Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL) and Tarveda Therapeutics, Inc. today announced an exclusive worldwide license agreement providing for the discovery, development and commercialization by Tarveda of products based on Madrigal’s HSP90 Drug Conjugate program, including the lead clinical candidate, PEN-866. Madrigal is a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapeutic candidates for the treatment of cardiovascular, metabolic and liver diseases, and Tarveda Therapeutics, Inc., is a biopharmaceutical company discovering and developing Pentarins™ as a new class of targeted anti-cancer medicines to advance the treatment of patients with solid tumors.
HSP90 drug conjugates are designed to increase cancer cell killing while reducing collateral damage to normal cells and overcome the challenges of current chemotherapies and other payloads, which are commonly limited by insufficient drug exposure in the tumor and/or systemic toxicities. HSP90 drug conjugates are small-molecule conjugates consisting of an HSP90 targeting molecule joined to an anti-cancer payload via a linker that is optimized for controlled release of the payload inside cancer cells. The conjugate’s sustained anti-tumor effect comes from selectively accumulating and retaining the conjugate and, importantly, its potent payload in tumors. HSP90 drug conjugates contrast with previous HSP90 inhibitors that were designed to only inhibit HSP90. Madrigal acquired the drug conjugate platform via its recent merger with Synta Pharmaceuticals, Inc.
The lead HSP90 drug conjugate, PEN-866, is a small-molecule drug conjugate that comprises an HSP90 ligand conjugated to SN-38, the highly-potent, active metabolite of the chemotherapeutic agent irinotecan. PEN-866 binds with high affinity to the intracellular HSP90 target. Once bound to its target, PEN-866 delivers the tumor-killing SN-38 payload. PEN-866 has shown an impressive degree of efficacy and durability of response in multiple preclinical tumor models, including patient-derived xenograft models. Studies demonstrate that SN-38 released from PEN-866 accumulated at high levels within the tumors and was associated with increased and widespread cancer cell death when compared with irinotecan alone.
Under the terms of the agreement, Madrigal will receive an upfront payment and is eligible to receive up to an aggregate of $163 million of contingent payments based upon the achievement of specified development, regulatory and sales milestones related to the first HSP90 drug conjugate product developed under the agreement. Madrigal is also eligible to receive a tiered, single-digit royalty based on future worldwide sales of HSP90 drug conjugate products. Potential development, regulatory and sales milestone payments related to a second HSP90 drug conjugate product would be lower. Tarveda will be responsible for all of the development costs for the HSP90 drug conjugate program.