Karyopharm Therapeutics Q1 2023 Earnings Call Transcript

Quartr
Provided by Quartr
May 4, 2023

There are 12 speakers on the call.

Operator

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 Karyopharm Therapeutics First Quarter 2023 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.

Operator

I would now like to turn call over to Elan Wepp, Senior Vice President, Investor Relations. Thank you. Over to you.

Speaker 1

Thank you, operator, and thank you all for joining us on today's conference call to discuss Karyopharm's Q1 2023 financial results and recent company progress. We issued a press release this morning detailing our financial results for the Q1 2023. 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, Soania, Reshma and Mike, who will provide an update on our Q1 results and recent clinical developments. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 as outlined on Slide 3.

Speaker 1

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 10 ks, which is on file with the SEC and

Speaker 2

in other filings that we

Speaker 1

may make with the SEC in the future. Any FLS represent our views as of today only. 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 these FLS as representing our views as of any later date. I will now turn the call over to Richard.

Speaker 1

Please turn to Slide 4.

Speaker 3

Thank you, Alhan, and thank you all for joining us today for Karyopharm's Q1 2023 earnings call. As we turn to Slide 5, we are making strong progress as we execute on Karyopharm's next stage of growth by deploying our novel mechanism of action, selective inhibition of nuclear export to expand our existing multiple myeloma franchise, currently centered around our commercial drug, EXPOVIO, which is now approved in over 40 countries and continues to move into earlier lines of therapy in multiple moment. As Sohanyu will discuss further, year over year total demand for XPOVIO continues to grow. However, this is not translating into growth in net product revenue due to increased distribution of free product to our carryforward patient assistance program, PAP, and higher gross to net discounts. These factors have caused us to revise our total revenue guidance for 2023 to a new range of $145,000,000 to $160,000,000 In addition, we have accelerated our closure of non priority programs, thus lowering our spend in 2023,

Speaker 4

to the next question. Our first question comes from the line

Speaker 3

of David. Please go ahead. Our first question comes from the line of David. Our first question comes from the line of David.

Speaker 4

Our first question comes from the line of David.

Speaker 3

Our first question comes from the line of David. Our first question comes from the line of David. 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. 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, to demonstrate efficacy at lower doses with improved tolerability and where we believe we will have the highest probability of success. We are conducting pivotal Phase 3 studies in both myel multiple myeloma and endometrial cancer with a 3rd pivotal Phase 3 study of myelofibrosis, which we expect to start in the first half of twenty twenty three.

Speaker 3

Collectively, we believe we have the potential to achieve multiple product approvals over the next 2 to 4 years as we deliver our next phase of growth, leveraging our proven and established commercialization and mid to late stage development capabilities as we work to generate value for patients and shareholders. As we look at our Q1 highlights on Slide 6, we achieved $28,300,000 in XPOVIO net product revenue for the quarter, which is consistent with the Q1 last year. Total demand for EXPOVEO grew year over year in a very competitive multimilum marketplace and we are encouraged by the continued growth in the community setting. Shifting to selinexor's position internationally, our continued global expansion provides further opportunities to treat patients in need with the additions of new license territories with Menarini in the Middle East and Africa, as well as full marketing authorization for Nexpovio in the UK, broadening our international footprint. We continue to advance a streamlined clinical pipeline focused on our 4 core programs.

Speaker 3

I want to highlight our recent data presented at AACR in treatment naive myelofibrosis where selinexor 60 milligram in combination with ruxolitinib demonstrated rapid, deep and sustained spleen response. Based on this, we are planning to initiate a pivotal Phase 3 study this quarter as we believe selinexor 60 milligram plus ruxolitinib as 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 elfinexor, our second novel sign compound in 30 patients with hard to treat to higher risk relapsed or refractory MDS, which Reshma will discuss. With that, I would now like to turn the call over to Sohanya on Slide 7 for her review of the commercial performance for the quarter and perspectives on our updated guidance for 2023. Sonya?

