Motif Bio PLC

Opportunities to overcome antibiotic resistance

13 May 2015

Motif Bio PLC (MTFB) is a drug discovery and development company targeting

Company Data

new antibiotic solutions. Modern medicine is under threat from antibiotic

EPIC

resistance, particularly for hospital-acquired infections (HAI). MTFB has an

Price (last close)

opportunity to help strengthen the physician's toolbox for antibiotic-resistant

Market cap

MTFB
32p
21m

bacteria.
MTFB recently raised 2.8m listing on AIM to support steps towards a Phase 3
Share Price, p

programme of its recently acquired novel antibiotic, iclaprim, in two significant HAI
indication areas. These could be worth up to $1bn in worldwide revenues, and highly

40

attractive to Big Pharma acquirers.

35

Recent FDA green light for iclaprim. The outcome of a recent meeting with the US

30

FDA (on 14 April) confirmed that iclaprim is ready for the clinic. Company is exploring
additional sources of funding to support this programme to completion - including non-

25

dilutive awards and grants, and corporate partnering.

Healthcare crisis imminent through lack of new antibiotics. MTFB should

enjoy worldwide government and regulatory support to help commercialise
iclaprim (and other product candidates), benefit from a fast-track approval process

20
01 April

11 April

21 April

01 May

11 May

Source: ADVFN
AIM IPO on 2 April, 2015 was at 20p/share

and a potential 10 years of market exclusivity.

Iclaprim - potential for treating skin infections and pneumonia. MTFB aims
to initiate Phase 3 trials for iclaprim in 2015. FDA confirmed that two successful
serious skin infection trials or one skin and one pneumonia trial would be required
for iclaprim's US approval.

Strategic partnership initiative underway to create value. An out-licensing

deal (probably for the skin infection indications) would allow MTFB to optimise the
clinical development timelines, and to potentially invest in the proprietary
development of the pneumonia indication - an additional value-enhancing move.

A successful partnering strategy and commercialisation outcome suggests

forecasts that support a valuation in the range of 45m-60m.
Positive Phase 3 results should be a multiplier for this figure, with potential M&A
activity adding a further premium.

Robin Campbell Ph D
02070652690
robin@equitydevelopment.co.uk

Andy Edmond
0207 065 2691
andy@equitydevelopment.co.uk

Please refer to the important disclosures shown on the back page and note that post MiFID this information is categorised as Marketing Material

Motif Bio PLC

13 May 2015

Executive Summary
An investment in MTFB represents an opportunity to be part of the resurgence in
research and development efforts to find novel antibiotic drugs to repel the
spectre of multiply drug-resistant bacteria. Notable

bacterial enemies

include

methicillin-resistant Staphylococcus aureus, or Staph. aureus (MRSA), Streptococcus

(Strep.) pneumoniae and Enterococcus species - particularly in the patient-vulnerable
intensive care unit (ICU) setting.
Anti-infective product development has become one of the new hot sectors for
small biotech companies and Big Pharma. Significant sums of money are being
invested into the sector, and we have seen an increasing number of M&A transactions
centred on this therapeutic space - most notably the recent $9.5bn acquisition of Cubist
Pharma by Merck & Co., Inc.
MTFB's product portfolio is being built around iclaprim, an intravenous (IV) antibiotic
active

against

Gram-positive

bacteria

and

particularly

those

resistant

to

conventional antibiotics in hospital-acquired pneumonia and complicated skin

infections. An oral form is in development, which would represent an additional clinical
benefit when switching patients from the inpatient to outpatient setting.
MTFB successfully completed its entry on AIM (2 April) with a 2.8m equity fund
raise. A recent meeting with the FDA (14 April) obtained agreement on the Phase 3 clinical
development plan suitable for a future NDA submission (the aim is to get first patients
dosed in H2 2015).
A future successful partnering strategy and commercialisation outcome could translate into
an earnings model that supports a near-term company valuation in the range of
45m-60m. Furthermore, a successful M&A approach from Big Pharma is likely to value
MTFB at a significant premium to any future fair value.
The company is composed of an experienced management team and top-class scientific
research group, supported by a well-respected Scientific Advisory Board.
It is some 30 years since consistent research effort was applied to find new
antibiotics, due to most active players leaving the industry as a result of low pricing, little
incentive to be creative and an overly tough regulatory stance.
However, this situation is changing. Government legislation and research incentives
support a growing awareness of a critical medical problem that needs solutions. Similarly,
national drug regulatory bodies (eg US FDA) are working with companies to facilitate
quicker passage of new, increased efficacy products.
On the back of this much more positive environment for new antibiotic discovery and
development, we believe that investment in the sector is primed for a significant
payback. On that basis, investors in Motif Bio are likely to have a number of valuable exit
options.

www.equitydevelopment.co.uk

13 May 2015

Motif Bio PLC

Motif's proposition
Motif Bio is a drug discovery and development (DDD) company based in New York
City (US). It was originally formed to exploit broad DDD opportunities across the antiinfective, overactive bladder and rheumatoid arthritis indication areas. Most recently it has
focused its attention on anti-infectives.
It operates with low fixed overheads around a consultant scientific team (10 people) which
has significant experience in drug development (each scientist has between 15 and 32 years
of pharmaceutical development experience, and collectively they are named inventors on
>160 patents). The scientific skill sets cover all the necessary areas from basic science and
biology, through medicinal chemistry and intellectual property assessment, to clinical
development.
The science engine is complemented by a highly experienced management team of
three, headed by Graham Lumsden (ex-Merck & Co., Inc. executive - see Bio) and a board
of directors and scientific advisory board boasting commercial experience and scientific
relevance.
MTFB identified an opportunity to acquire the intravenous (IV) antibiotic asset,
iclaprim, and related intellectual property (IP), owned by Nuprim. Iclaprim was
originally developed by Roche, and then subsequently taken through clinical trials by
Arpida AG (a public Swiss company). Arpida's development path was aimed, initially, at
gaining US and European approval for using iclaprim in treating complicated skin and soft
structure (tissue) infections (cSSSIs). However, the clinical dossier submission failed to win
US approval (in November 2008) and its separate European filing was subsequently
withdrawn.
As a result Arpida closed operations and the company assets were sold to Evolva, a Swiss
company, with drug development ambitions at the time (2009).
Many observers believed that Arpida had been treated over-harshly; a previously
'agreed' comparative metric (non-inferiority) with an already approved antibiotic (Pfizer's
Zyprox/ linezolid) was achieved. Unfortunately, between that understanding and Arpida
submitting clinical data to the FDA, the regulatory environment for the testing and approval
of new antibiotics had become tougher - possibly too tough in many experts' eyes.
The separate iclaprim assets were subsequently sold to Acino Holding AG for CHF 2.1m.
Nuprim was (recently) founded (management includes the ex-CEO and ex-CSO of Arpida) to
manage the sale of iclaprim and related IP.
MTFB completed necessary due diligence on iclaprim (ahead of its IPO). This included
a review of all of the preclinical and clinical data plus the US and European regulatory
correspondence, and determined that iclaprim can be rapidly returned to late stage
clinical testing with some improvements to the original development program.
The Company believes that a current more favourable regulatory environment (for antibiotic
NDA reviews), bolstered by national governments pushing to spur increased investment and
research to develop new antibiotic drugs, should allow the company to return to the
regulators with iclaprim (in a number of treatment indication areas) and achieve a
successful outcome this time.

