Q2 2023 Karyopharm Therapeutics Inc Earnings Call
Good morning, My name is Jason and I will be your conference operator today at this time I would like to welcome everyone to the carry of farm Therapeutics second 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 I would now like to turn the call over to Alan Weber Senior Vice President of Investor Relations.
Thank you operator, and thank you all for joining us on today's conference call to discuss carrier from second quarter 2023 financial results and recent company progress.
We issued a press release this morning detailing our financial results for the second quarter 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 two I'm joined by Richard raised your muscle Honey I'm, Mike who will provide an update on our results for the second quarter and recent clinical development.
Before we begin our formal comments I'll remind you that various remarks, we'll make today constitute forward looking statements for the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995 as outlined on slide three.
Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent Form 10-Q, which is on par with the S. E T and in other filings that we may make with the FCC and the.
Feature and yes, L as representing our views as of today only while we may elect to update these F. L. S. At some point in the future.
We disclaim any obligations to do so even if our views change. Therefore, you should not rely on these F. L S as representing our views as of any later date I will now turn the call over to Richard Please turn to slide four.
Thank you al and good morning, everyone and thank you for joining <unk> second quarter 2023 earnings call.
Turning to slide five we had a strong second quarter as we accelerate Carryall farm to its next stage of growth with our novel sine compounds Shovlin, XR and <unk> XR as.
<unk> will discuss further we are advancing a focused clinical pipeline with three ongoing phase III pivotal studies based upon our strong foundation of support of data. Our recently obtained fast track designation in myelofibrosis.
Set of pivotal catalysts over the next two years.
With our current approved multiple myeloma indication in the U S with Selinexor.
<unk> continued to expand and shift into earlier lines.
And so Hong you will discuss further.
Year over year total demand for <unk> continues to grow in a competitive multiple myeloma marketplace.
Selinexor is also expanding its global footprint with approvals in various indications and approximately 40 countries outside of the U S.
Providing us with a growing stream of payments from our royalties and milestones from our partners as the launches move forward globally.
As part of our continued prioritization of our late stage clinical pipeline.
We have taken additional actions to streamline our operations and optimize our cost structure.
As a result, we have reduced our workforce by approximately 20%, which.
Which is expected to enhance our financial strength provide us with the capital needed to deliver on our three phase III studies and maximize value for our shareholders.
Yes.
This was an extremely difficult decision given the direct impact this has on our employees.
However, after careful consideration this action was imperative.
Order to further focus the organization on the near term opportunities ahead of us.
I am sincerely grateful for the tireless work and commitment of our colleagues who are being impacted and to the colleagues that will enable carryover arm success moving forward.
As we move to slide six presented here is an overview of the timing of the upcoming key data Readouts, which we expect in 2024 and 2025.
Each of our ongoing phase III clinical trials if successful.
It represents an incredibly meaningful growth opportunity for our organization.
With the potential to deliver roughly $2 billion in annual peak revenues.
Starting with multiple myeloma and <unk>.
Access full phase III travel trial with SPD.
Anticipated in the second half of next year.
It accelerates selinexor into the second line treatment and enable continued growth in multiple myeloma.
In endometrial cancer, we believe <unk> has the potential to transform the treatment paradigm.
For key P 53, wild type endometrial cancer patients.
Given the unprecedented data, which was presented at the virtual <unk> series last week.
<unk> will speak to momentarily.
Finally in Myelofibrosis, we recently announced the initiation of our pivotal phase III.
With the potential to transform to frontline treatment for patients with myelofibrosis as.
As we build upon the rapid deep and sustained responses, we have seen thus far.
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.
Leveraging our proven and established commercialization and late stage development capabilities.
Shifting to Selinexor is position internationally on slide seven.
Our continued global expansion with our partners provides further opportunities to treat patients in need with Selinexor as our partners continue to commercialize and launch in additional global territories.
Our license agreements with our partners provide us with a steady stream of revenues through growing double digit future royalties and potential development and sales milestone payments of up to $400 million.
Moving to slide eight I would now like to turn the call over to arrangement to expand further on our clinical pipeline progress.
Thank you Richard I wanted to start off by highlighting our rapidly advancing pipeline on slide nine which includes three pivotal phase III trials with Selinexor that are enrolling in multiple indications of high unmet need. In addition, we are evaluating our second sine compounds. Okay next door in Myelodysplastic.
Neoplasms.
