Q1 2025 Revolution Medicines Inc Earnings Call
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Because such statements deal with future events and are subject to many risks and uncertainties actual results may differ materially from those in the forward looking statements.
For a full discussion of these risks and uncertainties. Please review our annual report on Form 10-K, and our quarterly reports on Form 10-Q that are filed with the U S Securities and Exchange Commission.
This afternoon, we released financial results for the quarter ended March 31, 2025, and recent corporate updates.
Speaker Change: Press releases are available on the investors section of our website <unk> dot com, along with an updated investor presentation, which we will be referencing during today's call with that I'll turn the call over to Dr. Mark Goldsmith Revolution medicines, Chairman and Chief Executive Officer Mark.
Mark: Thanks, Bryan it's good to be with you this afternoon.
Mark: Today I'll highlight some of the progress we've made this quarter against the strategic priorities, we outlined earlier this year.
Mark: I will then pass the call over to Dr. Steve Kelsey, who will walk through a strategic framework for our developing plans in non small cell lung cancer.
Speaker Change: Dr. Wei Lin will then highlight updated data from several of our ongoing non small cell lung cancer cohorts that provides support for our plans in lung cancer.
Speaker Change: Jack Anders will then provide a summary of our first quarter financial results before I share closing remarks, and open the call to Q&A.
Speaker Change: At Revolution medicines, we remained committed to revolutionizing treatment for patients with Ras addicted cancers through the discovery development and delivery of innovative targeted medicines.
Speaker Change: We continue to make important strides in pursuit of this mission as we execute advance and extend our understanding of our novel Rasp inhibitors.
Speaker Change: We believe and have increasingly been able to demonstrate that our compounds have the potential to become an important therapeutic options for patients living with Ras addicted cancers.
Speaker Change: Our first three clinical stage rason inhibitors with highly differentiated and promising clinical profiles include <unk>, a groundbreaking rason multi selective inhibitor.
Speaker Change: Alere on rapid a distinguished <unk> selective covalent inhibitor and sold on RASK.
Speaker Change: Really innovative <unk> 12, Deselected covalent inhibitor.
Speaker Change: We continue to make substantial progress advancing these programs with a vision to maximize the clinical impact across tumor types and lines of therapy through a mix of single agent and combination strategies.
Speaker Change: Pancreatic cancer is an important priority and our strategy involves executing on the ongoing phase III Resolute 302 trial.
Speaker Change: <unk> in patients with previously treated disease, while moving aggressively into earlier lines of therapy.
Speaker Change: We are working quickly to prepare for the initiation of two additional phase III studies with <unk> in pancreatic cancer in the second half of 2025.
Speaker Change: One of these trials will be in patients with first line metastatic disease and is expected to compare a reference arm of patients treated with chemotherapy to two investigational arms.
Speaker Change: One with patients treated with <unk> monotherapy, and one with patients treated with <unk> plus chemotherapy.
Speaker Change: The other early line trial will be as adjuvant treatment for patients with Resectable pancreatic cancer, who have undergone surgery and perioperative therapy typically including chemotherapy.
Speaker Change: In addition to this robust plan for <unk> to play an important role in the treatment of pancreatic cancer across lines of therapy.
Speaker Change: We have similar ambitions for broad development in Ras mutant non small cell lung cancer.
Speaker Change: We'll focus of today's call is to provide further color and support for our non small cell lung cancer strategy.
Speaker Change: I'd like to invite Dr. Steve Kelsey to walk you through our current conceptual framework Steve.
Speaker Change: Steve.
Steve Kelsey: Thanks Mark.
Steve Kelsey: Improving treatment options for patients with Ras mutant lung cancer is an important priority for evolution medicines.
Steve Kelsey: The majority of patients with non small cell lung cancer are either diagnosed with or.
Steve Kelsey: Or light to develop metastatic disease.
Steve Kelsey: Treatment objectives for these patients include symptom improvement by reducing tumor burden.
Steve Kelsey: <unk> disease progression.
Steve Kelsey: Morning, survival and improving quality of life.
30% of patients with non small cell lung cancer Hopper Ras mutation.
Steve Kelsey: There are still no full regulatory approvals for Ras inhibitors, and any Ras mutant lung cancer.
Steve Kelsey: Nevertheless, due to the commercial availability of <unk> inhibitors.
Steve Kelsey: Accelerated and conditional approval mechanisms.
Steve Kelsey: <unk> non small cell lung cancer is affectively evolved into two diseases in treatment paradigms.
Steve Kelsey: G C mutant disease, which represents around 12% of non small cell lung cancer and other Ras mutant non small cell lung cancer, which we are referring to non G 12 seat Ras mutant non small cell lung cancer.
Steve Kelsey: The second group accounts for around 18% and non small cell lung cancer.
Steve Kelsey: We expect segmentation of the Ras mutant non small cell lung cancer space.
Steve Kelsey: To continue into mutational groups as other mutant selective inhibitors advance through clinical development to receive regulatory approvals.
Steve Kelsey: Our aim at Revolution medicines is to establish our portfolio of <unk> inhibitors as the leading therapies the patients with Ras mutant non small cell lung cancer across all Ras mutations and lines of therapy.
Steve Kelsey: We strive to develop first and best in class Rasp inhibitors and combinations.
Steve Kelsey: Our strategy for metastatic disease, it depends on a number of variables first which Ras mutation the tumor harbors.
Steve Kelsey: And whether a mutant selective <unk> inhibitor has achieved proof of concept.
Steve Kelsey: Second the line of therapy for metastatic disease as the expectations and standards of care are different between initial therapy and salvage therapy.
Steve Kelsey: Direct some relative has shown encouraging antitumor activity in patients with tumors harboring a wide range of Ras mutations.
Steve Kelsey: Nonetheless in the face of Ras addiction by such tumors, we expect the mutant selective inhibitors should also have a role in treating schumer's with corresponding rest driving mutations.
Steve Kelsey: Combining these mutant selective inhibitors with a rationale multi selective inhibitor.
Steve Kelsey: They play an important role by delivering deeper target inhibition and overcoming resistance mechanisms in a way that neither approach can achieve on its own.
