Thank you very much, Eric. It's great to be here, and thank you all for joining us today to discuss Karyopharm's recent progress in our pursuit of improving the lives of patients with cancer.
Before I begin, let me remind you of the standard remarks I'll make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in Slide 2 of today's presentation and the Risk Factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC.
As we move to Slides 3 and 4, let me provide a brief overview of Karyopharm. Karyopharm is a commercial stage global pharmaceutical company with 1 FDA-approved drug in 3 oncology indications and 3 additional drug candidates in clinical development. We're the industry leader in targeting nuclear export dysregulation as a mechanism to treat cancer. Our lead drug, XPOVIO, also known as selinexor, received its first accelerated approval from the FDA in July 2019 for patients with penta-refractory multiple myeloma. And we are thrilled to announce on December 18 last year that the FDA expanded the approval of XPOVIO to also include patients with myeloma as early as first relapse.
In addition to 2 approvals in patients with myeloma, XPOVIO also received accelerated approval in June 2020 for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, or DLBCL. And we expect this to be just the beginning as we have ongoing clinical trials for XPOVIO and our next-generation programs in earlier lines of treatment, in combinations with other anticancer drugs and in additional tumor types across both hematologic and solid tumor malignancies. The extent of activity of XPOVIO beyond the hematological malignancies was recently demonstrated with the positive results in the Phase III SEAL study in patients with heavily pretreated dedifferentiated liposarcoma. This is the first of several important solid tumor studies. Further, we believe XPOVIO has patent protection, including composition of matter in the U.S. until at least 2032, giving us ample time to fully maximize the long-term potential this therapy can have on patients with a wide variety of cancers. We expect 2021 to be another important year for us with numerous key milestones expected.
Just a few weeks ago, and highlighted on Slide 5, we were delighted to announce that the FDA has now approved once-weekly oral XPOVIO for adult patients with myeloma as early as first relapse, significantly expanding the patient population to whom we can now offer a new and simple treatment option. More specifically, XPOVIO is now indicated in combination with once-weekly bortezomib, also known as Velcade, and low-dose dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy. And of course, XPOVIO is the first and only nuclear export, or XPO1 inhibitor, approved by the FDA. This last indication is now XPOVIO's third FDA approval in less than 2 years and its first full approval, not contingent on a confirmatory trial.
Moving to Slide 6. You will see that XPOVIO was also approved earlier in 2020 for the treatment of adult patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma after at least 2 lines of systemic therapy. This indication was approved under accelerated approval based on response rate and continued approval for the indication may be continuing, upon verification and description of clinical benefit in a confirmatory trial. Importantly, XPOVIO is now the only single agent oral therapy approved for the treatment of patients with previously treated DLBCL.
The safety highlights from XPOVIO's package insert are fairly straightforward and noted on Slide 7. There are no black box warnings nor contraindications in the label. A patient medication guide is available to educate patients on the expected adverse reaction profile for XPOVIO. And additionally, there are some important details regarding patient monitoring instructions and warnings and precautions included. The most common side effects are listed here within the warnings and precaution section includes cytopenias as well as gastrointestinal toxicity, infections, neurological toxicity such as dizziness, along with cataracts and others. Most of these side effects are reversible in days and many are preventable with standard prophylactic agents.
Through the first 3 quarters of 2020, XPOVIO sales demonstrated consistent mid double-digit sales and prescription growth. Sales growth was primarily driven by both increased utilization and time on treatment for patients with penta-refractory multiple myeloma, and to a lesser extent, but still a positive contributor from new patients with DLBCL being prescribed XPOVIO. We are particularly pleased with the feedback we continue to receive from both physicians and patients who've been positively impacted by treatment with XPOVIO, and I'll describe some of the dynamics now that impacted sales in the fourth quarter of 2020 as we move to Slide 9.
Earlier this morning, we announced preliminary unaudited Q4 2020 revenues of $35 million to $36 million and full 2020 revenues of $108 million to $109 million. We did see a slight decline in XPOVIO sales in the quarter driven by the surge in COVID-19, impacting both patient visits to their health care professionals as well as Karyopharm's commercial team's reduced ability to access their customers. In addition, we did see some increased competition in the penta-refractory myeloma setting as well as in the third line plus DLBCL settings. With that said, we're particularly encouraged by the recent FDA expanded approval of XPOVIO in myeloma, where the new indication includes 5x the number of eligible patients and 3x the expected duration of treatment relative to the initial penta-refractory myeloma indication. And we expect quarterly XPOVIO sales to return to growth beginning in Q1 2021.
