Q3 2024 Karyopharm Therapeutics Inc Earnings Call
Good morning, my name is Jenny, and I will be your conference operator today.
At this time, I would like to welcome everyone to carry a form of therapeutics, third quarter, 2,024 financial results conference call.
There will be a questioning answer session to follow. Please be advised that this call is being reported at the company's request. I would not like to turn the call over to Ahun Webb, seeing your vice president invest a relations. Please go ahead.
Ahun Webb: Thank you, and thank you all for joining us on today's conference call to discuss CARE Farm's third quarter 2024 financial results and recent company progress.
Speaker Change: We issue the press release this morning, detailing our financial results for the third quarter 2024. This release, along with a flight presentation that will reference during our call today, are available on our website.
For today's call, I've seen Osloide 2. I'm joined by Richard, Rajma, Sohanya and Mike, who will provide an update on our results for the third quarter 2024 and recent clinical development.
Speaker Change: Before we begin our formal comments, I'll remind you that various remarks we will make today a constitution for looking statements, SLS, for purposes of the SAF Harbor provisions under the private security, speedification reform act of 1995, our final slide.
Ahun Webb: Actual results made differ material from those indicated by these evidence as the result of various important factors.
Ahun Webb: including those discussed in the risk factors section of our most recent form, TENQ, which is on file with the SEC and in other fileings that we may make with the SEC in the future.
Ahun Webb: Any FLS we present our view as of today only.
While we may elect to update these FLS at some point in the future, we specifically disclaimer any obligation to do so even if our views change. Therefore, you should not rely on these FLS as you present our views as of a new later date.
Speaker Change: I will now turn the call over to Richard, please turn to slide forward.
Richard: Good morning, thank you, Elhan and thank you all for joining us today for Carrier Farm's Q3, 2024 earnings call.
Richard: Turning the slide five, I want to begin with the exciting news that we shared last week regarding our phase three, sensory trial in myelphibrosis.
We announced a very favorable regulatory update as we are changing the co-paramere endpoint of century to absolute TSS following productive discussions with the FDA.
Richard: Absolute TSS is supported by leading investigators and patient advocacy organization and increases our overall confidence in our trial.
We remain on track to report top line data from century in the second half of next year.
Cell and Exor's unique mechanism of action, compelling data, are targeted approach to clinical development and ongoing discipline and cost management, position us well to advance our prioritized late stage pipeline.
which may enable two transformative opportunities as we build on our multimagoma foundation.
Richard: With our existing commercialization capabilities, we are pleased to deliver our third consecutive quarter of net product revenue growth in the U.S., and our contract to deliver revenue in the upper half of the guidance outlined at the start of the year.
Our established commercial organization is well set up to potentially drive successful and rapid launches in MyLofiBrosis and the Metriol Cancer.
Turning to slide six in MyolphiBrosis, if the data from our phase three century trial is supportive, we believe we will have the opportunity to transform the treatment paradigm by providing the first combination therapy in Jack and Iyth MyolphiBrosis.
While Raksalitna Ballone has remained a standard of care for over a decade, less than half of all patients achieve meaningful, clean reduction.
Richard: We believe that combination therapy with a novel mechanism of action like X-F-O-1 inhibition holds the key for driving rapid, deep and durable responses for the vast majority of myelfibroce's patients.
Richard: We continue to estimate that our annual US peak revenue opportunity of mile firebrosis is approximately 1 billion dollars in the multi-billion dollar mile firebrosis market.
Richard: and Demetriol Cancer, the opportunity remains substantial given the evolution in the molecular-driven therapies.
Richard: Our data in TPP53 Wioship and Amitual Cancer offers the potential of a meaningful and unique mechanism in maintenance therapy for approximately half of all endometrial cancer patients.
Richard: This represents approximately a billion dollars annual US peak revenue opportunity as well.
and Rachma will expand in detail on both these near-term transformative opportunities.
Speaker Change: Now I'd like to turn the call over to Reshma, who will give an update on our clinical programs. Reshma.
Reshma: Thank you, Richard. Turning the slide A, I want to highlight the unique potential of our promising late stage pipeline, led by our three ongoing phase three studies.
Harry Affarme has the potential to establish these standards of care in solid and hematologic malignancies, building upon our foundation in multiple mile Oma.
Reshma: So I also optimize the patient experience by incorporating substantially lower doses of cell and F4 in the studies.