www.equitydevelopment.co.uk

Motif Bio PLC

13 May 2015

The positive outcome from its recent meeting with the FDA increases our
expectations and helps decrease the regulatory risk attached to this clinical
programme.
As a result of Nuprim's merger with MTFB (signed in December 2014 and completed upon
Admission to AIM), MTFB acquires iclaprim and associated assets (intellectual property,
clinical data, access to Nuprim/ex-Arpida consultants and 600kg of active drug). A key
rationale for the transaction was obtaining the exclusive worldwide development and
marketing rights to iclaprim.
In addition to iclaprim, MTFB is investigating the development of other antibiotics, including
those with novel mechanisms of action.

AIM listing and fund raising

First

dealings

for

the

newly-listed

AIM

company

took place

on

April,

accompanied by a fundraising of 2.8m (gross). This is sufficient to support the

initiation of MTFB's broader development ambitions for iclaprim.
Near term the aim is to raise further capital, preferably non-dilutive through awards and
grants, or from signing a strategic corporate partnership, in order to initiate the clinical
programme. The latter options are to partner in one or both indication areas. MFTB is
currently working on a strategic partnership initiative to help identify and prioritise potential
partners.
Following the positive FDA meeting the company has, in our opinion, significant leverage to
consider licensing a sole indication area - probably the skin infection project - and use the
potential deal terms (upfront and milestone payments) to support the proprietary
development of the pneumonia indication.
Motif is currently working on a detailed costing and timelines for the clinical programmes. In
our view, based on conversations with clinical research organisations, we are assuming that
each Phase 3 trial in 'acute bacterial skin and skin structure infections' (ABSSSI) is likely to
cost ~$20m, and a Phase 3 trial of iclaprim in nosocomial or 'hospital acquired bacterial
pneumonia' (HABP), ~$35m.

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13 May 2015

Motif Bio PLC

Development plans
MTFB's priority is the development and potential regulatory path for iclaprim. The
US FDA recently agreed that the company could proceed with a Phase 3 programme to
study IV iclaprim in ABSSSI, versus a standard of care comparator, vancomycin.
Importantly, we should remind ourselves that iclaprim, in two Phase 3 trials carried out in
2008 demonstrated excellent efficacy and safety in complicated skin and skin structure
infections (cSSSI), compared to Pfizer's Zyvox/ linezolid. The regulatory environment for
achieving a positive New Drug Approval (NDA) result for antibiotics at that time (20062011) was extremely tough.
MTFB believes that, with equivalent efficacy and safety results (versus 2008), a new
comparison with vancomycin conducted according to new clinical guidelines for ABSSSI
trials, coupled with a more positive regulatory environment (supported by a number of US
government-led incentive programmes to get more antibiotics approved) should see IV
iclaprim succeed with its NDA. In our opinion this is a route that is eminently achievable.
This

is

situation

that

has

been

experienced

by

number

of

companies/antibiotics that were unsuccessful with antibiotic NDAs in 2006-2011, that

have subsequently re-trialled the products under the new clinical guidelines and won NDA
approval

(examples

include

Dalvance/dalbavancin,

Sivextro/tedizolid

phosphate

and

Orbactiv/oritavancin).
Following the IPO - and being able to attract the necessary partnership or grant funding, we
are assuming that the ABSSSI trial starts in H2 2015, completing in early 2017, with the
NDA being filed in the US in Q2 2017. Fast-track approval under the GAIN Act (see later)
could see an approval by Q4 2017 and a potential first launch in early 2018.
In addition, the Company is designing a Phase 3 programme to demonstrate a noninferiority result between iclaprim and vancomycin for the treatment of nosocomial
pneumonia caused by Gram-positive pathogens. The primary endpoint is all-cause
mortality, that is death from any cause up to the 28th day following the start of antibiotic
treatment. Secondary endpoints are likely to include the following; Proportion of patients
with resolution of signs and symptoms of pneumonia, Clinical Pulmonary Infection Score
(CPIS) at start of treatment and at 72 hours, and the microbiology work up (bacteriological
outcome).
We would also highlight that vancomycin, despite being 'standard of care' (SOC) for
ABSSSI, is experiencing a widespread increase in resistance, and particularly in
hospital-acquired

bacterial

pneumonia.

Furthermore,

other

measures

to

titrate

vancomycin towards the upper range of serum levels to raise effectiveness can
tempt potential serious nephrotoxicity in patients.
As confirmed at Motif's meeting with the FDA, two skin trials or one skin trial plus
one pneumonia trial - successfully meeting pre-specified primary endpoints and using
vancomycin as comparator drug - would allow for approval of iclaprim (in potentially
two HAI indications).
MTFB believes that it has a convincing product profile and commercial rationale for the
pneumonia project. Indeed, there are already some known key features for iclaprim that
could translate into clinical and commercial advantages in both indications including:

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Motif Bio PLC

13 May 2015

Iclaprim concentrates in lung tissue (alveolar macrophages, x40; epithelial lining fluid,
x20) for an enhanced tissue penetration (HABP);

The drug has a novel mechanism of action (selective inhibitor of the enzyme
dihydrofolate reductase - DHFR-i class). Iclaprim is a synthetic diaminopyrimidine,
related to trimethoprim;

It has a broad and potent spectrum of activity against Gram-positive (G+ve) bacteria
and particularly those that feature in nosocomial pneumonia infections and ABSSSIs;
and

The Arpida Phase 2/3 clinical data (NDA submission, 2008 and other unpublished data)
suggest a better efficacy, toxicity and safety profile (than current antibiotic treatments
for pneumonia and ABSSSI).

Additional future development programmes (although timing is likely to be dependent

on available funds) include:

An IV iclaprim derivative for targeting additional indication areas;

An oral iclaprim formulation, for follow-on therapy to IV iclaprim (where appropriate);

and

A Best-in-class DHFR-i.

