Candidates: MP0420 and MP0423
Types: Multi-targeted direct acting antiviral therapeutic candidates developed through Molecular Partners’ DARPin® platform. DARPins are non-antibody-based small proteins where a variable region has been engineered for target binding. Ensovibep is designed to bind to the SARS-CoV-2 spike protein at three distinct locations to prevent viral entry into cells.
2021 Status: Phase II/III Trial Launched—Novartis and Molecular Partners said May 27 that they launched the Phase II/III EMPATHY trial (NCT04828161) designed to explore the use of ensovibep (MP0420) for the treatment of COVID-19. Novartis will conduct the clinical trial program for ensovibep, with Molecular Partners as sponsor of the studies.
EMPATHY will assess the safety and efficacy of ensovibep in patients with COVID-19 who are in the early stages of infection, to prevent worsening symptoms and hospitalization. The study will enroll 400 patients in Phase II to identify a dose with optimal safety and activity, with initial results anticipated in August 2021. At that point, the trial’s Phase III portion is set to advance with an additional 1,700 patients, with results anticipated in the first half of 2022. If initial EMPATHY trial results are convincing, Novartis will seek expedited approval via the FDA’s Emergency Use Authorization (EUA), the companies said.
Molecular Partners said April 6 that the first patient was dosed in a Phase IIa clinical trial of ensovibep (MP0420), designed to give researchers early insights into the viral clearance and pharmacodynamic behavior of the DARPin in the presence of the virus.
The single-arm study will enroll patients with symptomatic COVID-19, and is designed to evaluate dynamics of viral clearance, pharmacokinetics and tolerability of ensovibep. The study, recruiting in the Netherlands, is designed to enroll up to 40 patients in two dose cohorts, Molecular Partners said.
Molecular Partners added that together with Novartis, it aims to begin additional clinical studies of ensovibep throughout the first half of 2021 with the goal of achieving clinical proof-of-concept and potential submission for emergency use authorization during the year. The intended clinical program includes participation in the NIH’s ACTIV-3 clinical trial, as well as in the global Phase II/III EMPATHY trial set to start in the second quarter. EMPATHY will seek to enroll over 2,100 patients in the ambulatory setting to evaluate the ability of ensovibep to prevent disease worsening, hospitalizations and death.
On March 9, Molecular Partners and Novartis announced positive initial results from an ongoing Phase I study of ensovibep in healthy volunteers. Ensovibep was seen to be safe and well tolerated, with no significant adverse events reported, the companies said. Preliminary results showed extended exposure of the DARPin candidate in serum, with a half-life of 2-3 weeks, as expected based on preclinical experiments.
2020 Status: Novartis said October 28 it agreed to develop, manufacture, and commercialize Molecular Partners’ anti-COVID-19 DARPin® program, consisting of MP0420 and MP0423. The CHF 210 million ($234 million) collaboration aims to leverage Molecular Partners’ proprietary DARPin® technologies and Novartis broad expertise in global drug development, regulatory affairs, manufacturing and commercialization in order to develop the drugs for prevention and treatment of COVID-19.
The companies’ option and license agreement creates an option period, during which Molecular Partners has agreed to conduct Phase I clinical trials for MP0420, expected to begin in November 2020, and perform all remaining preclinical work for MP0423. Novartis has agreed to conduct Phase II and Phase III clinical trials, to be sponsored by Molecular Partners. Upon exercise of its option, Novartis would be responsible for all further development and commercialization activities.
During the clinical development stage, Molecular Partners has agreed to provide clinical supply, while the companies have agreed to work together to scale-up manufacturing capacity, in collaboration with Sandoz, the generics and biosimilar Novartis division, to provide worldwide supply.
According to Novartis, DARPin® therapeutics are ideally suited for antiviral therapy for reasons that include multi-specific target binding with the potential to prevent viral escape via mutations; the possibility for subcutaneous administration; long half-life for sustained activity; the potential to bypass cold storage; and typically high-yield, highly scalable production in bacterial fermenters.
Novartis agreed to pay Molecular Partners CHF 60 million ($67 million), including equity, upfront, and CHF 150 million ($167 million) upon Novartis exercising its option to both therapeutic candidates, plus “significant” royalty on sales. Molecular Partners agreed to forgo royalties in lower income countries, and has agreed with Novartis “to ensure affordability based on countries’ needs and capabilities,” Novartis added.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: