Market Overview

Poxel Provides Business Update and Reports Results for Full Year 2017

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  • Signed two strategic partnership agreements for Imeglimin for
    global rights with potential value of up to approximately $925 million
    plus royalties on net sales
  • Successfully completed Phase 2b for Imeglimin and initiated Phase 3
    TIMES program in Japan for the treatment of type 2 diabetes
  • Advanced PXL770, a direct AMPK activator, for the treatment of NASH

Poxel will host an investor conference call today at 2 pm EDT (7 pm
CET). To participate in the call, please use the dial-in numbers: USA:
+1 844-286-0643 UK: +44 (0) 2071943759 FR: +33 (0)1 72 72 74 03

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POXEL
SA
(Euronext – POXEL - FR0012432516), a biopharmaceutical company
focused on the development of innovative treatments for metabolic
disorders, including type 2 diabetes and non-alcoholic steatohepatitis
(NASH), today provided a business update and its results for the year
ended December 31, 2017.

"I am very pleased to report that over the last several months our
dedication and hard work have led us to achieve two significant
partnerships for Imeglimin that cover the global diabetes markets. We
believe our partnerships with Sumitomo Dainippon Pharma and Roivant
Sciences represent very important validations of Imeglimin's strong and
differentiated clinical profile, as well as our internal capabilities to
advance a program worldwide to a critical point," said Thomas Kuhn, CEO
of Poxel. "Over the last few months, we have also made substantial
progress for Imeglimin in Japan with the initiation of all three pivotal
Phase 3 TIMES trials and we are on track for the data readout in 2019
and the JNDA submission in 2020. For the U.S. and Europe, we are working
closely with Roivant Sciences with the goal to initiate Phase 3 in 2019."

"For our second program, PXL770, we are currently completing the Phase 1
multiple ascending dose study and data is anticipated mid-year. We
believe that PXL770 has the potential to treat several chronic metabolic
diseases, including those that affect the liver, such as NASH,"
continued Thomas Kuhn. "Pending successful completion of our ongoing
Phase 1 program, we are planning to initiate a Phase 2a proof-of-concept
study in patients with NAFLD, a condition in which fat builds up in the
liver. This study is expected to begin during the second half of 2018.
In addition, we are actively working to further leverage our internal
capabilities and are assessing additional development opportunities in
the metabolic area."

Recent Business Highlights and Full Year Financial Results

Imeglimin
Imeglimin is the
first orally-available drug candidate that simultaneously targets all
three key organs affected by diabetes: the pancreas, the liver and the
muscles. Imeglimin has completed several important milestones, which
include the following highlights below.

Signed Strategic Partnership Agreements
Covering Global Rights

A strategic corporate partnership
for Imeglimin was signed with Sumitomo Dainippon Pharma in October 2017
for Japan, China and 11 other Asian countries1 and with
Roivant Sciences in February 2018 for the U.S., Europe and all other
countries not covered in the Sumitomo agreement. These agreements will
enable the Imeglimin Phase 3 registration program to progress worldwide.

  • In total, Poxel received $92 million (or approximately €76 million) in
    upfront payments, which includes an equity investment of $15 million
    (or approximately €12 million) from Roivant.
  • Through these agreements, Poxel has the potential to receive up to
    approximately $857* million (or approximately €705* million) in
    development and regulatory milestones, and sales-based payments.
  • Poxel is entitled to receive escalating double-digit royalties on net
    sales.

Initiation of Phase 3 TIMES 1, TIMES 2 and
TIMES 3 trials in Japan

TIMES (Trials of Imeglimin
for Efficacy and Safety), the Phase 3 program
for Imeglimin in Japan for the treatment of type 2 diabetes, consists of
three pivotal trials involving approximately 1,100 patients. Following
the signing of the strategic corporate partnership with Sumitomo
Dainippon Pharma, the Phase 3 TIMES 1 trial was initiated at the end of
2017 and TIMES 2 and TIMES 3 trials were initiated during the first
quarter of 2018. The TIMES program includes the following three trials
performed using the dose of 1000 mg twice daily:

  • TIMES 1: A Phase 3, 24-week, double-blind placebo-controlled,
    randomized, monotherapy study to assess the efficacy, safety and
    tolerability of Imeglimin in Japanese patients with type 2 diabetes,
    using the change in HbA1c as the primary endpoint. Secondary endpoints
    of the trial will include other standard glycemic and non-glycemic
    parameters.
  • TIMES 2: A Phase 3, 52-week, open-label, parallel-group study to
    assess the long-term safety and efficacy of Imeglimin in Japanese
    patients with type 2 diabetes. In this study, Imeglimin will be
    administrated orally as a monotherapy or combination therapy with
    existing hypoglycemic agents, including a DPP4 inhibitor, SGLT2
    inhibitor, biguanide, sulphonylurea and GLP1 receptor agonist.
  • TIMES 3: A Phase 3, 16-week, double-blind, placebo-controlled,
    randomized study with a 36-week open-label extension period to
    evaluate the efficacy and safety of Imeglimin in combination with
    insulin in Japanese patients with type 2 diabetes and inadequate
    glycemic control on insulin therapy.