Steve Kelsey: Our previously published data show that the Rexam wraps. It is active against a broad range of Ras mutations that have been frequently identified as mechanisms of escape for mutant selective <unk> inhibitors.
Steve Kelsey: Consistent with this and as we recently presented at AACE al.
Steve Kelsey: New RASK point mutations are an infrequent pools of the state from direct some RASM in pancreatic cancer.
Steve Kelsey: Ah Rason inhibits a doublet combination has the goal of improving outcomes and potentially providing a chemotherapy sparing option for patients with Ras mutant non small cell lung cancer.
Steve Kelsey: In the previously treated metastatic setting use of a single agent Ras inhibitor may be sufficient to improve outcomes over the current chemotherapy standard of care.
Steve Kelsey: This is the approach we're taking with <unk> in patients with previously treated Ras mutant non small cell lung cancer and the resolve 301 study.
Steve Kelsey: For first line treatment of metastatic disease. The dominant standard of care includes immune checkpoints inhibitors, primarily <unk>.
Steve Kelsey: Demonstrating safety and Tolerability with Pembina is about is critical as a means of enabling first line therapy and maximizing the durability of any clinical benefit.
Steve Kelsey: These concepts have currently being reduced to practice by Revolution medicines single agent direct some rapid provides a foundation for the investigation of <unk> inhibitors in all Ras mutant non small cell lung cancer and second line and beyond <unk>.
Steve Kelsey: As recently presented at AACE, all zoned on Russia, I was encouraging activity as a single agent in second line plus rats G 12, D mutant non small cell lung cancer.
Steve Kelsey: In the first line <unk> 12, <unk> non small cell lung cancer setting, we a spa to develop chemotherapy sparing rason inhibits a doublet of direct some rested plus layer on <unk> with <unk> and thereby reserve platinum based chemotherapy for second line treatment.
Steve Kelsey: Doing so has the potential to contribute to an improvement in overall survival.
Steve Kelsey: In first line non <unk> non small cell lung cancer, we plan to develop direct some recipe in combination with standard of care.
Steve Kelsey: Eventually sold on Rasset, whether it's encouraging monotherapy profile might offer a path to another chemotherapy sparing restaurant and inhibits the doublet for patients with <unk>.
Steve Kelsey: And similar double as approaches may be possible with other Ras mutant selective inhibitors, such as RMC <unk> seven targeting <unk>.
Speaker Change: I will now turn the call over to Dr. Wei Lin to provide an update across our non small cell lung cancer clinical programs way.
Speaker Change: Thank you Steve.
Speaker Change: I'll start by providing monotherapy updates across our portfolio.
Speaker Change: Beginning with <unk>, our most advanced rason incubator.
Speaker Change: This multi selective inhibitor has demonstrated compelling results across multiple tumors, including lung cancer.
Speaker Change: And is currently being evaluated in a phase III.
Speaker Change: <unk> Registrational study for patients with previously treated non small cell lung cancer.
Speaker Change: Returning the activating study site for resolve 301.
Speaker Change: The study will randomize, approximately 420 patients to either <unk> monotherapy or docetaxel.
Speaker Change: These patients must have received either one or two prior lines of therapy, including immunotherapy and platinum based chemotherapy.
Speaker Change: Either concurrently or sequentially.
Speaker Change: Resolved 301 incorporates an estimate design.
Speaker Change: The primary analysis performed in the core population on non small cell lung cancer patients with Ras Chico acts mutations excluding <unk>.
Speaker Change: Extended population, we incorporate all patients with Ras mutant non small cell lung cancer.
Speaker Change: Including those with tumors harboring.
Speaker Change: <unk>.
Speaker Change: <unk> 13, or <unk> 61 mutations.
Speaker Change: The study has dual primary endpoints of progression free survival and overall survival.
Speaker Change: Moving to <unk> non small cell lung cancer.
Speaker Change: We've previously shown promising activity <unk> in patients with these tumors.
Speaker Change: And the ongoing <unk> 301 Registrational study.
Speaker Change: Such patients.
Speaker Change: Last month at ACR initial clinical results were presented so don't ratchet.
Speaker Change: Our rats on GE called selective <unk> inhibitor from the non small cell lung cancer cohort.
Speaker Change: I'll walk you through these data.
Speaker Change: <unk> was well tolerated with manageable and predominantly low grade <unk> treatment related adverse events.
Speaker Change: On the safety table.
Speaker Change: So the December 2nd 2024 data cutoff.
Speaker Change: At the 200 milligram once daily dose to.
Speaker Change: Two grade three adverse events.
Speaker Change: Our reported among 19 patients with only two dose interruptions and no dose reductions.
Speaker Change: So around rapid achieved a favorable meaning dose intensity of 98%.
Speaker Change: So what our math in monotherapy at the 200 milligram daily dose demonstrated encouraging anti tumor activity.
Speaker Change: The waterfall plot shows the best percentage change in tumor sites for patients with non small cell lung cancer, who received their first dose of sodium <unk> and <unk>.
Speaker Change: Just eight weeks prior to the data cutoff date.
Speaker Change: The objective response rate was 61%.
Speaker Change: <unk> patients with a confirmed response or a response that was pending confirmation.
Speaker Change: Do you need control rate was 89%.
Speaker Change: We will continue following these patients to define your ability.
Speaker Change: Now I'll move to our Ras <unk> mutant selective covalent inhibitor thereon rocket in non small cell lung cancer.
Speaker Change: We reported the first clinical data on <unk>.
Speaker Change: <unk> in non small cell lung cancer at the Triple meeting in 2023.
Speaker Change: And today I will share updated elong rats at monotherapy data that includes more patients and longer follow up.
Speaker Change: Foundation for combination strategies.
Speaker Change: Move into first line metastatic and eventually earlier lines of non small cell lung cancer.
Speaker Change: So the April seven 2025 data cutoff.
Speaker Change: 36 patients who had received prior treatment with standard care were treated with <unk> monotherapy at 200 milligrams twice daily.
Speaker Change: <unk> was generally well tolerated with treatment related adverse events consistent with previously reported data.
Speaker Change: The most frequently observed treatment related adverse events were gastrointestinal and asymptomatic QVC prolongation.