Beginning with Marlify Bruce's on slide 10, Selling Actors, a novel inhibitor of XP01 that prevents the new X4 of various proteins and messenger RNA molecules.
Reshma: By doing so, it promotes the nuclear localization and the activation of important tumor suppressor pathways such as C53, well, concurrently inhibiting the cytoplasmic activation of various calipyridids and pro-cylidrotic pathways linked to mylipygler's epiology.
In addition to these multiple pathways, positions, cell and exorbs, and unique potential therapeutic options in myelocybrosis.
The Board Highlighting are important us state to the co-prinary endpoint relating to total systems score. I will recap efficacy and safety data observed from the Phase 1 trial evaluating cell and export plus Rucksack-related in Jack and Hibiter and IE's MyLocic group of patients as outlined on slide 11.
Reshma: Among the 14 patients who received cell and F-16 milligrams of drug forbidden, all is valuable patients achieved in F-VR-35 at any time, and 79 percent of patients achieved F-VR-35 at the 24th in the ITT population.
Reshma: As you heard from some of the leading physicians in the space on our call last week, leading volume reduction in view that's one of the most important factors by treating physicians, given its correlation to overall survival. Having nearly 80% of patients achieved SBR 35 is viewed as very positive.
Reshma: Durability of response is also a key efficacy measure relevant to Jack Nyeye's patients.
Our Phase 1 data demonstrates a 100% probability of continuing with songs for both SBR 35 and PSA 50 at shown on slide 12. So we're a media generation of follow-up of 32 weeks and 51 weeks respectively.
Reshma: This is particularly meaningful as it suggests that once patients experience a response they remain in the sponge.
Reshma: On our call last week one of the Kailwell syndicated that this is why he believes treatment so an extortion he added to re-pollet med early on in the treatment journey. Given his views, a deeper plan to the early on or important and can improve outcomes for patients.
Reshma: Hearn in the slide 13, we were very pleased to announce last week that absolutely total systems for will replace PSS 50 as a co-primary endpoint in our country's day three trial in MyWelph, Röpick.
Reshma: A Fessing Me Outreach Improvement in Citizens over 24 weeks since this game support from the FDA, investigators, and patient advocacy groups. And is a more sensitive message to a sub-subjective improvement in viral fibresas.
Reshma: The combination of cell and exor and rungs of litinate has demonstrated promising evidence of improvement in absolute total symptoms of scores in our phase one trial. Can we look forward to utilizing this more comprehensive assessment of symptom improvement in moving forward?
Reshma: Building on our impressive SPR35 results from our Phase 1 trial.
Reshma: Changing our co-primary endpoint to absolute TSS further increases our overall confidence in the Sentry Phase III trial, and we look forward to potentially addressing a tremendous unmet need in myelofibrosis with this combination.
Reshma: On slide 14, the depth of symptom improvement with 60 milligrams of Selenexor plus ruxolitinib in our Phase 1 trials can be seen in comparison to historical data from ruxolitinib monotherapy. The average reduction, which signifies improvement.
Reshma: An absolute TSS of 18.5 points with our combination compared favorably to the average 11-14 point reduction that has been observed with Rexalutinib alone in prior phase 3 clinical trials conducted by others.
Reshma: The rapid, deep, and durable findings observed with SDR-35 is also observed with average TSS, as seen on slide 15.
Reshma: These are new data we are presenting for the first time today.
Reshma: These rapid improvements in symptoms are seen as early as week 4, despite any side effects that the patients may experience from the treatment. These symptom improvements continue through week 24, demonstrating meaningful, sustained symptom improvement for the entire 6-month duration evaluated.
Reshma: For the adverse events experienced, the most common were GI side effects such as nausea, anemia, thrombocytopenia, and fatigue. And I think it is worth considering what we heard from our KOLs on GI side effects last week.
Reshma: These GI side effects are most common at the start of treatment, only last approximately two cycles, and can be effectively managed with antiemetics.
Reshma: Given this well-documented profile, we believe patients and physicians can easily be educated around this profile, enabling patients to stay on treatment long-term, which ultimately is what drives meaningful screen reduction and symptom improvement.
Reshma: In summary, slide 16 highlights why the combination of Felonexor and Ruxolitinib has the potential to become the new standard of care if the combination is approved.
Reshma: Selenox's potential in myelofibrosis is strengthened by its well-established safety profile, as it has been administered to approximately 30,000 patients across multiple cancer indications.