In addition, in December 2020, the National Comprehensive Cancer Network, NCCN, updated their treatment guidelines adding 3 XPOVIO regimens to its myeloma treatment recommendations. Specifically, NCCN added 3 different XPOVIO combination regimens, including with Velcade, with Pomalyst and with Darzalex to its clinical practice guidelines in oncology for previously treated multiple myeloma. And in fact, we have already seen sales begin to rebound with strong sales seen in December of 2020 as compared to October and November, further adding to our confidence in XPOVIO's future growth prospects.
Finally, I'll mention that we have made further progress on the international front. First, we selected a commercial partner in Canada, which triggered a $5 million upfront payment. And second, we also received approximately $10 million in payments as a result of regulatory milestones achieved by our partner in the Asia Pacific region, Antengene Corporation, with submissions of new drug applications in Australia, Singapore and South Korea.
I'd now like to spend a few moments discussing Karyopharm's unique and innovative approach to targeting cancer cells while largely sparing normal cells. On Slide 11, you'll see there are 5 foundational pillars of cancer drug therapy, which are utilized across different tumors, often in combination to provide each patient the best chance of beating their disease. XPOVIO, which specifically targets a protein called XPO1, is the first approved anti-cancer drug whose primary activity is the activation of tumor suppressor proteins. There are about 20 of these tumor suppressor proteins including p53, BRCA1 and 2, retinoblastoma protein and the inhibitor of NF kappa B, which is called I kappa B. These tumor suppressors are a critical part of each cell's own natural defense mechanism to detect cancerous DNA changes and prevent the generation of malignant cells. In short, XPOVIO could direct a cell, which has become cancerous to commit suicide and potentially improve outcomes for a large variety of cancers.
Moving now to Slide 12. Over the past 5 years, it's become increasingly evident that the overexpression of XPO1 plays a critical role in oncogenesis, largely by removing tumor suppressor proteins from a cell nucleus where they normally function. And high XPO1 levels are associated with resistance to various therapies, including IMiDs and proteasome inhibitors. XPOVIO forces the retention of tumor suppressor proteins in the nucleus, restoring their function. This is why we've developed such a broad clinical program for XPOVIO across many different tumor types. By inhibiting the XPO1 protein, XPOVIO also traps oncoprotein messenger RNAs in the nucleus, preventing the translation and leading to reduced oncoprotein levels. It also retains activated glucocorticoid receptor in the nucleus, which can help increase its activity as an anticancer agent.
Next, I'd like to highlight XPOVIO's specific opportunity in patients with previously treated myeloma. On Slide 14, you will see that there are currently about 130,000 patients living with and battling myeloma in the U.S. alone. And importantly, you'll get a sense of just how much larger this expanded patient population is for XPOVIO's new indication relative to its previously approved penta-refractory indication. In 2020, they were estimated to be over 20,000 patients with myeloma being treated in the second-line setting and over 12,000 patients treated in the third line as well as more than 6,000 in the fourth line plus setting.
So XPOVIO's December 2020 FDA approval, based on the BOSTON study, expands the addressable patient population by fivefold. Additionally, these numbers continue to grow each year due to both the increasing incidents of myeloma, but also because newer and more effective myeloma drugs are keeping patients alive longer, which is a wonderful achievement for the greater myeloma community. The patients now available in the second- and third-line settings greatly expand on the prior indication of XPOVIO, which was restricted to only penta-refractory myeloma, typically patients treated with at least 4 or more lines of therapy.
As we move to Slide 15, I'll briefly highlight some of the key differences between the STORM study, which served as the basis for XPOVIO's 2019 accelerated approval in patients with penta-refractory disease as compared to the BOSTON study, which supported the recent expanded approval. As you can see, the patients who participated in the BOSTON study had received far fewer therapies than the patients in STORM, and consequently had myeloma that was far less refractory to treatment. Specifically, patients in BOSTON had a median of 2 prior therapies as compared to 8 in STORM. In BOSTON, the median progression-free survival and time on selinexor was substantially longer than that in the STORM study.