Speaker 2

Thank you, Richard, and good morning, everyone. On Slide 8, I will be discussing Q1 of EXPOVIO performance within an evolving and competitive multiple myeloma landscape. In the Q1, 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. Net product revenue was consistent with the same period last year and was adversely impacted by multiple external factors. When you look at what is positively driving our total demand, The community business continued to grow contributing to about 70% of Exovio's revenues in the Q1.

Speaker 2

In the community setting, exovio continues to be viewed increasingly favorably as an effective, convenient to oral and manageable therapy with a novel mechanism of action in second to fourth line. In the academic setting, we saw sustained demand year over year despite increasing uptake of the novel bispecifics and CAR Ts. 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 Reshma will expand upon shortly.

Speaker 1

Now let's take

Speaker 2

a look at some of the key headwinds we face that adversely impacted our net product revenues year over year. First, There was an impact from a higher gross to net discount, 5 points higher in Q1 2023 versus Q1 2022, driven by increased 340B discounts and Medicare and Medicaid rebates. 2nd, there was a significant increase in utilization to our Carry Forward Patient Assistance Program or PAP, where we provide free drugs to patients who qualify and who are unable to afford the cost of their medication. Many patients rely on financial assistance from independent non profit foundations dedicated to improving access to important medications by providing financial support, including programs supporting Medicare Part D patients who need co pay assistance for their multiple myeloma oral therapy. Medicare patients constitute about 60% of our total patient mix for to Pfovio.

Speaker 2

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. As a result, we faced an to unprecedented increase in the use of our patient assistance program in this period. Historically, our PAC program 20% in April. Patients entering PAP remain in the program through the year and course of treatment. Thus, there is a cumulative effect over subsequent quarters due to the refills associated with these new starts.

Speaker 2

Now moving forward in 2024, IRE related changes in the design of Medicare Part D will eliminate the patient burden of the 5% beneficiary coinsurance requirement and we expect significantly less need for Medicare Part D patients to utilize carryforward for co pay assistance. While there are several to external factors that can shift in the marketplace. The primary driver for revising our net product revenue guidance to $110,000,000 to $125,000,000 is higher year to date usage of PAP and their associated refill impact as well as our uncertainty around whether 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 are dedicated to continuing to provide free access to EXPOVIO for patients that qualify for our Carry 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.

Speaker 2

Importantly, we continue to make strong progress in shifting into earlier lines. 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 our intent to prescribe data, which showed an improvement in tolerability perception in the second to fourth line. Let's now turn to Slide 9.

Speaker 2

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 3 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 EXPOVIO in 3 targeted patient to the 2nd to 4th line post anti CD38 treatments as a novel class of therapy that is an effective, to the next available and convenient oral therapy. 2nd, as T cell therapies emerge and are used increasingly in the academic setting, EXPOVIO may be an optimal potentially T cell sparing therapy that can be used at any stage of a patient's treatment journey. Reshma will expand upon the building body of evidence that suggests XPO1 inhibition may be associated with preserving T cell health.

Speaker 2

Finally, in the academic setting, a third segment of patients is the elderly patients that constitute about 2 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 XPOVIO in multiple myeloma, We're encouraged by our XPD study, the triplet combination of selinexor with pomalidomide and dexamethasone and find our investment could lead to the only all oral potentially T cell sparing regimen in the marketplace if approved. Pomalidomide and 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 1 year post exposure. Additionally, pomalidomide is over a $2,000,000,000 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 our mission for XPOVIO that every eligible patient with multiple myeloma should receive selinexor during their patient journey.

Speaker 2

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 to the next slide, which is evaluating 2 complementary novel sign compounds selinexor and eltonxor across multiple cancers of high unmet need, including myelofibrosis, myelodysplastic neoplasms, to endometrial cancer and multiple myeloma. Turning now to Slide 12, we continue to optimize the dose of selinexor across our clinical programs. The lower doses of 40 or 60 milligrams weekly that are incorporated in all of our current selinexor to the Q1 of 2019.

