Verastem, Inc. (VSTM) Earnings Call Transcript & Summary

Good day, and welcome to the Verastem AVMAPKI FAKZYNJA CO-PACK FDA Approval Conference Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Julissa Viana. Please go ahead.

Thank you, operator. Welcome, everyone, and thank you for joining us today to discuss the FDA approval of AVMAPKI FAKZYNJA CO-PACK or avutometinib and defactinib combination therapy indicated for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer, or LGSOC, who have received prior systemic therapy. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent annual report on Form 10-K and the current report on Form 8-K filed today as well as other reports filed with the SEC. Any forward-looking statements we make represent Verastem's views as of today. Joining me on this call are Dan Paterson, President and Chief Executive Officer of Verastem, who will provide opening remarks and key highlights of the FDA approval; Dr. John Hayslip, Chief Medical Officer, who will provide an overview of recurrent LGSOC, the approved indication and label highlights and clinical data for AVMAPKI and FAKZYNJA; and Mike Crowther, Chief Commercial Officer, who will walk through the market opportunity, go-to-market strategy and patient access. After Dan provides closing remarks, we will open the call for Q&A, and Dan Calkins, Chief Financial Officer, will join us for questions. I will now turn the call over to Dan. Dan?

Thank you, Julissa, and thank you all for joining us. Today marks an extraordinary and historic milestone for the LGSOC community as we now have the first ever treatment specifically approved for KRAS-mutated recurrent LGSOC. As Julissa shared, the trade name for avutometinib is AVMAPKI and for defactinib, it's FAKZYNJA. AVMAPKI plus FAKZYNJA is only available as a combination pack with 2 prescription products and is known as the AVMAPKI FAKZYNJA CO-PACK. This FDA approval marks a significant milestone for the industry as we believe that this is the first-ever novel/novel drug combination approved in oncology. This is thanks to years of hard work and collaboration with investigators, patients and families who participated in the clinical trials as well as the patient advocacy community and the FDA. This patient community has been waiting a long time for a breakthrough to emerge and for a treatment that targets their specific disease. Our journey began nearly 5 years ago when we started our preclinical research and screening in KRAS-mutant models and the RAS/MAPK pathway. We identified synergy between AVMAPKI and FAKZYNJA, which sparked the launch of our development program with external experts. Through years of accelerating our efforts, this first novel/novel combination therapy in oncology represents a significant breakthrough in targeting the RAS/MAPK pathway. Specifically, the combination of AVMAPKI and FAKZYNJA is grounded in innovative science focused on improving outcomes for patients diagnosed with RAS/MAPK pathway-driven tumors. 70% of LGSOC tumors are driven by the RAS/MAPK pathway associated mutation with 30% being KRAS mutant. LGSOC is an insidious and persistent rare ovarian cancer where the vast majority of patients will recur and the median overall survival in patients that have received at least one line of therapy is between 25 and 29 months. We believe this novel combination will become the preferred treatment and potentially standard of care for patients living with KRAS-mutated recurrent LGSOC. As you may recall, this combination therapy received orphan drug designation, which recognize this rare cancer as distinct from high-grade serous ovarian cancer. It was also granted Breakthrough Therapy Designation and Priority Review, highlighting the importance of FDA support in the development of this new treatment. Ultimately, this accelerated FDA approval, which came well ahead of the anticipated PDUFA action date of June 30, represents significant progress in gynecologic oncology and underscores the urgency to address the unmet need among women living with LGSOC. The approval was based on a primary analysis of the Phase II RAMP-201 clinical trial, which John will review. In all, the combination of AVMAPKI and FAKZYNJA showed robust efficacy in the KRAS-mutant population with deep and durable responses and low discontinuation rates. Now I'd like to spend a few minutes on our commercial plans. As we've stated before, our go-to-market strategy is aligned to deliver success and includes a strategic collaboration with IQVIA to leverage its world-class infrastructure and established commercialization solutions. Mike will speak about our launch strategy in more detail, but we'll focus our efforts on both the large centers where the majority of patients are seen and the smaller community centers. In addition, we'll engage with patients, both those who have registered on our disease education site and others through robust programming for ongoing education and support. Over the last few years, as part of our prelaunch effort and educational work with our medical science liaisons and now with the addition of our field sales team, we've put together a highly experienced and motivated team. With our commercial and medical affairs teams in place, we're ready to help patients living with KRAS-mutated recurrent LGSOC gain access to this important new therapeutic option, which we expect will be available within the next week. Before I turn the call over to John, I'd like to take a moment to recognize our incredible team here at Verastem. Thank you for your unwavering commitment to advancing new medicines for people living with RAS/MAPK-driven cancers. We at Verastem are also deeply grateful to everyone who's helped us reach this milestone, including patients with LGSOC participating in our trials and their caregivers, the clinical trial investigators and support staff, the patient advocacy community and the FDA. The people living with LGSOC inspire us with their bravery, and it's been an honor for us to be on this journey with them. The patient advocacy community has been an incredible partner over the last few years. And as you can see from some of their reactions, they too are excited and have underscored the significance of this approval. I'll now turn the call over to Dr. John Hayslip to provide an overview of our work in recurrent LGSOC and walk us through the label. John?

