Molecular Partners and Novartis Announce Inclusion of COVID-19 Antiviral Candidate, ensovibep, in NIH-Sponsored ACTIV-3 Trial

Zurich-Schlieren, Switzerland, March 15, 2021. Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein drugs known as DARPin® therapeutics, and its collaborator Novartis, today announced today announced that ensovibep (formerly MP0420) is expected to be included in a global phase 3 randomized, controlled clinical trial as part of the National Institutes of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. The trial, ACTIV-3, is designed to evaluate the safety and efficacy of various therapies for the treatment of adults hospitalized with a COVID-19 diagnosis. Ensovibep is a DARPin® therapeutic candidate designed to bind to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein at three distinct locations to prevent viral entry into cells, and may provide added protection against variant strains.

“The NIH’s ACTIV-3 trial provides a major expansion of ensovibep’s clinical program and data collection, and recognizes the clinical and preclinical evidence we have delivered to-date supporting this candidate as a differentiated approach to COVID-19 treatment,” said Patrick Amstutz, Ph.D., chief executive officer of Molecular Partners. “Emerging variant strains and the challenges of vaccinating a global population create an ongoing need for effective antivirals to save lives. We will work closely with both our collaborator Novartis and the NIH to maximize support on this trial in parallel with the other clinical trials of ensovibep planned to initiate in the second quarter.”

ACTIV-3 is one of multiple ongoing trials in the NIH’s ACTIV program, a public-private partnership designed to speed development of the most promising treatments and vaccine candidates for COVID-19. In order to be selected for ACTIV-3, Molecular Partners provided the NIH with relevant data and in addition provided ensovibep for independent preclinical assessments by the NIH. Molecular Partners has recently submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for ensovibep.

Ensovibep is currently being evaluated in a Phase 1, randomized, double-blind, placebo-controlled single ascending dose study to evaluate the safety, tolerability, and pharmacokinetics of intravenously administered ensovibep. Initial data from this study, run by Molecular Partners, indicate that ensovibep is well tolerated with a half-life in the range of 2-3 weeks.

In partnership with Novartis, Molecular Partners expects the initiation of additional clinical studies of ensovibep to initiate throughout the first half of 2021 with the goal of achieving clinical proof-of-concept and potential emergency use authorization within 2021. The intended clinical program includes a smaller Phase 2 trial specifically evaluating the ability of ensovibep to reduce infectivity, as well as a global Phase 2-3 study (EMPATHY), which will seek to enroll over 2,400 patients in the ambulatory setting to evaluate the ability of ensovibep to prevent disease worsening, hospitalizations and death.

ACTIV-3 Clinical Trial Design

Once initiated, the ACTIV-3 trial arm evaluating ensovibep would initially enroll 300 participants who have been hospitalized with mild to moderate COVID-19 with fewer than 13 days of symptoms, who will receive either ensovibep or placebo. Participants will also receive standard of care for COVID-19, including the FDA-approved antiviral remdesivir. Five days after dosing, participants’ clinical status will be assessed, based on need for supplemental oxygen, mechanical ventilation, or other supportive care. If the ensovibep treatment arm appears to have a positive benefit:risk profile, the trial will enroll an additional 700 participants. Trial participants will be followed for 90 days following enrollment to analyze their response to treatment. The primary efficacy endpoint is the time from randomization to participants’ sustained recovery for 14 days after release from the hospital.
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