As seen on slide 11, we are expanding our multiple myeloma franchise with an important ongoing phase III trial that is evaluating selinexor at the low dose of 40 milligrams in combination with the well established backbone therapy of Palmer <unk> and dexamethasone.
Patients with relapsed refractory multiple myeloma, who have received an anti CD 38 antibody is their most recent therapy are randomized one to one to the oral regimen of Selinexor, <unk> dexamethasone or <unk> <unk> and dexamethasone.
Primary endpoint is progression free survival the potential approval of this combination could lead to the only all oral potentially T cell sparing regimen for patients with relapsed refractory multiple myeloma.
On slide 13, advanced and recurrent endometrial cancer is the most common form of gynecologic cancer in the United States with the current treatment landscape, primarily consisting of first line chemotherapy with the platinum and Taxane.
Upon completion of chemotherapy patients are observed until disease progression. This approach clearly needs improvement given that the five year survival rate in this patient population is only 17%.
Selinexor is administered orally and maintenance therapy is well established in other cancer types. We believe selinexor has the potential to offer a maintenance option in T. P 53, wild type patients and meaningfully improve the overall clinical benefit for these patients.
As seen on slide 14, endometrial cancer treatment will ultimately be based upon patient individual molecular classification, including assessment of their microsatellite instability and P 53 status.
Of the approximately 16000 patients diagnosed with advanced or recurrent endometrial cancer in the United States, roughly 50% of advanced or recurrent tumors are classified as T. P 53 wild type.
Within the subgroup, 70% of patients are microsatellite stable or MSS and 30% are microsatellite in stable or MSI high the long term follow up data observed from the Prespecified exploratory T. P 53, wild type subgroup analysis from the <unk> trial, which evaluated.
Selinexor as a maintenance therapy reinforces our rationale and ongoing confidence in the current phase three U C 042 trial.
Long term follow up data from the <unk> trial recently presented at the virtual Astro Plenary series on July 25th is seen on slide 15, with a median follow up of 25 months for the T. P 53, wild type exploratory subgroup. The median PFS for the Selinexor arm is now 27.
Four months compared to 5.2 months in those patients receiving placebo.
The hazard ratio for this subgroup is 0.42, representing a 58% decrease in the risk of disease progression or death.
Patients, whose tumors are either T. P 53, mutant or aberrant and treated with Selinexor demonstrated the median PFS of only four two months.
These data show that the potential clinical benefit achieved with Selinexor is isolated to women, whose tumors are T. P 53, wild type and demonstrate that T. P 53, wild type <unk> has the potential to be a robust biomarker.
As we turn to slide 16 patients with T. P 53, wild type endometrial cancer, where further classified by microsatellite instability status given the growing importance of this diagnostic marker in endometrial cancer.
While potential PFS improvements were seen regardless of microsatellite instability status. Most notable is the signal of a 68% decrease in the risk of disease progression or death corresponding to a hazard ratio of 0.32, and a median PFS that has not been reached in those patients whose disease.
It's P 53, wild type and MSS.
These data are important given the evolving data observed in the checkpoint inhibitors, which continue to show that the greatest clinical benefit is observed in the minority of patients whose disease is MSI high.
As seen on slide 17, we believe that the AE profile of Selinexor is generally manageable as a maintenance therapy the.
The most common treatment emergent adverse events seen in the T. P 53, wild type exploratory subgroup, where nausea, vomiting, and diarrhea, and overall grade three or four treatment emergent adverse events were rare with the most common being neutropenia nausea thrombocytopenia.
No grade five treatment emergent adverse events were observed.
<unk> emergent adverse event incidents and severity were generally similar in the subgroup of patients whose tumors were either T. P 53 mutant or aberrant.
Turning to slide 18, given the data we observed in the exploratory subgroup of T. P 53, wild type endometrial cancer, we see an opportunity to transform the treatment paradigm for endometrial cancer, given the cycle of approximately fivefold increase in the time to disease progression or death.
Compared to placebo.
And the P 53, Wild type MSS is especially notable in light of first line endometrial cancer trials evaluating the efficacy of checkpoint inhibitors.
Well some of those trials evaluated the efficacy of checkpoint inhibitors in both the treatment and maintenance settings.
Administrative the overwhelming benefit is largely observed in those patients whose disease is MSI high.
Given that 70% of patients whose disease is MSS did not achieve the same degree of benefit with these immunotherapies and in light of the recent approval of <unk> in combination with chemotherapy in first line endometrial cancer, whose diseases MSI high we anticipate that the majority of Selinexor will be administered.
