Revolution Medicines, Inc. (RVMD) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to Revolution Medicine Corporate Update Call. [Operator Instructions]. And now I'd like to introduce your host for today's program, Ryan Asay, Senior Vice President, Corporate Affairs. Please go ahead, sir.

Hello, everyone. Thank you for joining Revolution Medicines webcast to discuss the FDA approval of daraxonrasib, now approved under the brand named RASONQUE. We had 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. And 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, who will join us for the Q&A portion of today's call. With that, I'll turn the call over to our Chief Executive Officer, Dr. Mark Goldsmith. Mark?

Thank you, Ryan. Today marks a 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'm 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 multiagent systemic therapy. This approval validates more than a decade of work aimed at pancreatic cancer, 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-cellective 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 define its main cause, RAS. Before going further, I want to thank every patient in the Resolute 302 clinical program and their families. 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 clinical trials even before a medicine is validated. With RASONQUE now approved, let me highlight 4 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 United States. 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 RASON strategy, advancing both multi-selective and mutant selective inhibitors enabled by our proprietary tri-complex platform across multiple RAS-addicted cancers. And it is an important step towards building a leading global oncology company serving patients with RAS-addicted cancers. We view today not as a finish line, but as the 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 it as being beyond the reach of DIRECT inhibition, while meaningful treatment advances in metastatic pancreatic cancer, a disease primarily caused by RAS remained limited. Today, RASONQUE represents a transformative shift towards changing that. For patients, it represents the possibility of living longer than with chemotherapy and having more time before paying versions 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 Retina 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'll 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 Resolute 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 analysis 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 progressed from a premetastatic stage disease. In the pre-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 receive 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 a 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 antitumor 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 as on in these settings. This progression for early clinical evidence to broad registrational development is reflected in a first set of 5 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 4 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. RASolute 302, a global study comparing RAS monotherapy to standard of care cytotoxic chemotherapy in patients with previously treated metastatic pancreatic cancer is complete and led to today's approval of RASONQUE. This approval provides a significant element of Phase III validation for our RAS inhibitor approach to RAS-addicted cancers. The other Phase III studies are in progress and uses beyond the approved indication remain investigational. I'll now summarize RASolute 302 data supporting today's approval followed by key elements of the approved label. The results of RASolute 302 were presented in the plenary session at the 2026 ASCO Congress in May and published simultaneously in the New England Journal of Medicine. RASONQUE demonstrated an unprecedented overall survival benefit, reducing the risk of debt by 60% and nearly doubling median overall survival versus chemotherapy with a manageable safety profile. As a medical oncologist, the most important point to me is straightforward. Patients treated with RASONQUE lived significantly longer. As shown in the intent-to-treat population, which included patients with and without an identified tumor RAS mutation, RASONQUE produced a statistically significant and clinically meaningful improvement in overall survival versus standard chemotherapy. The overall survival benefit was also consistent across clinically relevant, predefined patient subgroups. As with any subgroup analysis, these results should be interpreted with appropriate caution. Nonetheless, considered in aggregate, this consistency supports confidence in the robustness of the overall results. RASONQUE also demonstrated a statistically significant improvement in progression-free survival as assessed by blinded independent central review. The alignment of the overall survival and progression-free survival findings further strengthens the evidence supporting approval. The patient-reported outcomes contribute an important patient center dimension to the RASolute 302 results compared with chemotherapy as I significantly delayed deterioration in patient-reported measures of both pain and overall quality of life. For patients with metastatic pancreatic cancer, delaying worsening of pain and preserving quality of life are essential treatment goals, making these findings meaningful alongside the survival benefit. Turning to safety. We did not identify any new safety signals in the profile observed in RASolute 302 compared to earlier studies. Treatment-emergent adverse events were generally manageable with established management and dose modification strategies and treatment discontinuations due to adverse events were substantially less frequent than with chemotherapy. Together with the efficacy findings, these results support a compelling benefit/risk profile for RASONQUE. The U.S. prescribing information reflects the strength of the evidence supporting this approval. RASONQUE is indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates multiagent systemic therapy. Importantly, the indication is not restricted by tumor RAS mutation status and no companion diagnostic is required. RASONQUE is administered orally once daily. The prescribing information includes detailed guidance on dosage and administration, prophylaxis, management of key adverse reactions and relevant drug interactions. Physicians should review the full prescribing information before prescribing. The label enables physicians to begin prescribing RASONQUE immediately for eligible patients translating years of clinical research into patient benefit. RASONQUE is available beginning today. With that, I'll hand it over to Anthony Mancini.

