Plixorafenib — Competitive Intelligence

Open questions

from the FRED board; 6 carry a landscape read

Flagged

3 GO/NO-GO

Q7 monotherapy · Q1 filing maturity · Q3 paediatric cohort

Competitors tracked

1 live dossier, 2 planned, 1 on watch

Evidence reports

3 live

tovorafenib dossier · CNS histology · discontinuations

Cadence

Weekly

delta-scan; full rebuild on inflection points

What this is

The competitive-intelligence hub for plixorafenib. Organised by decision, not by competitor. Each open question carries the current read, how confident we are in it, and the dossier sections behind it. The competitor registry and the source dossiers sit further down — they are the evidence layer, not the answer layer.

What it answers

Which of the eight open board questions the competitive landscape can actually speak to — and which it cannot. Three are flagged GO/NO-GO. Where the landscape has nothing to say, the page says so rather than manufacturing a read.

How it is organised

Decisions first, evidence beneath. Section 1 is the answer layer; sections 2 and 3 are the comparison axes and the source dossiers those answers resolve against. A competitor-by-competitor filing cabinet hides exactly the axes that decide things.

What makes it trustworthy

Competitor data is public and cited. Plixorafenib’s own cells are Fore-internal and stay marked pending, never blank — so no reader mistakes an empty cell for an unfavourable one. CNS response in RANO/RAPNO/iRANO, never RECIST. Every figure carries its denominator and source.

How it stays current

A weekly delta-scan across the tracked competitors flags material changes for sign-off; a full rebuild follows the inflection points — SNO, ASCO and EHA readouts, label changes, confirmatory data, earnings. Section 4 is the running record.

Comment in context on any section — answers anchor to what they answer. Internal: contains competitive positioning and unpublished Fore assessments.

01Where the landscape bears on our open questions

The eight open questions on the FRED board. Three are flagged GO/NO-GO. Only the questions the competitive landscape can actually speak to carry a read; the others say so.

Q7 · GO/NO-GO Is monotherapy positioning defensible against competitor BRAF/MEK combinations across all sub-protocols, or only in CNS?

Current read: defensible in CNS on penetration and tolerability grounds; harder to defend outside CNS, where dabrafenib+trametinib holds an approved V600E combination position. The distinguishing axis is not raw response rate but CNS exposure, paradox activation and fusion coverage — where the combinations do not reach.

Confidence: medium Needs: the monotherapy vs combination axis below, completed Fore comparison cells pending cleared data

Q1 · GO/NO-GO Is the CNS ORR + median-DoR package mature enough to support an accelerated-approval filing now, or do we wait for further DoR maturity?

Current read: competitor precedent is the sharpest available evidence. FDA declined FIREFLY-1’s own prespecified primary endpoint for tovorafenib (dossier §11), which sets the bar for what an agency will accept from a single-arm CNS package and is directly material to endpoint choice here.

Confidence: high on the precedent Tovorafenib dossier §11 — endpoint strategy

Q3 · GO/NO-GO Does the pediatric signal justify opening a dedicated pediatric expansion cohort now?

Current read: the competitive constraint is weaker than assumed. Neither the FDA nor the EMA tovorafenib indication carries an upper age limit — the “up to 25” claim is incorrect (dossier §10). Pediatric space is contested, not conceded, and the label-scope question needs re-reading before a cohort decision.

Confidence: high Tovorafenib dossier §10 — label scope

Q2 Which sub-protocol is the fastest, cleanest path to a registrational filing — A (CNS V600) or D (BRAF fusions)?

Current read: fusions are the less contested space — dabrafenib+trametinib is V600E-only and selumetinib is a MEK inhibitor, so neither competes directly on Class 2 fusions. CNS V600 is the more crowded lane. Speed still turns on our own enrolment, which the landscape cannot answer.

Confidence: medium Needs: the white-space axis below

Q5 For Class 2 fusions, is enrolment sufficient to support a label claim, or does it need a targeted fusion-screening push?

Current read: no competitor holds a fusion-specific label claim, so the precedent for what an agency requires is thin — that cuts both ways. The regulatory-precedent axis below is the place this gets answered.

Confidence: low — precedent thin

Q6 What is the resistance / next-line strategy for progressors, and does it imply a combination arm rather than monotherapy?

Current read: the discontinuations analysis is directly relevant and reassuring on one point — not one programme in the set was stopped for a class safety signal, and seven of ten exits were portfolio decisions. A combination arm is therefore not forced by class tolerability.

Confidence: medium BRAF & pan-RAF discontinuations

Q8 Does screening-funnel attrition warrant an NGS-first / fusion-panel diagnostic partnership?

Current read: a diagnostic partnership is also a competitive move — whoever owns fusion detection shapes which patients reach which drug. No tracked competitor has taken this position. Not yet analysed; flagged as a gap in the landscape coverage.

Confidence: not yet analysed

Q4 Once BICR reads are locked, what is the gap between investigator- and central-assessed ORR?

Not a competitive question. Internal data maturity; the landscape has nothing to say about it. Listed here so the set stays complete.

Owned outside this page

02The comparison axes

Rows are competitors; columns are the thing being decided. These are the tables the questions above resolve against.

A · Monotherapy vs combination — the Q7 axis

The axis that matters is not raw response rate. It is CNS exposure, paradox activation, fusion coverage and tolerability burden — the places a Type I BRAFi + MEKi combination cannot follow.

Asset	Mechanism & class	CNS position	Fusion coverage	Combination burden
Plixorafenib Fore	pending cleared data	pending cleared data	pending cleared data	Monotherapy — no MEKi partner
Tovorafenib (Ojemda) Day One / Servier	Type II pan-RAF	Approved pLGG indication; no upper age limit in FDA or EMA label	Covers fusions	Monotherapy
Dabrafenib + trametinib Novartis	Type I BRAFi + MEKi	Approved 1L pediatric V600E LGG; tumour-agnostic	V600E only — does not cover fusions	Two agents, two toxicity profiles, two adherence burdens
Selumetinib (Koselugo) AstraZeneca / Merck	MEK1/2 inhibitor	NF1-PN approval; used in BRAF-aberrant / NF1 R/R pLGG	Downstream — not BRAF-selective	Monotherapy, different class

B · Regulatory precedent — the Q1 and Q5 axis

What an agency has actually accepted, from whom, on what endpoint. This is where filing strategy gets decided, and it is the axis a competitor-by-competitor filing cabinet hides.

