Q1 2023 Karyopharm Therapeutics Inc Earnings Call
Speaker 1: You
Speaker 2: Good morning, my name is Ryan and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyu Farm Therapeutics First Quarter 2023 Financial Results Conference Call.
Speaker 2: There will be a question and answer session to follow.
Speaker 2: Please be advised that this call is being recorded at the company's request.
Speaker 2: I would now like to turn the call over to Alain Veth, Senior Vice President in Western Relations
Speaker 2: Thank you. Over to you.
Speaker 3: Thank you, operator, and thank you all for joining us on today's conference call to discuss Carrier Farms first quarter 2023 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first quarter 2023.
Speaker 3: This release, along with a slide presentation that we will reference during our call today, are available on our website. For today's call, as seen on slide 2, I'm joined by Richard, Sohanya, Reshma, and Mike, who will provide an update on our Q1 results and recent clinical developments.
Speaker 3: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute follow-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 as outlined on slide 3.
Speaker 3: actual results may differ materially from those indicated by these forward-looking statements, FLS, as a result of various important factors, including those discussed in the risk factors section of our most recent form, PAN-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future.
Speaker 3: Any FLS represents our views as of today only.
Speaker 3: While we may elect to update this 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 this FLS as representing our views as of emulator date.
Speaker 3: I will now turn the call over to Richard. Please turn to slide 4.
Speaker 4: Thank you, Alhan, and thank you all for joining us today for Kariofarm's Q1 2023 earnings call.
Speaker 4: As we turn to 5.5, we are making strong progress as we execute on Kerioharm's next stage of growth by deploying our novel mechanism of action, selective inhibition of nuclear export, to expand our existing multi-myelma franchise. Currently centered around our commercial drug expo-vio,
Speaker 4: which has now approved in over 40 countries and continues to move into earlier lines of therapy in Multimemailoma.
Speaker 4: As Sohanya will discuss further, year-over-year total demand for Expovio continues to grow. However, this is not translating into growth in net product revenue due to increased distribution of free product through our Carry Forward Patient Assistance Program, PAP, and higher gross-to-net discounts.
Speaker 4: These factors have caused us to revise our total revenue guidance for 2023 to a new range of 145 to 160 million.
Speaker 4: In addition, we have accelerated our closure of non-priority programs that's lowering our spend in 2023 and we are maintaining our guidance for cash runway through late 2025.
Speaker 4: We believe the factors resulting in the significant increased use of our PAP programs are expected to be mostly limited to 2023, and while we are not specifically commenting on our revenue expectations for 2024, we believe we will see a decreased impact of this challenge next year given the IRA-related Medicare Part D redesign.
Speaker 4: We have a focused pipeline and are rapidly advancing our mid and late stage clinical development programs that can help patients who suffer from cancers with high unmet need.
Speaker 4: demonstrate efficacy at lower doses with improved tolerability, and where we believe we'll have the highest probability of success.
Speaker 4: We are conducting pivotal phase three studies in both multiple myeloma and endometrial cancer.
Speaker 4: With the third pivotal phase three study of myocybrosis, what you expect to start in the first half of 2023.
Speaker 4: Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years as we deliver our next phase of growth.
Speaker 4: leveraging our proven and established commercialization and mid to late stage development capabilities as we work to generate value for patients and shareholders.
Speaker 4: As we look at our first quarter highlights on slide 6.
Speaker 4: We achieved $28.3 million in expo of next product revenue for the quarter.
Speaker 4: which is consistent with the first quarter last year.
Speaker 4: Total demand for Exposvio grew year over year in a very competitive multi-miming marketplace, and we are encouraged by the continued growth in the community setting.
Speaker 4: Shifting to cell and exorbitant position internationally, our continued global expansion provides further opportunities to treat patients in need.
Speaker 4: with the additions of new licensed territories with Menorini in the Middle East and Africa, as well as full marketing authorization for Nexpovio in the UK, broadening our international footprint.
Speaker 4: We continue to advance a streamlined clinical pipeline focused on our four core programs.
Speaker 4: I want to highlight our recent data presented at AACR in treatment naive myelophybrosis, where cell NXOR60 milligram in combination with Ruxilitinib demonstrated rapid, deep, and sustained spleen response.
Speaker 4: Based on this, we are planning to initiate a pivotal phase 3 study this quarter as we believe Selenexor 60 mg plus ruxolitinib has the potential to transform standard of care for frontline myelofibrosis. Additionally, earlier this week we announced encouraging interim efficacy data from the phase 2 study of Eltenexor, our second novel sign compound, in 30 patients with hard-to-treat higher risk relapsed or refractory MDS.
