We're Developing Innovative Drugs for Metabolic Diseases
At Poxel, we are a dynamic biopharmaceutical company developing innovative drugs for metabolic diseases, with a focus on type 2 diabetes and non-alcoholic steatohepatitis (NASH). Based in Lyon, France, Poxel was spun out in 2009 from Merck Serono, a global leader in the field of metabolic disorders at that time.
We believe that targeting cellular energy regulation pathways for the treatment of metabolic diseases, including type 2 diabetes is of critical importance as disbalances are at the root of those diseases. All three of our clinical stage pipeline programs address significant targets in the energy metabolism pathways. Imeglimin, our lead program, targets mitochondrial dysfunction, mitochondria being the power station of the cell, PXL770 activates the adenosine monophosphate-activated protein kinase (AMPK), an important energy sensor, and PXL065 (DRX-065) inhibits the mitochondrial pyruvate carrier (MPC).
Our Core Strengths
Our innovative pipeline of first-in-class drug candidates with disease-modifying mechanisms of action offers the potential for safer and more effective therapies for metabolic diseases, including type 2 diabetes.
- Developing first-in-class treatments for type 2 diabetes, NASH and other metabolic diseases with significant unmet medical needs.
- Leading clinical development expertise in metabolic diseases, including type 2 diabetes.
- Establishing global strategic corporate partnerships.
- Sumitomo Dainippon Pharma is our development and commercialization partner for Imeglimin for the treatment of type 2 diabetes in Japan, China and other Asian countries.
- Roivant Sciences has a strategic development and license agreement for Imeglimin in the U.S., Europe, and other countries worldwide*
- Enyo Pharma has a licensing agreement for our FXR (farnesoid X receptor) agonist. Enyo has completed a Phase 1 study and is currently conducting Phase 2 trials in Hepatitis B and NASH.
- Through an agreement with DeuteRx, Poxel acquired PXL065 (DRX-065), a clinical stage program for the treatment of NASH, as well as additional deutered drug candidates for metabolic, specialty and rare diseases.
- The Phase 3 TIMES program for Imeglimin in Japan is currently ongoing. Top-line results from the TIMES 1 trial were announced in April 2019 and the trial met its primary and secondary endpoints. The full Phase 3 TIMES 1 data results are expected later this year. The Phase 3 TIMES 3 16-week, double-blind, placebo controlled, randomized part of the trial is expected to report data mid-year 2019. The TIMES 2 and full results from the TIMES 3 trial are anticipated to report results in the fourth quarter of 2019. The Imeglimin Japanese New Drug Application (JNDA) is targeted for 2020. Phase 3 program-related work for Imeglimin in the U.S. and Europe is underway and a clinical trial in type 2 diabetes patients with chronic kidney disease 3b/4 is ongoing.
- Phase 3 program-related work for Imeglimin in the U.S. and Europe is underway and a clinical trial in type 2 diabetes patients with chronic kidney disease 3b/4 is ongoing.
- Our second clinical candidate, PXL770 is a novel direct AMPK activator. It has the potential to address a wide range of chronic metabolic diseases, including diseases that affect the liver, such as non-alcoholic steatohepatisis (NASH). Based on the favorable safety and pharmacokinetic profile in the completed Phase 1 program, we have initiated a Phase 2a proof-of-concept program for PXL770 in NASH. Results from this study are expected during the first half of 2020.
- Our third pipeline compound, PXL065 (DRX-065) (deuterium-stabilized R-pioglitazone), is a mitochondrial pyruvate carrier inhibitor. DRX-065 is the R-stereoisomer (single isomer) of pioglitazone. DRX-065 is currently in Phase 1 and is being developed for the treatment of NASH.
*The Poxel and Roivant agreement includes all countries other than those covered under the Poxel and Sumitomo Dainippon Pharma agreement, which includes Japan, China, the Republic of Korea, Taiwan, Indonesia, Vietnam, Thailand, Malaysia, The Philippines, Singapore, Republic of the Union of Myanmar, Kingdom of Cambodia, and Lao People's Democratic Republic.