Commercialisation strategy
There is likely to be significant corporate interest in iclaprim for the treatment of
serious skin infections. We anticipate a licensing deal for iclaprim in this indication
being completed in 2016.
The financial terms for this licence are likely to dictate MTFB's commercial strategy for the
HABP indication - which it could develop independently. This option could be a significant
value-creating opportunity for the company.
MTFB would aim to position iclaprim as a first-line choice antibiotic in nosocomial
pneumonia (HABP). There are a number of disadvantages attached to current competitor
products, for example the bacteriostatic action and myelosuppressive effects of linezolid
(>10 days of treatment), potentially serious adverse reactions with telavancin and growing
resistance to vancomycin.
Most recently, national governments have been keen and vocal for companies to step
on the gas in terms of developing new antibiotic drugs with novel mechanisms. For
example, the 'Generating Antibiotics Incentives Now' (GAIN) Act came into effect in the US
in 2012 and has been a necessary move to help create change to allow antibiotic drug
development to get back on track.
GAIN was incorporated into the FDA's Safety and Innovation Act (2012) that reauthorized prescription drug user fees and, importantly, provides added exclusivity for
antibiotics and earmarks the latter for Priority Review.
The three antibiotic products that achieved NDA approval - see above - were approved after
being designated as Qualified Infectious Disease Products (QIDP) under the GAIN Act. As a
QIDP, each antibiotic gains an expedited review ticket from the FDA. Furthermore,

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13 May 2015

Motif Bio PLC

another benefit for qualifying QIDPs is that each is granted marketing exclusivity. This
represents a significant incentive and a step in a very useful direction, signalling an
invitation for antibiotic developers to continue to invest in research and clinical development
(or re-boot investment plans).
Key to developing a commercial IV iclaprim product with high revenue potential:

A broad indication label across the nosocomial pneumonia landscape (hospital-acquired

pneumonia, healthcare-associated pneumonia, and ventilator-associated pneumonia),
specifically due to MRSA;

Support from hospital and clinic formularies, with intent to use across the inpatient and
outpatient IV settings;

Good safety and little toxicity; and

(Future) availability of an oral follow-on product, to allow switching from the IV

presentation (used in the hospital care environment) once a patient downgrades from
intensive care or switches to the outpatient setting. Additional potential applications in
chronic indications, like osteomyelitis (bone infections due to MRSA/ G+ve bacteria).

Exit strategy
Following the increasing amount of M&A activity in the antibiotics development space, a
clear exit strategy option would be a trade sale, potentially to a pharma company keen
to extend its own anti-infectives franchise or, simply, wanting to start one.
It's clear that the once unattractive and unprofitable area of antibiotic research is enjoying a
fast-paced renaissance. New collaborations and licensing deals in the space, as well as
recent antibiotic company IPOs have transformed the strategic landscape, with
companies hunting for novelty, new mechanisms and potential market exclusivity.
We understand that MTFB is likely to explore the potential for a NASDAQ listing later in
2015 to raise additional funds to help support the pneumonia programme and its other R&D
activities.
Tetraphase floated on Nasdaq in 2013, and now has a market cap of $1.3bn. Roche
committed to a total $560m price tag to re-enter antibiotic development and secure rights
to Polyphor's Macrocycle product in the same year. Cubist acquired Trius Therapeutics
for $818m in 2013, adding Sivextro to its pipeline.
More recently, we have seen the three new FDA fast-track approvals (Durata's
Dalvance/ dalbavancin, Cubist's Sivextro/ tedizolid phosphate and The Medicine Company's
Orbactiv/ oritavancin) in this space - and confidently expect more. Durata's Xydalba/
dalbavancin gained EU approval in March.
One company, Paratek, is developing omadacycline, a dual IV/oral tetracycline-like
molecule that is in Phase 3 development in RTI and skin infections.
This drug was another casualty due to the raised FDA review bar of the late-2000s, but
there is renewed hope that the current campaign should have a different outcome. The
company currently has a market cap of $369m.

www.equitydevelopment.co.uk

Motif Bio PLC

13 May 2015

Finally, we would highlight that the whole antibiotic sector has been emphasised for its 'new
old kid on the block' investment opportunities by Actavis' acquisition of Durata
Therapeutics for $675m (or >$800m if Contingent Value Rights are included) and, most
recently, by Merck & Co's purchase of Cubist Pharma for $9.5bn (including ~$1bn in
net debt), at an ~35% premium.

Valuation
In light of MTFB's clinical development plan ambitions to try to proceed with registration
trials in both HABP and ABSSSI, we have developed our earnings model to accommodate
the possibility of being able to launch iclaprim in both indications.
Furthermore, we have assumed that MTFB is able to successfully licence out both indications
to a potential pharmaceutical company as the financial sponsor and to be responsible for
commercialisation in the marketplace (in the event that the pneumonia indication is
progressed through clinical development by MTFB alone, the likely higher project value compared to out-licensing at this point - would help boost the overall company valuation
higher).
Our risk-adjusted revenue approach assumes that a total of $70m partnering milestone
payments (per indication) - including upfront, development, regulatory and launch
milestones - are due, as well as a 12% royalty income on in-market indication sales.
On the basis that the company raised ~2.3m (net), and using a discounted cash flow
analysis (discount rate 20%-25%, terminal growth rate 2.0%-3.0%), MTFB's ambitions to
move forward with both hospital-acquired infection indications on the back of the FDA green
light suggests a potential fair value for the company of between 45m-60m.

DCF valuation, m
Discount rate
15.0%

20.0%

25.0%

30.0%

35.0%

1.5%

89.1

60.2

44.9

35.7

29.5

Terminal

2.0%

90.6

60.7

45.1

35.8

29.6

Growth

2.5%

92.2

61.2

45.3

35.9

29.6

3.0%

93.9

61.8

45.6

36.0

29.7

Rate
Source: ED

With positive news on product development (particularly Phase 3 results) and other
catalysts, we anticipate additional significant value creation. Furthermore, a successful
M&A approach from Big Pharma is likely to value MTFB at a significant premium to
any future fair value.

www.equitydevelopment.co.uk

13 May 2015

Motif Bio PLC

Catalysts
We would reiterate the conservative nature of our forecasts, earnings model and
valuation. From discussions with management, we have identified some potential trigger
events that could translate into (future) share price moves:

(Possible) key developments

Calendar

Timing

Event

H1 2015

Successful AIM listing (raising 2.8m gross)

H1 2015

Successful meeting with the FDA - approval of clinical plans for both
indication areas.

H2 2015

First patient enters ABSSSI Phase 3 trial; First patient enters HABP
Phase 3 trial (estimated). Partnership negotiations initiated.

H1 2016

Licensing agreement for one, or both, indication(s) completes in 2016.

H2 2016
H1 2017

Q1/ABSSSI Phase 3 study completes. Q2/ABSSSI NDA filed in US.

H2 2017

Potential US approval for IV iclaprim in ABSSSI.

H1 2018

Initial launch - IV iclaprim in ABSSSI.

H2 2018

HABP Phase 3 study completes.

H1 2019

Q1/HABP NDA filed in US.

H2 2019

Potential US approval for IV iclaprim in HABP.