Speaker 4: finding to initiate a pivotal phase three study this quarter, as we believe, Stalin XOR 60 milligram plus Ruxilitinib, as the potential to transform standard of care for frontline myelofibrosis. Additionally, earlier this week, we announced encouraging in-term efficacy data from the phase two study of ELTHAN XOR, our second novel sign compound, in 30 patients with heart to treat, higher risk relapse or refractory MDS, which Rishma will discuss.
Speaker 5: With that, I would now like to turn the call over to Sohanya on slide seven for her review of the commercial performance for the quarter and perspectives on our updated guidance for 2023. Sohanya. Thank you, Richard, and good morning, everyone. On slide eight, I will be discussing first quarter of EXPOVIO performance within an evolving and competitive multiple mile of landscape. In the first quarter, EXPOVIO continued to show growth year over year in total demand and new patient starts despite facing a competitive landscape that intensified over the past year.
Speaker 5: In the academic setting, we saw sustained demand year-over-year despite increasing uptake of the novel by specifics and parties.
Speaker 5: The positioning of expovio is actively evolving in the academic setting with the emergence of T cell therapies, and we have an opportunity to serve key patient segments with an increasing body of evidence for expovio that Rayshma will expand upon shortly. Now let's take a look at some of the key headwinds we say that adversely impacted on NETS
Speaker 5: Second, there was a significant increase in utilization of our Carey Forward Patient Assistance Program or PAP, where we provide free drug to patients who qualify and who are unable to afford the cost of their medication.
Speaker 5: Many patients rely on financial assistance from independent nonprofit foundations dedicated to improving access to important medications by providing financial support, including programs supporting Medicare-Party patients who need copious assistance for their multiple Myeloma oral therapy.
Speaker 5: Medicare patients constitute about 60% of our total patient mix for expobio.
Speaker 5: However, these foundations did not have sufficient funding and were unable to provide financial support to patients in Q1 of 2023 and continuing through the end of April .
Speaker 5: As a result, we faced an unprecedented increase in the use of our patient assistance program in this period. Historically, our PAP program attributed to approximately 5% of total demand and has steadily really increased since February of this year approaching 20% in April .
Speaker 5: Patients entering PAP remain in the program through the year and course of treatment.
Speaker 5: Thus, there is a cumulative effect over subsequent quarters due to the refills associated with these new starts.
Speaker 5: Now moving forward in 2024, IRE-related changes in the design of Medicare Part D will eliminate the patient burden of the 5% beneficial insurance requirement, and we expect significantly less need for Medicare Part D patients to utilize care afford for copay assistance.
Speaker 5: While there are several external factors that can shift in the marketplace, the primary driver for revising our Net Product Revenue Guidance to $110 to $125 million is higher year-to-date usage of PEP and their associated refill impact.
Speaker 5: as well as our uncertainty around weather foundations supporting multiple myeloma patients will be able to provide financial support for new eligible patients throughout 2023.
We recognize the important role that expovio can play in patients that are battling multiple myeloma and we're dedicated to continuing to provide free access to expovio for patients that qualify for our Carey Forward program.
As we look to key drivers of growth for 2023 and beyond, we're pleased with the continued positive momentum across our leading indicators.
Importantly, we continue to make strong progress in shifting into early aligns.
In Q1, 2023, Expovio new patient share approached 60% in the second to fourth line compared to 45% in Q1 of last year.
This is encouraging, as it allows patients to potentially have a more optimal experience in the earlier lines and extend time on therapy. This is supported by intent to prescribe data which showed an improvement in tolerability perception in the second or fourth line.
Let's now turn to slide 9.
Amidst the crowded and evolving landscape, we believe we're strongly positioned as a novel class of therapy in the second to fourth line in between three major classes used in the first and second lines and T cell therapies in later lines.
And I remain confident in our potential for mid to long-term growth.
We are positioning X-FovIO in three targeted patient populations.
First, in the community setting where earlier line patients tend to be treated, Expovio is an optimal therapy in the second to fourth line post-anti-CD38 treatments as a novel class of therapy that is an effective, manageable, easily combinable, and a convenient oral therapy.
Second, as T-cell therapies emerge and are used increasingly in the academic setting, exposure may be an optimal potentially T-cells-bearing therapy that can be used at any stage of a patient's treatment journey. The racial model will expand upon the building body of evidence that suggests.