Thanks, Alan. Today's approval is grounded in the unprecedented overall survival benefit and broader clinical evidence demonstrated in RASolute 302. It marks an important advance for people living with metastatic pancreatic cancer. From the outset, our commercialization strategy has been focused on the patient. We will ensure that eligible patients can access RASONQUE quickly, and we will support them throughout their treatment journey. With RASONQUE now approved, our focus shifts from preparation to execution. Our launch strategy is anchored in 3 priorities: first, enable health care providers and eligible patients with the resources needed for an optimal treatment experience. Through education, patient services and field support, we aim to enable rapid adoption and to help patients remain on therapy. Second, establish RASONQUE as the new standard of care for eligible patients with metastatic pancreatic cancer. The Phase III RASolute 302 results that Alan just described, including the near doubling of median overall survival, a statistically significant improvement in progression-free survival, meaningful improvements in patient-reported outcomes and the manageable safety profile position RASONQUE as a truly practice-changing therapy; and third, ensure broad coverage and seamless patient access from day one. Our market access organization and patient services capabilities are fully operational and engaged. This remains a setting of profound unmet medical need where patients have historically had limited treatment options and poor outcomes. We believe RASONQUE can meaningfully change the treatment outlook for eligible patients. successful oncology launch requires more than a strong clinical profile. It requires reaching every stakeholder involved in the care of pancreatic cancer patients. Approximately 40% of patients are treated at academic centers, where many investigators and opinion leaders are already familiar with the RASONQUE clinical program which we believe will help drive early adoption. The remaining 60% of patients received care in community oncology practices, making broad community education and practice level engagement equally important. We've built a world-class commercialization organization with deep experience in oncology, oral oncolytics, gastrointestinal cancer and new product launches. Our U.S. medical science liaisons have been active for over a year, engaging clinical experts through scientific exchange. Our thought leader liaison team has been engaging appropriately with opinion leaders to gather perspectives on the treatment landscape and potential implementation needs. Those insights have helped shape our launch readiness. To date, our field-based market access teams have engaged key integrated delivery networks and large community accounts as well as payers representing more than 80% of covered lives through preapproval information exchange. Our sales team is set to engage with the broad oncology health care provider community. Overall, our field-based teams are deployed to enable a coordinated launch by advancing clinical understanding, preparing the breadth of accounts, addressing access barriers and helping eligible patients benefit from RASONQUE. Since launch priority is helping eligible patients begin therapy prompt and remain supported throughout treatment. RASONQUE is now commercially available in the United States at a wholesale acquisition cost of $3,800 for a 30-day supply based on the recommended daily dose. We believe the price reflects the unprecedented overall survival benefit and broader clinical value demonstrated in RASolute 302. Our market access and patient services infrastructure is fully operational to support broad patient access across channels. Our comprehensive patient services program on past provides integrated support from prescription through ongoing treatment. The program includes coverage navigation, financial support adherence support and educational resources for patients, caregivers and health care teams. Importantly, our team will also be focused on ensuring continuity of care for patients who have been receiving RASONQUE through the expanded access program, supporting a smooth and seamless transition to commercial supply and applicable insurance coverage. Eligible commercially insured patients may qualify for co-pay assistance as low as $0. Dedicated support teams will work with providers and specialty pharmacies to navigate coverage and coordinate access. Our goal is simple: help remove barriers to access, so physicians can focus on treatment and patients can focus on their care. In the United States, our launch is now underway with commercial supply, distribution, patient services and each of our field teams fully operational. Internationally, we have established teams in Europe and Japan and are rapidly expanding our capabilities in preparation for future potential pluses. The European Medicines Agency's phased review of daraxonrasib is underway. We intend to address the broader international opportunity in phases market by market. I should note that outside the United States, daraxonrasib is investigational and has not yet been approved by any regulatory authorities. We will, however, be able to respond to unsolicited requests from health care providers who have decided to prescribe daraxonrasib to suitable patients in countries where it has not yet received regulatory approval on a paid basis through global name patient access. This process will vary from country to country depending on local laws, regulatory and access requirements. Additional information about global name patient access is available on our website. Together, these capabilities provide the foundation for a successful U.S. launch and position us for future global expansion as additional approvals are updated. With that, I'll hand the call back to Mark.

