Good afternoon, and welcome to the Verastem Oncology RAMP 201 update conference call. My name is Gary, and I will be your conference operator today. As a reminder, this call is being recorded. After today's presentation, there will be an opportunity to ask questions. Beginning now, to ask a question, you may press star then one on your touchtone phone. To withdraw your question, please press star then two. I would now like to turn the call over to Julissa Viana, Vice President of Corporate Communications and Investor Relations.
Thank you, Gary. Good afternoon, and thank you for joining today's conference call to discuss the mature RAMP 201 data for the investigational combination of avutametnib plus defactinib in recurrent low-grade serous ovarian cancer. During this call, we will also provide a regulatory update regarding a rolling NDA submission. We issued a press release earlier today on the RAMP 201 abstract presented at the IGCS, which is available on Verastem's website, along with the slide presentation that we will reference on our call. 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 and as a result of the 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 this morning, as well as other reports filed with the SEC. Any forward-looking statements represent Verastem's views as of today. On today's call, we have from Verastem's management team, Daniel Paterson, President and Chief Executive Officer, who will provide opening remarks. Dr. John Hayslip, Chief Medical Officer, who will take us through the primary analysis of the mature RAMP 201 data. Mike Crowther, Chief Commercial and Strategy Officer, will follow with a review of the market opportunity and our preparations ahead of an anticipated launch in 2025. In addition, we are joined by Dr.
David O'Malley, Director and Professor, Division of Gynecologic Oncology at The Ohio State University and The James Comprehensive Cancer Center, and a RAMP 201 investigator and one of the authors of the IGCS presentation. At the end of the prepared remarks, we will open the call for Q&A, where our management team and Dr. O'Malley will be available for questions. I will now turn the call over to Verastem's President and CEO, Dan Paterson. Dan?
Thank you, Julissa, and thank you all for joining this afternoon's call. John Hayslip and I say hello from Dublin. We're in Dublin, attending the IGCS meeting. If there are any audio problems, the team in Boston is ready to kick in and back up for us. Today marks another significant day with meaningful progress for patients with recurrent low-grade serous ovarian cancer, or LGSOC. It's not often that a team gets to potentially deliver a first-ever approval for a new treatment regimen in a setting where nothing has been approved before, and we're very excited about this. Earlier today, we announced updated data from our phase II RAMP 201 clinical trial, and we presented additional data during an oral plenary session at the International Gynecologic Cancer Society Annual Meeting in Dublin.
We also provided regulatory updates following our latest interactions with the FDA. We have a robust set of updates to share today, and we're pleased with the progress we've made thus far as we continue to work towards bringing the unique mechanism provided by the combination of avutametnib and defactinib to patients. Summarize our news today. Now, with a minimum of twelve months of follow-up, the mature RAMP 201 data, evaluating the combination of avutametnib and Defactinib in patients with recurrent LGSOC, shows durable efficacy across various measures in heavily pretreated patients. While John will walk us through the specific details of the results of the study, I want to highlight some compelling data from the study. There was an overall response rate of 31%, with a 44% ORR in KRAS mutant and 17% in KRAS wild type.
82% of all patients experienced tumor shrinkage, and the duration of treatment was 14.5 months across all patients, 18.3 months in KRAS mutant, and 10.17 months in KRAS wild type. We also observed 12.9 months median PFS, with 22 months in the KRAS mutant patients and 12.8 months in KRAS wild type patients. The discontinuation rate due to adverse events of 10% was consistent with previous updates on the data. These results are truly incredible if you consider that the majority of these patients were heavily pretreated. All had prior chemotherapy. The majority also had prior hormonal therapy, with about half having received prior bevacizumab, and many had received prior MEK inhibitors before entering the study.
When you consider the historical trial data with other treatments, which had started around 2013, in these studies, the patients received, on average, two prior treatments, did not receive prior MEKs, and very few received prior bev. The standard of care in recurrent LGSOC of chemotherapy, hormonal therapy, has historically demonstrated low response rates between 6% and 13%, with a PFS below 12 months and high discontinuation rates due to toxicity. Press release earlier today, we provided a regulatory update on our rolling new drug application with the FDA. In a recent Type A meeting held with the FDA, we aligned with the agency on moving forward and completing the NDA for adult patients with recurrent KRAS mutant LGSOC, who received at least one prior systemic therapy.
Based on the mature data from RAMP 201 trial, the submission also included the FRAME study, which was the first study conducted with the combination in LGSOC, and is a key supportive study in our regulatory package. While we continue to believe the RAMP 201 data in patients with recurrent KRAS wild-type LGSOC are compelling and could potentially represent a meaningful advantage over available therapy, prior studies either included very few LGSOC patients, did not stratify by KRAS status, did not measure KRAS status in all patients, and/or did not look at response by KRAS status as a pre-specified endpoint, making cross-trial comparisons difficult. The plan we aligned on with the FDA provides a straightforward path for this NDA and an opportunity to bring a new treatment to patients with recurrent KRAS mutant LGSOC in mid-2025.
We previously guided towards completion of the NDA by the end of the year. I'm happy to report that we're on track to complete the submission later this month. We're filing for accelerated approval and plan to request priority review. We believe that the best thing for patients with LGSOC is to make sure that this therapy is available for prescribing by their physicians as soon as possible. I want to acknowledge for a moment that we're excited about the data from RAMP 201. The team and I have had a number of opportunities to discuss the study results with world experts in the treatment of LGSOC, and what we are hearing universally is that there's enthusiasm for this new treatment option across the entire recurrent LGSOC population, regardless of KRAS status.
It's important to recognize that KRAS wild-type LGSOC has a worse prognosis than KRAS mutant LGSOC. This is the opposite of what we've seen in a number of other cancers. Patients with KRAS mutant LGSOC live on average for 12 years with their disease, versus only 7 years for patients with KRAS wild-type LGSOC. It's just harder to treat regardless of the treatment chosen. We believe the data are very strong and demonstrate that responses are possible in patients who have seen the majority of available treatments previously. We're committed to making the combination available to patients with KRAS wild-type, including continuing to pursue a path for regulatory approval.
We plan to use the phase III confirmatory study, RAMP 301, which continues to enroll all comers and will serve as the confirmatory study for the initial indication, to also provide additional data to the FDA to support potential expansion of the regulatory indication to include KRAS wild-type patients. In parallel, we look to submit the full RAMP 201 dataset to the NCCN for their consideration for their guidelines, which is critically important for reimbursement in the United States. Nothing has significantly changed when you look at the market opportunity for recurrent LGSOC, as Mike will review. We continue to work hard to achieve launch readiness, with the plans of being fully prepared in early 2025, with an efficiently scaled commercial model that is maximize our market opportunity.
