Karyopharm Therapeutics Inc. Q1 FY2020 Earnings Call

Good morning. My name is Patrice, and I’ll be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics' First Quarter 2020 Financial Results Conference Call. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, Karyopharm's Vice President, Investor and Public Relations.

Thank you, Patrice. And thank you all for joining us on today's conference call to discuss Karyopharm's first 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 and Mr. Perry Monaco, Senior Vice President of Sales. On the call today, Dr. Kauffman and John will provide an overview of key recent corporate developments and an update on our commercial progress. Mike Mason will then highlight the first quarter 2020 financial results, and we'll conclude with the Q&A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the first quarter of 2020. This release, along with a slide presentation that we plan to reference, are available on our website 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 related 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 disclosed in the risk factor 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 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 any references we make to clinical trial data during today's discussion refer to interim unaudited site data, unless otherwise specified.

Thank you, Ian, and good morning, everyone. Despite these challenging times, I just want to share a couple of thoughts that I'm extremely proud to be part of this organization. It has been a remarkable several months now. Keep in mind that we are actively in dialogue with the FDA on our supplementary NDA for our SADAL study in patients with relapsed or refractory diffuse large B-cell lymphoma, and we've been working extremely hard to deliver the highest-quality supplementary NDA for the BOSTON trial for patients who have been previously treated for multiple myeloma. We are very pleased to report that this NDA will be submitted before the end of this month. And in the meantime, following some extremely strong scientific preclinical and clinical observations, we've developed an internal virology program focused on the SARS-CoV-2, which causes COVID-19. In less than six weeks from conception, along with several independent external scientific reports, we've initiated a randomized Phase 2 study in patients with severe COVID-19. What's even more remarkable about this program is the strength of the scientific foundation on which it’s built. And this foundation has supported the rapid regulatory approvals and excited a large number of hospitals across the world to join this study in short order. Now of course, it's still too early to know if low-dose selinexor will prove effective against SARS-CoV-2, but we remain cautiously optimistic. And I frankly could not be prouder of our employees and partners around the globe who work with remarkable urgency to initiate this study and help us make a difference during these unprecedented times. Now in the setting of these specific challenges created by the COVID-19 pandemic, we've still been extremely productive on the commercial, clinical, and corporate development fronts, and we expect this to be yet another transformational year for our company. For those following along with the slide presentation, please now turn to Slide 4. First quarter XPOVIO sales were $16.1 million with total revenues reaching $18.1 million. We did experience a 9% decrease in XPOVIO sales compared to the fourth quarter of 2019, but the decline was primarily due to minimal channel inventory built in the first quarter as compared to the previous two quarters as well as market effects from the COVID-19 pandemic, which primarily impacted the volume of new patient starts in the quarter. Importantly, we did see more than 150 new physician accounts prescribe XPOVIO for the first time in the quarter, and we saw demand for XPOVIO accelerate in April. The most significant event in the quarter was the positive top-line result from the Phase 3 BOSTON study. Our randomized trial of once-weekly selinexor, bortezomib, and dexamethasone against standard twice-weekly bortezomib and dexamethasone. The trial met its primary endpoint with a statistically significant increase in progression-free survival. This is now the first randomized Phase 3 trial to demonstrate clinically significant activity of once-weekly XPOVIO in combination with once-weekly bortezomib over a current standard-of-care anti-myeloma treatment in patients who have previously received one to three prior therapies. We believe these results represent significant events with a highly convenient, once-weekly regimen, our so-called BOSTON SVd regimen for patients with previously treated myeloma. The study results will be disclosed in an oral presentation at the upcoming ASCO 2020 Virtual Scientific Program at the end of May. As mentioned, we expect to submit a supplemental new drug application to the U.S. FDA by the end of this month, a bit earlier than originally planned. In addition, our sNDA for XPOVIO for patients with relapsed or refractory DLBCL after at least two prior lines of therapy received priority review from the FDA, and our application remains on track with an assigned PDUFA action date of June 23, 2020. On the corporate development front, we have improved our strategic position to enable future access of XPOVIO to markets outside of the U.S. Specifically, we amended our agreement with Antengene, our partner in China, to expand their exclusive rights to develop and commercialize selinexor and eltanexor in all human oncology indications in Australia, South Korea, and additional Asian Pacific markets, excluding Japan. Under the terms of the amended agreement, we will receive an upfront payment of $12 million in the second quarter of 2020 and are eligible for additional future milestone payments and royalties. Certain countries included in the expanded Antengene territory became available at no cost to Karyopharm, following our reacquisition of the exclusive development and commercial rights from Ono Pharmaceuticals last month. Importantly, in addition to the U.S. and Europe, we now retain the full rights to selinexor and eltanexor in Japan, following our reacquisition of these rights from Ono, again, at no cost to Karyopharm.