Source: ED; Company

Risks
There are always uncertainties in the drug development sector, and we note the risk of:

Lack of formal patent protection for iclaprim - we understand that all patents and
ongoing applications were abandoned by Acino. However, and critically, MTFB is
applying for 'Qualified Infectious Disease Product' (QIDP) status under the GAIN Act. If
successful, the company should benefit from certain incentives for the development of
new antibiotics, including priority review (6 months), eligibility for Fast Track status,
and if ultimately approved by the FDA, a five year extension of Hatch-Waxman
exclusivity for a total of 10 years (versus the normal five year period). We believe that
MTFB should be able to apply for 10 years of data exclusivity in the EU with Phase 3
data.

Dependence on the key members of the scientific team and the virtual network of
consultants based in the US to progress the support work for the planned registration
trials for iclaprim, the oral reformulation work and the lead generation and assay work
required to select appropriate lead drug candidates for the DHFR-i programme;

Technical and safety issues that could arise to delay late development trial progress
with iclaprim, in particular trial efficacy results which do not support previous study
results; and

Possible delays in achieving a licensing deal for iclaprim on beneficial commercial terms,
in the regulatory review and potential launch, requiring MTFB to return to the capital
markets to raise additional funds.

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Motif Bio PLC

13 May 2015

Market opportunity
The anti-infectives market is a significant commercial
opportunity
The anti-infectives market is a large one - and the demand for newer, more effective
and safer products is growing. Antibiotics represented a $43.9bn market in 2010
and a number of antibiotic products today have annual sales >$1bn.
US hospitals see ~18m patients with serious infections. Nosocomial pneumonia is the
2nd most common HAI in the US, with up to 30% of all ICU infections caused by hospitalacquired pneumonia and ventilator-associated pneumonia (with an extremely high mortality
rate, some 20%-50%). MRSA is the most common Gram+ve pathogen found in nosocomial
pneumonia cases. In aggregate these infections result in >50% of all antibiotics prescribed
in the ICU, and result in increases in patient length of hospital stay and cost of care.
Similarly, ~3.3m of these serious infections are bacterial ASSSIs. The latter
represent 3% of all hospital admissions, and most display evidence of cellulitis and wound
infections. In the US the majority of SSSIs in hospital patients is caused by streptococcal
organisms and Staph. aureus (and almost 60% of Staph isolates in the US are MRSA
strains). There is a high and growing prevalence of MRSA in the hospital setting.
Of those treated with IV antibiotherapy in the secondary hospital setting, that is some 2.6m
patients, this is a significant commercial opportunity. Aggregated therapy time for these
patients - 35m days - would equate to a potential $10bn market (assuming all products
at equivalent branded prices).
For many new antibiotics there are additional opportunities in more specialised
indications, like osteomyelitis and bacterial endocarditis.
Furthermore, the customer universe is highly concentrated - the Top 500 hospitals in the US
provide >40% of the market opportunity.
Outside the US, international markets are experiencing similar pressures from the rise of
bacterial infections and MRSA.

Market opportunity compounded by the rise in

antibiotic-resistant bacteria
The ability to adequately combat serious infections with drugs is often made ineffective,
requiring more potent but more toxic and expensive second- and third-line choices.
Antibiotic-resistant infections kill an estimated 50,000 people a year in the US and
Europe and the number is rising (according to the World Health Organisation).
More to the point, without effective antimicrobial agents, chemotherapy for cancer and
invasive surgical operations could become life-threatening due to the greater likelihood of
infection.
Unfortunately, inventing new, more potent antibiotics to replace those marginalised through
lack of a bactericidal ('killing') effect has suffered from a lack of industry support. Many
Big Pharma programmes were lost during the last 20 years on the belief that there was
enough diversity in marketed products and near-to-market pipeline candidates to banish all
microbial predators.

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Motif Bio PLC

Following the 'Golden Ages' of Antibiotic discovery and generating semi-/fully-synthetic new
antibiotic molecules (using medicinal chemistry, or Med Chem, techniques), this period of
stasis (the 'Innovation Gap') led to a diminishing number of active antibiotics.

The Rise of Antimicrobial Resistance

Antibiotic

Year deployed

Clinical resistance observed

1930s

1940s

Penicillin

1943

1946

Streptomycin

1943

1959

Chloramphenicol

1947

1959

Tetracycline

1948

1953

Erythromycin

1952

1988

Vancomycin

1956

1988

Methicillin

1960

1961

Ampicillin

1961

1973

1960s

Late 1960s

Sulfonamides

Cephalosporins
Nalidixic acid

1962

1962

1980s

1980s

Linezolidb

1999

1999

Daptomycinb

2003

2003

Retapamulin b,c,d

2007

2007

Fidaxomicin

2011

2011

Bedaquiline b,e

2013

Fluoroquinolones

Source: Table adapted from Walsh and Wencewicz (Nature 2014); b Represents a first-in-class drug for human use;
c Approved for topical use only; d Resistance to retapamulin observed in clinical isolates of S. aureus without
previous exposure to pleuoromutilins, but no case of resistance development during retapamulin therapy was found
in the literature; e Approved only for use in combination therapy for treatment of MDR TB.

Needless to say, the relatively bare cupboard of the last 10 years plus the inexorable
increase in multiple forms of antibiotic resistance - to the point where options for some
individuals are non-existent - has spurred activities by a number of small,
commercially-minded biotech firms that are now being acquired by newly-created or
existing Big Pharma R&D antibiotic divisions.

The Innovation Gap for Antibiotics

Source: Walsh and Wencewicz (Nature 2014)

From an investor's perspective the opportunities to lay bets on new antibiotic

assets in promising clinical pipelines that could be the next target for opportunistic Big
Pharma M&A is increasingly attractive.

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Motif Bio PLC

13 May 2015

Product development plans

Iclaprim
Iclaprim, is a diaminopyrimidine derivative, with potent activity against bacterial
respiratory pathogens. With regard to its potential use in treating bacterial pneumonia,
iclaprim penetrates and concentrates in lung compartments.
A Phase II clinical trial showed excellent clinical cure rates among patients treated
with iclaprim compared to vancomycin in patients with nosocomial pneumonia (Arpida unpublished).
Nosocomial pneumonia infections (in ICU) have a significant impact on morbidity, mortality
and cost of care. Early, appropriate therapy is critical, but there are few available therapies
approved in the United States. Furthermore, clinical experience suggests that these are
facing increased rates of resistance and reduced susceptibility.
Iclaprim's legacy is as a candidate treatment for complicated skin and skin
structure infections (combating Gram-positive bacteria, including MRSA). However,
Arpida's NDA submission to the US FDA in 2008 met with a non-approval and a Complete
Response Letter emphasising that the non-inferiority target (to a gold standard comparator
drug) was not met and more clinical trial data would be required to satisfy the review board
with respect to the drug's efficacy and potential safety.
However, the fact that the drug was turned down on lack of efficacy is, in our
opinion, a red herring - more likely due to a moved goalpost by the regulators. (Ketek/
telithromycin's US withdrawal in 2007 and issues connected with its regulatory review led
the FDA to toughen up on antibiotic approval reviews. Iclaprim, and the other 'nonapproved' antibiotics that we have mentioned previously were victims of this change).
As we have described earlier (see - 'Motif's proposition'), MTFB believes that it is
possible, with the recent FDA agreement to carry out a Phase 3 clinical programme to
potentially achieve marketing approval for iclaprim, such that:

The Phase 3 programme is designed to obtain marketing approval for an IV formulation

of iclaprim in the treatment of acute bacterial skin and skin structure infections
(ABSSSI) and hospital acquired bacterial pneumonia (HABP) caused by Gram-positive
pathogens,

including

resistant

strains

such

as

MRSA

(methicillin

resistant

Staphylococcus aureus) and MDRSP (multi-drug resistant Streptococcus pneumoniae);

and

The FDA confirmed that two ABSSSI trials or one ABSSSI trial plus one HABP trial
meeting their pre-specified primary endpoints, using vancomycin as comparator drug,
are required for the approval of iclaprim.

