Pharmaleads Announces the Entry in Phase 2 of PL37, the Lead Compound of a New Class of Painkillers, After a Successful Phase 1 Including Initial Efficacy Testing

Pharmaleads, a company specialising in the design and early development of small protease inhibiting molecules, for diagnostic and therapeutic use, announced today the positive results of two Phase 1 studies for PL37 by oral route. It is Pharmaleads’ first molecule and the lead compound of a new class of painkillers, Dual ENKephalinase Inhibitors (DENKI). Initial proof of its efficacy has been obtained using a neuropathic pain model. Publication of the results is in progress.

Out of 168 healthy volunteers, 126 received PL37 by oral route during two randomised, double-blind, placebo-controlled studies.

“Dual enkephalinase inhibitors (DENKI) induce natural pain relief by inhibiting the two enzymes responsible for the rapid degradation of enkephalins, the main endogenous opioids, thus increasing the level of these powerful physiological analgesics especially in pain-affected areas,” according to Professors Bernard Roques and Marie-Claude Fournié-Zaluski, inventors of these molecules and co-founders of Pharmaleads.

The first study, performed in France, involved administering a single ascending dose to 92 healthy volunteers including 16 women, with doses of up to 800 mg for men and 200 mg for women. It also enabled investigation of food interaction with PL37. The linear pharmacokinetics for the two active metabolites as a function of ascending doses of PL37 was demonstrated.

The second study, conducted in Great Britain, was made up of three successive groups:

• Group A, containing 8 subjects, revealed that the Maximum Tolerated Dose (MTD), which was not reached during the first study, was greater than 1 g.
• Group B enabled the study of 40 subjects administered with repeated doses over 5 days at daily doses between 800 mg and 4 g, administered over 4 separate intakes.
• Group C, including 28 subjects treated with 4 g per day over a 5-day period, provided the first proof of PL37 efficacy in clinical pharmacology using the intradermal capsaicin test. This test highlighted a significant effect of PL37 by oral route in comparison to the placebo, especially a significant decrease in the intensity of pain and mechanical allodynia.

Throughout the two studies, the safety and tolerability of PL37 proved to be very good and no opiate-type, central or peripheral adverse effects were detected.

“Pharmaleads now possesses a coherent pipeline of three different chemical families of DENKI painkillers at various stages of development and whose uses cover all needs in the field of pain”, according to Thierry Bourbié, Chairman and co-founder of Pharmaleads.

2012 will see the accomplishment of important steps for Pharmaleads:

- For PL37, the lead compound of the first DENKI family, which targets peripheral pain (of neuropathic and osteoarthritic origin in particular) by oral route as well as central pain by IV route (as a substitute, complement or temporary replacement for morphine), the beginning of Phase 2a is actively being prepared for the second quarter.

- PL265, the lead compound of the second DENKI family, will enter Phase 1 at the beginning of 2012. It mainly targets neuropathic pain by oral route and local pain via topical administration.

- Lastly, the first molecule in the third family will enter the pre-clinical regulatory stage in 2012 as well. Designed to penetrate the central nervous system, taken by oral and IV routes, it targets acute pain arising from excess nociception (cancerous, post-operative and trauma-related pain).

The global pain market generated € 25 billion in 2010; the market for neuropathic pain (due to diabetes, shingles, anti-tumorals, anti-virals, etc.) which affects between 6 and 8% of the population of developed countries is estimated at € 4 billion.

About Pharmaleads – www.pharmaleads.com

Founded in 2001 and based in Paris, France, Pharmaleads has developed a coherent set of first-in-class molecules, thanks to its world-class medicinal chemistry expertise, providing ground-breaking solutions in the treatment of pain. Pharmaleads designs and manages the early development of small protease inhibiting molecules, for diagnostic and therapeutic use.

Contact:

Pharmaleads
Thierry Bourbié
Président
thierry.bourbie@pharmaleads.com
+33-1-44-06-70-00
or
Media: Yucatan Agency
Annie-Florence Loyer
afloyer@yucatan.fr
+ 33-1-53-63-27-29/ + 33-6-88-20-35-59
or
Nadège Le Lezec
nlelezec@yucatan.fr
+ 33-1-53-63-27-27