Our innovative pipeline of first-in-class products with disease-modifying mechanisms of action offers the potential for safer and more effective therapies for type 2 diabetes and other metabolic diseases. Our lead clinical candidate, Imeglimin, has completed Phase 2 clinical development for type 2 diabetes in the United States, Europe and Japan, completing 8 Phase 2 clinical trials. The Phase 3 TIMES program for Imeglimin in Japan is currently underway.
Our Key Value Drivers
Imeglimin (Type 2 diabetes), PXL770 (NASH) and PXL065 (DRX-065) (NASH)
The Japanese/Asian Market
- Japan/Asia is a key focus for Poxel and is an integral part of our business strategy.
- Sumitomo Dainippon Pharma, a leading pharmaceutical company with an extensive and successful track record in late-stage development and commercialization in Asia, is our strategic partner for Imeglimin in Japan, China, and 11 other Asian countries.
- For Japan, Poxel and Sumitomo Dainippon Pharma are jointly conducting the Phase 3 TIMES program, which will be funded by Sumitomo Dainippon Pharma, and Sumitomo Dainippon Pharma will commercialize Imeglimin for this market. In China, South Korea, Taiwan and nine other Southeast Asian countries including Indonesia, Vietnam, Thailand, Malaysia, the Philippines, Singapore, Myanmar, Cambodia, and Laos, Sumitomo Dainippon Pharma will be solely responsible for the development and commercialization of Imeglimin.
- Japan represents the second largest single market for type 2 diabetes with approximately $4 billion in annual sales and is expected to grow to $6 billion in 2020.*
- Asia, in broader terms, is considered the most important geographic location with regards to treating the diabetes pandemic in the future.
- Our lead product Imeglimin met its primary and key secondary endpoints in the Phase 2b clinical study in 299 patients in Japan.
- We believe that Imeglimin's mechanism of action fits well with the pathophysiology of the disease for Japanese/Asian patients.
- The Phase 3 TIMES program for Imeglimin in Japan is currently underway. Top-line results of the TIMES 1 trial were announced in April 2019 and the trial met its primary and secondary endpoints.
We anticipate submitting a Japanese New Drug Application (JNDA) for Imeglimin for the treatment of type 2 diabetes in 2020
*Decision Resources, September 2014
The US/EU Market
- The US/EU offers a ~$32 billion* market opportunity for type 2 diabetes.
- We have a strategic development and license agreement with Roivant Sciences for Imeglimin in the U.S., Europe, and other countries worldwide**
- Activities in 2018 to support the initiation of a Phase 3 program will include differentiation studies to confirm imeglimin’s potential in sensitive patient populations, such as those with chronic kidney disease, as well as manufacturing of the drug product for use in the Phase 3 program.
- The goal is initiate the Phase 3 program in the U.S. and Europe in 2019
*Decision Resources, September 2014
**The Poxel and Roivant agreement includes all countries other than those covered under the Poxel and Sumitomo Dainippon Pharma agreement, which includes Japan, China, the Republic of Korea, Taiwan, Indonesia, Vietnam, Thailand, Malaysia, The Philippines, Singapore, Republic of the Union of Myanmar, Kingdom of Cambodia, and Lao People's Democratic Republic.
Targeting Type 2 Diabetes Cardiovascular Complications
- We have the unique opportunity with our programs to treat patients with type 2 diabetes who are at high risk of cardiovascular disease.
- Imeglimin has been shown in preclinical studies that it improves both endothelial and diastolic dysfunction.
- We are currently studying Imeglimin in preclinical and clinical studies to show benefits in cardiovascular complications.
- PXL770 targets the main risks of cardiovascular disease, such as hyperglycemia, high lipids, and weight.
Entering into NASH
- Our clinical candidate PXL770 is a direct AMPK activator that has the potential to treat numerous chronic metabolic diseases, including diseases that affect the liver, such as NASH, which is a severe form of nonalcoholic fatty liver disease NAFLD
- Based on the favorable safety and pharmacokinetic profile in the completed Phase 1 program, Poxel initiated a Phase 2a proof-of-concept program which will assess the efficacy and safety of PXL770 versus placebo in approximately 120 patients with NAFLD, a condition in which fat builds up in the liver. The Phase 2a program also includes a mechanistic component that will assess the effect of PXL770 on the inhibition of lipolysis (release of FFA from triglycerides stored in the adipose tissue) and hepatic de novo lipogenesis (triglycerides synthesis from glucose precursors).
