8 April 2021 - - Canada-based therapeutic antibody discovery and development specialist ImmunoPrecise Antibodies Ltd's (NASDAQ: IPA) (TSX Venture: IPA) subsidiary Talem Therapeutics LLC has advanced development of a candidate panel of vetted, novel, therapeutic antibodies, collectively referred to as TATX-112, against an undisclosed target, into formal lead candidate characterization, the company said.

It is well documented that certain genes, when mutated and expressed in different tissues and organs, may play a role in more than one disease.

The target is a protein receptor that is overexpressed in a variety of types of deadly cancers. In solid tumors, stimulation of the target by its ligand is described to result in activation of intracellular signaling pathways that promote cancer cell growth, survival, invasiveness, metastatic behavior, and suppress chemotherapeutic sensitivity of the tumor cells.

Therefore, interference with the target signaling is anticipated to be an attractive approach to induce tumor suppression, or halting tumor cell growth.

As current therapies focusing on inhibiting intracellular target signaling consist primarily of non-target selective small molecule inhibitors, they may be high risk for unintentionally causing undesirable side-effects to the patient by functionally blocking related receptor proteins, which are more widely expressed in the human body, in parallel.

In contrast, Talem has developed the TATX-112 antibodies with the goal of specifically blocking the interaction between the target and its ligand, e.g. functionally interfering with the target's biology, which is expected to significantly improve specificity of such tumor therapy due to its relatively higher expression levels in tumors compared to normal tissue.

That higher specificity is expected to increase the therapeutic window by lowering the potential risk of side effects and positively impacting treatment efficacy.

Additionally, the target's expression profile makes this membrane protein a promising candidate for antibody-drug conjugate-based therapies.

In addition to its role in oncology, the target plays a vital role in the nervous system by enhancing neuronal development, survival, protection, and function.

Alzheimer's and other neurodegenerative diseases are associated with reduced expression levels of the target and impaired receptor signaling.

Stimulating intracellular target signaling using agonistic antibodies is an appealing therapeutic approach to suppress disease progression with an expectedly higher safety profile than less-selective small molecules.

Such therapeutic strategy requires blood-brain-barrier passage which can be facilitated by a bi- or multi-specific antibody format, including an antibody fragment that induces transport over the blood-brain-barrier upon binding.

As the different clinical application options for TATX-112 antibodies require a functionally diversified set of lead candidates and antibody format flexibility, Talem relied on two of IPA's proprietary target-enrichment antibody discovery platforms, B cell Select and DeepDisplay.

Following selection of both target-reactive B cells from target immunized chicken and human scFvs from IPA's in-house phage libraries, 50 sequence-unique antibodies of particular interest were prioritized for more in-depth characterization to bin antibodies for further (indication-specific) clinical development.

In addition to TATX-112, Talem is continuing development efforts of its other potential products leveraging its pipeline of highly differentiated therapeutic antibody programs for the potential treatment of various disease areas, including heart disease, inflammation, infectious diseases and cancer.

The company's most advanced development program, TATX-03, is a fully human, synergistic, antibody cocktail containing potently neutralizing antibodies against non-overlapping epitopes on SARS-CoV-2.

IPA's B cell Select platform enables the interrogation of a greater diversity of an antibody repertoire. By interrogating isolated B cells, IPA can analyze full organism repertoires with very little manipulation.

This proprietary platform is species independent allowing for the generation of antibodies from samples not possible using other methods. B cell Select has the potential to develop antibodies from any species (including humans) as well as from any tissue.

As the platform explores the entire antibody repertoire, it provides the opportunity to develop antibodies for anything that is possible in an animal's immune repertoire including any protein class, complex therapeutic targets, post-translational modifications, and small molecules.

The B cell Select platform enables the interrogation of 10m blood cells to generate native monoclonal antibodies from immunized animals that specifically target an antigen.

The B cell Select process takes place early in the antibody development process allowing for the rapid selection of top candidates, drastically increasing the success rate of antibody discovery.

The platform also harnesses the power of the immune system to generate natural pairing of the antibodies produced by selected B cells.

IPA's DeepDisplay is a phage display approach based on building custom immune libraries from multiple species, including transgenic animals, or the selection of antigen-specific recombinant antibody fragments from our proprietary human or llama phage libraries.