Thank you, Michael. And let me first begin by saying how excited I am to be leading the Karyopharm commercial organization on behalf of the patients who may benefit from our medicines now and in the future, and the healthcare providers who care for them. These are truly exciting times for Karyopharm, and I'm thrilled to have joined the team. The launch to date for XPOVIO has been strong. As of March 31, more than 2,200 XPOVIO prescriptions have been filled in the U.S. since launch, which highlights the unmet medical need that XPOVIO is addressing. When looking at the sales for the first quarter, there are three important components to consider: inventory, new patient starts, and how existing patients are doing in terms of refills and duration of therapy. First, as Michael mentioned, the inventory build was negligible in Q1 as compared to Q4. As we launched, it took a couple of quarters for our distributors to build inventory levels to meet the ongoing needs of their customers, and as expected, these levels did not grow meaningfully in the first quarter of 2020. Second, despite the impact of COVID-19, we were able to maintain approximately flat demand in Q1 with 845 prescriptions, although new patient starts on XPOVIO were fewer than anticipated with fewer new patient visits to oncologists and fewer patients starting on new therapies. Third, importantly, we continue to see strong prescription refill rates for existing patients and an increasing average number of cycles per patient. Finally, we did see a good increase in XPOVIO prescription demand in April, which is encouraging as we continue to assess the ongoing impact of the COVID-19 pandemic. Slide 6 provides more detail on how existing patients are doing. I'm pleased to report that the XPOVIO real-world patient experience continues to be strong, often exceeding what was seen in the pivotal STORM trial. On the right side of this slide, we've highlighted several important metrics from our network of specialty pharmacy providers, which give us confidence that patients are having a positive experience on XPOVIO. First, we are pleased that more than 97% of prescriptions are being approved by insurance carriers. This approval rate underscores the terrific work that our market access team has been doing since launch to ensure broad and unencumbered access. Next, approximately 60% of eligible patients since launch have received a refill for their second prescription, and the per-patient average number of prescriptions continues to increase each quarter. One of the key factors that we believe is contributing to these refill rates has been our ability to educate healthcare providers regarding which patients are appropriate for XPOVIO. Also, only 13% of patients who have discontinued XPOVIO have indicated the reason was due to side effects. We believe our education efforts here on appropriate mitigation of side effects are improving the patient experience. This is particularly encouraging as we saw 27% of patients in the STORM study discontinue therapy due to side effects. Finally, across all prescription refills, we're seeing patients refill their prescriptions in about 34 days on average. This indicates that the XPOVIO package and dose sizes available are appropriate, and patients are not extending monthly dose packs much beyond 30 days. Moving to Slide 7, there are several COVID-19 dynamics that impact sales in the first quarter, as well as potential advantages of XPOVIO to patients in the context of the ongoing pandemic. The COVID-19 pandemic has unfortunately negatively impacted patient care with many physician practices, including oncologists, reporting fewer visits for patients without COVID-19. This reduction in visits had a particularly notable impact on the volume of new patient starts on XPOVIO in March. Additionally, just like other biopharmaceutical companies, our field sales force has been unable to make in-person calls to healthcare providers and have been working from home since the beginning of March. Because newly launched products in general require greater physician education before they are broadly adopted as compared to more established therapies and brands, we believe new patient starts were further impacted. In these current market conditions, XPOVIO's product profile offers some distinct advantages for myeloma patients, including oral administration and home delivery, which may limit the need to travel to hospitals or clinics as frequently as commonly used parenteral therapies. Supportive care resources are also available over the phone via our carry forward patient support programs. Finally, our commercial organization has made tremendous progress over the past few months to mitigate some of these pressures just highlighted and leverage the competitive advantages of XPOVIO. These are highlighted on Slide 8 and include rapidly launching multiple digital tools to facilitate continued sales force engagement with customers. According to a leading industry market insights provider, our sales force engagement remains the best among our peer group. We've also transitioned peer-to-peer programs to virtual channels in order to expand our commercial reach. We're increasing non-personal promotion via electronic medical record information at the point of diagnosis, search engine marketing, and media placement. Finally, we're actively preparing for a virtual omnichannel launch for XPOVIO in diffuse large B-cell lymphoma pending FDA approval.