Reshma: The low dose of 60 mg that is currently incorporated in the Phase III trial suggests that Selenoxor has the potential to be a tolerable, convenient once-weekly oral treatment, especially with the use of anti-emetics during the first two cycles of treatment.
Reshma: Given the strong enrollment, our expectations of top-line data remain in the second half of 2025.
Reshma: Furthermore, the co-primary endpoint will change from TSS50 to absolute TSS.
Reshma: The two co-primary endpoints, FVR35 and Absolute TSS, will be tested sequentially. FVR35 will be evaluated first, and if positive, the alpha will then be rolled down to Absolute TSS.
Reshma: Shifting focus to endometrial cancer on slide 19.
Cellinexor primarily functions by blocking the export of T53 from the nucleus to the cytoplasm. When T53 accumulates in the nucleus, it leads to disrupted DNA repair processes, cell cycle arrest, and increased apoptosis.
Reshma: As seen on slide 20, the P53 wild-type status continues to increase in relevance throughout the treatment landscape for advanced and recurrent endometrial cancer.
Reshma: Recently, the FDA approved checkpoint inhibitors in combination with chemotherapy, followed by maintenance therapy with checkpoint inhibitors for advanced recurrent endometrial cancer patients, regardless of MMR status.
Reshma: However, the efficacy in patients with MMR-proficient tumors is notably lower compared to those with MMR-deficient tumors, aligning with the mechanistic rationale for the effectiveness of checkpoint inhibitors in MMR-deficient solid tumors.
Reshma: Notably, patients with both MMR-proficient and T53-wild-type tumors make up approximately 50% of all advanced or recurrent endometrial cancer cases.
Reshma: On slide 21 in the CIENDO trial, exploratory subgroup data presented at ASCO revealed that Selenosor has the potential to provide promising outcomes
Reshma: for patients with P53 wild-type endometrial cancer, achieving a median PSF of 28.4 months compared to just 5.2 months for placebo, translating to a hazard ratio of 0.44.
Reshma: Looking more closely at the MMR coefficient subgroup on slide 22, our ASCO data on Siendo showed Selenexor demonstrates an encouraging signal of long-term median PFS benefit of 39.5 months.
Reshma: This was substantially higher than the 4.9 months observed placebo, corresponding to a hazard ratio of 0.36.
Reshma: Although we acknowledge the limitations of cross-trial comparisons, it's important to note that the PFS improvement with Selenexor in the subgroup exceeds the median overall survival.
Reshma: achieved by checkpoint inhibitors in MMR-proficient patients, emphasizing Selenexler's substantial efficacy for these individuals.
Reshma: The updated safety data in endometrial cancer patients from the Sander trial is displayed on slide 23.
Reshma: It's important to note that the adverse events associated with Selenexor were generally manageable and well-tolerated. Nausea, vomiting, and diarrhea were the most frequently observed adverse events, regardless of grade.
Reshma: Grade III plus treatment emergent events were infrequent with neutropenia, thrombocytopenia, and nausea being the most common.
Reshma: Notably, the prophylactic dual anti-emetics were not required during the standard trial, whereas dual anti-emetics are not only required in EC042, but all of our Phase III trials, including Sentry.
Reshma: which is why we anticipate the safety profile from our Phase 3 trials will be substantially improved.
On slide 24, we remain on track for top-line data readout for our Pivotal Export EC042 Phase 3 trial in early 2026.
Reshma: I remain encouraged with the potential of Selenexor to achieve clinically meaningful outcomes in the maintenance setting for patients with B53 wild-type endometrial cancer, especially those with MMR-proficient tumors.
Reshma: Lastly, our Phase 3 EMN 29 STD trial is outlined on slide 26.
Reshma: This trial aims to address the unmet needs of patients with multiple myeloma by offering an all-oral triplet treatment option that could also benefit those undergoing pre- and post-T cell engaging therapy.
Reshma: and built on the positive progression-free survival data previously observed with SPD-40.
Reshma: As we noted on our second-quarter earnings call, we have worked with the sponsor of the trial, the European Myeloma Network,
Reshma: to amend the Statistical Analysis Plan.
Reshma: We have completed screening for the planned approximately 120 patients and will provide an updated timeline for top-line data following regulatory feedback.
Reshma: We are very excited for what the future holds for Carrier Farm, working swiftly to progress our three physical phase three programs.
Reshma: fueled by increasingly compelling data.
