Good afternoon. My name is Jason, and I'll be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics Third Quarter 2022 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 Instructions] I would now like to turn the call over to Elhan Webb, Senior Vice President of Investor Relations.

Thank you, operator, and thank you all for joining us on today's conference call to discuss the Karyopharm's third quarter 2022 financial results and recent company progress. Today, I'm joined by Richard Paulson, President and CEO; Sohanya Cheng, Chief Commercial Officer; Dr. Reshma Rangwala, Chief Medical Officer; and Mr. Mike Mason, Chief Financial Officer. Today, we issued a press release detailing Karyopharm's financial results for the third quarter 2022. This release, along with the slide presentation that we will reference during today’s call, are available on our website. For today's call, as seen on slide 2, Richard will start with some opening remarks. Sohanya will provide a commercial update. Then Reshma will provide an update on our clinical development programs. Mike will then present an overview of financial highlights from the quarter and Richard will end with some closing remarks, before opening the call up for questions. 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. 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 quarterly report on Form 10-Q, which is on file with the SEC and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements, as representing our views as of any date subsequent to today. In addition, we will also be providing on this call outlook for non-GAAP R&D and SG&A expenses for 2022. We are not providing reconciliations of these forward-looking non-GAAP measures because projections of stock compensation expense, which is required for such reconciliations are not available without unreasonable efforts. I will now turn the call over to Richard. Please turn to slide 4.

Thank you, Elhan, and good afternoon to everyone joining us on the call and webcast. Today, I'm excited to provide an update on our plan, as we continue to execute on our growth strategy through our focused pipeline, targeting life-threatening cancers. Turning to slide 5, Karyopharm was founded in 2008 as an innovation and patient-focused company, developing first-in-class oral Selective Inhibitor of Nuclear Export which target XPO1 that mediates multiple processes, integral to cancer cell growth. Fast forward to Karyopharm today, where we are successfully leveraging that fundamental mechanism of action to build upon our existing multi-myeloma franchise, anchored around our commercial drug XPOVIO. XPOVIO's footprint now reaches 40 countries and combined with increasing use in earlier lines of therapy in multi-myeloma, we are currently expecting total revenue of between $155 million to $165 million in 2022. We are working to expand indications through advancing our focused clinical pipeline. This pipeline is comprised of mid and late-stage clinical development programs that is being purposefully built and strategically focused to 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. Based on compelling data signals, we are pursuing opportunities in endometrial cancer, myelofibrosis and myelodysplastic syndromes. Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years. We've also evolved our leadership with a team of dedicated and highly accomplished executives from across the biopharmaceutical industry, specifically with commercialization and mid to late-stage clinical development experience, to lead us in delivering our targeted mid and late-stage clinical pipeline. With a strengthened leadership team in place, we believe we can achieve both scientific and commercial excellence, while executing on our key corporate objectives.…

Thank you, Richard, and good afternoon, everyone. I am pleased to talk about the growth story of XPOVIO, the first and only drug in the novel class of sign therapy and a key combination partner in the second to fourth line multiple myeloma setting in an evolving marketplace. Turning now to slide eight and our commercial highlights for the third quarter of 2022. Net product revenue grew by 20% versus the same period last year and we continue to make progress across key indicators. Our team executed with strength to access and educate our physician community, resulting in the growth of both new patient starts and prescription refills. We continue to make progress with our primary growth driver and what we believe is most important to patients, which is the continued shift of XPOVIO into earlier lines, with over half of our patients in the second to fourth line. In fact, during the first half of 2022, we were the fastest-growing brand in third-line multiple myeloma. As patients move into earlier lines and physicians gain experience and confidence using XPOVIO at the new once weekly lower dose, we see that patients are continuing to stay on therapy longer. As we have seen increasing competition in the late-line setting at academic centers with new approvals and ongoing trials, our focus remains on expanding the use of XPOVIO in the community setting, which contributed over 65% of our business in Q3. With our continued focus on growing both breadth and depth of prescribing accounts, in Q3 we reached the highest number of total prescribing accounts since the launch of XPOVIO. Two-thirds of these accounts were in the community setting. Our focus is to continue to expand breadth of use while leveraging this broad base of accounts in building upon their positive experience…