Speaker 2

To substantially lower doses optimize the patient benefit by improving its tolerability, ultimately enabling patients to stay on therapy longer in improving their overall benefit. I'm going to spend most of my time today talking about our recent data in myelofibrosis to myelodysplastic neoplasms. But first on Slide 14, it is worth reviewing some of the evidence about the to the potential benefit of selinexor in T cell fitness. There are a number of published studies which have shown that selinexor maintains T cell function in mice and can help maintain the effectiveness of CAR T therapies in mice pretreated with selinexor. To further expand on these data, we are collaborating with academic institutions on additional preclinical research studies to further to explore the impact of sign mechanisms on T cell fitness.

Speaker 2

In addition, we are leveraging real world evidence data to to the treatment of the treatment

Speaker 4

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Speaker 2

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Speaker 4

treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the treatment of the

Speaker 2

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Speaker 4

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Speaker 2

treatment of the treatment of the treatment of the treatment of the Lastly, we are evaluating multiple clinical studies that will evaluate the benefit of selinexor when used before or after BCMA or CAR to T therapy in patients with multiple myeloma. This body of evidence will enhance our understanding of the role of PL-one inhibition has in maintaining the T cell environment, which may potentially augment the benefit achieved with subsequent T cell therapies. Now let's discuss the data that we presented a few weeks ago at AACR on the efficacy and safety of selinexor plus ruxolitinib in first line myelofibrosis patients. Since we already discussed these data at the event we hosted on April 18, 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 18, which is available in the Events and Presentations section of our website.

Speaker 2

Turning to Slide 16, to achieve an FCR35 and TSS 50. And there are notable subgroups, including men and those who start on low dose of ruxolitinib for fewer than 25% achieved in FCR35 at week 24. First, let's turn to Slide 17, to the team, which shows the trial design for our Phase 1,034 study from which the efficacy and safety data for the selinexor plus ruxolitinib combination have been observed. On Slide 18 are the SPR-thirty five and TSS-fifty results broken down by dose. In the efficacy evaluable in ITT populations, the SBR35 rates at week 24 achieved in the 60 milligram dose cohort were 92% 79%, respectively, which is almost double compared to the rates achieved at 40 milligrams.

Speaker 2

Furthermore, these reductions occurred rapidly with the 71% SVR35 rate observed at week 12 in the to the 60 milligram ITT patient population. Consistent with the FCR35 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 milligram dose of selinexor, PFS50 was observed in 78% of the efficacy evaluable population and 58% of the ITT population. Here as well, you see rapid improvement in symptoms with approximately 67% of the ITT population who received selinexor 60 milligrams to achieve a TSS-fifty as early as week 12. The waterfall on Slide 19 shows the to the Selinexor 60 milligrams to achieve a spleen volume response of 35% or more at any time.

Speaker 2

Moving to Slide 20, we have the subgroup data in patients treated with selinexor for 60 milligrams. In general, efficacy was similar across all of the subgroups that were evaluated. Highlighted in orange are 2 important subgroups, specifically the response rates for men and women in the ITT population, which were similar at 78% 80%, respectively. Similar efficacy was also observed by ruxolitinib starting dose with patients who are treated at starting doses of 15 or 20 milligrams of ruxolitinib, achieving an SVR35 of to 75% as compared to 83% amongst patients treated with 5 or 10 milligrams of ruxolitinib. On Slide 21, we show a unique subgroup analysis from patients that had their ruxolitinib dose reduced to 5 milligrams as early as cycle 2 and remain on that dose for the remaining duration of their therapy.

Speaker 2

Even with the sub therapeutic dose of ruxolitinib, All patients evaluable at week 24 achieved a spleen volume reduction of 35% or more. Similarly, symptom score improvement was observed in all patients with 5 out of 6 patients achieving a 50% or greater improvement in their total symptoms. These data suggest that Xpi01 is a fundamental mechanism in myelofibrosis. Slide 22 to the 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 neutropenia.

