German based Merck KGaA, and Mersana Therapeutics USA have signed a research collaboration and commercial license agreement to discover novel antibody-drug conjugates (ADCs) leveraging Mersana’s proprietary Immunosynthen STING-agonist ADC platform, directed against up to two targets.

The Immunosynthen platform is designed to generate systemically administered ADCs that locally activate Stimulator of Interferon Genes (STING-) signaling in both tumor-resident immune cells and in antigen-expressing tumor cells, unlocking the anti-tumor potential of innate immune stimulation.

“Building on our deep expertise and portfolio of two clinical and nine preclinical assets in the ADC space, we are focused on the discovery of next-generation state-of-the-art ADC drugs,” said Paul Lyne, Head of Research Unit Oncology at the Healthcare business sector of Merck KGaA, Darmstadt, Germany.

“An approach that can directly target the tumor microenvironment with an immunomodulatory ADC has the potential to bring the benefits of this immunotherapy to a broader group of patients. This collaboration with Mersana to design novel immunostimulatory ADCs that can harness the potential of the STING pathway is an ideal complement to our innovation in this area,” Lyne added.

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Anna Protopapas
President and Chief Executive Officer. © 2020 – 2022 Mersana. Used with permission.

Generating Immune response
The STING pathway is a well-studied. It is a fundamental means of generating innate immune response that can lead to anti-tumor activity and immunological memory.

A great number of studies have demonstrated  that the activation of STING, and the stimulation of type I IFN production, are critical for anticancer immune responses. In addition, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For example, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Furthermore, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells.[1]

Mersana’s extensive preclinical data demonstrate Immunosynthen’s ability to enable highly targeted STING activation within both tumor cells and tumor resident myeloid cells while avoiding unwanted systemic effects.

The company’s preclinical data show that the anti-tumor activity of Immunosynthen ADCs involves the targeted activation of the STING pathway in both tumor-resident immune cells and in tumor cells, in an antigen binding-dependent manner.

This “one-two punch” provides the potential for enhanced anti-tumor activity when compared to other innate immune approaches that activate only the immune cells. Further, we have generated preclinical data across multiple targets and tumor models showing complete regression of tumors in vivo after a single low, well-tolerated dose, consistent with increased cytokine expression and immune cell infiltration within the tumor and immune memory.

In addition, researchers at Mersana have demonstrated the tolerability and favorable pharmacokinetic profile of Immunosynthen ADCs in non-human primates, after multiple IV doses and at exposures significantly higher than those required for robust efficacy in mice.

“We are pleased to be partnering with Merck KGaA, Darmstadt, Germany to extend the reach of our Immunosynthen platform and bring novel new product candidates forward with the potential to benefit patients,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

Agreement
Under the terms of the agreement, Mersana will develop novel ADC product candidates against up to two targets utilizing its Immunosynthen platform to conjugate proprietary antibodies from Merck KGaA, Darmstadt, Germany. Pre-clinical activities will be split between the companies. Merck KGaA, Darmstadt, Germany will be solely responsible for all clinical development and potential commercialization activities relating to any resulting product candidates.

As part of the agreement, Mersana will receive an upfront payment of $30 million. Mersana is also eligible to receive reimbursement of certain costs, up to $800 million in potential regulatory, development and commercial milestone payments, and up to low double-digit percentage royalties on worldwide net sales of any approved ADCs developed under the agreement.

Reference
[1] Zhu Y, An X, Zhang X, Qiao Y, Zheng T, Li X. STING: a master regulator in the cancer-immunity cycle. Mol Cancer. 2019 Nov 4;18(1):152. doi: 10.1186/s12943-019-1087-y. PMID: 31679519; PMCID: PMC6827255.

Featured image: Laboratories. © 2020 – 2022 Mersana. Used with permission.

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