Executive Summary

Q4 2024 delivered continued operating scale-up to support multiple registrational programs: cash and investments rose to $2.3B following an upsized equity offering, while R&D expense increased to $188.1M and net loss widened to $194.6M, consistent with intensified clinical activity and pre-commercial build-out .
Management introduced FY 2025 GAAP net loss guidance of $840–$900M (including $115–$130M SBC) and reiterated cash runway into the second half of 2027, framing near-term expense ramp tied to registrational trial execution and commercial preparedness .
Clinical catalysts: Phase 3 RASolute 302 (2L PDAC) enrollment expected to substantially complete in 2025 for a 2026 readout; RASolve 301 (post-IO/platinum NSCLC) sites now activating; two additional pivotal PDAC trials (1L metastatic and adjuvant) targeted to initiate in 2H 2025 .
Narrative momentum: Q4 call emphasized intent to “own the PDAC space” across lines of therapy and advance chemo-free, immunotherapy-anchored combinations in NSCLC (including RAS(ON) doublets and triplet strategies), bolstered by tolerability and early activity signals from recent updates .

What Went Well and What Went Wrong

What Went Well

Strong balance sheet and runway: Cash, cash equivalents and marketable securities reached $2.3B at 12/31/24 after raising $823M net in December; runway projected into 2H 2027, enabling multiple registrational efforts and pre-commercial investments .
PDAC efficacy durability: 300 mg QD daraxonrasib showed median PFS of 8.8 months (KRAS G12X) and 8.5 months (any RAS); OS not estimable at cutoff; manageable safety without new signals. “We aim to increase impact... by enrolling the ongoing registrational trials and opening additional pivotal trials in earlier lines” (CEO) .
NSCLC path set: RASolve 301 randomized Phase 3 (daraxonrasib vs docetaxel) site activation underway; early combination tolerability established with pembrolizumab, supporting front-line chemo-sparing strategies and potential triplet with elironrasib .

What Went Wrong

Operating losses widened: Q4 net loss increased to $194.6M vs $161.5M in Q4 2023 on higher clinical trial and headcount expenses; reflects the cost of scaling registrational work and commercial readiness .
No collaboration revenue: Total revenue was zero in Q4 and FY 2024 following Sanofi collaboration termination, underscoring dependency on external financing until commercialization .
Expense trajectory elevated: FY 2025 GAAP net loss guide ($840–$900M) signals a step-up in OpEx for multiple pivotal trials and commercial buildout, a near-term headwind for P&L until clinical inflections or approvals .

Financial Results

Metric	Q2 2024	Q3 2024	Q4 2024
Revenue ($USD Millions)	$0.0	$0.0	$0.0
Net Loss ($USD Millions)	$133.233	$156.288	$194.569
Diluted EPS ($USD)	$(0.81)	$(0.94)	$(1.12)
R&D Expenses ($USD Millions)	$134.932	$151.752	$188.096
G&A Expenses ($USD Millions)	$21.711	$23.960	$28.214
Total Operating Expenses ($USD Millions)	$156.643	$175.712	$216.310
Cash, Cash Equivalents & Marketable Securities ($USD Billions)	$1.591	$1.549	$2.289

FY 2024 highlights (annual):

Total revenue: $0.0M .
Net loss: $600.093M .
R&D: $592.225M; G&A: $97.299M; Interest income: $86.883M .

Segment breakdown: Not applicable (no product revenue; collaboration revenue discontinued after 2023 Sanofi termination) .

KPIs (Clinical Efficacy – PDAC Daraxonrasib Monotherapy)

KPI (2L PDAC)	Q2 2024 (cutoff 5/11/24)*	Q3 2024 (cutoff 7/23/24)	Q4 2024 (300 mg QD subset; cutoff 7/23/24)
Median PFS – KRAS G12X (months)	8.1	8.5	8.8
Median PFS – Any RAS (months)	7.6	7.6	8.5
Median OS – KRAS G12X (months)	NE (lower bound > SOC)	14.5	NE
Median OS – Any RAS (months)	NE (lower bound > SOC)	14.5	NE
ORR – KRAS G12X (%)	—	29	36
ORR – Any RAS (%)	—	—	27

Safety notes: Rash and GI TRAEs primarily Grade 1–2; no Grade ≥3 TRAEs >10% at 300 mg; no discontinuations due to TRAEs .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
GAAP Net Loss ($USD Millions)	FY 2025	N/A	$840–$900	New FY guide; higher expected spend for registrational studies and commercial prep .
Stock-Based Compensation ($USD Millions)	FY 2025	N/A	$115–$130	New .
Cash Runway	Multi-year	“into 2027” (Q3 2024)	“into the second half of 2027”	Clarified timing window.
Trial Milestones	2025–2026	RASolve 301 initiation “Q1 2025” target (Q3 2024)	Sites activating now; substantial completion of RASolute 302 enrollment expected in 2025; 1L and adjuvant PDAC pivotal trials targeted to initiate 2H 2025	Timelines firmed and expanded.

