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spk02: I'm going to be a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a little bit of a Good morning. My name is Carolyn and I will be your conference operator today. At this time, I would like to welcome everyone to Carrier Farm Therapeutics' second quarter 2024 financial results conference call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Ellen Webb, Senior Vice President Investor Relations.
spk05: Thank you, Carolyn, and thank
spk11: you all for joining us on today's conference call to discuss Carrier Farm's second quarter Q2 2024 financial results and recent company progress. We issued a press release this morning detailing our financial results for Q2 2024. This release, along with a slide presentation that we'll reference during our call today, are available on our website. For today's call, as seen on slide two, I'm joined by Richard, Reshma, Sohania, and Mike, who will provide an update on our results for Q2 2024 and recent clinical developments. Before we begin our formal comments, I remind you that various remarks will make today constitute forward-looking statements, FLS, for purposes of the safe harbor provisions under the Privacy, Security, and Litigation Reform Act of 1995, as outlined on slide three. Actual results may differ materially from those indicated by this FLS as a result of various important factors, including those discussed in the risk factors section of our most recent form 10Q, which is on file with the SEC and in other filings that we may make with the SEC in the future. Any FLS represents our views as of today only. While we may elect to update these FLS at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these FLS as representing our views as of any later date. I will now turn the call over to Richard. Please turn to slide four.
spk10: Good morning. Thank you all, Anne, and thank you all for joining us today for CarioFarm's Q2 2024 earnings call. Turning to slide five, I would like to first focus on our innovation and growth strategy as we work to deliver our next stage of growth by advancing our late stage pipeline while continuing to strengthen our foundation in multiple myeloma. Starting with myelofibrosis, we are more excited than ever regarding salinexor's potential opportunity in this indication. Physician interest in enrolling patients into our phase three study is strong, and the competitive environment continues to evolve favorably for us. Building on our strong clinical data, the new preclinical data that we presented at EHA further reinforces the role that salinexor might play in myelofibrosis. In endometrial cancer, we presented updated data at ASCO, demonstrating nearly 40 months of progression-free survival when salinexor is used as a maintenance therapy in patients whose tumors are TP53 wild type, TMMR. This population represents approximately half of all patients who are diagnosed with endometrial cancer. It is noteworthy that the progression-free survival that salinexor is demonstrating in the maintenance setting in this subgroup exceeds the overall survival that is achieved by the checkpoint inhibitors in patients whose tumors are TMMR. As we continue to enroll patients in our EC042 phase three trial in endometrial cancer, we are also confronting the complexities of a molecularly targeted maintenance trial and are taking proactive actions, both of which Rishma will expand on. As a result, we now expect to deliver top line data in early 2026. In multimiloma, we are pleased to report our second consecutive quarter of growth in Expovio revenue, giving us confidence to raise the low end of our revenue guidance for 2024. The importance of Expovio's differentiated mechanism of action, its all-oral administration, and potentially T-cell sparing impact is increasingly resonating with community and academic positions, which Shohania will expand on. As we work to build on our commercial foundation of multimiloma, we expect to leverage our positively evolving SPD data at the 40 milligram dose to update the design of the phase three EMN29 trial, which will include targeting fewer participants for enrollment and lowering the projected cost of this trial. Finally, in light of our strengthening commercial performance, disciplined cost management, and focused approach to clinical development, we believe we're in a strong financial position to deliver on our prioritized late stage pipeline. Mike will expand on our lowered 2024 R&D and SG&A expense guidance. We continue to be very optimistic about our next stage of growth, and are well positioned to capitalize on the opportunities for sell and XOR with our diversely built late stage pipeline across three different cancer indications. We continue to believe the annual peak revenue opportunity for sell and XOR could be $2 billion in the US alone. I would now like to turn the call over to Raishma to expand on our recent data announcements and discuss our progress with each of the programs in our pipeline. Raishma?
spk03: Thank you, Richard. Turning to slide seven, I'd like to highlight our promising late stage pipeline led by sell and XOR's three ongoing phase three studies, each of which has the potential to enable a new standard of care, continuing to build upon the growing body of data, and utilizing the once weekly lower doses of either 40 or 60 milligrams. We continue to be very encouraged by the data generated to date supporting our three pivotal phase three trials, including the improving long-term follow-up data in endometrial cancer from the exploratory subgroup analysis in the CENDO trial that was presented at ASCO, which I'll expand on shortly. Starting with myelofibrosis on slide nine, we are incredibly excited by both our evolving data and physician interest in our work in this area. In June, we presented new preclinical data at the European Hematology Association Hybrid Congress. These data demonstrated the strong mechanistic rationale of XP01 inhibition in myelofibrosis and its ability to target both the JAK and non-JAK pathways. In light of our data that show that XP01 inhibits both JAK and non-JAK pathways, we believe that sell and XOR can be leveraged both in combination and as a monotherapy. We presented data from our phase one trial in myelofibrosis last year, as seen on slide 10. Sell and XOR 60 milligrams was evaluated in combination with Rexolitinib and JAK inhibitor naïve patients. Of the 14 patients who received the 60-milligram dose of sell and XOR, 79% and 58% achieved a SVR35 and TSS50 at week 24, respectively. Absolute TSS demonstrated very meaningful improvements with an average reduction of 18.5 points at week 24 in the efficacy-evaluable population. Diving deeper into the important aspect of durability on slide 11, as of the data cutoff, there was 100% probability of continuing responses in both the SVR35 and TSS50 over a median duration of follow-up of 32 weeks and 51 weeks, respectively, when sell and XOR 60 milligrams was used in combination with Rexolitinib, indicating that the responses are maintained well beyond 24 weeks. These findings support the potential of the combination of sell and XOR plus Rexolitinib to offer greater symptom improvement than Rexolitinib alone, as our ongoing phase three study may demonstrate. Moving to slide 12, we outlined the trial design for our phase three century trial, evaluating the combination of sell and XOR 60 milligrams with Rexolitinib compared to Rexolitinib alone in 306 JAK naïve myelofibrosis patients. We are encouraged by the strong enrollment into our phase three clinical trial given by the positive feedback that we are hearing from clinical trial investigators regarding sell and XOR's unique mechanism and clinical profile. Our momentum is also fueled by minimal competitive clinical activity and posse as effective therapies. Our guidance for reporting top-line results remains firmly on track for the second half of 2025. Turning our attention to endometrial cancer on slide 14, one of sell and XOR's primary mechanisms is to suppress the export of P53 from the nucleus to the cytoplasm. The accumulation of P53 in the nucleus leads to impaired DNA repair, cell cycle arrest, and ultimately increased apoptosis. Clinically, this mechanism is what drives anti-tumor activity in tumors dependent upon P53, including endometrial cancer. Advanced and recurrent endometrial cancer is the most common form of gynecologic cancer in the United States with approximately 16,000 patients diagnosed each year. We believe sell and XOR could play an important role for greater than half of these patients as the first novel oral maintenance therapy for patients with TP53 wild type tumors. As seen on slide 15, TP53 wild type status has an emerging role in the evolving landscape of advanced and recurrent endometrial cancer. Checkpoint inhibitors were recently improved by the FDA in combination with chemotherapy, followed by checkpoint inhibitor maintenance for advanced recurrent endometrial cancer patients, regardless of MMR status. However, the efficacy observed in patients whose tumors are PMMR is markedly less than in the DMMR, consistent with the mechanistic rationale for checkpoint inhibitor effectiveness in DMMR solid tumors. These checkpoint inhibitors have been included in combination with chemotherapy, followed by checkpoint inhibitor maintenance in the NCCN guidelines for all patients, regardless of MMR status since March of 2023. Patients whose tumors are both PMMR and P53 wild type represent roughly 50% of all advanced or recurrent endometrial cancer patients. Turning to slide 16, at ASCO we presented very encouraging long-term follow-up data from the exploratory analysis of CienDo, which evaluated sell and XOR maintenance therapy. Patients with P53 wild type PMMR tumors experienced a median PFS of 39.5 months with sell and XOR compared to 4.9 months with placebo, resulting in a hazard ratio of 0.36. Acknowledging the limitations in cross-trial comparisons, the median PFS improvement achieved with sell and XOR in the subgroup exceeds the median overall survival achieved by checkpoint inhibitors in PMMR patients, underscoring the meaningful efficacy achieved with sell and XOR in these patients. In all patients with P53 wild type tumors, sell and XOR demonstrated promising benefit with a median PFS of 