Thank you, John. On Slide 9, you can see the topline results from the Phase 3 BOSTON study. The study met its primary endpoint of a statistically significant improvement in PFS with a 47% increase in median PFS on the SVd arm as compared to the Vd arm, representing a 4.47 month improvement. The median PFS in the SVd arm was 13.93 months versus 9.46 months in the Vd arm, and the hazard ratio was 0.70. We believe this topline data represents a very meaningful improvement of PFS in the treatment of patients with previously treated myeloma. Because patients in the SVd arm received Velcade only once per week, while those in the Vd arm received Velcade on the standard twice-weekly schedule, the SVd arm received about 40% less Velcade and 25% less dexamethasone than in the Vd arm, and required about 37% fewer clinic visits over the course of treatment. The data also showed no new safety signals in the SVd arm relative to previously reported adverse events from our other selinexor myeloma trials. There was no imbalance in patient deaths across the treatment arms, and in fact, there were numerically fewer deaths in the SVd arm. Finally, we are also pleased to report that in the BOSTON study, the rate of peripheral neuropathy on the SVd arm was significantly lower than the rate in the Vd control arm. Remember that peripheral neuropathy is among the most common causes of treatment limitation and discontinuation of Velcade dex in combination Velcade dex regimens. We have seen particularly high rates of peripheral neuropathy in other Phase 3 trials, as noted on Slide 10. In that study, Vd as a control arm, often triplet-Vd regimens have even higher peripheral neuropathy rates than the standard backbone Vd. Turning on Slide 11, we believe the commercial opportunity for XPOVIO in the second and third line settings, subject, of course, to future regulatory approvals, represents a significant opportunity for Karyopharm, and more importantly, would meaningfully advance the treatment options available to patients battling myeloma. Specifically, there are approximately 32,000 patients treated in the second and third lines, which is dramatically larger than the number of patients in the fourth and later lines for XPOVIO as currently being prescribed based on its current FDA approved indication. In addition, we know that the average time patients with myeloma remain on any drug therapy, including XPOVIO, is much longer in earlier lines compared to later lines of therapy. I'd now like to spend a few minutes to discuss our new selinexor clinical program in patients with severe COVID-19, which begins on Slide 12. In addition to its roles in cancer, XPO1 may also be an important target in treating viral infections, by facilitating the transport of several important viral proteins from the nucleus of the host cell to the cytoplasm. Selinexor recently demonstrated potent anti-SARS-CoV-2 activity in cell cultures, with 100 nanomolar selinexor inhibiting viral replication by 90%. This is particularly exciting given that for patients taking the low 20 mg dose of selinexor, serum levels of the drug are expected to be over 300 nanomolar, suggesting that marked viral replication inhibition may be possible. In addition to its potential direct antiviral effects, selinexor and other compounds have demonstrated potent anti-inflammatory activity through the inhibition of nuclear factor kappa B. This is particularly relevant given that one of the most important aspects of COVID-19 is the marked pulmonary inflammation, with high levels of cytokines such as IL-6, IL-1, interferon gamma, and others. Selinexor or other compounds have shown reductions in all of these cytokines in a variety of models, and this may be particularly beneficial to hospitalized patients with severe COVID-19. Based on the strong scientific rationale in our highly motivated team, we're able to initiate and begin dosing patients in a global, randomized, multicenter, placebo-controlled study in April. The primary endpoint of the study is concrete clinical improvement based on an improvement on the ordinal scale consistent with COVID-19 trial recommendations. Additional secondary endpoints in the study include the overall death rate at day 28, as well as the rate of and time to mechanical ventilation. I am very proud of our team for advancing these programs so quickly, and we look forward to providing an update as quickly as possible. Finally, before I hand the call over to Mike Mason to highlight our financial results, I'd like to say a few words about our growing clinical development pipeline, which can be seen on Slide 14 and 15. For our other ongoing clinical trials, we do expect some delays in patient enrollment due to clinical site closures and disruptions caused by the pandemic. We will continue to update the investment community as we learn more about potential COVID-19 impact timelines, and remain committed to advancing our programs as expeditiously as possible. And with that, I'll now turn the call over to Mike Mason to review the financials. Mike?