Thank you, Sohanya. Before I go into more detail on select programs, I would like to highlight how we have been working to optimize the dose of selinexor and how it relates to our ongoing clinical development programs on slide 10. As Sohanya mentioned due to the growing confidence among physicians in using the lower once-weekly dose of XPOVIO-based triplet regimens, both the patient and physician experience, as well as adherence is improving. Since XPOVIO is launched in 2019, we have utilized real-world experience coupled with observations from our clinical trials to demonstrate that lower doses of selinexor can optimize the patient benefit by improving its tolerability, which will ultimately allow patients to remain on therapy longer improving their overall benefit. As a result all of our ongoing clinical trials incorporate selinexor doses at 40 milligrams to 60 milligrams weekly, which is a quarter to less than half of the originally approved dose of 80 milligrams twice weekly. Such dose optimization will further enable our opportunity to accelerate new approvals in the next two to four years. On slide 11, I would like to highlight the advancements we have made in our development pipeline, which include initiation of the Phase 3 EC-042 trial in women with endometrial cancer and completion of enrollment in the Phase 1 portion of the MF-034 trial. In our eltanexor program, we have stopped enrollment on the Phase 1 combination trial in treatment-naive MDS, so that we can reevaluate the combination regimen. We have completed enrollment in the interim analysis in our relapsed refractory program and are awaiting for overall survival data to mature. Now as we turn to slide 12, I would like to discuss the unmet need in endometrial cancer and why we find this opportunity so exciting for women. Endometrial cancer is the…

Thank you, Reshma. Since we issued a press release today with the full financial results I will just focus on the highlights, which begin on slide 22. Total revenue for the third quarter of 2022 was $36.1 million compared to $37.7 million for the third quarter of 2021, which included a $9.8 million milestone from Antengene. With increasing approvals and commercial launches for selinexor globally, we expect milestone and royalty payments by our partners to deliver a larger contribution to our total revenues in 2023 and beyond. Net product revenue from US. commercial sales of XPOVIO for the third quarter of 2022 was $32 million compared to $26.7 million for the third quarter of 2021 representing a 20% increase year-over-year. The gross to net discount for XPOVIO in the third quarter was 18%. We continue to expect gross to net discount to be in the 15% to 20% range for the full year 2022. We recognized $4.1 million of license and other revenue in the third quarter of 2022, which includes $2.4 million earned in royalties from our partners and $1.4 million earned in reimbursement of development expenses. R&D expenses for the third quarter of 2022 were $31.4 million compared to $45.8 million for the third quarter of 2021. The decrease was primarily driven by the recognition of $7.4 million of costs in connection with the acquisition of certain assets from Neumedicines in the third quarter of 2021. Additionally, clinical trial and related costs decreased primarily due to the prioritization of our core programs in the clinical pipeline. We continue to expect our 2022 non-GAAP R&D expenses to decrease by approximately 10% compared to 2021. SG&A expenses for the third quarter of 2022 were $34.6 million compared to $35.1 million for the third quarter of 2021. Cash, cash equivalents restricted…

Thank you, Mike. And in closing, I would like to thank all of our teams at Karyopharm and our investigators, as we work every day to positively impact the lives of patients with cancer, helping us deliver on our commitments as you can see on slide 24. With that, I would now like to ask the operator to open the call up to the question-and-answer portion of today's call. Operator?

Thank you. [Operator Instructions] Our first question comes from Maury Raycroft from Jefferies. Please go ahead.

