- Imeglimin Japanese New Drug Application (J-NDA) under review
following submission by Poxel’s partner, Sumitomo Dainippon Pharma,
with product launch anticipated in 20211
- Successful completion of PXL770 Phase 2a STAMP-NAFLD trial
in NASH with new data demonstrating greater response in high-risk
patients with co-existing type 2 diabetes (T2DM), estimated to
affect about 50% of NASH patients2
- 52-week Phase 2b trial evaluating up to two doses of PXL770
in approximately 100 patients per study arm with biopsy-proven NASH
and pre-diabetes or T2DM expected to commence in H2 2021
- PXL065 Phase 2 study underway with topline data readout
expected mid-2022
- Financial position strengthened through capital increase of
EUR 17.7 million in May 2020 and EUR 6 million in October 2020 in
non-dilutive funding in the form of a French Government Guarantee
Loan (Prêts Garantis par l’Etat or PGE) in the context of the
COVID-19 pandemic. This loan has an initial term of one year, with
a five-year extension option. The Company already decided to
activate the extension option
- As of December 31, 2020, cash and cash equivalents were EUR
40.2 million (USD 49.4 million)
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 announced its results for the year
ended December 31, 2020 and provided a corporate update.
“Looking back, 2020 was a strong year for Poxel in which we
achieved critical clinical milestones to advance our key programs
PXL770 and PXL065 into late-stage development with promising data
readouts, and further asserted ourselves as an industry leader in
metabolic diseases,” commented Thomas Kuhn, CEO of Poxel. “Further,
with the submission of the J-NDA for Imeglimin for the treatment of
T2DM we are in a strong position and moving toward a potential
market launch in Japan in 20212. We were also able to present
additional results from our Phase 3 TIMES 2 and TIMES 3 clinical
trials at the 56th EASD Annual Meeting, highlighting Imeglimin’s
unique position and strong therapeutic profile both as a
monotherapy and in combination with standard of care available in
Japan, including DPPIV inhibitors, a notable feature considering
that this drug class is the market leader in Japan and is
prescribed to approximately 80% of treated T2DM patients3. In
parallel with this, we are pursuing the development of our two NASH
candidates, PXL770 and PXL065. Results from our Phase 2a trial with
PXL770 showed consistently greater response in patients with
coexisting T2DM, highlighting its potential in this high-risk and
underserved patient population. Despite the pandemic, recruitment
for the PXL065 Phase 2 trial has been progressing as planned. Taken
together, all of these achievements show the tremendous potential
of the pipeline we are proud to build upon and the future we are
headed toward as we expand our AMPK activation and TZD
platforms.”
“2021 will be a very special year for Poxel. We have built the
Company to bring novel treatments to patients with chronic
metabolic disorders and this vision will become a reality once
Imeglimin is approved in Japan, anticipated this year. We will also
complete PXL065 Phase 2 recruitment and are planning to initiate a
Phase 2b study for PXL770 in biopsy-proven NASH patients. We remain
committed to advancing our programs alone and together with
partners in an effort to bring tangible solutions to patients
living with metabolic diseases,” continued Mr. Kuhn.
Clinical Development Updates
Imeglimin (Type 2 Diabetes)
- In November 2020, Poxel announced that, for strategic reasons,
its partner Metavant would not be moving forward with the Imeglimin
development program. This decision was not based on any efficacy,
safety or other data generated through the partnership. Poxel
regained all rights to Imeglimin at the end of January 2021.
- In September 2020, Poxel presented Imeglimin Phase 3 TIMES
results at the 56th European Association for the Study of Diabetes
Annual Meeting. Phase 3 TIMES 2 and TIMES 3 trial results
demonstrated Imeglimin met its primary endpoints and objectives and
was observed to exhibit a favorable safety and tolerability
profile.
- In July 2020, Poxel announced the submission of the Imeglimin
J-NDA for the treatment of T2DM by its partner, Sumitomo Dainippon
Pharma. The submission triggered a JPY500 million (EUR 4.1 million,
USD 4.7 million)4 development milestone payment to Poxel with the
potential for a JPY 1.75 billion (approximately EUR 13.8 million,
USD 16.9 million)5 milestone payment upon product approval. The
target product launch date is anticipated in 20216 which will
trigger the potential for sales-based payments and escalating
double-digit royalties on product sales.