Selenexor could significantly benefit various patient populations facing substantial unmet needs and also enhance or currently improve indications in multiple myeloma. I will now turn the call to Sohanya to provide updates on her commercial results from this quarter.
Sohanya: Thank you, Reshma, and good morning.
Sohanya: On slide 28, I'll discuss our commercial highlights for the third quarter of 2024. Expovio Net product revenue was $29.5 million, up 5% compared to our results in the second quarter.
Reshma: We are very pleased with our third consecutive quarter-over-quarter growth of Expovio U.S. revenues amidst a highly competitive marketplace.
Reshma: and are well on track to deliver in the upper half of the guidance that we outlined at the start of the year.
Reshma: In Q3, Expovia revenues were driven by double-digit demand growth versus the prior quarter, powered by an increase in refills and partially offset by an increase in gross-to-net, largely due to a higher 340B book of business.
Reshma: We achieved strong demand growth quarter over quarter in the community where Expovio tends to be used as a convenient oral and manageable option for patients as an earlier line of therapy or if the patients are unable to access a T cell therapy.
Reshma: We also delivered growth in demand in our academic setting as our use as a novel mechanism of action pre and post T cell therapies continues to increase.
Reshma: With our team's strong execution driving demand growth for Expovio year-to-date, we are confident in our ability to deliver on our revised full-year 2024 U.S. Expovio Net Product Revenue Guidance range of $110 to $115 million.
Reshma: I am pleased with our momentum as we expand our global footprint with continued reimbursement and regulatory approvals for Cellunexor across the world.
In the third quarter, Expovia received reimbursement approvals in Italy and France and continue to expand its global footprint with additional regulatory approvals globally.
Our commercial franchise continues to benefit an increasing number of multiple myeloma patients globally, and as a profitable business, serves as a critical driver in funding our pipeline.
With our dedicated commercialization team and partners, we have the capabilities for strong launches in potential future indications.
Reshma: I'd like to now present in detail the potential market opportunity that we see for Selenexor in myelofibrosis and endometrial cancer, each amounting to approximately a billion dollars in potential annual U.S. peak revenues.
Reshma: Turning to slide 30, starting with myofibrosis.
Reshma: As discussed by Reshma and on our call last week, Cellinexor has the opportunity to transform the frontline treatment paradigm in myelofibrosis.
Reshma: As we look at the myelofibrosis market in detail, there are roughly 7,000 estimated incidences in the U.S., about 6,000 of which are patients with intermediate to high-risk myelofibrosis.
Reshma: Approximately three-quarters of these patients with baseline platelet counts of a hundred or above make up the target patient population for Selenexor combination therapy.
indicated their intent to adopt combination therapies as a front-line standard of care, replacing roxalizumab monotherapy due to the potential of better efficacy with the combination.
Reshma: The survey results also showed a strong perception from physicians on the product profile of selinexor in combination with roxalizumab.
We would anticipate strong demand at launch if approved given our data to date showing Selenexor's ability to meaningfully improve spleen volume and symptom management when added to the current standard of care.
Reshma: Furthermore, we have an established commercial infrastructure in the hematology space and about 80% overlap in community-based physicians who treat multiple myeloma and myelofibrosis.
Reshma: This gives us a tremendous opportunity to build a strong presence for Selenexor in the multi-billion myelofibrosis market with a potential annual U.S. peak revenue opportunity of approximately $1 billion.
Now I'd like to shift your attention to endometrial cancer on slide 31, which is an equally attractive opportunity for us. We are very encouraged by the potential for Selenexor to address a significant unmet need in key molecular subgroups.
As we engage with key opinion leaders in this space, it is clear that they see the unmet need for a targeted treatment in unique molecular subgroups, including TP53 wild-type tumors.
Reshma: While frontline treatment options are emerging rapidly, a clear unmet need remains in the P53 wild-type and specifically PMMR subgroup.
Looking now at the potential market in more detail, endometrial cancer is the most common gynecologic cancer in the US with about 17,000 expected incidences in 2032, approximately 80% of which is expected to be PMMR and 20% DMMR.
Reshma: About 10,000 advanced or recurrent endometrial cancer patients are expected to have P53 wild-type status.
With about two-thirds of patients expected to respond to their front-line chemotherapy, roughly over 6,000 patients would be eligible for Selenexor, a potential novel and biomarker-specific oral maintenance therapy.