Thank you, Dan. I want to add my appreciation for the researchers, the advocates, the caregivers and the patients who have all partnered together to bring this much-needed therapy to people living with a difficult-to-treat, rare ovarian cancer. I've spoken to many investigators who have shared with me their positive experiences in the trial and who strongly believe in the transformative potential of this groundbreaking combination therapy. It's truly an honor to be speaking with you about AVMAPKI plus FAKZYNJA combination therapy today. People often ask me about LGSOC and why treatments used for other forms of ovarian cancer often do not induce responses in LGSOC. A decade ago, the World Health Organization recognized LGSOC as a distinct and different disease from high-grade serous ovarian cancer or HGSOC, in part because it requires a different approach to treatment. I would like to take a moment to clarify that low grade in this context refers to pathology findings, where LGSOC is characterized by having a low number of mitotic figures under microscope examination. To be clear, people with LGSOC often have high symptom burden and current treatment options for patients who recur after surgery are not sufficient for most patients. People diagnosed with LGSOC have struggled as the disease is less responsive to chemotherapy than high-grade ovarian cancer. In the United States, an estimated 6,000 to 8,000 people are living with recurrent LGSOC and approximately 1,500 will experience that first recurrence annually. A diagnosis of LGSOC is clearly a life-changing event and recurrence is even more impactful. LGSOC can affect women as young as their 20s and 30s. And the vast majority of these women, about 80% to 90% experience recurrence, highlighting the urgent need for more effective therapies. In the LGSOC Patient Impact Survey, we supported in collaboration with patient advocacy groups and leaders in the medical community. Most patients reported a negative impact from the disease on their mental and physical health, fertility and long-term quality of life. I would like to thank Amanda for allowing me to share her experience so that you might understand LGSOC a bit better. Amanda was first diagnosed with LGSOC at age 26. At the time, she had surgery to remove the tumors and then received chemotherapy. About a year later, she started experiencing symptoms again and learned that her cancer had recurred. She described her experience as devastating and was worried about her next treatment option, given that she knew there were so few and she had already received some of them as part of her initial treatment plan. Prior to her recurrence, she was hoping that she would receive targeted therapy like she had heard about for other cancers. Unfortunately, Amanda's story is not unique. Most people living with LGSOC will have a recurrence. This is why the approval of AVMAPKI and FAKZYNJA is so important. It gives people like Amanda an option to discuss with their doctor. This combination was chosen for evaluation in LGSOC because about 70% of LGSOC tumors are driven by the RAS/MAPK pathway and about 30% have a KRAS mutation. Avutometinib inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. Over the past decade, researchers have learned that blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. Defactinib is a FAK inhibitor. And together, the avutometinib and defactinib combination, now known under the brand name AVMAPKI FAKZYNJA CO-PACK, was designed to provide a more complete blockade of the signaling that drives the growth and resistance of RAS/MAPK pathway-dependent tumors like LGSOC. With this background, I'd like to now discuss the newly FDA-approved package insert in more detail. As Dan mentioned, AVMAPKI FAKZYNJA CO-PACK is approved as a combination therapy for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer who have received prior systemic therapy. Shown in the slide is a summary of the key highlights from the prescribing information. I'd like to point out that the approved dosing is unchanged from the dosing and administration used in the RAMP-201 study. The warnings and precautions are generally consistent with the RAMP-201 data presented at previous academic conferences and are listed as ocular disorders, serious skin toxicities, hepatotoxicity, increased creatinine phosphokinase and embryo-fetal toxicity. The dose modification guidelines are also generally consistent with the approaches utilized in the RAMP-201 study. In addition, AVMAPKI plus FAKZYNJA does not include any box warnings and no REMS program. The adverse reactions listed in the PI are generally monitorable, manageable and typically reversible with dose interruptions or reductions. As highlighted in Section 6.1, the clinical safety section of the label, the most common adverse drug reactions include elevations in creatinine phosphokinase, hyperbilirubinemia, diarrhea, edema and fatigue among several other reactions seen here. The combination of AVMAPKI plus FAKZYNJA utilizing a novel intermittent dosing schedule as described, provides most patients a tolerable and convenient orally dosed treatment. Guidelines are provided for treatment interruption or reduction for patients who may require either to address side effects. 