With these updates in hand, we've aligned with the FDA that there's a clear regulatory path forward for recurrent KRAS mutant LGSOC, based on the strength of the dataset in RAMP 201 and FRAME. Both our clinical and regulatory progress further validate and position us well to deliver the first-ever FDA-approved treatment specifically for recurrent KRAS mutant LGSOC to patients in 2025, pending approval. I'd now like to turn it over to John Hayslip to take us through the primary analysis of the mature RAMP 201 data. John?
Thank you, Dan. The RAMP 201 trial, a study of avutametnib in combination with defactinib, has enrolled over 200 women with LGSOC, either recurrent or progressing after prior systemic therapy, making it one of the largest clinical studies for patients with LGSOC in the past decade. During the course of our research, we have been fortunate to meet with people like Amanda, who are willing to share their experiences living with recurrent LGSOC. At just 26 years old, Amanda was faced with a rare-
So I think we might have lost the connection. So here to continue the conversation is Jonathan Pachter, our Chief Scientific Officer.
What we're saying is, at just 26 years old, Amanda was faced with a rare ovarian cancer diagnosis. After initial treatment, a while later, she went on to experience a cancer recurrence, and as she shares, she was thinking not only about needing to endure treatment again, but was even concerned if there were still treatment options available.
... Amanda is not alone in her experience with LGSOC. In the United States, 1-2 thousand women each year are diagnosed with recurrent LGSOC, and an estimated 6-8 thousand women are living with recurrence. LGSOC often impacts younger women, often as young as their early twenties, and unfortunately, most patients experience recurrence despite initial treatments. The standard of care currently, which largely consists of endocrine and chemotherapies, offers low response rates, and many patients discontinue these treatments due to toxicities. As there are currently no therapies specifically approved for LGSOC, treatment options are largely informed by clinical guidelines, such as the NCCN guidelines that Dan mentioned earlier.
An important point to remember as we discuss the RAMP 201 results, it is understood by LGSOC experts that LGSOC, without any changes in the KRAS gene, that is to say, KRAS wild-type, is typically more challenging to control than LGSOC with a KRAS mutation. This is perhaps most clearly seen-
On screen.
This is perhaps most clearly seen in how the median survival estimates have varied for patients based upon tumor KRAS status. To understand why this combination offers a unique approach, we should spend a moment to review the biology of LGSOC. It's estimated that 70% of LGSOC tumors are driven by RAS MAP kinase pathway-associated mutations, shown on the left side of the image. Specifically, about 30% of all LGSOC cancers are KRAS mutation positive. avutametnib acts as a RAF/MEK clamp, potently inhibiting the activity of MEK while also blocking the compensatory reactivation of MEK by upstream RAF. This is important because reactivation of MEK by RAF is thought to be one of the resistance mechanisms to earlier generations of MEK-only inhibitors.
Focal Adhesion Kinase, or FAK, is at the top of a key resistance pathway activated in response to MAP kinase inhibition, a key resistance pathway to the MEK-only inhibitors. Together, the avutametnib and defactinib combination was designed to provide more complete blockade of the signaling that drives the growth and resistance of RAS MAP kinase pathway-dependent tumors, with the objective to deliver deeper and more durable tumor responses. The RAMP-
Dr. Pachter, I believe we're back from Dublin.
Great.
Thank you very much. So turning now, the RAMP 201 study was a four-part, registration-directed, randomized, open-label, phase II trial to evaluate avutametnib alone and in combination with defactinib in patients with recurrent LGSOC. A few points to orient you to the study and the results we'll walk through today. In Part A, patients were randomized one to one to avutametnib as a single medicine, dosed at four milligrams by mouth twice weekly for three weeks, followed by a one-week rest period. That's a four-week cycle. Or avutametnib, three point two milligrams by mouth weekly, and defactinib, two hundred milligrams twice daily for four weeks, followed by a one-week rest period. Again, that's a four-week treatment cycle. Randomization was stratified to achieve equal numbers of KRAS mutant and KRAS wild-type patients in each regimen.
After full enrollment in Part A, which was approximately 32 patients per arm, Part B was opened and expanded to enrollment. The same two doses, again, stratified to KRAS status, up to an additional 72 patients. The combination treatment, avutametnib and defactinib, was identified as the go-forward regimen for further study in Part C. Subsequently, a low dose of avutametnib, 1.6 milligrams, was evaluated in combination with defactinib, same dose, 200 milligrams twice a day, to see if a lower starting dose may provide similar efficacy with less avutametnib. The RAMP201 study has included over 200 women with recurrent LGSOC. I'd like to take a moment to sincerely thank the patients, their families and supporters, the countless healthcare providers who have all joined in this tremendous collective effort.
We'd like to thank Professor Susana Banerjee, the Global Lead Principal Investigator of the study, who presented some of these results earlier today at the IGCS annual meeting. We'd like to also thank all of the RAMP 201 investigators for their contributions. Lastly, I'd like to thank specifically Dr. O'Malley for taking time out of his busy schedule here at the IGCS meeting to join us on this call today. As a RAMP 201 investigator and an author in the presentation, I know he'll be able to share his extensive experience with the trial and also provide his perspective on avutametnib and defactinib in recurrent LGSOC. But first, let's review the key results. For the combination of vutametnib and Defactinib, we saw an overall response rate of 31% across all the patients.
Further stratifying by KRAS status, we observed 44% response rate in KRAS mutation patients and 17% in KRAS wild type. Eighty-one percent of responding patients remained in response at six months, with 87% in KRAS positive and 63% in KRAS wild type.
The median progression-free survival was 12.9 months for all patients, 20 months in KRAS-positive, and 12.8 months in KRAS wild-type. As we've observed previously, the avutametnib Defactinib combination is well tolerated, allowing for prolonged treatment and only a 10% discontinuation rate due to adverse events. I will also review the results from the lower dose combination and of avutametnib as a single agent. Patients in both of those groups have seen benefit from these approaches to treatment. However, the best response rates and the lowest rates of discontinuation due to adverse events have been seen in the 3.2 mg combination dose of avutametnib with Defactinib, and that is where we'll plan to focus our ongoing efforts. When thinking about the results of the study, it's critical to understand the types of patients who enrolled.
These patients. Hi, this is Jonathan Pachter filling in again. These patients were on average, among the most intensely pretreated patients that we have seen in studies of LGSOC. Later, Mike will review some historical studies in which the average typical patient may have received two prior lines of therapy. In this study, the average patient received three prior combinations of treatment. RAMP 201 did not cap the number of prior therapies, and we saw patients with as many as nine prior lines. The number of prior regimens and what treatments make up those regimens has continued to evolve with time compared to historical studies. The vast majority of patients on this study have received both prior platinum-based chemotherapy and endocrine therapy.
Also, rather uniquely compared to historical studies, over half of all patients in this study received prior bevacizumab, and 22% of patients received prior MEK only inhibitor therapy. As I said, this is a quite different study from historical studies of LGSOC, and the relatively high rate of previous bevacizumab is also a key difference from what was seen in the FRAME study, the phase I study for the combination of avutametnib and defactinib. Turning now to the efficacy findings, we are excited to see deepening responses from the avutametnib and defactinib combination compared to the data we shared in May of 2024, with ORRs improving overall and in both KRAS mutant and in KRAS wild-type subgroups. As a reminder, a confirmed response requires a 30% reduction or greater in tumor sizes and must be confirmed over multiple sets of images.
