Lonza 2024

Innate Pharma S.A. and Sanofi have entered into a collaboration agreement with Sanofi applies Innate Pharma’s site-specific conjugation technology to the development of new Antibody Drug Conjugates.

“By combining some of Sanofi anti-tumor antibodies with our novel technology for conjugating cytotoxic compounds, this collaboration opens the gate to next-generation ADCs with a potentially improved therapeutic index for patients with cancer” noted Hervé Brailly, CEO and co-founder of Innate Pharma.

Sanofi-Aventis Recherche & Développement, the French Research and Development arm of Sanofi, will evaluate site-specific payload conjugation to enhance the pharmacokinetics, efficacy and safety of antibody-drug conjugates. In addition, the company has the option to enter into a licencing agreement with Innate Pharma. Other terms of the agreement are undisclosed.

A Novel technology
Innate Pharma’s innovative coupling technology uses bacterial transglutaminase (BTG) enzyme. This technology aims to address the heterogeneity associated with traditional ADC coupling technologies which limits the therapeutic index of antibody conjugates. With Innate Pharma’s technology, a single point mutation in the antibody’s heavy chain generates either two or four specific enzyme-recognition sites, and linkers have been optimized to couple quantitatively at these positions.

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Fig 1.0. Innate Pharma’s technology helps generate homogeneous ADCs in 2 steps with an exact antibody-drug ratio (DAR) (Figure Innate Pharma).

The method yields complete homogeneous antibody-drug conjugates with a defined stoichiometry and a drug-to-antibody ratio or DAR of exactly 2:1 or 4:1. The coupling is site-specific with minimal antibody scaffold modification, therefore only adding two steps in an already well-established manufacturing procedure widely accepted by regulatory agencies.[1]

Moreover, Innate Pharma’s novel bacterial transglutaminase or (BTG) enzyme-based process requires a minimal amount of cytotoxic drug compound, which can be critically important with regard to large-scale production of antibody-drug conjugates. Research has shown that this technology displays high versatility appropriate for testing various linkers and toxins such as Pyrrolobenzodiazepine dimers (PBD), a class of highly potent toxins, in high-throughput screening.

This chemo-enzymatic approach not only allows conversion of virtually any IgG1 into a functional antibody-drug conjugates, but also enables rapid evaluation of various antibody candidates, linker systems or cytotoxic compounds.

Previous comparative in vivo studies with xenografted mice the pharmacological profiles for enzymatically conjugated antibodies have shown to be better than those of chemically modified mice. In one specific case, BTG-ADCs had greater accumulation in tumors than in nontarget organs.[1]

Stable and low clearance
Innate Pharma’s BTG-ADCs are stable in vivo and have low clearance. Quantitative time-dependent in vivo biodistribution studies show high and specific tumor uptake, resulting in a favorable therapeutic index.

Additional potential
Innate Pharma uses the technology to expand its own portfolio of antibody-drug candidates – but is also forming strategic partnerships on the technology with other pharmaceutical companies. In addition, the company has two clinical-stage programs in immuno-oncology, a new therapeutic field that is changing cancer treatment by enhancing the capability of the body’s own immune cells to recognize and kill cancer cells. Innate Pharma’s science also has potential in chronic inflammatory diseases. To date, the the company’s innovative approach has translated into major alliances with leaders in the biopharmaceutical industry such as Bristol-Myers Squibb and Novo Nordisk A/S.



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