14% of patients discontinued therapy as a result of the adverse reactions in the trial setting. More information about these adverse events and dose modifications can be found in our prescribing information. The accelerated approval of AVMAPKI FAKZYNJA CO-PACK is based on the overall response rate and duration of response observed in patients with KRAS-mutated recurrent LGSOC in the Phase II RAMP-201 study. This study enrolled patients with and without a KRAS mutation. While we celebrate this advancement in KRAS-mutated recurrent LGSOC today, our work continues for patients with recurrent LGSOC whose cancer does not harbor a KRAS mutation, and I'll speak more about that in a few moments. When considering the study results, it's crucial to understand the baseline conditions of the patients with KRAS-mutated LGSOC who participated. These patients were, on average, amongst the most intensely pretreated patients that I have seen in studies of LGSOC. In RAMP-201, most patients had received 3 or more prior treatment regimen. And this trial did not cap the number of prior therapies allowed. The vast majority of patients in this study have received both platinum-based chemotherapy and endocrine therapy. 40% of patients had received prior bevacizumab and 21% had received a prior MEK inhibitor, the most common being trametinib. Amongst these patients, the AVMAPKI FAKZYNJA combination therapy provided an overall response rate of 44%. And those responses were observed as ongoing for up to 31 months. Many patients who achieved an objective response remain on treatment and in response at the time of the analysis. These long-lasting responses are important for patients with recurrent LGSOC. Beyond what we're doing with this new drug approval, I'd like to briefly review the broader experience we saw from the RAMP-201 study, including the analysis of all the patients enrolled. These results may further inform treatment guidelines and underpin our continued enthusiasm for the RAMP-301 study, the Phase III trial for all patients with recurrent LGSOC. In October of last year, Professor Susana Banerjee presented these analyses from the RAMP-201 study at the IGCS annual meeting in Dublin, Ireland. As many of you may know, the RAMP-201 study enrolled patients with recurrent LGSOC regardless of whether the cancer harbored a KRAS mutation or not. In the overall patient population, the response rate was 31%. Stratifying by KRAS status, we observed 44% response rate in KRAS mutation positive and 17% for KRAS wild-type. And these analyses were all performed by a blinded, independent radiology committee. This waterfall plot represents the individual experience of each patient enrolled to the combination. Reductions in the size of tumors were seen in many patients, including patients with KRAS mutations in blue and without KRAS mutations in teal. Overall, 82% of patients treated with the combination had a reduction in the size of their tumors. With what we've seen to date across the broader population of patients in our LGSOC studies, even going back to the Phase I experience, the FRAME study, where we saw an overall response rate of 42% across the entire enrolled population, I'd like to share our planned next steps. The National Comprehensive Cancer Network, or NCCN Guidelines are evidence-based recommendations that many oncologists use to inform treatment options and are critically important for treatment adoption in the United States. The NCCN Guidelines for recurrent LGSOC include chemotherapies and biologics, which are typically prescribed for high-grade cancer and also hormonal therapy and MEK-only inhibitors, which are specific to LGSOC. Recognizing the limitations of comparing across different studies, the response rate as adjudicated by a blinded committee in RAMP-201, and the tolerability are encouraging when considering what has been reported for the MEK-only inhibitors. Based on the results from the full RAMP-201 study, I'm pleased to share that today, the company submitted to NCCN for their consideration the inclusion of avutometinib and defactinib based on the entire patient population enrolled in the RAMP-201 trial. Lastly, our Phase III RAMP-301 trial is ongoing and actively enrolling patients with recurrent LGSOC, regardless of KRAS status, who have received at least one line of platinum-based chemotherapy. We look forward to reaching full enrollment targeted by the end of 2025 and having this trial serve as the confirmatory trial for the initial KRAS mutant indication and potentially support an expansion to a broader indication that includes KRAS wild-type. With that, I'll turn the call over to Mike to provide an overview of our U.S. launch plans. Mike?

