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    RVMD
    Earnings call· Dec 2024(Q4 FY24)

    Revolution Medicines, Inc. RVMD

    Feb 26, 2025 Source

    Executive summary

    Revolution Medicines Q4 FY24 — Advancing RAS(ON) Inhibitor Pipeline with Multiple Pivotal Trials

    Revolution Medicines continues to advance its pioneering RAS(ON) inhibitor pipeline, initiating multiple pivotal trials for daraxonrasib in pancreatic and non-small cell lung cancers, including novel earlier-line and adjuvant settings. The company is also progressing its mutant-selective inhibitors and earlier-stage programs, supported by a strong financial position and growing commercial capabilities, aiming to revolutionize treatment for RAS-addicted cancers.

    Highlights

    5

    • Ended Q4 FY24 with a strong cash and investments balance of $2.3 billion, including $823 million from an equity offering.

    • Anticipates cash runway into the second half of 2027, funding planned operations.

    • Initiated global Phase III RASolute 302 trial in second-line metastatic PDAC with strong enrollment interest, expecting substantial completion in 2025.

    • Activated investigational sites for Phase III RASolve 301 trial in previously treated metastatic RAS non-small cell lung cancer.

    • Reported initial clinical proof-of-concept for RAS(ON) inhibitor doublets (elironrasib + daraxonrasib) and encouraging safety/tolerability for daraxonrasib/elironrasib + pembrolizumab combinations.

    Concerns

    2

    • Full year GAAP net loss for 2025 is projected to be between $840 million and $900 million, an increase due to expanded clinical development and commercial preparation.

    • R&D expenses increased to $188.1 million in Q4 2024, up from $148.5 million in Q4 2023, driven by clinical trial expenses and personnel.

    Guidance & targets

    12
    CategoryTargetConfidence
    Full year GAAP net loss
    $840M-$900M
    high materiality
    High
    Estimated non-cash, stock-based compensation expense
    $115M-$130M
    medium materiality
    High
    Cash and investment balance runway
    Into the second half of 2027
    high materiality
    High
    RASolute 302 trial enrollment completion
    Substantially completing enrollment
    high materiality
    High
    RASolute 302 trial data readout
    Expected 2026
    high materiality
    High
    First-line metastatic PDAC trial initiation
    Initiated in the second half of this year
    high materiality
    High
    Adjuvant PDAC registrational trial initiation
    Initiated in the second half of this year
    high materiality
    High
    Zoldonrasib clinical data update
    Share additional clinical safety and antitumor activity
    medium materiality
    High
    Pivotal combination trials initiation (elironrasib or zoldonrasib)
    Initiate one or more pivotal combination trials in 2026
    high materiality
    Medium
    Clinical data supporting pivotal combination trials
    Sharing clinical data supporting these plans in the second or third quarter of this year
    medium materiality
    High
    RMC-5127 advancement to clinic-ready stage
    Advance to a clinic-ready stage this year
    low materiality
    High
    RMC-5127 first-in-human dose escalation Phase I clinical trial initiation
    Initiation of a first-in-human dose escalation Phase I clinical trial in 2026
    low materiality
    High

    Operational metrics

    8
    Cash and investments balance
    $2.3B
    Q4 FY24

    Ended the fourth quarter of 2024 with $2.3 billion in cash and investments, which includes $823 million in net proceeds from our upsized equity offering last December.

    R&D expenses
    $188.1Mvs $148.5M in Q4 FY23
    Q4 FY24

    R&D expenses for the fourth quarter of 2024 were $188.1 million compared to $148.5 million for the fourth quarter of 2023. Please note, the prior year quarter included $13.1 million in wind-down costs associated with the EQRx acquisition.

    G&A expenses
    $28.2Mvs $32.2M in Q4 FY23
    Q4 FY24

    G&A expenses for the fourth quarter of 2024 were $28.2 million compared to $32.2 million for the fourth quarter of 2023. The decrease in G&A expenses was due to $13.8 million in EQRx wind-down costs in the prior year quarter.

    Net loss
    $194.6Mvs $161.5M in Q4 FY23
    Q4 FY24

    Net loss for the fourth quarter of 2024 was $194.6 million compared to $161.5 million for the fourth quarter of 2023. Please note, net loss for the prior year quarter included a total of $26.9 million in EQRx wind-down costs.

    6-month Overall Survival (OS)
    97% to 100%
    Immature data

    Information regarding the 6-month OS for the 300-milligram cohort of the Phase I study, which was quite high, depending on which the safety looked at it was in the 97% to 100% range.

    RAS mutant lung cancer prevalence
    30%
    current

    RAS mutant portion of lung cancer, which represents about 30% of non-small cell lung cancer and in all lines of treatment.