Asset	Filed on	What the agency did	Label breadth	Confirmatory obligation
Tovorafenib	FIREFLY-1, single-arm	FDA declined the prespecified primary endpoint (§11)	No upper age limit, FDA or EMA (§10)	CONNECT TarGeT-B — readout not before May 2030 (§9)
Dabrafenib + trametinib	Pediatric LGG + tumour-agnostic	Approved	V600E-restricted	—
Selumetinib	NF1-PN	Approved	NF1-PN, not BRAF-defined	—
Plixorafenib	pending	pending	pending	pending

C · Where each competitor cannot go — the white space

The inverse of a competitor profile: not what they do, but the ground their label, mechanism or evidence base prevents them holding.

Asset	Cannot claim	Why
Dabrafenib + trametinib	Class 2 BRAF fusions	V600E-only indication and mechanism
Selumetinib	A BRAF-defined population	MEK inhibitor; approval is NF1-PN, not BRAF-driven
Tovorafenib	Mature confirmatory evidence before 2030	CONNECT TarGeT-B does not read out before May 2030 (§9)
Next-gen type II / pan-RAF	Anything, yet	Pre-readout; the watch list exists for when that changes

Read the pending cells honestly. Plixorafenib’s comparison cells are Fore-internal and remain unfilled pending cleared data. They are marked, not blank, so no reader mistakes an empty cell for an unfavourable one — and so the gap stays visible until it is closed. The competitor columns are public and cited; our own column is the one that needs work.

03The screen

USAEU4 + UKJapan Primary CNS with BRAF mutationBRAF fusion in a tumor with a CNS lesion Preclinical → Phase I → II → III → Approved BRAF inhibitor / degraderPan-RAF

Screened19All BRAF and pan-RAF assets identified from databases, company sites, PRs, publications and trial registries.

CNS-plausible11−8 removed: approved or developed only outside CNS, or trials that explicitly exclude primary CNS.

CNS-relevant6−5 removed: basket trials with no disclosed CNS population. These six are the tracked competitive set.

Screen provenance: the source deck states 18 assets (18 → −7 → 11 → −5 → 6). We carry 19 because brimarafenib (BGB-3245, SpringWorks) appears on the deck’s timeline slide but not in its funnel — held as unresolved rather than dropped. See open flags. Screening method: build a comprehensive asset list from databases → targeted review of company sites, press releases and publications → validate CNS relevance against ct.gov and other registries.

04Landscape at a glance

1 · Mechanism ladder — increasing differentiation and market opportunity

MOA class	Clinical validation	Assets	What it buys / costs
Type I BRAF inhibitor monomeric V600E only	H	Dabrafenib + trametinib	Established, but V600E-only, paradoxical MAPK reactivation, rapid acquired resistance, combination toxicity.
Type II RAF / pan-RAF inhibitor dimer-capable	H	Tovorafenib · claturafenib · belvarafenib	Reaches fusions and non-V600 biology monomer inhibitors miss; still carries class skin/hepatic/growth toxicity, and dimer reactivation is not fully solved.
Non-degrading molecular glue RAF–MEK complex held inactive	L	NST-628	Holds RAF–MEK in an inactive conformation and blocks active heterodimer formation; preclinical only, no human efficacy or safety yet.
Paradox breaker inhibits monomer + dimer, no paradoxical activation	M no approved paradox breaker	Plixorafenib · BDTX-4933 ¹ · mosperafenib ²	Prevents paradoxical MAPK activation, addresses acquired resistance to current RAF inhibitors, and widens the therapeutic window — the differentiating position, but no regulatory precedent yet.

¹ BDTX-4933 is a MasterKey orthosteric RAF inhibitor that Black Diamond describes as “designed to target the oncogenic conformation of RAF and avoid paradoxical activation” — a sponsor claim, not demonstrated equivalence; plixorafenib’s avoidance is established across RAF/MEK/ERK, BDTX-4933’s claim covers the RAF node only. ² Roche labelled mosperafenib a “paradox breaker” at AACR 2025, but development is CRC/melanoma-focused and internally discontinued. The MEK-inhibitor class sits outside this ladder and is tracked separately below.

2 · Cross-asset efficacy and safety — indirect, not head-to-head

Asset	ORR	N	Grade ≥3 AEs	N	Discont.	Provenance
Dabrafenib + trametinib	47% (vs chemo 11%) 1L pLGG · 33% HGG · 50% LGG · 25% R/R paediatric denominators wrong	151 · 45 · 24 · 36	47% (vs chemo 94%); pyrexia 8%, weight increase 7%	157	8%	public
Tovorafenib	51% — PR 36.8% (28), MR 14.5% (11), no CR; mTTR 5.3 mo, mDOR 13.8 mo criteria-dependent	76	42%; rash 12%, growth inhibition 5%, haemorrhage 5% (1 Gr5). SAEs 45%	137	7%	public
Claturafenib ± binimetinib	4/7 confirmed (57%) at 225 mg BID, incl. 1 CR in a BRAF V600E+ primary brain tumour; a 5th confirmed response after cutoff	7	Mono: blurred vision 6% Gr3 (only Gr≥3 reported); fatigue 44%/0%, headache 28%/0%. MTD not reached	30	—	public
Belvarafenib	0% in BRAF Class II/III (1 primary CNS patient) · 60% in BRAF fusions (CNS patients unknown). mPFS 13.7 mo vs 2.1 chemo; DCR 93.3% vs 50% denominators disputed	8 · 15	77% Cohort I / 38% Cohort J. TRAEs (N=133): dermatitis acneiform 54.1%, rash 28.6%, CPK increase 24.1% superseded	30 · 24	—	public
NST-628	Preclinical only — potent, deep, durable RAF–MEK inhibition in CDx/PDx models superseded	—	Preclinical only — GLP tox shows improved exposure margins vs other MEK inhibitors superseded	—	—	public
BDTX-4933	Preclinical only — PDx regression post BRAF/MEKi; survival benefit in intracranial V600E models	—	No clinical safety data reported. >10× selectivity for BRAF alterations in proliferation assays	—	—	public
Mirdametinib MEK inhibitor flank	87% in pLGG with MAPK activation, RP2D 3.0 mg/m² BID — single-centre academic see deltas	12	1 DLT (Gr3 thrombocytopenia); rash, weight gain, paronychia	12	—	public