Thank you, John. This is an incredible time for our organization and for the LGSOC community, both patients and oncologists as we bring the first-ever FDA-approved treatment specifically for KRAS-mutated recurrent LGSOC. And we are ready to execute a successful commercial launch of the AVMAPKI FAKZYNJA CO-PACK in the United States. Now with approval in hand, we can deliver a new treatment option that addresses all the important needs that physicians and patients have identified as critical in managing this condition. We have the potential to make a significant impact on the lives of patients who previously have no treatment options specific to their disease. We will work to ensure patients have seamless access to the AVMAPKI FAKZYNJA CO-PACK. Through our engagement with the oncology community and the insights gained from market research, we believe the current treatments leave room for significant improvement. Prescribers have told us that having a treatment for recurrent LGSOC that improves various efficacy outcomes such as overall response rate and meaningful disease control rate with favorable tolerability and good access would be beneficial. The AVMAPKI FAKZYNJA CO-PACK has the potential to deliver on these needs with the data outlined in the label, including a 44% overall response rate in KRAS-mutated LGSOC with a tolerability profile that led -- only led to a 14% discontinuation rate, which supported patients' ability to stay on treatment for an average of 18 months. Given the strong efficacy and safety results, we look to provide an extensive patient support program to ensure all patients who are eligible, regardless of insurance status, can access the therapy. And we'll touch on this in more detail in a few minutes. We've heard time and again that the LGSOC community is ready for the approval of this combination. Through our outreach efforts last year, we were able to support awareness of both the disease state and our data in the treatment of recurrent LGSOC. There is an increased positive sentiment regarding the combination from oncologists at the nation's leading treatment centers, along with great enthusiasm across the broader oncology community. To capitalize on this enthusiasm, we aim to execute against 3 strategic imperatives, which will enable a successful U.S. launch and ensure all eligible patients have access to this truly innovative combination therapy. Our first imperative is focused on effectively reaching all providers. As we have shared, we can address the vast majority of the market because almost 50% of patients with recurrent LGSOC are seen in the top 100 organizations, and these will be a primary focus for our field team starting on day 1. The remaining patients are seen at the smaller community centers, the majority of which are part of either large affiliated practice networks or are associated with group purchasing organizations. And we will be participating in their programs, and we plan on targeting them as well. We believe our focused launch efforts are rightsized for the market opportunity ahead. Our second imperative is focused on engaging and supporting patients with KRAS-mutated recurrent LGSOC. As we have said, this is a very difficult and persistent disease that requires ongoing management. There is a high unmet need for better treatment options for patients whose cancer has recurred as 80% to 90% of patients will recur after receiving first-line therapy. With the very limited treatment options available to them to effectively manage their cancer, many patients cycle through therapy and will likely be ready for the next treatment within 6 to 7 months. We have had a very effective outreach and engagement with the patient community through our disease education efforts prior to this approval. We are pleased to now to be able to share the news of this approval with the patient community, and we intend to continue to educate the patient community on the unique and distinguishing attributes of the AVMAPKI FAKZYNJA CO-PACK and provide resources for them to speak with their doctor and learn more about our comprehensive patient access program. Our third imperative is to ensure that our patient support programs provide seamless access, allowing health care professionals and their patients to access the AVMAPKI FAKZYNJA CO-PACK with minimal disruption and maximum benefit. As we look at the payer mix of patients who may receive combination therapy, about half the patients are commercially insured and 45% are on Medicare. There are very few patients with Medicaid or who are uninsured. We anticipate that some insured patients, for instance, those with employee-sponsored insurance, may face standard new-to-market blocks for the first 6 to 12 months prior to the plan making a formulary decision. Payers typically provide an appeals process to allow for medical exemptions. These exemption are commonly granted for new cancer therapies. For Medicare patients, we expect routine coverage to be in place within 90 days as the therapy will be considered part of a protected class under Medicare Part D. Until then, Medicare should cover the therapy through the expedited exemptions process. I'll speak about our specific access program in a few minutes. As John referenced earlier, approximately 6,000 patients are living with recurrent LGSOC and at least 30% of them harbor the KRAS mutation. This leads to an initial opportunity of reaching up to 1,800 patients. And on an annual basis, approximately 450 patients will experience their first recurrence after first-line therapy. As I mentioned earlier in our study, patients are on therapy for an average of 18 months. Verastem is committed to ensuring that insurance and affordability challenges do not become barriers for patients who need the AVMAPKI FAKZYNJA CO-PACK. We have developed a comprehensive set of support services through our Verastem Cares program to help people manage through these standard processes and the expected delays in coverage. Our best-in-class programs include a quick start program that will allow eligible patients to begin immediate access to AVMAPKI FAKZYNJA CO-PACK therapy if there are any coverage delays with the insurer. We have implemented a $0 co-pay card program for commercially insured programs and will establish a patient assistance program that will provide free medicine to eligible patients. Verastem will distribute the AVMAPKI FAKZYNJA CO-PACK via a limited distribution network with 2 independent, oncology-focused specialty pharmacies to fulfill prescriptions and support the patient community with their complementary and comprehensive services. We believe these efforts will remove real and perceived barriers and allow for timely reimbursement and rapid access to the AVMAPKI FAKZYNJA CO-PACK treatment. In our consideration of how to price the AVMAPKI FAKZYNJA CO-PACK, as we have shared today, this is the first novel/novel combination approved and the first-ever FDA-approved treatment for KRAS-mutated recurrent LGSOC. Our pricing reflects the value of the combination of 2 therapies in 1 co-pack, the robust clinical data on efficacy and safety and the value we believe this treatment will bring to patients and their physicians. The wholesale acquisition cost, or WAC, for a 28-day prescription of the AVMAPKI FAKZYNJA CO-PACK, which contains 2 medicines, will be $48,500. As a reminder, this does not account for discounts or rebates nor is it the price patients will pay. Based on our market research, we believe this pricing strategy is in line with similar recent oncology drug launches and is aligned with the payer and treating community' expectations. Importantly, we believe it reflects the real innovation and value that the AVMAPKI FAKZYNJA CO-PACK will bring to people living with LGSOC. Let me close by saying that we believe our strong, focused commercial team, strategic launch imperatives and segmented physician base provides us with the opportunity to deliver a best-in-class launch. We believe the combination will become the preferred treatment for physicians and likely the standard of care for patients with KRAS-mutated recurrent LGSOC. We are energized and ready to hit the ground running to have a positive impact on the lives of people living with this debilitating disease. I will now turn the call back over to Dan for closing remarks. Dan?