This was also driven by the mechanistic approach of combining 2 drugs with different mechanism of action in BOSTON as XPOVIO, our XPO1 inhibitor, was given in combination with once-weekly Velcade, a proteasome inhibitor, along with dexamethasone. And to reiterate, the average duration of treatment was 10 months in the BOSTON study as compared to 3 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 myeloma. We believe the greatest utility for XPOVIO in the future will be as a combination therapy with other potent anti-myeloma drugs, including Velcade. And now the combination of XPOVIO with Pomalyst and separately with Darzalex have been added to the NCCN guidelines, along with the FDA-approved Velcade combination. We hope that additional XPOVIO combinations will be added to the NCCN and other compendia listings in the future.
On Slide 16, I'll highlight the impressive efficacy data seen in the BOSTON study, which helped support XPOVIO's expanded approval and as published in The Lancet. Once-weekly oral XPOVIO plus once-weekly Velcade and low-dose dexamethasone delivered an early and sustained progression-free survival advantage compared to twice-weekly Velcade with moderate dose dexamethasone. More specifically, the XVd regimen demonstrated a 30% reduction in the risk of disease progression or death and demonstrated a median PFS of 13.9 months compared to 9.5 months in the Vd arm. And only 1 of the nearly 200 patients on the Vd arm in BOSTON progressed as compared to 10 on the Vd arm.
And what makes these results even more impressive is that in the study arm with XPOVIO, Velcade was dosed at only once per week. So the patient received approximately 40% less Velcade and 25% less dexamethasone as compared with the control arm. In addition, patients receiving XPOVIO had approximately 35% fewer clinic visits compared to those receiving the standard twice-weekly Velcade regimen. In fact, this is the first Phase III trial of a Velcade-based regimen for relapsed myeloma that used only once-weekly Velcade in the experimental arm. This is critical because many physicians employ only weekly vacating combinations in clinical practice, so the BOSTON trial results are directly applicable to real-world regimens.
Additionally, the depth of response observed with once-weekly XPOVIO plus Vd was significant versus twice-weekly Vd. The overall response rate was 76% on ex-Vd versus 62.3% on Vd. And the deep responses were much higher on the XVd arm as compared to the Vd arm. The higher response rate on XVd were observed regardless of prior therapies, the presence of high-risk cytogenetics, renal impairment or age, which will be very important as our commercial team now goes out to educate treating physicians on XPOVIO's updated indication and label. Finally, we note that the once-weekly XVd regimen appears to require the fewest total number of drugs and potentially the least amount of time in the clinic as compared with many other regimens approved to treat relapsed myeloma. Adverse reactions in at least 20% of the patients who received XVd in Boston included fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory infection, decrease weight, cataracts and vomiting. Grade 3, 4 laboratory abnormalities that occurred in more than 10% of patients on XVd with thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia neutropenia.
Moving now to Slide 19. As you may know, there are currently a number of different therapeutic options available to previously treated myeloma patients. So it will be critical for Karyopharm to clearly highlight the key unmet medical need that XPOVIO can help address. Importantly, in myeloma, many experts believe that treating with different mechanisms as early as possible is vital for long-term success. And thus, one of the key advantage XPOVIO brings is a novel mechanism of action that is synergistic with a proteasome inhibitor, like Velcade. But the primary focus of our messaging will be on the efficacy and safety that once-weekly XPOVIO plus Velcade and dex demonstrated in the pivotal BOSTON study. The weekly XPOVIO and Vd compared to rapid and sustained benefit, and this was achieved across patients with variety of cytogenetics, renal impairment, prior therapeutic exposure or age. And of course, XPOVIO is the first and only FDA-approved XPO1 inhibitor that works on the cells nucleus, leading to cell cycle arrest and in cancer cells, apoptosis. In fact, it's the first new mechanism approved since 2016 for the treatment of relapsed myeloma.