Thank you, Michael. Since we issued a press release earlier today with the full financial results, I'll just focus on the highlights which begin on Slide 17. Net product revenue for the first quarter of 2020 was $16.1 million and total revenue was $18.1 million. As previously mentioned, first quarter sales were driven almost entirely by patient demand with minimal channel inventory build in the quarter. As a reminder, our distribution partners typically keep about three weeks of channel inventory on hand and in 2019 purchased approximately $4.5 million of selinexor to reach this level by the end of the year. Moving forward, we would expect channel inventory levels to only increase in line with increases in patient demand. The estimated gross net discount for XPOVIO in the first quarter was approximately 15%, which is on the lower end of our annual expectations of 15% to 20%. Research and Development expense for the first quarter of 2020 was $34 million, compared to $38 million for the first quarter of 2019. The decrease in R&D expenses compared to the first quarter of 2019 is mainly due to a decrease in clinical trial costs. We expect our R&D expenses to remain relatively consistent quarter-over-quarter for the remainder of the year. For the first quarter of 2020, SG&A expense was $30.7 million compared to $27.1 million for the first quarter of 2019. The increase in SG&A expenses compared to the prior year was primarily due to activities to support the U.S. commercialization of XPOVIO, and in preparation for the potential launch of additional indications. Cash, cash equivalents, and restricted cash on investment as of March 31, 2020 totaled $385.2 million, compared to $265.8 million as of December 31, 2019. Looking ahead, we expect XPOVIO net product sales to be slightly higher in the second quarter of 2020 as compared to the first quarter of 2020. In addition, we expect total revenue to be higher in the second quarter due to the recognition of the majority of the upfront payment we expect to receive from Antengene in the second quarter in connection with the amendment agreement to expand Antengene’s territory. We're not issuing full-year 2020 XPOVIO revenue guidance at the current time, as we continue to monitor the ongoing commercial impact from the COVID-19 pandemic, as well as timing of key expected regulatory actions in 2020. These regulatory events include the potential approval of XPOVIO for patients with relapsed or refractory DLBCL, as well as our planned sNDA submission and subsequent FDA review period, requesting expansion of the approved indications for XPOVIO to include second-line treatment for patients with relapsed or refractory multiple myeloma. Finally, based on our current operating plans, including the reduction of some R&D costs as a result of trial delays due to the ongoing COVID-19 pandemic and overall expense management, we expect our non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense, for the full year 2020 to be at the lower end of the previously projected range of $240 million to $260 million. This estimate includes the additional costs associated with our new selinexor clinical trial in patients with COVID-19. In addition, we currently expect that our existing cash, cash equivalents and investments and the revenue we expect to generate from XPOVIO product sales will be sufficient to fund our planned operations into the middle of 2022, which puts us in a terrific position to further advance our strategic aspirations. I'll now turn the call back over to Michael for some concluding remarks.

Thank you, Mike. Before moving to Q&A, let me highlight some of the key milestones we expect for the remainder of this year. Please see Slide 19. First, the BOSTON clinical data will be presented in an oral session at the upcoming ASCO-2020 Virtual Scientific Program, and we expect to submit an sNDA based on these data before the end of May. Next, we anticipate a regulatory decision in June regarding our XPOVIO sNDA for patients with DLBCL after at least two lines prior therapy, and then the subsequent commercial launch if approved. We also expect to share the initial results from our Phase 2 study of low dose selinexor in patients with severe COVID-19, as well as the topline Phase 3 data from the SEAL study in liposarcoma. Finally, should the FDA approve our anticipated sNDA based on the BOSTON data before the end of the year, we expect the U.S. commercial launch in second-line myeloma, either by the end of 2020 or early 2021, depending on the FDA's review timelines. As you can clearly see, we have a robust list of expected milestones across our commercial and clinical stage portfolios, and we look forward to providing updates throughout the remainder of the year. We appreciate your ongoing support and look forward to keeping you updated on our 2020 progress. I'll now turn the call over to the operator for questions.

