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Edited Transcript of KPTI earnings conference call or presentation 6-Aug-19 12:30pm GMT

Q2 2019 Karyopharm Therapeutics Inc Earnings Call

Natick Aug 13, 2019 (Thomson StreetEvents) -- Edited Transcript of Karyopharm Therapeutics Inc earnings conference call or presentation Tuesday, August 6, 2019 at 12:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Christopher Brett Primiano

Karyopharm Therapeutics Inc. - Executive VP, Chief Business Officer, General Counsel & Secretary

* Ian Karp

Karyopharm Therapeutics Inc. - VP of Investor & Public Relations

* Michael G. Kauffman

Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director

* Michael P. Mason

Karyopharm Therapeutics Inc. - Senior VP, CFO & Treasurer

* Perry Monaco

Karyopharm Therapeutics Inc. - SVP of Sales

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Conference Call Participants

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* Arlinda Anna Lee

Canaccord Genuity Corp., Research Division - Analyst

* Brian Corey Abrahams

RBC Capital Markets, LLC, Research Division - Senior Analyst

* Edward Patrick White

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* Michael Eric Ulz

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Mitchell Swaroop Kapoor

Jefferies LLC, Research Division - Equity Associate

* Turner Andrew Kufe

JP Morgan Chase & Co, Research Division - Research Analyst

* Wei Ji Chang

SVB Leerink LLC, Research Division - MD of Emerging Oncology & Senior Research Analyst

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Presentation

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Operator [1]

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Good morning. My name is Skyler, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Second Quarter 2019 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

I would now like to turn the call over to Mr. Ian Karp, Karyopharm's Vice President, Investor and Public Relations.

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Ian Karp, Karyopharm Therapeutics Inc. - VP of Investor & Public Relations [2]

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Thank you, Skyler, and thank you all for joining us on today's conference call to discuss Karyopharm's Second Quarter 2019 Financial Results and Business Update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, our Chief Executive Officer; Mr. Perry Monaco, Senior Vice President of Sales; Mr. Mike Mason, Chief Financial Officer; and Mr. Christopher Primiano, Chief Business Officer and General Counsel.

On the call today, we'll provide an overview of key recent corporate developments, including an update on the initial commercial launch of XPOVIO as well as an overview of the second quarter 2019 financial results. Dr. Kauffman will then discuss our upcoming milestones and provide some summary remarks before we move into the Q&A portion of the call.

Earlier this morning, we issued a press release detailing Karyopharm's results for the second quarter. This release is available on our website at karyopharm.com.

Before we begin our formal comments, I'll remind you that various remarks we'll make today constitute forward-looking statements for purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical development and regulatory matters and time lines, the potential success of our product candidates, financial projections and our plans and prospects.

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 annual report on Form 10-K, 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 specifically 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, please note that references we make to clinical trial data during today's discussion refer to interim unaudited site data, unless otherwise specified.

I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [3]

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Thank you, Ian, and good morning, everyone. It's been a remarkable year so far for Karyopharm, which, of course, would accentuate by the recent accelerated approval of oral XPOVIO, also known as selinexor by the U.S. Food and Drug Administration.

XPOVIO is a first-in-class nuclear export inhibitor. It was approved in combination with dexamethasone for the treatment of adult patients with relapsed or refractory myeloma, whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents and an anti-CD38 monoclonal antibody.

XPOVIO is the first and only prescription medicine approved in the U.S. for this indication, and it is the first approved cancer drug that targets nuclear export dysregulation, which is increasingly recognized fundamental mechanism in the generation of malignant cells. Importantly, because multiple myeloma is an incurable disease, an increasing number of patients will need new therapeutic options once their disease has become refractory to the currently available standards of care.