Reported Robust Efficacy Results from the Phase
2b Study in Japan

  • The Phase 2b randomized, double-blind, placebo-controlled study tested
    three doses of Imeglimin (500 mg, 1000 mg and 1500 mg) administered
    twice-daily for 24 weeks in 299 Japanese patients for the treatment of
    type 2 diabetes. In May 2017, Poxel announced the study achieved
    statistically significant results for its primary and secondary
    endpoints. These data were presented at the European Association for
    the Study of Diabetes 53rd Annual Meeting in September 2017.
  • The primary endpoint achieved statistical significance (p<0.0001) for
    the change from baseline in glycated hemoglobin (HbA1c) versus placebo
    in all treatment groups at 24 weeks. Placebo-adjusted HbA1c reduction
    was 0.52%, 0.94% and 1.00% for the 500 mg, 1000 mg and 1500 mg dose
    twice-daily, respectively. Overall, the study showed that Imeglimin
    was safe and well tolerated and the adverse event profile was
    consistent to what was observed in the U.S. and EU Phase 1 and 2
    programs.

Advanced PXL770 for the treatment of NASH
PXL770
is a first-in-class direct adenosine monophosphate-activated protein
kinase (AMPK) activator. Through its unique mechanism of action that
directly activates AMPK, PXL770 acts on a very important biological
target. This target, which plays a key role as a master regulator of
cellular energy, has the potential to treat numerous chronic metabolic
diseases, including diseases that affect the liver, such as NASH2,
which is a severe form of nonalcoholic fatty liver disease (NAFLD). This
target is important because it has the potential to trigger benefits on
the three key pathophysiology processes involved in NASH development:
liver steatosis, inflammation and fibrosis. PXL770 may be differentiated
from other compounds in development for liver diseases since AMPK
activation has the potential to also treat NASH comorbidities,
specifically targeting cardiovascular risk factors, such as
hyperglycemia, insulin resistance, dyslipidemia, inflammation, and
obesity.

  • In September 2017, a Phase 1b multiple ascending dose (MAD) trial for
    PXL770 was initiated. Completion of this study is anticipated
    mid-2018. The MAD trial will include up to 76 subjects and evaluate
    the safety, tolerability and pharmacokinetics of PXL770 in at least
    four dose groups.

    • Results from the first part of the single ascending dose study
      indicate that PXL770 exhibited a favorable safety and tolerability
      profile with no reported serious adverse events.
  • Poxel is planning to initiate a Phase 2a proof-of-concept study in
    patients with NAFLD during the second half of 2018.
  • Poxel is also exploring other metabolic diseases for proof-of-concept
    studies for PXL770.

Corporate Update

  • Poxel expanded the depth of its management team during 2017 with the
    appointments of Anne Renevot as Chief Financial Officer and Christophe
    Arbet-Engels as Chief Medical Officer and Executive Vice President,
    Late Development & Medical Affairs.
  • In addition, Kumi Sato was appointed to its Board of Directors. Ms.
    Sato will help support Poxel's corporate strategy for Imeglimin in
    Japan.
  • During 2017, ENYO Pharma SA reported that the Phase 1a single and
    multiple ascending dose trial evaluating EYP001 in healthy subjects
    has been completed. The results show that EYP001 was safe and
    well-tolerated at all doses studied in 80 subjects. A Phase 1b
    randomized, double-blind, placebo-controlled study in chronic HBV
    patients was initiated at the end of 2017 to determine the safety and
    tolerability of daily oral administration of EYP001 over four weeks.
    EYP001 is an FXR agonist licensed to ENYO Pharma and Poxel is entitled
    to receive milestone payments and royalties on net sales.

Financial Statements for Full Year 2017 (IFRS
standards)

Income statement
Poxel reported annual revenues of €5.3
million, reflecting a portion of the €36 million upfront payment
received from Sumitomo Dainippon Pharma relating to the strategic
corporate partnership announced on October 30, 2017 and the Imeglimin
Phase 3 program costs in Japan incurred during the fourth quarter that
were re-invoiced to Sumitomo Dainippon Pharma. Both the upfront payment
and re-invoiced costs are recognized according to the percentage of
completion of the Phase 3 Trials of IMeglimin for Efficacy and Safety
(TIMES) program.

Poxel devotes the bulk of its resources to research and development
activities. Research and Development (R&D) expenses totalled €21.0
million in 2017, as compared to €17.7 million in 2016. They mainly
reflect the clinical study costs incurred for the Company's lead
program, Imeglimin and its second compound, PXL770. In 2017, they also
include the payment made to Merck Serono relating to the upfront payment
that Poxel received from Sumitomo Dainippon Pharma.

