth in mice. from Bertek Pharmaceuticals (Research Park Triangle.). the target is overexpressed in multiple cancers. 2004 P AGE A10 OF 20 Technology Briefing Mass Listeria When MedImmune Inc. and we’ve programmed the Listeria to stimulate CD8 cells. the companies have been working on the project for some time. noted that Listeria “is an intracellular bacterium. “Antibodies induce EphA2 internalization and degradation. “All you’re really doing is fermenting bacterium. including breast. from GlaxoSmithKline plc (LSE:GSK. Product documentation National Academy of Sciences report. AZN.K. EphA2 is a receptor tyrosine kinase that. president and CEO of CERS. SEC Guidance regarding the Management’s Discussion & Analysis ‘It’s the BioCentury’TM — Apokyn: FDA Talk Paper on the approval of injectable Apokyn apomorphine to treat immobility episodes in patents with Parkinson’s disease (PD).” David Cook. when overexpressed.BioCentury. — Steve Edelson Online links this week Links to the following documents reside online at BioCentury’s News Center at www. “EphA2 is an important oncogene. — Faslodex: EPAR for Faslodex fulvestrant to treat breast cancer in postmenopausal women. licensed rights to EphA2 from Purdue University in 2001.biocentury. It then enters the cytoplasm. “A Patent System for the 21st Century” (see A14). THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26.).” MEDI expects to start clinical trials of an EphA2 antibody next year. According to MEDI (Gaithersburg.C. GSK). having a vaccine would help you mop up. “It’s also been shown to correlate with poor patient outcomes. N. president of R&D at MEDI. . MEDI placed its bet with Cerus Corp. recognize molecular patterns and mount an innate immune response. promotes tumor growth and metastasis.

a favorable or improved therapeutic index. “That’s because it gets really pricey when you start to go into animals. Promising leads get grant funding. the research leading to the discovery of the company’s PT-523 compound took more than 24 years. The compound came with an $8 million grant from the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute. Specifically. Ahn expects to inlicense at least one additional cancer compound and to nearly double the company’s size from 8 to 15 employees. (South San Francisco. but we feel there are enough compounds. South San Francisco. Calif. The company plans to start clinical testing in brain cancer by year end. Beth Israel Deaconess Medical Center. In contrast. a halogenated nucleoside Cougar Biotechnology Inc. “The place where development in academia gets hung up is in whole animals. which thus far has taken its compounds from industry. nonpolyglutamatable analog of aminopterin. Hudson’s second compound. by the end of summer. In addition to having a different route of administration. a classical antifolate. Ahn expects the funds to last for at least two years. the company also raised $4. Calif. IpdR is an oral prodrug of intravenous IUdR.” See next page Hudson: It’s academic Hudson is looking to academia to fuel its engine with early-stage cancer compounds. “We are looking to find compounds that have some clinical experience. Cougar: Plenty to eat Cougar.7 million in a series A round. Hudson in-licensed PT-523 last February from the Dana Farber Cancer Institute at Harvard University. Technology: Small molecule anticancer compounds Disease focus: Cancer Founded: 2002 by Paramount Capital University collaborators: Yale University. Dana Farber Cancer Institute. believes there are enough clinical-stage compounds to keep everyone busy. But there is a natural attrition process conducted by the institution that picks the winners and losers.) have taken a more conventional approach. Mass. Los Angeles.” said Hudson CEO Mark Ahn. and Ahn expects the company to start Phase II testing in lung and possibly gastrointestinal cancer by year end or the first quarter of 2005. Calif. PT-523 is in Phase I testing in solid tumors.” he said. licensing their lead compounds from industry. “We believe that there is far more science going on outside companies than inside them. Massachusetts General Hospital. Technology: Testosterone synthesis inhibitor Disease focus: Cancer Clinical status: Phase I Founded: 2003 by Horizon BioMedical Ventures LLC and Alan Auerbach Corporate partners: BTG International plc University collaborators: NA Employees: NA Funds raised: $5 million Investors: Horizon BioMedical Ventures LLC CEO: Alan Auerbach Patents: NA .BioCentury. Also by year end.” Indeed. “Time and time again. According to Ahn.) is in-licensing early-stage compounds from academia. the compounds also should have an established target and/or known mechanism of action. In addition. Hudson Health Sciences Inc. Three newcos built on this model. (Los Angeles. all of which announced deals in the last few months.” said Cougar CEO Alan Auerbach. (Cambridge. clear IP status that ideally allows Hudson to have global rights. IpdR. was in-licensed from Yale University this February and came with a $4 million NCI grant.” Ahn noted that identifying preclinical and early-stage compounds in this way is difficult because fewer compounds have gone beyond early preclinical development. and it gets more competitive. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. Hudson Health Sciences Inc. The company said PT-523 has shown better selectivity for the target enzyme dihydrofolate reductase (DHFR) in vitro and has significantly better efficacy than methotrexate. Calif. Hudson is aiming to reverse-merge into a public shell and raise about $10-$12 million. Cougar Biotechnology Inc. PT-523 is a non-classical antifolate that is a water-soluble. Hudson believes the compound will side-step the gastrointestinal and myelotoxicities of IUdR. 2004 P AGE A11 OF 20 Emerging Company Profile A cancer trifecta By Keith Haan & Aimee Dingwell Staff Writers The spate of startups built on inlicensing begs the question of whether there are enough compounds to support the model and how each company will differentiate itself. have slightly different tacks on how they plan to make the model work in cancer. we come across programs in academia that would have gotten killed inside a company. At that time. and late preclinical or early clinical development status. Hudson believes the compound has potential in multiple cancer indications. “There are a lot of players looking for products in this space. third party research funding is one of about five criteria the company uses to evaluate potential in-licensing opportunities. Case Western Reserve University Corporate partnerships: NA Number of employees: 8 Funds raised: $5 million Investors: NA CEO: Mark Ahn Patents: NA analog belonging to a class of radiosensitizing pyrimidine analogs.) and Gloucester Pharmaceuticals Inc. which would include an equity investment by Rodman & Renshaw.

S. Ltd. B13 Centocor B6 Cerus (CERS) A10. from previous page . U.S. B7 Cougar A11 CuraGen (CRGN) B10 CV Therap (CVTX) B8 CytRx (CYTR) B3 Daiichi Pharma B4 Discovery Partners (DPII) B3 Dow (DOW) B3 Dragon (TSE:DDD. the biologically acAbiraterone is an oral inhibitor of Founded: 2003 by Jay Mohr. As an Mohr said he is likely to look to a Phase I or preclinical antifungal. A19. B9 Echelon B3 Edmond Pharma B5 Edwards Lifesciences (EW) B7 Elan (ELN) A19. and would likely Instead. pound would inhibit tumor survival/ “From what Fujisawa told us.” toconazole to treat prostate cancer based on its profile as a The company is looking to add one or two more compounds. the company is looking for small molecules that have require much smaller trials. April 19). there Employees: 15 by year end growth signaling through the androwere several companies interested in gen receptor.” an essential component of the fungal cell membrane. but did tional study. a depsipeptide histone deacety. London. hormone-refractory prostate cancer Last week. A16. relatively broad-spectrum steroid synthesis inhibitor. B7 Cognia B3 Conforma B7 Corgentech A2. Although Gloucester hasn’t disclosed how much money it Abiraterone has completed Phase I trials in 26 prostate has raised. Cougar initially will focus the com. the NCI is consive worldwide rights to develop and Technology: Histone deacetylase inhibitors ducting a Phase II trial in cutaneous T commercialize abiraterone acetate to cell lymphoma (CTCL) under a CRADA treat prostate cancer from BTG Inter. Gloucester plans to keep same target or MOA that has shown biologic activity. U.BioCentury. In addition. Cougar acquired exclu. that we could market the compound with a focused lase (HDAC) inhibitor from Fujisawa Pharmaceutical Co. Later this year. NMerc:CTIC) B10 CeNeS (LSE:CEN) A19. Mass. Gloucester acquired worldwide rights The indications we will be pursuing are small enough in the to develop and market FK228. B5. (see BioCentury. 2004 P AGE A12 OF 20 The compound is in Phase II trials for renal cell carcinoma (RCC) and Gloucester Pharmaceuticals Inc. which often requires Funds raised: NA licensing FK228. it plans to raise a new round that not provide a timeline for the start of Phase II trials.” a new mechanism of action and have shown biologic activity he said. B13 GlaxoSmithKline (LSE:GSK. “Our plan is to become an integrated company. from page A9 BioPure (BPUR) A4 Bioreason B7 Bioseek B3 Biotica B4 BioTrove B12 Boehringer B6 Boston Biomedica (BBII) B3.Cambridge.K. B10 Gilead (GILD) A9. rights. which is preclinical development with a significant pharm/tox package. (HRPC). blocking synthesis of ergosterol. the com. testosterone production. The company will seek a partner outside the U. A16. tive moiety of FK228 that is in preclinical the 17 alpha-hydroxylase/C17-20 lyase Martin Vogelbaum development. Part of Investors: Apple Tree Partners testosterone for activity. perhaps as few as 100 patients. A10.” Mohr said. and add to its clinical and regulatory capabilities. B4. “These are niche indications. what tilted the scale in Gloucester’s There is clinical proof of concept CEO: Jay Mohr favor was that it would be focused on the for the idea of inhibiting testosterone Patents: NA compound. or belong to a class of compounds sharing the Should FK288 reach the market. Earlier this month. Clinical status: Phase II rights to FR135313. Ltd. he said.Disease focus: Cancer with Fujisawa. commercial infrastructure. companies know that their comphysicians prescribe the antifungal kepound will get the attention it needs.determine which indication it wants to pursue in a registrapound as a second-line treatment for prostate cancer. Gloucester: MOA matters Mohr noted that Phase III trials in either RCC or CTCL Though an in-licensor. B7 Bristol-Myers (BMY) A9. According to Auerbach. By blocking cal Co.U. Gloucester also gained national plc (LSE:BGC. FK228 was put testosterone synthesis.” Mohr said.” said CEO Jay Mohr. “Because we are synthesis.S. will fund the registrational trial and enable it to in-license one or two compounds.). on their own. Mohr said it has enough to fund ongoing clinical cancer patients. colorectal. B3. on the block because Fujisawa (Tokyo. although the latter “would have to be late in alpha demethylase. Company Index. enzyme complex. many small. in which it showed the ability to suppress trials to the point where the company will be able to testosterone synthesis. Gloucester is “not looking at would require far fewer patients than cancers such as lung or reprofiling or rescuing old drugs. GSK) A9. B6 Bruker (BRKR) B12 BTG International (LSE:BGC) A12 Callisto (CLSP) B12 Carolina Pharma B7 Celgene (CELG) A13 Cell Signaling B3 Cell Therap (CTIC.don (FSE:CNW) B6. B3 Chiron (CHIR) A7 co. B3 Enzo (ENZ) B3 Enzon (ENZN) B2 ESP Pharma B5 Eyetech (EYET) A16 Fujisawa A12 Genelabs (GNLB) B4 Genencor (GCOR) B7 Genentech (DNA) A13 GeneProt B4 Genitope (GTOP) B7 Genta(GNTA) B5 Genzyme (GENZ) A6. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. which is involved in Corporate partners: Fujisawa PharmaceutiAccording to Mohr. Gregory Verdine. DRUG) B3 DSM B4 DxS B12 Dynavax (DVAX) A2 Dynogen B12 DynPort B2. B5 Gloucester A11 GTx (GTXI) B4 Harvard U B3 See page A19 Emerging Companies.University collaborators: NA Japan) was exiting the oncology space. ketoconazole is thought to inhibit P450 sterol C-14 compound.

THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. did note that an sNDA for At a meeting held to receive public MM is pending at FDA. (TEVA.” said Stephanie Simmons. “It doesn’t account for the cost of drugs and therefore however the parameters are defined. Calif. The bill’s authors “didn’t intend replacement under the project if the drug or biological it replaces is not to be a criteria. Simmons and other MS advocates said that funds should be A total of 40% of the $500 million will be reserved for cancer set aside to pay for three drugs: Rebif interferon beta-1a. ” s a i d K e v i n Brennan. They their advocates and caregivers made diametrically opposite contended that Celgene Corp. “Putting all patients in a single — The drug or biological must be of at least equal efficacy to selection pool would discriminate against orphan diseases. Madison. By Steve Usdin Washington Editor The decision to exclude off-label indications was attacked by Senior officials of the Centers for Medicare & Medicaid representatives of multiple myeloma (MM) patients. a staffer for Sen. The companies market Enbrel who believes they should be eligible. Moveover. 2004 P AGE A13 OF 20 Politics & Policy Zero sum game CMS’s criteria for selecting drugs. Germany). What we were trying to do is provide a benefit commonly provided incident to a physician’s services. SwitzerMedicare. program will address. president and COO of CELG (Warren. (DNA. a lobbyist for the Arthritis to launch a “Demonstration Project for Foundation. Mass. mandating it. reprewarned that the plan the agency is likely to people interested and sentatives of seniors suffering from comimplement bears little resemblance to the benefit Congress intended when lawmak. remainder should be reserved for treatments for these diseases. physicians Services got a full dose of rationing warfare last week.’s Thalomid thalidomide. N. and the 50. Pewin added that CMS’s focus on the word “replacement” Although last week’s meeting was supposed to focus on See next page criteria for beneficiary selection. and an aide to Sen. should be covered because it is the de demonstration project mandated by the new Medicare prescrip. by Genentech Inc. (BIIB Cambridge. as patients. arthritis (RA) and multiple sclerosis (MS) patients. which is demands for their fair share of a $500 million prescription drug not approved for MM.S. And based on last week’s meeting. Kay Bailey Hutchison (R-Texas). but CMS still is struggling to (AMGN. SRA.000-person etanercept for RA and other indications.eligible for this project mon diseases such as RA made a pitch based on numbers. Jerusalem. they need. and Copaxone glatiramer. however. Israel). advocates for patients with pulmonary arterial on April 14: — A drug or biological covered under the project must hypertension (PAH) have formed a coalition to lobby CMS to set eliminate the need for a drug or biological currently covered by aside $37 million of the Section 641 funds to pay for Tracleer bosentan from Actelion Ltd.J. As to beneficiary selection. marketed by CMS has not yet set limits on the types of other conditions the Teva Pharmaceutical Industries Ltd. They also reported that 57% of Medicare recipients with RA have incomes below $15. and solicited public comments on scope of coverage cancer group. Sol Barer. broadly for patient-administered drugs. is covered by Medicare. Geneva. marketed by Schering AG (FSE:SCH.Association. — Coverage of the drug or biological in the project is limited land). The fourth MS biologic.” he said. Berlin.). according to Bill Pewin. The 90-day Partners Wyeth (WYE. SHR. Coverage of Certain Prescription Drugs and Biologicals” within 90 days of enactment. deadline came and went in March.) also argued in favor of propordesign the program. participants also criticized .000 per year. strongly opposed proportional enrollment cap is not large enough to accommodate all of the potential participants. aides to two senators ‘There will be many more user fee deadline. with an October comments about how CMS should manage the program. Calif.’ apportioned based on prevalence in the Act (MMA) last November. South San Francisco. a spokesperson for the Pulmonary Hypertension — Use of the replacement drug or biological must repre.).BioCentury. drugs. Switzerland). Section 641 of the MMA instructs CMS — Stuart Guterman of CMS M e d i c a r e p o p u l a t i o n . but to the disappointment of advocates for rheumatoid marketed by Serono SA (SWX:SEO. Funds “should be ers passed the Medicare Modernization than we can include. to approved indications. elderly patients will not be won’t correct access barriers. which is marketed in the U. who felt the Betaseron interferon beta-1b. MS patient groups. Avonex interferon beta-1a from Biogen CMS announced five criteria for the demonstration program Idec Inc.stration program stem from CMS’s misinterpretation of the law cal. A few things are clear about the project: the $500 million is CMS to create enrollment criteria weighted toward low-income not nearly enough to cover drugs and biologics for everyone patients who lack drug coverage. N.) and Amgen Inc. allocation. It recently announced some tentative tional allocation according to disease prevalence within the nondecisions. Many of the concerns about implementation of the demonsent an advantage in terms of access and/or convenience for patients compared to the currently covered drug or biologi. Olympia — The drug or biological is not eligible for coverage Snowe (R-Maine). (SWX:ATLN.J. a quiet if they think they’re been excluded from receiving therapies representative of the National Multiple Sclerosis Society. and urged and criteria for selecting eligible patients.). Cara Ugolini. tion drug law.” said the covered drug it replaces. Allschwil. Thousand Oaks.facto standard of care.