Oral XPOVIO represents an entirely new mechanism of action and a novel approach in the treatment of multiple myeloma. Our commercial colleagues have been doing a tremendous job educating the myeloma community about this new treatment option. And I'll now ask Perry Monaco, our Senior Vice President of Sales, to provide a brief update on how the commercial launch is progressing so far in just the first month or so postapproval. Perry?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [4]

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Absolutely, Michael. And I'm excited to provide some early commentary. Thanks to the hard work and dedication of the Karyopharm team, XPOVIO became commercially available in the U.S. on July 9, 2019, less than 1 week after its official FDA approval. We have deployed more than 70 sales representatives and nurse liaisons, who are focusing on the 1,300 accounts who treat roughly 80% of all multiple myeloma patients. And not surprisingly, we are placing additional emphasis on those 400 higher volume accounts caring for roughly 1/2 of all patients. These commercial efforts are also being supported by our comprehensive, fully integrated KaryForward support program for patients, their caregivers and health care providers. The KaryForward program provides support services such as insurance benefits investigation, side effect management tools and nursing support.

Additionally, our focused network of 3 highly experienced specialty pharmacy providers are providing additional support to patients being prescribed XPOVIO.

Finally, we are pleased that so many patient advocacy organizations throughout the U.S., are excited about the approval and are also educating the myeloma community about new treatment options. We thank them for all they do for patients and their families, and we remain committed to supporting patients in the myeloma community.

While we are in the very early days post-FDA approval, the commercial launch thus far is off to a strong start. Early prescribing trends have been encouraging with robust demand from both academic and community-based physicians throughout the U.S. Additionally, we are seeing early prescriptions being built for patients with Medicare as well as for those with commercial insurance coverage. We are also already seeing encouraging progress within the payer environment as many payers clearly appreciate the urgency in which patients with heavily pretreated myeloma need new treatment options.

XPOVIO is already being covered by some of the largest national payers and has been quickly added to some key formularies, including that of Express Scripts, one of the largest PBMs in the U.S. We look forward to providing more details regarding the ongoing launch at our third quarter earnings call in November, when we will report on nearly a full quarter of XPOVIO sales. But so far, the early feedback from health care providers has been positive, and we remain optimistic in our ability to effectively bring this important new medicine to patients in need of novel treatment options.

I'll now turn the call back over to Michael.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [5]

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Thank you, Perry. Beyond this very important first accelerated approval, we continue to focus our efforts on gaining regulatory approval for XPOVIO beyond the U.S. market as well as expanding the breadth and depth of approved indications for selinexor. To that end, we fully enrolled the pivotal Phase III BOSTON study in January. BOSTON is evaluating selinexor in combination with Velcade and dexamethasone compared to Velcade and dexamethasone alone in patients with myeloma who have 1 to 3 prior lines of therapy.

As we have highlighted previously, the Data Safety Monitoring Board for BOSTON convened earlier this year and determined that first on the safety side, no new safety signals have been identified of the study and that there was no imbalance in mortality in the 2 arms of the study. And second, on the efficacy side, based on the first interim analysis, the Board recommended proceeding with the study as originally planned with no changes in patient numbers. Progression-free survival is a BOSTON primary endpoint, and we remain on track to have the top line results from this study by the end of 2019 or early into 2020 depending on the occurrence of progression events.

In parallel with the U.S. activities, we are also working with the European Medicines Agency on a Marketing Authorization Application, or MAA, requesting additional conditional approval for selinexor in combination with dexamethasone, based on the clinical data from the STORM study, which served as a basis for XPOVIO's U.S. accelerated approval. We expect to receive decision on this application by the end of 2019 or early 2020.

In addition to the BOSTON study, we are also investigating selinexor in combination with other standard of care myeloma drugs as a potential new backbone therapy in patients with earlier-line myeloma. 3 abstracts highlighting new and updated clinical data from Kyprolis, Darzalex and Pomalyst arms of the Phase Ib/II STOMP study were presented in June at the European Hematology Association 2019 Annual Meeting. We continue to be encouraged by this combination data as we believe the full commercial and therapeutic potential for XPOVIO in multiple myeloma will be as part of combination regimens, subject of course through additional future clinical trials, regulatory filings and approvals.

Turning now to our other selinexor development programs beyond myeloma. For diffuse large B-cell lymphoma following a presentation of updated positive data from Phase IIb SADAL study presented in June at the 2019 International Conference on malignant lymphoma. We are now working towards NDA and MAA submission. We hope submissions require accelerated and conditional approvals, respectively.

For patients with relapsed or refractory DLBCL, who have received at least 2 prior multi-agent therapies and who are ineligible for stem cell transplantation, including CAR-T therapies. We expect to submit the NDA and MAA packages during the fourth quarter of 2019 and the first quarter of 2020. We anticipate some further clarity on timing and feedback from our pre-NDA meeting we expect to schedule with the FDA in the fourth quarter of this year.