Read with caution: these are cross-trial comparisons across different populations, lines of therapy, response criteria and denominators — not head-to-head. Denominators are shown for every figure precisely because the percentages are not comparable on their own. Response criteria are not stated in the source deck for any asset — a blocking flag for CNS figures, which must be RANO/RAPNO/iRANO rather than RECIST. KOL benchmark internal withheld

05Tier 1 — tracked competitors

Competitor	MOA class	Dossier	Next catalyst	Refreshed	Links
Tovorafenib (Ojemda) Day One / Servier · Ipsen ex-US	Type II pan-RAF QW oral	LIVE · draft stale	FIREFLY-2 PIII topline, 1L pLGG — mid-2027 forward Enrolment completed May 2026 (~400 pts, randomised vs 4 chemo regimens); primary endpoint ORR by RAPNO-LGG. Prior PCD 02/2026 superseded. FIREFLY-1 3-year follow-up presented at SNO 2025. EU decision still to verify.	2026-09-03	Dossier Findings
Dabrafenib + trametinib Tafinlar + Mekinist · Novartis	Type I BRAFi + MEKi V600E only, TID burden	QUEUED	NCI-MATCH BRAF V600E solid tumour readout — PCD 12/2025 verify may support full approval in V600E solid tumours. No change found at the 3 Sep 2026 refresh — readout still not located in public sources; carried as open.	2026-09-03	—
Claturafenib PF-07799933 · Pfizer	Selective BRAF, Class I–III ± binimetinib per protocol	QUEUED	PI readout 03/2027 forward Landed ASCO 2026 (Jun): Phase 1b of brain-penetrant MEK inhibitor polfurmetinib (PF-07799544) + claturafenib in advanced BRAF-mutant melanoma (JCO 44:16_suppl, 9512). Pfizer is assembling a brain-penetrant BRAF+MEK doublet — read with §08. SCD 09/2028; next-phase trial 2029+.	2026-09-03	—
BDTX-4933 = S241656 · Servier (lic. from Black Diamond, Mar 2025)	MasterKey orthosteric RAF QD oral	QUEUED restructured	PI readout — late 2026 / early 2027 forward Slipped. Servier has said results will not be released until after study completion, late 2026 or early 2027 — prior PCD 06/2026 superseded. Registered Phase 1/2 with CRC / pancreatic combination arms — see Material deltas.	2026-09-03	—
NST-628 Nested Therapeutics	Pan-RAF–MEK molecular glue QD oral, non-degrading	QUEUED tier review	First clinical data landed — AACR 2026, 17 Apr verify Ph1 NCT06326411, N=69 (64 escalation + 5 expansion), cut-off 1 Feb 2026: 38% ORR, 85% DCR at the recommended dose in advanced NRAS and BRAF Class II/III melanoma after standard therapy, with early evidence of CNS activity. Prior entry carried only the PCD 11/2028 completion date and understated this asset. SCD 11/2029.	2026-09-03	—
Belvarafenib Hanmi · Roche licence terminated Apr 2024	Type II RAF dimer inhibitor	QUEUED	Hanmi Korean PII, NRAS-mutant melanoma — enrolling verify Programme moved. First patient dosed 23 Feb 2026 in a single-arm Korean Phase 2 across 10 centres — this, not TAPISTRY, is now the active development path. TAPISTRY PII completion 09/2031 retained as a long-dated forward item.	2026-09-03	—

Status chips: LIVE dossier published · QUEUED in the dossier build queue · STALE data-cut predates a known catalyst · WATCH monitored, no dossier planned. A dossier can be both LIVE and STALE — that pairing is the honest state of tovorafenib today and is what the weekly delta-scan exists to clear.

06Tier 2 — basket watchlist

In BRAF / pan-RAF basket trials with no CNS cohort disclosed to date. Monitored for a protocol amendment, a disclosed cohort, or an out-licensing event that would move them into Tier 1.