Thank you, Mike. Before we open the call to Q&A, I'll share a few final remarks to close out today's presentation. The Verastem team, as Mike said, is laser-focused on making a lasting positive change in the lives of people diagnosed with RAS/MAPK pathway-dependent tumors, starting with patients with KRAS-mutated recurrent LGSOC. As you can see, we're ready to serve patients in the U.S. and have been preparing for this opportunity for years. Now we must follow through and make AVMAPKI FAKZYNJA CO-PACK available to patients who will benefit as fast as possible. I'm confident that our team will deliver a successful launch. Part of market expansion opportunities will include leveraging data from the RAMP -301, our confirmatory study, to expand AVMAPKI FAKZYNJA CO-PACK indication to include KRAS wild-type. We have several other clinical development programs that we're excited about, including 2 that we hope will maximize the synergistic potential of AVMAPKI plus FAKZYNJA for additional advanced solid tumor market expansion opportunities. In first-line metastatic pancreatic cancer, we've seen very encouraging response rates from our early research thus far in RAMP-205, and we look forward to selecting our recommended Phase II dose and sharing additional data at ASCO this year. In non-small cell lung cancer, we're advancing RAMP-203, which includes the doublet combination of avutometinib and sotorasib and the triplet combination, which now includes defactinib. With the encouraging initial antitumor activity seen with the triple combination, we look forward to sharing an interim update on the trial in the second half of this year. In addition to our potential market expansions for AVMAPKI plus FAKZYNJA, we're also expanding our early-stage pipeline, starting with VS-7375, an oral KRAS G12D ON/OFF inhibitor, which has demonstrated oral bioavailability, no dose-limiting toxicities across several dose levels and multiple partial responses in both metastatic pancreatic cancer and advanced non-small cell lung cancer in the Phase I dose escalation study conducted by our partner, GenFleet in China. We will share preclinical data at AACR this month and clinical data from the Phase I study of VS-7375 in China will be presented at ASCO this year. We are excited to have filed the IND in the U.S. for VS-7375 in the first quarter and expect to initiate the Phase I/IIa trial by the middle of this year. In closing, we're incredibly proud of today's approval of AVMAPKI plus FAKZYNJA and are grateful for the position that we are in to deliver a much-needed therapy to the LGSOC community. With that, we'll open up the call for questions. Operator?