To patients classified as P 53, Wild type Atmos has pending the successful approval of Selinexor.
This highlights the importance of molecular testing early in the womens endometrial cancer diagnosis as novel therapies transformed treatment opportunities for these women.
On slide 19, our details and are actively enrolling E. C 042 pivotal phase III study evaluating selinexor as a monotherapy for patients with T. P 53, wild type advanced or recurrent endometrial cancer.
This study utilization utilizes foundation medicine's tissue based next generation sequencing test to identify patients and enroll approximately 220 women, whose tumors are T. P 53 wild type.
Patients are randomized in a one to one manner to perceive either once weekly selinexor at a dose of 60 milligrams or placebo.
Ultimately this trial will enable the development of a companion diagnostic and we anticipate the approval of the companion diagnostic would occur at the same time as selling next door if approved.
Study's primary endpoint is progression free survival with the key secondary endpoint of overall survival.
Study is a collaboration between carrier farm in and got the European network for Gynecological Oncological trial groups N G O G. The gynecology oncology group.
Given that this is an event driven trial. We currently anticipate topline data readout in late 'twenty four to early 2025.
Turning our attention now to myelofibrosis on slide 21, we are excited to announce that the FDA has recently granted fast track designation to selinexor for the treatment of patients with myelofibrosis.
This designation emphasizes the hyatt that need for new therapies and novel mechanisms of action given that the efficacy with the current standard of care is limited with less than 50% of patients achieving SVR 35, and TFS 50.
Furthermore, in subgroups, such as men and those who start on a low dose of <unk> efficacy is even lower with only approximately 25% of patients achieving an SPR 30 fives at week 24.
On Slide 22, you can see the phase one trial design of our frontline Myelofibrosis study evaluating the combination of Selinexor and <unk> in patients with treatment naive myelofibrosis with.
We presented updated phase one data at the Astro into your heart conferences in June 'twenty, 'twenty, three which can be seen on slide 23.
In the table you can see that the SVR 35 T. S has 50 results 60 milligram selinexor and the.
The ITT population the SPR thirty-five rate at week 24 achieved with the Lotus of Selinexor was 79%.
Furthermore, these reductions occurred rapidly with the 71% SVR thirty-five rate observed at week 12.
At week 24 T. S. With 50 was observed and 58% of patients here as well you see rapid improvement in symptoms with approximately 67%.
Patients achieving a T. S has 50 as early as week 12.
Rapid deep and sustained efficacy observed with Selinexor in combination with rux bulletin at substantially improved the potential benefit that JAK naive myelofibrosis patients may of cheese.
These data underscore our conviction on our ongoing phase III study as seen on slide 24 that was initiated in June .
Chile will enroll 306, symptomatic intermediate and high risk of JAK naive myelofibrosis patients patients will be randomized two to one to Russell at nib called Selinexor or <unk> plus placebo, we anticipate topline results in 2025.
Given the important subgroup data in patients who received suboptimal doses of rux or letting it as presented at Astro and eat ha. We are planning to initiate a phase two trial evaluating selinexor as a monotherapy in JAK naive patients with a baseline platelet count between 50 to 100000 this.
This is a uniquely high unmet need patient population with limited treatment options available.
This trial will allow investigators to add on rock solid nib or Procrit note that either week 12, or week 24, and the event suboptimal responses to Selinexor are observed this trial, coupled with the ongoing phase three has the potential to transform treatment of myelofibrosis patients and embed selinexor as a backbone therapy.
<unk> for treatment naive myelofibrosis.
With that please turn to slide 25, and I will now hand, it over to so honea for a review of our commercial performance for the quarter.
Thank you Rachel and good morning, everyone.
On slide 26, I am pleased to present the progress we have made in our second quarter performance were exposed Youll continue to show growth year over year in total demand of 9% in a competitive marketplace in.
In line with our strategy to expand use of exposure in the community setting total demand grew by 11% year over year in this setting contributing to about two thirds of exposure those revenues in the second quarter.
We also achieved total demand growth of 6% year over year in the academic setting driven by use of exposure, both pre and post T cell therapies.
Net revenue continued to be adversely impacted by higher utilization of carryforward, our patient assistance program or Pap, which provides free medicine to qualified patients unable to get financial support elsewhere.
This was a result of continued closures beginning late Q1 of many of the third party multiple myeloma foundations that provide financial support to Medicare patients.
In the second quarter, one of the four main multiple myeloma Foundation's was open for a period of time and continues to remain open.
This allowed for a reduction of new patients entering our patient assistance program. Although we continue to see the cumulative refill impact of patients who are already in path earlier in the year.
I have contributed to 14% of total demand in Q2, 2023, which amounted to a roughly $3 million revenue impact.
In comparison pop contribution to total demand was 9% in Q1, 2023 and 5% in Q2 2022.
Moving forward in 2024, I or a related changes in the design of Medicare part D will eliminate the patient burden of the 5% beneficiary co insurance requirement and we expect significantly less need for Medicare part D patients to utilize carryforward for copay assistance.
Additionally, net revenue was impacted by 5% higher year over year gross to net in the second quarter, driven by increased Medicare and Medicaid rebates as well as 340 be discounts.
Despite headwinds in the marketplace. We are pleased to see the progress we have made not only in growing total demand for it.
But also in shifting into earlier lines.
In Q2, 2023 exposure new patient share surpassed 60% in the second to fourth line compared to 49% in Q2 of last year.
I intend to prescribe data showed an improvement in third line use which continues to support the potential for patients to have a more optimal experience in earlier lines and extend time on therapy.
We reaffirm our U S exposure net revenue guidance of 110 to 125 million in 2023.
Let's now turn to slide 27.
Amidst an evolving landscape, we believe were strongly positioned to treat multiple myeloma as a novel class of therapy in the second to fourth line in three distinct patient populations in.
In the community setting where earlier line patients tend to be treated we believe exposure is an optimal therapy in the second to fourth line post anti CD 38 treatments as a novel class of therapy that is an effective manageable easily combinable and it convenient oral therapy.
It also has the advantage of decreasing the logistical burden of accessing a hospital for elderly or rural based patients.
In the academic setting exposure may be used as an optimal therapy with a novel mechanism of action pre or post T cell therapies.
As we turn to slide 28, we're encouraged by the future growth potential of our myeloma franchise in our S. P. D study the triplet combination of Selinexor at the lower dose of 40 milligrams with palm a littermate and dexamethasone could lead to the only all oral regimen.
Following and anti CD 38 therapy in the marketplace if approved.
Partner backbone of Pamela termite is a commonly used therapy in the second to fourth line generating over $2 billion in revenues in the U S. Given these characteristics that make up the S. P. D. Combination we are encouraged by the potential of unlocking significant value to patients with multiple.
Myeloma if approved.
Shifting to the opportunity in endometrial cancer on slide 29, we are encouraged by the potential for Selinexor to address a significant unmet need in key molecular subgroups.
As we engage with key opinion leaders in this space. It is clear that they see the augment need for targeted treatment in unique molecular subgroups, including T. P 53 wild type tumors.
Whilst frontline treatment options are emerging rapidly a clear unmet need remains in the P 53, wild type and specifically M. S. S subgroup.
As we look at the potential opportunity in this large market endometrial cancer is the most commonly common gynecological cancer in the U S with over 8000 patients in the U S and over 50000 globally that have P 53, wild type advanced or recurrent endometrial.
Cancer.
Which about 70% are P 53, wild type M. S S patients.
We are very encouraged by Selinexor as opportunity to help women, who need a more effective targeted and safe treatment option.
Given that Selinexor is being evaluated as a maintenance therapy convenience is a critical factor.
An oral therapy, we maximize treatment duration by eliminating the need for frequent clinic visits.
Turning now to slide 30, as you heard from race MA X P. O. One inhibition has the opportunity to transform the frontline treatment paradigm in myelofibrosis.
There are no other drug classes other than JAK inhibitors approved in the frontline.
As we look at the potential opportunity in the myelofibrosis market. There are over 4000 patients in the U S and over 26000 patients globally that are intermediate to high risk myelofibrosis.
We are very encouraged by Sally next source opportunity to transform myelofibrosis treatment paradigm.
Based on third party market research about 75% of health care providers, who are willing to adopt combination therapies as front line standard of care, replacing rock solidity mono therapy due to the potential of better efficacy.
Additionally, there is a strong perception around selinexor in combination with rux, alleging it with approximately 50% of health care providers, indicating that they would select selinexor plus rux alleging it as their preferred frontline combination therapy, if approved based on promise.
Thing initial SVR 35, and T. S. S 50 efficacy rates and a manageable safety profile.