The confirmed response rate by blinded independent central review was 31% for all patients, with 44% response rate for patients with KRAS mutation and 17% for patients without KRAS mutation. Importantly, the responses are relevant because they're durable. The median duration of response was 31 months in all patients. At six months, 81% of responding patients remained in response, and that rate is 87% for those with KRAS mutation and 63% for those that were KRAS wild type. At one year, the rate of duration of response is still at 72%. In this study, the median time to response was 3.7 months, ranging from as brisk as 1.7 months to as long as 19.2 months until the formal response criteria were first fulfilled.
These long-lasting responses are important for patients with recurrent LGSOC, who currently often cycle through treatments that offer low rates of response and high rates of discontinuation due to toxicities. We've heard from LGSOC physicians who have seen this waterfall plot, how enthusiastic they are to offer the RAMP 301 trial to patients based on these results from RAMP 201. This waterfall plot represents the individual experience of each patient enrolled to the combination at the proposed dose and schedule. A key takeaway from these results, 82% of patients treated with the avutametnib and defactinib combination had a reduction in their tumors, as you can see. As you can see by the colors, regardless of the mutation status of their tumor, reductions were seen across the majority of patients.
While we recognize that subgroup analyses are exploratory in their nature, they're also important because they help put the results in context with other data and also might help navigate future treatment decisions and areas for additional research. In oncology, it's a common expectation that the more lines of previous treatment previously given, the more resistant the cancer may become. In this study, we see patients responding regardless of the number of prior therapies, but you can appreciate that patients who have received fewer previous lines of treatment showed a higher response rate. Likewise, with or without prior bevacizumab use, we see both patients, both groups of patients responding, but those patients with no prior bevacizumab use showed higher response rates.
When looking at prior MEK inhibitor use, we see a 33% response rate in patients with no prior MEK inhibitor treatment, compared to a 24% response rate with prior MEK inhibitors. But most importantly, across all these different subgroups, patients are responding. We plan to look further into these and other subgroup details to be shared at future medical meetings. While responses are exciting, living free of cancer progression is key. Overall, the combination achieved a median PFS of 12.9 months, which is remarkable considering the lines of previous treatment that many of these patients had received. Looking specifically at the PFS by mutation status, patients with a KRAS mutation had a median PFS of 22 months, approaching 2 years, and for KRAS wild type, a median PFS of 12.8 months or more than a year.
To put these findings in context, I noted previously that LGSOC without a KRAS mutation, wild type was seen to be more quickly progressive and fatal in previous studies. Similarly, in RAMP 201, the rates of response and the duration of PFS trends better for patients with a KRAS mutation in their tumors. Yet patients without KRAS mutations have also achieved responses, and most impressively, the median PFS is greater than a year even for these patients. Safety and tolerability are also important, especially considering the durations of response observed for this combination and the high rates of discontinuation that patients face with the currently available treatments. The avutametnib and defactinib combination continues to demonstrate a consistent and well-tolerated profile with only a 10% discontinuation rate due to adverse events, and no new safety signals have been identified.
While low-grade adverse events are common, severe reactions are generally uncommon, and they are typically manageable by temporary interruption of treatment. Overall, discontinuations due to adverse events were only 10%, and about a third of those have been an artifact of the initial study design. Because initially, patients who experienced grade four CPK elevations or creatine phosphokinase elevations were directed to discontinue the study. However, as the study progressed, it was noted that these appeared largely without symptoms or consequence, and the FDA agreed that we could amend the protocol and allow patients with CPK elevations to remain on the study, with appropriate guidelines for treatment interruption or reduction. After we made this update, no further patients discontinued the study due to blood CPK levels, and no significant consequences from these abnormal tests, such as rhabdomyolysis, have yet to be seen.
In RAMP 201, when relevant adverse events occur, we first guided physicians to temporarily interrupt the treatment, and 80% of patients used a treatment pause during the study. That said, most patients were able to resume treatment and did so at the previous dose, and more than half of the time, no reduction in dose was needed. About one-third of patients used a dose reduction at some time on the study. All in, the tolerability of the regimen is generally favorable, and when we account for the dose interruptions or reductions, the overall dose intensity compared to the planned dose was approximately 80%. So importantly, no deaths have been related to study treatment.
Before we provide an update regarding other arms of the trial, because the combination regimen will be the focus of the program going forward, we'd like to pause here and ask Dr. O'Malley to share his experience in the RAMP 201 trial and how he views these data compared to his other experiences in LGSOC. Dr. O'Malley?
Well, thank you, and hopefully you guys can, everybody can hear us, from Dublin here. So, you know, I think it's, it is good that you paused on this slide with regards to experience, because what's really interesting, the other MEK inhibitors, and I was involved in both GOG-281 as well as MILO, is that the toxicity with even with the combination and the dual blockade, seems to be markedly better. Typically, with MEK inhibitors, I would expect about a third discontinuation rate, and it's, as you see here, again, less than about or right about 10%, discontinuation rate.
With those, about a third of them were from CPK, and as you just heard, elevations, CPK elevations, that is, a third of those, and now we've worked through the dosing through these CPK elevations, which do not seem to have clinical significance. Most importantly is the waterfall plot. If you really look at that, in about 85% of patients have disease regression. To me, that's the most impressive aspect, really beyond the overall response rate, is that almost all patients are getting clinical regression of their disease. I'm not a big fan of clinical benefit rate. Just if somebody has stable disease for one scan, that to me is not beneficial. But having disease regression, particularly in patients who have symptoms, is so very important.
So obviously, we're very excited to have these findings in the public domain and showing the justification for 301 . So overall, very excited about these results and the possibility in the future of the 301 study.
... Thank you, Dr. O'Malley. This is John Hayslip again. The RAMP 201 trial also enrolled 69 patients who received treatment with a higher dose of avutametnib as a single therapy. These patients had baseline characteristics similar to the patients evaluated in the go-f orward regimen. These patients also had a median of three prior lines of treatment and comparable prior Bevacizumab and MEK inhibitor use. Compared to the 31% response rate we observed regarding the doublet, patients receiving avutametnib monotherapy had a response rate of 17%. We don't plan to study the monotherapy further in LGSOC. Also, this study tested a lower starting dose regimen of 1.6 milligrams of avutametnib twice weekly, with the same dose of Defactinib, 200 milligrams twice daily. The lower starting dose was found to be suboptimal based on predefined analyses.