- Our drug candidate PXL065 (DRX-065) (deuterium-stabilized R-pioglitazone) is a mitochondrial pyruvate carrier (MPC) inhibitor. PXL065 (DRX-065) is the R-stereoisomer (single isomer) of pioglitazone. Pioglitazone, a drug approved for the treatment of type 2 diabetes, has demonstrated efficacy in NASH and is currently the only drug recommended in practice guidelines for biopsy-proven NASH patients1. However, pioglitazone’s use has been limited in NASH due to its side effect profile, which includes weight gain, bone fractures and fluid retention. PXL065 (DRX-065), a novel patent-protected drug candidate, offers a new approach for the treatment of NASH. PXL065 (DRX-065) is anticipated to show a better therapeutic profile than pioglitazone, including enhanced efficacy and a reduction of side effects.
- PXL065 (DRX-065) is currently in a Phase 1 program and is being developed for the treatment of NASH.
Discovery Research and Licensing
- Our licensing agreement with Enyo Pharma is focused on developing an FXR agonist for Hepatitis B and NASH. This program is in Phase 1 development by Enyo Pharma.
- We're well positioned to provide an opportunistic approach with our portfolio and leverage our drug development expertise with in-licensing opportunities, which we have demonstrated through the acquisition of exclusive rights to DeuteRx’s novel clinical stage drug candidate. DRX-065/PXL065 has broadened our pipeline to further expand into the treatment of NASH, as well as pursue additional deuterium stabilized programs for metabolic, specialty and rare diseases.
About Type 2 Diabetes
A Multifactorial Chronic Progressing Disease
Type 2 diabetes is one of the world's major health concerns and its incidence is growing rapidly. It is the most common form of diabetes, affecting about 90% of diabetic patients. The disease can result in severe vascular complications that affect large arteries, leading to cardiovascular diseases such as coronary heart disease or peripheral artery thrombosis, and small arteries, damaging the kidneys, retina and nervous system. It can lead to chronic renal failure (50% of cases), vision loss including blindness, and neuropathy, mainly affecting sensitivity in the legs (65% of cases).
Type 2 diabetes, sometimes referred to as non-insulin-dependent diabetes, is a glucose metabolism disorder characterized by an increase in the blood glucose rate, also known as hyperglycemia. For healthy people, glucose provided by food during a meal is distributed by the blood to the body's tissues that need it. Between meals, the liver produces glucose to maintain normal blood glucose concentrations. Insulin is a pancreatic hormone secreted by the pancreas' beta islets at meal times to permit the glucose uptake into insulin-dependent tissues as well as to slow down the liver's production of glucose between meals, to maintain the correct glucose balance. Type 2 diabetes results from both a decrease in the action of insulin (resistance to insulin) in the target tissues (primarily the liver, muscles and adipose tissue), and a lack of insulin secretion by the pancreas' beta islets in response to glucose (relative insulinopenia).
Type 2 Diabetes Offers a Significant Market Opportunity
- ~415M people between the ages of 20 and 79 worldwide were diagnosed with type 2 diabetes in 2015
- It's estimated that ~642M will be diagnosed by 2040*
- The type 2 diabetes market was worth $37B in 2014 in the top 7 countries
- It's estimated to reach $71B in 2024**
*IDF Atlas 2015 **, Decision Resources, September 2014
Backed by Years of Experience
Poxel was formed from the spin out of several metabolic drug candidates and a focused group of scientific and drug development leaders from Merck Serono.
Our scientific expertise is based on the understanding of key mechanisms involved in metabolic diseases and the innovation needed to make an impact on the current standard of care for these patients.
Our management team and Board of Directors have extensive pharmaceutical industry experience spanning the spectrum of drug research and development to commercialization, patient access and life-cycle management.
Interested in learning more about our programs and how we're combatting type 2 diabetes? Get in touch with us.