XPO1 inhibition may be associated with preserving T cell health. Finally, in the academic setting, a third segment of patients is the elderly patients that constitute about two-thirds of all myeloma patients.
And they typically are not able to access a T-cell therapy due to age and frailty.
As we think about the mid to long-term growth potential of expovia in multiple myeloma, we're encouraged via XPD study, the triplacombination of cell in XOR with pomolytomide and exomezones, and finite investment could lead to the only all-oral, potentially T cells faring regimen in the marketplace if approved.
Pomalidomide, an IMID, has shown no potential negative impact on T cell function, unlike alkylating agents such as cyclophosphamide that have shown to impact T cells at one year post-exposure. Additionally, pomalidomide is over a $2 billion drug and a critical backbone in second to fourth line.
with potential for increasing utilization accelerated by the need for T-cell sparing therapies in the future.
In summary, despite the headwinds in 2023, we continue to advance a mission for expoVIO that every eligible patient with multiple myeloma should receive Selenex or during that patient journey.
Please advance now to slide 10, and I'll turn the call over to Reshma to review our clinical pipeline progress. Thank you, Sohanya. Starting off with an overview of our clinical pipeline on slide 11, we are rapidly advancing our pipeline, which is evaluating two complementary novel sign compounds.
and Eltenexor, across multiple cancers of high unmet need, including myelofibrosis, myelodysplastic neoplasms, endometrial cancer, and multiple myeloma. Turning now to slide 12, we continue to optimize the dose of Selenexor across our clinical programs.
The lower doses of 40 or 60 milligrams weekly that are incorporated in all of our current cell and exor clinical trials are a quarter to less than half of the original approved dose of 80 milligrams twice weekly. These substantially lower doses optimize the patient benefit by improving its tolerability.
Ultimately enabling patients to stay on therapy longer and improving their overall benefit.
I'm going to spend most of my time today talking about our recent data in mylofibrosis and mylo dysplastic neoplasms. But first, on slide 14, it is worth reviewing some of the evidence about the potential benefit of selenector in T-cell fitness.
There are a number of published studies which have shown that Selenexor maintains T-cell function in mice and can help maintain the effectiveness of CAR T therapies in mice pretreated with Selenexor.
To further expand on these data, we are collaborating with academic institutions on additional preclinical research studies to further explore the impact of fine mechanisms on T-cell fitness.
In addition, we are leveraging real-world evidence data to determine whether patients who were treated with Selenexor prior to receiving CAR-T therapy benefit from improved outcomes with CAR-T. Lastly, we are evaluating multiple clinical studies that will evaluate the benefit of Selenexor.
when used before or after BCMA or CAR T therapy in patients with multiple myeloma. This body of evidence will enhance our understanding of the role of XPO1 inhibition has in maintaining the T cell environment, which may potentially augment the benefit achieved with subsequent T cell therapy.
the event we hosted on April 18th. I will cover these slides quickly. For anyone looking for additional details, I would encourage you to listen to a replay of our webcast from April 18th, which is available in the events and presentation section of our website. Turning to slide 16, the only approved class of therapy and myeloplasmic therapy, and myeloplasmic therapy.
at week 24.
First, let's turn to slide 17, which shows the trial design for our phase 103-4 study, from which the efficacy and safety data for the Selenexor Plus-Croxolitnib combination has been observed.
On slide 18 are the SVR35 and TSS50 results broken down by dose. In the efficacy of valuable and ITT populations, the SVR35 rates at week 24 achieved in the 60 milligram dose cohort were 92% and 79% respectively, which is almost double compared to the rates achieved at 40 milligrams.
Furthermore, these reductions occurred rapidly with the 71% SVR35 rates observed at Week 12 in the 60 mg ITT patient population.
Consistent with the SVR35 data, treatment with the 60 milligram dose showed greater symptom improvement compared to patients treated with the 40 milligram dose.
At week 24 for patients who received a 60-mg dose of cell and X-ore, PSS50 was observed in 78% of the efficacy-available population, and 58% of the ITT population. Here as well, you see rapid improvement in symptoms with approximately 67% of the I-
If you see 100% of the valuable patients treated with cell index or 60 milligrams, achieve a spleen volume response of 35% or more at any time.