In third-party market research, when U.S. physicians were shown multiple product profiles, Selenestor was the preferred regimen for 75% of patients with TP53 wild-type and PMMR status.
With our strong commercial presence in community accounts with Expovio, we expect to have roughly 80% overlap in community-based oncologists who treat multiple myeloma and endometrial cancer.
As a result, we expect a rapid potential launch of selinexor and metriocancer if approved, with a potential annual U.S. peak revenue opportunity of approximately $1 billion.
Speaker Change: Now I'd like to turn the call over to Mike to give an update on our Q3 financial results.
Mike: Good morning, everyone, and thank you, Sohanya. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which are on slide 33. Total revenue for the 3rd quarter of 2024 was $38.8 million, compared to $36 million for the 3rd quarter of 2023.
Net U.S. Expovio revenue for the third quarter of 2024 was $29.5 million compared to $30.2 million for the third quarter of 2023.
The growth to net discount for Expovio in the third quarter of 2024 was 31%, as compared to 21% in the third quarter of 2023 and 29% in the second quarter of 2024.
This increase was driven by increased 340B utilization and Medicare rebates. We expect GTN for the full year 2024 to be approximately 30 percent.
Our total expenses for the third quarter of 2024 were down year over year by 3% due to ongoing headcount reductions and other cost-saving measures harshly upset by our continued investment in our three ongoing phase three clinical trials.
R&D expenses for the third quarter of 2024 were $36.1 million, compared to $35.6 million for the third quarter of 2023. The increase in R&D expenses was primarily attributable to higher clinical trial costs related to our ongoing, pivotal Phase III trial in myelofibrosis.
SG&A expenses for the third quarter of 2024 were $27.6 million, compared to $30.8 million for the third quarter of 2023. The decrease in SG&A expenses was primarily due to ongoing cost reduction initiatives and lower headcounts.
Speaker Change: Cash Test Equivalents for Restricted Cash and Investments as of September 30th, 2024 totaled $133.9 million compared to $192.4 million as of December 31st, 2023.
Based on our current operating plans, we are narrowing our guidance for the full year of 2024 as follows. Total revenue is expected to be in the range of $145 to $155 million, as compared to previous guidance of $145 to $169 million.
Speaker Change: U.S. Expovio net product revenue is expected to be in the range of $110-$115 million as compared to previous guidance of $105-$120 million.
R&D and SG&A expenses are expected to be in the range of $255 million to $265 million, which includes approximately $20 million of estimated non-cash stock-based compensation expense, as compared to previous guidance of $250 million to $265 million.
And finally, we expect our existing cash-cash equivalent investments, the revenue we expect to generate from ExplovioNet product sales and other licensed revenues, and ongoing discipline and expense management and cost-saving measures will be sufficient to fund our planned operations into Q1 2026.
Note that our cash runway does not include paying off the remaining 2025 convertible notes in our $25 million liquidity covenant under the new term law.
We expect our 2025 operating expenses to be lower than 2024 to recognize the full-year benefits of our ongoing cost-saving initiatives.
In summary, we are focused on the advancement of our three Phase III trials and driving commercial performance while continuing to be very diligent when allocating our resources.
These trials have the potential to deliver new standards of care for patients and significantly advance our company as we work to deliver value for our shareholders.
Speaker Change: As we move forward, we will continue to work diligently towards unlocking the full potential of Selinexor and driving our next phase of growth.
Speaker Change: Thank you again for joining us today, and I would now like to ask the operator to open the call up to the Q&A portion of today's call operator.
Speaker Change: Okay.
Speaker Change: <unk> and gentlemen, we will now begin the question and answer session did you have a question. Please press the star followed by the one and then you touched on filing.
Speaker Change: Questions will be taken in the order received should you wish to cancel your request. Please press the star followed by the two.
Speaker Change: You're using a speaker phone please lift the handset before pressing any keys.
Speaker Change: Your first question is from Brian Abrahams from RBC capital markets. Your line is now open.
Brian Abrahams: Hi, good morning, Thanks for taking my questions.
Brian Abrahams: Best wishes to Mike as well in his future endeavors.
Brian Abrahams: Two quick ones from me I guess first on.
Brian Abrahams: The average total symptom score on slide 15 that you've shown.
Speaker Change: <unk>.
Speaker Change: Pretty meaningful.
Speaker Change: Notable reduction over that 24 week period.