We will not be pursuing the low-dose regimen as a starting dose. Disease progression by the second scheduled imaging assessment, which occurred at month four of treatment, was higher with the lower dose regimen than was seen in the selected combination regimen, further supporting that the proposed dose and schedule is optimized for most patients. Also presented at the IGCS meeting is a trial and progress poster for the ongoing and actively enrolling phase III study, RAMP 301. The eligibility criteria are similar to RAMP 201. We welcome patients with either KRAS positive or KRAS wild-type LGSOC. Patients may enroll regardless of the number of prior therapies, so long as they've received at least one line of platinum-based chemotherapy. This is a randomized study, and the comparator arm is based on the investigator's choice of treatment.
Perhaps most importantly, to many physicians I've spoken with, patients who are initially randomized to receive traditional therapy may cross over to the avutametnib and defactinib combination if they experience disease progression confirmed by the Central Radiology Committee while receiving standard treatment. We are targeting full enrollment by the end of 2025. The trial will serve as a confirmatory trial for the initial KRAS mutant indication and has the potential to support a broader indication, as it will be a randomized comparison against standard available therapy, and enrollment is stratified by KRAS status. With that, I'll hand the presentation over to Mike Crowther, Chief Commercial Officer. Mike?
Thank you, John. I'm going to walk you through how we see the combination of avutametnib and defactinib having the potential to change the treatment paradigm in recurrent LGSOC. I want to take a moment and walk you briefly through the patient experience in LGSOC. With no approved therapies, healthcare professionals use the NCCN guidelines to guide their treatment decisions. Often, patients will start on chemotherapy, but as symptoms progress and 80% of patients experience recurrences, they will often be provided with options like hormonal treatment, bevacizumab, and maybe on occasion, a MEK only inhibitor. But with poor response rates and high discontinuation rates, patients will still unfortunately cycle through multiple lines of treatments while living with LGSOC. Recurrent LGSOC treatment options today were developed for other indications and have demonstrated poor effectiveness and high rates of discontinuation when used to manage LGSOC.
I'm not going to go through this data in detail, nor can I make direct comparisons to RAMP 201 data, but this information highlights some important differences between the trials and underscore why better treatment options are needed. These studies started as early as 2013, when there was limited use of bevacizumab. The analysis of KRAS status was done retrospectively, only in a subset of patients. So there's not a genuine understanding of the performance of these products in relation to KRAS mutational status. But it's this historical data that has been guiding treatment decisions for years, and we want and need to do more for patients with LGSOC. We believe that avutametnib and defactinib regimen truly has the potential to address the key treatment gaps identified and make a meaningful difference in the lives of patients with recurrent LGSOC.
You've heard John walk through the compelling data of clinically meaningful response rates, durable benefit, long progression-free survival, and long durations of treatment, all with a low discontinuation rate due to AEs. With the matured RAMP 201 data in hand and a clear regulatory path forward, we feel that we are very well positioned to meaningfully support a change to the existing treatment paradigm. As we have stated before, we believe that the overall LGSOC market represents a significant opportunity, and we anticipate high market penetration in recurrent KRAS mutant LGSOC population, given the lack of FDA-approved therapies. With a total estimated prevalent addressable opportunity of over $1.7 billion, we plan to fully address this population over the first of three, 3-5 years following launch.
It's important to remember that patients cycle through therapies and do so relatively quickly in the prevalent setting. Recurrent LGSOC patients have a long overall survival of around 10 years, providing opportunities for patients to experience and benefit from new therapies and stay on those treatments if efficacious and manageable. While our current focus from a regulatory perspective is on KRAS mutant patients, I'd like to remind everyone that treatment and reimbursement for recurrent LGSOC has been driven by NCCN guidelines for many years. We plan to submit these findings from our mature 201 trial, inclusive of the entire patient population, for both publication and then NCCN consideration.
You'll see here how the NCCN categories are broken out from left to right, with general payer coverage correlating with each category and the corresponding recommendations and the clinical data that supported their inclusion and the category that they achieved. I know that I've already shown this slide, but I want to briefly show it again to reiterate the point that while the regulatory path will focus on the KRAS mutant initially, we will continue to try and address KRAS wild-type by compliantly introducing, educating, and promoting the product against the final label and the supporting evidence. Turning now to our pre-launch initiatives, we've been preparing an efficiently scaled model to deliver a best-in-class launch for a current KRAS mutant LGSOC.
Our pre-launch initiatives center around three key areas, including a focus on key healthcare organizations and accounts where we see most patients being treated, a focus on patient education with disease awareness resources and other support programs, and lastly, a focus on GPOs and large affiliation practices to ensure inclusion of all in all relevant pathways and EMR systems. While this is a rare disease, it is one where there's a concentration of patients. Over 50% of the actively managed patients are concentrated in only 100 centers, giving us an opportunity to execute a very focused launch. We've been conducting extensive market preparation activities across all stakeholder groups, and among the outcomes that we're encouraged by is that of the patients themselves, the prevalent pool within which will be initially indicated.
We have over 2,300 of those patients already engaged through our unbranded disease education website, giving us the opportunity to communicate directly with patients post-approval. We expect the speed of adoption will be high. Most physicians indicate they'll adopt within the first six months of approval, and a lot of physicians are saying that they'll reach out to their LGSOC patients, and if they're dissatisfied with their current management, they'll offer them an active switch to the vautametnib and Defactinib regimen upon approval. We'll naturally come to market with a broad set of access tools and programs to ensure both broad and early access to patients. Given the length of therapy we're anticipating, we'll also be making sure we have sufficient programs in place to support patients staying on therapy as long as possible, as well as starting.
In summary, the vutametnib and defactinib regimen have the potential to change the way recurrent LGSOC is treated. Between six to eight thousand women suffer from this rare cancer today in the U.S., and there is great potential for high market penetration in the KRAS mutant population at launch. We've stated and shown the different ways in which the current available treatment options leave clear areas of unmet need that we believe the avutametnib and defactinib regimen can address. And with the disease managed by NCCN guidelines, we look forward to submitting our entire RAMP 201 dataset for consideration. With our efficiently scaled launch model, we believe we can deliver a best-in-class launch for a current KRAS mutant LGSOC and bring patients a treatment option that was developed specifically for their needs. And with that, I will hand to Dan for closing remarks.
Thank you, John, Mike, and Dr. O'Malley, for your perspective. As we've met with several other investigators and treating physicians at IGCS, they share your enthusiasm for the potential of avutametnib and defactinib in treating recurrent LGSOC. As we walked through today, our positive RAMP 201 data have matured and continued to build our confidence and enthusiasm for potentially changing the way that recurrent LGSOC patients are treated. We remain laser-focused on execution as we work hard to potentially bring the first FDA-approved treatment specifically for recurrent KRAS mutant LGSOC in 2025. In closing, we're eager to keep executing against our milestones and further advancing our broader pipeline. As we're preparing for a near-term LGSOC launch, we're also working to prepare for potential expansion opportunities within larger, underserved patient populations.