Speaker 2

While 75% of patients experienced nausea, to the vast majority of these events for Grade 1 and transient with the majority of these events resolving within 2 cycles. Amongst the patients who received one prophylactic antiemetic, nausea rates both decreased and occurred at only a Grade 1 severity. We anticipate that these rates will further decrease in the Phase 3 study, which will incorporate mandatory dual antiemetics for the first two cycles. On Slide 23, even though some patients experienced nausea and vomiting, there was a median absolute weight gain of to 2.5 kilograms observed at week 24 in patients treated with selinexor 60 milligrams. As shown on Slide 24, we highlight the potential findings for disease modification given that the median hemoglobin levels return to baseline and there's a rapid normalization of platelet levels.

Speaker 2

Contrast this with findings from patients have received ruxolitinib as a single agent where hemoglobin levels drop after treatment initiation and stay low. The increase in hemoglobin over time coupled with the rapid normalization of platelet levels between cycles 2 to 3 maybe evidence of disease modification, a critical finding for patients given that thrombocytopenia is the leading cause for ruxolitinib discontinuation. In summary, as we turn to Slide 25, we believe selinexor 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 Stained spleen response and robust symptom improvement were found in patients treated with selinexor 60 milligrams in combination with to ruxolitinib appearing to work together synergistically.

Speaker 2

As seen on Slide 26, the planned Phase Patients will be randomized 2:one to ruxolitinib plus selinexor or ruxolitinib plus placebo. We are eagerly looking forward to initiating the Phase 3 trial this quarter. Now let's turn our to our research in patients with myelodysplastic neoplasms or MDS starting on Slide 28. Between 12,000 to 20000 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.

Speaker 2

However, only approximately 50% of

Speaker 4

to the next question.

Speaker 2

Thank you, everyone. Thank you, everyone. Thank you, everyone. Thank you, to the next 6 months and there are currently no approved therapies for HMA refractory MDS. Given the importance of to the P01 inhibition in MDS.

Speaker 2

Elsinexor has the potential to meaningfully improve survival and provide benefit to patients who are in need of effective therapies. Turning to Slide 29, you can see the design of our Phase 2 study of eltonexor in relapsed refractory to 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 2 dose of altenexor identified in the Phase 1, which was 10 milligrams daily for 5 days of each As shown on Slide 30, the objective response rate observed in the ITT population was 27%. All of the responses were MERA CRs with 2 of these patients also achieving hematologic improvement.

Speaker 2

Noteworthy was the transfusion independence rate served in 29% of the patients who are transfusion dependent on red blood cells or platelets at baseline. The median overall survival was 8.7 months, which is encouraging given the median overall survival for patients with higher risk relapse or refractory MDS It's typically only 4 to 6 months. Finally, on Slide 31, side effects were generally tolerable and manageable. The most common AEs were asthenia, diarrhea and nausea. The most common Grade 3 plus AEs were neutropenia, thrombocytopenia to anesthesia.

Speaker 2

There were no treatment related adverse events leading to death and 3 patients discontinued due to a treatment related adverse event. Overall, the data from our interim analysis points to the potential importance of Xpi-one inhibition in MDS. We plan to study these data further and determine the optimal development plan for eltenxor 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.

Speaker 5

I hope everyone is having a great morning, and thank you, Reshma. 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 Q1 of 2023 was $38,700,000 compared to $47,700,000 for the Q1 of 2022. Net product revenue from U. S.

Speaker 5

Commercial sales of XPOVIO for the Q1 of 2023 was $28,300,000 compared to $28,300,000 for the Q1 of 2022. As Sohanya discussed, net product revenue was adversely affected 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 growth to net discounts will be near the higher end of our range of 20% to 25% this year. Turning to costs. With our continued disciplined execution, we are pleased to be delivering a combined 16% year over year to our R and D and SG and A expenses this quarter.

Speaker 5

As we have discussed in the past, we have a focused pipeline and you are seeing this in our R and D spend. R and D expenses for the Q1 of 2023 were $32,300,000 down 23% compared to $42,100,000 for the Q1 of 2022. Likewise, SG and A expenses for the Q1 of 2023 were $35,900,000 down 7% compared to $38,800,000 for the Q1 of 2022. We are achieving this through to purposeful and comprehensive spend discipline, which includes the accelerated closure of our non core programs, while simultaneously rapidly advancing to 3 pivotal Phase 3 programs. Cash, cash equivalents, restricted cash and investments as of March 31, 2023, to $261,900,000 compared to $279,700,000 as of December 31, 2022.