Our understanding is that iclaprim should be the flagship asset for Motif and have
a potential rapid path to market. Assuming initial patient enrollment into clinical studies
in H2 2015 the company could potentially submit an NDA within 18 months (with a first
NDA filing for ABSSSI indication likely in H1 2017).

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Motif Bio PLC

Through government incentive programmes - GAIN and ADAPT (the potential successor to
GAIN, the 'Antibiotic Development to Advance Patient Treatment' Act) - Motif could be in a
strong position to obtain priority review and 10 years of marketing exclusivity for
iclaprim after its approval (other drug compounds get only 5 years). This situation should
also apply in the EU, with MTFB able to gain data exclusivity for the new Phase 3 trial
results.
Iclaprim is an antibiotic and potent inhibitor of dihydrofolate reductase (DHFR-i). Its effect is
similar to trimethoprim (from which it was derived), affecting bacterial RNA and DNA
biopathways to interrupt growth and help resolve infections. The clinical rationale behind
its development is to provide a new drug for current and new indication areas, and
to combat rising trimethoprim resistance.
Importantly, studies have shown that iclaprim activity is at least as good as the (often used)
combination of trimethoprim plus sulfamethoxazole. Furthermore, there are tolerance and
adverse event issues connected with the sulfa-drug component, particularly in senior and
geriatric patients. Iclaprim, therefore, represents a very attractive clinical option to continue
using a DHFR-inhibitor but without sulfamethoxazole.
The merger with Nuprim provides MTFB with access to all the pre-clinical and clinical data
relating to iclaprim's previous NDA submissions. Iclaprim was previously in development by
Arpida (Switzerland) for complicated skin and skin structure infections (cSSSIs) and an
application for marketing approval submitted to FDA in March 2008 and the European
regulatory agency, EMA, in August 2008. It was rebuffed by the FDA Advisory Committee in
November 2008 and formally turned down in January 2009.
In its Complete Response Letter (CRL) to Arpida in 2008 - on the basis of its changed
clinical criteria for assessing antibiotic performance - the FDA recommended an additional
clinical study, or studies, to demonstrate the drug's efficacy. At the time Arpida could not
afford to carry out this request and the programme was discontinued.
David Huang, MTFB's new Chief Medical Officer (see - Biographies), has reviewed the
available data on iclaprim and helped formulate MTFB's clinical development plans. Dr
Huang has a broad and deep experience of antibiotic development and clinical trial design
(he worked on Pfizer Inc's gold standard Zyvox/linezolid antibiotic for combating MRSAassociated infections, and helped develop recombinant proteins for treating drug-resistant
bacteria at ContraFect Inc).
We believe that there are a number of characteristics of iclaprim that could
translate into clinical benefits, particularly in the HABP indication versus current
standard therapies, including vancomycin, Zyvox (linezolid) and a newly approved drug
(Vibativ/ telavancin).
Despite the range of potential antibiotics, and combinations, that are available, clinical
failure in bacterial pneumonia often occurs. This is normally due to resistance
development, side effect intolerance and poor drug absorption/ tissue distribution factors.
In terms of antibacterial activity iclaprim is active against Staphylococcus aureus, including
methicillin-resistant strains (MRSA) and a single vancomycin-resistant one. It is active
against respiratory pathogens including Haemophilus influenzae and Moraxella catarrhalis,
as well as penicillin-resistant forms of pneumococcus (Streptococcus pneumoniae).

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13

Motif Bio PLC

13 May 2015

Iclaprim MICs versus standard antibiotherapy against relevant species

responsible for bacterial pneumonia.
Antibiotic
Iclaprim

Trimethoprim

Vancomycin

Linezolid

Erythromycin

S.aureus (MSSA)

0.06

16

S.aureus (MRSA)

0.12

16

S.pyogenes

0.03

64

32

Streptococcus agalactiae

0.5

128

0.5

S.pneumoniae (penicillinresistant)

>128

32

0.12

32

H.influenzae

0.5

128

64

M.catarrhalis

128

64

0.25

Species

Enterococcus species

Source: Company, ED

Iclaprim is a bactericidal antibiotic with a low risk for resistance development

(demonstrated by Arpida - unpublished). In studies to date, the drug has shown good
pharmacodynamic distribution into the lung, with concentrations significantly above plasma
concentrations (lung alveolar macrophages, x40; lung epithelial lining fluid, x20).
We understand that a Phase 2 study (carried out by Arpida - unpublished) of iclaprim IV in
patients treated with nosocomial pneumonia demonstrated excellent clinical cure rates,
confirming Motif's thesis that iclaprim may also be a treatment option for nosocomial
pneumonia/HABP due to Gram-positive pathogens.
Iclaprim and the comparator drug, vancomycin, were generally equally well
tolerated. No new or unexpected suspected reactions emerged. No notable differences in
the incidence of adverse events (potentially linked to the active drug being administered)
among the treatment groups were observed.

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13 May 2015

Motif Bio PLC

Iclaprim offers potential advantages over SOC in nosocomial pneumonia

STANDARD OF CARE (SOC) FOR GRAM-POSITIVE NOSOCOMIAL

POTENTIAL SOC

PNEUMONIA

TREATMENT

Vancomycin
glycopeptide

Zyvox/ linezolid
oxazolidinone

Vibativ/ telavancin
glycopeptide (derivative
of vancomycin)

Iclaprim
diaminopyrimidine
(derivative of
trimethoprim)

Spectrum of
activity:
Gram-positive
bacteria, including
MRSA

Streptococcus
pneumoniae

Not recommended

Bactericidal (Killing)
effect

Safe, with minimal

toxicities

Potential serious
adverse effects,
including: Bone marrow
suppression, low
platelet count (when
used >2 weeks);
Peripheral neuropathy,
optic nerve damage

Increased risk of
mortality among
patients with renal
impairment. Concern
over drug's effect on
renal status

Lung tissue
penetration

8X (ELF), 85X (alveolar

MAC) - above MIC90
for MRSA

Frequency of
dosing/Length of
therapy course

BID to QID (variable

period)

Key Advantages

1st line therapy

Key Disadvantages

Lack of effective oral

formulation

TID infusion over 30 to Once daily IV infusion

120 mins for 10-14 days over 60 mins for 7-21
days

20X (ELF), 40X

(alveolar MAC)

BID to TID for 7-14

days

IV-to-Oral option

Bactericidal

Bactericidal

Can be used in patients

with renal insufficiency

Once-daily dosing

Broad spectrum (for

G+ve bacteria)

Bacteriostatic

Vibativ should be
reserved when
alternative treatments
are not suitable

No G-ve cover for

empirical therapy

Restricted usage due to

development of VRE
Source: Company, ED

Potential add-on programmes

Developing an oral iclaprim, as a partner presentation to the IV form. This makes

clear commercial sense, but would be a strategic decision due to the time and cost
required. This could follow the IV iclaprim project by c.12-18 months. Furthermore, this
programme would need to explore the potential safety issues related to the raised liver
enzyme levels seen with an oral formulation (noted by the European regulator in 2009).