As Richard discussed in his opening remarks Perry of farm has a tremendous opportunity for growth by leveraging our strong commercial team and continuing to build on our base multiple myeloma business with the potential launches ahead of us.
Please advance now to slide 31, and I'll turn the call over to Mike.
Thank you Sonya.
It was $28.5 million compared to $29 million for the second quarter of 2022.
At Zhonya discussed net product revenue continued to be adversely affected by more patients using our patient assisted program as well as higher growth to net discounts.
Growth to net discounts for 22% in the second quarter of 2023 as compared to 70% in the second quarter of 2022.
Turning to cost with our continued focused on cost management. We are pleased to be delivering a combined 12% year over year reduction in our R&D and SG&A expenses in the first half of 2023.
As we recognize the cost benefits from our previous efforts to focus our pipeline are R&D expenses for the second quarter of 2023 $31.5 million down.
Down, 28% compared to $44.3 million for the second quarter of 2022 <unk>.
Likewise, we have reduced SG&A expenses in the second quarter of 2023 by 7% at $34.5 million compared to $37.3 million for the second quarter of 2022.
Cash cash equivalents restricted cash and investments as of June 30th of 2023, total $237.7 million compared to $279 $7 million as of December 31, 2022.
Based on our current operating plans, we are reaffirming revenue guidance for the full year of 2023 as follows total revenue in the range of $145 million to $160 million <unk>.
<unk> net U S product revenue of $110 million to $125 million.
With our cost reduction initiatives, we are lowering our expense guidance for 2023, we know anticipate non-GAAP R&D and SG&A expenses, which excludes stock based compensation expense to be in the range of $240 million to $255 million for the full year 2023.
Down from our initial guidance of $260 million to $280 million in February .
And finally coming to our cash guidance, we have entered into an amendment to our revenue interest financing agreement with affiliates of healthcare royalty partners extending our aggregate payment amount date by six months from December 31, 2024 to June 30th of 2025, and increasing the payment cap amount from 1.8521.
Max.
Taken together are existing cash cash equivalents in investments as well as the revenue we expect to January from exposure product sales and other license revenues will be sufficient to fund our planned operations through the end of 2025, excluding the maturity of our convertible bonds in October of 2025.
I will now turn to slide 34.
Richard for some final thoughts Richard.
Thank you, Mike turning decided 35 <unk>.
We have discussed today, we are rapidly advancing our pipeline.
Concentrating our investments in three phase III programs that are expected to read out through 2024, and 2025 as we work to create near and long term value for all our stakeholders.
I would like to thank our teams who continued to execute in a disciplined manner and who strive each day for patients with high unmet needs.
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.
Thank you we will now begin the question and answer session.
That's a good question you May press start than one on your Touchtone phone, if you're using a speaker phone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then too at this time, we'll pause momentarily to assembler roster.
Okay.
Our first question comes from Peter Lawson from Barclays. Please go ahead.
Good morning, and it's a shame for Peter Thanks for taking my question. So first just wanted to take it and maybe a little more color around three drug.
I believe this is Austin impact.
Any kind of you can provide around how this as compared to one Q and how you see this dynamic playing out for the remainder of 2023. Thank you.
Thanks, J, maybe for that I will turn to sew on you to kind of lay out how the patient assistance program and free drug has evolved from from Q1 to do too.
So anya.
Hey, Thanks for the question. So in terms of the foundations in two to one of the four main multiple myeloma Foundation's was open for a period of time in queue too, which helped to allow for a reduction in patient new starts entering Pat but we saw continued.
Phil impact in Pat Pat contribution in Q2 to total demand was 14% compared with in Q1 was nine per cent. If you compare it with Q2 of last year I hadn't historic normalcy. It was five per cent. So the total.
Net revenue impact from path loss alone due to foundation closures in Q2 was roughly 3 million.
As we think about Q3 and two four currently the one foundation that was partly open and Q2 continues to remain open to date now we have no line of sight all controlled into how these contact disseminated, but I'd guidance range does incorporate several factors like G.
T N impact, but also largely this uncertainty around the pack impact due to foundation closure.
Great. Thank you and maybe just a final quick question is around some of the cost refinements.
Workforce reduction this corner is there anything we the team has been thinking about in terms of whether they may be program assignments kind of later in the year.
Cost cutting us that we should be thinking about.
