Revolution Medicines' Earnings Call: RESOLUTE-302 Data Delays and NSCLC Timelines Clash

Date of Call: Feb 25, 2026

Guidance:

• Full year 2026 GAAP operating expenses expected to be between $1.6 billion and $1.7 billion.
• This includes estimated non-cash stock-based compensation expense of between $180 and $200 million.
• The increase is due to progression of clinical programs and increased commercial preparation activities.

Business Commentary:

Pipeline Progress and Clinical Trials:

• Revolution Medicines has advanced its pipeline with four novel investigational drugs targeting major oncogenic RAS drivers, supported by more than 2,500 patients who have received one or more of its RAS inhibitors.
• The company is conducting eight ongoing or planned Phase III registrational trials, reflecting its commitment to addressing significant unmet needs in RAS-addicted cancers.

Financial Position and Strategic Partnerships:

• The company ended Q4 2025 with $2.03 billion in cash and investments, bolstered by a strategic partnership with Royalty Pharma providing access to up to $2 billion in committed capital.
• This financial strength is attributed to increased clinical trial and manufacturing expenses, as well as personnel-related expenses, reflecting investments in expanding clinical programs.

Breakthrough Therapy and Regulatory Designations:

• Draxon RASib has been designated as a breakthrough therapy by the U.S. FDA, alongside receiving a commissioner's national priority voucher.
• This recognition is based on its potential to address significant unmet needs in pancreatic cancer, supporting the company's focus on RAS-targeted therapies.

Oncology Focus and Combination Therapies:

• The company is exploring combination therapies, such as with PRMT5 inhibitors and PD-1 antibodies, to enhance treatment options for patients with RAS-driven cancers.
• This strategy aims to leverage the potential of RAS inhibitors alongside other targeted therapies to maximize clinical impact.

Sentiment Analysis:

Overall Tone: Positive

• Management expressed 'substantial progress and growing momentum' for the RAS inhibitor pipeline, with a 'pivotal year' for 2025 and 2026 poised to be 'one of substantial impact.' They highlighted 'strong conviction' in clinical programs, multiple FDA designations, and a 'world-class' operational foundation for a commercial launch.

Q&A:

• Question from Albert Augustinus (Lyric Partners): Could you please share your thoughts or clarify in your plans to advance the durex and RAS combination in first-line non-small cell lung cancer this year? Are you still guiding towards the initiation of a registrational trial in this setting?
  Response: Commitment remains high to develop duraxone in first-line lung cancer; plans to share more information during the year, including ongoing combination testing and evaluation of new partners like ivanesumab.

• Question from Brian (unaffiliated): As we get closer to the top line for the second line PDAC trial, what is your latest thought on the efficacy measure that we could get at the time of the top line? And just curious if you can provide a bit more color on the rates of events towards this upcoming top line.
  Response: No higher-resolution details can be shared at this time; the readout is OS-driven and powered for OS, with an interim PFS read available, but benchmarks will be based on standard of care.

• Question from Michael (unaffiliated): To what degree do you think the RAS and RASLUT use in your first-line studies post-progression in the control arm could potentially impact OS outcomes in RASLUT 303 and 305? And how important is it to demonstrate OS in these studies in the first place?
  Response: There is some potential risk of crossover if approved, but timing and geographic enrollment (especially outside the U.S.) are expected to buffer against this concern, reducing the impact on OS.

• Question from Charles (unaffiliated): Can you talk about your decision to also combine your pipeline assays with Bristol's PRMT5 inhibitor and how this kind of fits in context with your ongoing in collaboration with Tango, and second, your collaboration with Ivan Nesimab. At what point might you make go-no-go decisions on later stage clinical development with your pipeline assets, and how do you weigh not only the emerging combination data that you're generating, but also the broader landscape amongst the various Harmony trials shaping up?
  Response: The PRMT5 inhibitor collaborations are an inclusive approach to allow compounds to be tested with multiple partners. For ivanesumab, decisions will be data-driven; the company is on the front lines evaluating combinations and will be in a position to decide with data in hand.

• Question from Mark (unaffiliated): Can you just confirm whether any event thresholds have been reached in 302 to trigger interim analyses? yet or if just none of those have been hit yet. And then thinking more broadly about pancreatic cancer, now you have several first-line trials either ongoing or getting started in the next handful of months. Just what is the kind of long-term vision you have for what the treatment paradigm in pancreatic cancer looks like in four or five years? How do Durex and RASIB, Zoldan and RASIB, chemo all get sequenced for maybe the typical patient?
  Response: No interim analysis has been triggered yet; the next disclosure will be upon unblinding. The long-term vision covers a broad spectrum from second-line to resectable disease, offering optionality with RAS inhibitors in combination with chemo and potentially in a chemotherapy-free setting.

• Question from Alex (unaffiliated): With the ivanesumab study now dosing patients, I guess, could you maybe speak a bit about the study design and which tumor types and lines of therapy you expect might enrich in the study as it enrolls? And longer term, how is this combo maybe emblematic of how you're hedging your RAS therapies alongside potential shifts in standards of care?
  Response: The APEX study is a Phase I trial evaluating combinations with all three RAS inhibitors across multiple solid tumors, with dedicated expansion cohorts in pancreatic cancer, non-small cell lung cancer, and colorectal cancer, positioning the company to hedge against shifts in standard of care.

