Repare Therapeutics’ drug exploits the genetic vulnerability of tumors to kill them, and the biotech’s early clinical data suggest its lead drug works in ovarian cancer and other tumor types.Roche sees promise in this DNA-damaging approach, and it’s forking $125 million Fight for the global rights of small molecules.
In addition to the upfront payment, the deal qualifies Quebec, Canada-based Repare for up to $1.2 billion in milestone payments — $55 million of which are “recent” milestones related to clinical progress with Roche’s drug camonsertib hand. Repare will also receive royalties if Roche commercializes the molecule. Given the challenges faced by any biotech company looking to raise capital in current market conditions, the upfront cash plus milestone payments will fund the development of the pipeline, the progress of which also poses problems.
“It may sound paradoxical, but we’re a little concerned about how good the rest of the pipeline looks and the investment it’s going to require,” Chief Executive Lloyd Siegel said on a conference call after the deal was announced Wednesday night. said. “We are more excited about the pipeline, including [early clinical drug candidate RP-6306] better than ever.this [deal] Enables us to have our cake and eat it. “
Segal said Repare’s balance sheet is strong, but the cash from the Roche deal gives the company enough money to stay afloat through 2026. Roche said it plans to explore camonsertib in a range of tumor types. Repare retained the option to share the drug’s development in the U.S., but in the near term, Repare’s focus will shift to RP-6306, which is currently in Phase 1 testing, and other programs that are advancing toward the clinic.
Repare’s drug exploits a concept called synthetic lethality, in which defects in gene pairs cause cells to die. While a defect in just one gene is not enough to kill a cell, a drug that targets the other gene in the pair can be a lethal trigger. A class of drugs known as PARP inhibitors pioneered the use of synthetic lethality as a way to target DNA repair pathways in cancer cells. FDA-approved PARP inhibitors include AstraZeneca’s Lynparza, GlaxoSmithKline’s Zejula and Clovis Oncology’s Rubraca. But Repare aims to surpass PARP by addressing other DNA repair enzymes.
Repare’s SNIPRx platform technology identifies these synthetic lethal pairs and matches them to molecules that can target them. Camonsertib, formerly known as RP-3500, is an oral small molecule drug designed to block the DNA damage response protein ATR. It is designed to address tumors with mutations in the ATM gene that pair with the ATR protein. In addition to identifying molecules that can harness synthetic lethality, Repare says its technology can also identify patients who would benefit from this precision oncology approach.
In addition to the relationship between ATR and ATM, Repare said its screen identified 19 additional genes that also had a combined lethal relationship with ATR, meaning the drug has the potential to address other patient populations.
An open-label Phase 1/2 clinical trial testing camonsertib begins in 2020.At the American Association for Cancer Research annual meeting in April, Repare reported that its drug caused lasting clinical benefit Alterations across tumor types and genomes. The company noted promising results in patients with ovarian cancer, breast cancer, head and neck squamous cell carcinoma, and melanoma.
The next program in the repair pipeline, RP-6306, is a small molecule that blocks PKMYT1. Repare said in its investor presentation that RP-6306’s approach has the potential to address a range of tumor types, including uterine, ovarian, gastric, colorectal and bladder cancers. Phase 1 clinical trials are ongoing, with one study evaluating RP-6306 alone or in combination with camonsertib in patients with advanced solid tumors. Kim Seth, head of business and corporate development, said the deal with Roche allows Repare to retain full rights to RP-6306, including in combination with camonsertib. Another Repare drug candidate that blocks polymerase theta has a combined lethal relationship with multiple genetic defects found in tumors. The biotechnology company is preparing the drug for preclinical studies to support investigational new drug applications.
Roche isn’t the first major company to take an interest in Repare’s research. In 2020, Bristol-Myers Squibb Advances $65M in Cash and Makes $15M Equity Investment to Start Partnership find the target for potential anticancer drugs. Unlike Roche’s partnership, which is focused on a single asset that has reached clinical proof-of-concept, the BMS alliance is focused on delivering proven targets that the pharma giant will develop, Segal said.
The Roche deal is expected to close in the third quarter of this year. If approved, the agreement would grant Repare an equitable share of the option to develop and commercialize camonsertib in the United States.If Repare exercises this co-development and profit-sharing option, it would still be eligible for milestone payments and royalties on sales of the drug outside the U.S.
Public area picture Stuart S. Martin via National Cancer Institute