Speaker Change: <unk> achieved favorable mean dose intensity of 94%.
Speaker Change: Here, we show the clinical activity in the same 36 patients treated with <unk> monotherapy in the.
Speaker Change: A dose of 200 milligrams twice daily.
Speaker Change: The objective response rate in these patients with 56%.
Speaker Change: The disease control rate was 94%.
Speaker Change: The estimated median progression free survival in these patients with nine nine months.
Speaker Change: I will now cover our combination clinical development to enable our goal of improving treatment outcomes for patients with Ras mutant non small cell lung cancer in the first line metastatic setting.
Speaker Change: The need for improved treatment options for patients with metastatic non small cell lung cancer remains high.
Speaker Change: And the first line setting two regiments alright widely used globally.
Speaker Change: And <unk> plus chemotherapy is the most commonly used treatment for all patients regardless of their tumor PD lone expression status.
Speaker Change: Measured by tumor proportional score or TPS.
Speaker Change: And <unk> monotherapy.
Speaker Change: The preferred regimen in patients with TPS greater than or equal to 50%.
Speaker Change: Which accounts for about one third of patients with non small cell lung cancer.
Speaker Change: While the introduction of immunotherapy has been transformative for patients with non small cell lung cancer.
Speaker Change: Especially those with high PD lone expression.
Speaker Change: But the data in these table indicate non small cell lung cancer remains a disease with high unmet need.
Speaker Change: Because the market the approximately two third of patients who have tumors with lower or no PD lone expression.
Speaker Change: Even the best available standard of care.
Speaker Change: And that resulted in reported response rates above 40%.
Speaker Change: In Ras mutant non small cell lung cancer in the second line and beyond.
Speaker Change: Treatment is generally either the chemotherapy docetaxel or.
Speaker Change: Hey, Ross <unk> op inhibitor.
Speaker Change: As illustrated in the table.
Speaker Change: Reported response rates for Docetaxel.
Speaker Change: We have been less than 15%.
Speaker Change: Even with the commercially available <unk> inhibitors of solar asset and underground Sip.
Speaker Change: <unk> patient outcomes.
Have been modest with response rates of approximately 30%.
Speaker Change: Combinations are likely to remain a foundation of first line metastatic treatment for non small cell lung cancer.
Speaker Change: <unk> objective is to determine the best way to bring targeted rasp inhibitors.
Speaker Change: Into combination with chemotherapy for the first line treatment of Ras mutant non small cell lung cancer.
Speaker Change: These figures.
Speaker Change: Some preclinical experiments illustrate two concepts to guide our clinical approaches.
Speaker Change: The first concept shown on the left is that two rasp inhibitors can be combined to increase anti tumor activity.
Speaker Change: In this experiment with a K raunchy trustee.
Speaker Change: Non small cell lung cancer model.
Speaker Change: They are on <unk> or <unk> alone significantly increased progression free survival compared to control as measured by time to tumor doubling.
Speaker Change: Notably the combination.
Speaker Change: Later on Ross it puts derived from massive.
Speaker Change: Prolonged progression free survival.
Speaker Change: Even further.
Speaker Change: Locating additive durability from the rasp inhibitor doublet.
Speaker Change: The second concept shown in experiment on the right.
Speaker Change: That fits rasp inhibitor doublet.
Speaker Change: <unk> synergizes with immunotherapy.
Speaker Change: In this experiment we used.
Speaker Change: <unk> immune refractory K ROTC across key non small cell lung cancer tumor.
Speaker Change: That was unresponsive.
Speaker Change: Anti PD, one inhibitor alone and.
Speaker Change: And only partially responsive to anti PD, one combined with either rasp inhibitor.
Speaker Change: Essentially no progression we're.
Speaker Change: We're seeing in this model.
Speaker Change: 100 days of treatment with anti PD, one combined with a <unk> inhibitor doublet.
Speaker Change: Encouraged by preclinical results of this sort.
Speaker Change: I would now describe new clinical data from our evaluation of pairwise combinations.
Speaker Change: <unk> plus <unk>.
Speaker Change: <unk> plus <unk>.
Speaker Change: <unk> plus <unk>.
Speaker Change: Does suggest these concepts may translate in patients with <unk> non small cell lung cancer.
Speaker Change: The first combination data set.
Speaker Change: His direction massive plus kemple, this map with or without.
Speaker Change: <unk> chemotherapy.
Speaker Change: There are some <unk>, plus <unk> with or without chemotherapy.
Speaker Change: <unk> has been generally well tolerated in patients with non small cell lung cancer.
Speaker Change: Previously.
Speaker Change: We showed acceptable tolerability for the combination of <unk> with Pembina listen that in later line patients.
Speaker Change: And.
Speaker Change: With further follow up the Tolerability profile in those patients has remained stable.
Speaker Change: Today, we're focusing on patients with first line disease.
Speaker Change: While the follow up is shorter for patients in the first line setting the tolerability profile of <unk> plus pemble. This map is consistent with what has been observed in the second line study.
Speaker Change: With or without the addition of chemotherapy.
Speaker Change: No new safety signals were seeing and the overall tolerability profile is consistent with that of direction, where asset plus standard of care agents.
Speaker Change: Rash gasoline testing toxicities and stone with tightest Mucositis remained the most commonly observed adverse events for <unk>.
Speaker Change: And neutral <unk> and thrombocytopenia.
Speaker Change: Merged with the addition of chemotherapy.
Speaker Change: The Tolerability profile supports the further development of <unk> massive cliff pemble isn't that with or without chemotherapy.
Speaker Change: Cost reductions and discontinuation for grants from asset <unk> map in this combination were modest.
Speaker Change: <unk> achieved a favorable mean dose intensity of 93% in combination with <unk> and 90% with additional chemotherapy.
Speaker Change: Only a limited number of first line patients.
Speaker Change: Had sufficient follow up to have had a tumor assessment.
Speaker Change: <unk> by the anti tumor activity seen to date.
Speaker Change: Let's figure patients had tumors with TPS greater than or equal to 50% and were treated with.
Speaker Change: <unk> plus chemical lithium app.
Speaker Change: Assistant with a population.
Speaker Change: Who would have received <unk> monotherapy a standard of care.