28.4 months compared to 5.2 months for placebo, resulting in a hazard ratio of 0.44. These robust exploratory subgroup data from CienDo continue to demonstrate the potential of sell and XOR to provide substantial benefit in a unique and sizable population. In a survey of US physicians who were provided long-term follow-up data achieved with sell and XOR in patients whose tumors are P53 wild type from the CienDo study, as well as efficacy with the checkpoint inhibitors, 75% indicated future intent to prescribe sell and XOR as a maintenance therapy for P53 wild type PMMR endometrial cancer patients. Overall, we believe if sell and XOR were to be approved in this indication, a majority of patients could benefit from this treatment option. Let's also review the updated safety data on endometrial cancer from the CienDo trial that we presented at ASCO, as shown on slide 17. Adverse events were generally manageable and well tolerated. The most common AEs observed with sell and XOR, regardless of grade, were nausea, vomiting, and diarrhea. It is important to note that dual antiemetics were not required in this trial. Grade 3 plus treatment emergent adverse events were rare, with the most common events being neutropenia, thrombocytopenia, and nausea. Finally, on slide 18, and as Richard mentioned, we are shifting our expected timeline for the top-line data readout for our Pivotal Export EC042 Phase 3 trial to early 26. Based on recent observations, an increasing interval between biopsy evaluation and chemotherapy completion has led to a higher than expected screen failure rate. Availability of new therapies is also impacting our enrollment, albeit to a lesser degree. Based upon these observations, we are enhancing our investments by adding additional sites to increase the total number of patients that will need to be screened for this trial. Overall, I continue to be extremely enthusiastic about the potential for sell and XOR to provide clinically meaningful outcomes in the maintenance setting for patients with P53 wild-type endometrial cancer, especially those with PMMR tumors, where our exploratory subgroup data has demonstrated a median PSS of nearly 40 months, which again exceeds the median overall survival observed with checkpoint inhalation. Lastly, turning to multiple myeloma on slide 20, we are very encouraged with the results from our STOMP and MM028 trials that evaluated sell and XOR 40 milligrams in combination with pomalidomide and dexamethasone. The promising data published in the Frontiers of Oncology Journal in May of this year underscores sell and XOR's potential to expand its position in the multiple myeloma and PMMR tumors. The results from our STOMP and MM028 trials in the Frontiers of Oncology Journal in May of this year underscores sell and XOR 40 milligrams in combination with pomalidomide and dexamethasone. The promising data published in the Frontiers of Oncology Journal in May of this year underscores sell and XOR 40 milligrams in combination with pomalidomide and PMMR tumors. The promising data published in the Frontiers of Oncology Journal in May of this year underscores sell and XOR 40 milligrams in combination with pomalidomide and PMMR tumors. The promising data published in the Frontiers of Oncology Journal in May of this year underscores sell and XOR 40 milligrams in combination with pomalidomide and PMMR tumors. The promising data published in the Frontiers of Oncology Journal in May of this year underscores sell and XOR 40 milligrams in combination with pomalidomide and PMMR tumors. Experts we are engaged with our teams in working on how to improve risk and assuredgaINT B cold upon and improved the already favorable data given that the STOMP and MM028 cohorts did not require dual anti-imetics. Our Phase 3 EAMN29 SPD trial in multiplemyeloma is outlined on slide 21. This trial is designed to address the unmet need present in patients with multiple myeloma with an all-oral triplet treatment option that can be beneficial to pre- and post- T-cell engaging therapies. We will be working with the European Myeloma Network, the sponsor of this study, to leverage the positively evolving PFS data observed with SPD-40 and amend the statistical analysis plan to enable a meaningful interpretation of the efficacy and safety of SPD versus EPD. Importantly, we are also seeing a slowdown in enrollment rates due to an increasingly global competitive trial environment with an increased number of Phase III studies targeting the same sites and a similar patient population. In fact, as of today, four large Phase III trials have already been initiated in 2024. The same number of trials initiated in all of 2023. We now plan to enroll approximately half of the planned sample size and pending the strength of the data, we will engage with regulatory agencies accordingly. Based upon these revised plans, we continue to anticipate top-line results in the first half of 2025. In conclusion, our rapidly advancing pipeline presents near-term late-stage opportunities backed by increasingly compelling data. Cellinxor has the potential to benefit multiple cancer patient populations with high-entit needs in the near future, enhancing our existing approved indications in multiple myeloma. I will now turn the call to Sohania for a review of our commercial highlights.