Our other RAMP trials and our G12D program all have important milestones in the near term and throughout 2025, which are outlined here. Verastem's full potential is yet to be unlocked, and we look forward to leveraging the positive momentum in LGSOC to further deliver meaningful treatments across other RAS/MAPK pathway-driven cancers. As we transition to a commercial stage company, our commitment is to delivering novel treatment that improve outcomes for patients and that drives us every day here at Verastem. Lastly, but importantly, we thank all the patients and their families, investigators, and the team members involved in RAMP 201. With that, we'll now transition to Q&A. Operator?
We will now begin the question-and-answer session. To ask a question, you may press star, then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. Our first question is from Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.
Hi, Dan and team. Congratulations on the data. I guess the first question that I have, you know, there was a decrease in the ORR, you know, observed between part A data, you know, presented at ASCO in 2023, you know, which were similar to the FRAME data. And the maturing data that includes part B and C patients. You know, can you just sort of help us understand why this may be the case? You know, is this a result of baseline characteristics of the patients enrolled in part B and C, you know, were different compared to part A in FRAME? And if Dr. O'Malley is on the line, I'd love to hear his perspective.
Yeah, thanks, Pete. Thanks for the question. You know, as we look at both the historical studies that the phase three studies that were done, the FRAME study, and interestingly, part A, there was less bevacizumab usage in those cohorts than there were in part B, C, and D. Yeah, B and C. And, you know, shown patients who have prior Bev don't do quite as well on the treatment as those who have not had prior Bev, and that's the most likely experience. I don't know, John, if you have any other comments or, or Dr. O'Malley wants to add to that.
Yeah, I would just say that in addition to that, our work remains ongoing. Of course, we're laser-focused with completing the rolling new drug application, and we'll continue to further evaluate the data in other ways and look at other subgroups, and we'll bring those results forward as they emerge. But I just pass that. Dr. O'Malley, additional comments?
Yeah, you know, I think I've gotten asked this before. You know, I'm really excited about the current data. You know, I think as we look at this in a heavily pretreated population, three prior therapies, Bev, as well as a fair amount of patients getting previous MEK inhibitors, that this activity that we're seeing is again very exciting in this group of very challenging patients to treat. So, compared to the FRAME study, you know, I'm excited about the current data that we have, and moving into the three hundred and one study gives me a ton of confidence that this will be a treatment option in the future for our patients.
All right, great. And, you know, also, for the subgroup analysis, you know, where you showed a greater response rate, for patients that were treated earlier in the course of therapy, you know, with the avutametnib and defactinib combo. You know, Dr. O'Malley, you know, and, and also to the company, some of the KOLs that you've been consulting with, you know, what is this sort of does this impact the way you're thinking about where to actually place it? You know, can you possibly see moving it up, you know, earlier, in the line of therapy and possibly even used as a, a debulking, you know, before you debulk, to shrink the tumor?
Don't, don't get crazy on me. You know, I think, you know, no. I mean, you have an active ingredient, an active agent. We're gonna always try to move it up. Now, you know, when we look at the current treatment paradigm, and this is a big change in our, in our treatment, is we still utilize platinum-based doublets, followed now by hormonal therapy, really anti-hormonal therapy with aromatase inhibitors. So I think at the-- moving forward, you're going to have the next line of therapy, to be this combination is absolutely where we're gonna be. Are we gonna wait till three or four prior lines? No, because your first lines are your platinum doublet, followed by your hormonal therapy, and your second line will be the combination.
So moving forward and trying to beat carboplatin paclitaxel versus hormones, you know, I think that will be something we'll look at in the future, particularly in a type of maintenance setting. This is me talking. This is the MEK. They've never had this kind of MEK. I want everybody to know that. But as a clinical investigator, obviously, I'm looking at those possibilities in the future, trying to get disease control and hopefully cure more patients.
All right. One last question, if you don't mind. You know, again, Dr. O'Malley, since you're a practicing physician as well, you know, can you just help us understand what are the more burdensome symptoms, you know, caused by the tumors in LGSOC? And like, you know, even if you don't, you know, cross that 30% threshold for OR, you know, is there any benefit in just shrinking the tumor a bit?
I'm gonna answer the second part of that. Absolutely, and that's why I emphasized that earlier. Disease regression is the key. And looking at the waterfall plot, I forget which slide that was, but you'll see about 86%, I think, was the official number of disease regression. What do I mean by that? Shrinkage of the tumor, the disease, that waterfall plot going below the zero curve, the zero line. As we look there, that is getting disease regression in a symptomatic patient is so important. What are the symptoms patients have? Your first part of your question. It's peritoneal disease, it's intra-abdominal disease, so pressure on other organs like the bowels, the pelvis, the bladder, the rectum.
GI, genitourinary, as well as bowel function, are usually the challenges that we have with patients as they become symptomatic.
All right. Thank you. Thank you for taking my questions. And congratulations.
Thanks, Pete.
Yep.
The next question is from Gregory Renza with RBC Capital. Please go ahead.
Great, thanks. Good afternoon, Dan, Verastem team, and Dr. O'Malley. Congrats on the data and the update. Thanks for taking my questions. Dan, maybe we could just start a bit with some of the discussions with FDA, and very helpful, and as you mentioned, more of a straightforward path now following the recent meeting. Just curious if you could comment a bit on, you know, what some of the discussions were around the bar for duration of response when it comes to mutant versus wild type, maybe what the FDA you think may be looking for. I appreciate that it can be, you know, difficult to play back to us, but I just wanted to ask. And maybe for Dr.
O'Malley, just on a related topic, you know, why does the KRAS wild type have that less favorable prognosis for LGSOC? And maybe, at what point would you put these patients with KRAS wild type, you know, on avutametnib if it is in fact listed on the NCCN guidelines? Thanks so much.
So I'll let John speak to the duration of response question. You know, in these discussions, you typically don't get a hard bar. It's a totality of the data. And I do think one of the challenges we had with the wild type is there weren't directly comparable data sets.
...And, you know, when you look for an accelerated approval, you know, arguably 17% is on the low end, and without a good direct comparative, that becomes a hard discussion to have. And we felt very strongly that the best thing we could do for patients is get this drug ASAP, and we do believe that it will be used across the board based on what we've seen. John, I don't know if you want to say anything more about the duration, but-
Yeah, I think maybe the only thing I would add is, I think as we interact with the FDA, you know, they think carefully about the measures of efficacy. They think carefully about the safety and tolerability, and they also think and look at what are the available information that can allow them to be confident about what can the available therapies deliver for patients. And as Dan has highlighted, although there have been trials now and started over a decade ago, talking about the GOG-281 and the MILO trial, those are important studies, but they're now started over 10 years ago. Neither study evaluated the KRAS mutation status in all of the patients. It's only a subset of patients.
I think for those reasons, you know, I think people would like to hear a single number that you need to beat. But the reality is that that's not how the agency approaches these questions. What they communicated to us is in the KRAS mutation group, the data we currently have provide, in their view, a clear path. Given the overview of data that we've discussed, you know, they share they see it as an important therapy for patients. Regarding the duration of response, we reviewed that with the agency, and they're quite satisfied with what they've reviewed and encourage us to go ahead and complete our rolling submission. I think you also had a question for Dr. O'Malley. I'll turn it over to him.