Thank you, Anthony. As you've heard today, this approval represents more than the successful development of one pioneering medicine. It validates the strategy Revolution Medicines has long pursued by combining deep biological insights, innovative chemistry and bold but disciplined clinical development we set out to create and validate new targeted medicines that transform outcomes for patients with RAS-driven cancers. Today, RASONQUE make that vision a reality and begins our next chapter. Our immediate priority is clear: deliver RAS ON-Q to eligible patients across the United States and establish it as a practice-changing new standard of care. In parallel with U.S. launch, we are advancing launch readiness in Europe and Japan and expect to address additional international markets in phases subject to regulatory approvals. The RASONQUE MDA is included in the FDA's Project Orbis initiative, which provides a framework for concurrent review of oncology applications by participating international health authorities. Today's U.S. approval provides a foundation for our ambition to build the leading global pancreatic cancer franchise. Our development strategy extends well beyond today's indication. Four additional global Phase III registrational programs are underway in pancreatic cancer, spanning first-line metastatic and resectable disease, and using complementary monotherapy and combination strategies involving RASONQUE and [indiscernible] our RASON-G12D- selective covalent inhibitor. These programs are designed to address diverse patient needs across the treatment continuum. Our ambition is not simply to participate in pancreatic cancer care, but to improve patient outcomes by redefining treatment across a wide range of cancer types caused by RAS. That ambition extends across our broader portfolio. RASONQUE is the first approved targeted medicine to emerge from our broad and differentiated pipeline of oral RAS inhibitors, spanning multiple RAS mutations, tumor types and treatment settings. The experience of successfully discovering, developing and now delivering RASONQUE strengthens every part of our organization. It deepens our understanding of patients expands our relationships with physicians and treatment centers, reinforces our commercial capabilities and create scientific and medical insights that can accelerate the development of future medicines. Discover, develop and deliver are more than words on a slide. Together, they describe an integrated strategy for fulfilling our mission, discovery fuels development, development creates opportunities to deliver innovative medicines. Commercialization in turn, generates scientific and clinical insights that inform the next generation of discovery and development. RASONQUE now approved and entering clinical practice that virtuous cycle can operate in a fundamentally new way for revolution medicines. For the first time, our research scientists development teams a commercial organization are connected through an improved medicine in everyday clinical use, which will enable us to incorporate feedback from an even broader patient and prescriber universe as we continue driving innovation on behalf of patients. This new phase provides a robust foundation for building an industry-leading global targeted medicine franchise RASONQUE is the first approval proof point for this strategy. And our mission is to translate the breadth of our science and pipeline into multiple transformative medicines that improve outcomes for patients with RAS predictive cancers. Today's approval is a compelling and exciting step towards realizing that vision. Before we open the call for questions, I want to close where I began with patients. Behind every data point is a person and a family facing an extraordinarily difficult diagnosis, bringing RASONQUE to these patients is essential to our mission. To the patients and families, investigators, employees, collaborators and shareholders who help make today possible, thank you. We also recognized the creative vision of Greg Bedin and the pioneering scientists at [indiscernible]. Their early work established both the initial technology foundation that became part of Revolution Medicines 8 years ago, and a new paradigm that inspired our discovery work leading to this consequential milestone. We are honored by today's approval, committed to bringing RASONQUE to patients and energized by what comes next as the revolution continues. With that, I'll turn the call over to the operator for the Q&A portion of the call.

