May 6, 2013

Howard Liang, Ph.D.

(617) 918-4857 Howard.Liang@Leerink.com

Rene Shen Reason for report:

(212) 277-6074 Rene.Shen@Leerink.com

PROPRIETARY - SURVEY

Gena Wang, Ph.D.

(212) 277-6073 Gena.Wang@Leerink.com

BIOTECHNOLOGY
Prostate Cancer Survey Finds Robust Uptake of New Hormonal Agents

Bottom Line: MEDACorp conducted a survey of 50 US urologists and oncologists (25 in each specialty) with a majority of them practicing in the community setting. The survey suggests significant use of Xtandi (MDVN [OP]/Astellas) in the pre-chemo setting already and a near-term sales trajectory that appears to be ahead of expectations. For DNDN's (MP) Provenge, the survey suggests declining use since the end of 2012. In aggregate, survey respondents manage twice as many prechemo castration-resistant prostate cancer (CRPC) patients as postchemo patients. Together with a longer treatment duration (expected to be 2x), the survey results suggest that the pre-chemo market is likely several times as big as the post-chemo market. Survey finds a substantial increase of Zytiga and Xtandi of 41% and 80%, respectively, from Dec. 2012 to March 2013. The magnitude of increase in Zytiga use matches the sequential sales growth reported for Zytiga. For both drugs, the growth was mainly driven by pre-chemo use and by urologists. Both Zytiga and Xtandi are projected to grow substantially through the rest of 2013, by 84% and 167%, respectively, relative to March 2013, indicating that the market is by no means saturated. By physician projections, the number of patients on Xtandi will have nearly caught up with Zytiga by the end of 2013. A little over half of current Xtandi patients had previously received Zytiga, although this differed significantly between oncologists and urologists, with the latter group having a much lower proportion of Xtandi patients post-Zytiga (28% vs. 70%) that also declined in the last 3 months (from 44% to 28%). Most physicians in both specialties treat to progression, although nearly a quarter (24%) of urologists indicated that in post-Zytiga patients Xtandi would be continued post-progression. Majority of survey respondents consider the efficacy and safety/ tolerability profiles of Zytiga and Xtandi to be similar in the postchemo setting. Differences in perception by urologists and oncologists may be explained in part by the limited promotion of Xtandi to date to urologists. Assuming PREVAIL demonstrates a statistically significant overall survival (OS) benefit, one-year after presumed Xtandi approval in the pre-chemo setting, Xtandi is projected to overtake Zytiga with a 43% market share in the first-line metastatic setting vs. 34% for Zytiga. If Xtandi shows only an OS trend, these shares would reverse. Survey respondents report declining use of Provenge since December 2012. However, Provenge usage is projected to rebound with robust growth by the end of 2013. Although many respondents indicated declining use of Provenge after Zytiga pre-chemo approval and Xtandi launch, interestingly this appears to mainly affect the casual users and to have limited impact on existing heavy users.

S&P 500 Health Care Index:

552.34

Companies Highlighted:

DNDN, JNJ, MDVN

Please refer to pages 28 - 31 for Important Disclosures, Price Charts and Analyst Certification.

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May 6, 2013

SURVEY DEMOGRAPHICS
Our survey sample consists of both urologists and medical oncologists with a majority of them practicing in the community setting. On our behalf, MEDACorp conducted a survey of 25 oncologists and 25 urologists to assess market dynamics in the treatment of castrate resistant prostate cancer (CRPC). The survey was fielded and followed up from April 5 to April 29, 2013. In order to get a respondent cohort that is experienced in treating CRPC, physicians had to treat at least 30 metastatic castration-resistant prostate cancer patients personally over the past 12 months. The survey respondents are composed of 14 physicians (28%) from the academic medical centers, 6 physicians (12%) from community hospitals, 1 physician (2%) from a VA hospital, 27 physicians (54%) from private practice and 2 physicians (4%) from a clinic. Practice settings were similar for oncologists and urologists in our survey. Survey Question: What best describes your primary practice setting?
All respondents (n=50) Academic medical center Community hospital VA hospital Private practice Clinic Other 28% 12% 2% 54% 4% 0% Oncologists (n= 25) 28% 12% 4% 52% 4% 0% Urologists (n=25) 28% 12% 0% 56% 4% 0%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

PRE- AND POST-CHEMOTHERAPY MARKETS

As expected, urologists treat a population with earlier stage disease. The surveyed physicians treat 248 prostate cancer patients on average for a total of >12,000 patients. Of CRPC patients, oncologists see 50 patients on average, while urologists see 63 patients on average, though the median is closer, at 40 and 43, respectively. Oncologists see a higher number of metastatic patients as a percentage of their overall prostate cancer practice at 53% on average vs. 16% for urologists, reflecting a generally earlier stage population seen by urologists. . Survey Question: How many prostate cancer patients do you personally manage currently?
Prostate cancer patients Total (n=50) Oncologist (n=25) Urologist (n=25) Mean 248 94 402 Median 155 80 450 Total 12,396 2,346 10,050 Mean 56 50 63 CRPC patients Median 42 40 43 Total 2,804 1,241 1,563 CRPC as % of overall Prostate Cancer Pts Mean Median Total 22.6% 26.8% 22.6% 52.9% 50.0% 52.9% 15.6% 9.6% 15.6%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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In aggregate, physicians manage approximately twice as many patients in the pre-chemo setting as in the post-chemo setting, with urologists seeing nearly 3 times as many. When we break out the CRPC population into the 1st line metastatic (or pre-chemo), currently undergoing treatment with 1st line chemotherapy, and post-chemo population we find that oncologists have a higher percentage of patients (vs. urologists) in the latter two categories. On average, oncologists are treating 20 patients in the pre-chemo setting, 16 patients in the 1st line chemo setting and 14 patients in the post-chemo setting. Urologists have 36 patients in the pre-chemo setting, 13 in the 1st line chemo setting and 13 patients in the post-chemo setting on average. For urologists, 58% of their CRPC patients are in the pre-chemo setting compared with 40% for oncologists. In the post-chemo setting, oncologists have 29% of their patients fitting this criteria compared with 21% for urologists. This highlights the change in prescriber base that occurs as medications such as Zytiga and eventually Xtandi move from the post-chemo to the pre-chemo space. Survey Question: How many of your castration-resistant prostate cancer (CRPC) patients are in the following categories?
# of patients by line of therapy Mean Pre-Chemo 1st Line Chemo Post-Chemo Total 28 15 14 Oncologists 20 16 14 Urologists 36 13 13 % of patients by line of therapy Pre-Chemo 1st Line Chemo Post-Chemo 50% 26% 24% 40% 32% 29% 58% 22% 21%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

ZYTIGA, XTANDI UTILIZATION TRENDS

Survey respondents, especially urologists, report a substantial increase in their use of both Zytiga and Xtandi from December 2012 to March 2013. Though urologists on average had fewer patients on Zytiga or Xtandi in December, they increased their usage of these agents by 76% and 209%, respectively, in 1Q:13. Oncologists also increased their usage of the two agents, though by a more modest percentage (18-36%). In aggregate, the average number of patients receiving Zytiga increased from 5.6 at the end of December 2012 to 7.9 at the end of March, representing a 41% increase. The average number of patients receiving Xtandi in our survey sample increased from 2.5 at the end of December 2012 to 4.6 at the end of March, corresponding to an 80% increase. JNJ (OP) reported a 41% revenue increase sequentially for US Zytiga sales in the 1Q:13, equal to the 41% reported by our survey respondents. However, there were inventory adjustments in the 4Q:12 for Zytiga sales that impacted the comparison. IMS script data had only a 14% increase sequentially. Furthermore, as the urologists and oncologists reported drastically different growth rates for Zytiga in our survey, the mix of specialty will be an important factor when determining the growth rate.