Your first question comes from Maury Raycroft at Jefferies.

Hi, morning everyone, and thanks for taking my questions. First question is just based on the 60% number for patients not choosing to get the second prescription. And then you mentioned that 13% of those patients stopped because of side effects. I guess, what are the reasons for the other 27%, and can you improve upon the 13% and 27% numbers? And what are the plans to do that?

Yes. I'll let John handle that.

Yes. So it's actually 60% of patients are getting a refill, not 60% not getting a refill of the second prescription, which is a strong number. Relative to the 13% discontinuation rate, that was about half of what we saw in the STORM trial, which suggests the education efforts are working and physicians are getting comfortable mitigating potential side effects with XPOVIO to provide patients a better experience. Other drivers of discontinuation, the top three drivers would include as expected; prescriber decision, patient deceased, or patient decision.

Got it. That's helpful. And then for the 60%/40% numbers, can you provide any perspective into what line of treatment those patients are on? I guess, can you provide any more details on that?

Most of the patients that we're seeing today are in the indicated patient population, so in the penta-refractory setting. So, these are heavily pretreated, relapsed/refractory patients in multiple myeloma.

Got it. Okay. And then last question just on the increase in demand in April that you're seeing. I'm just wondering what the driver is for that? I guess, is that coming from states that are reopening because of COVID or is there something else fundamental that's driving that?

I'll let John handle that.

So, I think there could be a combination of factors there. We saw an initial drop-off in March, as the market started to react to the dynamics around COVID-19. The market started to adjust to that. And we did see a rebound in demand with demand being higher for patient prescriptions in April than in March. And I'll ask Perry, do you have anything to add to that?

No. I think you covered it, John, other than I would say that in terms of our refill rates have been strong, and I think a lot of that increased volume that we saw in April was due to those strong refills after accounts got kind of used to the COVID environment and the increase in telemedicine.

Yes. Just to add to that, I think there's more and more of the cancer societies recommending oral treatments for patients, so they can minimize their time at the clinic. Selinexor is really a unique drug in that regard with potent activity in the late-line setting. And obviously, oral administration means that many of the monitoring activities can be done easily at a typical laboratory. There's nothing particularly special about complete blood counts and so on.

Got it. Thanks for taking my questions. And I'll hop back in queue.

Your next question comes from Brian Abrahams, RBC Capital Markets.

Hey, guys, thanks very much for taking my questions. I wanted to drill down a little bit more to better understand the dynamics for XPOVIO here. So, in March, obviously there's the potential for COVID-19 impact to a launching drug, but you also have to have the benefits of oral administration, which can be an advantage in this environment, and you presented compelling results from the randomized BOSTON study. So I'm curious, your understanding as to why those latter tailwinds didn't necessarily offset the COVID-19 headwinds? And should we be sort of thinking about this as the initial bolus that you saw maybe in the fourth quarter and earlier represented? Just pent-up demand from very late-line patients, who would be on XPOVIO for very short durations, and now you could start to convert to sort of a more normalized rolling type of volume curve? And then I had a couple of follow-ups.

Let me take it, and then I'll send it over to John. Look, headlines come out all around, and reaction times are not immediate, of course. So, what happened, we think, is that even in the early stages of COVID spreading, February and March for sure, people just kind of put the brakes on. And as mentioned, drugs that are not well-ingrained and are new to people tend to go on the back burner for a bit. Now, all of that are, of course, headwinds for us. And then what happened is what you also said is that, we have an oral drug, and people are recognizing that they can be prescribed and sent directly to the patient. It makes it much easier for the patients to get it, and they can be laboratory monitored in an easy lab, local to the patient's home, followed by the doctor and physician’s assistant or nursing staff just calling the patient. So it really took – it was not an immediate effect that we saw on the tailwinds of this. The other thing is that many physicians, we're very glad to see the topline data, but all physicians are cautious and are waiting for the presentation which will be at ASCO. So we expect that to help. And I think people will start to get used to the new norm now, and we're starting to see a pickup in April with the tailwind starting to overcome the headwind.