The R&D costs are net of the R&D Tax Credit (CIR) that resulted in
income of €3.1 million in 2017 as compared to € 3.2 million in 2016.

General and administrative expenses totalled €6.2 million, as compared
to €6.7 million in 2016. The €0.5 million decrease was mainly driven by
non-recurrent 2016 costs related to financing activities.

The financial expenses totalled €0.4 million, as compared to €0.2
million in 2016. They mainly reflect foreign currency exchange loss.

The net result for the financial period ending December 31, 2017 was a
net loss of €22.3 million, compared to a net loss of €24.5 million in
2016.

Cash
As of December 31, 2017, cash and cash equivalents were
€53.4 million ($64.1 million).* This figure does not include the upfront
payment and investment received from Roivant Sciences of $50 million
(approximately €40 million) in February 2018.

* Net cash position is €53,4m reflecting cash of €54,1m and overdrafts
for €0,7m

Condensed Income Statement In thousand €*

            31 Dec 2017      

31 Dec 2016

 

Turnover 5 291 70
Net research and development expenses (20 973) (17 675)
General and administrative expenses (6 219) (6 678)
Operating loss (21 902) (24 282)
Financial expenses/Financial income (396) (201)
Net loss (22 298) (24 482)

*The audit procedures have been performed and the certification report
is in process.

Number of shares and voting rights as of December 31, 2017:

Month       Date      

Total number
of shares
outstanding

     

Total of
theoretical
voting
rights (1)

     

Total of exercisable
voting rights (2)

December 12/31/2017 23,127,428 23,127,428 23,102,952

(1) The total number of theoretical voting rights (or "gross" voting
rights) is used as the basis for calculating the crossing of
shareholding thresholds. In accordance with Article 223-11 of the AMF
General Regulation, this number is calculated on the basis of all shares
to which voting rights are attached, including treasury shares whose
voting rights have been suspended.
(2) The total number of
exercisable voting rights (or "net" voting rights) is calculated without
taking into account the treasury shares with suspended voting rights, in
this case, shares held by the Company in the context of a liquidity
contract agreement with ODDO.

Next financial press release: Q1-turnover and cash position
April 23, 2018.

About Imeglimin
Imeglimin is the first clinical candidate in
a new chemical class of oral agents called Glimins by the World Health
Organization. Imeglimin has a unique mechanism of action ("MOA") that
targets mitochondrial bioenergetics. Imeglimin acts on all three key
organs which play an important role in the treatment of type 2 diabetes:
the liver, muscles and the pancreas, and it has demonstrated glucose
lowering benefits by increasing insulin secretion in response to
glucose, improving insulin sensitivity and suppressing gluconeogenesis.
This MOA has the potential to prevent endothelial and diastolic
dysfunction, which can provide protective effects on micro- and
macro-vascular defects induced by diabetes. It also has the potential
for protective effect on beta-cell survival and function. This unique
MOA offers the potential opportunity for Imeglimin to be a candidate for
the treatment of type 2 diabetes in almost all stages of the current
anti-diabetic treatment paradigm, including monotherapy or as an add-on
to other glucose lowering therapies.

About PXL770
PXL770 is a first-in-class direct adenosine
monophosphate-activated protein kinase (AMPK) activator. AMPK is a
central regulator of multiple metabolic pathways leading to the control
of lipid metabolism, glucose homeostasis and inflammation. Based on its
central metabolic role, targeting AMPK offers the opportunity to pursue
a wide range of indications to treat chronic metabolic diseases,
including diseases that affect the liver, such as non-alcoholic
steatohepatitis (NASH).

About Poxel SA
Poxel uses its development expertise in
metabolism to advance a pipeline of drug candidates focused on the
treatment of metabolic disorders, including type 2 diabetes and
non-alcoholic steatohepatitis (NASH). We have successfully completed the
Phase 2 clinical program for our first-in-class lead product, Imeglimin,
which targets mitochondrial dysfunction, in the U.S., EU and Japan.
Together, with our partner Sumitomo Dainippon Pharma, we are conducting
the Phase 3 TIMES program for the treatment of type 2 diabetes in Japan.
Our partner Roivant Sciences will be responsible for
Imeglimin's development and commercialization in countries outside of
Poxel's partnership with Sumitomo Dainippon Pharma, including the U.S.
and Europe. Our second program, PXL770, a first in class direct
adenosine monophosphate-activated protein kinase (AMPK) activator, is in
Phase 1 and we plan on developing it for the treatment of NASH. We
intend to generate further growth through strategic partnerships and
pipeline development. (Euronext: POXEL, www.poxelpharma.com)

1 including: South Korea, Taiwan, Indonesia, Vietnam,
Thailand, Malaysia, The Philippines, Singapore, Republic of the Union of
Myanmar, Kingdom of Cambodia, and Lao People's Democratic Republic.
*
Converted at the exchange rate at the date of the agreement.
2
Source: Smith B. K et al., (2016) Am J Physiol Endocrinol Metab 311,
E730 – E740

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