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May 6, 2013

Mean Total (n=50) Oncologists (n=25) Urologists (n=25)

Dec-12 # on Zytiga # on Xtandi Total Pre-chemo Post-chemo Total Pre-chemo Post-chemo Post-Zytiga 5.6 2.6 3.0 2.5 0.7 1.8 1.6 6.7 3.2 3.6 3.8 0.9 2.9 2.6 4.4 2.0 2.4 1.3 0.5 0.8 0.6

Mar-13 # on Zytiga Total Pre-chemo Post-chemo 7.9 4.8 3.0 8.0 4.7 3.3 7.8 5.0 2.8 Total 4.6 5.2 4.0 # on Xtandi Pre-chemo Post-chemo Post-Zytiga 1.9 2.6 2.4 1.3 3.9 3.6 2.6 1.4 1.1

% Increase Total (n=50) Oncologists (n=25) Urologists (n=25)

% Increase from Dec 2012 to Mar 2013 # on Zytiga # on Xtandi Total Pre-chemo Post-chemo Total Pre-chemo Post-chemo Post-Zytiga 41% 88% 1% 80% 174% 43% 51% 18% 48% -8% 36% 39% 35% 41% 76% 150% 15% 209% 433% 75% 100%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Dec-12 # on Zytiga # on Xtandi Mean Pre-chemo Post-chemo Pre-chemo Post-chemo Post-Zytiga Total (n=50) 46% 54% 28% 72% 61% Oncologists (n=25) 47% 53% 24% 76% 67% Urologists (n=25) 45% 55% 38% 63% 44% Mar-13 # on Zytiga # on Xtandi Pre-chemo Post-chemo Pre-chemo Post-chemo Post-Zytiga 62% 38% 42% 58% 52% 59% 41% 25% 75% 70% 64% 36% 65% 35% 28%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Zytiga (reported) Zytiga (survey: total) Zytiga (survey: oncologists) Zytiga (survey: urologists) Zytiga (IMS)

1Q:13 vs. 4Q:12 growth rate 41% 41% 18% 76% 14%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Overall use of both Zytiga and Xtandi saw substantial increase in the pre-chemo setting while post-chemo use held steady or had a more modest increase. In the pre-chemo setting, the average number of patients increased from 2.6 for each respondent in December 2012 to 3.9 in March 2013 (+50%), following the FDA approval in this setting in December 2012. Although Xtandi has not yet been approved for pre-chemo use and in fact has not yet reported Phase III data in this setting, the increase for Xtandi in the pre-chemo setting was more dramatic on a relative basis, from 0.7 to 1.9 patients per physician over the same period. In the post-chemo setting, Zytiga use held steady (average of 3.0 patients per respondent at the end of both December and March) and Xtandi use continued to increase from 1.8 to 2.6 patients per respondent. Therefore, for both products, there was more growth, on an absolute basis, in the pre-chemo setting as compared to post-chemo setting. For Zytiga, as of the end of December 2012, pre-chemo patients represented slightly less than half (46%) of the patients prescribed Zytiga by our survey respondents and this increased to 62% at the end of March due to growth in the pre-chemo patients. For Xtandi, the percentage of pre-chemo patients as a percent of total Xtandi patients increased from 28% to 42% over the same period. By physician specialty, increased pre-chemo use is predominantly driven by urologists. Oncologists had 48% more patients on Zytiga in the pre-chemo setting in March than in December. The increase in Xtandi is relatively modest from 0.9 patients on average to 1.3 patients on average. The increase for Zytiga was more pronounced but similar on a percentage basis from 3.2 to 4.7 patients over the same period. Urologists use more Xtandi and Zytiga than

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oncologists in the pre-chemo setting. On average, urologists in the survey had 5 patients on Zytiga and 2.6 patients on Xtandi in March of 2013, compared with 4.7 and 1.3 for oncologists. Urologists drove increased use of Zytiga and Xtandi in the pre-chemo setting both on a relative and absolute basis.

Oncologists Usage of Zytiga and Xtandi in the Pre-Chemo Setting

5.0 4.0 +48%

Mean number 3.0 of patients 2.0 treated 1.0 0.0 Dec 2012 Mar 2013
Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Zytiga Xtandi +39%

Urologists Usage of Zytiga and Xtandi in the Pre-Chemo Setting

6.0 5.0 4.0 Mean number of patients 3.0 treated 2.0 1.0 0.0 Dec 2012 Mar 2013
Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

+150%

Zytia

+433%

Xtandi

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In aggregate, a little over half of Xtandi patients had previously received Zytiga, but this differed significantly between oncologists and urologists. As of March 2013, approximately 52% of patients receiving Xtandi had previously received Zytiga and this declined somewhat from 61% three months prior in December 2012. There is a notable difference between specialties, and post-Zytiga patients represented 70% of Xtandi patients for oncologists but only 28% for urologists. We did not specifically ask whether post-Zytiga patients are also post-chemo, but based on our conversations with MEDACorp physicians, we believe that there is some use of Xtandi ahead of chemo in patients who progressed on Zytiga.

Total (n=50) Oncologists (n=25) Urologists (n=25)

% of Xtandi Usage in the Post-Chemo Setting Post-Zytiga Setting Dec-12 Mar-13 Dec-12 Mar-13 72% 58% 61% 52% 76% 75% 67% 70% 63% 35% 44% 28%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

The overall number of patients on Zytiga and Xtandi is expected to be significantly higher by the end of 2013. For Zytiga, a greater than 80% increase in patients is expected between March 2013 and December 2013. For Xtandi, the increase is even more steep, a >150% increase in patient numbers, albeit from a lower base. Thus the relative market share of Zytiga to Xtandi across all of CRPC was 63%/37% in our survey as of March 2013, but is expected to be 54%/46% by the end of 2013.

