Candidates: Coronavirus-neutralizing antibodies

Category: ANTIBODY

Type: Antibody based on IPA’s PolyTope platform. IPA says its SARS-CoV-2 PolyTope monoclonal therapies are designed to protect against mutagenic escape with an emphasis on efficacy for every patient, variant, and strain of SARS-CoV-2.

2021 Status: IPA on March 25 identified a lead COVID-19 antibody, citing preclinical data which the company said indicated that 23-H7 showed strong, protective anti-viral effects in SARS-CoV-2 infected Syrian hamsters via an uncommon mechanism of action.

Notably, IPA said, in vivo efficacy evaluation of antibody 23-H7 when administered as a passive vaccine, 24 hours prior to infecting Syrian hamsters with the SARS-CoV-2-D614G, resulted in undetectable replication competent virus titer in the lungs of four of the five animals 4 days post infection, with the remaining animal showing a replication competent viral titer barely above the lowest level of detection.

23-H7 also showed itself to be capable of perturbing the interaction between the Receptor Binding Domain (RBD) and the host receptor ACE2 indirectly, yet its epitope is not located on the mutation prone RBD/ACE2 interface. Instead, IPA said, its preclinical studies showed that 23-H7 maintained binding to the full (cell-associated) spike trimer as seen in emerging SARS-CoV-2 variants of concern B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil)

Next to the benefit of capturing multiple mechanisms of action in one therapy, IPA adds that its PolyTope antibody cocktail approach is also believed to reduce the risk of mutagenic escape, and thus is expected to increase its sustainability.

2020 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: 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: