Karyopharm Therapeutics, Inc. (NASDAQ:KPTI) Q3 2020 Earnings Conference Call November 2, 2020 4:30 PM ET
Ian Karp – VP, Investor and Public Relations
Michael Kauffman – CEO
Sharon Shacham – President and Chief Scientific Officer
Mike Mason – CFO
John Demaree – Chief Commercial Officer
Christopher Primiano – Chief Business Officer and General Counsel
Jatin Shah – Chief Medical Officer
Conference Call Participants
Jonathan Chang – SVB Leerink
Maury Raycroft – Jefferies
Brian Abrahams – RBC Capital Markets
Eric Joseph – J.P. Morgan
David Lebowitz – Morgan Stanley
Michael Ulz – Robert W. Baird
Edward White – H.C. Wainwright
Peter Lawson – Barclays Capital
Good afternoon. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics’ Third Quarter 2020 Financial Results Conference Call. [Operator Instructions] Please be advised that the call is being recorded by the company’s request.
I would now like to turn the call over to Mr. Ian Karp, Karyopharm Therapeutics’ Senior Vice President, Investor and Public Relations.
Thank you Kate, and thank you all for joining us on today’s conference call to discuss Karyopharm’s third quarter 2020 financial results and business update. This is Ian Karp, and I’m joined today by Dr. Michael Kauffman, Chief Executive Officer; Dr. Sharon Shacham, President and Chief Scientific Officer; Mr. Mike Mason, Chief Financial Officer; Mr. John Demaree, Chief Commercial Officer; Mr. Chris Primiano, Chief Business Officer and General Counsel; Dr. Jatin Shah, Chief Medical Officer.
On the call today, Michael and John will provide an overview of the key recent corporate developments and an update on our commercial progress, and then Mike Mason will provide an overview of the third quarter 2020 financial results. We will conclude with the Q&A portion of the call. Earlier this afternoon, we issued a press release detailing Karyopharm’s results for the third quarter of 2020. This release along with a slide presentation that we plan to reference are available on our Web site at karyopharm.com.
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. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations relating to the commercialization of XPOVIO, 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 quarterly 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, any 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.
Thank you, Ian, and good afternoon, everyone. I’m pleased to report that Karyopharm has continued to make tremendous progress so far in 2020, with the achievement of numerous commercial pipeline and operational accomplishments, positioning us well for what we believe to be continued and sustained future growth. As we get closer to the end of 2020 and hopefully closer to and end of the COVID-19 pandemic, we are already preparing for numerous significant opportunities for our company and the patients we serve in 2021, and beyond.
Before I begin, I’d like to take a moment to briefly put into some perspective the foundational and unique approach that we are taking towards innovating cancer drug therapy. On slide four, we have highlighted five core pillars of cancer drug therapy which are all foundational and used across tumor types, often in combination, to give each patient the best chance of clinical improvement. XPOVIO is the first approved anti-cancer drug whose primary activity is the activation of tumor suppressor proteins. There are about 20 of these proteins, including p53, BRACA 1 and 2, Rb, and the inhibitor of NF-κB, which are critical parts of each cell’s own natural defense mechanism to prevent the generation of cancer cells, and to direct a cell which has become cancerous to commit suicide. This broad anti-cancer mechanism is potentially relevant to any malignancy. Our goal is to continue to demonstrate the impact that XPOVIO can have in combination with drugs from all of the other pillars in order to maximize the impact that XPOVIO can have on improving outcomes for a large variety of cancers.
Moving to slide five, I’ll focus on our near-term and medium-term goals. First and foremost, we remain committed to increasing the positive impact we are having in the lives of patients battling cancer, and this is a core principle that guides everything we do in Karyopharm, and as you may have seen in a press release we issued this afternoon, we have just achieved another very important milestone with our announcement that the top line results from the Phase 3 SEAL study met its primary endpoint with a significant increase in progression-free survival in patients with unresectable dedifferentiated liposarcoma.
Additionally, over the next one to two years, there are a number of key goals that will be critical for us, including, first, securing the U.S. approval for XPOVIO and 2nd line multiple myeloma, which we believe will help significantly drive total XPOVIO sales higher. Second, receiving the initial approval for XPOVIO in Europe for patients with relapsed or refractory multiple myeloma. Third, launching our first solid tumor indication in the U.S. based on the data just announced, and fourth, continuing to generate supportive clinical data for our growing clinical portfolio, which includes XPOVIO, Eltanexor, and KPT-9274.
Looking a bit further out to the next three to five years, we anticipate that XPOVIO could be approved in multiple oncology indications across the globe, with substantial revenue contributions from ex-U.S. royalties and sales milestones. This next chapter is also anticipated to bring continued expansion of our pipeline across multiple assets, and finally the broad establishment of XPO1 inhibition as a core therapeutic approach in cancer treatment.
Please now turn to slide six, where I’ll highlight the exciting news we announced earlier this afternoon regarding our randomized Phase 3 SEAL study. As a reminder, SEAL evaluated the efficacy and safety of single-agent XPOVIO in patients with advanced unresectable dedifferentiated liposarcoma following two or more prior therapies. Unfortunately, there is no standard of care for patients with advanced disease, and we are thrilled to announce that the study met its primary endpoint with a significant increase in progression-free survival, and a hazard ratio of 0.70, with a p value of 0.023.
We believe that these results not only represent a significant advance in the treatment of patients with dedifferentiated liposarcoma, but we believe these data further support XPOVIO’s substantial potential across multiple solid tumors, representing a major advance for the development and commercial potential of XPOVIO in oncology more generally. This is also consistent with other earlier stage positive results from ongoing XPOVIO studies in diseases such as endometrial cancer, GBM, melanoma, lung cancer, and others. Liposarcoma also represents an important entry point for XPOVIO into the solid tumor treatment landscape where nine of the top 10 most common and fatal forms of cancer are solid tumors. We look forward to presenting the detailed results of SEAL at the upcoming Connective Tissue Oncology Society, or CTOS, Annual Meeting. We plan to submit a New Drug Application, or NDA, in the first quarter of 2021 requesting the FDA approval of XPOVIO to treat the patient population study in the SEAL Phase 3 trial.
Please now turn to slide seven. Our clinical strategy for XPOVIO continues to be innovative to be innovating with a purpose. Specifically, our approach has been to demonstrate meaningful activity in difficult to treat patient populations, and then to expand dramatically into earlier lines of treatment and additional tumor types, particularly in combination with other anti-cancer drugs. This strategy has been evident in our approach in both myeloma and DLBCL, where we began with our successful STORM and SADAL studies, and has led to subsequent development in earlier lines and combination settings. Similarly, now that we have seen the positive Phase 3 SEAL data, we plan to follow the same path and continue with expansion on our clinical development approach in a number of important and much larger solid tumor indications, including endometrial cancer with the SIENDO study, lung cancer, GBM, melanoma, and others which have been selected based on encouraging earlier clinical data and commercial potential.
Turning to slide eight, I’ll focus on other recent highlights. During the third quarter we achieved record quarterly XPOVIO net sales of $21.3 million, the strongest quarter since our July 2019 launch in penta-refractory multiple myeloma. These results reflect a 15% increase compared to the second quarter of this year. These strong results were driven by demand for XPOVIO in both new multiple myeloma patient starts and initial prescriptions in patients with relapsed or refractory diffuse large B-cell lymphoma. For our pipeline progress, I’ll remind you that the FDA recently accepted our supplemental New Drug Application seeking approval for XPOVIO for the treatment of myeloma after at least one prior line of therapy, and assigned a PDUFA action date of March 19, 2021.
In addition to a decision by the FDA, we are awaiting a decision in Europe from the EMA on our MAA seeking approval of XPOVIO for the STORM population. In addition to the SEAL study, we also made important progress with our development programs in other solid tumors. This includes several presentations of data at ESMO, in September, which show promising results for XPOVIO in combination with KEYTRUDA for the treatment of melanoma, and XPOVIO in combination with Carboplatin and Paclitaxel for the treatment of advanced or metastatic solid tumors.
Finally, on the financial front, we ended the quarter with a strong cash position of approximately $304 million that we expect will be sufficient to fund our planned operations into the second-half of 2022.
I’ll now ask John Demaree, our Chief Commercial Officer, to provide some additional details on XPOVIO’s sales performance during the third quarter. John?
Thank you, Michael, and good afternoon, everyone. As Michael noted earlier, I am proud of the commercial momentum seen during the quarter, a direct result of the dedicated Karyopharm commercial organization that continues to drive our educational initiatives forward virtually, and in person where appropriate, in support of our greater multiple myeloma and diffuse large B-cell lymphoma communities of patients, families, and caregivers.
On slide nine, we outline results for market research that highlight the key features of XPOVIO treatment that are resonating most with healthcare providers in helping to drive the increased usage of XPOVIO that we’ve now seen over the past few quarters. Specifically cited our XPOVIO’s rapid response data with some responses reported as early as one week, as well as the positive STORM data that showed a strong objective response rate in very difficult to treat patient populations which included 100% of patients being refractory to Daratumumab and 57% having high-risk cytogenetics.
Next, physicians noted that XPOVIO is the first and only FDA-approved oral XPO1 inhibitor that selectively binds to and blocks XPO1 whose over-expression in cancer cells is increasingly being recognized as a core driver of tumor growth, and finally, there’s increasing recognition and experience that XPOVIO’s side-effect profile can typically be manageable, and reversible with dose modifications and prophylactic treatments.
Slide 10 shows the positive and increasing quarterly sales and prescription trends for XPOVIO so far in 2020. The third quarter saw a 15% increase in both net sales, and patient demand compared to second quarter. Importantly, we saw a robust increase in new myeloma patient starts in the third quarter compared to the second quarter. The majority of prescriptions for the quarter continued to come for multiple myloma patients, but we get the important initial contributions from DLBCL patients as we continue to introduce XPOVIO to this segment of the market, and build momentum in this new indication.
Slide 11 highlights the increase in new account growth for the third quarter which jumped to 202 new accounts prescribing XPOVIO, bringing the total to 543 new accounts for the year. New accounts secured this quarter reflect multiple myloma and DLBCL treating physicians. These results are particularly promising as physician education in many geographies continues to be conducted via virtual and web-based tools due to ongoing restrictions related to COVID-19 pandemic.
The graph on slide 12 shows the prescription refill rate for XPOVIO over time for both the first and second refill for those patients eligible for these refills. These numbers remained stable for the third quarter, but are significantly higher as compared to our initial launch period. For instance, in September of 2019 which marked the first — which marked the end of the first quarter that XPOVIO became commercially available, roughly 42% of patients were going on to get a second prescription.
One year later, that number stands at 60%, a substantial increase. These promising and increasing refill rates coupled with an average of 2.9 treatment cycles per patient as of the end of September further reinforced a positive feedback we received from patients, and physicians regarding their experience in usage of XPOVIO. Importantly, the patient discontinuation rate due to side-effects remained relatively low at 13%, which we believe is a testament to more and more physicians gaining comfort in helping their patients manage the side-effect profile of XPOVIO with proper prophylactic therapies and dose modifications. The third quarter of 2020 represented the first full quarter of our launch in relapsed refractory DLBCL following approval in late June.
On slide 13, we’re pleased to share preliminary launch metrics for this period which showed two-thirds of prescriptions have come from community-based physicians. Early retail trends have been strong as well at 60% which matches what we’ve seen in the multiple myloma space and we were able to secure category 2A NCCN Compendium listing within two weeks of approval. These efforts are translated into positive initial feedback from treating physicians and their patients. Based on our market research, target physicians are most attracted to XPOVIO’s response rate as a single agent, oral option, and the ability to treat DLBCL patients in a completely new way. Additionally, we’ve seen positive care dynamics with no on-label patient denials seen to date.
And finally, the feedback we are hearing regarding XPOVIO’s side-effect profile has also been positive with most physicians reporting 60 milligram twice weekly dose, the approved dose being manageable for patients. We will continue to fully leverage the newly approved indication in DLBCL to access our key stakeholders, educate on this new indication, and also generate increasing excitement in multiple myeloma to help more patients impacted by these diseases.
Now, I’d like to turn the call back over to Michael to discuss our regulatory updates and clinical development priorities. Michael?
Thank you, John. On slide 14, I’ll provide a brief update on our key upcoming regulatory activities. The positive results from the BOSTON study served as the basis for sNDA submitted to the FDA for the treatment of patients with multiple myeloma after at least one prior line of therapy, our sNDA was accepted for filing in July, but the decision expected by March 19 2021.
In Europe, we’ve submitted the final additional re-monitoring data from the STORM study requested by the EMA in September of 2019, and in October 2020 Karyopharm received a further updated list of outstanding issues for the CHMP summarizing the remaining topics for Karyopharm to address and indicating the CHMP intends to consult Scientific Advisory Group for additional advice, we continue to expect a decision from CHMP by the end of this year. In addition contingent upon and following receipt of CHMP opinion, we expect to submit an MAA based on the data from the BOSTON study before the end of 2020. For DLBCL, we’re still in the process of evaluating the optimal approach and timing of future regulatory submissions and we look forward to providing you with an update in the future.
Please now turn to slide 15. The potential expansion of our XPOVIO label based on the promising BOSTON data results represent an important turning point in the multiple myeloma treatment paradigm. XPOVIO’s current pento-refractory multiple myeloma indication is largely applicable to the approximately 6,000 patients in the United States who are treated in the fourth and later lines of therapy annually, if approved and expanded label based on the population studied in the BOSTON trial would expand XPOVIO’s potential impact over 30,000 patients annually in the U.S. treated in the second and third line settings.
This slide highlights some of the key differences between the STORM and BOSTON population study and data generated from these trials. As you can see, the patient studies in the BOSTON trial had been previously treated with far fewer therapies and the patients in STORM and had disease was far less refractory to treatment, i.e. a median of eight prior therapies in STORM as compared to two in the BOSTON study. Subsequently, the response rate and median PFS seen in the BOSTON study was substantially higher than the STORM study. This was also driven by the mechanistic approach of combining two drugs with different and additive or synergistic mechanisms of action in the BOSTON study as XPOVIO and XPO1 inhibitor was given in combination with once-weekly Velcade, a Proteasome inhibitor, along with standard low dose Dexamethasone.
Importantly, the mean duration of treatment was 10 months in the BOSTON study, as compared to three months in the STORM study. This comparison of studies is key to why we believe XPOVIO has just begun to make an impact on the treatment paradigm in multiple myeloma. We believe the greatest utility for XPOVIO in the future will be as combination therapy with other potent anti-myeloma drugs such as Velcade and taking only once per week instead of the currently approved dose twice per week.
And finally, I’d be remiss if I didn’t mention some updates for a number of other exciting pipeline opportunities we’re pursuing for Selinexor, which can be seen on slide 16. In the hematologic malignancy space, we expect to dose our first patient by the end of the year in our confirmatory Phase 3 DLBCL trial, which will study Selinexor in combination with Rituximab and in chemotherapy regimen of Gemcitabine, Dexamethasone platinum-based therapy. We’ve also recently initiated two new trials in myelofibrosis, where we have been encouraged by some smaller investigator initiated studies, and we expect to begin enrolment in these new studies in 2021, and as I mentioned earlier, we have a number of important ongoing studies in the solid tumor setting both as a single agent and in combination, which follow nicely from the positive results we announced today.
With that, I’ll turn the call over to Mike Mason to review the quarterly financials, Mike?
Thank you, Michael. Since we issued a press release earlier today with a full range of results, I will just focus on our highlights which begin on slide 18.
Net product revenue for the third quarter of 2020 was $21.3 million, third quarter sales were driven by patient demand from academic and community based physicians with channel inventory sales growing in line with actual prescription growth. The estimated gross to net discount for XPOVIO in the third quarter was approximately 16%. We continue to expect the gross net discounts to fall between 15% and 20% for the remainder of this year. Research and development expense for the third quarter of 2020 was $37 million compared to $26.3 million for the third quarter of 2019.
The increase in R&D expenses compared to the third quarter of 2019 was mainly attributable to COVID-19 trial activity and continued activity in our other ongoing clinical trials. SG&A expense for the third quarter of 2020 was $30.9 million, compared to $25.3 million for the third quarter of 2019. The increase in SG&A expenses compared to the prior-year was primarily due to activity to support the U.S. commercialization of XPOVIO including expenses related to the launch of XPOVIO as treatment for patients with relapsed or refractory DLBCL.
As noted on slide 19, cash, cash equivalents, restricted cash and investments, as of September 30, 2020, totaled $304.2 million, compared to $265.8 million as of December 31, 2019. We currently project XPOVIO sales to grow modestly for the remainder of 2020 based on expected catalysts, with more significant growth expected following the potential expanded approval of XPOVIO based on the results from the BOSTON study. Based on our current operating plans, we expect our non-GAAP R&D and SG&A expenses for the full-year 2020 to in the previously projected range of $240 million to $260 million.
In addition, we currently expect that our existing cash, cash equivalents, and investments, and revenue we expect to generate from XPOVIO product sales will be sufficient to fund our planned operations in the second-half of 2022.
I’ll now turn the call back over to Michael for some concluding remarks. Michael?
Thank you, Mike. Before moving to the Q&A, let me highlight some of the key clinical and regulatory milestones that we expect for the remainder of 2020, as shown on slide 20. As you can see, we have achieved many key milestones throughout the year, but still have important goals to accomplish by the end of this year.
First, we expect a decision from EMA on the STORM MAA. Next, we plan to submit the full BOSTON data to the EMA before the end of the year continuing upon and following receipt of CHMP’s decision on the STORM MAA. And finally, we anticipate initiating our confirmatory Phase 3 studio of XPOVIO in DLBCL in support of our recent accelerated approval, and of course, we’ll continue to support the FDA through the review of our sNDA based on the BOSTON study, where we expect a decision from the FDA on or before the PDUFA date of March 19, 2021. We appreciate your ongoing support, and look forward to keeping you updated on our future progress.
I’ll now turn the call over the operator for questions. Operator?
We will now begin the question-and-answer session. [Operator Instructions] Our first question is from Jonathan Chang from SVB Leerink. Go ahead.
Hi, guys. Thanks very much for taking my questions, and congrats on the positive SEAL readout. First question, can you talk about the dedifferentiated liposarcoma treatment landscape, how you see this commercial opportunity? And what, if any, read-through this has on your broader thinking regarding the solid tumor opportunity for XPOVIO?
Sure. Let me dive in, I’ll be brief because we can’t give a lecture on this. Unfortunately, the dedifferentiated liposarcoma landscape is only populated by parenteral chemotherapy cytotoxic agents. Pretty much every patient will get anthracycline, like Adriamycin in combination with Gemcitabine or some other cytotoxic, and most patients will receive Eribulin and/or Trabectedin during their treatment course. Beyond that there are really no other treatments that have clear documented activity and are routinely used. XPOVIO potentially could be the first oral therapy approved in this indication, and furthermore, this is the largest study of liposarcoma ever performed, and I believe it’s the largest dedicated liposarcoma study ever performed. So we think we can really become one of the important drugs after chemotherapy is used, and could provide a real, better tolerated, we believe, oral option for these patients who are heavily pretreated.
Got it. Just one follow-up question then on a different topic, can you provide additional color on the outstanding questions from the CHMP that you received in October, I think you said.
Yes, I’ll turn that over to Dr. Shacham to comment.
I’m sorry, Michael, can you start, and I will follow-up?
Sure. I believe the question was can we provide additional color on some of the questions from the EMA that they continue to ask us, and I think as we’ve described previously, the EMA has requested additional information regarding some of the laboratory analyses in patients who were on the study, in particular, some of the responding patients, and we’ve provided those to the EMA. In addition, we’ve provided, as the EMA as asked us to continue to justify the benefit-risk, we provided the BOSTON data in support of the STORM MAA application.
Got it, thank you very much.
The next question is from Peter Lawson from Barclays. Go ahead.
Hi there. This is [Mitchell] [ph] on for Peter. Congratulations on the positive data, and thanks for taking our question. So the first question I have for the SEAL, the hazard ratio came in at 0.7, or just wondering, did the FDA say what would qualify as meaningful and how much you’d beat those expectations by?
The FDA doesn’t say that. What they do, both the FDA and EMA have provided advice, in particular scientific advice from the EMA, and post-meeting advice from the FDA, considering that this trial could potentially serve as the basis for an approval, and generally that means that you have to hit the statistical boundary of 0.05, which we did, and that the trial has to be well-conducted and internally consistent, which we also believe it has been. So we believe we hit the appropriate goalpost. I should also mention that the hazard ratio in the Phase 2 portion of this study was essentially identical to that in the Phase 3, so the FDA was aware of that, as was EMA. And they went into this Phase 3 expecting a hazard ratio of about 0.7, which is what it was designed for.
Great, thank you. And then if you could just comment on discontinuation rate for the SEAL study, is that consistent with the 13% you’d seen in the real world for myeloma, and then what additional data should we expect at CTOS beyond the PFS? Thank you.
Yes, I can’t speak to the exact discontinuation rate, but I can say that it was — these patients are not as heavily pretreated as patients with last-line myeloma. They also have much less systemic comorbidities that end-stage myeloma patients have. And one would expect the dropout rate therefore would be lower, and in addition the dose here was lower. So you might look at the dose being used in the SEAL study was more similar to the DLBCL SADAL study. You’ll see a complete presentation that, as far as time permits, at the CTOS. And this will be given by our lead investigator, and it should be a full dataset.
Thanks, and congrats.
Our next question is from Maury Raycroft from Jefferies. Go ahead.
Hi, everyone. Thanks for taking my questions, and I’ll offer my congrats on the liposarcoma data as well. I’ll ask a question about myeloma. So for XPOVIO in 3Q, and also DLBCL too, can you talk about the COVID impact? And for new myeloma patients what line of treatment are you seeing with some of the new patients, and if you can break out combo preferences as well, and then, you mentioned the average treatment cycles per patient at 2.9. Just wondering if you expect that to continue to increase in the current market opportunity in the last line setting or do you see a leveling off around 2.9, and then when you get into the expansion with the earlier line patients that that number could potentially go up?
Wow, Maury, that was quite an encyclopedia. So I’ll ask John Demaree, our Chief Commercial Officer, to being to address that. And we’ll keep it a little bit short, but go ahead, John.
If I missed any of those, keep me on it.
But let me answer the one about BOSTON first, and are we seeing XPOVIO use with Velcade in earlier lines of therapy. Currently, the majority of use for XPOVIO is in 4th line+, as indicated. We obviously do expect that to move earlier once the BOSTON indication in combination with Velcade is approved. You know from our market research that many of the academic and community-based physicians are prescribing XPOVIO in combination with other drugs, so it’s not just XPOVIO plus Dexamethasone, that they’re using it primarily in that 4th line+ setting now currently where it’s indicating. Again, we do expect significant acceleration in earlier lines of usage once we get the new indication for patients with approval on prior line of therapy.
In terms of the second question around impact of the pandemic, do you think the pandemic does still continue to have multiple affects, in-person visits by our sales force, nurse liaisons and payer teams to actually stakeholders continue to be impacted? Our data and research suggests about 15% to 20% of HCPs can be seen via in-person visits. We do continue to believe it’s harder to appropriately educate change behavior in a virtual environment as compared to maintaining prescribing habits, like the goal of more established brands. We have done and are doing a number of initiatives to offset the impact of being virtual, including increasing peer-to-peer education, increasing other non-personal promotion and digital content, training our field teams on how to be more effective in the virtual environment, and finally, targeting some large physician networks and their EMR systems to better identify patients in the penta-refractory setting. So, it’s two of the questions. What were the other questions?
I think one was about the average duration of treatment or the number of cycles, and maybe what I would just say there is — yes, I mean we’re close — we’re at 2.9 through the end of September which we’re excited to be at that level — a little bit over a year into the launch. I think to some extent, as we get closer and then into the launch on the BOSTON population, that number will hopefully go significantly higher because as Michael mentioned earlier, the average duration of treatment on BOSTON within — the mean duration of treatment in BOSTON was 10 months versus 3 months in STORM. So, potentially, it can go a little bit higher, but I think the reality is we’re going to come up pretty soon to — hopefully at BOSTON approval, and then I think patients who will be getting treatment much earlier with XPOVIO hopefully will stay on drug and be treated for longer.
Great, thank you, guys.
Our next question is from Brian Abrahams from RBC Capital Markets. Go ahead.
Hey guys, thanks for taking my questions, and congrats on the SEAL data. I’m curious how frequently physicians are looking to use XPOVIO in earlier line myeloma post the BOSTON presentation, but maybe can’t do the access, and the degree to which inclusion in NCCN guidelines might open up earlier line access even prior to label expansion. Any update on timing there or timing for the BOSTON publication?
Yes. Well, we do expect the BOSTON publication to come out soon, hopefully before the end of the year, but maybe sooner. We don’t know exactly, but it will be published in a good peer-reviewed journal, and that will hopefully facilitate an NCCN guideline edition. Again, the speed of that edition, we don’t know. Our expectation is that there are a — not insignificant number of places where you can use the NCCN guidelines as a basis for insurance coverage which is the major impediment right now to earlier line adoption. We believe that this combination of Selinexor or XPOVIO plus Velcade dex once a week is actually the simplest of all of the regimens for relapse or refractory myeloma patients with one prior therapy, and therefore could be really beneficial to folks. So, we’re hopeful that we can facilitate access once the NCCN guidelines come out and then of course ultimately will be FDA-approved.
Got it, and then, just as a follow-up, you mentioned some of the continued multiple effects that the pandemic is having, looking forward I guess in the near to medium term, I’m curious your expectations of how the second or even third wave of COVID that we’re seeing may impact near-term use and uptake. I guess I’m wondering if you’d expect continued challenges to physician and patient engagement, or conversely, if you may be able to take advantage of some of the benefits of the oral administration and perhaps fewer facilities available for administration of CAR-T in DLBCL. Thanks.
So, I think the answer to your question is yes, there are opportunities, and there are challenges in the current COVID situation. Obviously, for many patients, an oral therapy is preferred, particularly less visits during the time of peak pandemic impact. I think it is also, as you mentioned, more difficult to engage physicians in-person. We have tried to offset that and are continuing to do more and more to offset in terms of some of the digital non-personal promotion initiatives that I just mentioned earlier.
Our next question is from Eric Joseph from J.P. Morgan. Go ahead.
Hi, good afternoon, and thanks for taking the question. First, in relation to the SEAL in the liposarcoma opportunity, I’m curious to get a sense of whether you see an opportunity to advance Selinexor earlier up in the treatment paradigm for liposarcoma either as an alternative to chemo or as maintenance, and whether that’s strategically of interest, and then I have a follow-up on XPOVIO?
Well, although liposarcoma is a relatively small population that you differentiated, [type in] [ph] around 2,000 patients per year, it’s obviously an important disease and needs addressable therapy. There’s been a good bit of interest from various groups given the SEAL data which of course they’ve just heard about, and we expect to continue additional studies in earlier lines probably with outside groups if you will. Part of that is because we want to focus our internal resources in some of the larger tumor groups that were showing activity.
Our SIENDO study is ongoing. For those who don’t recall, this is a phase three randomized blinded study of once weekly Selinexor versus matching placebo in patients with endothelial cancer who receive frontline chemotherapy, typically a platinum-taxel couplet, and then, have at least a partial response which is approximately 80% of these patients, and then, right now, there’s no maintenance therapy for those folks unfortunately, and we know that essentially all of them will relapse. So, we’re conducting SIENDO study in the maintenance setting after first line chemotherapy in that group, and that’s a big focus. That study is ongoing. We expect data within — before the end of next year, and that’s a fairly substantial size population with a bigger medical need. So, that will be our next big focus in solid tumors, and then of course you heard about some of the earlier data at ESMO that mentioned and some of the other places in GBM where we show clear single agent activity which we intend to pursue. So, we’re going to try to move in all fronts, will take advantage of our CRADA with the NCI and other external groups that have shown interest to move in the sarcoma area.
That’s helpful, and maybe just a question on XPOVIO commercial, if you could, it sounds like you had pretty good visibility on where demand is coming from between myeloma and DLBCL. I’m wondering if you could just unpack how much demand — how much skip demand was actually coming from DLBCL, and I’m also just trying to just square some of the conservative expectation in terms of growth of the balance of the year, I guess how much of a growth opportunity do you see in third line DLBCL? Are you seeing kind of competition from other agents in the community setting? How much of the growth opportunity does third line DLBCL sort of represent in near term?
So, to address the first question, for competitive reasons, we don’t break out sales separately between multiple myeloma and DLBCL. What we can tell you is that the majority of prescriptions in the third quarter came from multiple myeloma. The DLBCL patients were an important contributor that we believe will continue to grow over time.
Yes, and just in terms of the competitive landscape and growth moving forward, I think we’ve mentioned a few — I think we’ve been as transparent as we possibly can be, which is we’re certainly quite pleased that we grew 15% quarter-over-quarter, this quarter, myeloma metrics continue to look good, and obviously we’re starting to get contributions from DLBCL, and we balanced that with — we’re still in the midst of the COVID pandemic which does create some challenges, and as you mentioned, obviously there are some new competitive entrants particularly in the DLBCL space, but we also have a number of catalysts that we’re expecting, and we’ll see when those come in including publication of BOSTON data we talked about, NCCN guidelines we talked about, and the actual DLBCL launch getting momentum. So, all those create sort of pushes and pulls. I think ultimately we continue to keep our eye on the BOSTON submission and working with the FDI in that piece as well as in Europe because we know that clearly the biggest driver of growth in the near-term is going to be upon BOSTON approval and our ability to sell into second line multiple myeloma. So, those are really the things that we think drive growth over the next three to — six to nine months, and we look forward to keeping you abreast of all those things.
Thanks for taking the question, John.
Our next question is from David Lebowitz from Morgan Stanley. Go ahead.
Thank you very much for taking my question. Given that prescription demand increased from 12% to 15% from second quarter to third quarter, sales growth ultimately stayed pretty similar between the two quarters, how was the cadence of those prescriptions relative to sales over the quarter, and what dynamics I guess are at play causing the convergence?
Yes. I think if the cadence is on a — I mean on a monthly basis, yes, that’s not something that we typically disclose on a monthly basis, I think in terms of where the scripts are coming from. Certainly in DLBCL they’re largely coming from the community base physicians, which is a little bit different than I think some of the early uptake we saw in multiple myeloma, which was coming from both large academic sites, as well as some community based sites as well. I think that was your question. If I missed it, John, I don’t know if you want to add anything?
And with respect to the liposarcoma data, given I guess, specifics regarding that tumor type, how does that I guess give you confidence going forward with respect to other solid tumors?
Well, I think I’ve said before, there’s similarities and differences and every tumor type is different. The fact that virtually there are really no very effective drugs in liposarcoma, and thankfully we have a regular approved — anthracyclines are generally approved and Trabectedin, but these are chemotherapies that are essentially all cytotoxic agents. These are large tumors. They’re difficult for drugs to access, and the fact that we could show a real benefit was in the third line very difficult population following at least two chemo therapies, we think is very important for reading to other solid tumors. These data show that XPOVIO clearly penetrates large masses, it can go and can slow tumor growth, we’ll see about some responses, perhaps which are quite unusual in this tumor, particularly in the second and third line setting, especially for a non-cytotoxic agent, and hopefully this gives those patients an option, but it does speak to the fact that this drug can penetrate into solid tumors, particularly connective tissue, which tend to be more difficult. So its positive results are always beneficial in cancer. This represents our third disease type, and quite different from the hematologic disorders that we’ve talked about before. We think this provides a great foundation. It also helps solidify some of the early data we’ve seen in combination that’s been reported from the ESMO place and other studies.
Thanks for answering my question.
Our next question is from Mike Ulz from Baird. Go ahead.
Hi, guys, thanks for taking the question and congrats on all the progress as well. I just had a follow-up on an earlier question related to the field data. Just wondering if you maybe comment a little bit further on the safety profile, you’re seeing there beyond discontinuation rate, and maybe how that compares to the label. Just trying to get a sense if there’s anything notably different there that we should be looking for, and I have a quick follow-up?
Sure, what we can say is kind of what we said in our press is that we see a safety profile that’s consistent with what you’ve seen before, qualitatively, quantitatively, it tends to be substantially less particularly on the cytopenias. Remember, these patients are coming in with only two prior cytotoxic therapy. So, not a lot of marrow suppression. They don’t have disease in their bone marrow. Bottom line is they have a much healthier marrow than the kinds of myeloma patients that we’ve treated even on BOSTON even as compared to BOSTON. So you expect a lot less cytopenias, which is what we saw, and frankly, unfortunately because these tumors are in the abdomen, and can often compress GI structures, and the like the patients often come in with baseline nausea, and fullness and abdominal pain, which may or may not get better or worse on XPOVIO. So expect higher baseline levels of nausea, but basically, this looks like still in extra without cytopenias.
Got you. That’s helpful, and then just a quick follow-up, you mentioned a couple other opportunities in solid tumors in this liposarcoma kind of gives you more confidence there. Maybe you can just talk a little bit about timeline for some of these other tumor types or your strategy in some of these tumor types? Thanks.
I think in 2021, we’re going to be elaborating some additional studies. We already have ongoing, Phase 1 combination study of Selinexor plus Docetaxel Phase ½, I should say was Seli plus Docetaxel based on some not yet public data from an investigator sponsored trial by the Atomic Group. This is in patient non-small cell lung both KRAS mutant and KRAS wild type previously treated non-small cell lung cancer where we were seeing some interesting things and we want to recapitulate that in the company’s hands. We have studies ongoing in GBM where we have announced and we’ll continue to update on a single agent approximately 10% or bonafide response rate in Temozolomide radiation relapsed or refractory GBM patients that have a dire prognosis. We have data with a bunch of different solid tumors with in combination of platinum-taxel, including in patients who’ve already seen Platinum and or Taxel and we’ll be moving on some of these both internally and again through our NCI collaboration going forward more in 2021 on those. Lastly, we thought very exciting data and our investigators are quite excited about the potential combination with KEYTRUDA.