” the report notes. people interested and eligible for this project than we can include. by “creating a procedure for third parties to challenge patents for a limited period after their issuance in an administrative proceeding before administrative patent judges of the USPTO. 2004 P AGE A14 OF 20 Washington Notebook Patents vs. “This is in part because the number of patents required for most R&D projects remains manageable and in part because the various players have improvised arrangePolitics & Policy. using substitute research tools.” said Stuart Guterman. The speed. especially on tools of precommercial laboratory research. To assess the validity of these concerns.BioCentury. the report suggested. “One of the most pervasive working solutions is infringement of patents. which will be some time this summer. assembling rights to a plethora of patents on basic technologies could constitute an insurmountable barrier. there is a widely held belief that private firms will not sue university investigators over patent infringement because there is little to be gained financially and a high risk of adverse publicity. CMS officials indicated that they will not reconsider the decision to limit the program to replacement products. and therefore are not eligible for an exemption from patents.” A Federal Circuit Court of Appeals ruling has shaken the confidence of academic researchers that they will be shielded from liability for patent infringement by law or custom. Many university and corporate respondents to the survey reported an even simpler expedient: patent infringement. “All other industrialized countries approach the non-obviousness of novel genes by focusing on the technical hurdle the inventors faced — cloning the gene. conducting 70 interviews with IP practitioners. For example. steps should be taken to ensure that overly broad biotech patents do not impede medical research. and clear exemptions from patents should be created for academic researchers. cost. CMS decided to limit the program to FDA-approved uses because establishing fair criteria for selecting off-label indications would delay starting the program. and the high costs associated with biotech patents could put academic researchers at a competitive disadvantage. the European Patent Office has “taken a strict stance on the obviousness of recent genomics invention. Tactics for overcoming IP barriers include “negotiating licenses and royalty payments. In the October 2002 Madey v. according to the NAS report. This could be accomplished. The NAS recommended that Congress consider narrow legislation creating “some level of protection for noncommercial uses of patented inventions.” the report says. and design details of this proceeding should make it an attractive alternative to litigation to determine patent validity and fair to all parties” (see Online Links. however.’ and in other cases on the assumption that patent holders will not sue over research uses.” The report also recommended that Congress consider enacting legislation intended to reduce the time and cost associated with IP litigation. according to a National Academy of Sciences report. With a few exceptions. Duke decision. Development and Information. these center on the following fears: broad patents on upstream discoveries “could impede follow-on research and development if access to the foundational intellectual property is restricted”.” the report notes. said CMS Chief Medical Officer Sean Tunis. The report also reviews concerns that biomedical biotech patent practice might be impeding medical and scientific progress. and locating research activity offshore. researchers and government officials. “A Patent System for the 21st Century. The project sunsets in 2006.” Thus EPO takes the position that a patent can be awarded to genomics inventions only if obtaining the sequence was a technical achievement or if some new or unexpected property associated with the gene has been discovered. has created a “quagmire” that inappropriately limits coverage. the study found that patent policies have not impeded research or drug development.” the report says. A10). research By Steve Usdin Washington Editor The bar for patenting gene sequences should be raised. according to Guterman. It is not clear. director of CMS’s Office of Research. Whatever criteria CMS adopts. according to the NAS. causing scientists and companies to avoid or abandon promising areas of R&D. the NAS commissioned a survey. circumventing patents by inventing around them. whether Madey has a direct bearing on biomedical research. Parameters of the program will be announced when it is launched. “In particular. from previous page ments or followed norms that mitigate the intellectual property complexities that exist. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. In particular. The NAS report. He also said that excluding off-label uses goes against the intent of Congress. “there will be many more BioCentury Extra: Online every business day. Federal courts have set a “low standard of nonobviousness” for patenting gene sequence-related inventions. when the new Medicare drug benefit is supposed to start. according to the report. . in some cases on the presumption that research is legally shielded from infringement liability by a ‘research exception.” also recommends the creation of an open review procedure that would make it easier for third parties to challenge patents. the appeals court ruled that universities are engaged in the business of scientific research.

noted Jim Young. Young said.150.” The good news is that MEDI’s higher R&D spend correlates MEDI was up $0. a IPOs YTD: $1102.” he noted.5 JNJ Procrit/ Eprex $3.7 million in the vaccine will rejuvenate its sales.9 billion in venture capital. THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. and Venrock (13. Vitaxin. 2004 P AGE A15 OF 20 Ebb & Flow Pipeline gardening By Steve Edelson stable formulation of FluMist. thus keeping EPS intact.6 $415.6%). Among other things.0M In the best of all possible worlds.6%). Two weeks ago. Principal stockholders include Perseus-Soros BioPharmaceutical Fund (22. generation antibody for RSV. Phase II Vitaxin data are expected this $3. as first quarter R&D spending MEDI plans to launch CAIV-T in 2007 and hopes that the increased 57% to $49. difference was in the R&D line. “We’ve used our venture president of R&D.9M up for planned increases in R&D spendstatic melanoma and metastatic prostate Total YTD: $7244. Totals include overallotments company’s first quarter net income grew complete additional analyses of its Phase III and warrants. through 2006. filing to raise up to $86. Sprout Capital (17. which use at about 20% of product sales. “In the front end.1%).8 million.9 million in cash. Schroder Ventures (10%).434. the year.41 to $23. and an anti-HPV vaccine that also In 2003 a total of $19. Lehman. “This year. Positive preliminary results $110 to $111 million. AMGN retorted that the price difference between Aranesp and competing drugs was “modest. and Biotech Growth (8. including didn’t happen. Much of the month (see BioCentury. MEDI’s antibody year for three compounds. and Thomas Weisel.6%). despite revenue from two Phase III trials were reported last growth of 13% from $431 million to $489 million. R&D spend isn’t huge.5 $2. MEDI decided to keep is in Phase II trials.0 $2.0 NA NA $4. When that cancer. 31.3 million in an IPO underwritten by Deutsche Bank. the company expects sales to grow in the low and could return to around 16%.0 NA NA $590.5 billion was raised. and Needham.269.0 $543. including CAIV-T.” friendly.3 billion in As a result of that decision. The company has one marketed product: Testim (AA2500) topical testosterone gel to treat hypogonadism. “the 2003 quarter. Principal stockholders include Arch Venture Partners (14.108.5 $41. spending up anyway. pipeline in part through more in-licensing.4% prior to the offering). and plans to continue that pace to prevent respiratory syncytial virus (RSV).” and noted that others also are discounting their EPO drugs.984. a nextTotal last week: $130.6%). Amgen (AMGN) and Johnson & Johnson (JNJ) fired shots related to their EPO drugs. Caduceus (9. the company plans to other fundraising.100 Nanotechnology company Nanosys filed to raise $115 million in an IPO underwritten by Merrill Lynch. MEDI filed INDs last growth in part reflects the maturity of Synagis.95 on the week.2 $2.7%). MedImmune expects to have four products in Phase III trials next year. See next page .430.6 $2.676. The company had $28.4 million in cash at Dec.5 million and ending the year with $38.260.600$5. Nanosys has about four years of cash. AMGN is still forecasting a solid sales trajectory. which is up from last year’s the money to fund the work they’re doing for us — it’s very P&L investment of 16%.0 $1.8 million from $31. $509 million in IPOs.8M enza vaccine would have more than made psoriasis.543. with pipeline visibility. CW Group (13. ($M) Product 2001 2002 2003 2004 1Q04 guidance AMGN Epogen Aranesp Total $2.100. Last week. Urology company Auxilium also threw its hat into the ring. At that time. Polaris (13. JNJ said “its competitor” was offering “aggressive” discounting of up to 40% off list. Last year.3M MedImmune’s FluMist intranasal influ(v)beta(3) that is in Phase II trials to treat Venture YTD: $2042. trend of higher R&D spending as a percent of sales will reverse” For 2004. the company is developing a nanowire-array molecular sensing system to detect analytes in real time using low voltage measurement technology. CIBC. metaOther YTD: $3011. a refrigerator- IPO watch EPO sales watch In their respective earnings calls last week.3M ing.6 million and revenues of $8. SCP Private Equity (22. Lehman Brothers (11. Money Raised in 2004 & Shaun Brown Three other compounds are slated for Senior Writers Phase III trials next year: Numax. Young said the company has been filling its early Given slowing revenue growth and rising R&D spending. double digits versus a 26% increase in 2002. rheumatoid arthritis (RA).4M revenues from the launch of humanized MAb against integrin alpha Follow-on YTD: $1087. Auxilium reported an operating loss of $29.7 $1. posting a 2003 operating loss of $9.0 $3. The slowing sales In addition to its late-stage products.BioCentury. March 8). the R&D will rise as a percent of total sales. we expect to see R&D investment capital arm to make equity investments in companies. Whether it’s discounting or old-fashioned competition that’s lowering EPO prices. and $11.978.7% prior to the offering). (Source: BioCentury Financial Center) only 1% quarter over quarter from CAIV-T data.8 billion in follow-ons.1%). Piper Jaffray.8 $3. Also this year. $3.0 $4.5%).

The other companies all added at least 3% on the day. allow IMCL and partner Bristol-Myers (BMY) to meet full commercial demand for colorectal cancer drug Erbitux cetuximab.0 $69.5 Lead program Ph III Ph II Original filing 2/6/04 1/27/04 Hoped for post-$ avg NDA submission ‘04 3/11/04 . On the week.90 to $47. from previous page THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. BB36 has FDA approval to manufacture Erbitux for investigational use. EYET gained $2.3 Up to $50 Up to $70 Up to $103. ONXX was up $3.41 to $23.3 Up to $92 Up to $51. ($M) Company Barrier Cytokinetics Not updated Acadia Alnylam Celldex CoTherix Critical Therapeutics Favrille Icagen Idenix Inhibitex Metabasis Momenta Threshold ViaCell Xenogen NA NA NA NA NA NA NA NA NA NA NA NA NA NA Up to $86.90 on the day and $2. and Swiss approval to manufacture commercial product.3 Up to $100 Up to $86. Nov. Onyx (ONXX) and OSI (OSIP) were mentioned. The company also said that it has established a national list price in Canada of C$16.S. 2003). AGIX had the smallest gain on Monday — a 1% increase — despite being the only company listed that holds full rights to its late-stage compound. where discounts to the list price may apply. OSIP led the way with a 10% pop.3 Up to $86. The PDUFA date for the sBLA is June 18.25 (US$12. ophthalmic company Eyetech (EYET) and cancer companies Millennium (MLNM). The increase to $725-$775 million from $700-$750 million reflects global demand. Branching out on Erbitux ImClone (IMCL) jumped $7. 40% of Viread’s $193. Ebb & Flow. (A) Assumes proposed shares (excluding overallotment) are sold at mean price.80 on the week.30 on 9. up $0.3 Up to $86. 2004 P AGE A16 OF 20 Barron’s bump Investors liked what they read in a Barron’s article last week that merely stated the obvious: pharma needs drugs and biotech companies have compounds available in late-stage development or on the market.21 to $35. with supplies produced at a Lonza Biologics facility. the queue has grown. as six companies have filed since the start of the second quarter.2 million.70. N. Approval would IPO queue update On the road Cancer play Pharmexa (CSE:PHARMX) was down DKK1.12. AGIX slipped $0.3 Up to $86.14.3 Up to $86. In the first quarter. The price is still under negotiation in certain provinces. The partners have met initial Erbitux demand in the U. Excluding the $809 million valuation garnered by Eyetech (EYET). Its AGI-1067 is in a Phase III trial for secondary prevention of coronary artery disease.44 to $24.J.1 million in sales came from outside the U. GILD said it would continue to provide the drug at no cost to patients enrolled in its Extended Access Program until the drug is on the formularies of all the provinces (see BioCentury. 10. Cardiovascular play AtheroGenics (AGIX).40 See next page Although a trio of IPOs have priced this month.0 $318.3 Up to $86.S. The 19 IPOs that have priced in this window had an average post-money valuation of $275.3 Up to $86.9 million shares on Monday following post-market news the prior Friday that FDA accepted for review a CMC supplemental BLA for IMCL’s BB36 manufacturing facility in Branchburg.5 Up to $86. MLNM added $0.8 NA NA NA NA NA NA NA NA NA NA NA NA NA NA TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD Ph II Preclin Preclin Approved Ph II Ph II completed Ph III Ph II Ph II ANDA submission this year Ph II completed Ph I/II Mkt 2/27/04 3/1/04 4/9/04 3/19/04 4/8/04 4/8/04 12/15/03 3/3/04 2/3/04 3/11/04 4/9/04 4/5/05 4/2/04 S-1 update 4/2 3/11 Original funding goal Up to $86.03 (12%) to $66.95. GILD closed Friday at $60.94 to $38.6 Shares 5.0 5.3 New funding goal (A) $75.5 million.0 $310. the average is $245.8 Price range $14-$16 $11-$13 Hoped for post-$ (A) $327.15.67. Viread sales go up… and north Gilead (GILD) bumped up 2004 guidance for its Viread tenofovir HIV drug on its earnings call after market Thursday. and OSIP rose $1.07) per day for Viread.BioCentury.