Novel 'best-in-class' DHFR inhibitor molecules. Motif estimates that it should have
a preclinical dossier within 18 months, and should be in a position to submit an IND
within 36 months. A more measured clinical development approach can be adopted,
designing both IV and oral formulations into programmes across a number of disease
indications.

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15

Motif Bio PLC

13 May 2015

Board of Directors & Senior Management

Chairman - Richard Morgan is the CEO of Amphion Innovations, a London and New York
based venture capital firm listed on AIM. In the course of his career, Mr Morgan has been
directly involved in the start-up and development of more than 30 companies in the
information technology, healthcare and biotechnology industries (including MediSense,
Sequus Pharmaceuticals, Celgene, Quidel and Vortech Data). Prior to this Mr Morgan spent
15 years with Schroders plc as a board member and head of the Schroders Strategy Group,
which he founded. Mr Morgan was a co-founder of Celgene Corporation (NASDAQ: CELG),
and held a board position with the company from 1987 to 2008.
Chief Executive Officer - Graham Lumsden. Previous experience includes commercial
leadership positions in worldwide Merck & Co., Inc. businesses, including contraceptives and
osteoporosis. Mr Lumsden is a member of the Royal College of Veterinary Surgeons
(MRCVS), holds a postgraduate diploma from the Chartered Institute of Marketing (MCIM)
and is a dual citizen of the US and UK.
Chief Financial Officer - Robert Bertoldi. Mr. Bertoldi is also President and CFO of
Amphion Innovations, a London and New York based venture capital firm listed on AIM
(ticker AMP). Previous experience includes James D. Wolfensohn, Inc., Hambro America Inc.
and KPMG. Mr. Bertoldi received a B.A. in Accounting and Economics from Queens College,
New York in 1976 and became a Certified Public Accountant in 1978. He is a member of the
AICPA and NYSCPA.
Chief Medical Officer - David B. Huang, M.D., Ph.D., MBA, JD. Previous experience as
Chief Medical Officer at ContraFect Corp (developing biologic anti-infectives), Pfizer
(projects included Zyvox/ linezolid) and Boehringer-Ingelheim (projects included Viramune
XR/ nevirapine XR, Aptivus/ tipranavir). Dr. Huang also has 15 years of clinical, academic
and research experience in medicine and in the subspeciality of infectious diseases, working
in public, government, private and academic institutions.

He is currently an adjunct

Assistant Professor at Rutgers New Jersey Medical School and has served as a faculty
member at Baylor College of Medicine. Dr. Huang has published over 100 publications in
leading peer-reviewed journals and is highly experienced in the design, execution and close
out of Phases 1/2/3 clinical trials for both antibacterials and antiviral agents.
Non-Executive Director - Mr Bruce Williams; previous experience at Ortho Biotech
(responsible for marketing Procrit, epoetin alfa, from pre-launch through to its first year on
the market), Celgene Corporation (Senior VP, sales and marketing to support the launch of
Thalomid, thalidomide) and Genta Inc. Currently serves on the board of Afaxys
Incorporated.
Non-Executive Director - Mary-Lake Polan, M.D., Ph.D., M.P.H.; currently Adjunct
Professor, Department of Obstetrics and Gynecology and Reproductive Sciences at Columbia
University School of Medicine. Previously the Chair of the Department of Obstetrics and
Gynecology at the Stanford University School of Medicine. Dr Polan specializes in
reproductive endocrinology and infertility and hormonal issues related to gynecology and
menopause. Dr Polan currently serves on the board of Quidel Corp and on the boards of
several privately held life sciences companies. She chairs an SAB in Womens Health for the
Proctor and Gamble Company and is also a Managing Director of Golden Seeds, an angel
investing group which invests in women led companies.

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13 May 2015

Motif Bio PLC

Non-Executive Director - Zaki Hosny; currently an independent consultant to life sciences

companies. Chief Executive Officer of Motif from 2006-13, and Deputy Chairman of its
Board of Directors. Previous experience at Merck & Co. Currently an advisor to the Albright
Stonebridge Group, ClinTec International, Harel Consulting and Mettle Consulting.
Non-Executive Director - Dr. John Stakes. Currently serving as a senior advisor and
a Physician Director of Network Development and Integration for the Mass General
Physicians Organization (MGPO). Previously Director of Specialty Care Development from
1995 until 2013, working for the MGPO and with the business development staff of the
Massachusetts General Hospital (MGH). He has been on the clinical teaching staff of Harvard
Medical School since 1982. Dr.Stakes was a member of the Board of Directors of Beijing
Med-Pharm Sunstone, a Nasdaq-listed company prior to the completion of its sale to SanofiAventis in 2011.
Non-Executive Director - Charlotta Ginman-Jones. Background in investment banking and
the telecommunications industry, with early roles at E&Y, JP Morgan, Deutsche Bank and
UBS. More recently, Director of Finance at Nokia Corporation. Board member at Kromek
Group, Pacific Assets Trust, Polar Capital Technology Trust, Consort Medical (and Wolfson
Microelectronics until its sale in 2014). Charlotta is a qualified Chartered Accountant in
England and Wales.
Non-Executive Director - Jonathan Gold. Previous experience as Partner with Amphion
Capital Partners LLC (the predecessor of Amphion), Wolfensohn Partners and Portfolio
Manager for the Federated Kaufmann Funds. Jonathan is currently Managing Director of JEG
Capital LLC, a family office and asset manager.
Scientific Advisory Board Chairman - Jay Tischfield, Ph.D. Professor of Genetics, Chair
& Professor of Pediatrics and Psychiatry at Rutgers University.
Scientific Advisory Board member - G. Ralph Corey, M.D. Professor of Medicine &
Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA.
Scientific Advisory Board member - Brad Spellberg M.D. Chief Medical Officer, LAC and
USC Medical Center, Professor of Clinical Medicine, Keck School of Medicine at the University
of Southern California, Los Angeles, California, USA.
Scientific Advisory Board member - Mark Wilcox B Med Sci, BM, BS, MD, FRCPath.
Consultant, Head and Professor of Medical Microbiology, University of Leeds, UK.