Another important feature for the once-weekly oral XPOVIO plus Vd regimen is that it can reduce the burden of having to come to the physician's office or hospital clinic for twice-weekly Velcade injections. Moreover, many patients prefer an oral drug to other options that may require intravenous infusions at the hospital or physician's office, and which means that many hours are spent in the clinic and traveling to and from. We also want to point out that our discussions with health care professionals will include the manageable safety profile that weekly XPOVIO plus Vd offers to a broad range of patients, with side effects that are typically reversible and manageable with dose modifications and standard supportive care. Furthermore, we know that the data from BOSTON were quite strong across nearly all of the subpopulations, including patients older than 65 years of age and those who are considered frail.
Finally, let me explicitly highlight on Slide 20 the kinds of patients that we believe physicians are most likely to consider for treatment of the newly approved XVd regimen. These include patients who have received Revlimid and Darzalex in the frontline setting and are Velcade naive when they first relapse, and patients who received only a short or course of Velcade in their previous treatment. With our new review of opportunity in myeloma now complete, I'll now highlight our current approach to the treatment of patients with DLBCL, which begins on Slide 22.
Our strategy in DLBCL is to position XPOVIO as a preferred DLBCL option after 2 prior lines of therapy instead of traditional intravenous chemotherapy by educating physicians on the deep and durable efficacy achieved in clinical studies with oral single agent novel XPOVIO. The most important feature of XPOVIO is its clinical activity, which resulted in meaningful and deep responses as illustrated by the results of the SADAL study. XPOVIO offers physicians and patients a novel mechanism of action to target the disease versus reusing therapy, efficacy seen across both ABC and GCB DLBCL subtypes, a manageable safety profile that does not include organ toxicities and an oral single agent treatment option that can be taken at home. Of course, we're just beginning to see where XPOVIO can impact the lives of patients battling cancer.
And now beginning on Slide 25, I'll update on some of our key pipeline programs and plans, particularly in solid tumors. Here you see our current and planned trials in the hematologic space in myeloma, DLBCL and myelofibrosis. And I'll highlight a new Phase III trial in myeloma that we plan to start in 2021, which includes XPOVIO plus Pomalyst plus dexamethasone, an all-oral regimen.
Next, while I don't have a lot of time to talk today about our plans and strategy for clinical development in solid tumors, it's important to see on Slide 26 the broader plans for XPOVIO, where we're currently studying it across a number of solid tumor indications, including in the Phase III SIENDO study as frontline maintenance therapy in endometrial cancer. And we have a variety of different trials that we'll be starting in the near future.
I'd also like to briefly highlight our Phase III SEAL study in patients with heavily pretreated dedifferentiated liposarcoma, which was recently reported to be positive with a hazard ratio of 0.7 and a p-value of 0.023. We believe that these results further support XPOVIO's substantial potential across multiple solid tumors, representing a major advance for the development and commercial of potential of XPOVIO in oncology more generally.
Now I'd like to provide an overview of some of the other recent developments and next steps for Karyopharm in 2021, beginning on Slide 29. First, we recently announced a Phase III SIENDO study following frontline chemotherapy in patients with endometrial cancer has passed its planned interim analysis, where the data safety monitoring board has recommended the study should continue without the need for additional patients to the trial or amending the study protocol. Top line data are expected in the second half of 2021. In Europe, based on ongoing discussions with CHMP, we now expect a final opinion on the MAA requesting conditional approval for patients with heavily pretreated myeloma by February of 2021. The following receipt of CHMP's opinion, we expect to submit a second MAA based on the data from the BOSTON study shortly thereafter. And then given the positive results on the SEAL study, Karyopharm is currently evaluating the optimal approach and next steps toward making XPOVIO available to patients with differentiated liposarcoma, including cost, commercial potential, compendia listings and regulatory strategy. We'll update our plans in the next several months.
And as we move to Slide 30, I'll highlight a number of commercial collaborations that we already established in the Asia Pacific region with Antengene in Israel and now in Canada, where we just announced our partnership with FORUS Therapeutics.
As you can see now on Slide 31, our cash position remains strong with an estimated $277 million in cash at the end of December of 2020, providing us with a cash runway expected to be sufficient to fund planned operations into at least late 2022, which is a bit longer than our previously stated guidance. Additionally, this cash guidance does not include any potential future partnership revenue, which we could receive from currently unpartnered, yet available, international territories.
