Every company that has halted, deprioritised, divested or written off a BRAF or pan-RAF inhibitor programme, with the reason each one actually gave. A companion cut to the plixorafenib competitive-intelligence hub, organised by cause of death rather than by competitor.
Not one BRAF or pan-RAF programme in this set was stopped because the mechanism failed on safety. Of ten sponsor decisions, seven were portfolio or capital-allocation calls — the asset was fine, the company changed shape around it. Two were efficacy shortfalls, both in first-generation compounds a decade old. One was a tolerability failure of a specific combination, not of the RAF agent alone.
The second finding matters more commercially: the asset usually outlives the decision. Five of the ten dropped programmes were picked up by someone else and are still in development — and one of them, tovorafenib, went on to become the only FDA-approved drug in the class. Plixorafenib is itself a survivor of exactly this pattern, having outlived the closure of Plexxikon.
Ordered by recency of the decision. "Reason" is the sponsor's stated rationale, not our inference. "Asset today" records whether the molecule is still being developed by anyone.
| Asset | Sponsor that stopped | Class | Stage when stopped | Decision & date | Stated reason | Category | Asset today |
|---|---|---|---|---|---|---|---|
| NaporafenibLXH254 · ERAS-254 | Erascalicensed from Novartis | Pan-RAF | Phase 3 (SEACRAFT-2) | Strategic review May 2025 → sought a partner; termination notice to Novartis Mar 2026, effective 3 Jun 2026 | Prioritise the RAS-targeting franchise (ERAS-0015, ERAS-4001); extend runway from H2 2027 to H2 2028. No efficacy or safety rationale stated publicly. | Portfolio | Rights reverted to Novartis |
| DCC-3084brain-penetrant RAF dimer inhibitor | Deciphera / Ono | Pan-RAF | Phase 1/2 | US development discontinued Sep 2025 | Strategic reasons — explicitly not safety or efficacy, per the sponsor. | Portfolio | Stopped in the US |
| BDTX-4933 | Black Diamond Therapeutics | RAF (pan-RAF / BRAF) | Phase 1 | Deprioritised in a restructuring Oct 2024; licensed to Servier Mar 2025 ($70M upfront, up to $710M milestones) | Concentrate resources on BDTX-1535 (EGFR) and extend cash runway; actively sought a partner for the RAF asset. | Portfolio | Live — Servier |
| BelvarafenibHM95573 · RG6185 | Genentech / Rochelicensed from Hanmi 2016 | Pan-RAF (type II) | Phase 1b / basket | Removed from the Roche portfolio 2024; enrolment stopped in two studies, enrolled patients continued on treatment | Broad portfolio reset — Roche cut roughly 20% of its new molecular entities, focusing on assets with a "lower likelihood" of success. | Portfolio | Live — Hanmi (Korea) |
| BrimarafenibBGB-3245 — combination arm only | MapKureBeiGene / SpringWorks JV | BRAF (next-gen) | Phase 1 combination | Trial BGB-3245-AU-001 terminated Jan 2025 | Lack of tolerability of brimarafenib given in combination with mirdametinib. Monotherapy and other combinations continued. | Tolerability | Live — other trials |
| ExarafenibKIN-2787 | Kinnate Biopharma | Pan-RAF | Phase 1 | Sold to Pierre Fabre 5 Mar 2024; Kinnate acquired by XOMA and wound down (Apr 2024) | Company-level pursuit of strategic alternatives. Pierre Fabre assumed 100% of programme costs and cited a potential best-in-class profile. | Portfolio | Live — Pierre Fabre |
| PLX8394now plixorafenib | Daiichi Sankyo / Plexxikon | BRAF "paradox breaker" | Phase 1/2 (already out-licensed) | Plexxikon R&D unit closed 31 Mar 2022 (announced Jan 2022, ~60 staff) | Daiichi Sankyo R&D reorganisation to concentrate on three ADCs — Enhertu, Dato-DXd, HER3-DXd. | Portfolio | Live — Fore Biotherapeutics |
| TovorafenibTAK-580 · MLN2480 · DAY101 | Takeda / Millennium | Pan-RAF (type II) | Phase 1 (adults) | Adult development ceased; out-licensed to Day One, agreement effective 16 Dec 2019 | Adult-oncology strategy; internal paediatric advocates pushed for an out-licence rather than a shelf. | Portfolio | Approved — Ojemda, Apr 2024 |
| LY3009120DP-4978 | Eli Lilly | Pan-RAF / RAF dimer | Phase 1 | Discontinued after the first-in-human study | Lack of clinical efficacy — unexpected, since exposures reached levels predicted to be therapeutic from preclinical work. | Efficacy | Discontinued |
| RAF265CHIR-265 | Novartis | RAF / VEGFR-2 | Phase 1/2, melanoma | Phase 2 dose-expansion cancelled by protocol Amendment 7, Dec 2011; study completed Nov 2013 | Modest single-agent activity — 8 of 66 evaluable patients responded (12.1%) at an MTD of 48 mg daily. | Efficacy | Discontinued |
| LifirafenibBGB-283 | BeiGene / BeOne Medicines | BRAF monomer + dimer | Phase 1b combination | No public discontinuation statement. Combination study NCT03905148 shows COMPLETED as of Jan 2026 | None given. Lifirafenib was not among the five oncology assets BeOne cut in May 2026. Programme appears dormant rather than formally stopped. | Unresolved | Status unclear |
The dominant mode by a wide margin. In every one of these cases the sponsor's public rationale was about the shape of its own pipeline or balance sheet, and in five of the seven the asset was deliberately placed with someone else rather than shelved.