spk04: Thank you, Reshma, and good morning, everyone. On slide 23, I will discuss our commercial highlights for the second quarter of 2024. In the second quarter, Expovio net product revenue was $28 million, up 8% compared to our results in the first quarter. Consecutive -over-quarter growth was driven by growth in both new patient starts and refills as Expovio is increasingly utilized in a flexible position across the treatment paradigm as a convenient oral regimen with a differentiated mechanism of action. The results and momentum from the first half of this year and continued strong execution have led us to raise the low end of our net product revenue guidance by $5 million to a new range of $105 million to $120 million. New patient mix remains stable in the -to-fourth treatment lines, with earlier line use per year primarily coming from the community setting, which contributed to approximately 60% of Expovio net revenues in the second quarter. Demand in the community setting grew more than 10% from the first quarter. Demand in the academic setting remained consistent with the first quarter, with Expovio being increasingly used immediately before or after T-cell therapies as a way to potentially preserve T-cell fitness. In academic institutions using Expovio as a bridging regimen prior to T-cell therapy use, we see shorter duration of therapy of Expovio, but this was offset by the increase in new starts in this setting. Overall, in a highly competitive marketplace, we are very pleased with the results that our commercial organization has delivered in the first half of the year with consecutive -over-quarter growth. Now I'd like to turn to slide 24 and shift our focus towards milestones accomplished outside of the U.S. I'm pleased with our momentum as we expand our global footprint with continued regulatory and reimbursement approvals for Cellin-Exor across the world. In the second quarter, following the positive recommendation from NICE, expanded reimbursement was achieved in the UK as well as South Korea. Additionally, Expovio continued to expand its global footprint with additional regulatory approvals in China and other international markets. In summary, CarioFarm's multiple myeloma franchise continues to impact an increasingly number of patients globally, while remaining a profitable business and serving as a critical driver in funding our pipeline. A dedicated commercialization team and partners have the capabilities for rapid launches and potential future indications as well. Now I'd like to turn the call over to Mike to give an update on our financials.