Before moving to the Q&A session, let me highlight the next couple of priorities in 2021 and '22. First and foremost, we intend to increase the impact we're having on patients battling cancers. We're actively in the process of launching XPOVIO into the second- and third-line settings in myeloma and we hope to see a substantial increase in annual sales, largely driven by the earlier use and longer duration. Next, we expect initial approvals and commercial launch of XPOVIO in Europe and other international markets as well as the readout of the top line data from the Phase III SIENDO study in endometrial cancer. And finally, we expect to continued clinical development for XPOVIO, eltanexor and KPT-9274 in additional cancer indications. And over the next few years, after this, we expect additional indications approval for XPOVIO, including in solid tumors across both the U.S. and international markets. We also expect to see meaningful revenue contribution from royalties and milestones for international XPOVIO sales.
In summary, we believe the future is extremely bright for Karyopharm and the patients. We hope to help treat, and we look forward to updating the investment community as we continue to make progress on our 2021 goals.
Thanks for spending the last 20 minutes hearing about both Karyopharm's recent progress as well as learning about our exciting plans for the future. And with that, I look forward to moving on to the question-and-answer portion of today's program. Thank you very much.
================================================================================
Questions and Answers
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [1]
--------------------------------------------------------------------------------
Great. Thanks, Michael, for that presentation and overview. Maybe just to start off Q&A here. Just picking up on XPOVIO commercial in the fourth quarter sales trend. A little lighter than expected. You kind of highlighted some of the headwinds that you're experiencing. Maybe I could get you to elaborate on those a little bit further. I guess, are the challenges that you're seeing with respect to patients' ability to access care. Is that sort of common or uniform across various lines of treatment? Or is it sort of more heavily weighted towards the penta-refractory patient population? And to what extent do you see yourselves being able to sort of overcome some of those challenges in the first half of '21?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [2]
--------------------------------------------------------------------------------
Yes. Maybe I'll start with Ian and John can pick it up.
--------------------------------------------------------------------------------
Ian Karp, Karyopharm Therapeutics Inc. - SVP of Investor & Public Relations [3]
--------------------------------------------------------------------------------
Yes. No. Thanks very much, Eric. I think, ultimately, there certainly was some pressure, particularly in October and November. As the surge in COVID in the U.S. really picked up, and that really had an effect, I think, both on the number of -- and the frequency of visits that patients have to their health care providers, but also on a company like Karyopharm, really any pharmaceutical companies' ability to have their sales force in person meet with customers, which had, in fact, begun to pick up over the summer, but then was set back a bit with the surge in the fall. We were quite pleased to see a nice return to growth in December on the back of, as Michael mentioned, NCCN guideline updates as well as the expanded approval towards the end of February. So we feel good about certainly how the quarter ended, but it just wasn't quite enough to make up for some of the weakness that we saw in October, November. I don't know, John, if you want to anything to that as well.
--------------------------------------------------------------------------------
John Demaree, Karyopharm Therapeutics Inc. - Chief Commercial Officer [4]
--------------------------------------------------------------------------------
And we look at a number of different secondary data sources, Eric, to look at patient volumes and patient seen. It's hard to break that out by line of therapy. In general, we do know there was pressure on patient visits based on the pandemic and getting in to see their physicians, hard to break that out specifically by line of therapy.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [5]
--------------------------------------------------------------------------------
Got it. Okay. Okay. And I guess, on the commentary around some of the competition that you're seeing. Is that specific to competition with other commercial products? Is that competition for patients in clinical trials in the penta-refractory setting? Can you just elaborate on that?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [6]
--------------------------------------------------------------------------------
John -- Ian, you want to take that? Or John?
--------------------------------------------------------------------------------
John Demaree, Karyopharm Therapeutics Inc. - Chief Commercial Officer [7]
--------------------------------------------------------------------------------
Yes, I'm glad to start. The competition we're referring to, Eric, is primarily commercialized assets. There were 2 new competitors introduced that did take some patients in the late-line setting as doctors tried those products. And we saw the impact on that, particularly in October and November. Again, as Michael mentioned, we did see sales recover and start resume growth in the month of December.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [8]
--------------------------------------------------------------------------------
Okay. Okay. I know -- as sort of, John, picking up on your comments that visibility by line of therapy can be a little bit tricky. But as you -- how do you triangulate, I guess, to get a sense of what the reception is with the label expansion for the BOSTON indication? And sort of how you -- are you able to track sort of the dynamic -- sorry, the pull through that's in that specific, let's call it, second- or third-line setting, apart from just seeing the expected growth in volume?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [9]
--------------------------------------------------------------------------------
John, do you want to take that?