Asset	Code	Sponsor	Phase	MOA	Future CNS likelihood	Why — and what would change it
Mosperafenib	RG-6344	Roche (discontinued, out-licensing)	PI	BRAF “paradox breaker”	Moderate	ORR 25% with efficacy in measurable and non-measurable brain lesions and brain metastases; MTD not reached at 3600 mg. European-only trial, registered on ISRCTN not ct.gov. Primary CNS disease excluded. Roche stopped internal development and is out-licensing — a licensee could open a primary-CNS cohort. Current centre of gravity is CRC (51/66 evaluable) then melanoma (11/66).
KIN-2787	= exarafenib	Pierre Fabre	PI	Pan-RAF	Moderate	Enrols BRAF Class I–III and NRAS-mutant melanoma — the same breadth that defines primary-CNS trials, so CNS enrolment is possible but undisclosed. PI, N=400, 36 sites, PCD 11/2028. Current focus is melanoma and lung. Patients must not have had surgery or radiotherapy, which likely excludes most primary CNS. Pierre Fabre holds Braftovi in the EU, raising the strategic odds of a CNS move.
Flezurafenib	JZP-815 = REDX-05358	Jazz	PI	Pan-RAF	Moderate	Active against BRAF Class I–III, BRAF fusions and CRAF mutants, and claims prevention of paradoxical activation. PI, N=332, 8 sites, PCD 04/2028. Uncontrolled brain metastases excluded, stable permitted. Jazz has not disclosed all cohort arms — a thyroid arm (Arm 7) is visible only inside the inclusion criteria, so an undisclosed CNS arm cannot be ruled out.
Lifirafenib	BGB-283	BeOne	PI	BRAF + pan-RAF, EGFR	Low	Both Part A (all comers) and Part B (NRAS) exclude tumours of the brain or CNS, and CNS metastases are excluded. PI, N=93, 6 sites, PCD 09/2025 verify. Likely pivot is melanoma — the only complete response seen (1 of 31). Ownership moved from SpringWorks, which explains the long start-to-readout gap.
DCC-3084	—	Ono (acq. Deciphera Apr 2024)	PI/II	Pan-RAF switch-control	Low	Discontinued in the US as of Sep 2025, which likely ends US CNS potential; ex-US development (e.g. Japan) remains possible. Broad inhibition of BRAF Class I–III, fusions and RAS-driven tumours; brain-penetrant with growth inhibition of intracranially implanted tumours. Focus had been NSCLC, PDAC, melanoma, mCRPC.

Unresolved sixth: brimarafenib (BGB-3245, SpringWorks), PI, PCD 03/2025 — listed on the deck’s timeline watchlist but absent from its asset funnel, and distinct from lifirafenib (BGB-283). Either a genuine omission from the screen or a mislabel. Resolve before the next refresh.

07Tier 3 — screened out

7 BRAF / pan-RAF assets reviewed and excluded — expand for the record

Kept visible deliberately: the evidence that the screen was exhaustive is the point of the exercise. These are in non-CNS indications without a basket study, or explicitly exclude primary CNS.

Asset	Sponsor	Phase	MOA	Rationale for deprioritisation
Vemurafenib (Zelboraf)	Genentech	Approved	BRAF	Approved in melanoma and Erdheim–Chester disease.
Encorafenib (Braftovi)	Pfizer	Approved	BRAF	Approved in melanoma, NSCLC and CRC.
Pazopanib (Votrient)	GSK	Approved	BRAF	Approved in RCC and soft-tissue sarcoma.
Regorafenib (Stivarga)	Bayer	Approved	Pan-RAF	Approved in CRC, GIST and HCC.
Naporafenib (ERAS-254)	Erasca (originated Novartis)	PIII SEACRAFT-2	Pan-RAF	Core focus is melanoma (PIII), NSCLC and RAS Q61X solid tumours. No basket study. Sponsor corrected: the source deck lists Novartis, but ERAS-254 / SEACRAFT-2 is Erasca’s programme.
Tagarafdeg (CFT-1946)	C4 Therapeutics	PI	BRAF degrader	Basket study, but the protocol explicitly excludes primary CNS. Worth re-checking on protocol amendment given the degrader modality.
LUT-014	Lutris Pharma	PII	BRAF	Developed for EGFR-inhibitor-induced rash and radiation dermatitis — supportive care, not oncology efficacy.

08MEK-inhibitor flank

Not RAF-directed, so outside the mechanism ladder — but competing for the same CNS patients, and carrying the single highest reported ORR in the landscape.

Asset	Sponsor	Status	Setting	Signal and read
Mirdametinib	Merck KGaA / SpringWorks	WATCH	PI/II single-centre academic, N=132, 1 site, PCD 06/2031. pLGG with MAPK activation; excludes HGG (WHO III/IV) and BRAF V600	ORR 87% (N=12) at RP2D 3.0 mg/m² BID — the highest reported ORR anywhere in this landscape, in the pLGG population tovorafenib owns. Only one DLT (Gr3 thrombocytopenia). Oral, BBB-penetrant, dispersible tablet. Caveats that matter: single-centre academic trial, N=12, no industry sponsor yet, and V600 patients excluded. PII cohorts 1–3 likely read out 2027–2030. If Merck KGaA / SpringWorks converts this into an industry-led registrational trial — the Black Diamond / silevertinib-style pivot — it becomes a Tier 1 asset. Escalate to a dossier on any industry-trial announcement. Re-checked 3 Sep 2026: trigger has not fired. SJ901 remains the St Jude-sponsored Ph1/2 (enrolment up to 130, ages 2–24); no industry-led registrational trial announced. SpringWorks now a healthcare company of Merck KGaA.
Polfurmetinib PF-07799544 · + claturafenib	Pfizer	NEW verify	Ph1a/b master study, advanced BRAF-mutant melanoma incl. baseline brain metastases; brain-penetrant MEKi paired with a next-generation BRAF dimer inhibitor	ASCO 2026 (Jun), JCO 44:16_suppl 9512. ORR 27% (N=41 dose escalation) and 32% (N=19 dose optimisation). In patients with baseline brain metastases, intracranial ORR 30% (N=23 DE) and 22% (N=9 DO). TEAEs any grade 95% — rash 40%, fatigue 37%, diarrhoea 32%, peripheral oedema 22%; Gr≥3 67% (rash 7%, PD 7%, anaemia 5%, fall 5%). Heavily pretreated population. Why it matters here: this is the first brain-penetrant BRAF+MEK doublet in the landscape with reported intracranial response data, and Pfizer owns both halves — claturafenib sits in Tier 1. Read the two rows together, not separately. Melanoma, not primary CNS, and cross-trial comparison caveats apply in full.
Selumetinib (Koselugo)	AstraZeneca / Merck	WATCH	Approved in NF1-PN; used off-label in BRAF-aberrant / NF1 R/R pLGG	Carried from the previous registry, where it was marked PLANNED. It is not in the source deck’s asset screen — the deck names it only in passing among MEK inhibitors used sporadically in CNS, alongside binimetinib. Retained as WATCH rather than deleted, but the deck’s evidence does not support a dossier; mirdametinib is the MEKi that warrants one. Decision flagged below.