Mean Number of Patients on Zytiga and Xtandi

18.0 16.0 14.0 12.0

# of Patients on Treatment

10.0 Total (n=50)

8.0 6.0 Oncologists (n=25) Urologists (n=25)

4.0
2.0 0.0 Dec-12 Mar-13 Zytiga Dec-13 Dec-12 Mar-13 Xtandi Dec-13

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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% Increase in Projected Patients from Mar to Dec 2013 Total (n=50) Oncologists (n=25) Urologists (n=25) Zytiga 83.7% 94.0% 73.2% Xtandi 166.7% 158.9% 176.8%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Total (n=50) Oncologists (n=25) Urologists (n=25)

Xtandi Market Share* Dec-12 Mar-13 Dec-13 31.4% 36.7% 45.7% 36.1% 39.3% 46.4% 22.5% 33.8% 44.9%

*Market share is defined as Xandi patients as a percentage of patients on Xtandi and Zytiga.
Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Most oncologists continue patients on Zytiga until progression; however, more urologists are willing to continue treatment past progression. In our survey, oncologists indicated that they treated with Zytiga until PSA or radiographic progression in most cases, with 16% willing to treat post progression as long as it was well tolerated by the patient. Urologists were more willing to continue treatment post progression, with 32% using this criteria, but 16% would stop treatment upon a rise in PSA. Survey Question: Please explain how you decide when to discontinue Zytiga treatment in the post-chemotherapy setting assuming tolerability is not limiting?
Continue treatment post-progression as long as the patient can tolerate it Treat to radiographic progression Treat to PSA progression Treat until PSA starts to rise Other: both PSA progression and ragiographic progression (1x) Oncologists 16% 36% 48% 0% 0% Urologists 32% 16% 32% 16% 4%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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The practice of continuing Xtandi beyond progression appears relatively uncommon. Since a substantial portion of current Xtandi use is in post-Zytiga patients, the duration of Xtandi could be expected to be relatively short as current data suggest that both drugs are much less effective in patients who had prior hormonal treatment such as ketoconazole. Anecdotally some physicians have indicated that they continue the patient on drug post-progression, and we were interested in how common this practice is. Based on our survey, treating beyond progression is relatively uncommon among oncologists (8% in our survey) and appeared more common among urologists but still represent less than a quarter of the surveyed urologists. Survey Question: If you have used or plan to use Xtandi in patients who were previously treated with Zytiga, please explain how you decide when to discontinue Xtandi treatment in these patients assuming tolerability is not limiting.
Continue treatment post-progression as long as the patient can tolerate it Treat to PSA progression Treat until PSA starts to rise Treat to radiographic progression I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga Other: both symptomatic radiographic progression and PSA progression (x1), not sure (x1) Oncologists 8% 48% 4% 36% 4% 0% Urologists 24% 16% 24% 8% 20% 8%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

The approval of Xtandi has an effect on the decision of when to stop treatment with Zytiga for 30% of the physicians in the survey. Overall, 30% of physicians indicated that they had changed their criteria on when to discontinue Zytiga treatment following the availability of Xtandi. It is likely that at least in some cases patients are no longer continued on Zytiga post-progression but switched to Xtandi instead. Most comments indicated that this was due to the availability of another agent that could demonstrate additional efficacy or be better tolerated in certain patients. Survey Question: Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the post-chemotherapy setting?

Yes
Total survey respondents (N=50) 30%

No
70%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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PHYSICIAN PERCEPTION ABOUT ZYTIGA AND XTANDI

More than 50% of respondents considered the efficacy and safety of Xtandi and Zytiga to be similar in the post-chemotherapy setting, although it is possible that the difference between oncologist and urologist perceptions may reflect the early stage of marketing efforts for Xtandi. This result was true for both oncologists and urologists in our survey. Only 1 or 2 of the 50 respondents considered there to be a meaningful differences in safety or efficacy between Xtandi and Zytiga. If we consider the difference in percentage of respondents that believe that Zytiga is better than Xtandi, we see that the percentage of oncologists that consider Zytiga to have better efficacy than Xtandi is approximately equal to the percentage that consider it to have worse efficacy. However, on safety, we see that 36% of oncologists (9/26) believe that Xtandi has better safety and tolerability than Zytiga, but only 4% (or 1 oncologist) believed the inverse is true. In contrast, urologists consider the safety and tolerability of Xtandi to be similar to Zytiga, but 28% consider Zytiga to have superior efficacy while only 8% consider Xtandi to be more efficacious. As Xtandi is only approved for the post-chemo setting, MDVN and partner Astellas have had limited presence in the urologist setting, therefore it is possible that the gap in physician perception between the specialties may have been contributed to by the stage of commercial promotion. Survey Question: Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the post-chemotherapy setting.
Post-chemo
Survey categories Zytiga meaningfully better than Xtanti Zytiga modestly better than Xtandi Zytiga and Xtandi are about the same Xtandi modestly better than Zytiga Xtandi meaningfully better than Zytiga Unable to rate due to lack of data and experience Oncologists Safety, Efficacy tolerability and convenience 4.0% 0.0% 16.0% 4.0% 64.0% 60.0% 12.0% 28.0% 4.0% 8.0% 0.0% 0.0% Oncologists Safety, Efficacy tolerability and convenience 20.0% 4.0% 64.0% 60.0% 16.0% 36.0% 0.0% 0.0% 4.00% -32.00% Urologists Efficacy 8.0% 20.0% 56.0% 8.0% 0.0% 8.0% Safety, tolerability and convenience 8.0% 16.0% 52.0% 16.0% 4.0% 4.0% Urologists Efficacy 28.0% 56.0% 8.0% 8.0% 20.00% Safety, tolerability and convenience 24.0% 52.0% 20.0% 4.0% 4.00%

Regrouping of categories Zytiga better Zytiga similar to Xtandi Xtandi better Unable to rate % considering Zytiga b etter minus Xtandi b etter

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Likely due to lack of Phase III data for Xtandi, urologists view the efficacy and safety of Zytiga to be superior to Xtandi in the pre-chemo setting while oncologists consider Zytiga to be better on efficacy but worse on safety/tolerability. In the pre-chemo setting, 12% of oncologists and 16% of urologists were unable to respond to the question due to lack of data and experience. Urologists experienced with both agents considered the safety and efficacy of Zytiga

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to be better than Xtandi, though 44% considered the two agents to be similar. While more oncologists considered the efficacy of Zytiga to be superior to Xtandi, a higher percentage viewed Xtandi to have the better safety and tolerability profile in the pre-chemo setting. We believe these impressions of the relative profiles of these agents will likely change upon the release of the Phase III PREVAIL results for Xtandi in the pre-chemo setting and once the Xtandi marketing team can promote the agent for the pre-chemo setting. Survey Question: Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the pre-chemotherapy setting.
Pre-chemo
Survey categories Zytiga meaningfully better than Xtanti Zytiga modestly better than Xtandi Zytiga and Xtandi are about the same Xtandi modestly better than Zytiga Xtandi meaningfully better than Zytiga Unable to rate due to lack of data and experience Oncologists Safety, Efficacy tolerability and convenience 16.0% 4.0% 28.0% 8.0% 20.0% 44.0% 20.0% 24.0% 4.0% 8.0% 12.0% 12.0% Oncologists Safety, Efficacy tolerability and convenience 44.0% 12.0% 20.0% 44.0% 24.0% 32.0% 12.0% 12.0% 20.00% -20.00% Urologists Efficacy 8.0% 28.0% 44.0% 4.0% 0.0% 16.0% Safety, tolerability and convenience 4.0% 28.0% 44.0% 4.0% 0.0% 16.0% Urologists Efficacy 36.0% 44.0% 4.0% 16.0% 32.00% Safety, tolerability and convenience 32.0% 44.0% 4.0% 16.0% 28.00%

Regrouping of categories Zytiga better Zytiga similar to Xtandi Xtandi better Unable to rate % considering Zytiga b etter minus Xtandi b etter

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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Lack of statistically significant OS benefit for Xtandi in PREVAIL is projected to lead to a less than 10% decline in market share over the scenario with only an OS trend, although this would correspond to a 20%+ loss on a relative basis. One year after presumed Xtandi approval in the pre-chemo setting, assuming PREVAIL shows a statistically significant overall survival benefit, Xtandi is projected to overtake Zytiga with a 43% market share as the first-line treatment for metastatic prostate cancer compared to 34% for Zytiga. If Xtandi shows a nonstatistically significant overall survival trend, these market share projections would reverse (34% for Xtandi vs. 44% for Zytiga). We believe this reflects physicians impressions that Zytiga does confer an OS benefit and that the agents are similar in efficacy and safety/tolerability in the postchemotherapy setting. Chemotherapy will still be appropriate for a minority of patients even with the new oral agents. Chemotherapy will continue to hold market share in the 1st line metastatic CRPC with ~23% of patients expected to receive these agents. A MEDACorp key opinion leader explained that for some patients with visceral metastases or aggressive tumor -- about 20% of the patients in this setting by his estimate -- it is appropriate to give chemotherapy first to attempt to control the disease before giving a hormonal agent. Generic Zytiga is projected to have a negative impact on Xtandi, but it appears to take more share from chemotherapy. Xtandi will lose market share once Zytiga is generic; however, there will still be substantial usage of Xtandi in 28% of the patients in our survey. With generic Zytiga, chemotherapy usage in frontline metastatic CRPC expected to fall from 23% to 14%. This would appear to indicate that the high cost of the oral hormonal agents may be another reason why chemotherapy is used as the first agent in metastatic prostate cancer patients. Survey Question: If both Zytiga and Provenge are approved in the pre-chemotherapy/1st line metastatic setting, how do you see your market share usage of the two agents in this setting?
One year after Xtandi pre-chemo approval, if Xtandi demonstrates statistically significant OS Oncologists Zytiga 1st line market share Xtandi 1st line market share Chemo 1st line market share Urologists Zytiga 1st line market share Xtandi 1st line market share Chemo 1st line market share 35% 44% 21% 34% 42% 25% One year after Xtandi prechemo approval, if Xtandi Once Zytiga is generic demonstrates non-statistically significant OS 46% 36% 18% 41% 31% 28% 53% 30% 17% 63% 27% 10%

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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The vast majority of physicians across both medical specialties would prefer to use the other hormonal agent first prior to chemotherapy after progression on 1 st line therapy. Many physicians cited the better tolerability of Xtandi and Zytiga over chemotherapy as their reason for sequencing the two agents prior to cytotoxic therapy. Survey Question: Do you anticipate using the alternate agent (Zytiga or Xtandi) once a patient progresses on 1st line therapy? Or would you prefer to use chemotherapy upon progression?
Yes, use alternative agent if patient progresses 76% 76% No, use chemotherapy upon progression 24% 24%

Oncologists (n=25) Urologists (n=25)

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

SEIZURE CASES ON XTANDI

More oncologists than urologists have prescribed Xtandi. For the 25 oncologists in our survey, only 8% (2/25) had not yet prescribed Xtandi, and one of those was looking to prescribe the agent to the appropriate patient. On the urology side, more than half of the survey respondents (13/25) had no clinical experience with Xtandi. Reasons for not having prescribed Xtandi spanned a range of responses, but reimbursement and not yet identifying an appropriate patient were common. Survey Question: Have you prescribed Xtandi? No, please explain.
Oncologists Urologists 92% 48% 8% 52% No clinical situation yet for use No candidates identified yet Reimb ursement issues Too expensive
I am not comfortab le. not covered with insurance Have not had approved yet Have preferred Zytiga I have one patient currently on Xtandi that was prescrib ed b y Medical Oncologist patient's can not afford post chemo Xtandi not yet not yet availab le on formulary Oncology shared patient plan to plan to in future

Yes No Reasons for not prescribing Xtandi

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

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For physicians prescribing Xtandi, urologists and oncologists had similar numbers of patients on drug. Of the 35 respondents who had prescribed Xtandi, on average they had prescribed the drug to 7-8 patients and the results were similar for oncologists and urologists. In total, there were 265 patients prescribed Xtandi under the care of physicians in our survey.

Oncologists (n=23) Urologists (n=12) Total (n=35)

Xtandi Patients Mean Median Total 7.7 5.0 178 7.3 5.0 87 7.6 5.0 265

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

There were a total of 4 patients with seizures in our survey. Two physicians had each seen two patient seizures after prescribing Xtandi. Both physicians indicated that these seizures had changed their willingness to prescribe Xtandi. We note that 4 seizures in 265 total Xtandi patients yield a 1.5% incidence rate, similar to the 0.9% rate listed in the FDA label.

PROVENGE UTILIZATION TRENDS

Survey respondents report declining use of Provenge since December 2012. We inquired about Provenge usage for the respondents. On average, each physician only treated 1-2 patients per month, thus we aggregated the number of patients by specialty. We see that the number of patients treated per month declined in January and February by 16% in each month compared to the previous month, but stabilized in March (1% decline month-over-month) for both urologists and oncologists. The average monthly number of patients treated with Provenge in 1Q:13 declined by 25% compared to December 2012, and the number of patients receiving Provenge in the last month of 1Q:13 (March) vs. 4Q:12 (December) declined by 30%. On an individual doctor basis, 18% of the survey respondents reported an increase in the average monthly Provenge volume in 1Q:13 vs. December 2012, 22% reported no change, but the majority (60%) reported a decline. This distribution is essentially identical for urologists and oncologists, therefore our survey did not detect a gain of Provenge among urologists during 1Q. Potential contributors to the Provenge volume decline may include the effect of Medicare and private insurance co-pay resetting at the beginning of the year, and Zytiga pre-chemo approval in December and the Xtandi launch in September and compendium listing in December. While it is difficult to tease out the contribution of each, continued decline from January to February leads us to believe that the decline is not only due to reimbursement resetting, and increased use of oral hormonal agents had an impact.

