Candidates: Coronavirus-neutralizing antibodies
Type: PolyTope mAb Therapy™, a defined antibody combination designed to target multiple epitopes and mechanisms of viral evasion, and enabled by IPA’s discovery platforms (including B Cell Select™ and DeepDisplay™) and ImmunoPrecise subsidiary Talem Therapeutics’ access to the transgenic animal platform OmniAb® for direct generation of human antibodies.
Status: IPA said September 17 that it would partner with Zymeworks to develop neutralizing antibodies against SARS-CoV-2. The collaboration—whose value was not disclosed—gives IPA access to Zymeworks’ Azymetric™ and EFECT™ platforms, with the goal of transforming IPA’s SARS-CoV-2 neutralizing antibodies into bispecific and multispecific antibodies.
Azymetric is designed to enable the transformation of monospecific antibodies into bispecific and multispecific antibodies, allowing simultaneous binding to several different disease targets. Zymeworks says it engineers Azymetric therapeutics to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life, and high stability. The EFECT platform is a library of antibody Fc modifications engineered to activate or suppress the antibody-mediated immune response.
An unspecified number of antibody candidates will be tested using SARS-CoV-2 spike protein provided by the National Research Council Canada (NRC) before preclinical manufacturing at the NRC for animal studies. According to IPA, timelines for the companies’ preclinical studies examining the efficacy of IPA’s PolyTope therapies using traditional antibody formats are not impacted by these additional investigations into antibody formulation.
“After the discovery of potently neutralizing antibodies in a combinatorial setting, it was a logical consequence for us to look into clinically-proven, multi-specific antibody platforms,” IPA President and CEO Jennifer Bath, PhD said.
In June, IPA said it identified “numerous” lead candidate antibodies with highly-potent neutralizing activity in vitro, which are being manufactured for further testing and possible inclusion in PolyTope mAb Therapy. The neutralizing antibodies resulted from functional screenings of the company’s top 300 lead antibodies analyzed from several proprietary discovery platforms leveraging the immune systems of humans and llamas.
In March, IPA said that its collaboration partner EVQLV submitted its first panel of candidate therapeutic antibody sequences, comprised of DNA sequences encoding for potentially therapeutic antibodies against SARS-CoV-2. The sequences—characterized and screened by EVQLV’s artificial intelligence—were generated in less than one week using computational antibody design, which combines mathematics, statistics, and computer science to identify high-affinity antibodies.
Since then, IPA said, it deployed discovery platforms leveraging not only the immune systems of humans and llamas, but also those of rabbits and Ligand Pharmaceutical’s OmniAb® genetically engineered rats producing human antibodies. Functional analyses of the remaining 1,300 lead antibodies from the rabbit and OmniAb rat campaigns were performed independently, IPA said, adding that it anticipates the release of preliminary functional data screens from the additional programs “in the near future.”
In February, IPA announced its PolyTope mAb Therapy approach to developing a COVID-19 treatment. The company also spoke of potentially developing a vaccine for COVID-19, but has not announced any such effort since then. IPA said it designated Ilse Roodink, PhD, chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.
COVID-19: 200 Candidates and Counting
To navigate through the >200 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: