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March 6, 2018

Magenta, Heidelberg Pharma Launch Bone Marrow Transplant ADC Collaboration

  • Magenta Therapeutics will license Heidelberg Pharma’s Antibody Targeted Amanitin Conjugates (ATAC) platform and combine it with its stem cell platform to develop targeted antibody–drug conjugates (ADCs) for conditioning regimens in bone marrow transplantation, through a collaboration that could generate up to $334 million-plus for Heidelberg, the companies said.

    Through their exclusive multitarget research agreement, Magenta and Heidelberg said, they plan to develop ADCs with proprietary antibodies across up to four exclusive targets. The companies plan to explore the use of Heidelberg’s platform for producing ATACs—which are ADCs that are based on the compound amanitin as a toxin—in Magenta’s bone marrow transplant conditioning programs.

    Amanitin is a member of the amatoxin group of natural poisons, which occur in the death cap mushroom (Amanita phalloides). It is designed to work by inhibiting RNA polymerase II, resulting in apoptosis. According to Heidelberg Pharma, RNA polymerase II inhibition offers the possibility of breaking through drug resistance or destroying dormant tumor cells, which could produce major clinical advances.

    “Amanitin is one of the promising toxins we are exploring in our targeted conditioning programs, and our partnership with Heidelberg Pharma will allow us to fully evaluate the potential of this payload,” Magenta CSO Michael Cooke, Ph.D., said yesterday in a statement.

    Magenta will gain access to Heidelberg Pharma’s amanitin toxin-linker platform technology, and holds an option for an exclusive target-specific license for global development and commercialization rights to each product candidate resulting from the research collaboration.

    In return, Magenta agreed to pay Heidelberg Pharma undisclosed up-front technology access and exclusivity fees and payments for research support, as well as up to $334 million in option fees and payments tied to achieving clinical development, regulatory, and sales-related milestones.

    “We believe this partnership further validates our technology and underscores our leadership in the field of Antibody Targeted Amanitin Conjugates, a new mode of action for attacking cancer,” added Heidelberg Pharma CSO Andreas Pahl, Ph.D. “We look forward to working with Magenta to expand the application of our ATAC technology to new targets to potentially address unmet needs in bone marrow transplantation.”

  • Third-Generation ADCs

    ATACs are third-generation ADCs, which according to Heidelberg are characterized by improved efficacy and hold potential to be effective in dormant tumor cells that are scarcely reached with existing standard therapies, contributing to tumor recurrence and resistance formation.

    The company also envisions ATACs as treatments for therapy-resistant tumors that no longer respond to standard chemotherapy or antitumor antibodies.

    Based in Ladenburg, Germany, Heidelberg Pharma has used ATAC to develop cancer therapies; its lead candidate HDP-101 is a B-cell maturation antigen (BCMA) ATAC for multiple myeloma.

    Magenta Therapeutics is based in Cambridge, MA, and focuses on developing treatments designed to advance bone marrow transplantation for patients with autoimmune diseases, blood cancers, and genetic diseases.

    The company’s lead program MGTA-456 (formerly HSC835), licensed from Novartis, aims to expand the number of cord blood stem cells used in transplants to achieve improved clinical outcomes compared to standard transplant procedures and enable more patients to benefit from a transplant. Magenta is developing MGTA-456 in multiple diseases, including immune and blood diseases.

    Magenta was launched in 2016 by Third Rock Ventures and Atlas Venture with $48.5 million in Series A financing. Its investors include GV (formerly Google Ventures), which last year led a $50 million Series B financing that included participation from Third Rock and Atlas, as well as Partners Innovation Fund, Access Industries, Casdin Capital, and Be The Match BioTherapies, a subsidiary of National Marrow Donor Program® (NMDP)/Be The Match®.

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