It’s been a busy week for Repare Therapeutics. On Tuesday, the cancer drug developer struck up an alliance with Bristol Myers Squibb (NYSE: BMY) that pays $65 million now and as much as $3 billion later, depending on the progress made in coming years. On Friday, Repare filed for an IPO that could bring in more capital much sooner.
Repare doesn’t yet have any drugs in clinical testing, but now that its approach to cancer has drawn the attention of a big pharmaceutical company, it’s betting it can also draw interest from a broader swath of investors. Montreal-based Repare, which maintains its US operations in Cambridge, MA, set a $100 million target for its IPO. The company has applied for a Nasdaq listing under the stock symbol “RPTX.”
Repare’s cancer drugs are based on a concept called synthetic lethality. The idea is to tap into a genetic vulnerability of tumors that will trigger cell death. But the vulnerability isn’t triggered by targeting the mutation directly. Instead, a synthetically lethal drug targets the other gene in the gene pair. This capability was first achieved by PARP inhibitors, a class of drugs that block an enzyme that cancer cells with specific mutations use to repair DNA damage. AstraZeneca (NYSE: AZN), GlaxoSmithKline (NYSE: GSK), Pfizer (NYSE: PFE) and Clovis Oncology (NASDAQ: CLVS) all sell PARP inhibitors.
The scientists at Repare aim to take synthetic lethality beyond PARP. The company’s CRISPR-based screening technology, called SNIPRx, identifies synthetically lethal gene pairs. Repare then matches them with molecules that could drug them. In the filing, Repare says its approach offers the ability to address tumor biology in ways that currently available technologies cannot while also providing a more targeted approach that spares healthy tissue. The company adds that its technology enables genetic stratification of patients, which could lead to the selection of patients most likely to respond to therapy. Finally, Repare says its technology is agnostic to the types of tumors it addresses, which lends itself to potential application in many cancers.
Lead product candidate RP-3500 is a small molecule designed to block the DNA repair protein ataxia telangiectasia as well as an enzyme called ATR that is activated by DNA replication stress, according to the filing. Repare says it expects to file the paperwork seeking FDA permission to begin clinical trials later this quarter; a Phase 1/2 study could follow in the third quarter of this year.
Repare isn’t the only company applying CRISPR to the search for synthetically lethal cancer drugs. Tango Therapeutics has five preclinical programs discovered by its CRISPR-based technology. The Cambridge-based company raised $60 million in a Series B round of funding last month. Repare and Tango have plenty of company. Lexington, MA-based Cyteir Therapeutics is also developing cancer drugs based on synthetically lethality. Other potential competitors listed in the Repare filing include Bayer, Merck Serono, and IDEAYA Biosciences (NASDAQ: IDYA).
The basis for Repare’s technology comes from company co-founder Daniel Durocher of the Lunenfeld-Tanenbaum Research Institute, the research arm of Mount Sinai Hospital. The Repare filing describes him as an early pioneer of using CRISPR to screen for synthetically lethal gene pairs. The other co-founders are Frank Sicheri, also of the Lunenfeld-Tanenbaum institution, and Agnel Sfeir of the NYU Langone Medical Center. Those scientists teamed with Versant Ventures to start the company in 2016.
Versant is Repare’s largest shareholder, owning a 30.1 percent pre-IPO stake, according to the filing. Other investors include MPM Capital and OrbiMed, which own 11.8 and 11.2 percent respectively. The company has raised $135.2 million; its most recent capital infusion was an $82.5 million Series B financing last September.
Bristol Myers is also set to become a Repare shareholder. According to the financial terms of the collaboration, the upfront payment consists of $50 million in cash and an agreement to purchase $15 million worth of Repare shares. Bristol gains access to some of the biotech’s research. Repare is responsible for early-stage research and identification of small molecules that have the potential to become drugs. Those candidates could include compounds addressing disease targets considered “undruggable.” If the pharma giant licenses any compounds from this research, it will then assume responsibility for further development. Repare could earn $301 million in milestones per program, according to the agreement. If any of these programs result in commercialized drugs, the biotech would receive royalties from sales.
At the end of the first quarter of this year, Repare reported that it had $83.7 million in cash. The company says it will apply the IPO proceeds toward clinical development of RP-3500 and to continue the preclinical development of its other programs.
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