[Operator Instructions] The first question today comes from Michael Schmidt with Guggenheim.

Congrats on the early FDA approval. Good to see the FDA approval there, especially given some of the uncertainty in the market right now. A couple of questions just as we think about the commercial launch. Yes, perhaps could you just talk a bit more about your expectations on the early launch trajectory, especially given some of the education efforts that you've already had ongoing for some time now? And for example, would you expect an early bolus of patients in the early months? Is there an expectation for meaningful in-stocking here following approval? And the other question I was wondering is how will academic centers handle putting patients either on commercial product based on the approval or perhaps enrolling them in the ongoing RAMP-301 study?

Michael, thanks for your question. No, this is an exciting day. We're actually very pleased that we got the approval on World Ovarian Cancer Day. and again, apparently, the election of a U.S. pope. So just your question on kind of launch dynamics, we don't expect a huge bolus at the beginning. This is a disease where patients will come off over time or if they're dissatisfied with their therapy, maybe they haven't progressed, but having suboptimal results, will come off. But this is -- and based on our market research, this is the most likely thing to go on next after whatever therapy they're on. But we wouldn't expect a huge bolus at the beginning. I do think one of the dynamics that will be important in this launch that's different from a lot of oncology launches is given the long time that patients are on therapy, we do believe it will act more like a rare disease where you build an annuity over time. Because with patients being on average, 18 months, you're not going to be cycling patients through as quickly as a lot of other oncology indications.

Maybe just a quick follow-up, if you don't mind. On the wholesale acquisition cost of the combination, what is a good modeling assumption for gross to net when considering payer mix and patient assistance programs and discounts and such?

Yes. We haven't given specific guidance on gross to net. If you look at similar products, it's probably in the 15% to 20% range.

The next question comes from Gregory Renza with RBC Capital Markets.

My genuine and our genuine congrats on the approval. Dan, maybe just building on the last question and certainly, Mike's introduction of the WAC. Just curious if you and the team could comment just a bit on some of that rationale, how you are kind of pricing for value? what aspects of the co-pack were you leaning on and the comparables that had you arrived at that price point in order to harness the value of the approval? And I have a follow-up as well.

Sure. No, thanks for the question, Greg. No, we did extensive payer research and looked at a lot of analogs. I would say the primary concern we had was making sure that we had programs in place to shield patients from the impact of pricing as much as possible. It's a relatively rare disease. And you see in this space prices -- and I'll let Mike comment on it a little bit. But our primary concern was making sure we have robust programs in place for patients. Mike, do you want to comment on some of the analogs?

Sure, Dan, and thank you for the question. I mean we developed over the last 2 years, extensive analog research. And it's difficult when you're pricing 2 novel/novel therapies simultaneously to get true analogs. But if you look at the recent approvals across rarer indications in oncology, the prices have ranged somewhere between $45,000 to $55,000. And commonly for doublets that are out in the marketplace that have developed over time, they have a not dissimilar combination price range. The most recent approval and the most proximate space, ELAHERE is around 450,000 a year, but obviously, they're addressing a much larger population with far less durable benefit to patients. So we feel, to the point that was made during the call, that the fact that it's 2 products, the fact that it is the first FDA approval in this particular disease and with the degree of clinical benefit we're bringing, we think the WAC is a fair and reasonable approach to the value that we're adding to the clinical practice within the management of LGSOC.

Thanks, Mike.

Yes, that's really helpful. I appreciate all that color. And just a follow-up question and certainly for modeling purposes, as we think about modeling royalties, could you just remind us the royalty obligations and even any milestones that we should be thinking about when it comes to Chugai and Pfizer across avuto and defactinib? And congratulations.

No. Thanks for the question, Greg. Dan Calkins, do you want to take that one?

Yes, I can take that one. So the -- for defactinib or FAKZYNJA, what we've disclosed is that there are regulatory and commercial milestones but we haven't disclosed specifically what those are. And then Pfizer is able to get royalties on the sales anywhere from high single digits to mid-double digits on those sales. On the Chugai agreement, which will be for AVMAPKI or avutometinib there are no regulatory or commercial milestones. But Chugai is able to get royalties on the net sales in the double-digit range.

The next question comes from Kelly Shi with Jefferies.

This is Clara on for Kelly. And really congrats on the approval. So just wanted to get a sense of where you're at for ex U.S. regulatory development and whether you had any conversations with regulatory agency in Europe regarding the possibility of approval based on the RAMP-201 study. And then in Japan, I understand you are running a bridging study to support a potential approval. So maybe you talk about the potential approval scenarios, whether it could be more similar to the U.S. approval?