CHIR said 2H04 will account for 75-80% of full-year EPS.15 $0.66 in 2003 and higher than the company’s guidance of $1. The subscription period will run from May 3 through May 17.66 $0.99 on the week after announcing that FDA wants additional product characterization for the company’s Oncophage cancer vaccine to treat renal cell carcinoma (RCC). 1Q04 EPS est -$0.87 to $9.82-$1.62 % chg -10% Mcap chg ($M) $(219. IVGN raised its revenue and EPS guidance to $1.01 36% $58.34 $0.94 $4.1M in 1Q03.10 Beat by $0.67-$0.74 on Monday after starting the first of four double-blind Phase II trials of its recombinant human thrombin (rhThrombin) to control bleeding See next page Analyst tracks John Sullivan joined Leerink Swann as an analyst in the firm’s biotech group. Amgen (AMGN) $0.60 $0. Investors likely are looking to 2005.20 7% $271.54 to $15.52 from $0. from previous page THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. Fiscal 2004 EPS came in at $1.9 Expects 2Q04 revenues of $93-$98M.3 $3.02 2% $23. Celgene (CELG) $0. but the news didn’t faze investors.9 Product sales were $2. For the full year. Ebb & Flow. The company also said that certain SG&A expenses that were expected in 1Q04 will now come in 2Q04. when the company hopes to start reporting sales of potential blockbuster cholesterol drug Zytorin.9M from $49. Forest (FRX) (B) $0. (A) The Street expects AFFX to be profitable on a full-year basis.9) $24. despite having lifted a partial clinical hold on the Phase III trial last November.70 Beat by $0.41 2% $101.2 LLY’s EPS guidance for 2Q04 is $0. Reiterated 2004 EPS guidance of $0. Chiron (CHIR) $0. AGEN said it will submit the data over the next several weeks. Clinical milestones Alkermes (ALKS) was up $0. CHIR noted that PowderJect revenues are recognized mainly in the second half. Eli Lilly (LLY) $0.85.83 -3% $(2. driven by sales of Thalomid thalidomide.03 on revenues of $78M.71 -9% $(2. PHARMX’s lead programs are HER-2 Protein AutoVac and HER-2 DNA AutoVac. For the year.42 $0. but that costs associated with PowderJect are incurred throughout the year.BioCentury. The company slid $0.57 Beat by $0. to DKK30 on the week after saying it plans to raise about DKK209 million ($33.01 -21% $66. Previously. CHIR expects to have backloaded EPS due to seasonal sales of its flu vaccine.6 million) through a rights issue of 12.15 -$6.50.5 Because of sales seasonality.80 5% $600.44 Beat by $0.04 15% $73.63 Beat by $0.40-$0.13 to $17.02 shy of the consensus estimate.” A15).38 Beat by $0.69. PHARMX estimates that it needs about DKK160 million ($25. The company reiterated full-year EPS guidance of $2.11 88% $60.02B and $2.74 on the week after completing enrollment in a Phase III safety trial of its Vivitrex injectable extended-release naltrexone in about 400 patients who are alcohol.9 The pro forma figures exclude acquisition-related amortization.59 to $16.56 $0.6B in 1Q03 (see “EPO Sales Watch.60.80-$2.03 Growth from 1Q03 NA 4/23 cls $31.95. The company also raised its revenue guidance to $365-$385M from $360-$380M.3 FRX said the quarter-over-quarter EPS decrease reflects increased selling expenses related to the launches of Namenda for Alzheimer’s disease (AD) and antidepressant Lexapro for generalized anxiety disorder.05 -27% $45.9 GILD raised its 2004 guidance for HIV drug Viread to $725-$775M from $700-$750M and increased its guidance for antifungal AmBisome to $170$190M from $160-$180M. up 35% from $1. ALKS expects interim safety data after six months and plans to use results to support an NDA submission in the first half of 2005 (see B9).74 $5.21 on the week.85 and sales growth in the low double digits.350. 2004 P AGE A17 OF 20 equity research analyst at Stephens. which have both completed Phase I studies in breast cancer. Invitrogen (IVGN) $0.5 $8. CELG increased its EPS guidance to $0. The seasonality in part reflects sales of Fluvirin.95 $0. Antigenics (AGEN) fell $0.39 Wk chg -$3.30 on the week.1) 4/23 Mcap ($B) $1. PHARMX’s shareholders will be offered 3 new shares for each share they hold.0 $5. up from $1.or opiate-dependent. Sullivan was vice president and senior EPS watch There were only two misses in last week’s earnings crush: one biotech and one pharma.31 -$1.43 $0.08 $0.27 $0.16.14 in the second quarter. as the company added $0.42-$0. MedImmune (MEDI) $0.88.6 1Q revenue rose 69% to $82. Schering-Plough (SGP) was nicked after coming in $0. with a loss of $0. where he covered companies with enabling technologies for discovery research. ZymoGenetics (ZGEN) added $0.37 $0. See next page .8 million) to get through to mid2006 at its current burn rate.12 $2. (B) FRX results are for fiscal 4Q.05 For 2Q04.27 to $45.53 9% $366.3 million shares at DKK17 each.9 Company Affymetrix (AFFX) (A) Outcome Beat by $0. Chiron (CHIR) missed the Street by a nickel.22 Missed by $0.464. Gilead (GILD) $0.04B and $2. The Street was expecting 2004 revenue and EPS of $1. an influenza vaccine that CHIR gained through its purchase of PowderJect in 3Q03. Analysts had expected EPS of $0.02 900% $56. The company’s market cap is DKK123 million ($20 million).50-$0.45 Beat by $0.70 1% $786.03 21% $74.6 $82.0 $4.92.8 $12.13-$0. The offering is partly underwritten by ING.08 1Q04 EPS actual -$0.2B.27 1% $50. the company expects EPS of $0.7) $74. and ING and Gudme Raaschou are lead managers.

04 to $6.21 -$0.9B on R&D this year. SRA) (see B10).51 $0. Vivus (VVUS) was up $0.4 Pharmaceutical sales increased 19% quarter over quarter to $4.57 using U.74 after starting a Phase II trial of its alagebrium (formerly ALT-711) in patients with diastolic dysfunction and impaired ejection fraction (see Product Development.72 $0. Inspire (ISPH) gained $1.56 Beat by $0.7) $104.64 (13%) to $14. up 8% from 1Q03. which in part reflects PFE’s 2003 acquisition of Pharmacia. Ebb & Flow Trimeris (TRMS) popped $1. MRK reiterated its EPS guidance of $3.S.3 The EPS figure excludes charges for employee termination costs and SGP’s exit from a European R&D facility. SWX:BMRN) wants to become a pediatrics-focused biopharmaceutical company.6 1Q sales of anticoagulant Angiomax bivalirudin for coronary angioplasty procedures increased 87% to $31.59 -1% $(785. TRMS and partner Roche (SWX:ROCZ) launched the injectable HIV fusion inhibitor last spring. 2004 P AGE A18 OF 20 in surgeries. up $0.6 million in the fourth quarter of 2003.76 -$0.77 and $3.9) $9.3B from $3. Neurobiological (NTII) slipped $0. Rebif sales grew 56% to $62. In the U. For 2004. Serono (SRA) $0.01 16% $36.05 on the week to $14.52 ($0.10 -$0. (MDCO) Outcome Beat by $0.2 million shares on Wednesday following its post-market earnings announcement on Tuesday. a 46% increase compared with 1Q03. down $0. Ilex (ILXO) gained $0. VVUS expects to complete enrollment in the trial by year end and data are expected in the first half of 2005 (see B11).149. Investors shrugged off BioMarin’s news that it will pay a total of $175 million for the Ascent Pediatrics business of Medicis (MRX).82.24 Wk chg $0. BioMarin (BMRN.13. in which it said worldwide sales of HIV drug Fuzeon increased 36% to $24 million from $17.06 on the week to $1.01 -$0.01 7% $46. R112 is a nasal spray Syk kinase inhibitor that inhibits mast cell activation.13.16 on the week to $4. will drive its turnaround.07.22 on the week. respectively.13 -1% $(191.S.1) $25. The company hopes to begin Phase III testing in early 2005 (see B11).52 Beat by $0. TRMS closed Friday at $15. Alteon (ALT) added $0. Schering-Plough (SGP) $0.S.53 $0. a combination of SGP’s Zetia and Merck’s Zocor.32 -1% $(711.38 after starting a Phase II trial of its avanafil (TA-1790) to treat erectile dysfunction (ED).2) $104. PFE expects to spend $7. BMRN closed Friday at $6.7M in 1Q03.49 after starting the first of two Phase III trials of Xerecept to treat peritumoral cerebral edema. Phase II trial of its R112 in allergic rhinitis (see B11). A6).08 Campath is marketed to treat refractory B cell chronic lymphocytic leukemia (B-CLL).0 Human pharmaceutical sales came in at $3.17 Met 89% $15. Merck (MRK) $0.01 Missed by $0. .2M in 1Q03. Next year.0 For the year. from previous page 1Q04 EPS est $0.42 -$1. the company hopes that cholesterol therapeutic Vytorin. up $1. A8).0 4/23 Mcap ($B) $1.666.6B. Ebb & Flow.25 after starting a Phase II trial of its INS37217 ophthalmic denufosol as a first-line therapy in patients with rhegmatogenous retinal detachment (RRD) (see B10).55 $0.03 Growth from 1Q03 NA 4/23 cls $34.50 after starting a U.22 on the week and closed Friday at $6.3M from $16.7 Human pharmaceutical sales came in at $11B. Rigel (RIGL) added $1. SGP plans to launch Vytorin in the second half.26 on the week and closed Friday at $24.78-$0. Global sales of Gleevec/Glivec imatinib to treat chronic myeloid leukemia and gastrointestinal stromal tumors (GIST) increased 51% to $351M.6M from $175. The Street expects 2Q and full-year EPS of $0.2B.37. Results are expected in the second half.17 on See next page Company Medicines Co. has Orphan Drug designation (see B10). a synthetic CRH peptide.75 on the week to $21. SEO expects net income growth of at least 20%. NTII has an SPA with FDA for both trials.9) $53.05 1Q04 EPS actual $0.20 after completing enrollment in a Phase II multiple sclerosis (MS) trial comparing its Campath alemtuzumab to Rebif interferon beta-1a from Serono (SWX:SEO. GAAP) NA NA $42.20 -3% $(9.11-$3. SWX: NOVN) $0. as the stock added $0.7M. and the drug has had a slow in an indication populated by oral drugs (see BioCentury.01 4% 39.17 $0.49 -3% $(3. from previous page THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. The company reiterated its full year adjusted EPS guidance of $2. Wyeth (WYE) $0. ZGEN closed Friday at $16.70 on 2. Novartis (NVS.. EPS Watch.9) $277.66 on the week.17. and plans to partner its non-pediatric pipeline products (see Strategy. Feb.36 -2% $(228.BioCentury.6 Global sales of Rebif interferon beta-1a to treat multiple sclerosis (MS) were up 48% to $259.47 % chg 1% Mcap chg ($M) $22. Pfizer (PFE) $0.92.43 -$1.89 on Wednesday’s announcement. and the compound. The company also provided 2Q EPS guidance of $0.02 NA $17.73 Beat by $0.79 -0. 9).

QLTI) B6 RegeneRx (RGRX) B8 Renovis (RNVS) A2 Rigel (RIGL) A18. B4. CERS’s Listeria vaccine technology will be used to develop a vaccine against MEDI’s EphA2 protein (see Technology Briefing. SSE:OXGN) B6 Pfizer (PFE) B6 Pharmexa (CSE:PHARMX) A16. while dropping early stage R&D (see BioCentury. The technology is used to improve the bioavailability of therapeutics. B10 Shire (LSE:SHP. B11 Watson (WPI) B4 Wyeth (WYE) A7. B11 Memory (MEMY) B12 Merck (MRK) B3 Metabasis B4 Metaphore B7 Metrika B6 Micromet B2 Millennium (MLNM) A16 MIV Therap (MIVT) B13 MJ Research B6 MP Biomedicals B4 Mylan (MYL) B6 Myriad (MYGN) B9 Nanogen (NGEN) B5 Nanosys A15. a small molecule immunosuppressant. prostate and colon.53 on the week after licensing its NanoCrystal technology to Roche (SWX:ROCZ) for use with an undisclosed compound (see B3).8 million ($14 million) in cash at Dec.3 million shares on Wednesday’s news that it partnered with MedImmune (MEDI) to develop and commercialize a vaccine to treat cancers of the breast. A13 Xenome B11 Yale U B3.47 (13%) to $4 on 2. 2003). A11 Icon B11 ID Biomedical (TSE:IDB. B10 Integrated Biopharma (INB) B12 Introgen (INGN) B10 Inverness Medical (IMA) B2 Invitrogen (IVGN) B13 Isotechnika (TSE:ISA) A19. Isotechnika (TSE:ISA) fell C$0. B13 Roche (SWX:ROCZ) A18.35 to $10.50 on Tuesday after reworking its deal with Roche (SWX:ROCZ) for ISA247. Ebb & Flow. On TSE. M6G morphine-6-glucuronide. from page A12 H. B2 MedImmune (MEDI) A7. B9 Scancell B8 Schering (FSE:SCH. Elan (ELN) was up $1. B6. A7).9p on the week after Nomura analyst Sam Fazeli began coverage with a “buy” recommendation and a fair value of 22p (see B16). B3. which had comCompany Index. SHPGY) was off 7. B13 pleted Phase II testing in psoriasis and kidney transplantation. and closed Friday at C$2. is expecting Phase III results mid-year for its lead program. the Bernstein Report on BioBusiness® — that is recognized by key decision makers as the best source of perspective. B10 ImClone (IMCL) A1. B7.61 to $28. Cerus (CERS) popped $0. B9 Scolr (SCLL) B7 Seer Pharma B11 Semafore B8 SeraCare (SRLS) B3 Serono (SWX:SEO. IDBE) for $120 million in cash and shares (see Strategy. CERS gave back some gains and closed Friday at $3.45 (15%) to C$2. B12 Pharming (Euronext:PHARM) B5 Pierre Fabre B3 Porton B2 Prana (ASX:PBT.D. A10.62 and IDBE was up $0. now that it has completed the acquisition and integration of CNS company TheraSci (see BioCentury. for its R&D and commercial teams. ISA continued to slide.35 on the week. its Canada-based vaccine business to ID Biomedical (TSE:IDB. which had £7. IDBE) A7. B13 Immuno-Designed B7 Inamed (IMDC) B5 Incara (ICRA) B12 Inflazyme (TSE:IZP) B2 Inhibox B6 InKine (INKP) B8 Inpharmatica B4 Inspire (ISPH) A18. B10. there is only one journal — BioCentury. B11 Zeptosens B3 ZymoGenetics (ZGEN) A17. CEN has a market cap of £30 million ($54 million). as well as metastatic melanoma. B4 Idenix A9 Ilex (ILXO) A18. B6. B4 Southern Research Inst B4 Spectrum (SPPI) B12 State U of New York B3 BioCentury makes people think We know you have many choices for headlines. PVLS) B5 Purely Proteins B6 QLT (TSE:QLT. B3.BioCentury.96. The office is expected to be based near Philadelphia and is slated to open midyear. and the companies dropped development of a mixed version of ISA247. London & the Continent Shire (LSE:SHP. B12 Nastech (NSTK) B7 Neoprobe (NEOP) B6 Neose (NTEC) B5 Neurobiological Tech (NTII) A18.S.5p to 530. The final step will be to open an office in the U. A15. IDB was up C$0.86 (28%) on the week.90 on the week. B2. On NASDAQ. B8 Vivus (VVUS) A18. B4. The company. Lundbeck (CSE:LUN) B4 Hudson Health Sci. 4. down C$0. Dec. 2004 P AGE A19 OF 20 the week. Structural GenomiX B8 Suzhou Zhongkai B3 Syn X (TSE:SYY) B5 Tercica (TRCA) B8 Teva (TEVA) A13 TheraSci A19 Tissera (TSSR) B8 Trimeris (TRMS) A18 U of Connecticut B3 Valeant (VRX) B4. ISA now will independently develop the trans isomer version of ISA247 for renal transplant and psoriasis. Neurological company CeNes (LSE:CEN) was up 0. But if you need to know what the news means. interpretation and analysis for top managers and investors in the biotech community. The move is SHP’s penultimate step before completing its new business model of in-licensing late-stage products and acquiring companies. B11 NPS (NPSP) B5 Nycomed B5 Onyx (ONXX) A16 Oriental Wave B3 OSI (OSIP) A16. 31.85 on the week. Anderson Cancer Ctr B3 Martek (MATK) B4 Medicis (MRX) A6. from previous page THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 26. A19. SHPGY) A7. B10 Novartis (NVS.5p on the week after saying it will sell Shire Biologics. CEN will be meeting with City investors over the next two weeks to retell its story. Aug.70 to $14.53 to $23. A16. SRA) A13. B13 J&J (JNJ) B6 Kissei B4 Laboratorios del Dr. SWX:NOVN) B6. B7 OxiGene (OXGN. PRNAY) B9 Prosidion B7 Protherics (LSE:PTI) B8 Provalis (LSE:PRO. B9. up $0. . 8.8p to 11. SHPGY was down $0. enough for about two years. B2 Lonza B6 M. A10). A9. B9 Vaso Active (VAPH) A3 Vertex (VRTX) B3 Vical (VICL) B3.22. 2003). A19. SHR) A13 Schering-Plough (SGP) B6. Esteve B5 Lexicon (LEXG) B13 LG Life Sci A9.

