Cambridge (MA) based Revitope Oncology, a biotechnology company advancing a new class of precision cancer immunotherapies, and Junshi Biosciences, a China-based biopharmaceutical company focusing on the discovery, development, and commercialization of novel therapies, announced that the companies have entered into a strategic research collaboration.

With a combined 33,000L fermentation capacity in two GMP-facilities in Shanghai and Suzhou (China), Junshi has established a manufacturing infrastructure to support manufacturing and commercialization and provide its partners with high-quality products through a global supply chain network.

Proprietary protein engineering
As part of the agreement, Revitope will leverage its proprietary protein engineering platform together with Junshi’s novel antibody components to develop first-in-class dual-antigen targeting cancer therapies. Revitope is granting Junshi a world-wide exclusive license on products arising from the research collaboration and will receive up to U.S. $ 160 million in development and commercialization milestone payments for each T Cell-engaging Antibody Circuit (TEAC) molecule selected by Junshi, plus tiered royalties.

In addition, Junshi also commits to making a direct equity investment in Revitope Oncology in the amount of U.S. $10 million for 9.99% of total Revitope Oncology shares on an as-converted basis with terms and conditions to be mutually agreed and subject to compliance with all applicable laws.

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Unique platform technology
“By leveraging Revitope’s unique two-component T-cell immunotherapy platform and our in-house antibody capabilities reaching from discovery to commercialization, dual targeting precision-based novel cancer immunotherapies can be brought into clinical trials in the near future,” said Sheng Yao, Ph.D., Vice President of Junshi Biosciences.

“As an innovation-driven company, we believe the collaboration with Revitope will empower us to generate a new generation of first-in-class immunotherapy compounds designed to improve both safety and clinical efficacy,” Yao added.

Because tumors typically do not express cell surface proteins unique to the tumor, conventional bispecific antibody therapeutics can generate unwanted and substantial “on-target, off-tumor” toxicity.

Sheng Yao, Ph.D., Vice President of Junshi Biosciences.

Revitope’s proprietary T Cell-engaging Antibody Circuit (TEAC) technology platform exploits co-expressed tumor antigens to enable the development of highly specific cancer drugs with improved safety and efficacy over conventional immunotherapeutic approaches. The company’s unique approach is based on a pair of tumor-targeted antibodies with a shared T-cell engaging domain which acts as inactive pro-drugs unless they encounter cancer cells co-expressing both antigens.

Developed with traditional tumor-targeting domains, TEAC therapies split the CD3 paratope (the T-cell recognition domain) into two halves, with one half on one molecule and the other half on the other molecule. This allows for true dual-antigen targeting to a unique tumor-specific address – two inputs coming together to enable one precision-targeted output, i.e. a true “and” gate safety feature. Only when the two molecules come together through binding to their different tumor targets on the same tumor cell can the two halves of the CD3 binding domain recombine and create a fully functional anti-CD3 domain (a TEAC).

Normal cells expressing only one or neither of the targeted antigens will not elicit activation of a TEAC pair thereby avoiding unwanted toxicity in healthy tissues.

“We are excited to partner with Junshi, a company with state-of-the-art antibody discovery technologies and world-class development capabilities, to advance our unique two-component T-cell engager therapies that have the ability to target tumor cells and deliver more efficacious and safer drugs to patients,” concluded Steve Arkinstall, Ph.D., Chief Executive officer of Revitope Oncology.

Summary

  • Traditional T cell-redirecting therapies can kill tumor cells in therapeutically useful ways but are limited by off-target and on-target/off-tumor toxicities
  • The goal of the T Cell-engaging Antibody Circuit (TEAC) platform is to focus T-cell redirection to the tumor and limit T cell-driven toxicities in the periphery to improve therapeutic index and expand treatment opportunities in both liquid and solid tumors
  • TEAC relies on several key principles to increase therapeutic index:
    • A requirement for selective dual antigen binding in the tumor to increase specificity,
    • Protease cleavage of the TEAC prodrug to activate the CD3 circuit in the tumor and
    • A dummy associated half-life extension domain that leads to rapid inactivation and clearance of activated TEAC in the periphery to limit off-target engagement of T-cells