I think the question is, what would it take for you to use this in wild type?
Well-
That's right.
You know, what would it take and, and why are they harder to treat? I don't know. I don't know that. You know, I think as you look at the machinery and with the mechanism of action with regards to the more resistant, the cellular, replication is probably the reason, because we cannot interrupt the machinery and the repair mechanisms in the cell. And so when you have that mutated, then you can target it. Would I use this in a wild-type patient? Absolutely. You know, I think as you look at the options, we're already using hormonal therapy in the first-line setting, so the best treatment for this is hormonal therapy. So we're already utilizing that. What else do I have?
The unbelievably modest response rates with pegylated liposomal doxorubicin, weekly paclitaxel, we have zero response rate in topotecan, and we're looking at single digit to 0% response rates in this. I would absolutely use this in wild-type. I look forward to the opportunity to have it earlier than that in our mutated patients. And, you know, obviously, the off-label utilization in practitioners' hands will be important, as we often do. The most important thing, and I wanted to go back really quick to the regulatory question. One of the most important aspects that we were able to do here is to get the FDA to recognize low-grade serous ovarian cancer as its own entity. We've really been talking to them for decades to get them to understand this is a completely different disease compared to high-grade.
That is the most important bar that they now realize, and the most important aspect, I believe, besides obviously the response rate and the amazing duration of response, that will benefit the earlier approval.
That's really helpful. Appreciate the color, Dr. O'Malley. Maybe just one back to you, Dan, just for one final question. You know, as we know, this submission is for the combination of two investigational drugs. Just curious if you could just comment about any of the considerations that we should be keeping in mind as to what makes that unique and how Verastem is navigating that. Thanks again, and congrats.
I think one of the reasons we were so anxious to engage the agency early and really start the rolling NDA early, even before the data was mature, is it is two full CMC packages. And so, you know, we've been in tight communication with them around that. Obviously, FDA guidance on novel drug approvals, you show the contract for each agent, really why we had part A of the study.
And so, you know, we've carefully gone through each thing with the agency and, you know, again, you know, when you have two drugs, novel, when you get a clear signal that there's a path forward and that there's the potential it might be harder, you choose the easy path forward, so you can make the drug available to patients, and then we will continue to work on broader regulatory approval. But if you, as you've heard, and you've heard about our plans through NCCN, we do believe it'll be used, and we do believe it'll be reimbursed, but we are committed to pursuing a regulatory path as well.
Fantastic.
I think an important point, O'Malley. Sorry if I'm talking out of turn.
No.
You know, the dose optimization has already been completed with the cohort D that you heard for the first time here today. So not only do we have the relative contribution worked out, and I say we, because this is, these are drugs I've used a lot, and I treat the patients are sitting in front of me. I have no connection to Verastem except I participated in the trial. So when I say we, I just mean drug investigators. That we have the dose optimization completed at this point, as well as the relative contribution, two huge barriers to overcome approval.
Great point.
Great, thanks again.
The next question is from Michael Schmidt with Guggenheim. Please go ahead.
Hey, guys. Thanks for taking my questions. And, yeah, congrats on that data presentation. You have super interesting data, I think, especially the fact that response rate obviously seems to improve meaningfully in less heavily pretreated patients. And I think you mentioned there's potential earlier line use in clinical practice, perhaps, than what has been studied in the trial here. But have you looked at duration of treatment or PFS in less heavily pretreated patients, perhaps in a second or third line setting? What would that look relative to the 12.9 months in the study?
Yeah. John, you want to speak to that?
Yeah, thanks for the question. That work is ongoing, and we're evaluating different conferences and medical meetings to bring that work out. But in general, the observations that you're seeing are, you know, we see across various endpoints, but that work is ongoing, and we look forward to sharing that in more detail as it comes out.
Okay, thanks, and then a couple of commercial questions just on the fact that the initial label presumably will be in the KRAS mutant setting, obviously appreciating the potential for broader use, but can you talk about perhaps how common KRAS testing is in LGSOC in clinical practice, and what, if anything, needs to be done to get a companion diagnostic approved as well?
Yeah, so we had planned for a companion diagnostic. We've had a diagnostic partner for quite a while, and so, you know, we will have that in place. You know, as far as adoption in the community, you know, there's going to be education, and, you know, again, I think part of it will depend on, you know, if physicians feel they need to know the answer to that to make a treatment decision. But, you know, there have been varying levels of adoption of new diagnostics as they become available. You know, and probably saw, you know, this, that happened in lung cancer when we had PD-1 checkpoint agents and, you know, other KRAS agents. I don't know, John, if there's any other comments you want to make.
Yeah, I can just add that, most of the patients who enrolled on our trials already had, local, analyses done. Not all, but the majority have. And we have Dr. O'Malley with this. Would you, Dr. O'Malley, care to mention your experience?
Yeah. Across the world, in the U.S. and in Europe, basically, metastatic recurrent disease per the ASCO guidelines and SGO and NCCN, the recommendation is the next-generation sequencing. So we have patient when they're diagnosed to make these type of treatment decisions outside of a diagnostic test. These are commercially available. It's part of our routine treatment paradigm with metastatic recurrent disease.
Right. And then just from a modeling perspective, so thinking about the potential launch next year, pending approval by midyear, how should we think about the launch trajectory with given absence of, you know, effective approved other drugs? Would you expect a quick launch? Is there a potential pent-up demand even at that time point? Are you planning to avail an early access program, perhaps for patients before approval? How should we think about the launch trajectory?
Yeah, Mike, do you want to speak to that, recognizing I'll hold you accountable for whatever answers you give?
Sure. I mean, it won't surprise you, Michael, to say that we're not guiding towards it. But to your points, you know, the degree of unmet need, as I spoke to, is pretty profound, particularly in the prevalent pool within which will be initially indicated. These are patients that are well known to the physicians, and they themselves understand what disease they have. They've experienced multiple lines of therapy and the disappointing outcomes. So we have information from both physicians and patients themselves that on commercial availability of the regimen, there will be proactive conversations in both directions, understanding whether they're a good candidate for early access to these therapies.
Naturally, there are certain steps that you need to go through in a drug introduction within the U.S. to gain access and reimbursement to get on formularies, and those will apply to us just as to any other product. But we do expect rapid adoption and reasonably quick penetration of the prevalent pool.
Yeah, and just to speak specifically to an early access program, our commitment is to getting 301 accrued, and it's got very broad entry criteria, and we want, don't want to do anything that would lead patients away from our commitment to getting 301 done.
With a scheduled, Excuse me, with an optional crossover to 301, so all patients will have access to the combination.
Yes.
Great. Great. Well, thanks, and congrats on the data presentation.
The next question is from Graig Suvannavejh with Mizuho. Please go ahead.