To build on what Michael said, the headwinds from the data we saw in the marketplace were immediate. The patient drop-off in terms of visits to the oncologist and new patients starting therapy was almost immediate with the impact of COVID-19, where the tailwinds are a more gradual switch to moving to oral therapies. We expect to initiate marketing programs to continue to build on that over time. In regards to your question about the bolus, with over nine months of prescription data now, we do believe that we saw a slight bolus of patients in the early months for our launch, driven by the high unmet need for patients with penta-refractory disease. We believe the bolus was relatively small because, unfortunately, patients with penta-refractory disease have a short-life expectancy. So in order to continue growth going forward, it won't be based on a bolus, but it'll be based on the ability to generate new patient prescriptions in relapsed refractory multiple myeloma.

Got it. And just as a follow-up, so that's really helpful. Can you give us any more specific sense on how demand in April compared to pre-COVID months? And then, what should we be thinking about as we look towards the BOSTON presentation in terms of both key updates there and impact you might see on overall prescribing habits? Thanks.

Yes. Look, we're not going to say a lot about the details in April. It was a very good month. We're very happy to see it. We do believe it represents sort of a restart if you will, a new trajectory now that this norm situation has become a little bit more normal. Obviously, BOSTON getting out data in BOSTON, showing graphs, we think what we believe and our investigators believe are compelling data. I’ll reiterate real-world data, meaning, many of these trials with Velcade essentially all of them are done with twice weekly Velcade on both arms in relapsed myeloma. When the regimen is approved in the market, they're only using once weekly Velcade. So no one actually knows what to expect when you get that. I think that's important both on the front end and back end. Obviously, it's more convenient for patients to come in once a week. But we have no idea what the kind of disease control rate is. We’ll be looking hard at early disease control with this once weekly regimen because twice a week Velcade has very good disease control. It will be interesting to see what the SVd can do once weekly. I think, obviously, over the longer term, we had a significant PFS benefit, and we’ll be looking at response rates and deep responses as well. I think there will be a lot of data for people to look at, and I hope get comfortable with. Lastly, there’s been concern over the last year or two, given some of the difficulties with survival in patients with relapsed refractory myeloma. Some of the trials have run into trouble with negative survival or no improvement in survival. We’ve been able to say, without giving too much detail that we have a numerically smaller number of deaths on the SVd arm than the Vd arm. That is extremely important and somewhat unexpected given this is an early-stage trial in patients with one to three prior therapies. So, lots of good data to come out, and I think it will really make a robust foundation for selinexor, even for doctors who had questions after the initial approval.

That's really helpful. Thanks so much.

Your next question comes from Peter Lawson, Barclays.

Hi, thanks for taking the question. Just on inventory. How should we be thinking about it? Is there any way of kind of breaking out the prior inventory levels?

Sure. So what we said is in 2019 with the launch in Q3 and Q4, there was about $4.5 million of channel inventory buildup. We saw really no change in channel inventory in the first quarter. So we would expect that inventory number to stay about the same until we saw an increase on the patient demand side.

Great. And then is there any way of kind of helping us back out normalized growth? If you think about, I guess the initial bonus, COVID, and inventory, any other moving factors that we should be thinking about?

Yes. I think the normalized growth is something that we're still working to assess in the context of COVID-19. And it will depend on the impact of new patient starts going forward, and it's something we continue to monitor very closely.

And just Peter, keep in mind, there are a large number of variables here. There are the usual variables of a new drug, a new mechanism entering the market, add on to that a pending FDA review and hopefully approval in diffuse large B-cell lymphoma, topline Phase 3 data, and then a submission, hopefully followed by an approval later this year. Then slap on top of all that a pandemic which the world has never seen before. You end up with a very great difficulty in figuring out what's going on. We do feel like people have sort of reset and are starting to move forward now.

Thank you. And I guess the final question. Do you think the side effect profile or monitoring has impacted your scripts during social distancing? And are you seeing any kind of regional effects from the script levels?

So, on the monitoring side, we really don't see any impacts. Selinexor side effects that require laboratory monitoring are quite simple. Patients with highly-advanced refractory myeloma are often receiving these kinds of monitoring tests, which include a complete blood count and serum electrolyte levels weekly. They get them anyway, if not weekly, certainly every couple of weeks. After the first two cycles on selinexor dex, we recommend moving to less frequent blood testing. So there's really nothing new coming out here. The fact that these tests can easily be obtained from commercial laboratories, and people are moving to that makes it much easier to do. As far as your second question goes, I'd push that over to John. Can you repeat?