Speaker Change: But I'm just wondering how the magnitude of that change is influencing your powering assumptions and the reason I ask because I believe <unk> original open label Phase two study on top of Rux showed at least a median absolute TSS improvement in that same 60% or so.
Speaker Change: Ballpark.
Speaker Change: And then ended up sort of just being on the cusp of statistical significance in a 400 plus patient phase III and then.
Speaker Change: Secondarily.
Speaker Change: TSS 50 is that still going to be a secondary endpoint in.
Speaker Change: In the phase III study and is that something that you think the FDA will still be looking at at least to even see.
Speaker Change: Some observed some trends there.
Speaker Change: Potentially supportive of approval or the regulators have the regulators completely shifted to really only focusing on absolute thanks.
Speaker Change: Thanks, Brian for the question. This is a very small.
Speaker Change: So in terms of average T. S. A so you noted on slide 15, yes, I think those are very meaningful data I'll, just reiterate as I did.
Speaker Change: On our prepared remarks.
Speaker Change: What those data show over time is that the average T. S. A substantially improved starting as early as week 24, and then you can see is the patients progress from week four to 24, you continue to see this document all the way to that average.
Speaker Change: 18, five reduction that we've reported as part of the absolute TSS. So it really reinforces this meaningful improvement, which again as signified by a reduction in that PSS score.
Speaker Change: When we look at our powering assumptions, what we're looking at is the delta across the two arms right. So the average or the absolute T. S. US is an average assessment of the change in TSS from baseline to week 24 in the manifest data.
Speaker Change: Observed in approximately two point difference across the two arms. It was not statistically significant our data suggests that we could observe something that is far higher you know well above two if not double to four or above so again I think the data are.
Speaker Change: Throng really shows a very meaningful improvement when you translate the likelihood to a phase three it really suggests that.
Speaker Change: You cannot only see statistical improved statistical significance and that absolute PFS, but a clinically meaningful results as well.
Speaker Change: In terms of your second question for T. S has 50. So you know we are we are in a very enviable position to replace TSS 15 with absolute tier. So the co primary endpoints again will be SVR 35, Paul.
Speaker Change: Road by absolute TSS.
Speaker Change: We will not be evaluating T. S has 50 I think we are really seeing an evolution in terms of how we assess symptoms within a JAK naive space.
Speaker Change: I think everybody is in alignment and when I say, everybody I'm really talking about our kols.
Speaker Change: Patient advocacy groups, certainly the regulatory agencies that absolute TSS, which again looks at the average over time is probably the more sensitive and their comprehensive way to analyze these symptoms.
Speaker Change: That's really helpful. Thanks, Thanks, Brian.
Speaker Change: Yeah.
Speaker Change: Thank you. Your next question is from Ed White from H C. Wainwright. Your line is now open.
Ed White: Good morning, Thanks for taking my questions.
Ed White: Congratulations on the new regulatory approvals outside of the U S.
Ed White: I'm just wondering if you can give us an update of where you stand in the countries that.
Ed White: We've already launched how the launches are going and outlook outside the U S through 2025.
Speaker Change: Yes, Thanks, Ed I'll turn this on you for that.
Ed White: Hi, Ed we continue to see.
Speaker Change: Approvals for reimbursement as well as regulatory approvals are in the past quarter.
Ed White: And we're very pleased with the global expansion of Selinexor.
Ed White: You compare to some of the U S launch.
Ed White: Launch experience says, they're starting and largely earlier lines of therapy versus penta.
Ed White: Our refractory and that obviously they have some good learnings in terms of anti emetic side effect management.
Speaker Change: And so as we look at 2025, we will obviously provide guidance on total revenues.
Speaker Change: Q4, 2024 call, but with the ongoing reimbursement approval and launches. This year, we anticipate royalties from ex U S. So even XR revenues to increase in 2025.
Speaker Change: Now in 2024, we achieved the majority of the major market reimbursement approvals. Therefore, we don't expect those to reoccur next year again, we'll provide more color on total revenue guidance on our Q4 'twenty four o'clock call.
Speaker Change: Okay. Thanks.
Speaker Change: Just to dig down into the <unk>.
Speaker Change: It needs to grow market you know just wanted to get your thoughts on some of the challenges of entering a maintenance therapy market.
Speaker Change: A treatment market.
Speaker Change: How the company is addressing that particular market.
Speaker Change: And getting patients to take the drug.
Speaker Change: Maintenance setting.