- In April 2020, Poxel announced the publication of Imeglimin
clinical study results in Clinical Pharmacokinetics. The two
clinical studies evaluated the potential for drug-drug interactions
of Imeglimin with two widely prescribed medications, metformin or
sitagliptin. Imeglimin was observed to be safe and well-tolerated
in both studies.
PXL770 (NASH)
- In December 2020, Poxel announced additional positive Phase 2a
results showing greater response in high-risk patients with
coexisting T2DM, and a Phase 2b Plan for PXL770, an oral
first-in-class AMPK activator, in NASH7.
- In November 2020, Poxel presented new preclinical data for
PXL770 at the AASLD The Liver Meeting® 2020. PXL770 revealed the
potential for direct effects on key components of NASH as both a
mono- and combination therapy producing anti-inflammatory effects
in mouse liver and adipose tissue and in human immune cells as well
as specific biomarkers related to improvements involving
mitochondria in mouse liver.
- In October 2020, Poxel announced positive results from its
Phase 2a NASH trial with PXL770. The trial met its primary efficacy
endpoint and was observed to be safe and well tolerated.
- In September 2020, Poxel presented PXL770 preclinical
cardio-renal results at the 56th European Association for the Study
of Diabetes Annual Meeting. PXL770 was observed to improve renal
and cardiac disease in a preclinical model which revealed its
utility for not only NASH co-morbidities but also additional
indications driven by metabolic dysfunction.
- In June 2020, Poxel announced positive pharmacokinetic (PK) /
pharmacodynamic (PD) study results for PXL770.
PXL065 (NASH)
- PXL065 is currently being evaluated in DESTINY-1, a Phase 2
study in biopsy-proven NASH patients, which seeks to identify the
optimal dose or doses for a Phase 3 registration trial.
- The recruitment for the DESTINY-1 Phase 2 study is expected to
be completed in 2021.
- In November 2020, Poxel presented Phase 1b clinical results for
PXL065 at the AASLD The Liver Meeting® 2020. Analysis of results
from the study predicts efficacy at 15 mg once-daily is equivalent
to 45 mg Actos®8, with little to no PPARγ-related side effects,
such as weight gain.
Early Stage Development
- In November 2020, at ALD Connect, the Company presented new
results in cell-based and in vivo preclinical models of
adrenoleukodystrophy. These data showed that both PXL770 and PXL065
produced significant improvements in disease-associated pathology,
providing a rationale to pursue this indication with next
generation molecules derived from both platforms.
- The potential of PXL770 and PXL065 with other agents in
development continues to be assessed in preclinical studies.
Further preclinical studies are ongoing to evaluate direct
adenosine monophosphate-activated protein kinase (AMPK) activation
and mitochondrial pyruvate carrier (MPC) inhibition in additional
metabolic, specialty and rare diseases.
Corporate Updates
- In October 2020, Poxel received EUR 6 Million in non-dilutive
financing guaranteed by the French government.
- In May 2020, Poxel successfully raised EUR 17.7 million in a
capital increase. The proceeds will enable the acceleration of
development plans for PXL770 and PXL065 for treatment of NASH, the
pursuit of development activities in other metabolic diseases and
will be used for general corporate purposes.
- In January 2020, Poxel appointed David E. Moller, MD, as CSO.
Dr. Moller is an industry leader in the discovery and development
of new therapeutic agents, particularly in diabetes and metabolic
disorders.
Significant Events after the Period
- In February 2021, Poxel announced the resolution of the
arbitration procedure with Merck Serono.
- In January 2021, Poxel regained Imeglimin rights from Metavant.
Metavant has returned all rights to Imeglimin to Poxel in addition
to all data, materials and information, including FDA regulatory
filings, related to the program. Metavant is not entitled to any
payments from Poxel as part of the return.
- Imeglimin’sinnovative MOA and Phase 2b/3 results in Japan were
published in peer reviewed journals.