09Catalyst calendar

Now past — unverified against public sources

Six catalysts the source deck placed in the future have since passed. Until the delta-scan closes them, no statement on this page about the current landscape should be treated as settled.

Date	Asset	Event	State
09/2025	Lifirafenib	PI primary completion (BeOne)	verify
11/2025	Mirdametinib	Phase I readout — the 87% ORR (N=12) datapoint	verify
12/2025	Dabrafenib + trametinib	PII NCI-MATCH BRAF V600E solid tumour readout — may support full approval	verify
mid-2027 was 02/2026	Tovorafenib	PIII FIREFLY-2 topline, 1L pLGG — the single most consequential event in the landscape; could lead to full FDA approval in R/R and 1L pLGG. No 02/2026 interim occurred: enrolment completed May 2026 (~400 pts, ORR by RAPNO-LGG), topline now mid-2027.	forward
1H 2026	Tovorafenib	Potential EU approval in pLGG (Ipsen; EMA filing accepted Apr 2025)	verify
late 2026 – early 2027 was 06/2026	BDTX-4933	PI results — Servier will not release until after study completion, late 2026 or early 2027. Still the nearest-term competitive readout.	forward

Forward

Date	Asset	Event	State
06/2026 landed	Polfurmetinib + claturafenib	ASCO 2026 — brain-penetrant MEKi + next-gen BRAF dimer inhibitor in BRAF-mutant melanoma; intracranial ORR 30% / 22%. See §08	verified
03/2027	Claturafenib	PI readout (PCD); potential next-phase trial 2029+	forward
11/2026–11/2028	Tovorafenib	Window for potential full FDA approval in 1L pLGG on FIREFLY-2 — range reflects no public Day One statement on whether they file after interim or final data	forward
02/2028	Tovorafenib	FIREFLY-2 final readout, 1L pLGG (60-month ORR time frame)	forward
04/2028	Flezurafenib	PI readout and study completion	forward
Apr 2026 landed · 11/2028	NST-628	First clinical data landed AACR 2026 (17 Apr): 38% ORR, 85% DCR at the recommended dose in NRAS and BRAF Class II/III melanoma, with early evidence of CNS activity (N=69, cut-off 1 Feb 2026). PI readout including the glioma dose-expansion cohort still forward to 11/2028	forward
11/2028	KIN-2787	PI readout (PCD); SCD 03/2029	forward
2027–2030	Mirdametinib	PII cohorts 1–3, most likely the later part of the range	forward
09/2031	Belvarafenib	TAPISTRY PII readout and study completion. Note: active development has moved to a Hanmi Korean Ph2 in NRAS-mutant melanoma, first patient dosed 23 Feb 2026	forward

Timing basis: primary completion date (PCD) as posted on ct.gov is used as the proxy for data availability, given the niche indications. Data-availability-to-approval baselines: FDA submit → approval 6 months priority review (4 with breakthrough designation); EMA 7 months to submission + 5 to approval; PMDA 9 months priority review (6 under Sakigake). Time to data availability varies by disease stage — earlier stages take longer.

10The evidence layer

Source dossiers and reports. Everything above resolves back into these.

Competitor registry

Competitor	Status	Last refreshed	Links
Tovorafenib (Ojemda) Day One / Servier · Ipsen ex-US · Type II pan-RAF	Live · part-refreshed	2026-08-31	Dossier & comparison core §1–8, data-cut 31 Aug 2026 Extended dossier · Findings §9–14, data-cut 20 Jul 2026 Two builds, not one. The 31 Aug rebuild refreshes the core dossier with adversarial verification (152 citations, 157 corrections) but does not cover §9–14 — development trajectory, label scope, endpoint strategy, guidelines, commercial infrastructure, KOL. Those remain from the July build, and the Q1 and Q3 reads above still cite its §10 and §11.
Dabrafenib + trametinib Novartis · Type I BRAFi + MEKi	Planned	—	V600E-only combo; approved 1L pediatric V600E LGG + tumour-agnostic. Next dossier candidate.
Selumetinib (Koselugo) AstraZeneca / Merck · MEK1/2	Planned	—	NF1-PN approval; used in BRAF-aberrant / NF1 R/R pLGG.
Next-gen type II / pan-RAF pipeline various	Watch	—	Emerging paradox-breaker programmes to monitor as they read out.

Disease-landscape reports

Report	Status	Last refreshed	Headline
CNS histology — age-specific incidence & outcome Pilocytic astrocytoma · ganglioglioma · PXA grade 2 · DLGNT	Live · draft	2026-07-20	Only pilocytic astrocytoma can honestly be charted; the others are subsumed in registry groupings, and PXA grade 2 can never be isolated — ICD-O-3 has one morphology code and no grade 3 code. Report

Cross-asset analyses

Report	Status	Last refreshed	Headline
BRAF & pan-RAF discontinuations — who stopped, and why 11 assets · 10 sponsor decisions · organised by cause	Live · draft	2026-08-24	Not one programme was stopped for a class safety signal; seven of ten exits were portfolio decisions. Report

11What changed

The weekly delta-scan runs across the tracked competitors — trial readouts, label changes, confirmatory data, safety signals, approvals, earnings, new entrants — and flags material changes for sign-off. A full rebuild follows the inflection points: SNO / ASCO / EHA readouts, label changes, earnings.

3 Sep 2026

Refresh — Tier 1 re-verified, 5 of 6 rows changed. NST-628 first clinical data landed at AACR 2026 with early CNS activity and is flagged for tier review; BDTX-4933 readout slipped to late 2026 / early 2027; belvarafenib development moved to a Hanmi Korean Phase 2; tovorafenib FIREFLY-2 enrolment completed with topline now mid-2027; Pfizer presented a brain-penetrant MEK + claturafenib doublet at ASCO 2026. Dabrafenib + trametinib re-checked, no change found. Tier 2: exarafenib enrolment closed Dec 2025 and its Phase 1 is now published.