... Hi, good afternoon or good evening. Congrats on the data. Thanks for taking my questions. I had just a couple. One, in relation to the presentation at the medical conference, could you give some color as to kind of how that went and whether there was an opportunity for Q&A or, or what the, you know, color around kind of the reception of the audience to the presentation was? So that's my first question. And then secondly, you know, awareness of any product as it's about, you know, to go from clinical stage testing to, you know, commercial stage product is important. So I'm just wondering if you can comment on the level of awareness of the combination therapy amongst, you know, the clinician and patient community.
And then lastly, if you could just remind me around the strategy of moving from the initial, perhaps, incident patient population to the prevalent population and the strategy on how you can execute on that. Thank you very much.
Yeah, I guess I'll just comment first on the presentation today. There was not an opportunity for audience Q&A. There is actually a seminar tomorrow morning that'll be a more in-depth review, where I think there'll be a lot more opportunity, for comment and questions. I don't know, Dr. O'Malley, what did you think the reaction was to the data in the presentation today?
Why don't you talk about the standing ovation? No, it was obviously exciting. You know, we have so few opportunities to study low-grade serous ovarian cancer. So to see exciting data like this maturing, overall was very overwhelmingly positive. I think we're all excited to have this option. We're all excited to enroll in 301 . So overall, very, very positive.
This is John. If I could just add, I was in the meeting, and so the way the presentation after the presentation by Professor Banerjee, there was a scheduled discussant, a professor, from France. And, as she discussed and put the data in context, she mentioned that the duration of response was beyond the best dreams before the study started. So I think, certainly the enthusiasm was quite high in the room.
Yeah, and I will say in general, I'd say awareness among physicians is quite high. Mike, maybe you can speak to some of the awareness programs we've done on the patient side, and then really our thoughts and the market research we've done about adoption by the incident and prevalent population.
Sure, happy to do that, Dan. Thank you, Graig, for the question. So yes, so awareness, as Dan indicated, among physicians is already very high. I think if you manage any reasonable volume of these patients, you're aware of the very few developments that are going on within the space, and we're clearly the most well-known among those because there aren't that many. Among the patients, to Dan's point, and I think I spoke to it a little bit, of the six to eight thousand prevalent patients, those that have at least suffered a single recurrence by the time we come to market, we have 2,500 of those patients already signed up with us through our unbranded website. And we also have approaching 750 physicians also signed up.
As you can imagine, there aren't that many physicians even within the U.S. that manage this disease. So both of those figures are very, very encouraging. In terms of adoption, what we've seen in the research is that each physician will start using the therapy at the point in which any individual patient experiences their next recurrence. But over time, I think to Dr. O'Malley's point, they'll be actively moving the therapy up so that when a patient suffers their first recurrence after their first-line debulking and chemotherapy and potentially anti-hormonal combination, we would be the next regimen that they would be anticipating using. So we would be used at our first indicated opportunity relatively rapidly.
Thank you very much. Congrats again on the data.
The next question is from Kalpit Patel with B. Riley. Please go ahead.
Hi, good afternoon. This is Jay for Kalpit. Thank you for taking my question. For RAMP 301, do you need to show a PFS benefit for each of the subgroups to secure approval in both wild type and mutant population? Or is hitting the primary endpoint for the overall population sufficient for a broad label in your view?
John, you want to speak to that?
Yeah, thank you for the question. So at the end of the day, it will be a review issue based on the totality of the data. Maybe one point I would just raise and elevate, the agency, all of the international experts, people do realize and recognize that, as was mentioned, there's about six to eight thousand women living in the United States with recurrent LGSOC. So, obviously, the studies are well conducted, they're well powered, but they'll also be of an appropriate size. In the clinical trials, an LGSOC will likely not be as large, for example, as an adjuvant breast cancer trial or something.
So I would think it's a reasonable expectation that so long as the overall population is positive, but also, you know, the trends need to be, let's say, encouraging across, you know, the different subgroups. So to answer your question specifically, that's a review issue. But I would anticipate that decision will be made with the awareness of the prevalence of the disease and will certainly take into account how in this randomized study the different subgroups of patients, you know, and tolerate the therapy.
Okay, thank you. And what's your expectation for PFS in the wild-type subgroup for RAMP 301? And what delta do you think would be needed for regulatory purpose?
Yeah, thank you again. So again, I think, as we shared today, the data we shared today, I find interesting and also compelling. As we've discussed in the RAMP 201 study, the median number of prior treatments was three. And that, to me, is understandable because at the time the study was conducted, there was less known about avutametnib and defactinib. I think it's possible that as the RAMP 301 study moves forward, now we know the data of 201. I think it's possible that the study could be offered to patients-- RAMP 301, that is, could be offered to patients on the average earlier in their treatment journey.
I think specifically the progression-free survival for both the control therapies as well as avutometinib and defactinib. Will it be a reasonable expectation that they may perform better the earlier in the therapy they're given. The study will enroll 270 patients. It's a well-powered study. But I think ultimately the final results will depend to some degree depending on the characteristics of the patients who enrolled in the 301 study.
Okay, thank you. And my last question is, what would be the distribution of a wild-type and the mutant patients in RAMP 301? Will it be fifty-fifty, like RAMP 201?
Yes, I understand the question. Thank you again for the follow-up.
Mm-hmm.
We have ongoing and regular meetings with the steering committee for the RAMP 301. The RAMP 301 steering committee is formed of really leading experts in LG associated research. And so we have approached this conversation about the concept of guardrails, right, so that we ensure there's-
Mm-hmm.
- at least, you know, a certain amount, no more than a certain amount. So it will not be, fifty/fifty precisely, reviewing the-
Mm-hmm.
potential and how, not just the potential. We're reviewing how to orchestrate the guardrails to ensure an appropriate balance.
Okay, got it. Thank you. That's very helpful.
The next question is from Bilal Jahangiri of Truist Securities. Please go ahead.
Hi, this is Bilal on for Kalpit. Congrats on the data. We're wondering, what is the likelihood of an Ad Com, and could that in any way change the potential for all-comer approval? And what was the rationale or feedback you got from the FDA for the wild-type subset? Was it the response rate or any other color? Thanks.
If I take that, this is John again. So we have breakthrough therapy designation for this combination. We have frequent interactions with the FDA. I do not anticipate an Ad Com. We're moving forward. Actually, as I shared back in May, we began the rolling New Drug Application after meeting with the agency. They actually have to invite you to initiate the rolling in a rolling NDA, so we have to reach agreement even before you start that. So we had agreement to initiate a rolling New Drug Application. The agency asked us to meet with them again when these data became mature, and we have done that. And so, we're moving forward now to complete this rolling New Drug Application. So I do not anticipate an Ad Com.