Moving to slide 20, we have the subgroup data in patients treated with Selenexor 60 mg. In general, efficacy was similar across all of the subgroups that were evaluated. Highlighted in orange are two important subgroups, specifically the response rates for men and women in the ITT population.
which were similar at 78% and 80% respectively. Similar efficacy was also observed by Ruxilitinib starting dose with patients who were treated at starting doses of 15 or 20 milligrams of Ruxilitinib, achieving an SBR 35 of 75% as compared to 83% amongst patients treated with...
Even with the sub-therapeutic dose of RuxolidMib, all patients are valuable at week 24, achieved a screen volume reduction of 35% or more.
Similarly, symptom score improvement was observed in all patients with five out of six patients achieving a 50% or greater improvement in their total symptoms.
These data suggest that XP-L1 is a fundamental mechanism in myelofibrosis. Slide 22 presents a breakdown of adverse events. The most common adverse events were nausea, anemia, fatigue, and thrombocytopenia, and the most common grade 3-4 AEs were anemia, thrombocytopenia, and fatigue.
tyemitic, nausea rates both decreased and occurred at only a grade one severity. We anticipate that these rates will further decrease in the phase 3 study, which will incorporate mandatory dual anti-emetics for the first two cycles.
On slide 23, even though some patients experience nausea and vomiting, there was a median absolute weight gain of 2.5 kilograms observed at week 24 in patients treated with cell and XOR60 milligrams. As shown on slide 24, we highlight the potential findings for disease modification.
initiation and stay low. The increase in hemoglobin over time coupled with the rapid normalization of platelet levels between cycles two to three may be evidence of disease modification. Critical finding for patients given that thrombocytopenia is the leading cause for ruxilitinib discontinuation. In summary, as we turn to slide 25,
We believe Selenexor 60 milligrams, in combination with ruxolitinib, has the potential to transform frontline myelofibrosis treatment paradigms. The combination is generally well tolerated and manageable, allowing most patients to remain on therapy. Rapid, deep and sustained spleen response and robust symptom improvement.
were found in patients treated with Selenex or 60 milligrams in combination with proxal itinib appearing to work together synergistically.
As seen on slide 26, the planned phase 3 trial will enroll JAK inhibitor-naive patients with intermediate and high-risk myelofibrosis.
306 patients will be randomized two to one to ruxolitinib plus selenexor or ruxolitinib plus placebo. We are eagerly looking forward to initiating the phase 3 trial this quarter.
Now let's turn our attention to our research in patients with myelodysplastic neoplasms, or MDS, starting on slide 28. Between 12,000 to 20,000 people in the United States are expected to have been diagnosed with higher-risk MDS in 2022.
Hypomethylating agents are the current standard of care for newly diagnosed higher risk MDS patients. However, only approximately 50% of patients respond.
Prognosis and higher-risk relapsed refractory disease is poor with an expected overall survival of only four to six months, and there are currently no approved therapies for HMA refractory MDS. you
Given the importance of XPO1 inhibition in MDS, LTNX-4 has the potential to meaningfully improve survival and provide benefit to patients who are in need of effective therapies.
Turning the slide 29, you can see the design of our Phase II study of ultinexore in relapse refractory higher risk MDS.
The data that we will be discussing today is from the 30 patients enrolled as part of the phase 2 interim analysis.
All patients were treated with the recommended phase two dose of El Tenexor identified in the phase one, which was 10 milligrams daily for five days of each week.
As shown on slide 30, the objective response rate observed in the ITT population was 27%.
All of the responses were meros CRs, with two of these patients also achieving hematologic improvement.
The median overall survival was 8.7 months, which is encouraging given the median overall survival for patients to retire, risk relapse or refractory MDF is typically only 4 to 6 months.
Finally, on slide 31, side effects were generally tolerable and manageable. The most common AES were Esthenia, diarrhea, an nausea. The most common grade 3 plus AES were Neutropenia, Thurombocytopenia, and Esthenia. There were no treatment-related adverse events leading to deaths.
and three patients discontinued due to a treatment related adverse event.
Overall, the data from our interim analysis points to the potential importance of XP-01 inhibition in MDS. We plan to study these data further and determine the optimal development plan for Elton Xor in MDS in the second half of this year. With that, please turn to slide 32 and I will now hand it over to Mike.
I hope everyone is having a great morning and thank you, Ragema. 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 begin on slide 33.
Total revenue for the first quarter of 2023 was 38.7 million compared to 47.7 million for the first quarter of 2022.