Speaker 5

As Tania outlined, we are lowering both our total revenue and XPOVIO net product revenue ranges by $15,000,000 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 PAP for co pay assistance due to IRA related redesign of Part D benefits. With these changes, we are now guiding to total revenue of $145,000,000 to $160,000,000 for 2023 and U. S. XPOVIO net to the company's financial performance and disciplined expense management.

Speaker 5

We are also lowering our expense guidance by $15,000,000 We now anticipate non GAAP R and D and SG and A expenses, which excludes stock based compensation expense to be in the range of $245,000,000 to $260,000,000 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 Spovio product sales and other license revenues will be sufficient to fund our planned operations until late 2025. I'll now flip to Slide 34 and turn the call over to Richard for some final thoughts. Richard?

Speaker 3

Thank you, Mike. Turning to Slide 35. As we have discussed today, we are rapidly advancing our pipeline with 3 Phase 3 programs to potentially expand our commercial indications as we demonstrate the benefit that XB-one inhibition can deliver to patients in areas with high unmet need. We continue to expand on our foundation in multiple myeloma and believe that every eligible patient should receive selinexor 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.

Speaker 3

Thank you again for joining us today. And I would now like to ask the operator to open the call up to the Q and A portion of today's call. Operator?

Operator

Thank you. We will now begin the question and answer Our first question comes from Peter Lawson from Barclays. Please go ahead. Peter, your line is unmuted. You could please go ahead with your

Speaker 6

Perfect. 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 PAP program, Is that still increasing and where do you think that could be as you kind of exit 2Q?

Speaker 6

And then for Mike, kind of What do you think the revenue impact on the quarter was from the PAP free drug program and gross to net?

Speaker 3

Sure, Peter. Thanks for the question. I mean, I think broadly, as you heard from Solania, There was a real unprecedented increase in the use of the PAP programs during the period and historically it's been about 5% And now in April approached about 20%. So obviously, we've built that range into our guidance with our guidance coming at the higher end, if there's less patients having to access our patient assistance program versus more towards the mid to lower end, if it continues at the same rates as it is. And then maybe I'll turn to Mike to talk about the impact with regards to gross to net.

Speaker 5

I think, Peter, your question was on impact on PAP for the quarter?

Speaker 6

Yes. And gross to net. So if there's a You can break out the revenue impact. Yes.

Speaker 5

So our gross to net for the quarter was about was 24%, which is about 5 points higher year over year. So we're guiding on the call today. We're keeping our range of 20% to 25%, but we're guiding that it will be on the higher end of that range for the rest of the year. And as far as HAP direct impact on the quarter, it was a hair over $1,000,000 or so in Q1. The impact is more forward looking as Sohanya mentioned in her script on where these foundations or when these foundations We're open for the year.

Speaker 5

So it's not a massive impact on Q1, but it's more forward looking.

Speaker 6

Perfect. Thank you. And then just On the foundations, is there any change there going forward? I mean and is all that is that spend being more focused around BCMA versus other therapies do you think?

Speaker 3

Yes, Peter, we don't really obviously The foundations play a really important role supporting patients with financial assistance that need access to that assistance and into the 5% extra cost moving forward. And so as we talked about looking at 2024 moving forward kind of this catastrophic coverage of the 5% co pay, the change driven through the IRA changes that We expect we'll require less patients to access patient assistance programs.

Speaker 6

Got you. Okay. And I guess just final question just for Mike around cost savings, whether that impacts SG and A or R and D and kind of how that kind of filters through to programs in the second half.

Speaker 3

Yes. The big part of

Speaker 5

it is really acceleration of closing our non prioritized program. So that's really to focus in order to bring down the R and D side of expense. And of course, we have our 2 ongoing Phase 3s and to start. So it's a mix across all three areas of R and D, commercial and SG and A, but it's a combination of cost discipline and Acceleration the closure of the non franchise program.