I was just thinking about regional differences you may be seeing from this impact from COVID.

Yes. We haven't seen a notable regional difference. We have seen continued strong news from both academic and community positions, and continue to see prescription demand from all regions across the country.

Great. Thanks so much.

Your next question comes from Jonathan Chang, SVB Leerink.

Good morning, and thanks for taking my questions. First question, can you provide any color on the month-to-month XPOVIO trends in the first quarter for Jan, Feb, March?

Hey, Jonathan. I think we're not going to get into specific details of monthly scripts or trends. I think, certainly what we've said and we'll continue to say is that, we were clearly impacted in March. We were very pleased to see a nice rebound and positive trajectory in April. And, we'll continue - obviously we're tracking May and we’ll track June. But it's still too early to really delve into kind of what we expect to see. We're encouraged that April was a very strong month.

Got it. Second question, can you help set expectations ahead of the ASCO BOSTON data? What kind of data should we be expecting in terms of additional efficacy and safety beyond the topline and in terms of the different patient subgroups?

Well, keeping in mind it’s a short presentation, we will pack in a lot of data on efficacy. We will provide the usual primary endpoint, of course, which is progression-free survival. The key secondary endpoints are overall response rate and overall survival. We actually have a key secondary endpoint of peripheral neuropathy rates, which was a pre-specified endpoint, very important, we believe, especially as we think about positioning this triplet. We will provide both safety updates and so on. It should be a pretty robust discussion. We do intend to provide some subgroup analyses, but it will be limited by the amount of time we have to present and so on. But we're excited about it. It should give a pretty good picture of what SVd can do.

Got it? And just one more. Can you provide more context on the reacquisition of rights in Japan from Ono? Thank you.

Sure. Yes. Hey, Jonathan. Happy to answer that. So, I think we all know given their internal strategic priorities regarding the pipeline programs they wanted to invest in, they opted to return their commercial rights to selinexor and eltanexor to Karyopharm, to allow us to advance the program in Japan and other Asian territory. I think what was largely fueling this is, in the U.S. and Europe there are accelerated our conditional approval programs. They don't have a similar program to take advantage of in Japan. So you really need large registrational trials in order to start moving into the commercial marketplace. So, in light of their other opportunities in their portfolio, they thought it made sense to give these rights back so we can maximize the program's potential.

Got it. Thank you.

Your next question comes from Mike Ulz, Baird.

Hey guys, thanks for taking the question. Maybe if you can just give us an update on the regulatory timelines in Europe for XPOVIO? In penta-refractory patients, it seems like there might be some modest delays there. And then, also, if you can just comment on your current thinking in terms of filing the BOSTON data for the U.S. as well. Thanks.

Yes, sure. So part of the discussions and requests from the Europeans was to remonitor certain data at sites across the world. Unfortunately, their EMA is well aware that there are some sites that are simply not accessible at the time. So we have a further extension of that by several months in order to allow us to enter those sites and do the requested remonitoring of data. We remain very confident that the data are strong and robust and don't anticipate any changes, but we need to go through the process again. So that'll be several months. We will be coordinating with EMA to file the BOSTON data in a way that works with the regulatory timelines and requirements in Europe.

Got it. Thank you.

Your next question comes from Arlinda Lee, Canaccord.

Thanks for taking my questions. Sorry if I missed this, but I was wondering on a couple of things on the inventory side. What kind of expectations do you have going forward on the levels of inventories now versus what you're planning to keep on hand going forward? And then curious on the demand side. The proportion of new prescribers that were maybe towards the end of last year that haven't really worked with you guys before. How is that looking in terms of dosing additional patients beyond the first one?

So, I'll take the first one. So on channel inventory in 2019, we built up about $4.5 million in inventory. The way it works is our distributors need approximately around three weeks of channel inventory, which is essentially what they had since demand was basically flat from Q4 to Q1, general inventory really didn't move in the first quarter. So we wouldn't expect channel increases until we saw demand increases.