520 -1.0.760 16% 5331 Hollis-Eden HEPH 8.63 1605. 700 650 600 550 500 450 400 350 300 250 200 150 Apr 23 Stocks with greatest % price decline (criteria as above).0.490 21% 63626 Quidel QDEL 8.860 1.780 -13% 1463 Vernalis 1 VNLS 2. Tier II <$1B. (00) 1183073 5320967 1235946 1544595 3688326 BC100 Stocks Declining declining vol.310 31. provider of market intelligence services to publicly held companies.000 minimum share volume) Company Ticker $Close $Chg %Chg Vol(00) Zonagen ZONA 3.010 19% 23401 Cytogen CYTO 14.350 12. Base =100 on Dec.390 -3. 1900 800 700 600 1700 500 1600 400 1500 300 1400 200 1300 100 1800 Stocks with greatest % price increase in the week ended April 23. The BioCentury 100 is a subset used to monitor price and volume trends. Tier I = market caps>$1B.940 -10% 9754 Dynavax DVAX 6.870 2.350 0.610 -0.030 19% 253289 DUSA DUSA 12.900 -1.940 2.420 20% 33424 Illumina ILMN 8. 31. %Chg 3615% 1005% 937% 852% 561% 490% 465% 435% 427% 396% 395% $Close $Chg 295p 14p DKK30 -DKK1. THE BERNSTEIN REPORT ON BIOBUSINESS Price Gains APRIL 26.300 5.100 -9% 5881 Labopharm DDS C5.550 -0.030 12.000 0.730 -8% 771 Volume Gains Greatest changes in volume above 25.960 0.500 -8% 3063 Antigenics AGEN 9.870 -8% 31326 Memory MEMY 8.550 3.16 1649.200 18% 14603 Iomed IOX 3. Bars show cumulative volume in millions (right scale). 12-week period. (00) 69 4078787 6 259998 65 2330186 68 2368397 25 1721026 Source: Thomson Financial BioCentury tracks 467 issues that report prices and volume daily.350 -12% 42568 Aerogen AEGN 3.850 -17% 3410 Medivir MVIR SEK101 -SEK16. Company Ticker $Close $Chg %Chg Vol(00) Sonus SNUS 5.780 3.500 1.040 26% 22909 Genta GNTA 13.700 -10% 1494 Corcept CORT 10. (Priced above $2.BioCentury.860 1.980 1. TFCG Life Sciences Indexes are compiled by Thomson Financial.000 Company Ticker Vol(00) NeuTec NTP 4185 Pharmexa PHARMX 4554 Aeterna 2 AELA 35631 Zonagen ZONA 6913 GPC GPC 11284 november NBX 1463 Cerus CERS 30455 BioVeris BIOV 23883 Nymox NYMX 11567 Affymetrix AFFX 177914 Pharmion PHRM 11416 shares.450 -0.620 24.950 -0.67 1600.980 -0.310 0.390 -3. Line shows Price Level change (Left scale.600 23% 194400 Avant AVAN 2.300 11.450 18% 2035 GTx GTXI 12.040 1.281 -0. 1996.0.29 BC100 Stocks gaining 31 94 34 30 75 Gaining vol.50. 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0 Apr 23 Tier II (180 companies) 1 Includes volume from London Stock Exchange with converted ADSs (ADS = 40 shares) 2 Includes volume from Toronto Stock Exchange Tier I (20 companies) BioCentury 100 Advance-Decline Trend Week ended Mar 26 Apr 02 Apr 08 Apr 16 Apr 23 BC100 Price level 1504.770 0.990 -0. 1996).950 1.550 -C0.00 .110 TFCG Life Sciences Indexes Weekly change in combined market capitalization.410 -20% 7835 Lynx LYNX 4. 12-week period.980 2.320 20% 18938 ImClone IMCL 70. 25.030 36% 6913 ImmunoGen IMGN 9.620 -10% 177914 Cholestech CTEC 8. 12-week period.409 -11% 1497 Affymetrix AFFX 31. Index base=1000 on May 10.010 -0.270 .270 . Index base =1000 on May 10.97 1587. 1998.210 -0.801 3.550 2.210 16% 21365 Price Declines 1200 0 BioCentury London Index Weekly change in the combined market capitalization for 14 bioscience stocks listed on the LSE or AIM. .4 7.5 -14% 1478 november NBX 5. 2004 P AGE A20 OF 20 BioCentury 100 Price & Volume Trend Cumulative weekly performance of 100 bioscience stocks.

Cyclacel Ltd. (SWX:SEO. SWX:BMRN) Regional Host and Regional Host Members Ernst & Young Wood Mackenzie Scottish Equity Partners Scottish Widows Investment Partnership BIA ITI Life Sciences Register Online at www. AVONTEC GmbH Basilea Pharmaceutica Ltd. Global Genomics AB GLYCART biotechnology AG IDEA AG igeneon AG Intercell AG Jerini AG Laxdale Ltd. Rowe & Maw Cooley Godward LLP Pharma Sponsor Astra Zeneca Contributing Sponsors Techno Venture Management Deutsche Bank DVC Deutsche Venture Capital SOFINNOVA Partners Bank Vontobel 3i Fortis Bank SWX Swiss Exchange CMS Deutsche Boerse BioEquity Europe also provides a venue explicitly designed to maximize financial networking. PAION GmbH PheneX Pharmaceuticals AG PIERIS Proteolab AG Probiodrug AG Serono S. (SWX:BSLN) BioMarin Pharmaceutical Inc.A. neurology. INVESTMENT PROFESSIONALS Register Now & Reserve Your Seat INTRODUCING Acknowledging the Support of Gold Equity Sponsor THE BIOEQUITY EUROPE PRESENTING COMPANIES Celebrating its 5th anniversary.A. BioXell SpA CareX S.A.and later-stage clinical milestones. Addex Pharmaceuticals S. Orexo AB Oxxon Pharmaccines Ltd. Speedel Group SWITCH Biotech AG TeGenero AG Trigen Ltd.D. (ENCY) Epigenomics AG Evotec OAI AG (FSE:EVT) Exelixis Inc. MediGene AG (FSE:MDG) Micromet AG Myogen Inc.IO QUITY B EUROPE 2004 Organized by BioCentury E. with the 2004 program offering small discussion sessions with a faculty of seasoned life science investors from Europe and North America. deCODE genetics Inc. Brown. BioEquity Europe has established itself as the magnet for financial dealmakers and the premier venue for life science companies positioning themselves to attract capital from international investors. VNLS) Wilex AG Y’s Therapeutics Co. Ardana Bioscience Ltd.A. (VXGN) Vernalis plc (LSE:VER. Ltd. U3 Pharma AG VaxGen Inc. Ark Therapeutics Group plc (LSE:AKT) Arpida Ltd. Newron Pharmaceuticals SpA OctoPlus B. Cellectis S. 2004 Sheraton Grand Hotel Edinburgh. CeNeS Pharmaceuticals plc (LSE:CEN) Coley Pharmaceutical Group CombinatoRx Inc. (MYOG) NeuroSearch A/S (CSE:NEUS) Neuro3d S. as well as a special track of companies building next-generation protein therapeutics. (BMRN. (DCGN) DeveloGen AG Domantis Ltd. . Ablynx N. especially in the areas of cancer. Group BIO May 17-18. U. Affibody AB Arakis Ltd.V.A. SRA) SiRENADE Pharmaceuticals AG Sosei Co. Ltd.K.A.biocentury.B.com Biolipox AB BioVex Ltd. Faust Pharmaceuticals 4SC AG Gamida-Cell Ltd. Encysive Pharmaceuticals Inc. The 2004 meeting focuses on Europe’s growing inventory of companies facing mid. (EXEL) ExonHit Therapeutics S. Silver Equity Sponsors Palmer & Dodge LLP Mayer. Lorantis Ltd. Onyvax Ltd. cardiology and metabolic diseases. ARYx Therapeutics Inc.V.

Pharmaceuticals. Renal. 19 THE COMPLETE REPORT OF BIOBUSINESS NEWS APRIL 26. Cardiovascular. Chemistry. Ophthalmic. Microfluidics. Pharmacogenetics. Antibodies. Anderson Cancer Ctr Elan (ELN)/Roche (SWX:ROCZ) Enzo (ENZ)/U of Connecticut Genelabs (GNLB)/MP Biomedicals GeneProt/Lundbeck (CSE:LUN) Gilead (GILD)/Southern Research Inst GTx (GTXI)/Beckman Coulter (BEC) ID Biomedical (TSE:IDB. Infectious. Biomanufacturing. The index on this page lists all the companies covered this week. Finance. SWX:BMRN)/Medicis (MRX) Bioseek/Cognia/Harvard U/State U of New York/Yale U Boston (BBII)/SeraCare (SRLS) Bristol-Myers (BMY)/Dow (DOW) Bristol-Myers (BMY)/Pierre Fabre Cell Signaling Tech/Zeptosens Cerus (CERS)/MedImmune (MEDI) CytRx (CYTR)/Vical (VICL) Discovery Partners (DPII)/Vertex (VRTX) Dragon (TSE:DDD. the biotech company is shown first. Functional genomics. Biopharmaceuticals. Musculoskeletal. N O. Hepatic.don (FSE:CNW) Immuno-Designed Molecules OSI (OSIP) Management Tracks (Page B7) Advanced Viral Res (ADVR) Agencourt . Endocrine. NMERC:CTIC) CuraGen (CRGN) Ilex (ILXO) Inspire (ISPH) Introgen (INGN) Neurobiological Tech (NTII) Rigel (RIGL) Vivus (VVUS) Xenome ZymoGenetics (ZGEN) See next page Regulatory (Page B5) Altana (FSE:ALT. Neurology. Hematology. Drug delivery. Diagnostic. Clinical News and Financial News. Dental. Bioinformatics.BioCentury Part II VOL. Nutraceuticals. Combinatorial biology. SHPGY) Inpharmatica/Biotica Isotechnika (TSE:ISA)/Roche (SWX:ROCZ) Kissei/Watson (WPI) Martek (MATK)/DSM Metabasis/Valeant (VRX) Nanogen (NGEN)/Syn X (TSE:SYY) Neose (NTEC)/BioGeneriX NPS (NPSP)/Nycomed Pharming (Euronext:PHARM)/Laboratorios del Dr. AZN) Avant (AVAN)/DynPort BioInvent (SSE:BINV)/Enzon (ENZN)/ Micromet BioMarin (BMRN. Metabolic. QLTI)/Novartis (NVS. 12. Genitourinary. Cancer. Agbio/Environmental. The news items in each department are organized alphabetically by company. Dermatology.D. Gene/Cell therapy. SWX:NOVN) Schering-Plough (SGP) DynPort Myriad (MYGN) Sales & Marketing (Page B6) Bristol-Myers (BMY)/Metrika co. Other. AAA) Antigenics (AGEN) Barbeau Pharma/ESP Pharma Genta (GNTA)/Aventis (AVE) Genzyme (GENZ)/Inamed (IMDC) GlaxoSmithKline (LSE:GSK. 2004 PAGE B1 OF 13 BioBusiness for the week ended April 23 COMPANY NEWS Deals (Page B2) Adprotech/Inflazyme (TSE:IZP) Anadys (ANDS)/LG Life Sciences Antisoma (LSE:ASM)/Inverness Medical (IMA) Astex/AstraZeneca (LSE:AZN. SSE:OXGN)/QLT (TSE: Other News (Page B6) Applied Biosystems (ABI)/MJ Research/Roche (SWX:ROCZ) co. High throughput screening. Each brief is labeled with one or more applicable business categories from the following list: ADMET. Pulmonary. PRNAY) Valeant (VRX) ZymoGenetics (ZGEN) Preclinical Results (Page B9) QLT. Genomics. Supply/Service.don (FSE:CNW) Inhibox/Purely Proteins Roche (SWX:ROCZ) Clinical Status (Page B9) Advanced Biotherapy (ADVB) Alkermes (ALKS) Alteon (ALT) Anika (ANIK) Cell Therap (CTIC. Computational chemistry/biology. Autoimmune. When more than one company is listed. Gastrointestinal. Proteomics. It is organized into three departments: Company News. DRUG)/Suzhou Zhongkai Echelon/M. GSK) ImClone (IMCL) J&J (JNJ)/Schering-Plough (SGP) Mylan (MYL) Neoprobe (NEOP) OxiGene (OXGN. PVLS)/Edmond Using BioCentury Part II BioCentury Part II is a comprehensive compendium of business news for management and investors in bioscience companies. Generics. Transplant. IDBE)/Shire (LSE:SHP. Veterinary Avecia Benitec (ASX:BLT) Bioreason Boston Biomedica (BBII) Carolina Pharma Conforma Corgentech Edwards Lifesciences (EW) Genencor (GCOR) Genitope (GTOP) MedImmune MEDI) Metaphore Nastech (NSTK) Protherics (LSE:PTI) RegeneRx (RGRX) Scancell Scolr (SCLL) Semafore Structural GenomiX Tercica (TRCA) Tissera (TSSR) Vical (VICL) CLINICAL NEWS Clinical Results (Page B8) Alexion (ALXN) Bioenvision (BIV) CV Therap (CVTX) InKine (INKP) Prana (ASX:PBT. Inflammation. Esteve Provalis (LSE:PRO. Microarrays.

