Leveraging Our Strengths to Combat SARS-CoV-2

Talem has been actively involved in SARS-CoV-2 research since January 2020. 

Monoclonal antibodies were derived from several animal species, including transgenic OmniRat® rodents, rabbits, human and llama phage libraries, to access a broad epitope coverage. We exploit multiple in vivo and in vitro discovery platforms (B cell cloning, hybridoma, and phage display) and multiple antibody formats (IgG, scFv, and VHH) to increase the chances of finding clones with unique/rare epitopes and facilitate their reformulation into bispecifics or other modular formats. Our multinational teams in North America and Europe have developed a rich SARS-CoV-2 antibody portfolio with deep epitope and functional diversity.

Cocktail therapies are widely believed to be a promising approach to fight the SARS-CoV-2 virus. The strategy of multi-antibody cocktails is believed to be more crucial now with the surge of new variants of concern and breakthrough cases (Figure 1).

Figure 1: PolyTope® TATX-03 Highlights

Figure 1: PolyTope® – Multi-Ab Cocktails Against SARS-CoV-2 and Variants of Concern (VOCs). Multi-antibody (Ab) cocktails (MACs) that consist of either 4-Abs (TATX-03b) or 5-Abs (TATX-03c). TATX-03b (4-Ab cocktail) has been selected for clinical development. TATX-03c (5-Ab cocktail) shown to illustrate ‘plug-and-play’ for potential future formulations. Each polytopic cocktail is rationally designed to provide enhanced, long-lasting protection by simultaneously targeting multiple epitopes on the spike trimer, thereby engaging multiple mechanisms of action and reducing mutagenic escape risk. [ᵅ Preclinical in vivo efficacy Syrian hamster model; ᵇ Tested against pseudotyped virus; ᶜ Reduced lung viral titers to undetectable levels in (13/15) animals.; ᵈ Roodink, et al. bioRxiv, Jul 2021.; *22-D9 Ab only included in TATX-03c.]

With the ongoing threat of COVID-19 and rising concerns from the frontlines about the effectiveness of existing vaccines and antibody therapies, IPA’s Polytope® antibody cocktail continues to demonstrate promising efficacy during studies conducted by the Talem, even when tested against newly emerged variants. New data reveal remarkable consistency in the ability of the PolyTope® TATX-03 antibody cocktail to retain its potent and complete in vitro neutralization against all variants, as demonstrated with Omicron pseudovirus reinforced with neutralization data against the wild-type parental virus (Wuhan) and all predominant variants of concern (Figure 2).

Figure 2: Pseudovirus Neutralization of TATX-03

Figure 2: Overview of TATX-03b and TATX-03c pseudovirus neutralization screenings towards SARS-CoV-2 and variants of concern (Wuhan-1, Alpha, Beta, Delta, Omicron). Green checkmarks indicate potent neutralization.

The PolyTope® TATX-03 antibody cocktail was developed to target multiple, non-overlapping epitopes on the spike trimer, reducing the risk of mutagenic escape, and facilitating engagement of mechanisms of action that are collectively distinctive from other SARS therapies obtainable to date

Taken together, we use a rich diversity of methods and platforms to increase the chance of converging upon a collection of lead candidates which can be rapidly reformulated and reformatted. This allows for PolyTope® to be continuously updated and optimized in response to emerging disease variants, improving durability of our SARS-CoV-2 therapies and enabling expanded use for novel, emerging, infectious diseases. 

Figure 3: TATX-03 (SARS-CoV-2) Timeline

Figure 3: Timeline of PolyTope TATX-03 including in vitro, in vivo, CMC, and regulatory submission. Green indicated completed and orange indicates on-going activities.

Please contact bd@talemtherapeutics.com, with scientific questions regarding our PolyTope® TATX-03 Program.

Disclaimer

This information was factually accurate on the date it was published. Talem assumes no duty to update the information to reflect subsequent developments. Readers should not rely upon the information on this page as current or accurate after its publication date. For the latest information on the Talem pipeline, readers should visit the News and Investors sections of our website. This information constitutes forward-looking statements relating to Talem’s business, including express or implied discussions regarding potential new products, potential new indications for existing products, or regarding potential future revenues from any such products. Such forward-looking statements reflect the current views of Talem Therapeutics LLC regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any new products will be approved for sale in any market, or that any new indications will be approved for existing products in any market, or that such products will achieve any particular revenue levels. 

In particular, management’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays or government regulation generally; the ImmunoPrecise Antibodies Ltd. Group’s ability to obtain or maintain patent or other proprietary intellectual property protection, including the uncertainties involved in the US litigation process; competition in general; government, industry, and general public pricing and other political pressures; and other risks and factors referred to in ImmunoPrecise Antibodies’ current Form 40-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.