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Total Number of Provenge Treatments by Specialty

120 100 Total Number of 80 Provenge Patients 60 Treated 40 20 0 Dec-12 Total Oncologists (n=25) Urologists (n=25) Dec-12 112 58 54 Jan-13 Jan-13 94 49 45 Feb-13 Feb-13 79 43 36 Mar-13 Mar-13 78 44 34

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

However, Provenge usage is projected to rebound, with a robust 73% growth in patient numbers for 4Q:13 compared with 1Q:13. Below we see a table with the monthly usage of Provenge from December 2012 to March 2013 as well as the projected usage in 4Q:13. Across both urologists and oncologists, there is a marked increase expected in Provenge usage. The vast majority of urologists in our survey (76%) expect to increase Provenge prescribing in 4Q:13 compared with 1Q:13. Similarly, 56% of oncologists expected an increase in prescribing. Only 8% of respondents in both specialties expected to decrease their Provenge prescribing. Relative to Dec. 2012 levels, total number of patients on Provenge in our survey sample is projected to increase by 34% in Dec. 2013, and this is relatively consistent between urologists and oncologists. On an individual prescriber basis, we see that there is a wide range of Provenge usage. A few physicians are projecting very high usage in December 2013, while many physicians are projecting no usage of Provenge at the end of December 2013.
Dec-12 # of Provenge Patients Total Oncologists (n=25) Urologists (n=25) % change Dec 12 to Dec 13 Total (n=50) Oncologists (n=25) Urologists (n=25) % change for 1Q:13 to 4Q:13 Total (n=50) Oncologists (n=25) Urologists (n=25)
Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Jan-13 94 49 45

Feb-13 79 43 36

Mar-13 78 44 34

Oct-13 142 75 67

Nov-13 142 75 67

Dec-13 150 80 70

112 58 54

34% 38% 30%

73% 69% 77%

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% of Respondents by Expected Change in Provenge Prescribing from 1Q to 4Q 2013 Increase No Change Decrease 66% 26% 8% 56% 36% 8% 76% 16% 8%

Total Oncologists Urologists

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Reported Provenge Pateints in Dec 2012

Projected Provenge Pateints in Dec 2013

30 25 20
# of Provenge Patients

30 25 20
# of Provenge Patients

15 10 5 0
Oncologists Urologists

15 10 5 0
Oncologists Urologists

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

From the change in projected Provenge usage by current use in Provenge, we see that the increase in usage is across a wide spectrum of prescribing physicians. Some physicians who are not prescribing Provenge currently intend to start prescribing the agent. Of the 27 physicians who had not prescribed Provenge in March 2013, 15 expected to prescribe the agent in December 2013. Furthermore, the most active users also intend to increase their prescribing. Only a couple of the current users expected their prescribing to decrease by year-end 2013. We do not fully understand the reason for the projected increased use of Provenge by the end of 2013, considering that Provenge has been approved for 3 years and its sales trajectory has been relatively flat.

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Change in Expected Number of Provenge Patients by Current Patients Treated

12

10

6
Projected Change in Provenge Patients in December 2013 4

Change in Number of Patients

0 0 2 4 6 8 10 12 14 16 18

-2

# of Provenge Patients Treated in March 2013

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Although many respondents indicated declining usage of Provenge after Zytiga pre-chemo approval and Xtandi post-chemo approval, this appears to mainly affect the casual users and to have limited impact on existing heavy users. When we examine the users of Provenge (who had prescribe the agent to at least 1 patient during March 2013), we see that the highest prescribers expect no effect from the recent label expansion of Zytiga or the Xtandi approval. However, users who only infuse 1 patient a month are more likely to decrease their usage of Provenge due to the availability of new agents.

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Survey Question: How has your usage of Provenge changed with the Zytiga pre-chemo approval and the Xtandi post-chemo approval?
# Provenge Pts Comments March 2013
16 14 6 5 5 it has not changed significantly so far. It has stayed relatively the same. I have used it less b ecause of more options. no. use of provenge has remained constant since more men b eing treated with one of three therapies, where in past chemotherapy was only option not much as i still use provenge No fifteenth rationale No. It remains foundational therapy It hasn't. less provenge use. provenge is lab or intensive to utilize

Usage Change No change No change Less No change No change No change No change No change No change No change

Specialty Oncologist Urologist Oncologist Oncologist Urologist Oncologist Oncologist Urologist Urologist Urologist

4 3 3 3 3 2 2 2 1 1 1 1 1 1 1 1 1 1

PROVENGE WILL BE USED IN BIOCHEMICAL FAILURE No WITH CASTRATE RESISTANT change Oncologist no, will still use provenge first No change Oncologist No i use provenge first No change Urologist slightly less use as Zytiga easier to arrange Less Oncologist have had prob lems with steroid use with ab iraterone Less Oncologist I reduced the use of Provenge Less Oncologist Decreased use of provenge Less Oncologist No change, the indications are separate No change Oncologist no change No change Oncologist decrease use of provenge since zytiga is oral Less Urologist I will not go up due to cost of Zytiga Less Urologist n/a No change Urologist Diminished. Much less complicated with Zytiga Less Urologist

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

Despite Xtandis lack of prednisone co-administration, physicians do not consider its approval as a positive for Provenge usage. However, for the vast majority of prescribers, they expect no change in usage from the approval of Xtandi in the pre-chemo setting. A few prescribers do expect less usage of Provenge due to another agent being available, while only a couple of physicians expect to increase usage of Provenge due to the lack co-administration of prednisone with Xtandi.

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Survey Question: Will your usage of Provenge change as a result of the approval of Xtandi in pre-chemo patients (which does not require co-administration of prednisone)? Please explain:
# Provenge Pts March 2013
16 14 6 5 5

Comments
It has not changed so far. It may. I will have to wait for more data b efore changing usage of provenge Yes, similar to reason ab ove. no use of provenge to remain same as more men now b eing treated for CRPC. not needing prednisone is nice b ut not significant enought to influence therapies. no No will not No. It remains foundational therapy It will not. less provenge use for same reasons ab ove NO. I AM USING PROVENGE ONLY IN A ELECTED GROUP OF PATIENTS no, will still use provenge first in all appropriate pts Yes more use if no prednisone not sure b ut possib ly will use with xtandi It is already minimal. If the patient requests Provenge it will b e fine. Decreased use of Provenge No change, the indications are separate no change same No. Prefer Zytiga yes b etter tolerance Yes. Provenge is more complicated to my practice routine.

Usage Change No Unclear Less No No No No No No Less No No Increase Unclear No No Less No No No No Increase Less

Specialty Oncologist Urologist Oncologist Oncologist Urologist Oncologist Oncologist Urologist Urologist Urologist Oncologist Oncologist Urologist Oncologist Oncologist Oncologist Oncologist Oncologist Oncologist Urologist Urologist Urologist Urologist

4 3 3 3 3 2 2 2 1 1 1 1 1 1 1 1 1 1

Source: MEDACorp survey, Treatment of Prostate Cancer, April 2013

MEDACorp performed this survey on behalf of a Leerink Swann LLC analyst. The analyst in conjunction with MEDACorp developed the questions contained in the survey.