    G12D mutation prevalence
    40%
    current

    Zoldonrasib, as you know, G12D has a prevalent of about 40% of pancreatic cancer.

    Resectable pancreatic cancer cases
    15%
    annual

    This population constitutes approximately 15% and of newly diagnosed pancreatic cancer cases in the U.S. each year.

    Deals & partnerships

    4
    Tango TherapeuticsDiscovery and clinical collaboration to explore combinations with inhibitors of novel targets (PRMT5 inhibitor).

    Collaboration to explore combinations with inhibitors of novel targets, exemplified by a PRMT5 inhibitor under their agreement.

    Aethon TherapeuticsDiscovery and clinical collaboration to explore novel approaches (bispecific antibodies).

    Collaboration to explore novel approaches, such as bispecific antibodies under their agreement.

    Breakthrough Cancer OrganizationCollaboration with leading industry academia translational research partners.

    Collaboration to uncover new patient-centric scientific insights to further inform ongoing commitment to transformative science.

    Pancreatic Cancer Action Network (PanCan)Relationship with a patient advocacy organization.

    Relationship to ensure patient needs are at the forefront as medicines are advanced, devoted to improving the lives of people living with pancreatic cancer.

    Risks & headwinds

    1
    Increased expenses due to progression and expansion of clinical development programs and commercial preparation.FY25

    Full year GAAP net loss to be between $840 million and $900 million in 2025.

    Mitigation: Supported by strong cash and investment balance funding operations into H2 2027.

    What to watch in Q1 FY25

    5

    RASolute 302 enrollment progress

    2025
    CurrentHighly encouraging enrollment at initial U.S. sites; activating ex-U.S. sites
    TargetSubstantially completing enrollment

    Why it matters

    Indicates progress towards a pivotal trial readout in second-line metastatic PDAC, a key value driver.

    We currently anticipate substantially completing enrollment in the trial this year to enable an expected data readout in 2026.

    Q&A highlights

    7

    Why move to earlier line PDAC, especially adjuvant? What's the conviction for adjuvant Phase III? How does RAS play a role in earlier lines?

    Management is confident in owning the entire PDAC space across all lines, based on existing monotherapy data. The adjuvant study targets resectable patients for significant long-term impact. RAS drivers are present in almost all PDAC patients, regardless of stage.

    “I think based on the data that we've already reported in pancreatic cancer, the monotherapy data, I think we have a strong conviction that we ought to trying to own the entire PDAC space across all lines of therapy.”

    asked by Samantha Meadows-Ortiz · answered by Mark Goldsmith

    1 min read5 chapters

    Detailed Narrative

    01

    RAS(ON) Inhibitor Pipeline Progress

    Revolution Medicines has pioneered three clinical-stage RAS(ON) inhibitors: daraxonrasib (multi-selective), elironrasib (G12C-selective), and zoldonrasib (G12D-selective), introducing the 'onrsaib' nomenclature. The company reported compelling monotherapy data for daraxonrasib in PDAC and NSCLC, and zoldonrasib in PDAC. Initial proof-of-concept for RAS(ON) inhibitor doublets (elironrasib + daraxonrasib, zoldonrasib + daraxonrasib) and combinations with pembrolizumab were also reported, enabling potential paths to first-line metastatic NSCLC.

    02

    Strategic Expansion in Pancreatic Cancer

    The company is pursuing an ambitious strategy to 'own the entire PDAC space.' This includes initiating a Phase III trial in first-line metastatic disease with daraxonrasib monotherapy and daraxonrasib plus chemotherapy arms, and actively designing a registrational trial for daraxonrasib as an adjuvant treatment in resectable pancreatic cancer. Both pivotal trials are anticipated to be initiated in the second half of 2025.

    03

    Mutant-Selective Inhibitor Development

    Revolution Medicines aims to generate sufficient data to inform development priorities for elironrasib and zoldonrasib, with plans to initiate one or more pivotal trials in 2026, potentially as monotherapy or in combination, likely based on a RAS(ON) inhibitor doublet. Additional clinical safety and antitumor activity data for zoldonrasib are expected in Q2 2025, and clinical data supporting future combination plans are expected in Q2 or Q3 2025.

    04

    Earlier-Stage Pipeline and Innovation

    The company expects to advance RMC-5127, a next-generation RAS(ON) G12D selective inhibitor, to clinic-ready stage in 2025, with a first-in-human trial planned for 2026. This reflects a commitment to sustained innovation beyond current development-stage assets.

    05

    Commercial and Operational Readiness

    Revolution Medicines is growing its commercial and operational capabilities, including expanding U.S. field teams and increasing pre-commercial activities in support of a potential daraxonrasib launch. The company is committed to retaining U.S. commercial rights and exploring ex-U.S. partnership opportunities to ensure global access.

    AI-generated summary of the company’s earnings call. Not investment advice.