Next, for the ongoing Phase III portion of the Phase II/III SEAL study, where selinexor is being investigated as a single agent versus placebo in liposarcoma, enrollment continues on track assuming a positive outcome on the primary endpoint of PFS. We intend to use the data from the SEAL study to support NDA and MAA submissions requesting approval for selinexor for the treatment of advanced, unresectable dedifferentiated liposarcoma. Top line data from the Phase III portion of the SEAL study are anticipated in 2020.

And finally, we are excited to present updated efficacy and safety data from the Phase II KING study evaluating single-agent selinexor in patients with recurrent glioblastoma, which was recently highlighted in the American Society of Clinical Oncology, ASCO, 2019 Annual Meeting. Of the 30 patients treated in the 80 mg dosing cohort, the overall response rate was 10% with 19% of patients achieving a 6-month PFS rate and 30% of patients achieving a 6-cycle PFS rate and most common treatment-related adverse events for cytopenias, along with gastrointestinal, constitutional symptoms and were primarily grade I and II events.

Based on these data, we have recently entered into an exciting new collaboration with the Ivy Brain Tumor Center at the Barrow Neurological Institute to conduct preclinical testing of several new drug combinations involving selinexor for the treatment of glioblastoma. If the preclinical work proves successful, viable selinexor combinations will advance in the Ivy's unique tissue-based Phase 0 clinical trial format, which enables researchers to understand the experimental therapies impacting an individual patient's brain tumor in as little as 7 days saving critical time in this highly aggressive form of brain cancer.

Before I turn the call over to Mike to discuss the financials, I'd also like to take a moment to mention that our Founder, President and Chief Scientific Officer, Dr. Sharon Shacham, recently received the esteemed New York Intellectual Property Law Association 2019 Inventor of the Year award. This award recognizes Dr. Shacham for her important research that led to a better understanding of nuclear transport abnormalities in cancer and her cutting-edge work, designing and developing oral selinexor as well as several other of our pipeline assets. Past winners of this award have included the inventors of CAR-T therapy, Gleevec, Valium and LASIK laser vision correction among many others. And of course, her work was the foundation for the accelerated approval of XPOVIO received last month. We offer our sincere congratulations to Dr. Shacham and the entire development team for winning this prestigious award.

With that, I will now turn the call over to Mike.

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Michael P. Mason, Karyopharm Therapeutics Inc. - Senior VP, CFO & Treasurer [6]

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Thank you, Michael. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights. As of June 30, 2019, cash, cash equivalents and investments, including restricted cash, totaled $217.9 million compared to $330.9 million as of December 31, 2018.

As XPOVIO was approved on July 3, 2019, we will begin booking product revenues in the third quarter of 2019. For the second quarter of 2019, license and other revenue was $9.5 million compared to $19.9 million for the second quarter of 2018, primarily related to the company's license agreements with Antengene and Ono, respectively. For the second quarter of 2019, R&D expense was $26.5 million compared to $44.7 million for the second quarter of 2018. We expect R&D expense on a quarterly basis to be relatively consistent for the remainder of 2019 compared to the second quarter 2019.

General and administrative expense for the second quarter of 2019 was $24.7 million compared to $9.5 million for the second quarter of 2018. The increase in G&A expenses compared to the prior year period was due primarily to the hiring of the Karyopharm commercial team and related commercial launch preparation activities to support the U.S. commercial launch of XPOVIO. We expect G&A expenses for the remainder of 2019 on a quarterly basis to be relatively consistent with Q2 2019. For the second quarter of 2019, we reported a net loss of $43.4 million or $0.71 per share compared to a net loss of $33.7 million or $0.60 per share for the second quarter of 2018. Net loss includes stock-based compensation expense of $4.1 million and $4.4 million for the second quarters 2019 and '18, respectively.

Based on our current operating plans, we continue to expect our full year 2019 operating expenses to be between $200 million and $215 million, excluding stock-based compensation. Additionally, we expect our existing cash, cash equivalents and investments will be sufficient to fund operations into the second half of 2020.