I think the other question was regarding maybe color or the agency reviewing thoughts about the wild type patients. And I think, again, you know, the challenge that the FDA has is that the available data, like these historical studies and other presentations. Well, one, the large studies now started enrollment over a decade ago, and they did not stratify or even have complete KRAS information on all the patients. So, again, I think the agency has communicated that they see the review path as clear in the KRAS mutant at this point. We think it's important, we have a responsibility to bring this therapy as quickly as we can to market so that patients can receive it and can benefit from it.
It seems to us the most expedient, the most clear and direct path is to proceed along this agreed-upon approach, and to complete this rolling new drug application.
Great, thanks. And, so on the topic of the rolling NDA, is there a potential for any additional updates that you would submit to the FDA, like more durability or deepening responses? And then, what needs to be done to get onto NCCN guidelines or compendial listing?
Yeah. So I think as we mentioned, the New Drug Application, we anticipate will complete this month. As you may know, after you complete a New Drug Application, you often are asked to give a safety update, and we expect and plan to do that. So, the data we think are on track and everything that's needed and typical is ongoing. Maybe regardless of NCCN, I think your question was, how does a drug get added to the NCCN guidelines? Is that correct?
Yeah. What do you think you guys need to show? Or what do you—what can you do? What's in your control? Yeah.
I guess that's a good question. Yeah. I mean, the general process, as you may know, the NCCN guidance committee are composed of really our nation's experts in a given disease space. So these are folks who certainly know the literature very well. And maybe one way to answer your question is there are today already NCCN guidelines for the treatment of LGSOC. And the therapies that are there, if you look at the available literature, you know, one, as I mentioned, these trials that supported these drugs getting on to the NCCN guidelines are some of them actually a decade or more old. Therefore, they don't represent necessarily the kind of treatments that patients are receiving during the modern era.
And if you look at the response rates that are known, what we do know about the response rates of the available therapies, both in K-RAS mutant and also what we know about in K-RAS wild type, the numerical response rates that have been presented here are higher. So I would think it would seem reasonable to me that the data that supported the current NCCN guidelines and has the therapies that are there, seeing how this is a 200-patient study here, all in the modern era, intensely pretreated, I think this. I mean, I expect that avutametinib and defactinib , and it will be on the guidelines after approval.
From a process perspective, we need a peer-reviewed publication, which we intend to have prior to approval, and then the NCCN Guideline Committee typically will meet when a new drug gets approved. And, a number of, folks within our organization have been through the process before.
Yeah, I sat on the NCCN guidelines for 10 years, so I reiterate that. We have to have approved agents. If the agents are approved in other indications, they can be listed, and you see that on the slides that were presented today. So once they have an approved agent, they have a publication, they will meet either regularly or talk to update the guide.
Thank you so much, and congratulations again.
Thank you.
The next question is from Justin Zelin with BTIG. Please go ahead.
Thanks for taking our questions, and congrats on those compelling data readout. Maybe just to follow up on the last question, just on the timeline for NCCN guideline consideration. Was just curious on when you'd expect to submit the RAMP 201 data to the NCCN and when they might include it. You know, would that be kind of an ad hoc meeting, as you described, or do they meet regularly throughout the year to be considered in one of their regular meetings? And maybe a question for Dr. O'Malley, if you could share any anecdotes on what the patient experience has been like on the treatment of the combination, you know, qualitatively, any improvements in quality of life and how was managing the adverse event profile? That'd be great. Thank you.
Yeah, I mean, our expectation is, you know, when the drug is approved, since it's the first drug to be approved for this indication, that there will be a meeting soon after the approval, and our goal is to have our peer-reviewed publication out prior to that, so there'll be no delay in the addition to NCCN guidelines. When we went through this with duvelisib, which frankly wasn't as a compelling drug as this is, we were on NCCN guidelines within a week of approval.
Yeah, I can just add, in my previous experience, it's been one or two weeks. So I think it would be hard, probably impossible, to know whether it's, you know, one day, one week, a couple weeks. But as we reviewed previously, the currently available therapies have response rates on the guidelines, you know, 0%, 5% or 10%. So I would anticipate that results like this and the enthusiasm that we see from the nation's experts, I would expect the NCCN to convene a meeting very quickly.
Yeah, 100%. You know, once we get a new FDA approval of the drug, we don't mess around. Again, I'm no longer in the NCCN guidelines, so I can speak to that, but I'm not breaking any confidence here, obviously. With regards to experience, you know, when you get disease regression, if you can control disease, people feel better. When you get disease regression, if they're having symptoms, their quality of life is better. Obviously, you know, rash and GI, as you saw, we've gotten much better over the years with regards to treating these two types of side effects. The antiemetics, which is not a big deal, actually, but if patients do have nausea, we have added medications to really control that.
So, you know, from a standpoint of the CK elevations, that somewhat was alarming when we first started using these agents. We've learned so much about it over the lifespan so far of the 201 trial. So, and obviously, the FDA weighed in, seeing that there is no clinical significance, that when we first started was a little, you know, brought us to pause because it's not something we normally you worry about muscle degeneration, all these other things, and we've just not seen that. They actually really don't even have any kind of muscular pain. So from an overall standpoint, particularly compared to the other MEK inhibitors, I've been really pleasantly surprised that of the tolerance.
Obviously, it takes some knowledge with regards to manage this, the side effect profile, but it's a very manageable side effect profile.
... Great. Thanks for taking my questions, and congrats once again.
Thanks.
The next question is from Sean Lee with H.C. Wainwright. Please go ahead.
Hi, good afternoon, guys. Thanks for taking my questions. I just have one on the phase three studies. I was wondering, early in the call, you mentioned that bevacizumab use could be a key factor in affecting the overall response rate of these patients. Is there any way you are able to control that in the phase three study, especially, considering that the standard of care arm is physician's choice of therapies?
Yeah, for prior therapies, the fact that this is a randomized study will give us a more balanced choice, opportunity to compare against other therapies. Because, again, you know, we've been doing cross-trial comparisons of patients with more prior lines of therapy, more Bev, you know, they didn't have prior MEK. You know, we'll be on a more even ground here because it's a randomized study.
I see. And, in terms of the physician choice therapies, then, a quick follow-up. Since there isn't anything specifically approved, what therapies do you think will likely be used for the comparator arm, and what are the typical response rates we see with those?
Yeah. Thank you. This is John again. Thanks for that question. So let me just clarify. The protocol allows for predefined options for the physician's choice, and those options came, again, working with the steering committee, which again, experts LGSOC, to identify in current practice, in other trials, what have been commonly chosen and are commonly chosen options. I think, like you're pointing, you don't want an endless menu of choices because you do want the ability to, at the end, compare this study to other studies. And you need to be able to power the study, which means you need to know and have some idea about how the therapies have behaved in the past. So the in this trial are paclitaxel, pegylated liposomal doxorubicin, and anastrozole and letrozole.
Those were chosen again by the steering committee, based upon the frequency and the commonness of those being chosen therapies for patients with recurrent LGSOC.
Great. Thanks for that. That's all I have.
This concludes our question and answer session. Thank you for attending. This now concludes our call.