Revolution Medicines, Inc. Common Stock FDA announcement

Thank you for joining Revolution Medicines webcast to discuss the FDA approval of daraxonrasib, now approved under the brand name RASONQUE. We have issued a press release announcing the approval and posted the presentation that accompanies today's remarks on the investors section of our website. Before we begin, I would like to remind everyone that today's discussion will include forward-looking statements regarding our business, commercialization plans, clinical development programs, and other future events. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those described. Please refer to our SEC filings for a discussion of these risks. Joining me today are Dr. Mark Goldsmith, our Chairman and Chief Executive Officer, Dr. Alan Sandler, our Chief Development Officer, and Anthony Mancini, our Chief Global Commercialization Officer.

Dr. Wei Lin, our Chief Medical Officer, and Jack Anders, our Chief Financial Officer, will join us for the Q&A portion of today's call. With that, I will turn the call over to our Chief Executive Officer, Dr. Mark Goldsmith.

Mark? Thank you, Ryan. Today marks an historic step forward for patients living with metastatic pancreatic cancer.

Eligible patients now have a new treatment option that directly addresses the main cause of their disease. I am gratified to share that the U.S. Food and Drug Administration has approved RASONQUE for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multi-agent systemic therapy. This approval validates more than a decade of work aimed at pancreatic cancer, a primarily RAS driven disease and one of the most difficult challenges in medicine, cancer biology, and drug discovery. RASONQUE, known generically as daraxonrasib, is an oral, once daily, RAS(ON) multi-selective inhibitor targeting RAS proteins. This groundbreaking medicine is supported by compelling clinical evidence in this aggressive cancer that has been characterized by a high symptom burden, bleak prognosis, and few meaningful therapeutic advances.

This approval confirms the potential for bold scientific innovation to fundamentally change how RAS-driven cancers are treated. At Revolution Medicines, we invested our full resources and capabilities into one of the most important challenges in oncology, discovering and developing oral medicines capable of directly inhibiting multiple common cancer-causing forms of RAS, a disease target that had frustrated scientists for decades. Meeting this ambition requires scientific innovation while standing on the shoulders of others, boldly challenging dogma, deep collaboration and perseverance across our organization, and close partnership with investigators worldwide. Today, that collective effort has resulted in RASONQUE, the first FDA-approved targeted medicine in pancreatic cancer that defies its main cause, RAS.

Before going further, I want to thank every patient in the RASolute 302 clinical program and their families, the investigators, research nurses, study coordinators, and site personnel who made the results possible, the advocacy organizations that support this community, and the entire Revolution Medicines team. We are profoundly grateful for the trust patients place in us by generously participating in clinical trials even before a medicine is validated. With RASONQUE now approved, let me highlight four messages that frame what today means for patients and for Revolution Medicines. First, the approval is grounded in the unprecedented overall survival benefit demonstrated in the registrational phase III RASolute 302 trial, which we believe is one of the most meaningful treatment advances achieved in metastatic pancreatic cancer.

Second, today's approval positions RASONQUE to becoming a practice-changing new standard of care for patients with previously treated metastatic pancreatic cancer and for those who are not candidates for multi-agent systemic therapy. We believe it has the potential to change expectations for patients across these settings. Third, Revolution Medicines is launch-ready and fully operational in the U.S. Our commercialization organization, manufacturing and supply network, market access capabilities, and patient support infrastructure enable us to begin serving patients immediately. Finally, beyond marking the successful development of a single pioneering medicine, this approval provides the first definitive proof point for our bold RAS(ON) strategy, advancing both multi-selective and mutant-selective inhibitors enabled by our proprietary tri-complex platform across multiple RAS-addicted cancers. It is an important step toward building a leading global oncology company serving patients with RAS-addicted cancers.

We view today not as a finish line, but as a beginning of a much larger opportunity to improve outcomes for patients. Before we review the clinical data, I want to highlight what this image represents. For decades, RAS was viewed as being beyond the reach of direct inhibition, while meaningful treatment advances in metastatic pancreatic cancer, a disease primarily caused by RAS, remains limited. Today, RASONQUE represents a transformative step toward changing that. For patients, it represents the possibility of living longer than with chemotherapy and having more time before pain worsens or quality of life declines. For physicians, it represents having a new targeted medicine to offer eligible patients and with it, renewed hope in a setting where meaningful advances have been limited. For investigators, it reflects years of scientific innovation, collaboration, and clinical excellence.

And for the Revolution Medicines team, it marks the moment we have pursued tirelessly for years, delivering to patients a highly innovative and impactful medicine that we discovered and developed. I will now turn it over to Alan, who will put the historical treatment landscape in context, explain how the early clinical evidence informed our phase III development strategy, and then walk us through the pivotal phase III RASolute 302 result that supported today's approval.

Alan? Thank you, Mark. Historically, metastatic pancreatic cancer has been one of the most devastating and difficult to treat cancers.

Despite being predominantly driven by RAS, targeted therapies have been available only to a very small number of patients whose tumors carry rare, actionable non-RAS mutations. Published epidemiology and treatment pattern analyses indicate that approximately 55,000 patients are diagnosed each year in the U.S. with metastatic pancreatic cancer, including both new diagnoses and patients who progress from a pre-metastatic stage of disease. In the RASONQUE era, approximately 74% of these patients, or 41,000 per year, received first-line treatment with cytotoxic chemotherapy, while approximately 26% received no systemic therapy. Of those who received first-line treatment, fewer than half, approximately 19,000 patients, went on to receive second-line treatment.

Intravenous chemotherapy regimens based on either 5-FU or gemcitabine have been widely used across all lines of treatment for metastatic disease, typically requiring regular visits to a hospital or infusion center. These patterns illustrate both the aggressive nature of metastatic pancreatic cancer and the substantial attrition across lines of therapy that characterize the treatment landscape. Against that backdrop, we look for evidence that directly inhibiting active RAS could produce meaningful clinical activity across RAS-driven cancers. Across separate phase I studies, RASONQUE, as a single agent, demonstrated encouraging and differentiated anti-tumor activity in previously treated and first-line metastatic pancreatic cancer, as well as in other tumor types, including previously treated RAS mutant non-small cell lung cancer.

The strong signals of clinical activity in single-arm studies across multiple tumor types and in different lines of treatment supported our decision to initiate a wide-ranging phase III program, which is still underway, to rigorously evaluate RASONQUE in these settings. This progression from early clinical evidence to broad registrational development is reflected in a first set of five randomized phase III trials with RASONQUE shown here. More than 2,000 patients have now been treated with RASONQUE in a wide set of early and late-stage clinical studies in multiple tumor types and treatment settings, providing a substantial and growing body of clinical experience. So far, the phase III program includes four trials in pancreatic cancer, spanning previously treated metastatic disease, first-line metastatic disease, and the adjuvant setting for resectable disease, as well as a fifth trial in previously treated RAS mutant non-small cell lung cancer.