24 Aug 2026

Discontinuations analysis published — 11 assets, 10 sponsor decisions, organised by cause rather than by competitor. Bears on Q6.

20 Jul 2026

Tovorafenib dossier expanded to 14 sections (from 8), 151 open flags. Six new sections answer the Shubin slide review, including §9 development trajectory, §10 label scope, §11 endpoint strategy, §13 commercial infrastructure (18 US reps, ~200 accounts) and §14 KOL perception. 59 of 79 candidate claims were refuted and excluded. Bears on Q1 and Q3.

20 Jul 2026

CNS histology incidence report published. Bears on population sizing.

Guardrails. Competitor data is public and cited. Plixorafenib’s own figures are Fore-internal and are never fabricated by the pipeline. CNS response is reported in RANO / RAPNO / iRANO, not RECIST. Every figure carries its denominator and its source. Each dossier ships an open-flags appendix.

12Sources

How to read this. This page is a rebuild of an internal deck, not an independent literature review. Every competitor figure above is currently sourced to that deck; the registry identifiers below were captured on 2026-07-23 so the next refresh can re-cite each figure to its primary record. Verification chips: confirmed identifier verified against the registry record · not captured identifier not yet established — do not cite until verified.

1 · Primary source of this page

Source	Type	Data cut	Scope and standing

2 · ClinicalTrials.gov — trial registry

The registry is the deck’s stated backbone for CNS-relevance screening, trial design, enrolment, site counts, eligibility, and the primary completion dates used throughout as the data-availability proxy. The deck itself contains no NCT numbers — these were captured for this page.

Trial	Asset	Identifier	Status	Used on this page for
FIREFLY-1 (PNOC026)	Tovorafenib	NCT04775485	confirmed	Accelerated-approval basis; ORR, DOR, TTR, Gr≥3, discontinuation
LOGGIC / FIREFLY-2	Tovorafenib	NCT05566795	confirmed	PIII 1L confirmatory design, N, sites, RAPNO-LGG primary endpoint, catalyst timing
TADPOLE	Dabrafenib + trametinib	NCT02684058	confirmed	pLGG full-approval basis; ORR vs chemo, PFS, Gr≥3
Study X2101 (CTMT212X2101)	Dabrafenib + trametinib	NCT02124772	confirmed	Paediatric R/R LGG / HGG ORR; the primary-CNS-only eligibility point
ROAR	Dabrafenib + trametinib	not captured	not captured	Tumour-agnostic AA basis; HGG and LGG ORR
NCI-MATCH	Dabrafenib + trametinib	not captured	not captured	The 12/2025 catalyst
PF-07799933 PI	Claturafenib	NCT05355701	confirmed	Design, N, sites, binimetinib and cetuximab combination arms, CNS eligibility
S241656 PI/II formerly BDTX-4933-101	BDTX-4933 = S241656 (Servier)	NCT05786924	confirmed	Design, eligibility, CNS-metastasis exclusions. Record verified as retitled: lead sponsor Institut de Recherches Internationales Servier, phases Phase 1/2, interventions listed under `S241656`. Compound identity confirmed via the Servier–Black Diamond licence (Mar 2025) and the ASCO GI 2026 abstract naming “S241656 (BDTX-4933)”.
NST-628 PI	NST-628	NCT06326411	confirmed	Part A / Part B structure and the glioma-with-BRAF-alterations cohort
TAPISTRY (BO41932)	Belvarafenib	NCT04589845	confirmed	Cohorts I and J, dosing, eligibility, endpoints, site status
KN-8701	KIN-2787 / exarafenib	NCT04913285	confirmed	Class I–III + NRAS eligibility, sites, MTD, CNS-likelihood assessment
SJ901	Mirdametinib	NCT04923126	confirmed	The 87% ORR (N=12), RP2D 3.0 mg/m² BID, non-V600 eligibility
Mirdametinib + vinblastine, 1L pLGG	Mirdametinib	NCT06666348	confirmed	Not in the deck. Phase 1/2, sponsor St. Justine’s Hospital — academic, not the industry registrational trial. Verified via the registry API.
FORE8394 PI/IIa	Plixorafenib	NCT02428712	confirmed	The earlier single-agent study underlying the safety narrative
Lifirafenib PI	Lifirafenib	not captured	not captured	Part A / B design, CNS exclusions, PCD 09/2025
Flezurafenib PI	Flezurafenib	not captured	not captured	Undisclosed cohorts, the hidden thyroid arm, brain-mets eligibility
DCC-3084 PI/II	DCC-3084	not captured	not captured	Part 1 / 2 eligibility; US discontinuation
SEACRAFT-2	Naporafenib	not captured	not captured	Screened-out rationale
CFT-1946 PI	Tagarafdeg	not captured	not captured	The explicit primary-CNS exclusion

3 · Other trial registries

Registry	Asset	Why it matters
ISRCTN (UK)	Mosperafenib (RG-6344)	The mosperafenib study is a European-only trial registered on ISRCTN rather than ct.gov. Any screen that queries only ClinicalTrials.gov will miss it — a standing methodology note for the weekly scan. Identifier not captured.

4 · Regulatory sources

Source	Used for
FDA approvals and labels	Tovorafenib accelerated approval (Apr 2024, R/R BRAF-altered pLGG). Dabrafenib + trametinib: melanoma AA 2014, tumour-agnostic BRAF V600E AA Jun 2022, paediatric LGG full approval Mar 2023 — plus the label as the only clinical content on the product website. Selumetinib NF1-PN approval. Approved-elsewhere rationales for all seven screened-out assets.
EMA	Tovorafenib filing accepted Apr 2025; EU decision expected 1H 2026 (Ipsen ex-US).
Regulatory timing baselines	FDA priority review 6 months (breakthrough 4); EMA 7 months to submission + 5 to approval; PMDA 9 months (Sakigake 6). Applied uniformly in the catalyst calendar.
Product websites	Promotional-posture analysis: tovorafenib’s four stated pillars vs the dabrafenib + trametinib site carrying no efficacy or safety content.