Yeah that actually I think as as we have highlighted you know we continue on an ongoing basis to make sure we're gonna optimizing and focusing our our cost structure. So we've continued to do that with the approximately 20 per cent reduction or a workforce this quarter.
To really ensure we're focused on being able to deliver our three phase three programs with our investments obviously in multiple myeloma.
And to make sure a cancer on my own fibrosis and on an ongoing basis. Obviously, we can change you evaluate our cost to insure were really being diligent in our in our allocating our capital.
Okay. Thank you.
Our next question comes from Mare Raycroft from Jeffries. Please go ahead.
Hi, This is Kevin on for Maureen. Thanks for taking my questions just for endometrial could you say, whether the the shift in timeline there for the readout was.
Was that due to competition with PD ones and then also could you talk about the powering for this study and whether you will look at the M. S. S and M S I high patients as pre specified subgroups.
Within that B 52, I'll type patient population. Thanks.
Yeah, Thanks, Kevin I'll, I'll turn to duration to kind of put all that together and talk about the the focus on the progress in endometrial cancer as we advance R. E C 042 trial.
Hi, Kevin Uhm. This is <unk>. So thanks for the question you know in terms of the timelines.
Slight modification from you know end of late 2024, beginning of 2025 of course. This is an event driven trial. So when we see the events actually occur you know that will trigger our ability to perform the analysis for progression free survival.
With that said we're closely looking how at how the data is positively evolving. This most recent recent update that Brian <unk> presented at the <unk>. We now see the median P. F S and those T. P 53, wild type patience evolved from the 13.7 months that we initially disclose.
Back in the beginning of last year to now 27.4 months or more than a doubling in that medium P. S. US that is gonna have a slight impact on how fast is events accrue taking that into account debrief projected and anticipate again those P. S. That's events to occur either late 20th.
24, or beginning of 2025 would probably looking at approximately you know a couple of months spread in terms of.
Looking at the at the Pizza Fifty-three Wild type M. S. S. So great question. Obviously, the data are very encouraging in that subgroup, which does comprise the vast majority of all patience the way that the E. C O four to try out the phase three is designed specifically focused on that P 53 wall.
Type <unk>, regardless of whether M. S. S. M S I and largely because this is a novel subgroup and again, we believe that the data specifically observed in that P. 53, while type subgroup truly is unprecedented of course, we will be looking at the subgroup patient tour P 53, one type of.
M S. As in separately P 53, wild type MSI, but right now our focus truly is on that large P 53 wild type subgroup.
Or patient population I should say.
Great. Thanks for sure that makes a lotta sense and then just to follow up on Myelofibrosis. You know we saw that one of your competitors recently top line data base free data showing the hits that big on spleen size, but not symptom score. There's also another update expected. This fall could you just talk.
About how you view the evolving treatment landscape here and then what gives you confidence that you'll be able to succeed on the on the symptom score co primary interface.
Yeah, Yeah, yeah. So I I saw that press release too I'm not privy to any additional data beyond what you saw as well you know what I found it very intriguing is actually how that Ruxolitinib arm performed it was actually an S. B R rate of approximately 30 per cent right, which is a little.
Surprising to me lower than what the data that was presented in the comfort trial, you know analyzed more than 10 years ago. It really suggests to me that the benefit that ruxolitinib is having on that important spleen volume reduction probably lower than what we expected when I look.
<unk> our data from the phase one trials, specifically assessing selinexor at 60 milligrams in combination with Ruxolitinib My confidence goes up given the fact that we saw 78 per cent, so that 78% compared to that 30 ish per cent weirdly suggests that we can have a very meaningful benefit on screen volume <unk>.
Option in our ongoing phase three study.
In terms of the T. S. That's 50, so to a certain degree I'm not that surprised so you know my understanding from the earlier transform phase two trials is that their T. S. As 50 was marginal at best now why is it marginal hard to say right. We know that a lot of aspects can contribute to T. S.
That's 50 scores, including toxicity as well as.
Patients not completing out there for them. So <unk> in that data obviously add these can continue to analyze.
Their data and hopefully <unk> you know report on more mature data later this year, maybe even beginning of next year I go back to our data in which we had an opportunity to look at the T. S. That's 50 data obtained from the patient enrolled as part of that phase one and again very encouraged by the 50.
Eight per cent T. S. S data that we saw again compared to rocks alone, which T. S. That's fifties or in the low forties. It really does suggest that the combination selinexor plus ruxolitinib can meaningfully improve both S. B R. E N T S. As 50, both important and points that we need to <unk>.