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TREATMENT OF PROSTATE CANCER

Respondent Distribution Specialty Trend Number of Respondents Respondent Distribution Survey Date Oncology and Urology Prostate Cancer 25 Oncologists and 25 Urologists United States April 2013 Geographic Distribution
Source: Google Maps

Responses represent an average of the aggregate responses (n=50) unless otherwise noted. Inclusion Criteria Screener 1: How many metastatic castration-resistant prostate cancer patients have you personally managed over the past 12 months? Mean Number of metastatic castration-resistant prostate cancer patients I personally managed over the past 12 months Screener 2: What is your medical specialty? 50.0% 50.0% 0.0% Survey Questions 1. Which best describes your primary practice setting? 28.0% 12.0% 2.0% 54.0% 4.0% 0.0% 2. Academic medical center Community hospital VA hospital Private practice Clinic Other Oncologists Urologists Other 82.4 Median 50 Sum 4,121

How many prostate cancer patients do you personally manage currently? Of these, how many are castration-resistant prostate cancer (CRPC) patients? Mean Total number of prostate cancer patients that you personally manage Castration-resistant prostate cancer (CRPC) 247.9 56.1 Median 155 42 Sum 12,396 2,804

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How many of your castration-resistant prostate cancer (CRPC) patients are in the following categories? Mean Metastatic castration-resistant prostate cancer (mCRPC) before receiving chemotherapy mCRPC currently receiving first-line chemotherapy mCRPC after first-line chemotherapy 27.7 14.6 13.5 Median 21 10 10 Sum 1,384 729 676

How many of the patients you personally managed were treated with Provenge during the following time periods? Mean December 2012 January 2013 February 2013 March 2013 2.2 1.9 1.6 1.6 Median 1 1 1 0 Sum 112 94 79 78

How many of the patients you personally managed were treated with Zytiga and Xtandi at the end of December 2012 and at the end of March 2013, respectively? At the end of December 2012 Mean Number of patients receiving Zytiga Of patients receiving Zytiga, how many patients had already received chemotherapy? Number of patients receiving Xtandi Of patients receiving Xtandi, how many patients had already received chemotherapy? Of patients receiving Xtandi, how many patients had already received Zytiga? At the end of March 2013 Mean Number of patients receiving Zytiga Of patients receiving Zytiga, how many patients had already received chemotherapy? Number of patients receiving Xtandi Of patients receiving Xtandi, how many patients had already received chemotherapy? Of patients receiving Xtandi, how many patients had already received Zytiga? 7.9 3.0 4.6 2.6 2.4 Median 5 3 2 2 2 Sum 393 151 228 132 118 5.6 3.0 2.5 1.8 1.6 Median 4 2 1 1 1 Sum 278 149 127 92 78

Please project the number of patients on Provenge during the following time periods: Mean October 2013 November 2013 December 2013 Please project the number of patients on Zytiga and Xtandi at the end of 2013. Mean Number of patients receiving Zytiga Number of patients receiving Xtandi 14.4 12.2 Median 10 9 Sum 722 608 2.8 2.8 3.0 Median 2 2 2 Sum 142 142 150

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3.

Please explain how you decide when to discontinue Zytiga treatment in the post-chemotherapy setting assuming tolerability is not limiting? 26.0% 40.0% 8.0% 24.0% 0.0% 2.0% Treat to radiographic progression Treat to PSA progression Treat until PSA starts to rise Continue treatment post-progression as long as the patient can tolerate it I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga Other: both PSA progression and radiographic progression (1x)

4.

Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the postchemotherapy setting? 30.0% 70.0% Yes No

Please explain. See Appendix for a summary of responses 5. If you have used or plan to use Xtandi in patients who were previously treated with Zytiga, please explain how you decide when to discontinue Xtandi treatment in these patients assuming tolerability is not limiting. 22.0% 32.0% 14.0% 16.0% 12.0% 4.0% 6. Treat to radiographic progression Treat to PSA progression Treat until PSA starts to rise Continue treatment post-progression as long as the patient can tolerate it I have not used or do not plan to use Xtandi in patients who were previously treated with Zytiga Other: both symptomatic radiographic progression and PSA progression (1x)

Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the postchemotherapy setting. Efficacy Zytiga meaningfully better than Xtanti Zytiga modestly better than Xtandi Zytiga and Xtandi are about the same Xtandi modestly better than Zytiga Xtandi meaningfully better than Zytiga Unable to rate due to lack of data and experience 6.0% 18.0% 60.0% 10.0% 2.0% 4.0% Safety, tolerability and convenience 4.0% 10.0% 56.0% 22.0% 6.0% 2.0%

Please indicate your perception of the relative efficacy and safety / tolerability / convenience of Zytiga and Xtandi in the prechemotherapy setting. Efficacy Zytiga meaningfully better than Xtanti Zytiga modestly better than Xtandi Zytiga and Xtandi are about the same Xtandi modestly better than Zytiga Xtandi meaningfully better than Zytiga Unable to rate due to lack of data and experience 12.0% 28.0% 32.0% 12.0% 2.0% 14.0% Safety, tolerability and convenience 4.0% 14.0% 42.0% 18.0% 8.0% 14.0%

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7.

Have you prescribed Xtandi? 70.0% 30.0% Yes No: See Appendix

How many patients have you prescribed Xtandi to in any setting? (n=35) Mean Number of patients to whom youve personally prescribed Xtandi to in any setting Have you seen a case of seizure in patients receiving Xtandi? (n=35) 5.7% 94.3% Yes No 7.6 Median 5 Sum 265

How many patients have had seizures after receiving Xtandi? (n=2) Mean Number of patients who have had seizures while receiving Xtandi Has this experience changed your willingness to prescribe Xtandi? (n=2) 100.0% 0.0% 8. Yes No 2.0 Median 2 Sum 4

If both Zytiga and Provenge are approved in the pre-chemotherapy/1st line metastatic setting, how do you see your market share usage of the two agents in this setting? One year after Xtandi prechemo approval, if Xtandi demonstrates statistically significant OS Zytiga 1st line market share Xtandi 1st line market share Chemotherapy 34.2% 42.8% 23.0% One year after Xtandi prechemo approval if Xtandi demonstrates nonstatistically significant OS trend 43.7% 33.5% 22.8%
st

Once Zytiga is generic

58.0% 28.1% 13.9%

9.