Hi. This is Kevin Strang on for Maury. Thanks for taking the questions and congrats on the update. Just a quick question on the myelofibrosis data. You showed 19 patients in the abstract and you mentioned that you had the 24 patients enrolled. Could you just say how many of those patients we might see at ASH? And how many of those patients would be on the 40 milligram dose? And based on what you're saying so far how the dose is influencing safety and efficacy? Thanks.

Yeah. Thanks, Kevin. I'll turn to Reshma to go through those questions.

Yeah. And thank you for the question. So you're correct. In the ASH abstract and this is from a July data cut, we included 19 patients who received at least one dose. The SVR data and the TSS50 data are from those patients who are efficacy evaluable for both the SVR as well as the TSS endpoints. When we look forward to ASH, we are going to provide additional updates both in terms of patient numbers as well as follow-up, and expect to provide TSS and SVR data on approximately 21 patients from the entire 24 patient cohort. In terms of the breakdown between the 40 and 60 milligram doses, so we enrolled 10 patients as part of the 40 milligram dose level and 14 patients as part of the 60 milligram dose level and we'll be providing safety and efficacy data at ASH across those two dose levels. And then lastly, in terms of AE rates dose dependency, you're correct. So this is a phenomenon that we are seeing with selinexor across all of our indications including endometrial cancer, multiple myeloma, as well as myelofibrosis in that there is a dose dependency between AE rates, grades with the doses. And this is again, an observation that we're seeing also with the MF program in which we're combining with ruxolitinib.

Great. Thank you. And then just a follow-up for the TSS50 that you're seeing. At ASCO, we saw that there were three out of seven responders I believe, in the abstract today we're seeing nine out of 13. Can you talk about if these are new responders or if this is potentially a deepening of response? And why is the symptom score getting better? Is there any -- are there any learnings that you can carry forward into future studies?

Yes. So, again the TSS50 that we're presenting in the ASH abstract similar to the ASCO or from the efficacy of valuable patients. And we are seeing a very nice improvement in that TSS score at week 12 from 43% to now 69%. And that includes, in symptoms that are deepening in the patients that are initially responded in the ASCO data set, as well as the new patients who are responding as well so really very encouraged by these symptom scores that are occurring as early as week 12.

Thank you.

The next question comes from Colleen Kusy from R.W. Baird. Please go ahead.

This is Abi Gray on for Colleen. Thanks for taking our questions. First off, congratulations on the myelofibrosis update. And then, I was wondering on the TSS50, do you have any update on the TSS50 scores on those patients that have followed out to 24 weeks? And if not, do you have any commentary on how the symptoms are changing over time?

Yes. it’s a great question. So, we weren't able to provide the TSS50 data at week 24 in the ASH abstract. This is again a July data cut. And unfortunately, we just had some missing data at that time, but we look forward to presenting week 24 data in the ASH presentation come December.

And then I have a follow-up. It looks like the rates of nausea and vomiting increased from the last update at ASCO. So is there any additional color, on the GI toxicities you're seeing? And is it mostly presenting at the beginning of the study or does that present later, and how persistent is it throughout the study follow-up? And have you implemented any anti-MC protocols to help with that medic, sorry antiemetic to help with that?

Yes. I appreciate the question. So as you know, selinexor causes nausea. This is an AE that has been observed in multiple myeloma, as well as our other cancer types including myelofibrosis as well as endometrial cancer. It's important to note that while we see the nausea, this isn't dose limiting for the patient. So we aren't seeing patients who are discontinuing therapy, due to the nausea nor does it limit their ability to stay on therapy. We also see nice improvements as you know in the TSS50 scores. And while nausea is not included in that TSS50 domain specifically, it really is a testament to their overall global symptom improvement. So, again it is not clinically relevant to this patient population. Lastly, I'll note we do incorporate antiemetics with selinexor. And this is again, just a standard mitigation strategy that we use across all of our programs.

Great. Thank you so much. A – Richard Paulson: Thanks, Abi.