I'll now turn the call back over to Michael for concluding remarks. Michael?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [7]

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Thank you, Mike. Before moving to the Q&A, I'd like to provide a quick overview of our key upcoming milestones. First, we will execute upon our commercial launch initiatives as we've just begun to see the initial impact XPOVIO can have in the marketplace, and more importantly, on expanding the treatment options for patients battling multiple myeloma.

Next, we continue to work closely with the EMA in support of our MAA requesting conditional approval for selinexor and we expect to receive a decision by the end of 2019 or early 2020. For our next potential indication in relapsed or refractory DLBCL, we plan to submit an NDA to the FDA with a request for accelerated approval based on the SADAL trial results sometime during the fourth quarter of 2019 and the first quarter of 2020. We expect greater clarity on time lines following a pre-NDA meeting with the FDA. We also plan to submit an MAA in Europe with request for conditional approval in the same time frame.

For the pivotal Phase III BOSTON study, enrollment was completed in January and top line data are expected by the end of 2019 or early 2020 depending on the occurrence of progression events in the trial. If positive, these data could support regulatory submissions in 2020 in second-line myeloma.

Next, the various arms of Phase Ib/II STOMP study continue in myeloma and we look forward to presenting updates from the various combination arms at future medical meetings. And finally, we will continue to progress our solid tumor programs and liposarcoma and endometrial cancer.

In summary, 2019 is shaping up to be a truly exciting and transformational year for Karyopharm and for patients battling multiple myeloma as we work to drive awareness and adoption of our first marketed product, XPOVIO. We are also working in parallel to expand upon selinexor's clinical and commercial potential in new territories and clinical studies where there are patients with high unmet medical need. We appreciate all of your support, and we look forward to keeping you updated on progress in the coming months and quarters.

I'll now turn this call over to the operator for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from Maury Raycroft with Jefferies.

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Mitchell Swaroop Kapoor, Jefferies LLC, Research Division - Equity Associate [2]

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This is Mitchell on for Maury. My first question is, can you remind us what were the prespecified criteria for determining whether to upsize the BOSTON study or not?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [3]

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I can't -- not to be cynical, but I can't remind you because we didn't announce this. The trial is designed to show approximately a 30% reduction in the risk of progression or depth against the control arm. So you can imagine, with the hazard ratio of about 0.70%, if we were far off from that, this trial would have been stopped for futility. And if we were close to that, but not in that zone, we would have outsized trial. We did neither. So you can assume that we were in the range.

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Mitchell Swaroop Kapoor, Jefferies LLC, Research Division - Equity Associate [4]

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Okay. And then what more can you say about the prescribing trends you're seeing? Are you seeing docs combine XPOVIO with other myeloma drugs? And can you talk about the types of patients that you're treating?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [5]

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So I can't, but it's still too early to really see trends in terms of how they're exactly using the drug. What I can tell you is that we've seen some encouraging demand from all parts of the country, and we're seeing demand come from both community and academic institutions. But again, we're still in the first month. So it's really hard to really see what kind of trends it looks like in terms of each individual prescription that's coming through.

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Mitchell Swaroop Kapoor, Jefferies LLC, Research Division - Equity Associate [6]

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Okay. And then maybe my last one, could you talk a little bit about the KaryForward program? And how involved the support program gets?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [7]

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Yes. So the KaryForward program is a very comprehensive program that provides nursing services to patients to help with getting them through if they're experiencing any side effects. They will also put patients on our quick start program. We know that -- we understand that the dynamic of the patient that's receiving XPOVIO a lot of times is they're out of treatment options and a lot of times, patients can't wait for insurance verifications, so they will put them on a quick start in order to get drug into a patient quickly and then they're transferred over generally to our specialty pharmacies. They will also provide support to caregivers and family members to help support the patient through their treatment.