from previous page Other Research News (Page B11) Agrobiogen Icon Novartis (NVS.” BMRN said it will partner its non-pediatric pipeline products.000 in cash and up to $1. Malmo. Regulatory. Europe. Business: Neurology AZN selected for further development specific molecules from the companies’ 2003 ADMET deal (see BioCentury. (ANDS). and NeuroTrans for delivering proteins across the blood-brain barrier. the pediatrics business of MRX. BioMarin Pharmaceutical Inc. Seoul.J. Business: Inflammation BMRN will pay a total of $175 million for Ascent Pediatrics. R1549. BMRN will pay MRX $10 million at closing. Micromet and ENZN will share the revenues under their 2002 development and marketing deal (see BioCentury. has an ongoing 10-year contract with the Department of Defense to develop vaccines against biological warfare agents.BioCentury Part II APRIL 26.C. (ENZN). BMRN said the move will help it become a “fully integrated pediatrics-focused biopharmaceutical company. AstraZeneca plc (LSE:AZN. March 10.K. valued at C$18. The compound is expected to have net sales of about $42 million this year. Inverness Medical Innovations Inc.C. which are mouse and humanized variants of the HMFG1 antibody. Department of Defense (see BioCentury. Inflazyme Pharmaceuticals Ltd. (IMA). Mass. BMRN plans to See next page BioTrove Memory (MEMY) MIV (MIVT) Clinical News. Needham. and preclinical compounds Chondroitinase for spinal cord injury. including Vibrilase in Phase I testing for burns and wounds. is in Phase III trials for ovarian cancer. a yttrium-90 radiolabeled antibody against PEM. (Washington. The money will support human clinical trials of AVAN’s plague vaccine candidate. Switzerland). a non-refrigerated formulation that could be launched in 2005. Sweden Enzon Inc. N. Antisoma plc (LSE:ASM). 27. U. Va. B. Two additional formulations of Orapred are in development: Orapred 2. Basel. Micromet AG. Frederick. Vancouver.7 million shares. Sales & Marketing. Mass. Cambridge.K. SWX:NOVN) Yale U Callisto (CLSP) DxS Dynogen Incara (ICRA) Integrated (INB) Spectrum (SPPI) Analysts (Page B13) Amgen (AMGN) Antigenics (AGEN) CeNeS (LSE:CEN) Gilead (GILD) ImClone (IMCL) Invitrogen (IVGN) Isotechnika (TSE:ISA) Lexicon (LEXG) MedImmune (MEDI) Rigel (RIGL) Proposed Offerings (Page B12) Auxilium Nanosys Pharmexa (CSE:PHARMX) FINANCIAL NEWS Completed Offerings (Page B12) Bruker (BRKR) Other Financial News (Page B12) Array (ARRY) . The selection triggered a second milestone to Astex. Korea and Southeast Asia. Business: Infectious AVAN received $3 million from DynPort under a subcontract to discover and develop an oral combination vaccine against anthrax and plague for the U. London. is in a Phase I trial to treat locally advanced or metastatic breast cancer. Anadys Pharmaceuticals Inc.4 million (US$13. AZN).K. U. Calif. London. U. Astex Technology Ltd. SWX:BMRN). D. Medicis Pharmaceutical Corp. DynPort. Business: Cancer ASM will pay IMA $300. ANDS obtains exclusive commercialization rights in North America. (AVAN).45 on April 20. BINV will apply SCA to its antibody library and can use the technologies for both internal programs and development partnerships. 2003). which is a joint venture between DynCorp (Reston. MRX also will receive $145 million in cash over the next 5 years plus $20 million in stock in 2009. BioInvent International AB (SSE:BINV). Micromet receives an upfront payment and annual maintenance fees plus potential sublicensing fees. (TSE:IZP). 2002). South Korea Business: Infectious ANDS exercised an exclusive option to license LG’s LB80380. (BMRN. LG Life Sciences. Avant Immunotherapeutics Inc. a humanized HMFG1 antibody against MUC1. Novato. Both compounds are being co-developed with Roche (SWX:ROCZ. Management Tracks DEALS Adprotech Ltd. Calif.).. Waltham.. April 12). R1550. Munich. a corticosteroid to treat asthma in children.5 million in milestones to acquire IMA’s royalty rights to ASM’s R1549 and R1550 compounds. BMRN also will assume $15 million of MRX’s debt.7 million) using IZP’s pre-deal closing price of C$1. The companies will jointly develop LB80380. Ascent markets Orapred. Germany Business: Antibodies BINV obtained non-exclusive access from Micromet to Micromet’s and ENZN’s shared IP covering single-chain antibody (SCA) technologies. March 1). 2004 PAGE B2 OF 13 COMPANY NEWS/Deals. a nucleotide analog in Phase II testing to treat chronic HBV infection (see BioCentury. Japan and most countries worldwide excluding China. The companies will pay each other royalties on sales in their respective territories. Business: Inflammation IZP completed its previously announced acquisition of Adprotech for 12. Ariz.) and Porton International Inc. BINV also can sublicense the technology to collaboration partners. India.S. April 15. Cambridge. LLC. The deal was announced earl i er t hi sm ont h (see BioCentury. Bridgewater.K. San Diego. DynPort Vaccine Co. and a rapid-dissolve tablet dose formulation that could be launched in early 2007. (MRX). 2003). Md. U. Jan. Phoenix.

Norcross. Suzhou. San Diego.J.. (ENZ). will license and co-develop therapeutics to stimulate and See next page .Y. The company plans to use that sales force to market its Aryplase enzyme replacement therapy to treat MPSVI. Dec. Cambridge. The center will receive warrants to buy Echelon stock. New York. and the combined company plans to offer generics chemical intermediates (see BioCentury. The companies said an antiEphA2 vaccine showed antitumor responses in mice.J.. Zhongkai’s product is approved in China to increase white blood cell counts in cancer patients receiving chemotherapy. The company said it will give more specific guidance in the third quarter. The products will be marketed in the U. Austin..S. France Business: Cancer BMY received rights from Pierre Fabre to develop and market Javlor vinflunine. Inc. Texas Business: Cancer Echelon and the center will collaborate to develop therapeutics against new cancer targets beginning with PI3 kinase. including phospho-specific antibodies. Dow Chemical Co. Dragon Pharmaceuticals Inc. by BMRN through a 73-person sales force that BMRN acquired in the deal. (MEDI). Supply/Service The companies partnered to combine Cell Signaling’s reagents. BBII expects the deal to close by Aug. Under a 2001 deal. Cambridge. expects the deal to be accretive to EPS. and is eligible for milestones and royalties. prostate and colon. Salt Lake City. ENZ subsidiary Enzo Therapeutics Inc. Korea and selected Southeast Asian countries. (VRTX).S. Business: Bioinformatics Cognia licensed its molecular information management system to Bioseek and the universities. except for prostate-specific membrane antigen and four infectious disease targets that CYTR previously licensed to Merck & Co. in the U. Canada. manufacturing and commercialization. but did not provide specific guidance. with Zeptosens’ ZeptoMark protein microarray technology. Harvard University. Vertex Pharmaceuticals Inc. which provides biological material manufacturing services. Enzo Biochem Inc. (MRK. In exchange for providing formulation services and access to the technology. Javlor is in European Phase III trials to treat bladder cancer and non-small cell lung cancer (NSCLC) and Phase II trials to treat breast and ovarian cancer. Calif. Calif. Business: Gene/Cell therapy CYTR received a $100.S. for which Phase III data are expected this quarter. Switzerland Business: Antibodies. State University of New York. to Zhongkai’s recombinant human granulocyte colony stimulating factor (G-CSF). Japan. (TSE:DDD. Supply/Service SRLS signed an agreement to purchase BBII’s BBI Diagnostics and BBI Biotech Research Laboratories divisions for $30 million in cash. and Echelon will receive an option to market compounds developed under the deal. excluding China. Mich. from previous page launch Orapred in markets outside the U. N.Y. Bristol-Myers Squibb Co. Business: Cancer The companies partnered to develop and commercialize a vaccine APRIL 26. Under the deal. Ga. and Dowpharma is eligible for milestones and royalties. (CYTR). Discovery Partners Inc. (BMY). (SRLS). BMRN expects the acquisition to decrease its estimated 2004 loss of $68-$70 million. Yale University.J. which uses CYTR’s TranzFect technology. Princeton. Conn. Boston Biomedica Inc. Vancouver.. The combined product will be used for protein expression analysis and protein activation profiling.BioCentury Part II Deals. N. Binghamton. 2001). Business: Diagnostic. Mass. CytRx Corp. CERS will participate in development and will receive an upfront payment and development funding. Ltd. Concord. BMY will fund feasibility studies.. N. Whitehouse Station. N. Burlingame..) (see BioCentury. B. University of Connecticut Health Center. China Business: Cancer DDD received exclusive worldwide rights. DRUG). Business: Supply/Service DOW’s Dowpharma subsidiary will use its particle engineering technologies to improve the solubility of undisclosed compounds from BMY. Calif. Mass.D. West Bridgewater. a vinca alkaloid chemotherapeutic. Vical Inc. Bioseek Inc.C. (VICL). Cognia Corp. Princeton. Oceanside. (British Virgin Islands). Conn. Suzhou Zhongkai Bio-Pharmaceuticals Co. DDD is merging with Oriental Wave Holding Ltd. (DOW). Switzerland Business: Drug delivery ROCZ licensed ELN’s NanoCrystal technology for use with an undisclosed compound in development. Zeptosens AG. MedImmune Inc. Mass. N. (BBII). Dublin. (DPII). Utah M.S.000 milestone from VICL triggered by the start of a Phase I trial of VICL’s plasmid DNA vaccine for cytomegalovirus (CMV). Farmingdale. N. Pierre Fabre will retain development and marketing rights in all other countries. Mass. ELN will receive research revenues and is eligible for milestones and royalties. Calif. Cell Signaling Technology Inc. Basel. Anderson Cancer Center. New Haven. Md. SRLS. SeraCare Life Sciences Inc. (BMY). 15. Bristol-Myers Squibb Co. Beverly. CERS’s Listeria vaccine technology will be used to develop a vaccine against MEDI’s EphA2 protein. 24. (CERS).Y. Pierre Fabre Medicament. Midland. March 29). 2004 PAGE B3 OF 13 to treat cancers of the breast. MEDI is responsible for clinical development. Witterswil. Ireland Roche (SWX:ROCZ). by early 2006. VICL has exclusive rights to CYTR’s TranzFect poloxamer technology to enhance viral or non-viral delivery of polynucleotides. Business: Musculoskeletal Under two deals with the university. Business: Chemistry DPII will use its focused library synthesis and medicinal chemistry capabilities to support VRTX’s drug discovery efforts for an undisclosed research program. will be necessary to submit an NDA. and metastatic melanoma. San Diego. and said the sale will let it focus on its Pressure Cycling Technology (PCT). Cerus Corp. Farmington. BMY said it will discuss with FDA whether additional clinical trials in the U. Echelon Biosciences Inc. Gaithersburg. Castres Cedex. plc (ELN). Elan Corp. NanoCrystal technology is used to improve the bioavailability of therapeutics.

Japan) are preparing an NDA. Business: Infectious SHP will sell its vaccine business. Neurology GeneProt will use its MicroProt process to study the proteomics of fluid samples taken from a rodent model of CNS disease. DSM gained access to MATK’s IP related to ARA manufacturing. Calif. DSM N. Calif. Quebec. and UBS and Canaccord advised IDB. Vancouver. ENZ holds an exclusive license to the technology and is a co-inventor along with the university.BioCentury Part II Deals. Nagano. (MATK). Under See next page . Calif. Kissei is eligible for milestones and royalties. Valeant Pharmaceuticals International (VRX). Canada and Mexico to develop and market Kissei’s KMD-3213 silodosin. neisseria meningitidis. Genelabs Technologies Inc. Biotica Technology Ltd.V. Columbia. (TSE:IDB. a selective adrenergic receptor alpha 1a antagonist for benign prostatic hyperplasia (BPH). The loan will be repaid out of income generated by IDB’s non-Canadian sales of the APRIL 26. Lundbeck A/S (CSE:LUN). In 2003. As amended. Mass. April 15. U. which supplies ARA to MATK. Geneva. Business: Genitourinary. ISA will independently develop the trans isomer version of ISA247 for renal transplant and psoriasis. (GTXI). an intramuscular influenza prophylactic to treat influenza. SHPGY).8 million and a net operating loss of $21. U. Calif. ROCZ has an option to assume development and marketing rights to trans-ISA247 for transplant indications up to 90 days after a planned Phase II renal transplant trial.. Inpharmatica Ltd. B. Copenhagen. Calif. ISA said development of the mixed version of ISA247. Business: Genitourinary GTXI and BEC’s Hybritech Inc. (GNLB).C. Redwood City. a mixture of cis and trans isomers of a small molecule immunosuppressant (see BioCentury. (TSE:ISA). Alberta Roche (SWX:ROCZ). Cambridge. Stearns advised SHP. ISA said trans-ISA247 is in Phase I doseranging trials. as well as rights to use MATK’s technology for non-human applications. Isotechnika Inc. (BEC). Business: Diagnostic GNLB completed the sale of its diagnostics business. Irvine. Denmark Business: Proteomics. MATK received rights to certain DSM IP. U. 2004 PAGE B4 OF 13 injectible flu and other pipeline products. (GILD). the vaccines business generated revenues of $24. Business: Infectious Under a 2001 deal. The business employs 400 in Quebec City and Laval. as well as certain ARA production rights. Cancer WPI received exclusive rights in the U. London. Switzerland Business: Transplant ISA and ROCZ renegotiated a 2002 deal covering ISA247. Foster City.. 2002). Corona. The technology relates to the modulation of signaling pathways in cell development and differentiation by signaling proteins and small molecules that act in both osteoblasts and the primitive cells of the hematopoietic system. Southern Research Institute. Md. Phase II trial. Gilead Sciences Inc. Martek Biosciences Corp. ISA would receive a $75 million payment and milestones. Heerlen. Calif. Metabasis Therapeutics Inc. Kissei Pharmaceutical Co.K. which IDB can draw down over the next 4 years to fund development of injectible flu and pipeline products within the vaccine business. and Northborough. The compound has completed a U. SHP will receive $60 million in cash through two equal payments at closing and 12 months later.9 million. selling all shares of Genelabs Asia Pte. from previous page enhance bone formation. The company plans to begin a Canadian Phase III psoriasis trial by year end. Under the licensing deal. Shire Biologics. The Netherlands Business: Nutraceuticals The companies expanded a 1997 manufacturing and supply deal to include cross-licensing of IP relating to arachidonic acid (ARA) and joint R&D to expand applications for ARA. Tenn.S. Inpharmatica will provide ADME services to improve the pharmacokinetics of rapamycin analogs and other antiproliferatives in development at Biotica. Calif. (WPI).. is no longer being pursued. Switzerland H. Metabasis received a $1 million milestone payment from VRX triggered by the decision to start a Phase II trial of remofovir (formerly Hepavir B) to treat chronic HBV infection. GTXI will provide clinical samples from its Phase IIb trial of Acapodene to reduce the incidence of high-grade prostatic intraepithelial neoplasia (PIN). also will expand its manufacturing capacity for ARA. analysis and interpretation of ADME data. Bear. GTx Inc. DSM. unit partnered to develop assays for prostate cancer. Basingstoke. to vaccine company IDB for $120 million. Shire Biologics also is developing vaccines for streptococcus pneumonia.K. Japan Watson Pharmaceuticals Inc. Ltd. ISA also would be eligible to receive royalties. The remaining $60 million will be paid in about 5. Edmonton.. BEC will use the samples to determine whether its panel of proPSA serum markers can help diagnose the presence of PIN. IDBE). IDB said the deal gives it an antigen supply for IDB’s FluInsure intranasal influenza vaccine.S. and NeisVac-C for meningitis C.K. (Tokyo. which had completed Phase II testing in psoriasis and kidney transplantation. Business: ADMET Under a two-year deal. Memphis. Fullerton. In Japan.4 million IDB shares or cash in the first 22 months following closing. Basel. Birmingham. Kissei and partner Daiichi Pharmaceutical Co.. GNLB said the sale will allow it to focus on drug discovery and development. Ltd.. Beckman Coulter Inc. ID Biomedical Corp. group B streptococcus and group A streptococcus. SHP will provide IDB with a loan facility of $100 million. and a Phase IIb renal transplantation trial in the first quarter of 2005. The services include in vitro ADME screening. Also included are two products marketed in Canada: Fluviral. If exercised. GeneProt Inc. and lead optimization. Shire Pharmaceuticals Group plc (LSE:SHP. and ROCZ would be responsible for 70% of future development costs. Ltd. San Diego. LUN will have exclusive rights to commercialize results. Costa Mesa. Ala.. ISA retains worldwide rights to develop and sell the product for non-transplant indications. MP Biomedicals LLC. Business: Chemistry The institute will provide chemistry and screening services to GILD for an undisclosed early drug discovery program. to MP Biomedicals. ISA has about $59 million in cash.

