COVID-19 has completely transformed our society on a global scale and has had a devastating effect particularly on the frail elderly. We have been very eager to answer the calls from our industry, as well as national and international organizations to join the global effort to fight this pandemic.

The COVA study evaluates the therapeutic efficacy and the safety of Sarconeos (BIO101) as a treatment to prevent further respiratory deterioration in patients who experience severe respiratory manifestations due to COVID-19.

The Coronavirus SARS-CoV-2 can cause Acute Respiratory Distress Syndrome (ARDS) by disrupting the renin angiotensin system (RAS), which has a key role in regulating respiratory function. It is believed that SARS-CoV-2 enters the lung cells using the Angiotensin 2 Converting Enzyme (ACE-2), a key enzyme in the RAS, inhibiting the system’s protective arm.

Sarconeos (BIO101) activates the MAS receptor, a key component of the protective arm of the RAS, and has been shown to significantly improve respiratory function in several preclinical models.

Sarconeos (BIO101) activates the protective arm of the Renin Angiotensin System (RAS) with the potential to stimulate respiratory function in COVID-19 patients

Sarconeos (BIO101) has demonstrated a good safety profile during the SARA development program which is evaluating its ability to improve muscle function in frail elderly patients with sarcopenia (the phase 2b study, SARA-INT, is currently underway). Sarconeos (BIO101) is also being developed to improve the respiratory function of children with Duchenne muscular dystrophy (DMD). COVA is based on clinical and preclinical data from Sarconeos (BIO101) in these neuromuscular diseases.

Objectives

In the context of the world crisis caused by COVID-19, the aim of Biophytis is to bring in the shortest time a medical treatment that will help to prevent further respiratory deterioration in individuals who present with severe respiratory manifestations of COVID-19. Biophytis is bringing its expertise in ageing science to a patient population particularly susceptible to such deterioration, as old age and frailty are important risk factors.

Our objective is to apply for a fast-tracked conditional approval, based on a Phase 2/3 study that will recruit several hundred participants worldwide. The study received approval and recruiting patients in the US, Brazil, France, Belgium and the UK.

The study is titled: “Testing the efficacy and safety of BIO101, for the prevention if respiratory deterioration, in patients with SARS-CoV-2 pneumonia (COVA study)” and is designed as a global Phase 2/3, randomized, double-blind, placebo-controlled, adaptive and seamless design study, with 2 parts:

Recruitment will occur into 2 parts, with similar features. There will be a total of 310 (potentially increased by 50%, i.e. up to 465, based on an interim analysis) patients aged 45 and above, with proven COVID-19, and severe respiratory symptoms with COVID-19, with evidence of respiratory decompensation ≤7 days before start of study medication.

The primary endpoint is confirmation of the effect of Sarconeos (BIO101) in preventing further respiratory deterioration. Secondary and exploratory endpoints include, safety and tolerability, improvements in COVID-19 patients’ respiratory function, and effects on biomarkers associated with the RAS, the target of Sarconeos (BIO101).

The study will go through 2 interim analyses. The first, on the participants of Part 1 (50 patients in total), to assess the safety of BIO101 and provide an initial indication of activity. The second will take place after 50% of the study participants to Part 2 are recruited (155), and will include a safety & a futility analysis and the potential reassessment of the sample size. These analyses are conducted by an independent Data Monitoring Committee (DMC).

The DMC recommended the continuation into part 2 recruitment during Q1 2021 based on the analysis of the first 50 patients. More than 155 patients were enrolled as of May 2021 in 34 clinical centers. The second interim analysis (155 patients) is expected in Q3 2021 and topline results on the full study in Q4 2021.