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Operator [8]

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Our next question comes from Brian Abrahams with RBC Capital Markets.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [9]

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Congrats on the XPOVIO launch and congratulations to Sharon for the award. I want to drill down a little bit more on the launch dynamics. And I guess I'm curious how the openness for and maybe capabilities for safety management, how that's been overall, maybe how that's differed between -- perhaps between academic versus community sites and the ways in which this management is being accomplished either through supportive therapies, dose reduction, interruptions, et cetera? And then I had a follow-up.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [10]

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Yes, I'll start, and then I'll turn it over to Perry. The label for XPOVIO was fairly general and often included words like used institute of standards, supportive care, which gave us some leeway. And then in addition, for the typical side effects of XPOVIO, which, as you know, are nausea, anorexia and fatigue and low platelets, there are very standard protocols out there with a number of drugs and often NCCN guidelines that can handle this. So sites have been very open to us relaying all of the knowledge that we gained during the clinical trials. And I think doctors are very willing to use the best practices that so far have been determined for all of this, so there's been really a great openness, I think, for standard and supportive care and prophylaxis as well. Perry, do you want to add?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [11]

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Yes, I don't have a lot to add to that, other than that our supportive care guidelines and our dose modification criteria are clearly laid out in our label and our reps are trained to do that. On top of that, a very critical piece is our team of Karyopharm nurse liaisons. They are working with practices to provide additional education on managing patients with XPOVIO. And then as mentioned earlier, our KaryForward program is a comprehensive support program for both the physicians and the patients. We also have our network of highly specialized pharmacies, and they provide some of those same services as well. So what we're trying to do is we're trying to wrap that patient with the right amount of care in order for them to have a good experience with XPOVIO.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [12]

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That's really helpful. And then you've talked about the interim -- the first interim analysis for BOSTON. I'm also wondering what sort of -- what level of real-time safety or mortality data might you and the FDA have coming out of the BOSTON study and whether this might give you any additional insights or confidence as far as the safety or efficacy of selinexor in the earlier line population?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [13]

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Yes. So on safety, as the medical monitors -- for the sponsoring medical monitors for the study, we have a very good view of ongoing safety adverse events and any fatalities that are on study and even after patients leave the study. Sitting here today, we feel as confident as we did 6 months ago, saying that there is no imbalance in depths on either arm of the study and we are privy to these in real-time. And for adverse events, again, we've not seen any new adverse events.

On the efficacy side, we do not see compiled or rolled up information on efficacy, so we can't speak to that. And of course, it's a Phase III study, so we wouldn't.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [14]

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Congrats again on all the progress.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [15]

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Thank you very much.

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Operator [16]

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Our next question comes from Eric Joseph with JPMorgan.

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Turner Andrew Kufe, JP Morgan Chase & Co, Research Division - Research Analyst [17]

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This is Turner on for Eric. So just looking ahead to the BOSTON data, I'd like to get a sense of your expectations for the proportion of patients that require Darzalex for anti-CD38 treatment? Was it a stratification factor within the study design? And is there the potential for that level of granularity in the readout?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [18]

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Yes. We don't have rolled up demographic data at this point, and we'll have to wait for a medical meeting to announce that. I will say that there is no stratification for prior CD38 because it's not known to be a major component of a response or not to sel/Vel/dex or to Vel/Dex itself. So that will have to await an analysis. I should also point out that the trial is being conducted in U.S., Canada, Europe as well as Australia, and India. And therefore, it's -- the use of Darzalex is not quite as prevalent as in the U.S. So we don't expect it to be a major component of people's prior therapies in BOSTON.

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Turner Andrew Kufe, JP Morgan Chase & Co, Research Division - Research Analyst [19]

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Okay. And then on total maximum DLBCL. Is the current expectation that a confirmatory study would be required for full approval? And if so, how should we think about the design of that trial? And any time line?

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [20]

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Yes. The -- as with all accelerated approvals, there will be a commitment, which we hope to be a postmarketing commitment for a confirmatory randomized trial. The design of that trial is being investigated now. We'll be proposing several designs. But in general, I should think of it as a chemotherapy-type backbone or a novel accepted therapy type backbone plus or minus selinexor. And that will be a randomized study, most likely in patients with at least one prior therapy.

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Turner Andrew Kufe, JP Morgan Chase & Co, Research Division - Research Analyst [21]

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Okay. Great. That's helpful. And just one last quick one for me. Just in follow-up, tumors in the ongoing Phase III SEAL study in liposarcoma, I'm just wondering if we can expect any interim analysis to be performed.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [22]

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Yes. As soon as we have any major endpoints from the SEAL study, we'll be happy to disclose them, but I'm not going to discuss anything -- any more details at this point.