Speaker 6

Got you. Okay. Thanks so much.

Speaker 7

Thanks, Peter.

Operator

Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Speaker 8

Hi, good morning. This is Kevin on for Maury. Thanks for taking my questions. First question I had was on myeloma. You pointed out that almost 60% of the new patient share is from the earlier line setting versus I believe around 55% or close to that earlier this year.

Speaker 8

Could you say what proportion of that is due to volume increase in the earlier line or whether that's primarily due to increased competition in the later line. Thanks.

Speaker 3

Thanks, Kevin. Maybe I'll turn to Sohanya to expand on that.

Speaker 2

Yes. Hi, Maury. Thanks for the question. So yes, so We are approaching 60% of XPOVIO new patient starts moving into the earlier lines. And that means that the remainder of the patients are in the 4th line, 5th line plus.

Speaker 2

Now that is driven by primarily in the community where we're seeing an increased use of to Expovio as well as use in the earlier lines.

Speaker 8

Okay, great. Thanks. And then just on the dose response relationship that you saw in Turning to myelofibrosis in the Phase 1, 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 for that.

Speaker 7

Yes. Reshma, do you want to expand

Speaker 2

on that? Yes. Great question, Kevin. So what you can see across all of our programs, myelofibrosis, endometrial and multiple myeloma, we've incorporated these to lower doses of either 40 milligrams or 60 milligrams dosed weekly. A lot of that really suggests that regardless of tumor type, you can drive efficacy again with these lower doses of selinexor.

Speaker 2

Now there are going to be differences, right, given the underlying tumor type, whether it's a monotherapy or in combination. To stay on therapy and of course ultimately drive that efficacy. So it is nice to see that consistency again in that to positive benefit risk around these lower doses of selinexor regardless of tumor type.

Speaker 8

Great. Thanks. And just a final quick follow-up for ASCO. You have a myelofibrosis Should we expect any new data, in terms of maybe durability or dose intensity or anything like that?

Speaker 2

We haven't guided on the actual content of ASCO. Again, we did have a recent presentation, to the next question. As you know, at AACR with the February data cut, but with that said, we're always going to have opportunities to provide 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 this study.

Speaker 3

Okay. Thanks, Reshma. Thanks, Kevin.

Operator

Thank you. Our next question comes from the line of Mike Ulz from Morgan Stanley. Please go ahead.

Speaker 9

Hi, this is Wen Zhang on line for Mike. I just have a question about this TAP program utilization. So what do you see the main And although you said like in 2024, you are expecting like lowering utilization,

Operator

what do you see the evolving in

Speaker 9

the next three quarters maybe beyond 2024. Thanks.

Speaker 3

Yes. So Hania, do you want to touch on that?

Speaker 2

Yes. So the main driver 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 qualified uninsured and underinsured patients broadly, but this includes Medicare Part D patients that need financial with their 5% beneficiary coinsurance requirement above the catastrophic coverage threshold. Now this segment of patients We're 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.

Speaker 2

So the 5% beneficiary coinsurance requirement above the catastrophic coverage threshold is eliminated. So that Segment of patients will lead less financial assistance and less reliance on to patients assistance programs in 2024. As for the remainder of this year, again, as Richard commented earlier, We've incorporated into the guidance range this to the 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.

Speaker 9

Okay. Thank you.

Speaker 6

Thanks, Menja.

Operator

Thank you. Our next question comes from the line of Colleen Kashy from Baird. Please go ahead.

Speaker 10

Great. Good morning and thanks for taking our questions. On Ex Fovio ex U. S, can you talk about some of the drivers there? And what gives you confidence in hitting the ex U.

Speaker 10

S. Portion of your guidance?

Speaker 3

Yes. Thanks, Colleen. When I look at what's happening ex U. S, I think as we've talked to you earlier that the commercial launches have taken in Germany and Austria. Menarini is working through the pricing reimbursement process in the EU this year and over the next kind of 12 months.