Net product revenue from U.S. commercial sales of Expovio for the first quarter of 2023 was $28.3 million compared to $28.3 million for the first quarter of 2022. As Sohanya discussed, net product revenue was adversely affected by the pandemic.
by more patients using our patient assistance program, as well as higher gross-to-net discounts, which were 24% for the quarter. We now expect our gross-to-net discounts will be near the higher end of our range of 20% to 25% this year.
Turning to costs, with our continued discipline execution, we are pleased to be delivering a combined 16% year-over-year reduction in our R&D and SG&A expenses this quarter. As we have discussed in the past, we have a focused pipeline and you are seeing this in our R&D spend. It has systemplayers of all different markets around the world. That's clearly correct.
R&D expenses for the first quarter of 2023 were 32.3 million, down 23% compared to 42.1 million for the first quarter of 2022.
Likewise, SG&A expenses for the first quarter of 2023 were $35.9 million, down 7% compared to $38.8 million for the first quarter of 2022.
We are achieving this through purposeful and comprehensive spend discipline, which includes the accelerated closure of our non-core programs while simultaneously rapidly advancing three pivotal Phase III programs. Cash, cash equivalents, restricted cash and investments as of March 31, 2023, total $261.9 million.
compared to $279.7 million as of December 31st, 2022.
At Cahanya Outline, we are allowing both our total revenue and expoVO net product revenue ranges by 15 million, primarily due to the higher than anticipated use of our patient assistant programs and associated free drug.
In 2024, we expect this to improve with fewer patients utilizing our path for copay assistance due to IRA-related redesign of Part D benefits.
With these changes, we are now guiding to total revenue of $145,260 million for 2023.
and US expover you a net product revenue of 110 to 125 million.
On the cost side, as we've accelerated our closure of non-party programs and disciplined expense management,
We are also lowering our expense guidance by $15 million. We now anticipate non-GAAP R&D and SG&A expenses which excludes stock based compensation expense to be in the range of $245-$260 million for the full year of 2023.
And finally, that our existing cash, cash equivalents, investments, as well as the revenue we expect to generate from expo, product sales, and other licensed revenues will be sufficient to fund our planned operations into late 2025.
I'll now flip to slide 34 and turn the call over to Richard for some final thoughts. Richard? Thank you, Mike. Turning to slide 35.
As we have discussed today, we are rapidly advancing our pipeline with three Phase III programs to potentially expand our commercial indications as we demonstrate the benefit that XBL-1 inhibition can deliver to patients in areas with high unmet need. We continue to expand on our foundation and multiply well enough.
and believe that every eligible patient should receive Selenexorg during their patient journey. I would like to thank our teams that continue to execute in a disciplined manner and who strive each day for patients with high unmet needs as we work to generate value for patients and shareholders. 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?
the operator to open the call up to the Q&A portion of today's call. Operator? Thank you.
We will now begin the question and answer session. To ask a question you may press star then one on your telephone k-pad. If you are using a speaker phone please pick up your handset before pressing the keys.
To withdraw your question, please press star then 2. At this time we will pause momentarily to assemble our rostral.
Our first question comes from Peter Lawson from Barclays, please go ahead.
Peter, your line is unmuted. You could please go ahead with your questions. Thank you so much. Thanks for the detail this morning around the quarter. I wonder if you could just add to it on free drug and path program.
Is that still increasing and where do you think that could be as you kind of exit 2Q? And then for Mike, what do you think the revenue impact on the quarter was from the PAP free drug program and grossed note? Sure Peter, thanks for the question. I mean I think broadly.
our guidance with with our guidance coming at the higher end you know if there's less patients having to access our patient assistance program versus more towards the mid to lower end you know if it continues at the same rates
And then maybe I'll turn to Mike to talk about the impact with regards to grossing it. I think Peter, your question was on impact on PAP for the quarter.
Yes, and of course, the net. So if you can break out the revenue impact. Yeah, so our growth to net for the quarter was about, was 24%, which was about five points higher, year over year. So we're guiding on the call today, was we're keeping our range of 20 to 25% for regarding that it'll be.
on the higher end of that range for the rest of the year. And as far as direct impact on the quarter, it was a hair over a million dollars or so on Q1. So the impact is more forward-looking, as Sahanya mentioned in her script on where these foundations, or when these foundations would open for the year. So it's not a massive impact on Q1, but it's more forward-looking.