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17

Motif Bio PLC

13 May 2015

Financial Forecasts
We have developed our earnings model to accommodate the development and launch of IV
iclaprim in both the ABSSSI and HABP indications. This is based

on a detailed market

penetration and revenue model for both indications. Furthermore, we assume that MTFB
licenses the global marketing rights to a strategic partner.
Our risk-adjusted revenue approach assumes that a total of $70m partnering milestone
payments (per indication) - including upfront, development, regulatory and launch
milestones - are due, as well as a 12% royalty income on in-market indication sales.
Our earnings model makes a number of assumptions based on the current available
financial information for Motif Bio:

Reporting currency is GBP ;

The IPO raised ~2.3m net in April. MTFB issued 64.2m ordinary shares. The Company
had previously raised ~470k ($715k) in January 2015 - ~130k was used to pay off
outstanding balance sheet liabilities.

Amphion Innovations plc lent MTFB ~$9.5m, mainly in the form of convertible
promissory notes (CPNs). Of the total loan notes outstanding (mainly CPNs), a total of
$6m was converted into equity at the IPO. A newly issued CPN, of $3.5M, remains
outstanding;

The interest expense (on the CPNs) is ~150k pa, interest accruing until Dec 2016 or
the date of repayment;

Amphion's post-IPO equity stake of 44.1% means that it is unlikely to convert the CPNs
into equity at the present time (a potential ~14.5m shares).

Adding the latter to other outstanding options (13.5m) and warrants (11.7m) would
potentially produce a fully diluted share number of ~104m.

The Nuprim merger is to be accounted for as an acquisition of an (intangible) asset of

~4m - the amortisation charge over 20 years is likely to be ~200k pa;

A milestone of $500k is to be paid by MTFB to Acino upon completion of the Phase 3

ABSSSI programme in 2017;

A potential 1%-5% royalty is payable by MTFB on future income from its licencee(s) we have assumed a 2% rate for our workings; and

In the ABSSI and HABP revenue models, we build a forecast based on the likely launch
and penetration of IV iclaprim into the potential hospital patient population in the
separate markets (US, EU and RoW). Furthermore, we have made an assumption
regarding the probability that the projects proceed through to market launch.

For both the ABSSSI and HABP indications we apply a 50% risked probability to
revenues. This figure is set to rise (and increase the revenue potential) as the Phase 3
clinical programme gets underway - to 60%, once it completes - to 70%, and when the
NDA is filed - 75%).

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13 May 2015

Motif Bio PLC

Apart from what is outlined above and specified in the income and cash flow statements we
have made no other adjustments for D&A, share based payments, changes in working
capital, investment in capex, potential acquisitions, or any financing activities.
Clearly any changes to these assumptions could have a material impact on the
valuation.

Revenue Breakdown, 000s

Year end 31 Dec

2015e

2016e

2017e

2018e

2019e

2020e

iclaprim IV revenues

30,000

15,000

21,186

8,397

7,038

- o/w HAP indication royalty (12% on inmarket sales)

252

1,034

- o/w partnering milestones

15,000

5,000

10,000

5,000

- o/w ABSSSI indication royalty (12% on

in-market sales)

1,186

3,145

6,004

- o/w partnering milestones

15,000

10,000

10,000

Total revenues

30,000

15,000

21,186

8,397

7,038

Source: ED

Income Statement, m
Year end 31 December

2015e

2016e

2017e

2018e

2019e

2020e

Total revenues

30.0

15.0

21.2

8.4

7.0

Cost of goods
Gross profit

30.0

15.0

21.2

8.4

7.0

0.00
-1.44

-0.60
-1.00
-30%

-0.61
-1.1
7%

-0.42
-1.1
7%

-0.17
-1.2
7%

-0.14
-1.3
7%

Total costs
EBITDA

-1.4
-1.4

-1.6
28.4

-1.7
13.3

-1.6
19.6

-1.4
7.0

-1.5
5.6

Depreciation
Amortisation
EBIT before exceptional costs

0.0
-0.2
-1.6

0.0
-0.2
28.2

0.0
-0.2
13.1

0.0
-0.2
19.4

0.0
-0.2
6.8

0.0
-0.2
5.4

Exceptional costs
EBIT after exceptional costs

0.0
-1.6

0.0
28.2

0.0
13.1

0.0
19.4

0.0
6.8

0.0
5.4

Financial income
Interest expense
Net financial income/ (expense)

0.0
-0.1
-0.1

0.1
-0.2
-0.1

0.1
-0.2
0.0

0.2
-0.2
0.0

0.2
-0.2
0.1

0.3
-0.2
0.1

Earnings before tax

-1.7

28.1

13.1

19.5

6.9

5.5

Taxation
Effective tax rate

0.0
0%

-5.1
30%

-3.9
30%

-5.8
30%

-2.1
30%

-1.7
30%

Earnings after tax

-1.7

23.1

9.2

13.6

4.8

3.9

Number of shares (m)

EPS (pence)

64.2
-2.6

64.2
35.9

64.2
14.3

64.2
21.2

64.2
7.5

64.2
6.0

R&D
Sales & Marketing
General & Admin
Other costs
Total operating expenses
% change

Source: ED

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19

Motif Bio PLC

13 May 2015

Cashflow statement, m

Earnings after tax

Adjustments

2015e

2016e

2017e

2018e

2019e

2020e

-1.7

23.1

9.2

13.6

4.8

3.9

Depreciation

Amortisation

0.2

0.2

0.2

0.2

0.2

0.2

Finance income

0.0

-0.1

-0.1

-0.2

-0.2

-0.3

Interest expense

0.1

0.2

0.2

0.2

0.2

0.2

Share based payment expense

-1.4

23.3

9.4

13.8

4.9

3.9

-1.4

23.3

9.4

13.8

4.9

3.9

Acquisitions

Purchases of PPE

Purchase of Intangibles

Net cash used in investing activities

2.8

-0.6

0.0

0.0

0.0

0.0

0.0

Repayment of bank borrowings & other

loans

-0.1

-0.3

Interest paid

-0.1

-0.2

-0.2

-0.2

-0.2

-0.2

Finance income

0.0

0.1

0.1

0.2

0.2

0.3

Net cash (used in)/ from financing

activities

2.0

-0.1

-0.3

0.0

0.1

0.1

Net increase/ (decrease) in cash &

cash equivalents

0.6

23.3

9.1

13.8

5.0

4.1

Cash & cash equivalents at start of FY

0.0

0.6

23.8

32.9

46.7

51.7

Cash & cash equivalents at end of FY

0.6

23.8

32.9

46.7

51.7

55.8

Operating cash flow

Working capital changes
Net CF from operating activities
Investing activities

Financing activities
Proceeds from share issue
IPO/ share issue costs
Proceeds from bank borrowings