Speaker Change: Of the seven efficacy evaluable patients, who had undergone at least one tumor assessment.
86% of these TPS greater than or equal to 50% patients.
Speaker Change: A recess response.
Speaker Change: And <unk> had achieved disease control remained on treatment.
Speaker Change: While the data set will continue to evolve with the addition of more patients and longer follow up.
Speaker Change: This is a very encouraging start.
Speaker Change: In the figure on the right.
Speaker Change: Patients with TPS less than 50% Berkshire.
Speaker Change: Were treated with drugs from asset plus timber lithium app and chemotherapy.
Speaker Change: With roughly two third of first line patients, who would likely we see <unk> plus chemotherapy standard of care.
Speaker Change: Of the 10 efficacy evaluable patients who had undergone at least one scan hits.
Speaker Change: 60% of these TPS nothing 50% patients had a recess response and.
Speaker Change: And 90% achieved disease control.
Speaker Change: These data support the continued development of <unk> plus standard of care in first line Ras mutant non small cell lung cancer.
Speaker Change: I'll now touch on the <unk> plus <unk> combination.
Speaker Change: Demonstrating the safety of this combination is important as we take a pair wise approach toward our goal of developing a chemotherapy sparing triplet combination.
Speaker Change: <unk> <unk> and <unk> in patients with first line metastatic <unk> non small cell lung cancer.
Speaker Change: We previously showed.
Speaker Change: Acceptable tolerability for the layer on <unk>, plus <unk> combination in the second line plus site.
Speaker Change: With further follow up.
Those patients.
Speaker Change: We have not observed an increase in additive toxicity.
Speaker Change: Today, we'll focus on initial results in patients with first line non small cell lung cancer.
Speaker Change: The February 10th 2025 data cutoff.
Speaker Change: Combination of <unk> with Pembina as Matt showed a wall tolerated profile.
Speaker Change: With few grade three or higher treatment related adverse events.
Speaker Change: No new safety signals were observed.
Speaker Change: This tolerability profile translated to an acceptable dose modification rates in either the second line or first line study.
Speaker Change: And you'll hear on <unk>.
Speaker Change: Maintained a favorable meaning dose intensity at 85%.
Speaker Change: The combination of <unk> with Pembina as map shows.
Speaker Change: <unk> preliminary anti tumor activity.
Speaker Change: Amongst site efficacy evaluable patients with first line non small cell lung cancer, and a GPS greater than or equal to 50%.
Speaker Change: <unk> achieved a reset response.
Speaker Change: Our development strategy in first line <unk> mutant non small cell lung cancer is to replace the standard of care with the triplet regimen of <unk>.
Speaker Change: <unk> and chemical this map a chemo sparing regimen.
Speaker Change: I've just shown data supporting the combinability and <unk> tumor activity of <unk>, plus <unk> and beyond.
Speaker Change: <unk> plus <unk>.
Speaker Change: The third pillar wise combination needed to support this triplet regimen.
Speaker Change: Congrats on inhibitor doubly.
Speaker Change: We are an asset plus dropdown asset.
Speaker Change: Okay.
Speaker Change: This rasp inhibitor doublet.
Speaker Change: Concept is supported by strong results in preclinical models.
Speaker Change: Including models that are refractory to monotherapy approaches.
Speaker Change: In these preclinical models deep and durable responses are seen in rasp inhibitor doublets.
Speaker Change: In December 2024.
Speaker Change: Sure. Its initial clinical data for the <unk> inhibitor doublet of <unk> plus dropdown asset.
Speaker Change: She established the mechanistic proof of principle for this combination.
Speaker Change: We evaluated challenging population of colorectal cancer patients.
Speaker Change: Who had been previously treated with not only standard of care chemotherapy, but also with <unk> inhibitors.
Speaker Change: Anti Egfr antibodies.
Speaker Change: These early results demonstrated.
Speaker Change: And acceptable Tolerability profile, along with encouraging anti tumor activity.
Speaker Change: Very difficult to treat patient population.
Speaker Change: These results provided strong rationale for continued development of these routes on inhibitor doublet approach across tumor types and lines of therapy.
Speaker Change: Today.
Speaker Change: I'll share initial dose finding data from discounts on you've got a doubling in patients with non small cell lung cancer.
Speaker Change: The data in this table demonstrates the combinability of <unk> with <unk>.
Speaker Change: With a tolerability profile that is largely consistent with that of direction around Sip itself.
Speaker Change: Even with longer follow up to the.
Speaker Change: Hydro toxicity did not emerge.
Speaker Change: <unk> signal in this larger cohort of lung cancer patients.
Speaker Change: Qt prolongation ECG with not central <unk>.
Speaker Change: <unk> is not comp but.
Speaker Change: With a great three rate of only 3%.
Speaker Change: This tolerability profile translated.
Speaker Change: No treatment discontinuation.
Speaker Change: And a favorable mean dose intensity of 95%.
Speaker Change: Alright, the R&R asset and 85% for direction Ratchet.
Speaker Change: The combination of <unk> plus direction of asset.
Speaker Change: Shoji encouraging preliminary anti tumor activity in 2006 patients with <unk> treated <unk> non small cell lung cancer.
Speaker Change: Who had been previously treated with a <unk> in Japan.
Speaker Change: Because dose optimization of the Ras inhibitor doublet is ongoing.
Speaker Change: We're sharing direction routes it at doses ranging from 100 milligrams to 200 milligrams.
Speaker Change: Yes.
Speaker Change: On the left.
Speaker Change: We're showing the <unk> monotherapy data in patients who were previously treated with a K Ras tchiakovsky off incubator.
The response rate and disease control rate for <unk> monotherapy for 42% and 79% respectively.
Speaker Change: On the right.
Speaker Change: But the combination of Aero more asset and <unk>. The response rate was 62% disease control rate with 92%.
Speaker Change: Well above the activity seen in this population with <unk> monotherapy.
Speaker Change: The majority of patients on the combination remained on treatment ourselves to February 10th 2025 data cutoff date.
Speaker Change: Taking a step back and looking at our data driven lung cancer strategy. We believe we have a clear path to pursuing our ambition to change the standard of care for patients with Ras mutant lung cancer.