Thank you and then just on the foundations is there any change there going forward some in it and is all that is that spend being more focused around
BCMA versus other therapists, do you think? Yeah, Peter, we don't really obviously have insight into what kind of patients are accessing the foundations programs. So I think as we touched on, obviously the foundations play a really important role. This issue is not a tool to cross-check that, in order to show true understanding, we need to approach awareness through it out into rewarding memories that it will fade.
supporting patients with financial assistance that need access to assistance, and especially in the Medicare Part D patients who need co-pay assistance.
especially with regards to looking at what's happening to patients as they transition into the 5% extra cost moving forward. And so as we talked about, you know, looking at 2024 moving forward, kind of this catastrophic coverage of the
5% copay, the change driven through the IRA changes that we expect will require less patients to access patient assistance programs.
I guess just a final question just for Mike around cost savings, whether that impacts SG&A or R&D and how that filters through to programs in the second half.
Yes, the big part of it is really acceleration of closing our non-prioritized programs. So that's really the focus in order to bring down the R&D side of expense. And of course, we have our two ongoing phase threes and one to start. So it's a mix across all three areas of R&D.
commercial and SG&A, but you know it's a combination of cost discipline and acceleration that closure of the non-prioritized program. Thanks so much.
in SG&A, but it's a combination of cost, discipline, and acceleration, that closure of the non-paradise program. Good, okay, thanks so much. Thanks, Peter.
Thank you. Next question comes from the line of Maori Raycroft from Jeffries. Please go ahead. Hi, good morning. This is Kevin on for Mori. Thanks for taking my questions. First question I had was on on myeloma. You pointed out that almost 60% of the new patient shares from the earlier
Thanks, Kevin. Maybe I'll turn to Sohanya to expand on that.
Yeah, hi, Maureen. Thanks for the question. So, yeah, so, we are approaching 60% of Exovio new patients starts moving into the earlier lines. And that means that, you know, the remainder of the patients are in the fourth line, fifth line plus.
Now, that is driven by primarily in the community where we're seeing an increased use of exposure as well as use in the early aligns.
Okay, great, thanks. And then just on the dose response relationship that you saw in turning to myosibrosis in the phase one, in the 60 versus the 40 milligram doses.
What would you expect or what do you expect in the ongoing endometrial and myeloma phase 3s where you're running studies at lower doses than you previously looked at?
Yeah, Rachman, do you want to expand on that? Yeah, great question, Kevin. So what you can see across all of our programs, MiloFibrosis, Endometrial, and Multiple Miloma, we've incorporated these lower doses of either 40 milligrams or 60 milligrams dose weekly.
But what we are triangulating around is that these, again, lower doses, improve the tolerability, enable patients to stay on therapy, and of course ultimately drive that efficacy. So it is nice to see that consistency, again, in that positive benefit risk around these lower doses of Selenex Thor.
regardless of tumor type. Great, thanks. Just a final quick follow-up for ASCO. You have a malefibrosis poster there. Should we expect any new data in terms of maybe durability or dose intensity or anything like that? We haven't guided on the actual content.
follow-up patients long-term and have collected multiple samples. So again, can't comment specifically at what's going to happen at ASCO, but there are going to be new data. And we hope to be able to present new data over the course of the next 6, 12, 18 months from the study.
Okay. Thanks, Rishma.
Okay, thanks, Rishma. Thanks, Kevin. Thank you.
Next question comes from the line of Mike Ulz from Morgan Stanley . Hi, this is Wenjuan online for Mike. I just have a question about this PAP program utilization. So what do you see the men driving factor of the increasing, like from 5% to 20% within just two months?
in terms of the significant increase in the utilization of PAP was driven by, particularly, the Medicare Part D patients. Now, our PAP program provides free drug to qualify uninsured and underinsured patients broadly, but this includes
Medicare Part D patients that need financial assistance with their 5% beneficiary co-insurance requirement above the catastrophic coverage threshold. Now this segment of patients were a particular driver in terms of financial assistance that they needed.
and the impact that we saw as a result of the foundation closure. Now looking into 2024, this is the piece that is eliminated in the redesign of the Part D benefits per the IRA. So the 5% beneficiary coinsurance requirement above the catastrophic coverage threshold is eliminated. There's nothing
So that segment of patients will lead less financial assistance and less reliance on patient assistance programs in 2024. As for the remainder of this year, again, as Richard commented earlier, we've...
incorporated into the guidance range, this uncertainty factor on whether foundations can support new patients for the rest of the year, as well as the guidance incorporates the year-to-date impact of PAP as well as subsequent refills.