[Operator Instructions]. Our first question comes from the line of Michael Schmidt from Guggenheim.

Yes, congratulations on this great accomplishment. It's clearly a great day for patients. Mark, as we think about the potential launch ramp here, to remind us of the patients that are already on the early access program, what are the logistics and timing for those to potentially roll over to becoming commercial patients? And what is your expectation longer term, how fast you can reach patients in that community as well beyond epidemic centers?

Yes. Thank you for your questions, Michael. I think Anthony Mancini can comment on both of those.

Yes. Thanks, Michael, for the question. The patients on the on the U.S. EAP following the U.S. approval will be transitioning to within a few months. I think it's important to note that on path, our patient support program will be available to assist all patients who've been prescribed a on, including those in the EAP program and new patients. for U.S. patients who are already receiving daraxonrasib and the EAP. We will work very closely with treating physicians at all sites to support transition to commercially available treatment as clinically appropriate. And those who are pending medical review or who have been medically approved but not yet shipped product. at the time of approval, we'll need to access RASONQUE through commercial channels. So the E&P portal will be closing today, but available for a limited transition period. And our intent is really to support continuity of care for eligible patients and work very closely with all of the key centers to ensure this happens as quickly as possible, but we estimate that will take a couple of months.

Thank you. And our next question comes from the line of Brian Cheng from JPMorgan.

As we think about the launch here, what kind of metrics could we get during their upcoming earnings call to track the launch over time? And then we have a quick follow-up.

Thanks, Brian, you're giving Anthony more opportunity to speak than in any prior meeting.

Yes. Look, we're going to evaluate launch progress across a range of different indicators, including physician adoption and patient access, treatment continuity and, of course, financial performance. will provide appropriate context on launch progress based on the indicators we believe are most relevant at each stage of the launch and will include things like net sales some patient adoption metrics, prescriber adoption and coverage. And that information, of course, may evolve over time as the launch matures and as we gain additional experience in the market.

Great. And then just on the RASONQUE potential usage in locally advanced setting, I'm just wondering if there's any potential for NCCN guideline to enable usage there as we do see some usage some usage for other therapies enabling usage off-label for local events. So I'm curious if there's any to potential there.

Thanks for that question. I think Dr. Sandler can comment on that.

Yes. So again, thanks for the question. We -- in terms of locally advanced, that is an area certainly of interest that we're going to be looking to pursue specifically in the future. The label itself is based specifically, of course, on 302 in the previously treated population, and then those patients not a candidate for multi agent systemic therapy.

Dr. Lin, do you want to add something to that?

Yes. Historically, the NCI guideline does provide guidance based on the metastatic standard care and translate that data for use in local advanced. However, to date, I think that's going to be a decision that's going to be weighed by the physician and their patients.

And our next question comes from the line of Tyler Van Buren from TD Cowen.

Congratulations on this transformative approval of milestone for patients. So I understand that RASONQUE is now available by prescription. But for the new non-EAP commercial patients, how long will it take for them to get commercial or pay drug ENHANZE? Could this be faster than the EAP? And do you expect it to be a matter of days or weeks? And perhaps as a follow-up, how do you expect coverage to progress? Thank you.

Nice to hear from you. Back to Anthony.

Yes. Thanks, Tyler, for the question. I think as far as the availability of the product, as we discussed earlier, the product is available. and physicians can prescribe it as of today. As far as coverage, a couple of comments, I think, in terms of what is normal in an oncology launch is that in the early stages, we expect that very quickly that payers will prescribe their medical policy will change their medical policy and publish those. But in the meantime, it's quite common that approval will be gained through medical exception, and we expect that to happen with RASONQUE. And -- but we expect patients to be able to access that relatively quickly. So we're -- again, as I mentioned, we've had very robust payer preapproval information exchanges and we expect to be able to get approval through medical exception relatively quickly that answers the question, Tyler.

And our next question comes from the line of Charles Zhu from LifeSci Capital.