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Operator [23]

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(Operator Instructions) Our next question comes from Arlinda Lee with Canaccord.

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Arlinda Anna Lee, Canaccord Genuity Corp., Research Division - Analyst [24]

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I had a couple on -- if you could provide some color on discussion with payers and what we might hear about in the update from the next call? And then secondly, you've talked about education to help ameliorate severity or duration of AEs. Can you talk about how KaryForward might be helping with that? And then thirdly, on BOSTON, what is the bort dose modification scheme in BOSTON versus your current label? And what's allowed for bortezomib dose changes as well?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [25]

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All right. So I'll start. So with regards to payers, so far, the response from the payers has generally been positive, and we're not encountering significant roadblocks. Of course, it's still early in the launch cycle, but our sense is that the payers understand the urgency in which the indicated population for XPOVIO need new treatment options. We're already seeing prescriptions generated and subsequently approved from both large commercial payers and Medicare Part D plans. And as I mentioned earlier, XPOVIO has already been added to a number of payer formularies, including Express Scripts being one of the nation's largest PBMs.

In terms of AE management and how the KaryForward program works with that, what they -- what the KaryForward team of nurses will typically do is they will set up a series of calls with patients based upon patient needs and their desire for those services, and they will check in with them, find out how they're doing. If the patient reports having some AEs, KaryForward will then report back to their health care providers so that they can make any adjustments to supportive care or anything like that, that a patient might need. Michael, you have anything that you want to add or...

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [26]

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No. As far as BOSTON is concerned, well, the current dosing reduction scheme is actually very simple for the indications for the STORM patients and that's starting at 80 milligrams twice a week with low dose dexamethasone. And then the first dose reduction moved to 100 milligrams once a week, and then 80 milligrams once a week and 60 milligrams once a week. The BOSTON dosing regimen starts at 100 milligrams once a week for selinexor, moves down to 80 and 60 and then the lowest dose on BOSTON is 40, which we do believe does confer some synergy with Velcade. Velcade dosing is standard for the control arm, and that's 1.3 mg per meter square twice a week, given subcutaneously, 2 out of every 3 weeks for the first 8 cycles and then it moves into the more maintenance regimen. On the selinexor arm, importantly, Velcade begins at once weekly. And this is a fundamental difference between BOSTON and most of the other Phase III studies that have been done with Velcade, so the real-world use of Velcade is once weekly in most cases, and we're instituting that from the get-go with selinexor. So it's sel/Vel/dex once a week at 1.3 mg per meter square of Velcade and then dose reductions for Velcade are always 1.3 down to 1.0 and 0.7, which is standard.

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Operator [27]

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Our next question comes from Jonathan Chang with SVB Leerink.

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Wei Ji Chang, SVB Leerink LLC, Research Division - MD of Emerging Oncology & Senior Research Analyst [28]

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First question regarding the early launch, any color on physician feedback? And any similarities and differences between academic and community-based physicians?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [29]

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So it's still too early to say whether there is any significant difference between academic and community-based physicians. But the general feedback is that things are going well, and we're getting results that we would have expected.

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Wei Ji Chang, SVB Leerink LLC, Research Division - MD of Emerging Oncology & Senior Research Analyst [30]

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Got it. And can you talk about the implications of the BOSTON readout on the path forward in DLBCL?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [31]

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Well, just -- obviously, these are different diseases. But FDA is always looking for randomized data. We will be meeting with the FDA in a pre-NDA meeting, specify the exact timing of the DLBCL submission. The data are complete. We're cleaning them and preparing the NDA, so we don't see a major interaction between those 2 studies. But if the FDA would like to see data from BOSTON as they did for the STORM review, we, of course, will provide it.

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Wei Ji Chang, SVB Leerink LLC, Research Division - MD of Emerging Oncology & Senior Research Analyst [32]

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Got it. And then just last question. Any updated thoughts on how you're thinking about business development opportunities for selinexor?