Speaker Change: Both in first line metastatic and in earlier lines of treatment.
Speaker Change: We launched our initiative in non small cell lung cancer.
Speaker Change: With our Registrational study for <unk> monotherapy in <unk> treated patients with Ras mutant lung cancer the.
Speaker Change: The emerging so darn rapid data.
0.2 clear opportunities to continue evaluating <unk> in patients with Ras <unk> nuclear non small cell lung cancer.
Speaker Change: Monotherapy and in combination.
Speaker Change: The three <unk> combinations of <unk> plus.
Kimball: Kimball lithium app.
Kimball: <unk> plus <unk> map.
Kimball: And the <unk> inhibitor doublet of <unk> plus <unk>.
Kimball: <unk>.
Kimball: Show acceptable tolerability and encouraging anti tumor activity and create options in the first line treatment setting.
Kimball: For patients with tumors harboring <unk>.
Kimball: We plan to pursue a chemo therapy, sparing rassam easier better doublet treatment.
Kimball: Including the Arrow asset plus <unk>, along with checkpoint inhibitor.
Kimball: For patients with non G costly disease, we plan to develop <unk> in combination with standard of care chemotherapy.
Kimball: Along with the checkpoint inhibitor.
Kimball: We believe each compound.
Kimball: In our clinical stage <unk> inhibitor portfolio has.
Kimball: <unk> has the potential to transform treatment for patients living with Ras mutant non small cell lung cancer.
Jack Anders: With that I'll turn the call over to Jack.
Jack Anders: Thanks Roy.
Jack Anders: We ended the first quarter of 2025 with $2 1 billion in cash and investments, which we projected can fund planned operations into the second half of 2027 based on our current operating plan.
Jack Anders: R&D expenses for the first quarter of 2025, or $205 7 million compared to 118.0 million for the first quarter of 2024.
Jack Anders: The increase in R&D expenses was primarily due to increases in clinical trial related expenses and manufacturing expenses for our three clinical stage programs with <unk> being the largest driver of the increase given the program is now in two phase III trials.
Jack Anders: Personnel related expenses and stock based compensation expense also increased in 2025 due to additional head count.
Jack Anders: G&A expenses for the first quarter of 2025, or 35.0 million compared to $22 8 million for the first quarter of 2024.
Jack Anders: The increase in G&A expenses was primarily due to increases in personnel related expenses and stock based compensation.
Jack Anders: Associated with additional head count and commercial preparation activities.
Jack Anders: Net loss for the first quarter of 2025 was $213 4 million compared to 116.0 million for the first quarter of 2024.
Jack Anders: The increase in net loss was due to higher operating expenses.
Jack Anders: We are reiterating our 2025 financial guidance and continue to expect projected full year 2025, GAAP net loss to be between $840 million and $900 million.
Jack Anders: Which includes estimated noncash stock based compensation expense of between $115 million and $130 million.
Jack Anders: That concludes the financial update I will now turn the call back over to Mark.
Speaker Change: Thank you Jack.
Speaker Change: We are making meaningful progress as we successfully execute on our 2025 strategic priorities in pursuit of our goal to revolutionize treatment for patients with <unk> cancers.
Speaker Change: A key focus this year is executing on the <unk> Registrational studies in both previously treated pancreatic and non small cell lung cancers.
Speaker Change: I am pleased to share that resolute 302, our ongoing global phase III trial in patients with second line metastatic pancreatic cancer.
Speaker Change: <unk> its strong pace of enrollment in the U S.
Speaker Change: Following regulatory clearances in the EU and Japan, we've also begun enrolling patients in those geographies. We are confident that we'll be able to substantially complete enrollment this year to enable an expected data readout in 2026.
Speaker Change: We are also currently activating study sites for resolve 301, our phase III trial in patients with previously treated Ras mutant non small cell lung cancer.
Speaker Change: We're making good progress toward advancing <unk> into earlier line randomized pivotal trials with planning underway to initiate registrational trials for <unk> in first line and adjuvant pancreatic cancer in the second half of this year.
Speaker Change: Today, we've shared important data that create exciting opportunities for us in both previously treated and first line metastatic non small cell lung cancer and eventually earlier lines of treatment, including treatment approaches that include our new selective inhibitors.
Speaker Change: We continue to expand our clinical programs and follow study patients to enable the initiation of one or more pivotal combination trials in 2026.
Speaker Change: Progressing our earlier stage pipeline, including advancing next generation innovations continues to be an important priority.
Speaker Change: At ACR recently, RMC 527, or $2 12.
Speaker Change: Newton selective <unk> inhibitor was presented in the new drugs on the horizon session.
Speaker Change: We continue to advance the program and expect to reach a clinically stage later this year to enable the initiation of a phase one study next year.
Speaker Change: Finally, we continue to make substantial progress in growing our commercial and operational capabilities and in advancing launch readiness activities in support of our first potential product launch.
Speaker Change: We are making good progress in building, our commercialization capabilities in the United States across functions, including Onboarding, Our U S field medical team.
Speaker Change: We also recognize our important responsibility for ensuring patient access to <unk> globally pending regulatory approvals.
Speaker Change: I'm very pleased to announce that Anthony Van <unk> has joined <unk> as our Chief Global commercialization officer and member of our senior management team.
Speaker Change: Anthony who will oversee the comprehensive commercialization strategy and operations for our portfolio.
Speaker Change: Bring substantial experience from his successful decade long career in the biotech and biopharmaceutical industry.
Speaker Change: Zinc lead significant product portfolios launches, an organizational builds in the U S and major international markets as well as overseeing significant strategic partnerships.
Speaker Change: He will contribute additional strength.
Speaker Change: Two our approach to the U S market.
Speaker Change: And to our evaluation of options for reaching patients internationally.
Speaker Change: Our vision remains to create the industry, leading targeted medicine franchise for patients with Ras cancers.
Speaker Change: This vision is built on three foundational pillars.
Speaker Change: First our pioneering clinical stage <unk> inhibitors have shown our discovery capabilities to be among the most innovative and productive in the industry.
Speaker Change: Second our first class development capabilities have been demonstrated by efficiently progressing multiple assets through first in human studies and advancing into late stage development.