Hello, everyone. Congrats on everything, A couple of quick ones from me. First, how is chemo in eligibility being defined? Are there clinical criteria only? Or is there some sort of a patient desire factored in as well? And the second one, can you comment a little bit more on the paid process for patients outside the United States to access daraxonrasib perhaps how you might be thinking about ex U.S. pricing in general?

Thanks, Charles. I think we'll start with Alan and then Anthony can address your second question.

Yes. Thanks, Charles. So the U.S. prescribing information doesn't define specific criteria for determining whether a patient is a candidate or not for multiagent systemic therapy. So that said, treatment decisions among approved option should be made by the treating physician in complication, of course, with the patient and taking into account individual needs of the patients, circumstances, supporting evidence and importantly, the risks and benefits of available treatment options. And this allows, again, for the flexibility for patients as with other treatment decisions to allow physicians those flexibilities in having multiple treatment options for interactions with patients.

Very good. So maybe, Charles, I'll start with the question on the global evasion access. And really, this is to support health care provider initiated unsolicited requests for RASONQUE on behalf of eligible patients. It provides an interim and compliant pre-approval access pathway in countries where it's permitted under local laws and regulation. It reflects our commitment to responsibly expand access for eligible patients while we continue to advance clinical development, regulatory approval and work towards broader commercial availability. Again, this is a program that is -- that provides daraxonrasib a paid basis in accordance with terms that are specific to the country in question. Our loan goal is to make their aftertaste available to the broadest possible patient population through regulatory approvals and through commercial availability. And maybe I'll comment a little bit on your ex U.S. question as well. Clearly, we will make launch and access decisions market-by-market, taking into account regulatory requirements, local reimbursement and asset consideration, and of course, the evolving policy environment. And we've set up a U.S. price really that's grounded in demonstrated clinical patient and societal value of RASONQUE, and we're optimistic about our overall pricing strategy and approach as we continue to build our launch plans, excuse me end markets outside the U.S. And I think I'll leave it there, Charles.

And our next question comes from the line of Cory Kasimov from Evercore ISI.

Let me add my congrats on this landmark approval. So two questions for me as well. I suspect you're aware that there are other news out there this afternoon that the Trump administration plans to announce new drug pricing deals with several mid-cap biotech companies next week. I'm wondering if the timing of that is not a coincidence. And if RASONQUE part of this. Is this something you're able to comment on at all right now?

We don't have any comments on that at this point.

So the other question was just related to that, with the pricing, how should we think about gross to net in the first handful of quarters? Should we assume something like roughly comparable to the G12Cs when they launch? Or is this like should we be looking at this in a kind of completely different lens?

Thanks again for that question. Jack Anders, our CFO, has been waiting for his opportunity.

Cory, we expect the gross to net discount to be to initially be in the range of 20% to 30%. This is ultimately going to depend based on the peer mix. We do expect a significant proportion of eligible patients to be covered through government payers, particularly [indiscernible]. And as you know, utilization through government payers comes with mandatory discounts and rebates.

And our next question comes from the line of Faisal Khurshid from Jefferies.

Congratulations on this milestone. I just wanted to ask if you can help us understand the interplay of dose reduction with realized price for the drug I understand you're supplying the drug in 100 and 150-milligram bottles, but the label says at the dose reductions are 300, 200 and 150. So I just want to understand how that may or may not impact what you ultimately realize on a net price per patient?

Thanks for your question. Anthony?

Yes. So I'll address that, Faisel. Thanks for the question. So as you said, RASONQUE is available in [indiscernible], both the 150 and the 100 milligrams, and those support the recommended dose in the approved prescribing information. each is plant priced. So the 100-milligram count bottle and the 150-milligram count bottle [indiscernible]. So that should hopefully clarify things.

Got it. But petition has 2 dose reductions and we're at the 150 mg dose, what does that mean then?

Well, so the recommended dose is 300 milligrams and the recommended dose reduction, which we saw in the clinical trial can happen is 200. There -- we expect there to be very few patients below that.