In June, Repare Therapeutics Inc (RPTX) raised $220 million by offering 11 million shares at $20, the high end of the upwardly revised range of $18 to $20.
Repare is a pre-clinical biotech company developing gene therapies for solid tumors based on a synthetic lethality (SL) approach to drug development.
The company has advanced a proprietary, genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair.
Using its SNIPRx® platform, Repare is building a pipeline of SL product candidates, including its lead product candidate, RP-3500, an oral small molecule inhibitor for the treatment of solid tumors with specific DNA damage repair-related genomic alterations. According to SEC documents filed in June 2020, the company anticipates filing an investigational new drug, or IND, application in the second quarter of 2020 and initiating an open-label Phase 1/2 clinical trial of RP-3500 in the third quarter of 2020.
The company’s SL-based approach to the development of new precision oncology therapeutics has multiple potential benefits:
• Ability to address previously untargetable tumor biology, including, for example, loss-of-function mutations;
• Enhanced benefit-risk profile, by precisely targeting tumor cells with the defined mutation while sparing normal, non-cancerous cells;
• Genetic stratification of patients, potentially enabling higher response rates; and
• Tumor-agnostic approach, focusing on specific genetics and enabling the application to multiple tumor types.
The Synthetic Lethality Opportunity and Challenge
SL is a powerful approach and opportunity in oncology drug development that combines two key principles in treating patients with cancer through precision oncology: (1) identifying and selecting patient subgroups with specific genomic alterations in tumors that are most likely to benefit from these therapies and (2) improving tolerability and reducing toxicity by not affecting normal, non-cancerous cells. SL arises when deficiencies in a pair of genes occur simultaneously to result in cell death, but if that deficiency exists in only one gene, the cell will survive. As depicted below, cancer cells that contain an alteration in one gene of a SL pair are susceptible to therapeutic intervention targeting the other gene pair, resulting in cell death, whereas normal cells are not affected by the inhibition of the targeted gene and remain viable.
On May 26, 2020, Repare announced it had entered into an exclusive, worldwide research collaboration with Bristol Myers Squibb (BMS).
“This collaboration will help to ensure that our novel discoveries are being broadly prosecuted in the search for the next generation of precision oncology medicines,” said Lloyd M. Segal, President and Chief Executive Officer of Repare Therapeutics. “Bristol Myers Squibb brings key strategic capabilities to this partnership and the resources to maximize our platform’s potential while allowing us to independently focus on our proprietary clinical and near-clinical programs.”
“We look forward to collaborating with Repare and to applying their SNIPRx® technology to enable the identification of novel precision oncology therapeutics,” said Rupert Vessey, M.A., B.M., B.Ch., F.R.C.P., D.Phil., Executive Vice President, Research & Early Development, Bristol Myers Squibb. “Repare’s distinctive team and technology have the potential to lead to the discovery of important targeted drug candidates that can result in new precision therapies for patients.”
Under the terms of the agreement, the companies will leverage Repare’s proprietary, CRISPR-enabled genome-wide synthetic lethal target discovery platform, SNIPRx®, to jointly identify multiple synthetic lethal precision oncology targets for drug candidates. Repare will grant BMS exclusive worldwide rights to develop and commercialize therapeutics for select validated synthetic lethal precision oncology targets discovered under the collaboration.
As part of the agreement, BMS will make an upfront payment of $65 million which includes a $15 million equity investment in Repare. Repare will be eligible to receive up to approximately $3 billion in license fees, discovery, development, regulatory and sales-based milestones, in addition to royalty payments on net sales of each product commercialized by BMS.