Speaker Change: Yeah, we are thrilled about the opportunity to launch in endometrial cancer as a potential novel and biomarker specific oral maintenance therapy.
Speaker Change: For a couple of different reasons, I think as you've seen the marketplace evolve rapidly, particularly in the past year. There continues to be a significant unmet need in specific specific molecular subgroups and.
Speaker Change: And in our case, particularly focused on the P 53, wild type and P. M. M. R subgroup and this is where our data is reach my has discussed is most compelling.
Speaker Change: Now as we look at our product profile as a maintenance therapy.
Speaker Change: It is a highly compelling profile as supported by our market research as I mentioned when U S. Physicians were shown multiple product profiles.
Speaker Change: Selinexor was the preferred regimen for a majority 75% of patients with T. P. P. III wild type M. P MMR status so.
Speaker Change: My belief is we have a potentially groundbreaking therapy in this maintenance space in a highly targeted subgroup with a compelling profile and a convenient oral therapy important to also reinforce that as our commercial team we have very strong overlap.
Speaker Change: Lap with treating physicians, both in the multiple myeloma space and the endometrial space in the community, which enables us to hit the ground running with our messaging on day of approval. So.
Speaker Change: We are very excited about the potential opportunity to launch in this maintenance setting.
Speaker Change: Okay. Thanks for taking my questions.
Speaker Change: Thanks, Ed.
Speaker Change: Thank you once again that is star one should you wish to ask a question and your next question is from Peter Lawson from Barclays. Your line is now open.
Peter Lawson: Great. Thanks, so much thanks for taking the questions.
Peter Lawson: Just initially on the quarter.
Speaker Change: Sonya.
Speaker Change: <unk> seen three quarters of quarter over quarter growth for the future.
Speaker Change: You can make any comments about any.
Speaker Change: Any underlying trends there or anything that was different from the last couple of quarters for that quarter over quarter growth in kind of the.
Speaker Change: The mix between.
Speaker Change: Price and volume and then academic versus community settings. Thank you.
Speaker Change: Thanks, Peter for the question.
Speaker Change: We're very pleased with our three consecutive quarters of net revenue growth very proud of the team for the resilience and success they have demonstrated particularly.
Speaker Change: Q3 in driving double digit demand growth quarter over quarter.
Speaker Change: As we look at some of the dynamics here in terms of settings of care in the community setting we achieved strong growth quarter by quarter. This remains the majority of our business about 60% of our business came.
Speaker Change: Came from the community setting.
Speaker Change: Importantly in Q3 as well, we did see an uptick in demand in our academic setting as well quarter over quarter and this is really driven by the body of evidence that we have worked hard to build in the past year around this concept of T cell fitness.
Speaker Change: And selinexor its potential ability to preserve the immune environment with respect to T cell therapy. So as we look at this current year to date and our performance.
Speaker Change: Our team is working hard to continue to drive demand and position exposure.
Speaker Change: As a flexible combinable manageable drug that allows for a class switch.
Speaker Change: Even though the marketplace is highly competitive it's clear that we are in a space, where our multi mechanistic approach is increasingly needed for successful patient outcomes and that's exactly.
Speaker Change: We're selling XR comes in as a differentiated mechanism of action so.
Speaker Change: Again, very pleased with our performance this quarter, we narrowed our guidance for the full year end.
Speaker Change: Feel confident in meeting that range.
Speaker Change: Got you. Thank you and then.
Speaker Change: Freshman just one.
Speaker Change: The MMR proficient patients do you need any kind of alignment with the FDA around cooling.
Speaker Change: Is it.
Speaker Change: Okay.
Speaker Change: Just kind of as.
Speaker Change: Enrollment.
Speaker Change: Yeah. Thanks Peter.
Speaker Change: No we don't largely because the patient population that we're targeting is P 53, wild type and that P. 53, Wild type I think the regulatory agencies and the FDA, particularly really appreciate is going to include.
Speaker Change: Multiple molecular subgroups, including MMR proficient.
Speaker Change: So you know, there's there's no need to specifically call them out with that said, we will we be looking at potential subgroups by MMR status. Yes, that's something that we will be we will be considering in terms of enrollment enrollment is going well, we're certainly on track too.
Speaker Change: Report top line results in the early part of 2026.
Speaker Change: A lot of that is fueled by again, just I think strong enthusiasm for the data.
Speaker Change: You know as we presented at <unk> and then you know again had an opportunity to.