Okay, thank you. Thanks, Sanjay. Thank you. Our next question comes from the line of Colleen Cussy from BED. Please go ahead.
Great, good morning and thanks for taking our questions. On ExpoViewXUS, can you talk about some of the drivers there and what gives you confidence in hitting the X-GRAC portion of your guy? You are feeling that love between you and
Thanks Colleen, when you look at what's happening ex-US, as we've talked to earlier, the commercial launches have taken place in Germany and Austria. Manorini is working through the pricing reimbursement process in the EU this year and over the next 10 or 12 months.
I think in those markets, obviously they were able to launch in the second line plus indication to start. So I think that enables them to move forward, I think with the learnings we have here in the U.S. and a more rapid uptake. And I think when we look outside of the U.S., also we know in Asia PAC, you know, expolvios is commercially available in mainland China, Australia.
South Korea, Singapore and Taiwan. And the commercial launch in mainland China took place in May of 22. At the same time, they're working through the China NRDL strategy. It's under evaluation, depending on label expansion and timing. And further discussion with the China authorities. So.
I think our partners across the globe making really good progress with regards to moving forward from the commercial launch perspective. Great, that's helpful. Thank you. And then just based on the the MDS data that you put out this week, what are the potential next steps for that program and are any of those next steps currently including your cash guidance? Okay, Colleen, I'll take that one.
poor, unfortunately, at four to six months, so again encouraged by those 8.7 median overall survival that we observed from the interim, also encouraged by the ORR. You know, we're going to take a look at these data, interrogate them further, and define the next steps in the next half of the second year.
I'll turn that financial question over to Mike. Hey Colleen, we do have some L10 extra costs in our you know cash guidance. Ultimately depending what happens with the MDS program is where you know those costs will be but for now we have some some probable ice placeholders for sure.
Understood. Thank you. Last question, just on myelofibrosis and the competitive landscape there, I know we're going to get some Phase III data by the end of this year from the Manifest II study. How do you expect that data would impact your development and regulatory plans on myelofibrosis? Yeah. Okay. Bye-bye.
Yeah, great question. So, you know, at a high level, I don't think it really impacts, you know, what we do with our phase three, you know, again, very encouraged by the phase one data. Right now, our entire focus is really initiating the phase three, which we anticipate is going to start.
and transform, we have an opportunity to be best in class and to really transform the first-line myelofibrosis space, not only based upon the numerical SVR and TSS50 data that we've presented at week 24, but also the very important improvement in cytopenias given the underlying disease modification.
that our current data suggests, but also importantly, the fact that we potentially may have monotherapy activity with Selenex4, and those data are really based upon that suboptimal Rux data in which efficacy is preserved for both SVR and TSS50.
even when the ruxolitinib doses are reduced all the way down to 5 milligrams. That affords physicians a lot of flexibility to potentially discontinue rux due to, let's say, toxicity and continue a patient on with Stellan X4.
Again, I think there's a lot of differentiating factors with Selenex4 plus rexelitinib that can potentially enable it to be a best-in-class, really regardless of what happens with some of the other competitors. Okay, great.
There's a lot of differentiating factors with Selenex4 plus rexelitinib that can potentially enable it to be a best-in-class, really regardless of what happens with some of the other competitors. Great. Thanks for taking your questions.
Our next question comes from the line of Chris Raymond from Piper Jaffray. Please go ahead.
Good morning. This is Nicole Gobresian for Christy. Thanks for taking the question. Sorry if I missed this, but just as we think about the rest of the year in terms of guidance, I guess is there any certain quarter where most of the impact of these headlines for exovia might be recognized or I guess how should we be thinking about that? And then just quickly for mylofibrosis. Thanks.
Just, you know, as we look at the other Milo Fibrosis program in development, those tend to have a single primary endpoint of SBR35. Can you just maybe talk about the rationale or drivers behind having co-primary endpoints for your phase three study? Thanks, Nicole. I'll comment on the first and turn it over to Terracima. But, you know, when you look at the evolution of recorders, I think you can expect you are kind of consistent.
differences that you see quarter over quarter, you know, in line with our historical patterns. And then as we talk to, you know, looking at the impact of patient assistance programs, we just need to see how that evolves during the year. And that's obviously something which we have to see what comes in in terms of patients requiring assistance through our programs. And as we've said, you know, in our guidance range, you know, with less patients having access to our patient assistance program that'll move us towards higher end.
