Alphamers™ harness the body’s natural antibodies      and redirect them to diseased tissues

Primates have high natural antibody titres to certain sugars

Avvinity’s proprietary Alphamer™ platform harnesses a powerful and clinically validated immune mechanism which redirects naturally existing antibodies to treat life-threatening diseases. Primates, including humans, have a unique immune adaptation: 1-2% of our antibodies are targeted to certain natural sugar molecules (alpha-gal and rhamnose) presented by bacteria in our gut. These antibodies represent several types of antibody types (IgG and IgM) and are polyclonal (contain a range of antibodies that bind to the sugars in different places).

The destructive power of the anti-gal or anti-rhamnose drive immune response is the primary cause of tissue rejection upon xenotransplantation from a non-primate species into primates.

Hyperacute rejection of pig kidney (expressing alpha-gal) after being xenografted into a primate

Alphamer’s leverage the anti-sugar immune response

By adding either alpha-gal or rhamnose sugars to molecules (such as antibodies) that bind to markers of disease on the surface of target cells, Avvinity can teach the immune system (innate and adaptive) to destroy such cells.

Individual anti-sugar antibodies have only low individual affinity for their sugar targets. However, by presenting numerous sugar molecules to the immune system, the overall strength of binding (Avidity) becomes sufficient to trigger an immune response capable of killing the target cells. Importantly, healthy tissues that may bind low levels of the Alphamer, do not elicit the immune response, avoiding concomitant toxicity in the body.

While our Alphamer platform has potential application in treating a wide range of diseases, Avvinity is focused on treating cancers, both solid tumours and also hematological (‘liquid’) tumours. Our lead program is an antibody based Alphamer which recognises a validated cancer target called EGFR, which is elevated in more than half of all tumours. Linking sugars to an anti-EGFR antibody, our lead Alphamer can trigger a robust immune response involving both the adaptive and innate immune systems.

Alphamers™ are tunable drugs

Alphamer molecules are composed of three parts: a targeting domain (TD), a proprietary linker and an effector domain (ED). The targeting domain, such as an antibody or antibody fragment, binds a cancer cell surface target. The effector domain binds to pre-existing antibodies in the bloodstream. This technology redirects these antibodies to the selected target and triggers an immune response to target and kill the tumour cells.

Our platform is highly tunable, with the ability to alter both efficacy parameters and also the drug properties of our Alphamers. We select the most desirable Alphamers through rapid in vitro screening, ready for testing in vivo.

Alphamer representation

Targeted cancer cell killing – a robust, durable immune response

Alphamers™, as a single agent, can engage multiple important immune mechanisms concurrently (via complement activation, antibody dependent cellular toxicity and target cell phagocytosis). This pre-existing polyclonal immune response leads to targeted cancer cell killing and enhanced neo-antigen presentation. Tumour antigens are processed by dendritic cells during their migration to the lymph node. The tumour antigens are then presented to naïve T-cells which differentiate to generate antigen specific effector T-cells. These effector cells then migrate to the tumour site to eliminate the tumour cells.

Our lead program: EGFR targeted Alphamer™ with broad clinical utility

Targeting EGFR – leveraging a validated target for a novel purpose

Our lead Alphamer targets EGFR, which is overexpressed in a large fraction of solid tumour indications. These include gastric cancer, Head and Neck cancer and Small Cell Lung Cancer. EGFR is an important cell surface molecule (receptor) that is activated by various ligands outside of the cell, results in a signal that triggers various intracellular activities, including cell proliferation, cell survival, growth and development.

A number of currently marketed products successfully target EGFR by blocking the transduction of the signal to prevent cell proliferation. However, the clinical utility of such products is limited by existing and acquired resistance. Avvinity’s approach is different: our Alphamer program exploits the overexpression of EGFR by cancer cells, but rather than blocking signal transduction within the cell, it simply alerts the immune system to the presence of the cells. In this way, we believe that all our program will have broader clinical utility, addressing a major unmet medical need.

The video shows EGFR over-expressing cancer cells being engulfed by macrophages (red events), induced by Alphamer® and anti-Gal antibodies

“Our mission is clear and focused.

First and foremost, exploit our Alphamer technology through our proprietary pipeline of novel cancer programs.

Secondly, make our technology available to other companies working in other disease areas.”

Nick Staples, CEO (Interim)

Partnerships

Avvinity has exemplified the use of antibodies, antibody fragments, RNA/DNA aptamers and small molecules as targeting domains with its linker technology. When conjugated to these targeting domains, Avvinity’s linker technology can drive immune destruction of tumours or diseased tissue with minimal impact on healthy tissue.

The linkers fine-tune for efficacy and PK properties (e.g. linker length, rigidity, clogP). The linkers are stable and designed to be non-cleavable. Syntheses are scalable with high-yielding routes.

Avvinity actively seeks partnerships with academic groups or companies with novel antibodies, peptides or small molecules to expand the portfolio of Alphamers that specifically target cancer cells and other conditions of high unmet medical need.

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