Speaker 3

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 at outside of the U.

Speaker 3

S, also we know in Asia Pac, to SVovial is commercially available in Mainland China, Australia, South Korea, Singapore and Taiwan. And the commercial launch in Mainland China took place in May of 2022. And 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.

Speaker 10

Great. That's helpful. Thank you. And then just based on the MDS data that you put out this week, what are the potential next to the next steps for that program and are any of those next steps currently included in your cash guidance?

Speaker 2

Hey, Colleen, I'll take that one. And thanks for the question. So yes, encouraged by to the data that we reported from the interim analysis. Just to provide background again and to highlight, this is a very hard to treat patient to the next question. We enrolled these higher risk relapsedrefractory MDS patients.

Speaker 2

Overall survival It's very poor unfortunately at 4 to 6 months. So again encouraged by those 8.7 median overall survival that we observed from the interim. Also encouraged by the ORR. We're going to take a look at these data, interrogate them further and define the next to the next half of the second year. I'll turn the financial question over to Mike.

Speaker 5

Hey, Colleen. We do have some LT and Extra costs in our cash guidance. Ultimately, depending what happens with The MDS program is where those costs will be, but for now we have some problemized placeholders for sure.

Speaker 10

Understood. Thank you. And last question, just on myelofibrosis and the competitive landscape there, I know we're going to get some Phase to the 3 data by the end of this year, from the MANIFEST 2 study. How do you expect that data would impact your development and regulatory plans in myelofibrosis?

Speaker 2

Yes, great question. So at a high level, I don't think it really impacts to what we do with our Phase 3, again, very encouraged by the Phase 1 data. Right now, our entire focus is really initiating the Phase 3, which we anticipate is going to start this quarter and being able to enroll the trial enrolled the trial. With that said, I think looking at the data, I think regardless of what the MANIFEST to look like potentially even transform. We have an opportunity to be best in class and to really transform the first to the first half of twenty nineteen.

Speaker 2

We are pleased to announce that we have a very important also the very important improvement in cytopenias given the underlying disease modification, that our current data suggest, but also importantly, the fact that we potentially may have monotherapy activity with selinexor and those data are really based upon that suboptimal rux data in which efficacy is preserved for both SVR and TSS-fifty, even when the ruxolitinib doses are reduced all the way down to 5 milligrams. That affords physicians a lot of flexibility to potentially discontinue rox due to, let's say, toxicity, and continue a patient on with to selinexor. So again, I think there's a lot of differentiating factors with selinexor plus ruxolitinib that can potentially enable it to be a best in class really regardless of what happens with some of the other competitors.

Speaker 10

Great. Thanks for taking our questions.

Speaker 3

Thanks, Joi.

Operator

Our next question comes from the line of Chris Raymond from Piper Jaffray. Please go ahead.

Speaker 10

Good morning. This is Nicole Gebrecht here on for Chris. 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 headwinds for Exovio might be recognized? Or I guess, how should we be thinking about that?

Speaker 10

And then just quickly for myelofibrosis, just As we look at the other myelofibrosis programs 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 3 study?

Speaker 3

Thanks, Nicole. I'll comment on the first and then turn it over to Reshma. But when you look at the evolution over quarters, I think you can expect your kind of consistent differences that you see quarter over quarter in line with our historical patterns. And then as we talk to 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 are requiring assistance through our programs.

Speaker 3

And as we've said, in our guidance range, with less patients having to to our patient assistance program that will move us towards the 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 Reshma, do you want to expand on the second part of the question?

Speaker 2

Yes, absolutely. And thank you for the question, Nicole. So we're really focused on 2 main endpoints, the FCR35 and TSS50. Ultimately for the patients, it's really critical that we show Significant improvement in both of those endpoints. Of course, the SVR is a potential surrogate for overall survival.

Speaker 2

That Reduction is key in showing a significant improvement potentially portends overall long term improvement for the patient. Of course, that symptoms, it affects directly how they feel. So again, we're focused on both of those endpoints. To the data to date in the Phase 1 really suggest that we can maximize benefit for both of these endpoints compared to ruxolitinib and it's going to be our focus in our Phase 3 trial as well.