And if we continue to see high rates of patients accessing our patient assistance program that moves us towards the middle to lower end. And Ration, would you want to expand on the second part of the question? Yeah, absolutely. And thank you for the question, Nicole. So we're really focused on two main end points. The FCR 35 and TSS 15, ultimately for the patients. It's really critical that we show significant improvement in both of those end points. Of course, the SBR is a potential surrogate for overall survival. That reduction is key in showing a significant improvement. Potentially, potentially portends overall long-term improvement for the patient.
and it's going to be our focus in our phase 3 trial as well.
Great. Thanks. Thanks, Nicole.
Great, thanks. Thanks, Nicole. Thank you.
Our next question comes from the line of Eric Joseph from JP Morgan. Please go ahead. Good morning. Interesting in the questions. Just following up on the commercial outlook with ExpoView in 2024, I get that you anticipate less happy utilization, but outside of that, he just...
comment on expectations on net pricing. We typically have seen some price hike. I can just kind of comment on whether those would actually flow through ultimately on the net price.
For Elson XOR, I know that you're, you know, the sounds like you're just, you're currently evaluating sort of the Delta-PAT-4 there. Is combination therapy part of the consideration there? Can you just talk about the potential combination path with Elson XOR? Thanks.
Yeah, maybe I'll turn to Sohanya for the first part of that and then Reshma on the second part. Yeah, thanks, Eric, for the question. Again in terms of 2024, we're not providing guidance for 2024 revenues. To your point, in 2024, because of that IRA-related change, we do expect to see significantly increased lows for 2021 starting from the very, very Junes. – Vince
mid to long term, I remain confident in our growth potential.
And I can take the next one, Eric. Thank you for the question. Great question. Yeah, as you noted, we're not talking about the next steps in the development at this time. With that said, the fact that Altanexor is showing monotherapy activity in this hard-to-treat patient population for many years puts Return to the Neurocentric Off l Lyft INFLU other
of opportunities, but again, it's built upon the foundation that Eltonuxord does have monotherapy activity. And in addition, the myelofibrosis is now showing in this different tumor type that XP01 is a fundamental mechanism in this heart-to-treat cancer.
Just first one, any updates on the regulatory interactions for the myelofibrosis phase 3? And are you able to discuss any of the statistical assumptions behind the study? And then I'll follow up. Thanks. Sure, Matt. I'll turn to Rachel for that. Yeah. Thanks, Matt, for the question. Thanks for the Zantacin.
So we've had productive discussions with the FDA and have incorporated their feedback into our design. We don't talk about any specifics of those FDA interactions. And, you know, as I mentioned earlier on the call, you know, really our focus at this point is initiating this trial likely this quarter.
In terms of the statistical assumptions, so there, too, we haven't disclosed any of the details. With that said, we're looking very closely not only at the data that we've observed as part of our Phase I for both SPR and TSS50, but also looking at the historical data that we know that ruxolitinib has provided.
again for both of those end points. So really have utilized those data to ultimately design the most efficient trial that can enable this treatment to patients who have myelocybrosis. It is definitely possible put three specific things in mind that are great.
Great, that's very helpful. And then just following up on the ELTNX or data that you just released, we noticed there was a high degree of censoring in some of the survival data. I was wondering if you could provide any, you know, color on those patients and, you know, what happened with them. And then also...
if you were able to provide any detail on the patient experience for patients that were post both venetoclax and azacytidine. Thanks. Yeah. Great question. So, we still have quite a few patients who are still in survival follow-up, hence one of the reasons that they are censored. This trial is ongoing. We continue to follow those patients for survival, and hopefully we'll have an opportunity to present updated survival over the course of the next few months.
In terms of the post-venetoclax azacitidine, so great point, and this is a key differentiation from our Phase 1 study in that we had a subgroup of patients who did receive prior venetoclax, which is a BCL-2, a smaller subgroup of patients who received a combination of venetoclax plus HMA inhibitors.
Why is this such an important point? Largely because there are some preliminary data coming out of MD Anderson that suggests that patients who have received prior BCL-2 may have poor prognosis compared to the already very poor prognosis in relapsed refractory MDS. So, you know, this is something that we're looking at more closely. But, again, it gives us opportunity to further develop L-10x sports.
Thank you. Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back to Mr. Richard Paulson for any closing remarks.
Thank you, operator. And thank you again to everyone for joining today's call. I'm wishing everyone a great day.
Thank you. The conference of KRIPAM has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.
Have a great weekend.
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