spk09: Good morning, everyone, and thank you, Sohania. 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 26. Total revenue for the second quarter of 2024 was $42.8 million, reflecting strong momentum compared to $37.6 million for the second quarter of 2023. Net U.S. Expovio revenue for the second quarter of 2024 was $28 million compared to $28.5 million for the second quarter of 2023. The gross connect discount for Expovio in the second quarter of 2024 was 29 percent, as compared to 22 percent in the second quarter of 2023. This was driven by increased 340B utilization, Medicare rebates, and expired product returns. We continue to expect 25 to 30 percent GTN for the full year 2024. Our total expenses for the second quarter of 2024 were up slightly, year over year by 6 percent, driven by our investments in our late-stage clinical pipeline with three ongoing phase three trials. R&D expenses for the second quarter of 2024 were $38.4 million compared to $31.5 million for the second quarter of 2023. The increase in R&D expenses is primarily attributable to higher clinical trial costs related to our pivotal phase three programs. SG&A expenses for the second quarter of 2024 were $31 million compared to $34.5 million for the second quarter of 2023. The decrease in SG&A expenses was primarily due to ongoing cost reduction initiatives and lower headcount, partially offset by approximately $1 million in debt financing-related expenses. We reported net income of $23.8 million for the second quarter of 2024 compared to a net loss of $32.6 million for the second quarter of 2023, mostly due to a one-time non-cash net gain of $44.7 million on the extinguishment of debt and $14.3 million in gains that were recognized in connection with the refinancing transactions that we concluded in May, which you can see in detail on the related slide in the appendix. As a reminder, these transactions extended the vast majority of our maturities into 28 and 2029, well beyond our expected data readouts from our three phase three trials and potential launches. Cash, cash equivalents restrict cash and investments as of June 30, 2024, totaled $152.5 million compared to $192.4 million as of December 31, 2023. Based on our current operating plans, we are raising the lower end of our guidance for both total revenue and exposure net product revenue by $5 million and lowering and tightening our overall range of expense guidance by $10 to $15 million. The operating expense reductions for the remainder of 2024 include lower expected expenses for our EMN 29 trial with the plan resizing as well as continued discipline in our operating costs, including headcount. Specifically, since the beginning of last year, we have reduced our budget headcount by approximately 30%. Our updated guidance ranges for the full year of 2024 as follows. Total revenue expects to be in the range of $145 to $160 million as compared to previous guidance of $140 to $160 million. Exposure net US product revenue expected to be in the range of $105 to $120 million as compared to the previous guidance of $100 to $120 million. We are also lowering our expense guidance for the full year of 2024 as follows. R&D and S&G expenses expected to be in the range of $250 to $265 million, which includes approximately $20 million of estimated non-cash stock-based compensation expense as compared to previous guidance of $260 to $280 million. And finally, we expect our existing cash, cash equivalents and investments, as well as the revenue we expect to journey from exposure net product sales and other license revenues, will be sufficient to fund our plan operations into Q1 2026. Note that our cash runway does not include paying off the remaining 2025 convertible notes in our $25 million minimum liquidity covenant under the new term loan. We expect our 2025 operating expenses to be lower than 2024 as we recognize the full year benefits of our ongoing cost-saving initiatives. In summary, we are focused on the advancement of our three phase three trials and driving commercial performance while continuing to be very diligent when allocating our resources. I'll now flip to slide 27 and turn the call over to Richard for some final thoughts. Richard?
spk10: Thank you, Mike. As you can see on slide 28, we have several meaningful milestones ahead of us in the near future. We believe our continued focus on disciplined capital allocation and expense management provides us with cash runway to achieve these milestones. We're enthusiastic about our innovation and growth strategy, which provides us valuable optionality with our phase three clinical trials in myelofibrosis, endometrial cancer, and multimyloma. These trials have the potential to bring transformative benefits to patients and drive substantial progress for our company. As a company, we will continue to strive towards unlocking SalonXR's full potential as we execute in a disciplined manner and deliver on our next phase of growth. 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.
spk05: Operator?
spk02: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any key. One moment, please, for your first question. Our first question is from Peter Lawson from Barclay.
spk08: Hey, good morning. This is Alex on for Peter. Thank you for taking our questions. I just wanted to ask, I was wondering if you could expand a little bit on what is driving the change in timelines for the endometrial trial and the higher screen failure rates and beyond adding additional sites, are there any other changes being implemented in the trial here?
spk10: Thanks, Alex. I'll turn to Rashmi for that. I think she highlighted it at a high level, but to go into some more detail when I look at the learnings we have in the endometrial trial and what's happening and how we're addressing it. So I'll turn that to Rashmi.