In exchange. NTEC will receive an upfront fee and will have commercialization rights in the U. Canada. France Product: Genasense oblimersen Business: Cancer The partners began an expanded access program to make GNTA’s Genasense available to chemotherapy-naive patients with advanced melanoma. (NTEC). Esteve S. GlaxoSmithKline plc (LSE:GSK. 2004 REGULATORY PAGE B5 OF 13 Altana AG (FSE:ALT. Provalis plc (LSE:PRO. ESP Pharma Inc. Portugal and Greece to treat hereditary angioedema (HAE). Product: Advair Diskus 100/50 fluticasone propionate 250 µg and salmeterol 50 µg inhalation powder Business: Pulmonary FDA granted marketing approval for Advair Diskus to treat children ages 4-11 with asthma who are symptomatic on inhaled corticosteroid monotherapy.3 million using NGEN’s close of $7.. (TSE:SYY). ALT did not disclose when it plans to launch Alvesco but said it hopes to coordinate launch timing in several European countries. Product: Oncophage (HSPPC-96) Business: Cancer AGEN plans to submit over the next several weeks additional product characterization data requested by FDA for the company’s Oncophage cancer vaccine to treat renal cell carcinoma (RCC). London.A.V. Cardiovascular NGEN completed its previously announced acquisition of point-ofcare diagnostic company SYY for 1.6 million shares. U. Salt Lake City. (Euronext:PHARM). Strasbourg. the Commonwealth of Independent States and Turkey. (NGEN).68 on April 20. NPSP also is eligible for up to $25 million in milestones plus royalties.. Calif. Berkeley Heights. granted marketing approval for Alvesco inhaled corticosteroid to treat persistent asthma in adults. Esteve.to deep dermis to correct moderate to severe facial wrinkles and folds. (NPSP). milestone and royalties.BioCentury Part II Deals. NPSP plans to submit an NDA by year end for Preos. Genta Inc. Ontario Business: Diagnostic. market and sell rhC1INH in Spain.S. Mannheim. BioGeneriX AG. San Diego.J. which values the deal at $12. an injectable full-length recombinant human parathyroid hormone. Aventis SA (AVE). Spain Business: Cardiovascular The companies signed a letter of intent under which PHARM will license its recombinant human C1 inhibitor (rhC1INH) to Laboratorios del Dr. where the partners submitted an NDA in December 2003. rhC1INH has completed Phase II studies. The antisense agent targeting Bcl-2 is under FDA review in combination with dacarbazine for the indication. The product is partnered with Aventis SA (AVE.800) in installments towards development and regulatory costs. See next page ‘It’s the BioCentury’TM .J.K. Antigenics Inc. from previous page the original deal. Nycomed will purchase $40 million of NPSP stock and assume responsibility for conducting Phase IIIb and IV trials in Europe. the day before the deal closed. Paderno d’Adda. PRO will pay 200. representing at least a $25 million investment. Strasbourg. and BioGeneriX is responsible for clinical expenses. Germany Product: Alvesco ciclesonide Business: Inflammation The U. Edmond Pharma SpA. Toronto. Barcelona. VRX is responsible for clinical development of the compound. Utah Nycomed Group A/S. They will partner to develop.. (AGEN). Barbeau Pharma Inc. Nanogen Inc.K.S. Penn. Genzyme Corp. Bad Homburg. PHARM will receive R&D contributions. PVLS). APRIL 26. Pharming Group N. New York.Y. The companies hope to close the deal by June 30.. NGEN announced the acquisition in February (see BioCentury. and PHARM expects to begin Phase III trials by mid-year. ALT said the U. Mexico and Japan.K. FDA lifted a partial clinical hold on the compound last November. Denmark Business: Musculoskeletal NPSP granted development and marketing rights to Nycomed for osteoporosis candidate Preos in Europe. Alvesco was approved in Australia in February. 16). Syn X Pharma Inc. and Ireland for at least 10 years. Cambridge. Hematology The companies partnered to use NTEC’s GlycoPEGylation technology to develop a long-acting version of granulocyte colony stimulating factor (G-CSF) to promote white blood cell production. an oral prodrug of the antiviral adefovir. U. GENZ developed and manufactures Hylaform. The partners said no pre-treatment skin test is required and that they will start shipping the product immediately. Leiden the Netheralnds Laboratorios del Dr. (GENZ). IMDC holds worldwide marketing and distribution rights. Feb. Edison. Germany Business: Biomanufacturing. Product: Hydralazine Business: Cardiovascular FDA granted Orphan Drug designation for the companies’ Hydralazine peripheral vasodilator to treat severe intrapartum hypertension associated with severe pre-eclampsia and eclampsia of pregnancy. Santa Barbara. AAA).. Inamed Corp.K. The companies will receive royalties on each other’s sales. Ill.K. Horsham. Deeside. Product: Hylaform (Hylan-B gel) Business: Dermatology FDA granted marketing approval to IMDC and GENZ for Hylaform. Roskilde. Erdotin is undergoing European registration.000 ($239. Northfield. GSK). PRO will be the exclusive distributor for the first 5 years and has the option to acquire Erdotin — a mucolytic agent to treat chronic bronchitis or chronic obstructive pulmonary disease (COPD) — for a predetermined amount after three years. and has a PDUFA date of June 8. a hyaluronic acid-based dermal filler for injection into mid. NPS Pharmaceuticals Inc. will serve as the Reference Member State under the European Mutual Recognition Procedure. FDA’s Oncologic Drugs Advisory Committee will review the Genasense NDA on May 3. Neose Technologies Inc. N. Calif. The companies will share preclinical development expenses. France) in the U. N. N. (GNTA). Mass. BioGeneriX will have rights in Europe and the rest of the world. (IMDC). Italy Business: Diagnostic PRO will distribute Erdotin erdosteine from Edmond Pharma in the U.

C.. which was submitted in January 1997. The second phase.. 2004 PAGE B6 OF 13 QLT Inc. Princeton.K. In February. (NEOP). The court’s decision concludes the first phase of a two-phase trial. New York. because the jury found infringement of four of the patents to be willful. New York. The compound is in Phase II testing in the U. Schering-Plough Corp.195. Princeton.).S. which will review MJ Research’s counterclaim that See next page . MJ Research Inc.J. N. N. B. The combination of Remicade and methotrexate is approved to reduce the signs and symptoms. Basel. kinases and proteases. IMCL said it and partner Bristol-Myers Squibb Co.J. APRIL 26.656. from previous page ImClone Systems Inc. Germany Business: Dermatology CNW launched its chondrotransplant Disc. The jury found that MJ Research infringed the following U. Penn. Penn. OTHER NEWS Applied Biosystems Group (ABI). to treat Crohn’s disease and in Europe to treat Crohn’s disease and ankylosing spondylitis.K. N. Boehringer Ingelheim (Ingelheim. Ind.610. Pittsburgh.Y. The antibody against epidermal growth factor (EGF) receptor also was approved as monotherapy in patients who cannot tolerate Camptosar irinotecan from Pfizer Inc.) for its Apokyn to treat “off” episodes associated with Parkinson’s disease (PD).475. 4.. Dublin. Product: Apokyn apomorphine injection Business: Neurology FDA granted marketing approval to MYL’s Bertek Pharmaceuticals Inc. (PFE. Switzerland Product: Visudyne verteporfin Business: Ophthalmic The partners’ Visudyne received reimbursement in Japan to treat wet age-related macular degeneration (AMD). N. and Swiss approval to manufacture commercial product. Mylan Laboratories Inc.J. Business: Supply/Service The partners launched screening services for phosphatases.188. MYL expects to launch the product by July and said it must perform post-marketing studies. U. (Indianapolis.8 million in damages. Basel.683. (MYL). sales and distribution rights to Metrika’s A1cNow diabetes monitor. FDA requested additional clinical data after completing its review of NEOP’s BLA.Y. Calif. Vancouver. submitted an NDA in Japan requesting approval of Peg-Intron in combination with its Rebetol ribavirin to treat chronic HCV.S. Mass. ABI said the companies will pursue enhancement of the damages.K. Cambridge. The discovery services combine computational technologies from Inhibox and laboratory-based screening technologies from Purely Proteins. Novartis AG (NVS. patents: 4. The NDA has priority review. U. SALES & MARKETING Bristol-Myers Squibb Co. Product: Manufacturing plant Business: Cancer FDA accepted for review a CMC supplemental BLA for IMCL’s BB36 manufacturing facility (Branchburg. Ohio Product: RIGScan CR49 (125I-CC49 monoclonal antibody) Business: Diagnostic NEOP said FDA told it to run an additional Phase III trial of RIGScan for the intraoperative detection of metastatic colorectal cancer. (SGP). Kenilworth. 5.. Germany) also manufactures the drug in Europe. QLTI). Apokyn has Orphan Drug status. Waltham. OxiGene Inc. subsidiary (Research Triangle Park. Kenilworth. Roche Ltd.493.) launched in Europe its Amplicor human papillomavirus (HPV) PCRbased test kit. Berlin. U.965. If BB36 is approved.) to manufacture Erbitux for commercial use in the U.683. Purely Proteins Ltd. (TSE:QLT. ABI and ROCZ were awarded $19. and that supplies of the drug manufactured at Lonza’s facility would be used to meet initial demand. The anti-TNF alpha antibody also is approved in the U. an autologous disc cell transplant to treat disc degeneration.J.S.675. (BMY. 4.202. Sunnyvale. Business: Diagnostic BMY received exclusive U. New Brunswick. Schering-Plough Corp. 5. N. N.S. Calif. BB36 has FDA approval to manufacture Erbitux for investigational use. Oxford. N. (SGP). SWX:NOVN). Product: Peg-Intron peginterferon alfa-2b Business: Infectious SGP subsidiary Schering-Plough K.K. Metrika Inc. District Court for the District of Connecticut.333. Inhibox Ltd.don AG (FSE:CNW). (IMCL). N. Roche (SWX:ROCZ). Mass.) is a subsidiary of JNJ. Switzerland Business: Supply/Service ABI said that a jury in the U. Basel. Visudnye was approved in Japan in October 2003. Foster City.. (BMY). Erbitux was approved in combination with irinotecan to treat metastatic colorectal cancer. (OXGN. IMCL and BMY said that FDA had approved Lonza Biologics (Slough. Switzerland Business: Diagnostic ROCZ’s subsidiary Roche Diagnostics Corp.S.C. The PDUFA date for the sBLA is June 18. Centocor (Malvern. and 5. N. The kit has CE mark approval. co. Neoprobe Corp. Watertown. Product: Remicade infliximab monoclonal antibody Business: Autoimmune FDA accepted for filing Centocor’s sBLA for Remicade to treat ankylosing spondylitis. an OTC product to measure blood sugar control.).J. In February. The test detects all 13 DNA genotypes of the HPV. Johnson & Johnson (JNJ). Product: Combrestatin A4 Prodrug (CA4P) Phosphatase activated tumor vascular targeting agent Business: Cancer EMEA granted Orphan Medicinal Product designation to CA4P to treat anaplastic thyroid cancer (ATC).) will be able to meet “full commercial demand” for colorectal cancer drug Erbitux cetuximab. decided in favor of ABI and ROCZ’s Roche Molecular Diagnostics unit in a patent infringement suit against MJ Research concerning patents covering PCR and thermal cycler technologies. for the indication. Remicade is marketed in Europe by SGP.BioCentury Part II Regulatory.J. inhibit the progression of structural damage and improve physical function in patients with moderately to severely active RA who have had an inadequate response to methotrexate alone. (SWX:ROCZ). SSE:OXGN).S.

See next page MANAGEMENT TRACKS Boards of Directors Corgentech Inc. former institutional bond salesman at Goldman Sachs & Co.. Business: Infectious Promoted: Lota Zoth to SVP and CFO from VP and controller. a subsidiary of Johnson & Johnson Genencor International Inc. Business: Drug delivery Appointed: Wayne Pines. vice chairman and CEO of the Prostate Cancer Foundation. a director. U.K. (GCOR). formerly VP of business development at Galileo Pharmaceuticals Inc. and expects to begin clinical trials in 2005. Business: Endocrine. South San Francisco. Christine Dingivan to VP of clinical development and head of strategic operations from director of medical sciences. Wash.4 million) in cash at Dec. formerly district sales manager for New England at Applied Biosystems Group Avecia Ltd. formerly president of Strategic Pharmaceutical Solutions Inc. Joan Brandt to VP of corporate quality control from senior director. IDM said production of Collidem... ABI said MJ Research filed for bankruptcy protection in March. Cary.’s Leeds & Kellogg subsidiary Scolr Inc.C. Germany Business: Dermatology The company restructured and reduced its head count by 23% to 24 from 32. Calif. will begin in July. Lori Weiman to VP of corporate communications from senior director. Yonkers.. (BBII). and Gerald Stanewick. Business: Supply/Service Hired: Daniel Moore as VP of manufacturing and Avecia’s Avecia Biotechnology Inc. OSI Pharmaceuticals Inc. Immuno-Designed Molecules SA. Business: Diagnostic. The cuts will reduce its annual burn rate by 33% to less than 2 million ($2. assistant controller. N. Palo Alto. . (GTOP). Md. (EW).. CNW had 2. Michael Cowan to VP of corporate quality assurance from senior director.BioCentury Part II Other News. France Business: Cancer IDM opened in Irvine. as CEO Carolina Pharmaceuticals Inc. Genitope Corp. Business: Infectious Hired: Philip Haworth as VP of business development for health care. a therapeutic vaccine containing autologous dendritic cells loaded with peptides. N. N.M.Y. West Bridgewater. Leslie Michelson.J.. formerly SVP-international at Cordis Corp. Business: Cancer Hired: Christopher LeMasters as VP of corporate development. Bellevue. formerly senior director of research and preclinical development information systems at Amgen Inc. The first installment of $10 million has been invested. Redwood City. Mass. becomes acting CFO Take advantage of BioCentury Extra.. Calif. Beverly. Business: Neurology. Calif. Calif. formerly EVP and CFO of Incyte Corp. Bothell. Business: Cardiovascular Hired: John Alexander Martin as president of the North America region. subsidiary Bioreason Inc. Business: Cancer Hired: John Vuko as VP of finance and CFO. U.. Business: Bioinformatics Hired: Andrew DePristo as president and CEO. and Michael Sorell. (NSTK). 2004 PAGE B7 OF 13 Agencourt Bioscience Corp. The restructuring follows slower than expected market development for CNW’s tissue engineered products. APRIL 26. Business: Infectious Hired: Daniel Fisher as VP of business development. chief of press relations and associate commissioner for public affairs at FDA. Calif. Prosidion Ltd. Inflammation Hired: Per Lindell as VP of corporate development. N. and Peter Young to VP of information technology from senior director Metaphore Pharmaceuticals Inc. Business: Drug delivery Appointed: Myron Holubiak. (MEDI). Manchester. Berlin. Fort Lee. (SCLL). Paris. Business: Cardiovascular Appointed: Richard Brewer. from previous page ABI violated antitrust laws.8 million ($3. MedImmune Inc. Wash. which brings to 81% OSIP’s stake in the company. Supply/Service Hired: Richard Schumacher. The company said it has enough cash to last until 2005.. Boston Biomedica Inc.. former chief of consumer education and information. a cGMP manufacturing center dedicated to the production of its Cell Drugs for clinical trials. Business: Infectious Departed: Alan Gallantar as CFO and treasurer. 31.Y. Santa Fe. Cancer OSIP will invest a further $40 million in its majority-owned subsidiary. Melville. former president of Roche Laboratories Inc. (OSIP). Irvine. Collidem is in Phase I/II trials to treat colorectal cancer. co. formerly VP of business development at Avalon Pharmaceuticals Inc. Edwards Lifesciences Corp.). The subsidiary is developing small molecules targeting glucokinase activation and glycogen phosphorylase inhibition. Business: Genomics Hired: John Linnan as VP of sales. (ADVR). Mass. Conforma Therapeutics Corp. Gaithersburg. began in January. managing member of MS Capital Management Advanced Viral Research Corp. Martin Bookman. Autoimmune. Inc.K. (Oxford. formerly a corporate business development executive at Eli Lilly and Co. founding partner of Crest Asset Management Nastech Pharmaceutical Co. 2003. N.don AG (FSE:CNW).4 million). OSIP formed Prosidion last year in order to focus on oncology. San Diego. Calif.