Source: ED

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13 May 2015

Motif Bio PLC

Hospital acquired pneumonia model

2015e

2016e

2017e

2018e

2019e

Projected HAP patients (that are Gram positive)

2021e

2022e

2023e

2024e

2025e

LAUNCH

US market (US$'000)
Current HAP patients in ICU - currently

2020e

400000
40% 161,600 163,216 164,848 166,497 168,162 169,843 171,542 173,257 174,990 176,740

Launch price - assume annual price increase

178,507

3800

Projected iclaprim IV $ price ($380/day, 10 day

course)

3,990

Projected iclaprim IV share of available patients

4,190

4,399

4,619

4,850

5,092

5,347

1%

4%

6%

8%

11%

13%

16%

Number of HABP patients treated with IV iclaprim

1,682

5,945

10,292

13,861

19,249

22,976

28,561

Projected iclaprim IV revenues ($'000)

6,710

24,905

45,276

64,021

93,354 117,003

152,716

Risk-adjusted iclaprim IV revenues ($'000)

3,355

12,452

22,638

32,010

46,677

58,501

76,358

40% 121,200 122,412 123,636 124,872 126,121 127,382 128,656 129,943 131,242 132,555

133,880

LAUNCH

EU market (US$'000)
Current HAP patients in ICU
Projected HAP patients (Gram positive)

300000

Projected iclaprim IV $ price ($380/day, 10 day

course)

4,190

Projected iclaprim IV share of available patients

4,399

4,619

4,850

5,092

5,347

1%

2%

3%

5%

7%

9%

Number of HABP patients treated with IV iclaprim

637

2,573

3,898

6,562

9,279

12,049

Projected iclaprim IV revenues ($'000)

2,668

11,319

18,006

31,825

47,251

64,427

Risk-adjusted iclaprim IV revenues ($'000)

1,334

5,660

9,003

15,913

23,626

32,213

40% 141,400 142,814 144,242 145,685 147,141 148,613 150,099 151,600 153,116 154,647

156,194

LAUNCH

RoW market (US$'000)

Current HAP patients in ICU
Projected HAP patients (Gram positive)

350000

Projected iclaprim IV $ price ($380/day, 10 day

course)

4,399

Projected iclaprim IV share of available patients

4,619

4,850

5,092

5,347

1%

2%

3%

5%

7%

Number of HABP patients treated with IV iclaprim

1,501

3,032

4,593

7,732

10,934

Projected iclaprim IV revenues ($'000)

6,603

14,005

22,278

39,376

58,461

Risk-adjusted iclaprim IV revenues ($'000)

3,301

7,002

11,139

19,688

29,231

Total hospital acquired pneumonia revenues

($'000)

6,710

27,573

63,198

96,031 147,458 203,630

275,604

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

4,194

17,233

39,499

60,020

92,161 127,269

172,253

2,097

8,617

19,749

30,010

46,081

GBP/$ rate
Total hospital acquired pneumonia revenues
('000)
Risk-adjusted hospital acquired pneumonia
revenues ('000)

50%

1.6

63,634

86,126

Source: ED

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Motif Bio PLC

13 May 2015

ABSSSI hospital model

2015e

2016e

2017e

US market (US$'000)
Current ABSSSI patients
(Hospitalisations)
Projected ABSSSI
patients (Gram positive)

2018e
LAUNCH

2019e

2020e

2021e

2022e

2023e

2024e

2025e

2000000

80% 1,616,000 1,632,160 1,648,482 1,664,966 1,681,616 1,698,432 1,715,417 1,732,571 1,749,896 1,767,395 1,785,069

Projected iclaprim IV $
price ($380/day, 10 day
course)

Projected iclaprim IV
share of available patients

3,800

3,990

4,190

4,399

4,619

4,850

5,092

5,347

1%

1%

2%

2%

3%

3%

3%

3%

Number of ABSSSI
patients treated with IV
iclaprim

8,325

16,816

25,476

34,308

43,314

47,247

53,022

58,015

Projected iclaprim IV
revenues ($'000)

31,634

67,096

106,734

150,921

200,065

229,143

270,007

310,204

Risk-adjusted iclaprim IV
revenues ($'000)

15,817

33,548

53,367

75,461

100,033

114,571

135,003

155,102

EU market (US$'000)
Current ABSSSI patients
(Hospitalisations)
Projected ABSSSI
patients (Gram positive)

LAUNCH
1000000
80%

Projected iclaprim IV $
price ($380/day, 10 day
course)

808,000

816,080

824,241

832,483

840,808

849,216

857,708

866,285

874,948

883,698

892,535

3,990

4,190

4,399

4,619

4,850

5,092

5,347

1%

1%

2%

2%

3%

3%

3%

Projected iclaprim IV
share of available patients
Number of ABSSSI
patients treated with IV
iclaprim

4,204

8,492

12,866

17,326

21,874

23,860

26,776

Projected iclaprim IV
revenues ($'000)

16,774

35,578

56,596

80,026

106,085

121,503

143,171

Risk-adjusted iclaprim IV
revenues ($'000)

8,387

17,789

28,298

40,013

53,042

60,751

71,585

849,216

857,708

866,285

874,948

883,698

892,535

4,190

4,399

4,619

4,850

5,092

5,347

1%

1%

2%

2%

3%

3%

RoW market (US$'000)

Current ABSSSI patients
(Hospitalisations)
Projected ABSSSI
patients (Gram positive)

LAUNCH
1000000
80%

808,000

816,080

824,241

832,483

840,808

Projected iclaprim IV $
price ($380/day, 10 day
course)
Projected iclaprim IV
share of available patients
Number of ABSSSI
patients treated with IV
Iclaprim

4,246

8,577

12,994

17,499

22,092

24,098

Projected iclaprim IV
revenues ($'000)

17,789

37,730

60,020

84,868

112,503

128,854

Risk-adjusted iclaprim IV
revenues ($'000)

8,894

18,865

30,010

42,434

56,251

64,427

Total ABSSSI revenues

($'000)

31,634

83,871

160,101

245,247

340,111

420,095

504,012

582,229

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

1.6

19,771

52,419

100,063

153,280

212,569

262,559

315,008

363,893

9,886

26,210

50,031

76,640

106,285

131,280

157,504

181,946

GBP/$ rate
Total ABSSSI revenues
('000)
Risk-adjusted ABSSSI
revenues ('000)

50%

Source: ED

22

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Head of Corporate
Gilbert Ellacombe
Direct: 0207 065 2698
Tel:
0207 065 2690
gilbert@equitydevelopment.co.uk

Investor Access
Hannah Crowe
Direct: 0207 065 2692
Tel:
0207 065 2690
hannah@equitydevelopment.co.uk

Ben Ferguson
Direct: 0207 065 2693
Tel:
0207 065 2690
ben.ferguson@equitydevelopment.co.uk

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