spk03: Yeah, thank you. So I want to start off in the endometrial space just highlighting the data that we have observed with Selenexor in this unique population defined by their P53 status. We first presented long-term data back in July of 2023. This was part of the ASCO Plenary Series it was really important to note, especially from one of the moderators who described the data as truly unprecedented and it underscores the benefit that Selenexor can achieve in this patient population defined by P53 status. Those data have only gotten stronger. In fact, at ASCO just a couple of months ago, Vicki Macher, who is at MSKCC, presented updated, the most recent updated data for Selenexor in this population. In those patients who are defined by both P53 wild type and PMMR status, their data now show an unprecedented 40-month median PFS. That 40 months actually exceeds the overall survival observed with the checkpoint inhibitors in that PMMR patient population. You are correct, you know, we are seeing challenges in our enrollment. One of the main drivers, and it's a recent observation, is this increase in screen failure rate and it's very unique to a biomarker-driven trial. I say that because many of the physicians are submitting their biopsies relatively early during the chemotherapy process. That biopsy is evaluated by foundation for that P53 status. With that said, even if that biopsy is evaluated as P53 wild type, those patients need to complete months of chemotherapy and during that time, we have been seeing that they can screen fail for a myriad of reasons, whether it's for lab reasons, scan reasons, they may need to have surgeries, they may decide that they don't ultimately want to participate in a clinical trial. Those reasons contribute to that higher screen fail rate and as such, we are actively looking at multiple initiatives, increase the total pool of patients that we can screen. The major initiative is going to be activating new sites, you know, in our current existing countries and potentially in new additional countries. Other initiatives that we are looking at is, you know, of course, doubling down on our medical affairs support, looking at outside vendors. We continue to partner very closely with the GOG and Engott. Ultimately, we are committed to completing enrollment of this trial and updating everybody on top line results in early 2026.
spk05: Great, that's helpful. Thank you very much. Thanks, Alex. Next question
spk02: will be coming from Morrie Raycroft from Jefferies.
spk07: Hi, thanks for taking my questions. Maybe just a quick follow up to the last one. Are you saying anything more about how many new sites you anticipate opening and in what regions you plan on opening those sites in?
spk03: Yeah, thanks for the question, Morrie. No, we're not providing any additional color on those details. Just, you know, primarily looking at, you know, opening up some new sites, you know, in our existing countries and like I said, you know, potentially additional countries and then continuing to support, you know, the many sites that have already been activated in our current trial. So I think those, you know, main focus, you know, really will enable that increased screening pool that we need to achieve to enable those top line results in the first, in early 2026.
spk07: Got it. And is there any way to potentially help mitigate the issue with the biopsy process? I guess can Carry Up Farm do anything to help on that front? And then could part of the outcome of this lead to an enrichment of the P53 wild type PMMR population or how are you thinking about that?
spk03: You know, I will say the biopsy process is already going very smoothly. You know, in endometrial cancer, molecular classification is really becoming the standard of care, both because physicians are evaluating the MMR status as well as other biomarker classifications, including P53, POLI, etc. So physicians are really used to evaluating biopsies in the case of our clinical trial. They just submit that biopsy to foundation medicine, they process it very quickly. And you know, the results are turned around within a matter of days. The main driver specific to our trial is again, that interval between when the biopsy is submitted and the months of chemotherapy that they still need to complete. And that unfortunately is nothing, there's nothing that we can do to offset that process. In terms of your second question, it's a good one. And I think like naturally, we are going to see patients who are PMMR as well as P53 wild type based upon local testing, you know, disproportionately submitting tumors to SMI. So I think we will see that rate rise over time.
spk05: Okay, thanks for taking my questions. I'll hop back in the queue. Thanks, Maury. Next question will be coming from Colleen Cassie from Baird.
spk12: Hi, good morning. Thanks for taking our questions. Among those enrolled for another question on the endometrial study, can you comment on any sort of PFS metrics so far and how that tracking versus your expectation and whether kind of enrolling some of these PMMR, TP53 wild type patients might be pushing out the data as well, just given how strong the CNDO data is.