Speaker 10

Great. Thanks.

Speaker 7

Thanks, Nicole.

Operator

Thank you. Our next question comes from the line of Eric Joseph from JPMorgan. Please go ahead.

Speaker 11

Hi, good morning. Thanks for taking the questions. Just following up on The commercial outlook with XPOVIO 2024, I guess that you anticipate less half utilization, but outside of that, can you just to comment on expectations on net pricing. We typically have seen some price hike. I've seen just kind of comments on whether those might actually flow through ultimately on to net price.

Speaker 11

And then for Altanexor, I know that you're it sounds like you're just you're currently evaluating sort of the delta path forward there. Is combination therapy part of the Reshma, can you just talk about the potential combination path with ELZONEXR? Thanks.

Speaker 3

Yes. Maybe I'll turn to Soania for the first part of that and then Reshma on the second part.

Speaker 2

Yes. Thanks. 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 to your patient utilizing carry forward, copay assistance in that segment that we discussed earlier.

Speaker 2

Again, we don't comment on future pricing strategy for 2024. But As far as growth in 2024, again, growth potential for 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.

Speaker 2

So Yes. As you noted, like we're not talking about the next steps in the development at this time. With that said, The fact that Ultanoxor is showing monotherapy activity in this hard to treat patient population just gives us a lot of to the next steps in our development, whether it's continuing to evaluate as a monotherapy, looking at different patient populations or to your point potentially even looking at combination. So again, lots of opportunities, but again, it's built upon the foundation that elkinesorg does have monotherapy activity. And in addition to myelofibrosis is now showing in this different tumor type that to

Speaker 7

Thanks, Eric.

Operator

Thank you. Our next question comes from the line of Jonathan Chang from SVB Leerink. Please go ahead.

Speaker 7

Hey, guys. This is Matt Kalper on for Jonathan. Thanks for taking my questions. 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?

Speaker 7

And then I have a follow-up. Thanks.

Speaker 3

Sure, Matt. I'll turn to Reshma for that.

Speaker 2

Yes. Thanks, Matt, for the question. So we've had productive discussions with the FDA, and have incorporated their feedback into our design. We don't to talk about any specifics of those FDA interactions. And as I mentioned earlier on the call, really our focus at this is initiating this trial likely this quarter.

Speaker 2

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 as part of our Phase 1 for both SBR and TSF50, we're also looking at the historical data that we know that ruxolitinib has provided, again for both of those endpoints. So really have utilized those data to ultimately design the most efficient trial that can enable this treatment to patients who have myelofibrosis.

Speaker 7

Great. That's very helpful. And then just following up on the elk Nexor data that you just released. We noticed there was a high degree of censoring in some of the you're able to provide any detail on the patient experience for patients that were post both venetoclax and azacitidine. Thanks.

Speaker 2

Yes. 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.

Speaker 2

In terms of the post venetoclax azacitidine, So great point and this is a key differentiation from our Phase 1 study and that we had a subgroup of patients who did receive prior venetoclax, which is a BCL-two, a smaller subgroup of patients who received a combination of venetoclax plus

Speaker 4

to HMA inhibitors. Why is

Speaker 2

this such an important point? Largely because there are some preliminary data coming out of MD Anderson that suggests Patients who have received prior BCL-two may have poor prognosis compared to the already very poor prognosis in relapsedrefractory MDS. So this is something that we're looking at more closely, but again Gives us opportunity to further develop eltenexor, especially as venetoclax and azacitidine is expected to move as a new potential first line therapy, leaving a gap right to further develop to new therapies in this relapsed refractory space.

Speaker 7

Great. That's it for me. Thanks for taking my questions. Thanks, Matt.

Operator

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.

Speaker 3

Thank you, operator, and thank you again to everyone for joining today's call. We're wishing everyone a great day.

Operator

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

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Earnings Conference Call
Karyopharm Therapeutics Q1 2023
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