Speaker Change: Third we are building high quality organizational capabilities to ensure we can successfully deliver products to patients.
Speaker Change: Underlying all of this is an exceptionally strong financial position that gives us the wherewithal to continue executing on our strategy and solidifying our position as leaders in the treatment of patients with Ras addicted cancers.
Speaker Change: As we continue to deliver compelling clinical observations and build on our track record of execution.
Speaker Change: We never lose sight of our primary focus patients living with cancer.
Speaker Change: Before we open the call for the Q&A session I'd like to thank the patients and caregivers clinical investigators scientific and business collaborators advisors and shareholders for their commitment.
Speaker Change: Without this support none of the progress we've made would be possible.
Speaker Change: I'd also like to recognize the extraordinary efforts of Radnet employees, who embody tireless commitment to patients and the work they do every day.
Speaker Change: This concludes our prepared remarks for today and I'll now turn the call over to the operator for the Q&A session.
Speaker Change: Thank you.
Speaker Change: At this time, we will conduct a question answer session. As a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced in the interest of time, we will allow one question per participant if you have further questions you may rejoin the queue.
Speaker Change: To withdraw your question. Please press star one one again please.
Speaker Change: Please standby will be compile the Q&A roster.
Speaker Change: Our first question comes from the line of Michael Schmidt of Guggenheim. Your line is now open.
Michael Schmidt: Hi, Thanks for taking my questions and congrats on the progress a lot of information here.
Speaker Change: Just today, but.
Speaker Change: Yes, I had a question on your first line non small cell lung cancer strategy obviously.
Speaker Change: Interesting new data disclosed today for some of the various tablets and.
Speaker Change: Based on your slide it seems like for the <unk>.
Speaker Change: First line patient population, you have sort of focusing in on a triplet of and they are under asset there Exxon and Pembroke as well.
Speaker Change: The only combination, but we haven't seen data yet today, but.
Speaker Change: Looking at some of the other doublets may perhaps could you just comment on your confidence and Tolerability of that trip flat just based on some of the rash rates that <unk> seen in some of the tablet and some of the dose reductions there.
Michael Schmidt: Hi, Michael Thanks for your question, maybe we can speak to that.
Michael Schmidt: Thanks for the question so.
Michael Schmidt: We are optimistic.
Michael Schmidt: Given the profile we've seen so far obviously, we are still in the dose optimization and we have not yet defined the final dose for the triple combination.
Michael Schmidt: We have characterized the monotherapy fairly well, we're not seeing any new safety signals emerging and regarding 67 are known characterized such as rash regarding broadcom asset.
Michael Schmidt: Bob I'd, just add that QVC, both are within what we have expect to observe with the monotherapy.
Michael Schmidt: I think when we have a longer follow up and define the dose.
Michael Schmidt: Be sharing those prior to initiating our phase III trial.
Okay.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Marc Frahm of TV Cowen. Your line is now open.
Marc Frahm: Hi, Thanks for taking my questions and congrats on all the data sets today.
Speaker Change: Maybe just looking across the various combination data sets you presented.
Speaker Change: Struck by I mean, it looks like the vast majority of the responders are still ongoing as of the last.
Speaker Change: Data cutoff.
Speaker Change: Again, PFS is clearly immature, but maybe can you give us a sense of just kind of the average follow up in those cohorts.
Speaker Change: Maybe you can give a sense of where durability and PFS may be headed and then kind of looking longer term.
Speaker Change: What type of data set do you think you need to gather before you can.
Speaker Change: Formally declare phase III intent for.
Speaker Change: For these various combinations you just need to get a little bit more data to get more comfortable on safety and select the final dose or is it you need real robust PFS estimates kind of what's needed there.
Marc Frahm: Hey, Mark Thanks for your question I think the first question.
Speaker Change: Really it's something that refers faxes swimmer plot that we provided.
Speaker Change: In December and I think those are available. So I'd recommend just taking a look at those in terms of.
Speaker Change: Follow up time for those we don't have an update today.
Speaker Change: On that because we haven't done a fresh data cut the December data.
Speaker Change: Had those duration of treatment.
Speaker Change: Parameters listed.
Speaker Change: Your second question. Your main question I think is about what's really gating now to the triplet.
Steve Kelsey: Steve you want to comment on that.
Speaker Change: So I mean, let's be clear.
Speaker Change: There is a differentiation here between the <unk> C program and the non <unk> program.
Speaker Change: The <unk> 12, the non GE Telsey program is pretty much on gates. It it's more of a sort of operational execution type question I think we've shown very conclusively that.
Speaker Change: Adding <unk> to the <unk> schedule is tolerated and the efficacy is pretty impressive.
Speaker Change: I don't think we need any more data to press ahead with that we just have to grind through the.
Speaker Change: The operational and regulatory milestones that you have to go through in order to get a study off the ground.
Speaker Change: As way alluded to in his prepared remarks.
Speaker Change: The GE 12 seat program is currently gated by optimizing the dose of that Russell doublet combination of direct from Russia or they are all <unk>.
Speaker Change: We have to because it's a novel novel combination is going into patients who have never received treatment for that.
Speaker Change: So that would also wholesale loan cap. So we really have to get the dose right to get that.
Speaker Change: Dose right to the SaaS faction of the company, but also to the satisfaction of the regulators on the payers on the prescribers.
Speaker Change: So a little bit more refinement is needed we're pretty close we have a range within which we're operating.
Speaker Change: I don't think it will take too long, but that's essentially what's gating. The GE 12 see first line non small cell lung cancer program.
Speaker Change: Okay.
Speaker Change: And so again.
Speaker Change: <unk> is PFS required or waiting for PFS, and I think thats, a simple answer to that.
Speaker Change: This is really not driving that decision we understand TFS based on the second line data and now we have confidence that the response rates are very competitive.
Speaker Change: So I think we're good to go from that perspective, yes, we should say we should add both from.
Speaker Change: Published literature, and historical data and from our own.
Speaker Change: Sorry.
Speaker Change: Intense in house analysis.
Speaker Change: Response rate is.
Speaker Change: Reasonable a PFS and <unk> cell lung cancer that has not been the case for pancreatic cancer, but for lung cancer. It is so we were.