spk03: Yeah, thanks for the question, Colleen. So no, you know, we do not have any insight in terms of the PSS results from this trial. It's a double blinded trial. We also are very much blinded to the results across either one of these arms. So no insight there. You know, I think I'll just go back to the CNDO data and that P53 wild type subgroup that we've had an opportunity to report on multiple times. You know, that data just continues to get stronger, right? You know, in that large P53 wild type subgroup, we are now seeing a median PFS of 28.4 months. And I'll reiterate in that P53 wild type PMMR subgroup, those data now demonstrate a median PFS of 40 months, truly unprecedented data and really underscores the strength of the benefit that can be achieved with cell and XOR. We've incorporated those PSS into our assumptions. So, you know, we assume a very meaningful PSS benefit at the time of the top line results and again, have already been incorporated into the projections that inform that early 2026 top line result readout.
spk12: Got it. That's helpful. Thank you. And then on the screen failure rate, can you comment if the TP53 wild type biomarker is roughly as prevalent as you thought it was so far in the screening process? Is it still roughly around 50%?
spk03: Yeah, it is. It is. It's, you know, sitting nicely in that assumed rate of, you know, more than half of all patients.
spk12: Great. And then one commercial question if I can. So, Hania, can you just give us a sense of the duration of treatment for the pre and post T cell therapies you're seeing in the academic centers? Is it like a one month or, you know, maybe low single digits, but just kind of help us get a range on that,
spk04: please. Yeah, thanks, Colleen. So, we don't disclose exact months of duration because we have to triangulate multiple data sources, takes time for that to mature. However, take a step back and look at trends overall. Obviously, we see a long term trend since the launch of the drug in terms of increasing duration. The recent dynamics in the competitive landscape, obviously, with bridging and post T cell therapies have obviously impacted duration, but this is a smaller proportion of our patients. The large majority of our patients remain in the early align second, third, and fourth lines, and really that helps to propel our duration up.
spk05: Great. Thanks for taking our question. Thanks, Colleen. Next on the line is coming from Brian Abraham from RBC.
spk06: Hi, good morning. Thanks for taking my questions. Maybe shifting gears to myelofibrosis. The phase 3, 03-4 study is based on some of the data you presented on slide 10, where you showed quite robust benefits for selenX on top of RUX, but in a relatively small number of patients. I guess I'm curious as the trial is continuing, if there may be any opportunities to adjust the powering or design of the study based on the ongoing data or on regulatory outcomes from a prolaborative, the late stage drug that's also in development. Then maybe secondarily on MF, it looked like the selenX or monotherapy study was pushed out just a bit there. Just wondering if you could tell us how that study is going and the extent of the data we should be looking for now at the end of this year or early next. Thanks.
spk03: Thanks for the question. We remain really confident about myelofibrosis. As you mentioned, the strength of the data are unparalleled. The reason I say that is because, yes, although we have a smaller cohort of patients in which we evaluated the efficacy with selenX or plus -Lint-Nib, specifically a 79% SVR35 rate and a 58% TSS50 rate at week 24, it only builds upon the data that we have evaluated with not only selenX or but the combination. I'll underscore the preclinical data, the mechanistic data that really suggests that selenX or an XP01 inhibition is targeting both JAK and non-JAK pathways, as well as the totality of the data that really suggests that when selenX or is combined with -Lint-Nib, you can see additive, if not, synergistic effects. Layer on now the clinical data that have demonstrated monotherapy activity. This goes back to the essential trial in that relapsed refractory previously exposed JAK population. Now, of course, you have the phase one data specifically evaluating selenX or in combination with -Lint-Nib. When I evaluate our opportunity and the strength of the data, it's really looking at all of those data sets that really inform the potential of selenX or in myelofibrosis. What we also know from both patients as well as physicians is that the efficacy has to extend beyond just as SVR35 and TSS50 rates. I add that because we are also seeing very impressive durability. At the time of the most recent data cutoff, none of the patients had actually progressed either from an SVR35 standpoint or a TSS50. What we are seeing is remarkable SVR35 and TSS50 rates as well as the corresponding durability that extend well beyond that week 24 time point. Lastly, I'll mention in terms of 044, yes, we did push out the timelines a little bit. Now we are looking at end of 24, beginning of 25. It's a smaller patient population, so these are still JAK-naïve patients. However, their platelet count needs to be within that 50 to 100. It is a smaller population as compared to that patient population enrolling in the phase 3. Still lots of enthusiasm and we look forward to providing data from that study shortly.
