Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, and Novartis today announced that Part A of the EMPATHY clinical trial1, that compared single intravenous doses of ensovibep, a DARPin antiviral therapeutic candidate vs. placebo to treat COVID-19, met the primary endpoint of viral load reduction over eight days. The two secondary endpoints also showed clinically meaningful benefit over placebo – (1) composite endpoint of hospitalization and/or Emergency Room (ER) visits or death, and (2) time to sustained clinical recovery. Novartis confirms it will now exercise its option to in-license ensovibep from Molecular Partners and, following exercise of the option, will seek expedited access globally, first via the FDA’s EUA process.
The global EMPATHY clinical trial, which is being conducted by Novartis, with Molecular Partners as sponsor, is a randomized, double-blind, placebo controlled study in ambulatory (non-hospitalized) adult patients with COVID-19. EMPATHY Part A enrolled 407 patients to identify a dose of ensovibep with optimal safety and efficacy and recruited patients in the USA, South Africa, India, the Netherlands, and Hungary to explore three doses: 75mg, 225mg and 600mg.
Results from the study showed that the primary endpoint was met with a statistically significant reduction in viral load over eight days, compared to placebo, for all three dosing arms. The secondary endpoint of hospitalization and/or ER visits related to COVID-19, or death showed an overall 78% reduction in risk of events across ensovibep arms compared to placebo. Treatment arms were generally balanced in terms of demographic, baseline and disease characteristics. The placebo arm with 99 patients had a total of six events (event rate of 6%); five patients were hospitalized, two of whom died due to worsening of COVID-19 and one patient had an ER visit only. In the 301 patients treated with ensovibep, there were four events; hospitalizations occurred in two patients and two needed to visit ER (event rate of 1.3%). No deaths occurred in any of the patients treated with ensovibep. All doses were well-tolerated and no unexpected safety issues were identified for any of the doses2. The lowest dose of 75mg is the planned dose for further development. The data will now undergo further review so that Novartis and Molecular Partners can determine the appropriate next steps for the program.
“These encouraging results come at a time when the need for therapies with pan-variant activity, such as ensovibep, has never been greater. We are incredibly excited about the opportunity to provide a potential therapeutic option for patients around the world who require access to effective COVID-19 treatments,” said Patrick Amstutz, Ph.D., CEO of Molecular Partners. “Today’s data are a culmination of a persistent team effort, between ourselves and Novartis, to deliver a tailored antiviral with demonstrated safety and efficacy in global clinical trials. As pioneers of DARPin therapeutics, our team has the unique ability to rapidly generate and develop multi-specific DARPin therapeutics. We look forward to continue to demonstrate our capabilities and the potential of our pipeline in oncology and virology for patients in need.”
As the SARS-CoV-2 virus evolves, a multi-solution strategy is needed to combat the pandemic and there will be a need for antiviral treatments to complement the global vaccination efforts. Despite availability of vaccinations, there continues to be disease transmission, either through pockets of unvaccinated populations, in patients with compromised immune systems and co-morbidities or through emerging variants, and breakthrough infections are likely to continue. A recent in vitro analysis3 also showed that ensovibep maintains full neutralization of the pseudoviruses containing the mutations identical to the Omicron variant of concern.
“We are pleased that the results from the EMPATHY trial demonstrate the positive therapeutic effect of ensovibep, with the potential to be an important new treatment option to combat the rapidly evolving SARS-CoV-2 pandemic,” said Vas Narasimhan, CEO of Novartis. “As COVID-19 continues to burden healthcare systems across the globe, a range of treatments will be needed, and Novartis is proud to continue our collaboration with Molecular Partners on this unique treatment for COVID-19 and contribute ensovibep to this suite of options.”
Given the pressing public health emergency and the rapid spread of the Omicron variant across the world, Novartis and Molecular Partners are in close liaison with regulatory bodies to seek expedited review and approval of ensovibep as soon as possible. If approved, ensovibep will be the first multi-specific antiviral molecule for the treatment of COVID-19.
Novartis has informed Molecular Partners of its intent to option its exclusive license to global rights of ensovibep, which will lead to a milestone payment of CHF 150m. In addition, Molecular Partners will be eligible to receive 22% royalty on sales. Molecular Partners has agreed to forgo royalties in lower income countries and is aligned with Novartis’ plans to ensure affordability based on countries’ needs and capabilities. With the decision made to exercise the option, Novartis will become responsible for development, manufacturing, distribution and commercialization activities of ensovibep. Novartis has already initiated scale-up activities in its large-scale biologics production facilities.
Financial guidance update
The Company expects approximately CHF 133 million cash and cash equivalents as per December 31, 2021. Upon receipt of the CHF 150 million option exercise milestone from Novartis, Molecular Partners now estimates its cash runway to extend well into 2025, excluding any potential royalty income as well as excluding potential further cash flows to or from R&D partners.