Do you anticipate using the alternate agent (Zytiga or Xtandi) once a patient progresses on 1 line therapy? Or would you prefer to use chemotherapy upon progression? 76.0% 24.0% Yes, prefer to use alternate agent if patient progresses on 1 line therapy No, prefer to use chemotherapy upon progression
st

Please explain: See Appendix for a summary of responses 10. How has your usage of Provenge changed with the Zytiga pre-chemo approval and the Xtandi post-chemo approval? Please explain: See Appendix for a summary of responses 11. Will your usage of Provenge change as a result of the approval of Xtandi in pre-chemo patients (which does not require coadministration of prednisone)? Please explain: See Appendix for a summary of responses

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Appendix: Summary of responses. Question 4: Has the approval of Xtandi in the post-chemotherapy setting changed when you stop treatment with Zytiga in the postchemotherapy setting? Please explain. 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 46 47 48 49 50 No, PFS benefits seen with both. Generally go to Xtandi prior to Jevtana Still have chemotherapy in between prior to using Xtandi Use Zytiga until response ends and then move to Xtandi I still treat till clinical or radiographic progression I use Xtandi after Zytiga Approval of Xtandi is for chemotherapy failures so use or no[ne] use of Zytiga should not be an issue Has influenced no change No impact of one over the other I generally do not stop Zytiga for Xtandi I use Zytiga until it is no longer clinically helpful for the patient. Xtandi after Zytiga No. PSA doubling in 3 months or less would be a clear indication for change. Otherwise 2 consecutive progressions 3 months apart. Decrease its use in favor of Xtandi Use less I have been using Zytiga in pre chemo setting My pattern of treatment remains the same due to expense of Xtandi Still treat to PSA progression One more agent available to treat patients after they fail Zytiga Still treat to progression or toxicity I have more Zytiga experience Additional option now available. Will still treat to PSA progression I switch to Xtandi on PSA progression Dont think that will make a difference. I imagine both will be approved pre and/or post chemo. Has not changed current practice No, I continue to use Zytiga in the post chemotherapy setting despite the approval of Xtandi. I am using more Zytiga in pre-chemotherapy setting however. Proceeding with recommendations from medical oncology here Has not changed as far as I am aware. I still use Zytiga as first line Rx Have not used Xtandi yet Quicker to switch It has had no impact Would be more apt to switch from Zytiga to Xtandi after PSA progression Yes. We have had some responders that have failed or progressed on Zytiga No effect Difficult for patient to afford out of pocket Xtandi, Xtandi is more expensive than Zytiga Easier use of this class of med. Adrenal sparing Not sure about latest change I would still use. No clear superiority of one agent over the other Can continue Zytiga No bearing on when to stop Zytiga Adverse reaction About to start using Xtandi. No experience thus far Zytiga end-point is determined by clinical response Cost prohibitive to patient

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Question 7: Have you prescribed Xtandi? No, please explain 8 23 28 30 31 32 33 35 36 39 41 43 44 45 48 No clinical situation yet for use Too expensive No candidates identified yet Reimbursement issues I am not comfortable. Not covered with insurance Have not had approved yet Have preferred Zytiga I have one patient currently on Xtandi that was prescribed by Medical Oncologist Patients cannot afford post chemo Xtandi Not yet Not yet available on formulary Oncology shared patient Plan to Plan to in future
st

Question 9: Do you anticipate using the alternate agent (Zytiga or Xtandi) once a patient progresses on 1 line therapy? Or would you prefer to use chemotherapy upon progression? 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 I would switch back to cytotoxic chemotherapy. Depends on many circumstances however to include pace of disease Different mechanism of action To avoid chemotherapy As most patients dont want chemo. Especially for visceral disease It will be up to the patient to decide They work by different mechanisms so patients will ultimately see both drugs most of the time Seems like it would be better tolerated Would like to maximize hormonal tx just like in breast cancer, prior to starting chemo Both Zytiga and Xtandi has shown efficacy Prefer oral medications whenever possible. Patients prefer pills to chemo I considered and still consider to use either Zytiga or Xtandi. We (oncologists) in this case I always use another hormonal agent after first line hormonal failure Would need data showing that one can do it. Dont think its different I prefer to keep chemo last. Toxicity issue If a patient has no response or short response to Zytiga or Xtandi , I would want a proven survival benefit with chemotherapy to give to appropriate patients It depends on rapidity or aggressiveness of disease Options available come handy to treat Want to delay chemo as long as possible It depends on PS Other chemotherapy has demonstrated some efficacy on progressed tumors. The alternate agent can be considered in the future with additional trial results proving their superior efficacy. Better side effect profile More tolerable Would be able to manage patients myself this way as opposed to referral to Med Onc. No data yet to help guide this situation - unable to answer If patients fail Zytiga or Xtandi, they will have better disease free survival if they are started on chemotherapy Might not need oncology right away Too many medications with toxicity, I don't want to use it unless approved and am comfortable with. I may add hi dose ketoconazole, avodart and consider chemotherapy

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33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

Better other before chemo Less toxicity Have seen benefits from chemo I believe these oral agents are preferable to chemo from convenience and toxicity standpoint. Cost remains a significant concern. In conjunction with med onc, would prefer to delay chemo rx as long as possible Less side effects Will use Zytiga, more affordable, better reduction in PSA Yes I believe hormonal manipulation early handsome benefits I understand that some of these agents are/were not approved before first line chemo in prostate cancer patients. I like to use these agents wherever the indications are. Chemo better. Less toxic side effects and better tolerability and compliance NCCN guidelines before change Consider other options Limit chemotherapy toxicity, ease of administration Depends on the patient, a shift to chemotherapy happens very rarely (less than 1%) but can happen. Otherwise, would rather the alternate agent. Zytiga is much well tolerated than chemo and easier to administer Less toxic. Treatment in my hands, rather than oncologist Continue to monitor the patient.

Question 10: How has your usage of Provenge changed with the Zytiga pre-chemo approval and the Xtandi post-chemo approval? 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 I have used it less because of more options. Slightly less use as Zytiga easier to arrange Have had problems with steroid use with abiraterone Using it less Not much as I still use Provenge About the same I reduced the use of Provenge Still use Provenge for minimally symptomatic patients No Decreased use of Provenge It has not changed significantly so far. It has not changed, since I do not use it. Dont use Provenge No change Much deceased No real rationale, just practice patterns. I have been using less and less of Provenge with Zytiga approval. I do use it in biochemical failure prostate cancer with minimal bone disease or no appreciable metastatic disease in selected group of patients. None No change, the indications are separate No change Decreased No, will still use Provenge first Didn't change No. Don't use Provenge. Less Provenge use down. No change - I believe Provenge should be used in many patients before Xtandi and Zytiga Use of Provenge has remained constant since more men being treated with one of three therapies, where in past chemotherapy was only option No

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31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 48 49 50 19 20 21 22 23 24 25 26

I have not used Provenge yet. Decrease use of Provenge since Zytiga is oral No I use Provenge first No. It remains foundational therapy I will not go up due to cost of Zytiga I don't use much Provenge although our cancer center is a recently approved site. Our patients still have to travel a considerable distance for the apheresis. I believe it still has a role in managing CRPC but will probably use more now for those patients who have failed Zytiga/Xtandi and prior to chemo. Decreased Stopped Yes, use Provenge first, and then Zytiga, only Xtandi if patient can pay out of pocket Not much do not believe in usefulness Yes It hasn't. Decrease use of Provenge Earlier use of Zytiga Decrease No change. Do not use Less Provenge use. Provenge is labor intensive to utilize Diminished. Much less complicated with Zytiga It has stayed relatively the same. I have used it less because of more options. Slightly less use as Zytiga easier to arrange Have had problems with steroid use with abiraterone Using it less Not much as I still use Provenge About the same I reduced the use of Provenge Still use Provenge for minimally symptomatic patients