It is part of our phase three trial.
Great. Thank you very much freshmen.
Our next question comes from calling Kelsey from <unk>. Please go ahead.
Great. Thanks, Good morning, and thanks for taking our questions. So in the sea and a presentation from the <unk> <unk> <unk> <unk> continued to see an increase in PFS first placebo can you share with the average time on therapy has been just trying to think about that in context of the market opportunity for a duration and endometrial cancer.
Yeah I appreciate the question, calling uhm. So we have it reported on that median duration of treatment yet and it's only because those data are still maturing we actually still have patience on treatment and as the data continue to mature will have an opportunity to present that median duration of treatment likely add an upcoming presentation and the Netflix.
12 months Uhm now, we we do know that median duration of treatment and P. S. S. <unk> track one to one uhm. However, we are seeing an interesting trend as medium P. S. That's what gets longer. We're also seeing that median duration of treatment also get longer. So I think that is a very meaningful evolution.
From the progression free survival, but time on therapy as well.
That's helpful. Thank you and then congrats on getting the the phase three mile of hypnosis study up and running in the fat check status. There I know, it's early but how challenging is it to find naive myelofibrosis patience and how many centers do you think you'd target for this study.
Yeah. So yeah, yeah, very important milestone to get that pays three initiated you know we've got a lot of momentum behind this trial, writing a think again you know many of our investigators I'm very encouraged by the aggregate data that we've been able to <unk>.
Designs from that phase one trial evaluating sell the next door in combination with Ruxolitinib began not only the spleen volume reduction in T. S. It's 50, but those key aspects that really suggests that the combination is having a positive disease modification.
And its potential monotherapy. So it's this holistic profile that really suggests that this combination can be a game changer for patients who are treatment naive myelofibrosis in terms of competition will there is not right. So there's no. Other you know large phase three trials.
You know by and large this is gonna be a global trial. We are you know activating sites in the U S. Europe as well as Asia. We're looking at approximately 150 sites and again, there's really no competition for those treatment naive myelofibrosis patients that are diagnosed uhm throughout the globe. So you know we're we're encouraged.
By the enthusiasm the lack of competitive headwinds and just really strong support from all of our investigators.
That's great. Thanks, <unk> and last one from us on the mono therapy mild fibrosis study you talked about in the call can you say about the rationale and why you picked that patient population to look at.
Yeah. So this is a really innovative trial design for us and it's largely based upon this really intriguing finding we're fine we've seen from the phase one study specifically in that same group of patients who are treated with suboptimal Joseph Ruxolitinib, we're finding that patients are still achieving that in.
<unk> S. P. R 35, and T. S. S. 50, again, you don't see that with Ruxolitinib alone really suggest a X P. O. One is a fundamental mechanism and so the next door potentially has monotherapy activity. So this trial allows us to better investigate that hypothesis.
How this trial is going to be conducted is that patients who are treatment naive myelofibrosis, specifically, who are have baseline completely counts of 50 to 100000 I was going to be treated with selinexor monotherapy at either the 60 milligram or 40 milligram doses and then in the event date.
They they achieve a suboptimal response to sell a next door they have an opportunity to add on either <unk> or ruxolitinib why are we looking at this patient population because we know that patients whose baseline platelet counts are between 50 and 100 really has very limited treatment options buying.
Large the only therapies available to them are gonna be <unk> and ruxolitinib. Despite these therapies. There S. P. R and T. S. That's 50 with the snare of fees are still quite marginal so it's an opportunity to assess sell the next door monotherapy and potential these novel combination too.
Great. Thanks for taking our questions.
Alright, and the interest of time, please limit yourself to one question.
And our next question comes from Chris Raymond from Piper Sandler. Please go ahead.
Hi, Good morning. This is Nicole <unk>. Thanks for taking my question, maybe just try an overall survival in an endometrial. So I know that was a secondary endpoint in the sand a trial and kind of came up as a topic of discussion during the <unk> plenary session. So I guess I was just wondering if we should expect.
You to disclose any Oh S data from the trial in the future and then just quickly for Elton XOR. I know you guys are focused on your link to each program, but just wondering how you were thinking about the password for I'll connect swearing M. B S. At this point and maybe just how we should think about the the prioritization of that program.
Yeah. Thanks uncle.
Yeah, not that thanks, Bye <unk> I think you know as a restaurant was indicating yeah over the next six to 12 months as we continue to see that.