___________________ *Actos is the branded version of
pioglitazone and a registered trademark of Takeda Chemical
Industries, Ltd.
Financial Statements for Full Year 2020 (IFRS
Standards)
Revenue
Poxel reported revenues of EUR 6.8 million for the year ended
December 31, 2020, as compared to EUR 26.6 million during the
corresponding period in 2019.
The revenues for 2020 include the JPY 500 million (EUR 4.0
million) milestone payment that Poxel received from Sumitomo
Dainippon Pharma for the submission of the Imeglimin J-NDA. To a
lesser extent, it also includes an allocated portion of the EUR
36.0 million upfront payment received from Sumitomo Dainippon
Pharma relating to the strategic corporate partnership announced on
October 30, 2017, as well as the residual Imeglimin Phase 3 program
costs in Japan incurred in 2020 that were re-invoiced to Sumitomo
Dainippon Pharma. Both the allocated portion of the upfront payment
and the re-invoiced costs of the Phase 3 Trials of
IMeglimin for Efficacy and Safety (TIMES)
program have been recognized based on the accounting percentage of
the completion of this program, which has been fully completed, and
therefore led to the decrease in revenue in 2020.
EUR (in millions)
FY
FY
2020
12 months
2019
12 months
Roivant Agreement
18
276
Sumitomo Agreement
6,787
26,179
Other
1
101
Total revenues
6,806
26,556
The audit procedures have been performed and the issuance of the
audit report is in process.
Income Statement
Poxel devotes the bulk of its resources to research and
development (R&D) activities. R&D expenses totaled EUR 26.7
million in 2020, as compared to EUR 40.2 million in 2019. R&D
expenses in 2020 primarily reflected the clinical costs incurred
for the ongoing Phase 2 programs of PXL770 and PXL065, the
Company’s two compounds for the treatment of NASH. To a lesser
extent, they also included the residual clinical study costs
incurred for Imeglimin Phase 3 TIMES program over the period, which
were mostly re-invoiced to Sumitomo Dainippon Pharma. The decrease
in R&D costs was mostly driven by the completion of the TIMES
program in Japan, for which expenses of EUR 1.3 million were
incurred in 2020, compared to EUR 20 million in 2019.
R&D costs are net of the R&D Tax Credit (CIR) that
resulted in income of EUR 2.5 million in 2020, as compared to EUR
4.4 million in 2019.
General and administrative expenses totaled EUR 9.9 million in
2020, as compared to EUR 11.1 million in 2019. The decrease in
G&A costs reflects non-recurring costs incurred in 2019,
partially offset by increasing personnel costs in 2020, reflecting
recruitments to support the continuous growth and development of
the company.
The financial income amounted to a loss of EUR 2 million in
2020, as compared to a loss of EUR 1.1 million in 2019. The
financial loss in 2020 includes interest expenses for EUR 1.3
million, a EUR 1.3 million non-cash income reflecting the change in
IPF warrants fair value and a EUR 1.7 million exchange rate loss,
mostly reflecting year-end reevaluation of deposit in Dollar.
The net result for the financial period ending December 31, 2020
was a net loss of EUR 31.9 million, as compared to a net loss of
EUR 25.7 million in 2019.
Condensed Income Statement
EUR (in thousands)
FY
FY
2020
12 months
2019
12 months
Revenue
6,806
26,557
Net research and development
expenses**
(26,718)
(40,177)
General and administrative expenses
(9,935)
(11,051)
Operating gain (loss)
(29,847)
(24,671)
Financial income (expenses)
(1,975)
(1,071)
Income tax
(36)
(1)
Net income (loss)
(31,858)
(25,743)
**Net of R&D tax credit
The audit procedures have been performed and the issuance of the
audit report is in process.
Cash
As of December 31, 2020, total cash and cash equivalents were
EUR 40.2 million (USD 49.4 million), as compared to EUR 37.2
million (USD 41.8 million) as of December 31, 2019. Cash and cash
equivalents net of financial liabilities (excluding lease and
derivative debts) were EUR 17.1 million as of December 31, 2020, as
compared to EUR 27.4 million as of December 31, 2019.