5 · Congress presentations and peer-reviewed literature

Venue	Contribution
Nature Medicine	The phase 2 FIREFLY-1 primary report — the source of the RANO-HGG vs RAPNO-LGG ORR split now flagged in the deltas table.
NEJM	Dabrafenib + trametinib in paediatric glioma with BRAF V600 mutations — the TADPOLE primary report.
BMC Cancer / JCO (TPS)	LOGGIC/FIREFLY-2 trial-in-progress design and endpoints; FORTE master-protocol design (JCO 2025 TPS); FIREFLY-1 TPS.
Neuro-Oncology (SNO abstracts)	SJ901 phase 1 and expansion results — the mirdametinib 87% ORR. SNO 2025: tovorafenib 3-year follow-up.
AACR	2026: NST-628 initial clinical activity and tolerability. 2025: Roche describing mosperafenib as a “paradox breaker”. 2024: NST-628 preclinical. 2023: exarafenib preclinical Class II/III and NRAS melanoma activity.
ESMO	2024: NST-628 trial-in-progress disclosing the optional BRAF-mutant glioma and Class II/III cohorts — the original CNS signal.
ASCO / Annals of Oncology / JCO Oncology Advances	Belvarafenib in BRAF Class II/III TAPISTRY cohorts; exarafenib phase 1 monotherapy; mosperafenib AACR/ASCO 2025 readout; claturafenib phase 1.

6 · Corporate and investor disclosure

Source	Contribution
Press releases	Day One / Servier FIREFLY-2 enrolment completion; Day One acquisition of Emi-Le (B7-H4 ADC) from Mersana, Nov 2025; Nested AACR 2026 clinical update and the NST-628 IND clearance; Ono discontinuation of DCC-3084 in the US, Sep 2025; Ono–Deciphera acquisition, Apr 2024; Roche–Hanmi belvarafenib licence termination, Apr 2024.
Investor updates	Ipsen Q3 2025 IR update — the EU tovorafenib approval expectation. Black Diamond corporate updates — out-licensing to Servier and the silevertinib glioblastoma pivot.
Company pipeline pages	Asset-status and MOA claims, including belvarafenib remaining on Hanmi’s pipeline after removal from Roche’s, and sponsor descriptions of BDTX-4933, NST-628, flezurafenib, DCC-3084 and KIN-2787 quoted as claims rather than findings.

7 · Commercial databases

Source	Contribution
Citeline, plus unnamed asset databases	Named in the deck’s methodology as the basis for building the initial asset list and for shaping timelines from analogous trials. Which assets came from which database is not recorded in the deck — so the completeness of the 19-asset screen cannot be independently reproduced. That gap is the likeliest explanation for the brimarafenib discrepancy.

8 · Primary research internal · KOL

Source	Contribution and limits

9 · Not yet used — gaps to close in the refresh

No real-world evidence source is cited anywhere, though tovorafenib’s own promotion rests on a “real-world data matching trial data” claim. No pricing or reimbursement source, despite a KOL objection turning on a “~10× cost over chemo” argument. No patent or exclusivity source, despite the loss-of-exclusivity argument for dabrafenib + trametinib. No epidemiology source sizing the BRAF-fusion versus V600E populations, which is what makes the fusion-majority positioning load-bearing. And the six not captured registry identifiers above.

13Open flags

Blocking (whole page): response criteria are not stated for any ORR figure in the source deck. CNS response must be reported in RANO / RAPNO / iRANO, not RECIST. Until each figure is tied to its criterion, no cross-asset ORR comparison on this page is defensible externally.

Flag	Issue	Disposition on this page
Claturafenib ORR	Deck reports “ORR 51% (N=7)”, which is not attainable for N=7. The underlying slide reports 4 of 7 confirmed responses at 225 mg BID.	Published as 4/7 (57%) with the deck figure footnoted. Recheck against the primary Pfizer presentation.
Brimarafenib	BGB-3245 (SpringWorks), PCD 03/2025, appears on the deck’s timeline watchlist but not in its 18-asset funnel. Distinct from lifirafenib (BGB-283).	Screen count carried as 19, asset listed as an unresolved sixth in Tier 2.
Double-named assets	KIN-2787 also appears as “exarafenib”; JZP-815 also as “REDX-05358” — the deck’s timeline slide uses a different name set from its funnel slides, inflating the apparent asset count.	Canonical name ↔ code ↔ sponsor map applied throughout; both aliases shown in Tier 2.
Naporafenib sponsor	Deck attributes ERAS-254 / SEACRAFT-2 to Novartis.	Corrected to Erasca, Novartis noted as originator.
Belvarafenib sponsor	Deck lists Roche on the asset table but notes elsewhere that the asset was removed from Roche’s pipeline and remains on Hanmi’s after the Apr 2024 licence termination.	Attributed to Hanmi, Roche exit noted.
Belvarafenib US sites	Deck says “almost all US sites withdrawn or closed” in one place and “still recruiting in the US, Italy, and Spain” in another.	Both statements carried; reconcile against ct.gov site status.
Selumetinib	Was PLANNED in the previous registry but is absent from the deck’s screen; the deck profiles mirdametinib instead.	Downgraded to WATCH in the MEKi flank, not deleted. Decision needed: drop the planned dossier, or keep it.
Funnel arithmetic	Deck states 18 → −7 → 11 → −5 → 6. This reconciles.	No issue. Carried as 19 → 11 → 6 only because of the brimarafenib addition above.
Tovorafenib dossier	Part-resolved 31 Aug 2026. The core dossier (§1–8) was rebuilt at data-cut 31 Aug 2026 with adversarial verification — 152 citations, 157 corrections. Still open: §9–14 were not rebuilt, so development trajectory, label scope, endpoint strategy, guideline positioning, commercial infrastructure and KOL perception still carry the 20 Jul 2026 cut and its open flags. The Q1 and Q3 reads on this page cite §11 and §10 of that build.