Earnings Call Themes & Trends

Topic	Previous Mentions (Q2 2024)	Previous Mentions (Q3 2024)	Current Period (Q4 2024)	Trend
PDAC strategy (owning the space; move into earlier lines)	Plan to advance 6236 into earlier lines; exploring chemo combos; Phase 3 2L planned	First patient dosed in Phase 3 2L; reiterated 1L intent	Expect substantial 2L enrollment completion in 2025; plan single 3-arm 1L metastatic trial and adjuvant registrational trial in 2H 2025	Strengthening
NSCLC program (registrational path)	Phase 3 2L design contemplated; combinations with pembro and doublets ongoing	Phase 3 timing pushed to Q1 2025; design alignment ongoing	RASolve 301 site activation now; pursue chemo-sparing triplet in G12C; daraxonrasib prioritized for non-G12C	Progressing
Combination strategies (pembro; RAS(ON) doublets; triplets)	Doublet 6236+6291 and 6236+pembro planned; focus on safety (hepatotoxicity)	Initial doublet and pembro combo disclosures scheduled; safety priority reiterated	Pembro combos generally well tolerated; doublet (6291+6236) showed initial activity in CRC; triplet (6291+6236+pembro) targeted for 1L NSCLC	De-risked safety; building activity signals
Commercial preparation	Building capabilities; leadership hires	Continued preparation; expense ramp expected	Expanding U.S. field teams; retain U.S. rights; exploring ex-U.S. partnerships	Scaling
Financing/Runway	$1.59B cash; runway into 2027	$1.55B cash; runway reiterated	$2.3B cash post offering; runway into 2H 2027	Strengthened

Management Commentary

“In 2025 we aim to increase impact for patients with RAS-addicted tumors... by enrolling the ongoing registrational trials and opening additional pivotal trials in earlier lines of therapy.” – Mark A. Goldsmith, CEO .
“We currently anticipate substantially completing enrollment in [RASolute 302] this year to enable an expected data readout in 2026.” – CEO .
“Activation of investigational sites is now ongoing, in the Phase III RASolve 301 randomized controlled trial comparing daraxonrasib to docetaxel.” – CEO .
“We aim to... own the entire PDAC space across all lines of therapy.” – CEO (Q&A) .
“We ended the fourth quarter of 2024 with $2.3 billion in cash and investments… we project that our cash… can fund planned operations into the second half of 2027.” – CFO .

Q&A Highlights

PDAC first-line and adjuvant commitment: Management emphasized rationale to pursue 1L metastatic and adjuvant PDAC trials in 2H 2025, aiming to “own the PDAC space,” with dosing and design informed by ongoing chemo-combo cohorts and regulatory dialogue .
NSCLC segmentation strategy: Daraxonrasib prioritized for non-G12C RAS-mutant NSCLC; elironrasib + daraxonrasib triplet planned for G12C 1L, leveraging combinability with pembrolizumab and full-dose feasibility .
Chemo combinability context: Company clarified concerns are about maintaining dose intensity amidst chemo toxicity rather than fundamental incompatibility; monotherapy arm will be central in 1L PDAC design .
Regulatory endpoints: For 2L PDAC, trial is OS event-driven; accelerated approval via PFS viewed as unlikely historically in PDAC, underscoring focus on OS .
Zoldonrasib path: Additional data in 2Q 2025 expected; pivotal combination trials targeted for 2026, including potential doublets with daraxonrasib across tumor types .

Estimates Context

Wall Street consensus EPS and revenue estimates for Q4 2024 and prior quarters were unavailable due to S&P Global daily request limits at the time of retrieval; as a result, formal beat/miss analysis versus consensus cannot be provided at this time (values would be retrieved from S&P Global).

Key Takeaways for Investors

Balance sheet strength is a core asset: $2.3B cash supports multiple registrational trials and pre-commercial scaling, reducing financing risk through key clinical milestones into 2H 2027 .
Clinical durability in PDAC continues to underpin pivotal strategy: median PFS 8.8–8.5 months at 300 mg QD with NE OS at cutoff and favorable tolerability bolster conviction to expand into 1L and adjuvant PDAC in 2H 2025 .
NSCLC program is transitioning from planning to execution: RASolve 301 site activation is a tangible step; tolerability with pembrolizumab and rationale for chemo-sparing triplets in G12C provide multiple shots on goal .
Near-term financial optics: FY 2025 GAAP net loss guide of $840–$900M flags higher OpEx; investors should expect expense ramp tied to pivotal trials and commercial readiness ahead of potential 2026 PDAC readout .
Pipeline optionality: Mutant-selective zoldonrasib (G12D) expands addressable PDAC biology (~40% G12D), with further clinical data due mid-2025 and potential doublet strategies positioning for 2026 pivotal starts .
Execution narrative is a catalyst: Substantial completion of PDAC Phase 3 enrollment in 2025, NSCLC pivotal activation, and initiation of earlier-line PDAC trials in 2H 2025 are likely stock-moving milestones .
Strategic focus on U.S. commercialization: Retaining U.S. rights and building field teams signal confidence in launch readiness pending future approvals, with ex-U.S. partnerships under consideration .

Notes and Sources

All financial and clinical data cited are from RVMD’s Q4 2024 8-K and press release, Q4 earnings call transcript, and prior-quarter documents: .
Revenue remains zero post-Sanofi collaboration termination; no product revenue yet .
Estimates were unavailable due to S&P Global daily limit; beat/miss analysis versus consensus deferred (estimates would be sourced from S&P Global).

Revolution Medicines, Inc. (RVMD)·Q4 2024 Earnings Summary