Speaker Change: <unk> very recently at IGT us in Dublin.
Speaker Change: Those data and specifically the benefit that Selinexor provides to P. 53, wild type is almost unprecedented right. I mean, we are seeing in that piece of the three wild type subgroup of $28. Four month median PFS, if you're specifically looking at sub group, who are both P 53.
Speaker Change: Wild type and MMR proficient again that PFS now climbed to 40 months, which I mentioned earlier on the prepared remarks.
Speaker Change: Cross trial limitations aside exceeds the overall survival that you see with the checkpoint inhibitor. So strong enthusiasm about you know the trial largely due to the benefit that we're seeing with selinexor.
Speaker Change: And the strong anticipation that these results are going to translate in our ongoing phase III.
Speaker Change: Great. Thank you so much.
Speaker Change: Thanks Peter.
Speaker Change: Yeah.
Speaker Change: Thank you. Your next question is from Maury Raycroft from Jefferies. Your line is now open.
Maury Raycroft: Hi, good morning, Thanks for taking the question.
Maury Raycroft: Best wishes to Mike as well next steps.
Maury Raycroft: I was going to ask one on the ongoing multiple myeloma SPD <unk> phase III study just if you could talk about the powering assumptions of the new trial design.
Maury Raycroft: What else do you need to align with regulatory agencies to get to go out there and when do you anticipate you'll be able to clarify the timeline to data for this study.
Speaker Change: Yeah. Thanks, so much mark for the question.
Speaker Change: So what we were able to do is to really leverage the positively evolving data that was specifically observed with SPD <unk> the median PFS.
Maury Raycroft: I've mentioned previously a substantially larger longer than what we previously assumed so that ability allows us to target not only a smaller number of total patients and as you can see is sort of like from earlier earlier his prepared remarks, where I'm now gonna be targeting 120.
Speaker Change: Patience is part of the ongoing trial, but it also allows us to reduce the total number of PFS events, that's going to trigger that primary analysis for PFS without compromising any of the power that had already been built into the trial. So we don't specifically call.
Maury Raycroft: Comment on our exact powering assumptions with outside and all of our phase III as we power above 80%. This trial is no different.
Maury Raycroft: So you know again that ability is just based upon you know.
Maury Raycroft: Our ability to leverage the positively evolving efficacy.
Maury Raycroft: In terms of.
Maury Raycroft: Alignment with the FDA, so the updated enrollment as well as the updated statistical assumptions were incorporated two an amendment and that has been sent to the FDA we expect.
Maury Raycroft: Any kind of feedback to be coming in the next few weeks at that time, we will update our topline results.
Maury Raycroft: While stones accordingly.
Speaker Change: Got it okay, and maybe one follow up.
Speaker Change: Just for the Myelofibrosis study.
Speaker Change: So he goes out to 24 weeks do patients continue on treatment and what's the likelihood that youll have to have a longer term follow up potentially going out to 48 weeks.
Speaker Change: Yes, so patients are going to continue on therapy, well beyond 24 weeks.
Speaker Change: So the 24 week marks just indicates you know when that SVR and the absolute TSS are gonna be analyzed patients are going to be continuing we have multiple longitudinal end points that we are going to evaluate including PFS and overall survival in terms of long term.
Maury Raycroft: Term endpoints.
Maury Raycroft: Right now based upon our discussions with the regulatory agencies. The key endpoints that are going to drive regulatory decisions are again week 24, we'll have the opportunity to provide longer term data, but right. Now we're really focused on that 24 week data for again regulatory decision making.
Speaker Change: Got it okay. Thanks for taking my questions.
Maury Raycroft: Thanks Mark.
Maury Raycroft: Thank you.
Speaker Change: No further questions at this time. Please proceed.
Speaker Change: Thank you operator, and thank you everyone for joining us today as we mentioned as an organization. We are focused and excited about delivering our innovation and growth strategy, which offers transformative opportunities with our phase III clinical trials in myelofibrosis in endometrial cancer as we build on our multi myeloma Foundation.
Maury Raycroft: As trials, we've heard the potential for them to really deliver new standards of care and significantly advance our company as we work to deliver value to our shareholders. Once again, thank you for joining us today.
Maury Raycroft: Thank you.
Speaker Change: Ladies and gentlemen, the conference has now ended thank you all for joining you may all disconnect your lines.
Speaker Change: Goodbye.