--------------------------------------------------------------------------------
John Demaree, Karyopharm Therapeutics Inc. - Chief Commercial Officer [10]
--------------------------------------------------------------------------------
I'm glad to take that. The answer is absolutely. When I mentioned difficulty by line of therapy, that's just looking -- that was just specific to visits and how visits were down because of COVID-19. In terms of our performance by line of therapy, that is something we track. And we look at a number of different secondary share metrics and data sources to look at our share, for instance, in the penta-refractory setting. We're also looking at our source now and second -- our shares in the second- and third-line setting as we go forward using a number of different data sources. We also track that obviously in DLBCL. So we can see our business by line of therapy. We can also see our business by whether it's a doublet combination. Like we saw with STORM Data Xd or we're able to now transition more to the triplet combination with the XVd combo.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [11]
--------------------------------------------------------------------------------
Having sort of identified that rev Darzalex experienced patient population, right, as where you want -- where you think there's really good fit with SVd as a second-line therapy. I guess, can you help us sort of triangulate the size of that addressable patient population? I guess what penetration does rev Darzalex kind of currently happen in that first-line setting?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [12]
--------------------------------------------------------------------------------
John, you want to handle that?
--------------------------------------------------------------------------------
John Demaree, Karyopharm Therapeutics Inc. - Chief Commercial Officer [13]
--------------------------------------------------------------------------------
Yes. So the most used regimen by far currently in the U.S. marketplace is RVd. So Darzalex is not most commonly used in the first-line setting, but is the most used agent in the second-line setting today. And as we talked to physicians, we are able to leverage the currently ingrained behavior that they already have. They want to switch classes. They want to use the different backbone therapies early in a patient's course of disease, which positions XPOVIO as a new backbone in combination with Velcade very well for either a second line patient, for certain types of patients or a third-line patient.
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [14]
--------------------------------------------------------------------------------
Yes. To the -- just to add to that, Eric, to the extent that DRD is growing in the community because it doesn't really have long-term toxicities. And there's no neuro -- there is much less neuropathy with DRD than DVD. We think we're uniquely positioned really to be in that perfect second-line setting as the first partner with Velcade, particularly as our data are directly addressable to current practice, which is once-weekly Velcade.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [15]
--------------------------------------------------------------------------------
Okay. Okay. And I guess the guidance for the lack of a better word when it comes to EU, the European regulatory situation sounds on track. I guess, any incremental thoughts internally as to how to pursue that opportunity commercially. And to what extent, is there potential for not only myeloma registration and commercialization, but also in DLBCL or is that subject to additional registration type of drop?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [16]
--------------------------------------------------------------------------------
Sure. Let me start off with that. The main focus in Europe has to be the BOSTON population and the approval there. We do hope to get the STORM approval that is in the refractory group with the current review, really for 2 reasons. One is we think these patients deserve an option to receive a novel therapy, which as a quick aside, you may know has shown very positive survival benefit in 2 case report studies or 2 case cohort studies published with the Flatiron and the -- and the MAMMOTH cohorts suggesting that not getting XPOVIO really is associated with a lower survival overall. So we do want patients to have access to that.
But also the -- if STORM is approved, it will allow a 6-month shorter review period for the BOSTON population. The size of the storm population and the DLBCL population in Europe, pale in comparison to that BOSTON population. So we're really focused initially in getting out there in BOSTON. And our hope is that we can get the STORM approved. And then BOSTON will be officially submitted as a separate MAA, follow-on MAA in February, and then we would have about a 6-month turnaround on the review. Does that help clarify it?
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [17]
--------------------------------------------------------------------------------
Yes. Well, I guess, you have that and then just sort of looking beyond potential approvals in terms of accessing the market. Is it -- you've talked about different options that you might pursue, a go alone strategy, a partner strategy. I guess, has that been refined? Or is that still evolving -- so thinking sort of evolving that.
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [18]
--------------------------------------------------------------------------------
Yes. Let me turn it to Mike for that, Mike Mason, for that.
