Therapeutic Approaches to Combat Age-Related Diseases

We recently spoke to Stanislas Veillet, Chairman and CEO of Biophytis to learn more about their efforts to develop first-in-class drugs to treat degenerative illnesses associated with aging. Stanislas discusses the company's approach to developing novel therapeutics, the commencement of a Phase 2b study in patients with sarcopenia – a disease associated with the loss of muscle mass, strength and function related to aging, as well as other age-related indications currently being explored.

Laura Mason (LM): Could you tell us about Biophytis, the company mission and goals?

Stanislas Veillet (SV): Our mission at Biophytis is to develop first-in-class drugs to treat degenerative illnesses associated with aging. Our most advanced programmes are therapeutic-candidates in mid-stage clinical development to treat sarcopenia (loss of muscle function) and age-related macular degeneration (AMD).

LM: There seems to be a therapeutic gap when it comes to age-related diseases, why is research in this area currently underserved?

SV: Some age-related illnesses have not yet been defined by regulators and healthcare payers. In addition, many age-related illnesses involve gradual degeneration and are therefore difficult to study, requiring large, lengthy clinical trials. These two reasons make it challenging to raise money from investors, who typically want a clear path to market and a more rapid return on investment than most therapeutic candidates in this area can offer. We have addressed this by focusing some of our resources on degenerative orphan diseases, like Duchenne Muscular Dystrophy (DMD), which can be studied in shorter trials and which have a clear path to regulatory approval.

LM: When it comes to the development of novel therapeutics, what approach does Biophytis take? Could you expand on the company’s scientific platform and development strategies?

SV: Our origins are based in the scientific research of Dr René Lafont, a biochemist and Professor Emeritus at the Sorbonne University. His work to elucidate mechanisms of degeneration and identify new compounds, many from natural sources, such as the forests of Brazil, gave birth to Biophytis, which he co-founded with me in 2006. Together with Sorbonne University, Biophytis has built a collection of natural active substances derived from plants that increase resilience to stress of cells and tissues through original pathways, slowing down degenerative processes associated with aging. Since then, Biophytis has built a discovery platform that leverages phytochemistry, biology and clinical research activities at every stage of its research, a first of its kind. The company’s approach enables it to create strong intellectual property protecting its molecules and assuring that they can attract sufficient investment for pharmaceutical drug development.

LM: You recently announced the commencement of a Phase 2b study in patients with sarcopenia. What is sarcopenia?

SV: Aging of muscles is accompanied by degeneration, specifically leading to a loss of muscle mass and muscle function, such as muscle strength and mobility; this is sarcopenia. Muscle loss arises in particular from a reduction in protein synthesis linked to the reduction in anabolic factors and an increase in proteolysis. To address this, Biophytis has focused on the activation of a receptor in the renin-angiotensin system (RAS); the Mas receptor. Our compounds are the first Mas receptor non-peptide agonist molecules to be the subject of pharmaceutical development. Preclinical tests on our compounds on muscle cells have shown a significant increase in protein synthesis and in the myotube diameter. This is explained in greater detail here.

Figure 1: Sarcopenia. Biophytis focuses on sarcopenia in obese subjects, for which there is no registered treatment.

LM: Firstly, could you tell us more about the study objectives and trial design, and secondly, the drug candidate, Sarconeos which is being investigated in the study?

SV: The study, called SARA-INT, is a double-blind, placebo-controlled Phase 2b clinical trial that will include about 334 patients in 22 clinical centres in Europe (Belgium, France and Italy) and in the United States. About half of the patients will be recruited from an observational study, SARA-OBS, which has been run by Biophytis at some of the key clinical centres of SARA-INT over the past year. The other half of the patients will be recruited from 11 new clinical centres, which are in the process of opening.

The objectives of SARA-INT are to evaluate the safety and efficacy of two doses of Sarconeos (175 mg bid and 350 mg bid) administered orally for 26 weeks against placebo in a population of men and women over 65 years with a risk of disability. Specifically, we hope to estimate the effect of treatment, improvement of physical function, and decreased risk of motor disability after six months of treatment with placebo in the target population. To do this walking speed will be measured during a 400 meters walking test, the variation compared to the baseline at the 6th month will be compared between the groups treated (each dose compared to placebo). We also will be monitoring secondary endpoints, such as patient reported outcomes, body mass, body composition, muscle strength, climbing stairs and walking speed and distance over six minutes.

LM: In addition to sarcopenia, what other age-related indications are you focusing on?

SV: We are preparing to start in 2018 mid-stage clinical testing of Sarconeos to treat DMD and also in 2018 of our second product, Macuneos to treat AMD. Macuneos is a PPAR nuclear receptor agonist selected because of its ability to protect retina from phototoxic stress in preclinical testing. Some Phase I testing has been completed and we’re preparing further studies.

Stanislas Veillet was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.