The majority of the data and the endometrial cancer <unk> trial, and I will report out on the O S.
And maybe I'll turn to <unk> talk about Alpha next door, which obviously is a very important for us as we continue to move forward and looking at potential benefit we can bring patients reddish ma'am.
Yeah. Thanks. Thanks, Nicola So you know <unk> next door is one of our four core programs are specifically evaluating myelodysplastic syndrome.
Syndromes neoplasms, specifically relapse refractory M D S with Elton XOR very encouraged by the data that we reported from the phase two will have an opportunity in the next few months to really define that optimal development plan, specifically with Elton XOR in this high risk patient population.
Great. Thank you.
The next question comes from Brian Abrams from our B C capital market. Please go ahead.
Good morning. This is Joanne for Brian . Thank you for taking my question with the full of data would ask of just going back to the endometrial cancer and all data can change it seem very encouraging and I know you just mentioned that some patients continue to remain.
<unk> continued to show up yet that PFS benefits there too. So I'm just wondering if there's any expedited pathway for approval.
Mm mm and before this hotline <unk> 24, or early 25 or is this something that you have discussed with the F. D. A M.
So far thank you.
Yeah. Thanks, Joe So we don't comment on our interactions with the F. D. A you know with that said you C 042, uhm remains our opportunity to get both sell the next or the drug as well as the companion diagnostic in the form of the N. G. S platform in which we assess P 53 <unk>.
As our approval opportunity in the U S as well as X U S. Two E.
E C 042, as well design trial and that we are prospectively evaluating patients who are P. 53, wild type. It's a well powered study that was specifically allow us to assess that important progression free survival and overall survival compared to placebo. So we remain focused on that E. C 042.
<unk> trial that is Billy evolving quite nicely C Endo, though and the data that we've observed from Seattle very much as informing our <unk> informed our design of that trial. We remain encouraged those data only increase our confidence in the likely outcome from E. C 042.
Our next question comes from Eric Joseph from J P. Morgan. Please go ahead.
Hi, This is Noah on for Eric Thanks for taking our question.
Guards are easier for it.
If you owe for to study what median PFS in the placebo arm is anticipating the pet for that you're powering assumptions.
In your guidance for the read out and is it similar or more generous than that of the <unk>.
P 53, Wild type group and this yet Sanders study.
Yeah. So so great question. So we haven't disclosed on those kinds of details you know with that said we are assuming it medium P. S. S for stolen up for exceeding that 13.7 months right. So those with the data that we observed at the time of the initial data <unk> again in the beginning of 2022.
Two given the fact that medium P. S. S continues to increase quite nicely again, we're quite confident that that median P. F. S is gonna be in the excess of 13.7 months. It is you know all of our phase three trials are well powered well about that 80%. So again very confident that at the time.
<unk> there were able to read out the P. S. Fast anticipated end of 24, beginning of 25, we're going to see a very meaningful improvement in that P. S asked with the selinexor treated patients compared to placebo.
Got it thank you.
And the next question comes from Jonathan Chang from Leerink Partners. Please go ahead.
Hey, guys just knock helper on for Jonathan Thanks for taking my question you mentioned, there's some enthusiasm around the <unk> <unk> and the data are certainly impressive I was just wondering you know with the upcoming you'll combination readouts, an obsessional poodles, they're how does that impact the development and regulatory interactions for.
Your trial, given it's only against the rocks monotherapy. Thanks.
Yeah, we we don't really anticipate in any kind of impact with either the data Readouts my data read that or just the hotline results. Obviously the companies need to go through the extensive regulatory process. We anticipate you know our trials to be enrolled her almost close to <unk>.
Close to enrollment completed enrollment by the time that regulatory approval is obtained again, assuming that those data are positive for both S. V. R and T. S. That's 50. So we can work very confident not only in the data button the design of our phase three trial.
Got it. Thank you so much for taking my <unk>.
This concludes our question and answer session I would like to turn the conference back over to Richard Paulson for any closing remarks.
Alright, your operator, and thank you everyone for joining our call today, you know as I indicated at the beginning of the call. We had a very strong second quarter as we continue to accelerate carry all farm to its next stage of growth with our novel sign compounds, both Selinexor announced the next door and once again I'd like to thank our team to execute in a very disciplined manner.
It's driving each day for patients with Iron man needs and I grabbed one for joining a call today.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
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