--------------------------------------------------------------------------------
Michael P. Mason, Karyopharm Therapeutics Inc. - Senior VP, CFO & Treasurer [19]
--------------------------------------------------------------------------------
Sure. Yes. I think, Eric, if you asked that question a year ago, certainly would have reserved the right to kind of look both ways, right? Whether do -- some sort of stage build on our own, obviously, versus a partner track. In the COVID environment, it certainly seems a little more daunting to do something on our own versus a true all license. Just remember, Japan is also available, so -- but the goal for us is to be ready commercially upon BOSTON approval in Europe, whether that's summer or early 22, that's really the target.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [20]
--------------------------------------------------------------------------------
Okay. Okay. Great. Great. Yes. I guess in thinking about the upstream opportunity in DLBCL, right, without being abled by the 030 trials getting underway. Can -- I guess, is there -- at this point, are you able to sort of help shape timelines, timeline expectations there? And what level of benefit relative to GDP alone on either best overall response or PFS sort of might inform next steps or the decision to move forward with a Phase III study -- Phase III trial?
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [21]
--------------------------------------------------------------------------------
Sure. It's a Phase II/III study. So it's sort of built-in to go into Phase III immediately. In the Phase II portion, we're looking at 2 different doses of XPOVIO, 40 milligrams weekly or 60 milligrams weekly, which is useful. And then against the standard GDP with our rituximab alone. And I think a hazard ratio in the 0.7 neighborhood is always a great effect to have in these kinds of diseases. Especially with a therapy that you can't give continuously. So it's important to remember that all of these chemotherapies are given for 6 weeks -- 6 cycles typically or less. And then you have to stop them. But the XPOVIO will be continued, and there is a maintenance component in that trial, which would be a very unique approach in that kind of a situation. So I don't have any timelines yet. We're definitely being affected in terms of accrual, we're definitely affected by COVID. Things will become a lot clearer once the vaccines are better distributed and things start to get back to normal later this year.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [22]
--------------------------------------------------------------------------------
Okay. Okay. Great. Maybe just a final question in endometrial, it's the Phase III SIENDO trial, just sort of set the stage there in terms of where accrual currently stands and sort of time line sort of to read out? And I guess, how we should be -- what would stand as a meaningful benefit on time to -- excuse me, I guess, time to progression, I guess, is what we focus on here.
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [23]
--------------------------------------------------------------------------------
Yes. Got it. So again, the hazard ratio in that particular trial, which is a maintenance study. So just to clarify for everybody, this is a trial for patients who have been treated with frontline platinum based chemotherapy, typically platinum taxol, who have at least a partial response that's about 80% of the patients. So about 80% of the 14,000 patients who are diagnosed with this disease would be eligible for this therapy. Right now, unfortunately, all the patients will progress. Overall, it's about a 4- to 5-month PFS median right now with no additional treatment, and there is no additional treatment in the maintenance setting. So taking a page out of the playbook from the PARP inhibitors, which came into the maintenance setting after first-line ovarian cancer treatment. We're looking at this trial.
Again, the hazard ratio here, target is 0.6, so moving from about 4 months to about 6 or 7 months. And we think this would be a very important benefit for patients. We'll also be able to look at the tail. We're using once a week XPOVIO versus placebo, and it's a blinded study. And the real beauty of this study is we don't have to worry about the specific type of uterine cancer this is. This is just for patients who have chromosomally stable uterine cancer, where a PD-1 inhibitor is not indicated. That's about 85% of these patients to begin with. The trial accrual is good. COVID luckily hasn't had much effect on it, partly because once you start down the therapeutic path, you really need to continue it. And we do expect to have data by the end of this year, top line data, and we'll be filing next year on this indication if the data are positive.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [24]
--------------------------------------------------------------------------------
All right. Great. Well, thanks so much, again, guys for your time this afternoon, been really helpful, really informative. And thanks, everybody, for tuning into the webcast. Everybody, have a great evening.
--------------------------------------------------------------------------------
Michael G. Kauffman, Karyopharm Therapeutics Inc. - Co-Founder, CEO & Director [25]
--------------------------------------------------------------------------------
Thanks very much, Eric. Be well.
--------------------------------------------------------------------------------
Eric William Joseph, JPMorgan Chase & Co, Research Division - VP & Senior Analyst [26]
--------------------------------------------------------------------------------
Thank you.