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Christopher Brett Primiano, Karyopharm Therapeutics Inc. - Executive VP, Chief Business Officer, General Counsel & Secretary [33]

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Sure. Yes. This is Chris Primiano. So obviously, we intend to maintain commercial rights in the U.S. And so then the question is how do you handle Europe. And there are a couple of different options that we have that we're continuing to assess. So one option can involve partnership. And we, of course, will look for a partner that would have a mutually beneficial relationship with us and with a partner and maximize the potential of selinexor in the European market. And it will be really important that we find a partner that aligns with our philosophy regarding long-term development and commercialization plans. It has the expertise in marketing in both heme and solid tumor drugs in EU. And then the second option would be to potentially launch selinexor on our own in select European countries where reimbursement negotiations and decisions typically occur more quickly and at acceptable levels and then you sort of have a step-wise approach to expanding throughout Europe. So our view is that the value of selinexor will build over time as we progress through our discussions with FDA, EMA and the various different indications that we've been discussing, and we'll be focused on making sure that we are achieving the best value of selinexor for the company.

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Operator [34]

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Our next question comes from Mike Ulz with Baird.

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Michael Eric Ulz, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [35]

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Congrats on the launch as well. Just a quick question on the European filing. Just wondering if you can comment on your interactions with the EMA and if there's been any noticeable differences compared to that with the FDA.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [36]

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The interaction with EMA are intense. We received a list of questions as expected, the 90-day questions and so on. And it's been a very, very scientific discussion back and forth. So very comprehensive set of questions, spanning the entire development program. And I would say, it's similar to the FDA and perhaps in some areas, even more delving into details.

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Michael Eric Ulz, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [37]

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Got it. And then in your prepared remarks, you mentioned thinking about additional combinations with standard of care and beyond Velcade, which you're using in BOSTON. Maybe if you can just give us your current thinking there? Maybe timing of starting some of those studies, if there's a particular combo you're thinking to go with next after Velcade?

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Perry Monaco, Karyopharm Therapeutics Inc. - SVP of Sales [38]

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Sure. We haven't firmed up the next registrational studies in myeloma. And part of this is a larger, more comprehensive discussion about whether we expand broadly in myeloma and/or expand into other different tumor types. As you know, one of the unique aspects of XPOVIO is that it's relevant to the generation of various types of malignancies, potentially any malignancy, and therefore, can be used broadly. So we're exploring liposarcoma, uterine cancer and brain cancer as well as some of the immunological malignancies.

In terms of the exact combinations in myeloma, the initial strategy is really to have the BOSTON data come in, hopefully, positively. And that will be -- and then support that with NCCN guideline listings for the other various combinations that we're using. We're quite excited about all the different combinations, as highlighted at -- recently at the EHA meeting, and we'll have additional highlights, I think, later this year, the combination with Darzalex is particularly exciting. This is a once-weekly regimen as are all of our selinexor dosing regimens. The combination with Kyprolis, although early, looks extremely promising and is consistent with the Velcade data, and these are in more heavily pretreated patients that we would see with BOSTON. The all-oral combination with Pomalyst, where we see approximately a doubling of the expected response rate for Pomalyst itself and a much longer PFS than what you see with Pomalyst itself makes that all-oral regimen particularly intriguing.

And finally, we intend to update on combination with Revlimid later this year as well as -- as new mechanisms come into play, we'll expect to be a simple, oral once a week partner for essentially any new mechanism. So this is really a broad-based backbone type of therapy where we've seen additivity or synergy with essentially all these combinations. Again, just to close what we -- where we go in terms of approvals with the combinations, we have not decided yet. But we will have guideline-based ambitions.

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Operator [39]

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Our next question comes from Ed White with H.C. Wainwright.

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Edward Patrick White, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [40]

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So all of my XPOVIO questions have been asked and answered already. So I just wanted to ask about eltanexor, if you can just give us an update there and when we'll see the next expected data.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [41]

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Sure. We've presented data in prostate cancer in combination with second-generation antigen inhibitors earlier this year, and we expect to expand on those data later this year or early next. And then potentially -- we'll be planning potentially an approval study for eltanexor most likely in prostate, but we haven't decided exactly yet.

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Operator [42]

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And at this time, I'm showing no further questions. I'd like to turn the call back over to Michael Kauffman for any closing remarks.

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Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [43]

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Just to thank everybody for joining us, and we look forward to updating you on the launch in the rest of our progress in the 3 months.

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Operator [44]

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Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.