The management team will host a conference call on Thursday,
March 25th in English at 9:30 am EDT (New York time) / 2:30 pm CET
(Paris time). A presentation will be available in the Investors
section of the Poxel website.
To register for the video-conference:
https://us02web.zoom.us/webinar/register/WN_X5epv0UiQPyA6NRZRo3t_A
The replay of the video conference will be available on Poxel’s
website:
https://www.poxelpharma.com/en_us/investors/company-information/corporate-presentations
Planned Presentations and Participation at the Following
Upcoming Events (virtual)
- Mitochondria-Targeted Drug Development Summit, April 27-29
- Kempen Life Sciences Conference, May 5
- Japan Diabetes Society, May 20-21
Next Financial Press Release: First Quarter 2021
Financial Update, April 21, 2021
About Imeglimin
Imeglimin is a new chemical substance classified as a
tetrahydrotriazine compound, and the first clinical candidate in a
chemical class. Imeglimin has a unique dual 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 pancreas, muscles, and the liver, 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 NASH
NASH is a metabolic disease with no clear disease origin that is
quickly becoming a worldwide epidemic. It is characterized by the
accumulation of fat in the liver causing inflammation and fibrosis.
The disease can be silent for a long period of time, but once it
accelerates, severe damage and liver cirrhosis can occur, which can
significantly impact liver function or can even result in liver
failure or liver cancer. Typical risk factors for NASH include
obesity, elevated levels of blood lipids (such as cholesterol and
triglycerides) and type 2 diabetes. Currently no curative or
specific therapies are available.
About PXL770
PXL770 is a first-in-class 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
NASH.
About PXL065
PXL065 is a novel, proprietary deuterium-stabilized
R-pioglitazone. Although pioglitazone is not approved by the FDA
for the treatment of NASH, it is the most extensively studied drug
for NASH and has demonstrated “resolution of NASH without worsening
of fibrosis” in a Phase 4 trial9 . Pioglitazone is the only drug
recommended for biopsy-proven NASH patients by the Practice
Guidelines published by the AASLD and the European Association for
the Study of the Liver (EASL)10. Pioglitazone’s off-label use for
NASH, however, has been limited due to the PPARγ-related side
effects, which include weight gain, bone fractures and fluid
retention. Pioglitazone is a 1:1 mixture of two mirror-image
compounds (R- and S-stereoisomers) that interconvert in vivo. Using
deuterium, we stabilized each stereoisomer and characterized their
different pharmacological properties. In in vitro studies, PXL065
has been shown to target mitochondrial pyruvate carrier (MPC) as an
inhibitor. In preclinical animal models, PXL065 exhibits the
anti-inflammatory and NASH activity associated with pioglitazone
with little or no weight gain or fluid retention, side effects
which are associated with the Stereoisomer. Based upon preclinical
and Phase 1 results to date, Poxel believes that PXL065 may have a
better therapeutic profile than pioglitazone for NASH.
About Poxel SA
Poxel is a dynamic biopharmaceutical company that uses its
extensive expertise in developing innovative drugs for metabolic
diseases, with a focus on type 2 diabetes and non-alcoholic
steatohepatitis (NASH). In its mid-to-late-stage pipeline, the
Company is currently advancing three drug candidates as well as
earlier-stage opportunities. Imeglimin, Poxel’s first-in-class lead
product, targets mitochondrial dysfunction. Poxel has a strategic
partnership with Sumitomo Dainippon Pharma for Imeglimin in Japan,
China, South Korea, Taiwan and nine other Southeast Asian
countries. A Japanese new drug application (J-NDA) is under review
by the Pharmaceuticals and Medical Devices Agency (PMDA) to request
approval for the manufacturing and marketing of Imeglimin for the
treatment of type 2 diabetes. After successfully completing a Phase
2a proof-of-concept trial for the treatment of NASH, which met its
primary endpoint and study objectives, for PXL770, a first-in-class
direct adenosine monophosphate-activated protein kinase (AMPK)
activator, Poxel plans to initiate a Phase 2b program in the second
half of 2021. PXL770 could also have the potential to treat
additional metabolic diseases. PXL065 (deuterium-stabilized
R-pioglitazone), a MPC inhibitor, is in a streamlined Phase 2 trial
for the treatment of NASH. Poxel also has additional earlier-stage
programs from its AMPK activator and deuterated TZD platforms
targeting chronic and rare metabolic diseases. The Company intends
to generate further growth through strategic partnerships and
pipeline development. Listed on Euronext Paris, Poxel is
headquartered in Lyon, France, and has subsidiaries in Boston, MA,
and Tokyo, Japan. For more information, please visit:
www.poxelpharma.com
In the context of the COVID-19 outbreak, which was declared a
pandemic by the World Health Organization (WHO) on March 12, 2020,
the Company is regularly reviewing the impact of the outbreak on
its business.
