Tarveda licenses HSP90 drug conjugate platform

Deal with Madrigal Pharmaceuticals could be worth in excess of $249 million

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CONSHOHOCKEN, Pa. & WATERTOWN, Mass.—Madrigal Pharmaceuticals Inc. and Tarveda Therapeutics Inc. have 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 is a biopharmaceutical company discovering and developing Pentarins as a new class of targeted anticancer medicines to advance the treatment of patients with solid tumors. Madrigal itself acquired the HSP90 drug conjugate platform via its recent merger with Synta Pharmaceuticals Inc.
According to Suzanne Elvidge in an article at BioPharmaDIVE.com, licensing the rights for the HSP90 drug conjugate platform is a strategy which will let Madrigal focus on its own main objectives. Madrigal’s current pipeline includes liver-directed thyroid hormone receptor-ß agonist MGL-3196, a small-molecule therapeutic for dyslipidemia/hypercholesterolemia and nonalcoholic steatohepatitis (NASH). According to Madrigal’s website, they have recently begun a Phase 2 study of MGL-3196 in patients with NASH.
“This transaction is a key element of Madrigal’s strategy to out-license our novel oncology assets to organizations with the oncology focus and resources to fully exploit the opportunity for product development and commercial success,” said Dr. Paul A. Friedman, chairman and CEO of Madrigal. “We are pleased to have completed this important and potentially valuable agreement with Tarveda.”
Under the terms of the agreement, Tarveda will be responsible for all of the development costs for the HSP90 drug conjugate program. Madrigal will receive an undisclosed upfront payment, and is eligible to receive up to $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. Potential development, regulatory and sales milestone payments related to a second HSP90 drug conjugate product would be lower. Madrigal is also eligible to receive a tiered, single-digit royalty based on future worldwide sales of HSP90 drug conjugate products.
“The HSP90 drug conjugate platform with its lead drug candidate PEN-866, which is scheduled to be in the clinic during the first half of 2017, is an ideal fit for our growing Pentarin pipeline of novel oncology therapeutics,” Drew Fromkin, president and CEO of Tarveda, commented in a press release. 
HSP90 drug conjugates are designed to increase cancer cell killing while reducing collateral damage to normal cells, and to 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 anticancer payload via a linker that is optimized for controlled release of the payload inside cancer cells. The conjugate’s sustained antitumor 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.
According to Xconomy’s Ben Fidler, Tarveda’s Pentarins are “essentially tinier versions of antibody-drug conjugates, or ADCs, a type of cancer treatment that links antibodies to toxins to attack tumors. The difference is Pentarins use peptides—much smaller molecules than antibodies—to shepherd the drug to tumor cells, which in theory might help them penetrate tumor tissue more easily than ADCs. Tarveda says PEN-866 is different than past failed HSP90 inhibitors because it’s a conjugate—it doesn’t just block HSP90, it carries a byproduct of…irinotecan.”
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.
“Tarveda is developing therapeutics to overcome the limitations of current cancer treatments through our Pentarin platform. Pentarins leverage their miniature size and improved pharmacokinetics to penetrate into solid tumors and cause cancer cell death with highly selective cell surface and intracellular targeting, tuned linkers and potent payloads,” said Fromkin.
“The Tarveda pipeline also includes PEN-221, our Pentarin conjugate that binds to the somatostatin cell surface receptor, after which the conjugate’s potent payload is internalized into the cancer cell. PEN-221 is scheduled to enter Phase 1 trials this year to treat patients with neuroendocrine and small-cell lung cancer tumors,” Fromkin said. “We look forward to advancing both of these novel Pentarin drug candidates into clinical studies in the near term and expanding the Pentarin platform pipeline by developing new conjugates linked to other potent payloads, including challenged but promising payloads being developed by potential pharmaceutical partners.”

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