Product: Eculizumab (5G1. Business: Cancer Resigning: Martha Demski as VP. professor of biological chemistry at The University of Michigan RegeneRx Biopharmaceuticals Inc. N. Calif. director of the Mario Negri Institute for Pharmacological Research. Calif. formerly CEO of Synaptica Ltd. and David Engelke. Business: Dermatology Appointed: Jo-David Fine.005). Phase Ib trial in 11 patients showed eculizumab therapy resulted in 76% fewer packed red blood cell transfusions compared to the 12 month clinical history (p=0. Bioenvision Inc.001).005). (INKP). ribonucleotide reductase Description: Second-generation nucleoside analog Indication: Treat older patients with acute myelogenous leukemia (AML) for whom chemotherapy is not suitable Endpoint: Response rate Status: Phase II data Milestone: NA Interim data from a Phase II trial of clofarabine as a first-line therapy showed 9 of 14 (64%) evaluable patients have had a complete response. Cancer Hired: Sally Waterman as director of R&D. placebo were <1. and Claudio De Simone. Results were presented at the Bristish Society of Hematology meeting in Cardiff. Conn.K. CV Therapeutics Inc. Blue Bell. Indianapolis. Inc. the study has enrolled 18 of an expected 25 patients.K. Palo Alto. professor of pediatric oncology and hematology at Emory University School of Medicine Tissera Inc. Patients showed significant improvements in several quality of life parameters. formerly director of development operations at Xenova Group plc Scancell Ltd.Y. treasurer and secretary Scientific Advisory Boards Benitec Ltd. Cheshire. U. (RGRX). U. Nottingham. . (TSSR). (ALXN). San Diego.. associate professor of experimental medicine at the University of L’Aquila Semafore Pharmaceuticals Inc. Bethesda. (TRCA). professor of surgery at the National University of Singapore Try the searchable BioCentury Archives. Penn.0 msec at 500 mg & 1000 mg doses. (BIV). Data were presented at the British Society of Hemotology meeting in Cardiff.BioCentury Part II CLINICAL NEWS Clinical activities and selected announcements for the week ended April 23. The number of paroxysm events was reduced 94% from 3. Australia Business: Functional genomics Appointed: Cy Stein. San Diego.1) Business: Hematology Molecular target: Complement 5 (C5) Description: Humanized monoclonal antibody targeting C5 Indication: Treat Paroxysmal nocturnal hemoglobinuria (PNH) Endpoint: Need for blood transfusion Status: Phase Ib data Milestone: NA Cumulative 12-month results from a previously reported openlabel. South San Francisco.K. Data were published in the Journal of the American College of Cardiology. Product: Ranexa Business: Cardiovascular Molecular target: Enoyl-CoA-hydratase Description: Partial inhibitor of enoyl-CoA-hydratase Indication: Treat chronic stable angina Endpoint: Exercise duration Status: Phase III data Milestone: NA Previously reported result from the Phase III MARISA trial in 191 angina patients showed Ranexa increased symptom-limited exercise duration (p<0. APRIL 26. Ranexa also increased the secondary endpoint of time to onset of angina pain during exercise testing and time to electrocardiographic evidence of ischemia (p<0. Business: Endocrine Hired: Thomas Silberg as COO. Sir Roy Caln. laxative effects See next page Management. Structural GenomiX Inc. formerly senior director of cancer and cardiovascular biology at Millennium Pharmaceuticals Inc. (CVTX). Ind. Business: Chemistry Hired: Neill Giese as SVP of drug development. Tercica Inc. Business: Inflammation.2 days of paroxysms/patient/month to 0. CFO. 2004 PAGE B8 OF 13 CLINICAL RESULTS Alexion Pharmaceuticals Inc. U. urology and molecular pharmacology at the Albert Einstein College of Medicine. Business: Cancer Appointed: Donald Durden. Vical Inc. professor of medicine. formerly EVP and COO of Ligand Pharmaceuticals Inc. To date. professor of dermatology at the University of Kentucky School of Medicine. Product: Clofarabine Business: Cancer Molecular target: DNA polymerase. Israel Business: Transplant Appointed: Giuseppe Remuzzi. New York. InKine Pharmaceutical Co. from previous page Protherics plc (LSE:PTI).. Business: Cancer Hired: Michael Capaldi as CEO. Macclesfield.. Md. Product: Visicol (INKP-100) Business: Gastrointestinal Molecular target: NA Description: Sodium phosphate gastrointestinal cleansing/purging agent Indication: Treat chronic functional constipation or constipationpredominant irritable bowel syndrome (IBS) Endpoint: Safety. (ASX:BLT). Tel Aviv. Mean QTc differences for Ranexa vs.001). (VICL). Queensland. Calif. Calif.2 days (p<0.

The compound is in Phase III testing in combination with pegylated interferon alpha 2b. Melbourne.BioCentury Part II Clinical Results. rF1V protected against both bubonic and pneumonic forms of plague. The trial has completed enrollment. PRNAY). ALL RIGHTS RESERVED. Frederick. No part of this publication may be photocopied or reproduced in any form.and opiate-dependence Endpoint: Safety Status: Phase III completed enrollment Milestone: Complete Phase III 1H05. President & Publisher. No patients in the 4 tablet group withdrew due to adverse events. ZymoGenetics Inc. and stool consistency when compared to baseline. Mass. N. LLC. Data were presented at the International Springfield/Montreal Symposium on Advances in Alzheimer’s Disease.) markets Peg-Intron peginterferon alfa-2b. Product: TNF alpha inhibitor Business: Infectious Molecular target: NA Description: Tumor necrosis factor (TNF) alpha inhibitor Indication: Treat HIV infection Endpoint: Safety. Both groups showed significant improvements in constipation-associated symptoms such as straining. and The Clear Route to ROI™ are trademarks of BIOCENTURY PUBLICATIONS INC. Karen Bernstein. (ASX:PBT. safety.. Australia Product: PBT-1 Business: Neurology Molecular target: Cu ion. Phase III safety study comparing once-monthly injections of Vivitrex (380 mg) to once-daily oral naltrexone (50 mg) in more than 400 alcohol. The Viramidine group had a significantly lower incidence of anemia (2% versus 24%. Zn ion Description: Small molecule that binds copper and zinc to prevent aggregation of amyloid beta Indication: Treat Alzheimer’s disease (AD) Endpoint: ADAS-Cog. serum amyloid levels Status: Phase II updated data Milestone: NA Results from a 48-week extension of a previously reported 36week Phase II trial showed that PBT-1 slowed decline in cognitive function. The longer-term treatment was well tolerated. Fax 650-595-5589. 2004 PAGE B9 OF 13 of Viramidine (400 mg. Alkermes Inc. Phase I study in 9 lumbar spinal surgery patients. All contents © Copyright 2004.S.. Prana Biotechnology Ltd. U. Phone 650-595-5333. Basel. Woodland Hills. During the last week of therapy (week 4) all patients in the 4 tablet group responded and 92% of those in the 8 tablet group responded. (ZGEN). the same proportion as those receiving ribavirin and peginterferon alfa-2a. 4 patients withdrew from the study due to non-serious adverse events. U. Calif. 88% responded to Visicol treatment during the first week. Calif. PO Box 1246 San Carlos CA 94070-1246. twice daily) were comparable to ribavirin 1000 or 1200 mg/day. David Flores. cramping. Phase IV trial in 40 evaluable patients. Phase II trial in 180 treatment-naïve patients showed 83% of those given Viramidine plus peginterferon alfa-2a had ≥2 log10 reduction or had non-detectable HCV RNA at 24 weeks. p<0. bloating. Product: rhThrombin Business: Hematology Molecular target: NA Description: Recombinant human thrombin Indication: Control blood loss during surgery Endpoint: Safety Status: Phase I data Milestone: Phase I data 2H04 In an ongoing. viral load. Patients received either a single 4 tablet dose or an 8 tablet regimen. . BIOCENTURY PUBLICATIONS INC.001). with 4 tablets dosed twice over 15 minutes. from previous page Status: Phase IV data Milestone: NA In a dose-ranging. Product: Viramidine Business: Infectious Molecular target: NA Description: Ribavirin prodrug Indication: Treat hepatitis C virus (HCV) Endpoint: HCV RNA levels Status: Phase II data Milestone: NA Interim results from an open-label. In the 8 tablet group.S. submit NDA 1H05 ALKS completed enrollment in an open-label. PRECLINICAL RESULTS DynPort Vaccine Co. INKP intends to use doses of 2-4 tablets in the future. (MYGN).S. increase in CD4 count Status: Phase I started Milestone: Phase I data 2004 ADVB started an open-label.J. Product: rF1V Indication: Prevent Yersinia infection DynPort said that in mice. (ALKS). The Bernstein Report on BioBusiness®. All 3 tested doses APRIL 26. Utah Product: MPC-4505 Indication: Treat chemotherapy-induced nausea and vomiting MYGN said that in a monkey model. Switzerland) markets Pegasys peginterferon alfa-2a.and opiate-depenSee next page BioCentury Part II BioCentury Part II is published by BIOCENTURY PUBLICATIONS INC. New Brunswick. Wash. MPC-4505 achieved significant blood levels and had peak blood levels about 4 hours after oral dosing. or stored in a retrieval system without prior written consent of the publisher. 600 mg and 800 mg. Seattle. Md.D. (ADVB). Cambridge. U. Myriad Genetics Inc. CLINICAL STATUS Advanced Biotherapy Inc. ZGEN said instances of hemostatic response with rhThrombin were observed. Costa Mesa. Salt Lake City. open-label. U. Phase I trial in about 10 patients who are in virologic failure. Valeant Pharmaceuticals International (VRX). retransmitted. Roche (SWX:ROCZ. Product: Vivitrex Business: Neurology Molecular target: Opioid receptors Description: Injectable sustained-release formulation of naltrexone in polylactide co-glycolide polymer microspheres Indication: Treat alcohol. Ph. Chairman & Editor-in-Chief BioCentury®.S. The BioCentury 100™. while Schering-Plough (SGP. Data were presented at the European Association for the Study of the Liver conference in Berlin.

overall survival. (CRGN). The trial will measure 2 oral doses of alagebrium (35 mg daily or 210 mg twice daily) for a total of 24 weeks. Texas Product: Campath alemtuzumab Business: Autoimmune APRIL 26.K. Phase II trial of INGN’s Advexin to treat about 60 patients who will receive Advexin at the time of surgery. Austin. Cambridge. placebo-controlled Phase II trial of INS37217 as first-line therapy in about 160 patients. Ilex Oncology Inc. Product: INS37217 Business: Ophthalmic Molecular target: P2Y(2) receptor Description: Second-generation P2Y(2) agonist Indication: Treat rhegmatogenous retinal detachment Endpoint: Surgery-free retinal attachment Status: Phase II started Milestone: Phase II data 2005 ISPH began a U. (GENZ.. open-label Phase II trial comparing Campath to Rebif interferon beta1a from from Serono SA (SWX:SEO. Product: CG53135 Business: Other Molecular target: NA Description: Human fibroblast growth factor 20 (FGF-20) Indication: Treat oral mucositis in patients undergoing bone marrow transplantation Endpoint: Safety. double-blind. New Haven. corticotropin-releasing factor (CRF2) receptor Description: Synthetic human CRF Indication: Treat peritumoral cerebral edema associated with brain tumors Endpoint: 50% reduction in steroid use at 3 weeks Status: Phase III started Milestone: NA NTII began a U. SRA. Product: Xerecept Business: Cancer Molecular target: Corticotropin-releasing factor (CRF1) receptor. quality of life as measured by Minnesota Living with Heart Failure questionnaire Status: Phase II started Milestone: NA ALT began a U. The protocol allows for up to 2 more injections of INS37217 in patients showing signs of improvement after the first intravitreal injection. Alteon Inc. (CTIC.S. Calif.S. NTII said it will start a second Phase III trial this summer in 120 steroid-naïve patients who will be given either Xerecept or dexamethasone. Product: R112 Business: Inflammation Molecular target: Syk See next page . (ISPH). pilot trial in about 45 patients. Woburn. Mass. Neurobiological Technologies Inc. antitumor activity Status: Phase I/II started Milestone: NA CTI started an international. (RIGL). Introgen Therapeutics Inc.S. Conn. ILEX is being acquired by Genzyme Corp. Wash. South San Francisco. open-label Phase II trial in 20 patients. (INGN). Ramsey. U. ALKS said an interim safety analysis will be complete in about 6 months. overall response rate Status: Phase II started Milestone: NA The Southwest Oncology Group began a U.J. response Status: Phase I started Milestone: Start Phase II 2004 CRGN started an open-label. N.). Both pivotal trials have been given a Special Protocol Assessment by FDA. Cell Therapeutics Inc. Phase I study in 15 cancer patients. Seattle. Product: CT-2106 Business: Cancer Molecular target: Topoisomerase I Description: Camptothecin topoisomerase I inhibitor attached to polyglutamate polymer Indication: Treat colorectal cancer Endpoint: Maximum tolerated dose. from previous page dent patients. (ANIK).BioCentury Part II Clinical Status. CuraGen Corp. NMerc:CTIC). and Canadian Phase III trial in about 200 patients who are taking high doses of dexamethasone. open-label Phase I/II trial of CT-2106 plus 5-fluorouracil/folinic acid in about 45 patients with metastatic colorectal cancer who have failed front-line therapy with oxaliplatin. Product: Incert-S Business: Musculoskeletal Molecular target: NA Description: Bioabsorbable. Patients will then receive chemotherapy and radiation. (NTII).C. 2004 PAGE B10 OF 13 Molecular target: CD52 Description: Humanized monoclonal antibody against CD52 Indication: Treat previously untreated relapsing/remitting multiple sclerosis (MS) Endpoint: Time to sustained accumulative disability (SAD) Status: Phase II completed enrollment Milestone: NA ILXO completed enrollment of 240 patients in an international. Texas Product: Advexin (INGN 201) Business: Cancer Molecular target: NA Description: Adenovirus p53 tumor suppressor gene therapy (Ad5CMVp53) Indication: Treat stage III or IV squamous cell carcinoma of the oral cavity Endpoint: Progression-free survival. Calif. Mass. chemically modified hylauronic acid Indication: Prevent internal adhesions and scarring following spinal surgery Endpoint: NA Status: Pilot trial started Milestone: NA ANIK began a U..S. (ALT). Rigel Pharmaceuticals Inc. Inspire Pharmaceuticals Inc. Anika Therapeutics Inc. (ILXO). N. Richmond. Geneva. safety.S. Durham. Switzerland). San Antonio. Product: Alagebrium (ALT-711) Business: Cardiovascular Molecular target: Advanced glycosylation endproduct (AGE) Description: AGE crosslink breaker Indication: Treat diastolic dysfunction in patients with grade II-IV heart failure Endpoint: Quantification of left ventricular mass and diastolic function as measured by Doppler evaluation.