14Material deltas

Read this before using any figure above. Capturing the registry identifiers below surfaced eight contradictions between the source deck (Nov 2025 cut) and the public record as of today. Five records were verified field-by-field through the ClinicalTrials.gov API — title, lead sponsor, phase, interventions — rather than from secondary coverage; that is how the BDTX-4933 restructuring below was caught, and it is why the remaining figures should not be trusted until the same treatment is applied. Figures on this page are still the deck’s; they are flagged, not overwritten, because replacing them requires reading the primary presentations and registry records. That is Phase 1 of the refresh.

Asset	What this page says (deck, Nov 2025)	What the public record now indicates
NST-628	“Preclinical only” for both efficacy and safety; Part B has 2 cohorts, N=30	No longer preclinical. Nested reported initial clinical activity and tolerability at AACR 2026; Part A dose escalation enrolled 64 patients across seven dose regimens, and Part B expansion is specified as up to 6 cohorts, one of which is glioma with BRAF alterations. The “multi-year head start” framing needs re-testing against actual human data.
Tovorafenib criteria, not data	ORR 51% (76); mDOR 13.8 mo	Both numbers are criteria-dependent. FIREFLY-1 reports ORR 67% by RANO-HGG (met the Arm 1 primary endpoint, n=77) and 51% by RAPNO-LGG, with mDOR 16.6 mo and mTTR 3.0 mo on the RANO-HGG read. The deck used the RAPNO figure without naming the criterion — exactly the blocking flag above, now with a concrete example.
Tovorafenib timing	FIREFLY-2 interim readout PCD 02/2026; possible full approval from 11/2026	Timeline has moved. Day One / Servier announced completion of enrollment; primary analysis is described as roughly 12 months after the last patient enrolled, with preliminary insights expected in 2027. The near-term catalyst this page treats as overdue may simply not have been due.
Belvarafenib	ORR 0% (8) in Class II/III; Gr≥3 77% Cohort I / 38% Cohort J (30 · 24)	Denominators and safety differ. Published TAPISTRY reports 26 efficacy-evaluable in Cohort I and 23 in Cohort J with no confirmed responses in either, and dermatitis acneiform at 43% (I) / 25% (J). The deck’s N=8 appears to be a subset, not the cohort.
Dabrafenib + trametinib	ORR 47% “in 151 pediatric LGG pts”; 25% in “36 R/R pediatric”; 33% HGG / 50% LGG	Denominators are misattributed. TADPOLE ORR 46.6% in n=73 — the dabrafenib+trametinib arm, not the 151 randomised. Study X2101 reports 25% in n=47 LGG with mPFS 36.9 mo, not 36. ROAR: 14/45 (31%) in HGG and n=13 in LGG, against the deck’s 33% and n=24.
BDTX-4933 population	“Patients must harbor a BRAF V600E mutation” (Class I only)	Population is broader. The registered population spans BRAF Class I, II and III, KRAS non-G12C, and NRAS, across NSCLC, melanoma, histiocytic neoplasms and other BRAF-mutant solid tumours. The “Class I only, so not a fusion competitor” read is weaker than the deck implies.
BDTX-4933 whole programme	Phase I, N=100, 10 sites, PCD 06/2026; dose expansion recruits NSCLC only; “the closest competitor” on timing	The programme has been restructured. Following the Servier licence (Mar 2025) the asset is designated S241656 and the registry record — same NCT — is now titled for S241656, sponsored by Institut de Recherches Internationales Servier, and registered as Phase 1/2, not Phase 1. Registered interventions now include cetuximab, panitumumab, FOLFIRI, FOLFOX, gemcitabine and nab-paclitaxel, i.e. a colorectal and pancreatic combination programme, and a fresh trial-in-progress abstract appeared at ASCO GI 2026. Treating this as a Phase 1 monotherapy asset with a 06/2026 CNS-relevant readout is no longer accurate.
Mirdametinib	“Single centre academic trial, 1 site”; would become Tier 1 on an industry-led registrational trial	A second trial exists, but it is not the industry pivot. SJ901 is sponsored by St. Jude Children’s Research Hospital — the deck’s single-institution characterisation is broadly fair, and secondary coverage calling it multi-centre is unconfirmed. Separately, mirdametinib + vinblastine in newly diagnosed / previously untreated pLGG with MAPK activation is registered as Phase 1/2 — but sponsored by St. Justine’s Hospital, so it is a second academic trial, not the Merck KGaA / SpringWorks registrational trigger. It still matters: it puts a MEK inhibitor into the newly-diagnosed 1L setting that FIREFLY-2 is contesting.

15The repeatable process

1 · Generate
A parameterized agentic pipeline builds a cited dossier for any competitor (7 workstreams → adversarial verification → synthesis) — one run, consistent structure.

2 · Publish
The dossier + a findings-at-a-glance page land here in FRED as a study, with the full comment feature so the team reviews in-context.

3 · Refresh — weekly
The pipeline re-runs on a weekly cadence (a lighter what-changed delta-scan), with a full rebuild after major readouts (SNO, ASCO, label changes, financials); each dossier is dated and flagged for sign-off.

Guardrail: competitor data is public + cited; plixorafenib figures are Fore-internal and completed by the team (never fabricated). Every figure carries a provenance tier and a denominator. Every dossier carries open verification flags to resolve before external use.

Competitive Intelligence Hub · plixorafenib · maintained in FRED · leave comments right on this page.
Draft for review, 2026-07-23. Landscape screen sourced from “Plixo CNS deep dive 2.9.26_MC.pptx” (Fore internal, data-cut Nov 2025). Public competitor figures to be re-cited to primary sources during the dossier builds. Default page state excludes Fore KOL research and embargoed plixorafenib figures.