Speaker Change: We're more confident about.
Speaker Change: A link between our response rates that we have just.
Speaker Change: Disclosed in lung in the lung cancer patients and the.
Speaker Change: Predicted PFS that we will achieve.
Speaker Change: And of course, PFS in lung cancer more compelling as a regulatory endpoint. Unlike in pancreatic cancer, where we have the overall survival. So so it's going to look at it.
Speaker Change: A lot more going forward.
Speaker Change: <unk>.
Speaker Change: Okay. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Eric Joseph of Jpmorgan. Your line is now open.
Eric Joseph: Thanks for taking the questions and let me also just incur lucky data.
Speaker Change: Okay is there a lot to digest.
Steve Kelsey: Maybe Steve I could.
Speaker Change: You can expand a little bit on your last comment.
Steve Kelsey: The types of datasets.
Speaker Change: Publications, perhaps.
Steve Kelsey: Greg your confidence.
Steve Kelsey: Response rate higher response rates will be a predictor for better PFS outcomes.
Speaker Change: Outside of your own.
Steve Kelsey: Pipeline work.
Speaker Change: Okay.
Speaker Change: I'm also curious about whether you are continuing to enroll the frontline lung.
Speaker Change: Lung cancer cohorts.
Speaker Change: <unk>.
Speaker Change: To sort of build upon the dataset that you are observing so far.
Speaker Change: Finally on the safety side. This is more than one question, but.
Speaker Change: On the safety side.
Speaker Change: Non clinical the subclinical Qt signal that youre seeing with the right combination of your confidence that it falls.
Speaker Change: Sure.
Speaker Change: It comes with a greater with the triplet regimen. Thank you.
Eric Joseph: I think the first part was a question. Thank you. Thank you Eric I think the first part was a question about the literature, reflecting predictive utility response rates durability, and we can provide provide some references.
Eric Joseph: I'll find that.
Eric Joseph: By the way, it's something we've heard from investors for the last several years why don't we use response rates more so I think it's pretty generally well known in our observations are very consistent with that do you have anything you want to ask.
Eric Joseph: What was the second part.
Speaker Change: Thank you T J D. I'll take your question on the <unk> signal.
Speaker Change: I thought it would be greater if you want to comment on that yes, we have not seen that could be the case certainly we've reported eqt's signal here its actually on par, we even lower than what we serve with the monitor obviously with longer follow up.
Speaker Change: And then larger patient sample, we do not expect.
Speaker Change: There is going to be enhanced in the Q T. So I think well we can line up what the market.
Speaker Change: As reported.
Speaker Change: In their label.
Speaker Change: I don't think and consistent with the larger earlier on and longer follow up there on rapid data set that we showed at <unk>.
Speaker Change: Beginning here, which I think makes that makes that point pretty clear.
Speaker Change: Middle question was whether you are continuing to enroll.
Speaker Change: These political overtime.
Speaker Change: Okay.
Speaker Change: Well theres dose optimization now ongoing so.
Speaker Change: Pretty much answers that.
Speaker Change: Okay. Thanks for taking the questions and congrats on the updates.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Jonathan Chang of Leerink Partners. Your line is now open.
Speaker Change: Hi, guys. Thanks for taking my question.
Speaker Change: How are you thinking about the duration of clinical benefit of <unk>.
Speaker Change: Persistent mutant selective inhibitors like <unk> and <unk>.
Speaker Change: <unk>.
Speaker Change: What are the reasons for why one could be more careful than the other and how could this and other factors impact how you're thinking about future development strategy.
Speaker Change: Al.
Speaker Change: Yeah.
Speaker Change: Thanks, Jonathan maybe I'll comment on that a minute.
Speaker Change: <unk> wants to add anything to it I don't think we have any direct.
Speaker Change: Head to head comparison, because the <unk> study was done.
Speaker Change: Tumors that carry different mutations than the Alere aggressive studies, so we really can't compare though so we can't say which is <unk>.
Speaker Change: So the other and they are not matched for other prognostic factors as well.
Speaker Change: Don't think we have any information on it.
Speaker Change: <unk>.
Speaker Change: If you're wondering what what we might predict I don't know we will see.
Speaker Change: And ultimately we're combining these anyway.
Speaker Change: Both ways.
Steve Kelsey: When Steve talked about and so what ought to get the benefit of whatever the pros are on each side of that.
Okay.
Speaker Change: Is there anything more specific that you are trying to get out there.
Speaker Change: Okay.
Speaker Change: I was just thinking about how in situations, where you might be considering.
Speaker Change: Advancing <unk> or a new collective one or maybe a combination of both.
Speaker Change: How you might consider.
Speaker Change: Things like duration of clinical benefit.
Speaker Change: How long patients stay on treatment.
Speaker Change: In addition to other considerations.
Speaker Change: It's the number one consideration.
Speaker Change: That's the key driver of the sort.
Speaker Change: Patient experience is assuming that we obviously have.
Speaker Change: Combination.
Speaker Change: <unk> can tolerate for the time that they are all in the treatment without having a miserable life.
Speaker Change: It's the number one consideration.
Speaker Change: The the mechanisms of escape.
Speaker Change: From the maintenance selective inhibitors are very different from the mechanisms of escape from direct silver asset we have only disclosed mechanisms of escape data for direct some restaurant in pancreatic cancer, but it is very different pattern of escape from what's been disclosed for mutant selective inhibitors of non small cell lung cancer that's why.
Speaker Change: We are so enthusiastic about the combination because.
Speaker Change: All of those putative mechanisms of escape all covered by the combination.
Speaker Change: The novel Ras mutations that emerge on selective inhibitors are inhibited by <unk>.
Speaker Change: And the putative amped.
Speaker Change: Amplification of mutant K, Ross that we might see in lung cancer, which we have seen in pancreatic cancer is suppressed by hitting the mutant harder with the combination of the two restaurant inhibitors together. So so we do expect the PFS to be longer with the combo with either agent.
Speaker Change: Alone and.
Speaker Change: As we as we described the increase in response rate as a good harbinger of that we just have to wait for that data to mature in order for it to be worthwhile disclosing publicly because immature PFS data isn't helpful to anybody.
