Repare shelves its early work
Although synthetic lethality is hot, Repare Therapeutics hasn’t reaped the benefits of being active in this space. The company’s stock has been depressed since it lost Roche as a partner in February, and yesterday Repare cut a quarter of its staff and said it would focus only on its clinical programmes. With little known about the group’s preclinical work, it’s unclear what projects it’s losing. But chief among its remaining assets are the PKMYT1 inhibitor lunresertib and the ATR inhibitor camonsertib, which are being tested together in the Mythic trial. Solid tumour data released last year were tricky to interpret, and Repare will have to hope for a better reception from investors when it reports an update in gynaecological cancers in the coming months. Roche’s decision to opt out of camonsertib dealt a blow to the ATR field, which has also seen the discontinuations of Bayer’s elimusertib and Merck KGaA’s berzosertib. The most advanced project here is AstraZeneca’s ceralasertib, currently in the phase 3 Latify study in NSCLC, with data due in 2025. Astra is a leading proponent of synthetic lethality, but fell short with another approach, Wee1 inhibition, and isn’t working on the other targets that Repare is pursuing.
Repare’s pipeline
Project | Description | Key trial | Note | Competition |
---|---|---|---|---|
Lunresertib | PKMYT1 inhibitor | Ph1 Mythic: data due Q4 2024 with lunresertib + camonsertib in platinum-resistant ovarian & endometrial cancers; data due 2025 with lunresertib + Debio 0123 in solid tumours* | Potential to begin a registrational trial in 2025 | Schrödinger has a Wee1/PKMYT1 inhibitor, SGR-3515, in ph1 |
Camonsertib | ATR inhibitor | Ph1 Mythic, as above; ph1/2 Tresr has camonsertib monotherapy NSCLC cohort, data due 2025** | Roche dropped project Feb 2024 | Rivals include AstraZeneca (ceralasertib, ph3) & Merck KGaA (tuvusertib, ph2) |
RP-1664 | PLK4 inhibitor | Ph1 Lions in TRIM37-high solid tumours | Ph1/2 planned in paediatric recurrent neuroblastoma (no specific timelines given) | Treadwell has ocifisertib in ph1/2 |
RP-3467 | DNA Pol θ inhibitor | Ph1 Polar to start Oct 2024, +/- Lynarpza in solid tumours | Trial recently listed on ct.gov | GSK/Ideaya (GSK4524101, ph1/2), Artios (ART6043, ph1/2), Moma (MOMA-313, ph1), Varsity (Novobiocin, ph1) |
Notes: *patients have CCNE1 amplification, or FBXW7 or PPP2R1A mutations; **patients have ATM mutations. Source: OncologyPipeline.
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