Yes. Thanks for the question. Yes, what we have said about -- first of all, obviously, the biggest market for us and the most important is the U.S. market. And so being able to get on the market there is a huge milestone for us. What we've said about those other 2 geographies is in Europe, we are having discussions. We do not yet know whether we can get approval on 201 or whether we're going to have to have the full confirmatory study. I will say the way the reimbursement works in a lot of these countries, even having approval on the single-arm study might not be enough to get reimbursement. And so I would say the base case is probably robust reimbursement in Europe once we have the 301 data. It is a very different story in Japan. I think reimbursement will be better. We are well into a bridging study that we will be using to file for conditional approval, and then those sites will be rolled over into the confirmatory study to contribute some Japanese patients to that as well. We've not given specific guidance on timing for either one.

Congrats again.

The next question comes from Graig Suvannavejh with Mizuho.

I'll offer my congratulations on the approval. If I could just go back to the NCCN Guidelines and potential inclusion in those time lines. I think I heard that you already filed for that today. But can you just remind us kind of from a blocking and tackling perspective, like the time lines with which you think you might hear back? And maybe with the drug now approved, your latest view on what uptake could look like, assuming that you get inclusion in the guidelines for broader use.

Yes, Graig, thanks for the question. As was mentioned, we did file the application today. We can't control the timing of the meeting. Typically, when there's a new approval, they'll have an ad hoc meeting. So it's literally when they can get people together on a Zoom call and then they do their process. So we're hoping that the delay is not much. I will say that a number of the investigators that we know are very excited about the drug. And so I think will make any effort possible to be available to be able to do that. And as far as uptake, we will be out educating on the drug itself and how to use the drug. Obviously, we can't promote directly for the wild type. But we do believe with the manuscripts coming out both for FRAME and for RAMP-201, which we are able to share with investigators doing it properly, we think there'll be good awareness around the drug. And while in our own model, we do model faster uptake in the mutant patients, we do think the unmet need in wild type, especially after patients have gone through a couple of therapies and don't have a lot of options is still high, and we would expect significant uptake there as well.

If I could just come up with a follow-up question just on awareness of the product within the community. Is it fair to assume that the level of awareness amongst patients and oncologists is high? Or is that perhaps not accurate and there's still some work that needs to be done there?

No, great question. There's always more work that can be done. I will say, based on the market research we've done between results that we got recently versus a year ago, awareness has gone up quite a bit on both the disease and the involvement of the MAPK pathway and the fact that there are new drugs like this in development. That will obviously go up quite a bit when we can actually go out and talk about the drug itself. But I would say among OB/GYNs in particular, I would say awareness is pretty high, probably not quite as high in the general med onc community, and there is more work to do. But I will say it was pretty heartening to see the increase in awareness over the last year or so.

Congratulations again.

The next question comes from Kalpit R. Patel with B. Riley.

Many congrats here on the early approval. One more for the NCCN Guidelines part. Did you guys think you can get Category 1 recommendation for both the mutant and wild-type population, assuming that gets included? Or do you think it might be more closer to Category 1 for the mutant population and maybe 2A for the wild type?

I can't speak for the NCCN. Typically, to get Category 1, you need a randomized Phase III, although this was a well-designed study with central review of scans and all the bells and whistles you need for -- to develop good evidence. I think 2A gets us reimbursement with almost everybody. It's always great either to get 1 or maybe we end up with 2A, but we're preferred. There's some subtleties in there. We think with the level of evidence we have, we'll get a good enough recommendation that it shouldn't interfere with reimbursement.

Okay. And then related to that, KRAS testing might not be a standard in low-grade serous ovarian cancer. So I guess what steps are you taking to drive routine testing, particularly in the community centers where it may not be common? Are you guys offering any free testing or working with any diagnostic partners?

We do have a diagnostic partner for development of the companion diagnostic, which is a post-marketing requirement that we will have one out. Now having said that, KRAS testing is widely available. And when patients with ovarian cancer have a workup normally, remember for high grade, which typically they do all the testing -- even though high-grade versus low grade is a pathology test and you're looking for a microscope. Typically with ovarian cancer patients, they are doing broad panels because they're looking at things like BRCA mutations and things for choosing treatment if they're high grade. So I don't think it's a big departure from standard of care even in the community now. And the research we did, we saw rates of testing like up in the 80%, much higher than one would normally see in some of the numbers that have been reported for lung cancer, which continues to surprise me. I actually think in lung cancer, in particular, not getting testing is kind of malpractice. But we did see, based on our research, higher rates in ovarian cancer than in lung cancer. So we don't think it will be a big barrier. Obviously, we'll continue to educate both patients and physicians. But paying for the test itself, that starts to get into areas where potentially -- particularly with Medicare patients where potentially you're paying for something that's done before the treatment decision is made, you might run afoul of some regulations.