The next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

All right. Thanks for taking my questions. Congrats on all the progress. Continuing on the theme of the myelofibrosis data as you mentioned the TSS scores look like they improved versus the last cut. And I'm curious what sorts of TSS50 scores, would you be looking for to be confident that you're getting additive activity over ruxolitinib just given the challenges of an open-label study.

Yeah. I got to say, Brian, we're very encouraged by these data right now as well as the evolution in the TSS50 over time. At ASCO, as you know, we presented 43% of the patients achieving that TSS50, and now we're seeing a nice evolution to 69%. So again, we're very encouraged, especially when we couple that with a very meaningful FBR and hemoglobin stabilization, as well as improvement score as well, really does suggest that this combination one is additive if not synergistic in combination with ruxolitinib. We're having meaningful improvement on all efficacy endpoints in the context of a manageable safety profile. So, again, very encouraged by the data so far.

Great. And you mentioned that as expected you saw some dose dependence to the tolerability profile. Did you also see a dose dependence related to spleen response or TSS response?

So those data are maturing and we look forward to presenting that data at ASH. Ultimately, we will identify the recommended Phase 2 dose, either 40 milligrams or 60 milligrams based upon the totality of data, including safety efficacy and both pharmacokinetic data.

Great. And then maybe one last one on – also on MF. Wondering I think in the past you sort of alluded to consistency of response across different patient profiles and risk profiles. Just wondering, if you're continuing to see that or if there are any predictors of who might have the deepest and most durable responses here?

Yeah. We are seeing improvement really across all the patient demographics. It's also notable to know that approximately 70% of our patients are classified into or high risk. So these really are a high-risk patient population. Despite that, again, we're really seeing meaningful improvement across all efficacy domains in this patient population. In terms of are we seeing anything predictive still interrogating the data. But right now the data again really are very encouraging and we're seeing it across all patient demographics.

That's great. Thanks so much and look forward to the next update at ASH.

Thanks, Brian.

[Operator Instructions] And our next question comes from Eric Joseph from JPMorgan. Please go ahead.

Good evening. Thanks for taking the questions. I guess, with the – in getting more efficient on the R&D spend, I'm just curious to get a sense of whether you see the need to sort of prioritize between selinexor development in combination with RUX in the treatment-naive setting versus in the RUX experience population. I guess, ultimately do you see both regimens advancing to later stage development? And I guess, as it relates to the treatment-naive setting is – it's still a pretty conservative sample size. I'm just wondering if that is sufficient to make a call on the prospects of potentially advancing the RUX-combo forward as part of a pivotal study? Thanks.

Yeah. Thanks Eric. Maybe I'll turn to Reshma to talk to that really in terms of the totality of building the multimyeloma or sorry the myelofibrosis franchise, and I'll come back to talk to the spend.

Yeah. And thanks for the question. I mean, I think one of the key differentiating factors for selinexor is the fact that it has robust monotherapy activity especially in that relapsed refractory patient population. This builds upon preclinical non-clinical data that demonstrates selinexor's active and JAK resistant cells. We see that again in that Phase 2 ESSENTIAL trial. But that allows us again to be able to develop selinexor in the widest patient population of myelofibrosis really why we are focused on both the treatment-naive opportunity in combination with ruxolitinib, but also as a monotherapy in those patients that have been treated with at least six months of prior JAK inhibition.

And we look at our plans Eric and in terms of our pipeline the work we've done I think over the last year and year an half really prioritize the pipeline both the relapse setting and the frontline setting are in our plans moving forward. And as we're really very encouraged, how the data is evolving we're excited to keep moving forward with them. Operator?

There are no more questions in the queue. This concludes our question-and-answer session. I would like to turn the conference back over to Richard Paulson for any closing remarks. End of Q&A:

Thank you everyone again for joining the call today, and we wish everyone a great evening. Good night.

Conference has now concluded. Thank you for attending today's presentation. You may now disconnect.