What attracts BioNTech to expand its antibody and cell therapy layout with over $790 million in cooperation?

January 16, 2022 / eMedClub PR News/--Recently (January 10, 2022), BioNTech SE announced that it has entered into a multi-target discovery collaboration with Crescendo Biologics Ltd.
to develop treatments for cancer and novel immunotherapies for other diseases
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The collaboration will leverage BioNTech's proprietary multimodal immunotherapy expertise with Crescendo's proprietary fully human heavy chain antibody domain Humabody® VH platform to develop precision immunotherapies, including mRNA-based antibodies and engineered against BioNTech's selection cell therapy
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BioNTech will have exclusive global development and commercialization rights to all immunotherapies resulting from the collaboration
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Crescendo will receive an upfront payment of $40 million, including a cash payment and equity investment from BioNTech, as well as research funding, and will be eligible for development, regulatory and commercial milestone payments totaling more than $750 million, as well as grading of global net sales royalties
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What are the advantages of heavy chain-only antibody molecules? BioNTech's Humabody® VH platform is proprietary to Crescendo, and its technology produces a Humabody molecule with the light chain removed and only the heavy chain
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The Humabody VH platform is able to specifically bind to the smallest portion of an antigen-antibody, approximately one-tenth the size of a standard antibody
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This small size enables excellent tissue accumulation and penetration, resulting in higher therapeutic conversion rates compared to traditional IgG
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At the same time, the small size also enables it to be administered by multiple routes, including intravenous, subcutaneous, topical, pulmonary, oral, and ocular
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Crescendo's Humabody VH platform enables the development of not only antibody therapeutics but also novel T cell-related therapies
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Its advantages include: fully human VH domain, no humanization steps required The half-life of antibodies can be regulated by multiple routes of administration in sexual form.
The company's flagship product developed by itself is CB307, a CD137(4-1BB)xPSMA bispecific T cell engager for PSMA target-positive tumor patients
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▲ Schematic diagram of the mechanism of action of CB307 CB307 prolongs the half-life, and can conditionally activate tumor-specific T cells and initiate the tumor microenvironment of the CD137 (4-1BB) co-stimulatory mechanism
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Activated and proliferated tumor-specific T cells can drive widespread tumor cell killing while acquiring an anti-cancer "memory" effect
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Thus CB307 can achieve potent tumor-specific killing while avoiding systemic toxicity
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This technology platform has also won the cooperation attention of many enterprises
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Crescendo and Takeda have a $790 million collaboration in immuno-oncology, ADCs and CAR-T
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Takeda's selection of targets includes immuno-oncology (IO) modulators and Humabody drug conjugates (HDCs) and expanded in 2019 to include the development of the Humabody VH domain for inclusion in Takeda's CAR-T therapies
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In 2018, Zai Lab signed a global exclusive license agreement with Crescendo to develop Humabody therapeutic drug ZL-1102 (formerly CB001), which has already achieved Phase 1b proof-of-concept clinical trials
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Zai Lab plans to advance a Humabody VH fragment antibody ZL-1102 targeting IL-17A
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▲ Crescendo R&D pipeline (Source: official website) In addition, Crescendo also cooperated with Cancer Research UK to develop CB213 in 2020, a new bispecific PD-1xLAG-3 antagonist, designed to overcome cancer-induced of T cell exhaustion and enhances the activity of patient-derived T cells
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Preliminary clinical data are currently available
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BioNTech's existing antibodies & cell therapy antibodies: double-antibody cooperation products are the main products In fact, this is not the first time that BioNTech has deployed antibodies and cell therapy fields
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BioNTech's progress report in the third quarter of 2021 mentioned the next-generation immune checkpoint inhibitors BNT311 and BNT312 in cooperation with Genmab, and briefly reported the progress of the two trials
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▲ BioNTech’s antibody research and development pipeline (source: official website) ➤ BNT311 (ie GEN1046) is a dual-antibody drug targeting PD-L1x4-1BB (CD137), and is currently undergoing a multi-expansion cohort for solid tumor patients.
In the Phase 1/2 clinical trial, as of May 2021, a total of 40 patients have been enrolled
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The pharmacodynamic effects of BNT311 were shown to be consistent with its proposed mechanism of action
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In addition, an association was observed between disease control and the level of tumor expression of PD-L1, as well as time since last anti-PD-1 therapy
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Phase 2 trials of BNT311 as monotherapy and in combination with pembrolizumab are scheduled to begin in the fourth quarter of 2022 in patients with relapsed/refractory metastatic NSCLC
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➤ BNT312 (also known as GEN1042) is a double antibody targeting CD40x4-1BB and is also directed against a variety of solid tumors
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CD40/CD40L is also a popular target to compete for the "successor" of PD-1/L1
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BioNTech will present clinical data from the dose-escalation portion of the ongoing Phase 1/2 trial in a small oral presentation at the 2021 SITC Congress
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Overall, the data demonstrate a favorable safety profile, as well as biological and early antitumor activity, in patients with advanced solid tumors
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As of June 11, 2021, 25 of 49 patients (51%) achieved disease control, including two confirmed partial responses in melanoma and neuroendocrine lung cancer according to RECIST1.
1
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Cell therapy: CAR-T therapy is progressing the fastest Data from extended trials
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BNT211 is a CAR-T solid tumor therapy targeting Claudin-6
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The data showed a favorable safety profile, with three of the five patients showing initial tumor shrinkage and four showing stable disease
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➤ In addition, another novel antigen-targeted T cell therapy by BioNTech, BNT221, has also entered the clinical stage, aiming to treat patients with immune checkpoint inhibitor unresponsive or refractory metastatic melanoma
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Preclinical data from this product candidate show its ability to induce CD8+ and CD4+ T cell responses in peripheral blood mononuclear cells from ovarian cancer patients
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Summary Crescendo's Humabody VH platform includes not only heavy chain-only novel antibody molecules, but also the development of novel T cell engagers, which coincides with the novel antigen T cell therapy in BioNTech's R&D pipeline
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This technology platform can also be extended to the solid tumor treatment areas that BioNTech is also interested in, such as Toll-like receptors
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This cooperation can be vaguely seen that BioNTech, with its rich experience in mRNA research and development in multiple fields, is expanding into the field of solid tumor treatment
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References: 1.
https://investors.
biontech.
de/news-releases/news-release-details/biontech-and-crescendo-biologics-announce-global-collaboration Progress does not constitute any medical guidance.
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