As of the date of this press release, and based on publicly
available information, the Company has not identified the
occurrence of any material negative effect on its business due to
the COVID-19 pandemic that remains unresolved. However, the Company
anticipates that the COVID-19 pandemic could have further material
negative impact on its business operations. The worldwide impact of
COVID-19 may notably affect the Company’s internal organization and
efficiency, particularly in countries where it operates and where
confinement measures are implemented by the authorities. In
addition, COVID-19 may impact market conditions and the Company’s
ability to seek additional funding or enter into partnerships.
Particularly, delays in the supply of drug substance or drug
products, in the initiation or the timing of results of preclinical
and/or clinical trials, as well as delays linked to the
responsiveness of regulatory authorities could occur, which could
potentially have an impact on the Company’s development programs
and partnered programs. The Company will continue to actively
monitor the situation.
All statements other than statements of historical fact included
in this press release about future events are subject to (i) change
without notice and (ii) factors beyond the Company’s control. These
statements may include, without limitation, any statements preceded
by, followed by or including words such as “target,” “believe,”
“expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,”
“project,” “will,” “can have,” “likely,” “should,” “would,” “could”
and other words and terms of similar meaning or the negative
thereof. Forward-looking statements are subject to inherent risks
and uncertainties beyond the Company’s control that could cause the
Company’s actual results or performance to be materially different
from the expected results or performance expressed or implied by
such forward-looking statements.
___________________ 1 Year noted is Fiscal Year from April 2021
to March 2022, which is Sumitomo Dainippon Pharma’s Fiscal Year. 2
Prevalence of T2DM in patients with NASH estimated to be 47%;
approximately 26% of T2DM patients have NASH; clinical and economic
burden of NASH in T2DM greater than with either disease alone
(Younossi ZM et al, Hepatology 2016, 64, 73–84; Cusi K, Diabetes
Care 2020, 43:275-79; Younossi ZM et al, Diabetes Care 2020,
43:283–89). 3 Year noted is Fiscal Year from April 2021 to March
2022, which is Sumitomo Dainippon Pharma’s Fiscal Year. 4 IQVIA
data FY2016 and NDB data FY2016. 5 Converted at the exchange rate
as of July 28, 2020. 6 Based on the JPY/EUR exchange rate at
December 31, 2020. 7 Sumitomo Dainippon Pharma’s Fiscal Year, from
April 2021 to March 2022. 8 Prevalence of T2DM in patients with
NASH estimated to be 47%; approximately 26% of T2DM patients have
NASH; clinical and economic burden of NASH in T2DM greater than
with either disease alone (Younossi ZM et al, Hepatology 2016, 64,
73–84; Cusi K,Diabetes Care 2020, 43:275-79; Younossi ZM et
al,Diabetes Care 2020, 43:283–89). 9 Cusi, et al., Ann Intern Med.
2016, 165(5), 305-315. 10 J Hepatol. 2016, 64(6),1388-402;
Hepatology 2018, 67, 328-357.
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Poxel SA
Catherine David Investor Relations &
Communication Manager catherine.david@poxelpharma.com +33 7 64 57
61 78 Investor relations / Media - EU/US Trophic
Communications Stephanie May or Valeria Fisher poxel@trophic.eu +49
171 185 56 82 or +49 175 804 1816 Investor relations / Media -
France NewCap Emmanuel Huynh or Arthur Rouillé poxel@newcap.eu
+33 1 44 71 94 94
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