BIO101 drug candidate development in rare neuromuscular diseases. Preclinical proofs of concept in DMD and in SMA and clinical perspectives


Pre-Clinical Research

Poster Number: 255


Pierre Dilda, PhD, Biophytis, Cynthia Bézier, PhD, Biophytis, Cendrine Tourette, PhD, Biophytis, Benoit Canolle, PhD, Biophytis, René Lafont, PhD, Biophytis, Stanislas Veillet, PhD, Biophytis, Frédéric Charbonnier, PhD, Université Paris Cité, Olivier Biondi, PhD, Université Evry Val d'Essonne, Mathilde Latil, PhD, Biophytis

Biophytis has developed BIO101, a pharmaceutical grade oral preparation of 20-hydroxyecdysone that activates MAS receptor, a key member of the renin-angiotensin system (RAS). BIO101 is currently developed in Sarcopenia. Following promising results on physical performance from the phase 2 study, Biophytis is now preparing to start a phase 3 program in sarcopenia in 2023. In parallel, BIO101 was assessed for efficacy in preclinical models of two rare neuromuscular diseases: DMD and SMA.
Our preclinical data suggests that BIO101 improves respiratory function in preclinical DMD models. Indeed, as a single agent, BIO101 improved respiratory functions and airway responsiveness (Penh) as well as lungs mechanical properties (resistance, elastance and compliance). These effects were observed from 1 month of oral treatment of BIO101 and were sustained for up to 6 months in C57BL10-mdx mice.
In severe SMA-like mice (SmnΔ7/Δ7; tgSMN2+/0), BIO101 has demonstrated beneficial effects on the entire motor unit (muscle fibers, motor neurons and neuromuscular junctions), leading to an enhancement of muscle fatigue resistance, which is also observed more markedly in mild SMA-like mice (SmnΔ7/Δ7; tgSMN2+/+). Interestingly, these benefits were independent of SMN expression. In combination with ASO therapy, BIO101 demonstrated synergistic effects on body weight and increased survival. Most importantly, the co-treated SMA-like mice improved their moving capacity (+40%) and their fatigue resistance (4,2-fold) compared to SMA-like mice treated only with ASO.
Altogether, these data suggest the potential of BIO101 in the therapeutic armamentarium of DMD and SMA. With an ODD granted in both US and EU, Biophytis intends to start a clinical development in non-ambulatory DMD patients in 2023. Based on very promising preclinical results in SMA, Biophytis intends to meet with patients’ association and KOLs in 2023 to discuss further clinical strategy.