And in terms of new prescribers in Q1, we did add more than 150 new accounts prescribing XPOVIO. We're excited about continuing to grow the breadth of physicians that are prescribing XPOVIO for the appropriate patients.

And then I guess, curious, but sorry, just following-up on the new accounts in 4Q. How many of those dosed additional patients in 1Q?

Yes. I don't think we have that data right at our fingertips. I would say maybe Perry can give some additional commentary. I think we're clearly seeing new physicians and new accounts prescribing XPOVIO for the first time. We're seeing physicians that have prescribed to one or two patients increase their number of prescriptions. We want to continue to encourage new physicians to try XPOVIO and get physicians who have only treated one or two patients to find additional patients that are appropriate to add to that. Of course, we have some accounts that are really quite comfortable with this drug and really see the value of it, and have dozens and dozens of patients on therapy. So we kind of run the gamut, but to break it down in terms of how many prescriptions came from each group and each quarter, that's not something we're going to detail at this time.

Okay. Thank you.

Your next question comes from Ed White, H.C. Wainwright.

Good morning. Thanks for taking my questions. So maybe just to follow up on Europe. Do you still expect to have the DLBCL submission coincide with the submission from the BOSTON data? And while delayed, could this still be a 2020 event?

I'll turn this over to Ian.

So the question I think is, correct me if I'm right, is how are we thinking about the submissions in Europe for the BOSTON data and DLBCL data, based on what's going on with EMA and the data. Is that the question, Ed?

Yes. That's correct.

Thanks, Ed. As I said, we're working with European regulators to sort this out. We're kind of in new territory, as are they, given the requests for re-monitoring sites that are not currently open and then coordinating the additional ones. We do intend to submit the BOSTON data in Europe in 2020. But we're just getting the exact timing will depend on how our conversations with the EMA go.

Okay. Thanks, Michael. And maybe you could just talk about your strategy? What your plans are to go it alone or to have a partner there and the timing of that? Is that also sometime in 2020, after approval? Or how does that work or after submission, or how does that work?

I'll send that over to Chris Primiano.

Sure, Ed. It's Chris. First of all, I think just to follow on my answer to the other question, we're excited about the potential opportunities that Japan rights hold for us. As we've said many times, we look for philosophical alignment with a partner, minimizing the number of partners, maximizing value to Karyopharm and access for patients. So when we think about Europe, as we said, we continue to assess the different options for potential commercialization. Now that we've regained the development of commercial rights in Japan, the potential options are certainly increased, and all of those could be a partnership. As we look forward to what this might look like, we would want somebody that aligns philosophically with us in terms of long-term development and commercialization plans for selinexor, and has expertise in marketing hematological malignancy drugs in the EU. We haven't closed the door to launching this on our own, but we are looking carefully at partnership opportunities, especially as options have expanded with the return of Japanese rights. We believe the value of selinexor will build over time as we progress through MAA as you mentioned, delayed by a couple of months. The important thing to remember is that in terms of the commercial opportunity, the most significant opportunity in Europe will come following approval from BOSTON. While we plan to continue having these conversations with partners over the near-term, we're also focused on the bigger picture, which is maximizing commercial value and understanding where that comes from. So we should have more to report soon as we keep that all planned.

And just wanted to ask a question on COVID delays. You had mentioned about the impact on your studies. You had the export studies in DLBCL in colorectal cancer, non-small cell lung cancer, and glioblastoma. Maybe if you could just give an update there as if they're able to get off the ground? And since these are newer studies, do you expect enrollment there to suffer more than your other studies that are currently ongoing? Thanks.

Yes. Dr. Sharon Shacham will take that.

So the study in colorectal cancer and lung is already ongoing. This study is done in Israel. As you might know, they are opening up, so we continue to enroll in that study throughout the pandemic. I hope enrollers will be able to pick up faster now that things are opening up. The GBM studies on glioblastoma will open in the U.S. very soon. So for the XPORT study in DLBCL, we are pushing this study along. This study will be done in the U.S. and EU. If we will have any delay so far, we are expecting small delays on that study.

Great. Thank you.

I'm showing no further questions at this time. I would now like to turn the conference back to CEO Michael Kauffman.

Thank you, everybody. Thanks for joining us today. Good luck, stay safe, and we'll talk soon. Bye-bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.