• Question from Leo (unaffiliated): I guess, does this address secondary mutations, or does it really only work directly on RAS mutations themselves? And I guess, said another way, do you think you'll ultimately need to be selecting patients that might be amenable to this? And then, you know, just based on some of the clinical work you've shown, it looks like it drives very deep responses even relative to direxon RAS. So are you seeing this ultimately be positioned as a, you know, next line option or can this be something that ultimately replaces and is a better direxon?
  Response: The new class of inhibitors (Rm055) is designed to address RAS-driven resistance through pathway reactivation, not secondary mutations. More details will be shared at a scientific meeting; its positioning will become clearer with further data.

• Question from Poonah (unaffiliated): I just want to understand how soon can you get to commercialization of data in case the first interim is positive? What are some of the aspects within the commercialization preparations that you still need to work through?
  Response: Launch readiness is advancing well, with leadership teams in place and field sales teams being recruited; the company is achieving broad organizational readiness across the U.S., Europe, and Japan, and will provide more color as filing and launch approach.

• Question from Jay Olson (Oppenheimer): Since you're making a lot of headway in PDAC and non-small cell lung cancer, can you talk about your vision and strategy in colorectal cancer and how are you prioritizing the CRC opportunity for RevMed? Is CRC an area that you would prefer to focus on with partnerships, for example, in combination with ivanesumab? Or is CRC something that you plan to pursue independently? And from a BD perspective, would you consider in-licensing some molecules to have synergy with your RAS portfolio so you wouldn't need to rely on partnerships in CRC?
  Response: Colorectal cancer is not deprioritized but is biologically complex, requiring combinations. The base plan is to develop combinations internally; partnerships may be considered if the right collaborator is found. The company is not looking to change its standalone global model based on disease type.

Contradiction Point 1

Disclosure Policy for RESOLUTE-302 Trial Data

Inconsistent stance on sharing trial specifics during a disclosure period.

Brian Nowak (Morgan Stanley) - Brian Nowak (Morgan Stanley)

2025Q4: The company is in a period where they indicated they would provide disclosure, so they cannot give higher-resolution details at this time. - [Jack Anders](CFO)

As we approach the top-line readout for the RESOLUTE-302 PDAC trial, could you provide an update on the efficacy measures and event rates? - Lut Ming Cheng (JPMorgan)

20260226-2025 Q4: No higher-resolution details can be shared at this time, as the company is in a disclosure period. - [Mark Goldsmith](CEO)

Contradiction Point 2

Timeline for Sharing First-Line NSCLC Development Plans

Contradiction on when detailed plans for a key asset will be disclosed.

Albert Augustinus (Lyric Partners) - Albert Augustinus (Lyric Partners)

2025Q4: More information on the plans for advancing duraxan-rasib in first-line NSCLC will be shared during the course of this year. - [Steve Kelsey](President of Research and Development)

Could you clarify your plans to advance the duraxan-rasib combination in first-line non-small cell lung cancer (NSCLC) this year and whether you remain on track for a registrational trial initiation in this setting? - Albert Agustinus (Leerink Partners)

20260226-2025 Q4: More information on plans will be shared during the year. - [Stephen Kelsey](President of Research and Development)

Contradiction Point 3

Timeline for Updated Durability Data in First-Line PDAC

Contradiction on when updated data for daraxonrasib will be released.

Albert Augustinus (Lyric Partners) - Albert Augustinus (Lyric Partners)

2025Q4: More information on the plans for advancing duraxan-rasib in first-line NSCLC will be shared during the course of this year. - [Jack Anders](CFO)

Could you clarify your plans to advance the duraxan-rasib combination in first-line non-small cell lung cancer (NSCLC) this year and whether you're still guiding towards initiating a registrational trial in this setting? - Morgan Lamberti (Goldman Sachs)

20251106-2025 Q3: Updated durability data for daraxonrasib monotherapy and combination in first-line PDAC is expected in the first half of 2026. - [Mark Goldsmith](CEO)

Contradiction Point 4

Strategy to Mitigate Crossover Risk in First-Line Pancreatic Cancer Trials

Contradiction on the primary method to prevent patients from crossing over to an approved drug in trials.

Michael Zhang (BMO) - Michael Zhang (BMO)

2025Q4: The company believes they can mitigate this risk through the timing of the first-line trial (establishing momentum before potential approval) and geographic enrollment (with significant contributions expected outside the U.S. where the drug is unlikely to be approved during the study). - [Jack Anders](CFO)

How could the potential use of an approved duraxan-rasib in second-line settings post-progression impact OS outcomes in your first-line pancreatic cancer studies (RASLUTE-303 and RASLUTE-305), and how important is demonstrating OS in these studies? - Laura Prendergast (Stifel)

20251106-2025 Q3: The frontline trial design is fully powered to demonstrate survival benefit. Data from second-line studies provide confidence in the monotherapy benefit, which informs the combination arm. They are designing to account for potential U.S. availability impact on crossover by assigning more sites outside the U.S. - [Dr. Wei Lin](Chief Medical Officer)

Contradiction Point 5

Disclosure Strategy and Timeline for RESOLUTE-302 Top-line Data

Contradiction on when and how data from the pivotal trial will be disclosed.

Brian Nowak (Morgan Stanley) - Brian Nowak (Morgan Stanley)

2025Q4: The company is in a period where they indicated they would provide disclosure, so they cannot give higher-resolution details at this time.... They will not be providing any specific expectations beyond this. - [Jack Anders](CFO)

As the top-line readout for the RESOLUTE-302 PDAC trial approaches, could you share your latest thoughts on the efficacy measure and provide more details on the event rates? - Marc Alan Frahm (TD Cowen)

2025Q2: Data readout is expected in 2026. - [Mark A. Goldsmith](CEO)