Speaker Change: Yes.
Speaker Change: Steve's comments are entirely consistent with what we have reported in the preclinical context I think we showed.
Speaker Change: Two figures are representative of a much larger data set that we presented over several scientific meetings that the combination does tend to deliver significantly greater benefit and including the figure on the right side of that slide slide.
Speaker Change: I'm not sure what it is in your deck, but that right figure shows the combination of the doublet plus anti PD one it basically.
Speaker Change: Abided for no progression in any of the animals and that experiment across 100 days. So I think the totality of the evidence is supportive of what you suggested.
Speaker Change: Okay.
Speaker Change: Got it thanks for taking the question.
Speaker Change: Okay.
Speaker Change: Thank you. Our next question comes from Kelly <unk> of Jefferies. Your line is now open.
Speaker Change: Hi, This is Claire on for Corey Thanks for taking our question congrats on the data.
Speaker Change: Sure.
Speaker Change: So for lung cancer.
Speaker Change: The combination of data and it seems like you have multiple paths to pursue the opportunity.
Speaker Change: You also have to conclude that it's development Thats why all of us.
Speaker Change: Maybe other early initiatives such as Keith can you tell me so maybe from a resource allocation perspective, what are the key criteria.
Triumph.
Speaker Change: Already between those developments.
Speaker Change: Also for lung cancer, specifically, how should we think about the cadence of initiating pivotal combination trials and you mentioned.
Speaker Change: You might initiate combination trials in time Tony.
Speaker Change: Thank you.
Speaker Change: Okay. Thank you Clara let.
Speaker Change: Let me start with the second comment about timing I mean, we have provided some timing and I think that's all we can provide today. We do have of course direct sub massive in non small cell lung cancer already underway in the 301 study.
Speaker Change: But then in terms of first line.
Speaker Change: And combination studies, we would expect to begin rolling those out.
Speaker Change: In 2026.
Speaker Change: In terms of resource allocation I don't think Theres, a simple single word or sentence answer too.
Help clarify that for you, it's obviously, a pretty complex and rich set of opportunities.
Speaker Change: We have an embarrassment of riches.
Speaker Change: Each clinical study we've done so far opens up three exciting new pivotal trials that we could consider doing so.
Speaker Change: It certainly does create some need for prioritization, we start with the clinical data the biological rash.
Speaker Change: Rationale behind the data we look at the competitive landscape.
Speaker Change: As Steve pointed out ultimately what's most important is to provide durable clinical benefit. So that's a key characteristic that gets ranked in all of this.
Speaker Change: So many many factors.
Speaker Change: And at this point, we're able to proceed.
Speaker Change: With a large chunk of the.
Speaker Change: The priorities that we have defined.
Speaker Change: Sickly moving everything forward right now that that is ready to move forward in 2025, and we will continue to do that into 2026th constantly looking at justification for for the investments, but also trying to achieve the goal.
Speaker Change: That we've alluded to several times here, which is to deliver.
Speaker Change: Significant changes on behalf of patients across Ras mutations tumor types.
Speaker Change: And lines of therapy, and we think we're best positioned in the industry to do that.
Speaker Change: Okay.
Speaker Change: Thank you.
Speaker Change: Our next question is from Ellie Merle of UBS. Your line is now open.
Ellie Merle: Hey, guys. Thanks for taking my question and congrats on all the progress.
Ellie Merle: Just curious your latest thinking on a potential commercial strategy ex U S.
Ellie Merle: And your general philosophy around potential partnering.
Ellie Merle: And then just in terms of the designs for the pivotal combination trial or trials.
Ellie Merle: Could you give us maybe any more color on when you might expect to meet with FDA to discuss the design.
Ellie Merle: And when we might be able to learn more about the specifics.
Ellie Merle: From our end.
Speaker Change: Hi Ali Thanks for your question on the second point.
Speaker Change: Unfortunately, no we don't typically sort of lay out the timeline for our future interactions our ongoing interactions with the FDA.
Speaker Change: Our pattern that we've tried to establish is.
Speaker Change: Once we have definitive plan for a close to a definitive plan.
Speaker Change: Often provide some sort of update including the data to support.
Speaker Change: Or whatever commitment were making but.
Speaker Change: Beyond that I can't give you any further.
Speaker Change: Higher resolution answer to it.
Speaker Change: Yeah.
Speaker Change: With regard to the ex U S strategy, that's obviously very much on our minds as I think it is on our investors since I first raised.
Speaker Change: Almost two years ago now the possibility that we might.
Speaker Change: Engage with others to help us.
Speaker Change: Commercialize outside the U S. While we would certainly focus on retaining the U S.
Speaker Change: The U S market.
Speaker Change: We have had strong interest from multiple.
Speaker Change: Global pharma companies.
Speaker Change: We've had concrete and productive dialogue with them and without a doubt we could enter an attractive partnership and Thats really.
Speaker Change: Creates a great deal of.
Speaker Change: Optionality for us.
Speaker Change: We've also felt no need to rush into such a partnership and we've continued to use time to our advantage. We continue tracking that portfolio tracking the assets progress trajectory. We've also tracked organizational.
Speaker Change: Progress and trajectory and all of those have continued to exceed our expectations. So now we're in the position to assess.
Speaker Change: The pros and cons of all the options.
Speaker Change: That are available to us and we have to make a strategic judgment, which we're just not ready to make today, which is what's the best approach for serving patients not only in the U S. But also internationally and it also serves our business and we are continuing to look at that but now through the lens of where we are in 2025.
Speaker Change: With a very different organization in terms of depth and breadth.
Speaker Change: Program's maturity programs and also with the addition, now of Anthony who joins the team and can bring a <unk>.
Speaker Change: Broad commercial perspective to it as well so we will complete that analysis at some point and continue to provide updates as appropriate.
Speaker Change: Great. Thanks.
Speaker Change: Thank you.
Speaker Change: Now concludes the question answer session I would now like to turn it back to Mark Goldsmith for closing remarks.
Speaker Change: Thank you operator, thanks to everyone for participating today and for your continued support of Revolution medicines.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change: Yeah.
Speaker Change: Okay.
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