The most consequential recent exit, because it removed a Phase 3 pan-RAF asset from the competitive set. Erasca ran a strategic pipeline review in May 2025 as ERAS-0015 (pan-RAS molecular glue) and ERAS-4001 (pan-KRAS) approached the clinic, decided to seek a partner for naporafenib, and when none materialised served notice on Novartis in March 2026, terminating effective 3 June 2026. The stated driver was focus and runway — extending cash from H2 2027 to H2 2028.
Caught in Roche's broad portfolio reset, which cut roughly a fifth of its new molecular entities on a "lower likelihood of success" screen. Genentech stopped enrolment in two studies and removed the asset from the portfolio, while continuing to treat and monitor patients already enrolled — the standard responsible-exit pattern, and a useful signal that this was not a safety action.
A company failure rather than an asset failure, and the distinction matters for how the exit reads. Kinnate announced a search for strategic alternatives, sold exarafenib and the rest of the pan-RAF programme to Pierre Fabre on 5 March 2024 — closing on signing, with Pierre Fabre taking on 100% of programme costs and $30.5M in contingent milestones tied to dosing in a first pivotal trial — and was then acquired by XOMA, which wound down operations.
Deprioritised in an October 2024 restructuring to concentrate on the EGFR asset BDTX-1535 and fund operations into Q2 2026, with the company saying openly that it was seeking a partner. Servier took it five months later for $70M upfront and up to $710M in milestones. Phase 1 data has since slipped to late 2026 or early 2027.
The cleanest statement of cause in the whole register: dropped for strategic reasons, with the sponsor explicitly ruling out safety and efficacy. It followed Ono's $2.4B acquisition of Deciphera in April 2024, which is the more likely proximate driver — an acquirer rationalising an inherited early pipeline.
The single most instructive case in the class. Takeda stopped developing TAK-580 in adults around 2019; rather than shelving it, internal paediatric advocates pushed for an out-licence, and the agreement with Day One took effect on 16 December 2019. In April 2024 the same molecule won FDA accelerated approval as Ojemda in relapsed/refractory paediatric low-grade glioma.
Daiichi Sankyo announced an R&D reorganisation in January 2022 and closed the Plexxikon unit — roughly 60 people — on 31 March 2022, to concentrate on Enhertu, Dato-DXd and HER3-DXd. PLX8394 had already been licensed worldwide to Novellus, now Fore Biotherapeutics, in June 2020.
The clearest genuine efficacy failure in the class. The Phase 1 publication records that the absence of clinical activity was unexpected given strong preclinical efficacy and pharmacokinetic exposures at levels predicted to be therapeutic in RAS- and RAF-mutant tumours.
The first-in-human study enrolled melanoma patients irrespective of BRAF mutation status and produced responses in 8 of 66 evaluable patients (12.1%) at an MTD of 48 mg once daily. The Phase 2 dose-expansion was cancelled by protocol amendment in December 2011 and the study closed in November 2013.
Trial BGB-3245-AU-001 was terminated for lack of tolerability of brimarafenib when given in combination with mirdametinib. Brimarafenib itself continued in other studies, including a combination with panitumumab in RAS-mutant colorectal and pancreatic cancer.
Lifirafenib does not appear in BeOne's May 2026 cull, which covered BG-60366 (EGFR), BGB-53038 (pan-KRAS), BG-89894 (MAT2A), BG-68501 (CDK2) and the CCR8 antibody BGB-A3055. The lifirafenib plus mirdametinib study NCT03905148 is recorded as completed as of January 2026, and we found no sponsor statement about the programme's future.
Sourcing this page surfaced material discrepancies against
Competitive_Intelligence_REVIEW.html. They are flagged here, not silently rewritten there.
| What the hub says | What the public record shows | Severity |
|---|---|---|
| Mosperafenib · RG-6344 listed as "Roche (discontinued, out-licensing)" in the Tier 2 basket watchlist | Roche has not discontinued it. Mosperafenib (RG6344 / RO7276389) is in active Phase 1 dose escalation as monotherapy and with cobimetinib, with data presented at AACR and ASCO 2025 — a 24.2% ORR in BRAF V600E-mutant solid tumours and no class cutaneous toxicities reported. The hub's own source list cites that readout, so the status label contradicts its own evidence. | Medium |
| Naporafenib tracked as an active Erasca Phase 3 (SEACRAFT-2) asset | Superseded. Erasca stopped development and terminated the Novartis licence effective 3 June 2026; rights have reverted. The asset should move from the tracked set to this register. | High |
Four conclusions that follow from the register, stated at the level the evidence supports.
Fore/competitive_intelligence/Competitive_Intelligence_REVIEW.html, the plixorafenib CI hub, and CI_PROCESS.md.