ZGEN said it plans to start this quarter 3 other identical studies in patients undergoing lumbar spine surgery. OTHER RESEARCH NEWS Agrobiogen GmbH. The antibody. showed antitumor activity in culture. Product: rhThrombin Business: Hematology Molecular target: NA Description: Recombinant human thrombin Indication: Control blood loss during surgery Endpoint: Safety as measured by immunogenicity. development and sustainability of life science ventures in 2005 and beyond. Munich. from previous page Description: Nasal spray Syk kinase inhibitor that inhibits mast cell activation Indication: Treat allergic rhinitis Endpoint: Change from baseline in global symptom score. SWX:NOVN). Icon Genetics AG. NOVN markets Gleevec imatinib to treat CML. curcumin restored the nasal membrane potential. Vivus Inc. Yale University. time to onset of effect.). In the model of B-ALL. Wash. Switzerland.. Xenome Ltd. ZGEN expects to complete all 4 Phase II studies this year. Conn. Product: r38M bispecific single-chain antibody Use: Treat cancer Researchers published in the Proceedings of the National Academy of Sciences the production of a bispecific single-chain antibody in the serum of transgenic rabbits and cattle. Also. Australia Product: Xen2174 Business: Neurology Molecular target: Norepinephrine transporter Description: Synthetic peptide modeled on a peptide isolated from the venom of the marine coneshell Indication: Treat severe cancer pain Endpoint: Safety Status: IND filed Milestone: Start Phase I 06/04 Xenome filed an IND to begin a placebo-controlled Phase I trial in 4 groups of 5 healthy volunteers. and a 28day follow-up test for antibodies against rhThrombin. ZymoGenetics Inc. Basel. Germany. Hilgertshausen. placebo-controlled Phase II trial in 300 patients who have had seasonal allergic rhinitis during the spring pollen season for at least 2 years. But finding real intelligence is a lot harder. et al. (VVUS). Calif. (ZGEN). U. 2004 PAGE B11 OF 13 Status: Phase II started Milestone: Complete Phase II 2004 ZGEN started a double-blind. but did not significantly increase survival in a mouse model of chronic myelogenous leukemia (CML). The endpoints in all 4 studies includes safety. the Bernstein Report on BioBusiness® for its leading perspective on the strategic issues essential to the formation. Phase II study in 40 patients undergoing liver resection. crossover Phase II trial in about 250 patients. time-to-hemostasis.S. the compound promoted the accumulation of the mature CFTR protein in cells grown in culture.. Seattle. lower extremity peripheral artery bypass surgery. Mountain View. rhThrombin antibodies at 28 days APRIL 26. Product: Curcumin Use: Treat cystic fibrosis (CF) Researchers published in Science that in a mouse model of CF. Brisbane. et al. designated r28M. New Haven. U. Product: CGP76030 Src kinase inhibitor Use: Treat leukemia Researchers published in Nature Genetics that CGP76030 increased survival compared to control in a mouse model of B cell acute lymphoblastic leukemia (B-ALL). Yale has licensed the technology to Seer Pharmaceuticals LLC (Southport. at-home. safety Status: Phase II started Milestone: Phase II data 2H04 RIGL began an outdoor. Phase II data 1H05 VVUS began a U. Conn. and for the formation of vascular access grafts for dialysis. time-to-hemostasis.S. Germany Product: Bacterial expression system Use: Biomanufacturing Researchers published in the Proceedings of the National Academy of Sciences the development of a system that uses bacteria to deliver protein expression vectors to plants. Novartis AG (NVS.. Product: Avanafil (TA-1790) Business: Genitourinary Molecular target: Phosphodiesterase-5 (PDE-5) Description: Fast-acting oral PDE-5 inhibitor Indication: Treat erectile dysfunction (ED) Endpoint: Optimal dose range Status: Phase II started Milestone: Complete enrollment Phase II 2004. The search for intelligent life We know you have many choices for headlines.S. ‘It’s the BioCentury’TM . That’s why top managers and investors in the life sciences community depend on BioCentury. double-blind. animals given CGP76030 plus imatinib survived longer than animals receiving monotherapy with either agent. et al.BioCentury Part II Clinical Status. placebo-controlled.

(ICRA). Great Point Partners Note: Investors also received warrants to purchase an additional 16.3 million Shares: To be determined Price: To be determined Shares after offering: To be determined Underwriters: Deutsche Bank. UBS.1610. Fletcher Spaght.J.75 Shares after offering: 13.1 million shares at $10 Completed Offerings Bruker BioSciences Corp.C. Mass.6 million Investors: Alexandra Investment Management.. Integrated Biopharma Inc. 2004 PAGE B12 OF 13 convertible into common shares at $10. Abingworth. These shareholders are offering an additional 1. (Proposed:AUXL). bringing to $40.1 million Note: Existing shareholders may purchase 3 shares for every share held Other Financial News Array BioPharma Inc. Business: Diagnostic. New York.6 million) Shares: 12.000 shares at $7 to cover over-allotments from its IPO earlier this month.3 million Shares: 41 million Price: $0. including common stock. Shares after offering refers to shares outstanding. (SPPI). Mass.40.. Chemistry Date announced: 4/22/04 ARRY filed a shelf registration covering the sale of up to $70 million of securities. Perceptive Life Sciences Fund.BioCentury Part II OFFERINGS & SECURITIES TRANSACTIONS Week ended 4/23/04.5 million Shares: 3 million Price: $4.7427.6 million shares outstanding. Horsholm. A. Boulder. Montvale.000 Note: In conjunction with the follow-on. Business: Cancer. Business: Supply/Service Date announced: 4/22/04 Type: IPO To be raised: Up to $115 million Shares: To be determined Price: To be determined Shares after offering: To be determined Underwriters: Merrill Lynch.25 Shares after offering: 29. Business: Microfluidics Date announced: 4/15/04 BioTrove raised $2. Denmark Business: Cancer. HealthCare Ventures.J. Business: Supply/Service. Gastrointestinal Date completed: 4/19/04 Type: Venture financing Raised: $50 million Investors: Schroder Ventures.5 million Price: $10.000 Shares after offering: 10.7967 Dynogen Pharmaceuticals Inc. CB Health Ventures. N. ARRY. preferred stock and warrants.000 common shares at $14.2 million Price: $7.4 million shares at $0.6 million Underwriter: NA Shares outstanding prior: 10.3 million through the sale of 750. Investors also received warrants to purchase an additional 425.5 million worth of debentures into shares. Business: Cancer. (INB). U.2 million Note: Investors also received 1year warrants to purchase up to an additional 1. bringing to $19 million the total amount raised in the series B round. Business: Cancer. Atlas Venture. which closed Friday at $9.8 million shares to cover overallotments. (MEMY). £=$1. BioScience VCT.25 Shares after offering: 88. N.3 million the total raised in the offering. CIBC World Markets. Generics Date completed: 4/21/04 Type: Private placement of common stock and warrants Raised: $25 million Shares: 3. Memory Pharmaceuticals Corp.2 million Placement agent: Punk Ziegel DxS Ltd. Oxford Bioscience Partners. Manchester.1990.4 million Placement agent: SCO Securities Investors: Biotechnology Value Fund. East Norriton. Computational chemistry/biology Date completed: 4/23/04 Type: Follow-on Raised: $13.8 million Shares: 2. Zero Stage Capital. Business: Neurology Date completed: 4/19/04 Type: Private placement of common stock and warrants Raised: $10.50 Shares after offering: 89 million Underwriters: Bear Stearns. SG Cowen Overallotment: 450. Needham Overallotment: To be determined ‘It’s the BioCentury’TM .15. High throughput screening Date completed: 4/19/04 Type: Venture financing Raised: £10 million ($18 million) Investors: Northern Venture Managers. Callisto Pharmaceuticals Inc. Spectrum Pharmaceuticals Inc. Irvine.Y. British Smaller Technology Companies VCT2. (ARRY). N. North West Business Investment Scheme Pharmexa A/S (CSE:PHARMX). Neurology Date announced: 4/21/04 Type: IPO To be raised: $86. and BioFrontier Partners. Hillside. and other investors Note: The series B convertible shares have a 7% dividend and are APRIL 26.K.3 million Underwriter: ING Investment Banking Shares outstanding prior: 4.M. Investors included Catalyst Health and Technology Partners.. Inflammation. Thomas Weisel Partners Nanosys Inc. Currency rates used in the week: C$=US$0. New York. Business: Metabolic. Musculoskeletal Date completed: 4/19/04 Type: Private placement Raised: $4. DKK=$0. (BRKR). Business: Genitourinary. has 28. N. not net. Proteomics. (Proposed:NNSY). 4 selling shareholders sold 12 million BRKR shares in a secondary offering.2 million Price: $2. Lehman. Medica Holdings. Shares offered don’t include overallotments.8 million in a second tranche of a January financing. Echelon Ventures. BioTrove Inc. Research Triangle Park. Pappas & Associates Incara Pharmaceuticals Corp. Along with the offering. (CLSP). ICRA announced that Goodnow Capital LLC converted its remaining $2. Autoimmune Date announced: 4/20/04 Type: Rights offering To be raised: DKK209 million ($33. Investors may purchase an additional 425 series B convertible preferred shares and related warrants over the next 18 months. See next page Proposed Offerings Auxilium Inc. Calif. Proceeds are gross. Colo. Boston.Y. Mass. Wellcome Trust. Business: Cancer Date completed: 4/21/04 Type: Private placement of convertible preferred stock and warrants Raised: $8. Woburn. Penn. N. Business: Neurology Date announced: 4/20/04 MEMY raised an additional $5. Piper Jaffray. =$1. Billerica.

Calif. including R112. MEDI reported first quarter EPS of $0. (LEXG). Alberta Business: Transplant.” He said the stock is fairly valued and expects that GILD will have to increase R&D and SG&A expenses in order to improve its top line via new drugs.50 and $1.99. Gilead Sciences Inc. GILD closed Friday at $60. Thousand Oaks.63.65. Business: Autoimmune Needham analyst Mark Monane began coverage with a “buy” rating and a $33 price target. SG Cowen. N. Autoimmune Dundee Securities analyst David Martin lowered his price target to C$2. WR Hambrecht analyst Jason Kantor said GILD’s increased guidance is conservative. Deutsche Bank analyst Dennis Harp raised his 2004 and 2005 EPS estimates to $1.38 and $1. (IVGN).04 billion and $2.K. ImClone Systems Inc. Calif.66 billion. The agency had a partial hold on the compound.88 and $1. Edmonton. SG Cowen analyst Eric Schmidt began coverage and expects the company to turn profitable this year. AGEN closed Friday at $9. RIGL closed Friday at $21. The company also raised its sales guidance for HIV drug Viread and antifungal Ambisome.44. and Fortis. Lexicon Genetics Inc.03 better than the consensus estimate of $0. Carlsbad. plus a strong presence at ASCO. Foster City. On Wednesday. Business: Biopharmaceuticals Deutsche Bank analyst Dennis Harp raised his 2004 EPS estimate to $2. He expects the company to turn APRIL 26.BioCentury Part II ANALYST PICKS & CHANGES Amgen Inc. South San Francisco. Md. The Woodlands.53 from $0. N.84. (IMCL).06.45. On Tuesday. bringing to C$3 million the total raised in the offering. Infectious Needham & Co.02.24 billion and $1. IVGN raised its revenue and EPS guidance to $1. beating the Street estimate by a penny and up 36% from EPS of $0. are likely to propel the stock. is in Phase II studies to treat neuropathic pain.27 billion and $1.Y. Business: Neurology Nomura analyst Sam Fazeli began coverage with a “buy” rating.50-$0. Genomics WR Hambrecht analyst Jason Kantor began coverage with a “buy” rating and a $10 price target. (TSE:ISA).30.12.9p.88. Last week. The trans isomer version of ISA247 is in Phase I dose-ranging trials for renal transplant and psoriasis.31. Business: Cancer. U. CeNeS Pharmaceuticals plc (LSE:CEN). 2004 PAGE B13 OF 13 profitable next year on strong sales of colorectal cancer antibody Ertibux cetuximab. Texas Business: Functional genomics.74. CEN closed Friday at 11.6 million shares at C$0. He expects 2004 Viread sales of $809 million versus the company’s new guidance of $725-$775 million. Calif. (GILD). Invitrogen Corp. overallotments from a March private placement.60.50.57.2 billion. AMGN reported first quarter adjusted EPS of $0. (RIGL).55 and $1.38 from $2. IVGN closed Friday at $74. the reagent and tool supplier reported first quarter pro forma EPS of $0. He said a value driver for the company will be partnerships for its clinical compounds.2 million shares outstanding. Business: Cancer WR Hambrecht analyst Jason Kantor began coverage with a “buy” rating and an $83 price target.60. Banc of America Securi- ties. MedImmune Inc. MEMY has 20. ISA closed Friday at C$2. His 2004 and 2005 EPS estimates are $0. MIVT has 43. a glutamate receptor NMDA ion channel blocker. (AGEN).95. Cambridge. Other Financial News. restoring development rights to ISA and giving ROCZ an option to assume development after the start of Phase II transplantation trials. Product sales were $2. (AMGN). Vancouver.84 and $1. New York.11. up 35% from $1. On Tuesday. Schmidt said potential upside to sales estimates of Erbitux. and CNS 5161. (MEDI). the company said that FDA is still seeking additional product characterization for its Oncophage cancer vaccine to treat renal cell carcinoma (RCC). IMCL closed Friday at $70.6 billion in the first quarter of 2003. MIV Therapeutics Inc. Calif. British Columbia Business: Cardiovascular Date announced: 4/21/04 MIVT raised an additional C$700. Business: Supply/Service Pacific Growth analyst Adam Chazan raised his 2004 EPS and revenue estimates to $2. ISA and Roche (SWX:ROCZ.22.68 billion from $1. .Y. beating the Street’s $0.50 in 2004 and to $0. Cancer Deutsche Bank analyst Dennis Harp raised his EPS estimates to $0. Last week.36. Business: Infectious.01 billion.42 in the same period last year.03 billion from $2.52 in 2005 based on first quarter 2004 results and company guidance. Isotechnika Inc. AMGN closed Friday at $58.000 through the sale of 1. Basel. analyst Mark Monane lowered his rating to “hold” from “buy” because of a lack of near-term drivers. which was $0. Business: Infectious Leerink Swann analyst William Tanner raised his 2004 and 2005 revenue estimates to $1. beating Street expectations by $0. but lifted it last November. New York. For the full year. LEXG closed Friday $7. an intranasal mast cell activation inhibitor that is in Phase II testing for allergic rhinitis. Rigel Pharmaceuticals Inc. respectively.2 million shares outstanding. (MIVT). Fazeli expects positive news flow from these two compounds to drive the stock in the next 6-12 months. Ducan Capital LLC served as the placement agent. Antigenics Inc. Legg Mason analyst Edward Nash lowered his rating to “hold” from “buy. Kantor expects new partnerships to be the primary driver for the stock over the next 12 months.44 to cover BioCentury Extra: Online every business day. GILD reported first quarter non-GAAP EPS of $0.96 from $1. Switzerland) renegotiated a 2002 co-development deal for ISA247. The company reiterated 2004 EPS guidance of $0. Gaithersburg. CEN has two products in development: M6G morphine-6-glucuronide is in Phase III testing to treat post-operative pain.34 estimate by $0. Last week. MEDI closed Friday at $23. from previous page Underwriters included UBS.52 from $0.