Okay. Okay. And one last one. Are you guys going to allow the claims data available for prescription tracking purposes via IQVIA or Symphony?

Yes, we're not going to block that. It's not a particularly competitive space where we have a head-to-head competitor where we're trying to withhold things. I've been in that situation before, and it just didn't feel like that here.

Congrats again.

The next question comes from Jeet Mukherjee with BTIG.

Congrats on the approval. A great day for you and for patients. Two questions, maybe just coming back to an earlier one. Are you expecting a large inventory stocking component early in the launch? And the second question was, will you be having a granular level of detail or visibility into potential off-label use in KRAS wild-type patients over the course of the launch?

Yes. No, those are great questions. I mean we -- as was mentioned by Mike, it will be a limited distribution model where we can control that and actually can limit the amount of inventory in the channel, and we'll be watching that very carefully. So we don't expect a huge amount of stocking, and we'll monitor that. As typically happens in these types of launches in a controlled distribution scenario, you have both the specialty pharmacy, which we have very good visibility into individual patients, who -- what their diagnosis is and how long they're on therapy. And so we'll have a good sense there. Things that go through the specialty distributor channel, you tend to have less visibility at a patient level. And so we'll have to get both field intelligence from our field force that's out there as well as proxy from the SP channel.

[Operator Instructions] The next question comes from Sean Lee with H.C. Wainwright.

Congrats on the approval. I was wondering if you could provide some color on the size of the commercial force that you have right now and whether you believe it's sufficient to cover the U.S. -- the whole U.S. geography? Or do you expect to expand it further later this year?

Thanks for the question, Sean. Good question. So I don't think we would launch with a sales force we didn't think was sufficient to cover the United States. I think the dynamics of this market are such that about half the patients are concentrated in about 100 sites. And so that's very reachable one-on-one with a direct sales force, and we've guided that we'll have somewhere between 16 to 18 oncology reps that will call on those sites. We also have a med affairs group that's been out deployed for over 2 years from 8 to 12. And those will be both assisting with those large sites as well as a huge component of this market is the community physicians. But a large proportion of those community physicians belong to very large practices that are aligned with the GPOs, and so the Florida Cancer Specialists, the TOPAS, The US Oncologies, the Sarah Cannon, those. The most efficient way to reach those doctors is not to try and call on them one-on-one for detail. Those organizations don't like their doctors spending a lot of time that way. And then if you contract with them, which we are, they facilitate your participation in their events. And so they hold in services and they really help facilitate the education of their physicians on the newest treatments. And then those organizations are also very guideline-driven and they actually have embedded in their electronic medical records, the guidelines. And the first step on getting into those guidelines is to get in the NCCN Guidelines. And then you're working through their GPO affiliates, you make sure you're, again, part of their in services and you're in the guidelines. And that's really the most efficient way to get to them. We also have nurse educators because if you remember when Mike went over the strategic imperatives, one of them is keeping patients on therapy. And so we'll be working very closely with the groups they have within their organizations to make sure they have all the resources and information they need from us to be able to keep patients on therapy. And then as was mentioned earlier, an important part of this market is the patients themselves. They tend to be younger. They're more Internet savvy. They belong and affiliate with these patient organizations. And as Mike had mentioned, we've got over 2,500 that signed up voluntarily through our non-branded website. And so we feel confident that with those 3 approaches and then layering digital on top of that -- and again, one of the important parts of our strategic relationship with IQVIA is we get access to some of the state-of-the-art stuff that maybe a small biotech wouldn't be so expert at. And so digital will be an important part of this as well.

This concludes our question-and-answer session. I would like to turn the conference back over to Dan Paterson for any closing remarks.

No, I'd just say thank you for everybody listening. I know it was probably a little longer than folks would have liked. But it's a very exciting day for patients. We've been working to do this for a long time. We've had the pleasure of getting embedded into the patient community here and have just thoroughly enjoyed the ability to be able to offer something for these patients that haven't had anything before. We're very excited. We're very excited about our other programs to expand this. And this is a very exciting year for Verastem, and we're really looking forward to hitting the ground running on the launch and then sharing some exciting data at ASCO and then continuing to move all these programs forward. So thank you all for your attention.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.