spk06: That's really helpful. Thank you. I guess I was thinking if the effect size in the phase 3 was maybe even more robust than what you had seen in the phase 2, if there might be an opportunity to maintain powering but cut the trial size down a bit and accelerate timelines there.
spk03: Yeah, it's a good question. I mean, we are completely blinded to the results, so that's not something that we can do. But like all of our phase 3s, we do have an independent DMC that is evaluating the results and based upon their assessment, we'll certainly consider if that opportunity exists for the trial.
spk05: Thanks. Thanks, Brian. Ladies
spk02: and gentlemen, if you have any questions, please press star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Again, if you have any questions, please press the star followed by the number one on your touchtone phone and you will hear a prompt that your hand has been raised. Last question on the line will be coming from Jonathan Chang from Learing Partners.
spk01: Great. Hi, guys. This is Matt on for Jonathan. Thanks for taking my question. Just looking at some of the details of the cash runway, including the liquidity covenant, etc., how confident are you that you have sufficient cash runway to get to the updated endometrial cancer top line readout? And how should we be thinking about the monetization of assets such as KPT 9274 as it relates to making the timeline work? And lastly, can you comment if there are other programs in the pipeline with potential for out licensing such as 9274? Thank you very much.
spk09: Yeah.
spk10: Thanks for the question. I'll let Mike talk to the first part and then I can jump into the second and third question.
spk09: Sure. So reminder, our previous cash runner was into the end of 2025. We've tightened our 2024 OPEX guidance to be 250 to 265 million, which includes 20 million of on-camp, which is down from 260 to 280 million previously. And part of that lowering expenses was the planned resizing with our EM 29 trial and just the continued discipline on operating costs. Yes, we realized the importance of extending that cash runway. We have three pivotal readouts. First one is myeloma, which is in the first half of 2025. Second one is myelof fibrosis in the second half of 2025. And the third in endometrial and early 2026. So putting all of those together, our cash when we get this into the early 20s, like excluding the convert that we have that to do in October 2025.
spk10: Yeah. And I think if we build on, you know, as you mentioned talking about KPT 9274, you know, it's a novel first in class, oral small molecule dual inhibitor of the pack for an amputee that was discovered by Karyo Farm and is part of our early stage programs. So obviously recently, as we, you know, announced today, we were able to receive both rare pediatric disease designation and orphan drug disease designation. So I think a really strong opportunity where we're going to be looking to partner out license, you know, that asset to make sure that we can recognize the full value of it and help to work to bring it to patients or enable someone else to work to bring to patients. So that's a strong opportunity for us, obviously with some strong value behind it, given those designations and given the high unmet need in both rhabdo sarcoma and Ewing's sarcoma. Also, I think as we've talked to before, we have eltenexor, which is our second novel sign compound, which we will look at potential partnerships in terms of that asset across the globe. Right now, it's currently partnered just in Asia pack. So that gives us, you know, optionality to look at moving forward. And then, yes, we have a couple other assets within the pipeline that we're always opportunistic to see what's the best way to recognize value from those assets. So, you know, I think some good optionality in terms of RBD area and obviously with KPC 9274 and the recognition and the areas that have just been recognized by the FDA, I think that adds, you know, significant value
spk05: and
spk10: looking to recognize
spk05: that value. Thank you so much. Thanks. There are
spk02: no further questions at this time. I'd now like to turn the call back over to Mr. Richard Paulson for final closing comments.
spk10: Thank you, operator, and thank you everyone for joining us on today's call. You know, we are focused on accelerating the momentum as we look to deliver on our next phase of growth and our people continue to strive each day for patients with high-end met needs as we work to generate value for patients and shareholders. So thank you
spk05: for joining again and have a great day, everyone.
spk02: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. And we all have a good one.
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