Amongst nine patients with untreated melanoma, we saw 55% response rate including 2 CRs in that initial study, and importantly, there were no major autoinflammatory side effects recorded, which is quite distinct from similar multi-immune modifier combinations, and if we’re able to combine with KEYTRUDA melanoma that opens up possibilities in other tumors, but importantly, it may open up those possibilities in melanoma and other tumors without the major autoinflammatory side effects that some of the sort of Opdivo plus Yervoy types of combinations can deliver.
Okay, great, thank you.
Our next question is from Ed White from H.C. Wainwright. Go ahead.
Congratulations on the field data and just a couple of questions on solid tumors. So I think you had mentioned the GBM study, and the Phase 1/2 trial, that first patient was enrolled in June with this large 400 patient trial. I’m just wondering how the enrollment is going in that, it has been impacted by the pandemic, when could we see data and then the question is just what are your thoughts on the launch strategy in solid tumors? So liposarcoma small, what is your strategy for hiring a sales force? How many people and how do you build up in solid tumors? Thanks.
Sure, so I’m going to ask Dr. Shacham to take the first question about the approval on the GBM study. Sharon?
The study has three arms, including two arms in patients with GBM that are newly diagnosed and then another arm looking at patients with relapsed refractory disease, and enrollment is going well in all arms with a three plus three design, and we don’t see any impact from the CORONA study on enrollment for this study, decide to engage and the studies moving forward.
Maybe just quickly on the solid tumor side of things, I think certainly, within the liposarcoma space, vast majority of patients in the U.S. will be treated for with all sarcomas are treated as Centers of Excellence across the U.S., there’s probably about 90 or so of them total, and then you can narrow that down to probably 30 or so that are seeing the Lion’s share of patients here in the U.S. That’s something we could certainly do from a commercial standpoint, with a handful of folks, whether those are medical science liaisons, or sales reps or combination, but that’s certainly a fairly straightforward call point at the Centers of Excellence. As you start to get out to the Endometrial cancer study, that’s ENDO study, knock on wood, should that study be positive? That’s obviously a much larger, solid tumor indication, these patients are seeing at vastly a significant number of sites. So we’d have to take a look at what that commercial model looks like and make a decision, But certainly, that would be a terrific, issue to have to think about how we would commercialize in Endometrial cancer.
And we have a follow-up from Peter Lawson from Barclays. Go ahead.
Hey, thanks for taking my questions, but just congrats on Sarcoma data and will you be able to submit that to the EU, would you need a different trial and how should we think about the patient you can initially treat with that, using that data as a label?
Well, this trial did receive positive expert advice from the EU Scientific from their Scientific Advice Group. So it’s been — it was discussed with them. It was approved with them and we do believe it could start for approval in the EU, the on-label indication there would be patients with dedifferentiated liposarcoma that have received two prior systemic therapies.
And what number of patients because there’s a room for 2000 patients, what we’d be thinking about, okay, and then on the endometrial, is that the next data after Sarcoma or what should we think about is the next solid tumor?
In terms of randomized Phase 3 data, yes, I can say with a little tongue in cheek, it’s hard, these are huge trials, it’s hard to conduct a lot of especially with a company of our size, but yes, that is the next one, and that should be out by the end of next year. There’ll be updates during the year with other combinations, including in both hematologic and solid tumors, as well as potentially data within the next year, say in myelofibrosis and other areas.
Got you, and then just on multiple myeloma DLBCL, do you get a sense of the duration of treatment in multiple myeloma or DLBCL?
Well, I mean, we’re at about — I mean across our specialty pharmacy network, it’s about three months on average per patient. Now again DLBCL just started, so those patients are not at three yet, and you’ll have patients out for 10, 12 months, some longer, and you’ll have patients that don’t get a response after one or two months, but the average right now is about three months, and it’s been climbing. Someone asked an earlier question, how much higher can it go? We think it’ll probably go a little bit higher, but it probably can go substantially higher, once if and when we get the BOSTON indication, because those patients in the second and third line, obviously stay on drug for much longer periods of time.
Great, thanks, and just final question just around guideline changes, when do you think that happens?
I assume you mean for myeloma, the way it works procedurally is you have to have a publication and we believe that publication will be out before the end of the year, there will be a publication in a peer reviewed journal coming out, with that will be submitted to the NCCN Committee and they will determine the timing of when if and when they add the regimen to their recommendations.
Could that be year-end or do you think that kind of more than 2020?
Eventually, it really depends on the publication. It could be, it depends on the publication timing and the timing of the NCCN Committee. In addition to BOSTON publication, we will be submitting the other single-arm study results, particularly with Daratumumab, Kyprolis, and Pomalyst, and those could potentially follow, but all of this is dependent upon of course publication in the NCCN adjudication.
Great. Okay, thank you so much. Thanks.
Well, thank you, everybody. Appreciate your following with us and we look forward to talking to you again in the near-future.
The conference has now concluded. Thank you for attending today’s presentation. You may now disconnect.