Why Repare Therapeutics could be a game-changing biotech company

Last week, Repare Therapeutics, an Amplitude portfolio company, announced the closing of an upsized Initial Public Offering of $220M, a significant increase from the initial $100M IPO plan earlier this month.

We believe Repare has the opportunity to be a game-changing company due to several factors:

Synthetic lethality is emerging as a goldmine for novel cancer targets:

Repare is currently one of the leading precision oncology companies targeting a synthetic lethal (SL) approach to discover new disease-modifying cancer targets. SL is a powerful approach to oncology drug discovery as it can identify patients with specific genomic alterations in tumours that are most likely to benefit from the therapies, and if targeted correctly, can improve the tolerability and toxicity profiles by not affecting normal, non-cancerous cells.

The first clinically validated SL gene pair is PARP-BRCA1/2. First discovered in 2005, inhibition of PARP in cells that were BRCA1/2-null was shown to have improved cancer cell killing. This discovery has been commercialized, and AstraZeneca, GSK, Pfizer and Clovis all have products in the market that have generated~ $1.6B in sales in 2019 and expected to reach $6.1B in sales by 2024.

Multiple biotech companies and pharma players are now utilizing SL, including Artios, Ideaya, Cyteir, and ForX therapeutics. GSK recently signed a $120M deal with Ideaya, and it’s likely we’ll see more activity in this space as the years progress. Repare remains a leader in this field as it is founded upon the academic expertise of Dan Durocher and his CRISPR-based target discovery and patient selection approach coupled with Frank Sicheri and his crystallography-based drug design. With the pharma validation of Ono Pharmaceuticals and the recent partnership announcement with BMS, we are excited about how these different parts of Repare’s platform will come together to bring new drugs for patients.

SNIPRx platform — a full-stack discovery platform:

Repare has shown, through its SNIPRx platform and the structure-based drug design approach, its ability to discover and develop potentially best in class orally available small molecule inhibitors against a variety of targets. For instance, Bayer, AstraZeneca and Merck Serono are all developing ATR inhibitors. However, Repare’s lead program, RP-3500, has shown to have increased potency, similar/improved selectivity and a favourable PK profile in multiple preclinical models.

Moreover, by utilizing its discovery platform, Repare has been able to discover and validate small-molecule inhibitors against novel targets. This is evidenced by its discovery of a CCNE1-SL inhibitor which has not been previously published as an SL target, and currently has no advanced drug discovery efforts against it. This is an interesting target because amplification of CCNE1 is found in many tumour types and these tumours don’t respond well to platinum or PARP inhibitor treatment, thereby representing a significant unmet need and untapped market.

Repare has proven its ability to not only discover and select a target against a specific genetic lesion but also to develop potent, orally available small molecules against these lesions that could be game-changers for cancer patients.

STEP2 platform — a new approach to clinical trials:

The idea behind precision medicine is to give the ‘right therapy’ to the ‘right patient’ at the ‘right time’, and Repare is a classic example of this. Once a small molecule inhibitor has been identified, Repare conducts a SNIPRx Targeted Expansion of Patient Population (STEP2) screen that utilizes a set of cell lines which, when treated with the clinical candidate, elucidate genes that, when knocked down, cause (hyper) sensitivity to their inhibitor. These not only confirm the SL relationship with the original tumour lesion but also identify additional genomic alterations that confer a response to the product candidate.

For RP-3500, Repare has been able to identify up to 19 additional genomic subtypes, in addition to ATM deficiency, where the therapy is most likely to achieve clinical benefit, thereby expanding the patient population beyond current understanding. This, we believe, is the most interesting aspect of the platform because Repare has been able to potentially increase its chances of success in clinical trials, which ultimately could secure an accelerated regulatory approval path in certain targeted patient populations.

This represents a compelling opportunity going forward as oncology drugs represent 41% of current blockbuster drugs (over $1B in sales), half of which target biomarker-labelled indications. As an example, Loxo Oncology followed this blueprint and was ultimately sold to Eli Lilly for $8 Billion, showcasing how significant a precision medicine opportunity can become.

Management — a world-class team:

Companies ultimately live and die based on the people running them and Repare has shown its ability to recruit an exceptionally talented and experienced team. Led by Lloyd M. Segal, an experienced entrepreneur, Repare has been able to recruit Steve Forte, former CFO of Clementia which was sold to Ipsen for >$1B USD, Maria Koehler, former CMO of Bicycle Therapeutics and former VP Strategy for Pfizer Oncology, and Michael Zinda, former executive director of Cancer Biosciences at AstraZeneca. Recently, Samarth Kulkarni, CEO of CRISPR Therapeutics (>$4B USD in market cap), has joined the board as an independent director, adding to an already stellar board of investors and company builders.

Canada has the ability to create and foster world-leading companies

Repare is just the latest example of how Canada is becoming a hot-bed for innovation. For the longest time, Canada didn’t have the entrepreneurial talent nor the abundance of big pocketed investors to truly accelerate the biotech ecosystem and create anchor companies. However, a recent string of successes such as Zymeworks, Clementia, Abcellera, and Fusion amongst others, has demonstrated that there’s a significant and compelling interest in the Canadian life science innovation ecosystem from both local and global investors alike.

Becoming a leading, world-class company is no easy task, but with a powerful discovery platform, a robust pipeline, unique patient selection processes, an exceptional management team, and a stellar group of investors, Repare has demonstrated exceptional potential to become something truly remarkable. We are thrilled that this company is in our portfolio. It’s definitely an exciting time to be in the Canadian healthcare ecosystem and it feels like we’re only getting started.