Question 11: Will your usage of Provenge change as a result of the approval of Xtandi in pre-chemo patients (which does not require co-administration of prednisone)? Please explain: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Yes, similar to reason above. Not sure but possibly Will use with Xtandi Will increase AFTER maximal endocrine therapy No No It is already minimal. If the patient requests Provenge it will be fine. No will use in low symptom patient No Decreased use of Provenge It has not changed so far. No. Dont use Provenge No change Yes, decrease No will not No. I am using Provenge only in a selected group of patients Less use No change, the indications are separate No change Yes, decreased further No, will still use Provenge first in all appropriate patients No

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24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 19 20 21 22 23 24 25 26

No No Moderately. Probably remain the same. Zytiga already approved pre chemo. No change - I believe Provenge should be used in many patients before Xtandi and Zytiga Use of Provenge to remain same as more men now being treated for CRPC. Not needing prednisone is nice but not significant enough to influence therapies. Possibly less I havent used Provenge yet Same Yes more use if bo prednisone No. It remains foundational therapy No. Prefer Zytiga See above answer. Will use Xtandi more after developing castrate resistance, especially since don't need prednisone, prior to using Provenge or chemo. Would also delay referral to Med Onc if using Xtandi first. Yes it will decrease because these pts have better performance status earlier in the disease stage and they would have been candidate for Provenge but will now likely try Xtandi first Limit it Yes, will use Xtandi, definitely a benefit not to have to use prednisone No still not using it much It will go down It will not. May decrease No Yes No. Do not use Yes better tolerance Less Provenge use for same reasons above Yes. Provenge is more complicated to my practice routine. It may. I will have to wait for more data before changing usage of Provenge Yes, similar to reason above. Not sure but possibly Will use with Xtandi Will increase AFTER maximal endocrine therapy No No It is already minimal. If the patient requests Provenge it will be fine. No will use in low symptom patient

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Disclosures Appendix Analyst Certification

I, Howard Liang, Ph.D., certify that the views expressed in this report accurately reflect my views and that no part of my compensation was, is, or will be directly related to the specific recommendation or views contained in this report.

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Distribution of Ratings/Investment Banking Services (IB) as of 03/31/13 IB Serv./Past 12 Mos. Rating BUY [OP] HOLD [MP] SELL [UP] Count 107 68 0 Percent 61.14 38.86 0.00 Count 32 0 0 Percent 29.91 0.00 0.00

Explanation of Ratings
Outperform (Buy): We expect this stock to outperform its benchmark over the next 12 months. Market Perform (Hold/Neutral): We expect this stock to perform in line with its benchmark over the next 12 months. Underperform (Sell): We expect this stock to underperform its benchmark over the next 12 months.The degree of outperformance or underperformance required to warrant an Outperform or an Underperform rating should be commensurate with the risk profile of the company. For the purposes of these definitions the relevant benchmark will be the S&P 600 Health Care Index for issuers with a market capitalization of less than $2 billion and the S&P 500 Health Care Index for issuers with a market capitalization over $2 billion. From October 1, 2006 through January 8, 2009, the relevant benchmarks for the above definitions were the Russell 2000 Health Care Index for issuers with a market capitalization of less than $2 billion and the S&P 500 Health Care Index for issuers with a market capitalization over $2 billion. Definitions of Leerink Swann Ratings prior to October 1, 2006 are shown below: Outperform (Buy): We expect this stock to outperform its benchmark by more than 10 percentage points over the next 12 months. Market Perform (Hold/Neutral): We expect this stock to perform within a range of plus or minus 10 percentage points of its benchmark over the next 12 months. Underperform (Sell): We expect this stock to underperform its benchmark by more than 10 percentage points over the next 12 months. For the purposes of these definitions, the relevant benchmark were the Russell 2000 Health Care Index for issuers with a market capitalization of less than $2 billion and the S&P 500 Index for issuers with a market capitalization over $2 billion.

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Leerink Swann LLC Equity Research

Director of Equity Research John L. Sullivan, CFA (617) 918-4875 (617) 918-4544 (617) 918-4875 (617) 918-4544 (617) 918-4857 (617) 918-4575 (415) 905-7221 (617) 918-4588 (415) 905-7256
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john.sullivan@leerink.com alice.avanian@leerink.com john.sullivan@leerink.com alice.avanian@leerink.com howard.liang@leerink.com joseph.schwartz@leerink.com marko.kozul@leerink.com michael.schmidt@leerink.com irene.lau@leerink.com rene.shen@leerink.com gena.wang@leerink.com dan.leonard@leerink.com john.sullivan@leerink.com justin.bowers@leerink.com seamus.fernandez@leerink.com swati.kumar@leerink.com jason.gerberry@leerink.com chris.kuehnle@leerink.com danielle.antalffy@leerink.com richard.newitter@leerink.com robert.marcus@leerink.com david.larsen@leerink.com chris.abbott@leerink.com maryellen.eagan@leerink.com bob.egan@leerink.com amy.sonne@leerink.com

Associate Director of Research Alice C. Avanian, CFA Healthcare Strategy John L. Sullivan, CFA Alice C. Avanian, CFA Biotechnology Howard Liang, Ph.D. Joseph P. Schwartz Marko Kozul, M.D. Michael Schmidt, Ph.D. Irene Lau
Rene Shen Gena Wang, Ph.D.

Life Science Tools and Diagnostics

Dan Leonard John L. Sullivan, CFA Justin Bowers, CFA

(212) 277-6116 (617) 918-4875 (212) 277-6066 (617) 918-4011 (617) 918-4576 (617) 918-4549 (617) 918-4851 (212) 277-6044 (212) 277-6088 (212) 277-6084 (617) 918-4502 (617) 918-4010 (617) 918-4837

Pharmaceuticals/Major

Seamus Fernandez Swati Kumar

Specialty Pharmaceuticals, Generics Medical Devices, Cardiology & Orthopedics

Jason M. Gerberry, JD Christopher W. Kuehnle, JD Danielle Antalffy Richard Newitter Robert Marcus, CFA

Healthcare Technology & Distribution Sr. Editor/Supervisory Analyst Supervisory Analysts Research Assistant

David Larsen, CFA Christopher Abbott Mary Ellen Eagan, CFA Robert Egan Amy N. Sonne Paul Matteis

(617) 918-4585

paul.matteis@leerink.com

New York 1251 Avenue of Americas, 22nd Floor New York, NY 10020 (888) 347-2342

Boston One Federal Street, 37th Floor Boston, MA 02110 (800) 808-7525

San Francisco 201 Spear Street, 16th Floor San Francisco, CA 94105 (800) 778-1164