Karyopharm Therapeutics Inc (KPTI) 2017 Q4 法說會逐字稿

Good morning. My name is [Ayela], and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Fourth Quarter and Year End 2017 Financial Results Conference Call. (Operator Instructions). I would now like to turn the call over to Mr. Christopher Primiano, Chief Business Officer of Karyopharm Therapeutics.

Thank you, [Ayela], and thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter and year-end 2017 financial results. This is Chris Primiano, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer; Mr. Michael Falvey, Chief Financial Officer; Dr. Sharon Shacham, our Founder, President and Chief Scientific Officer; and Dr. Jatin Shah, Vice President, Clinical Strategy.

On the call today, Michael Kauffman will make some introductory comments and provide a short update on the clinical development programs and plans, then Mike Falvey will present -- will provide an overview of the fourth quarter and year-end 2017 financial results. Dr. Kauffman will then discuss our key upcoming milestones and provide some summary remarks. We will then open the call up for questions where Sharon, Jatin and I will also be available.

Earlier this morning we issued a press release detailing Karyopharm's results for the fourth quarter and full-year 2017. The release is 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 product candidates, financial projections, and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our quarterly report on Form 10-Q for the quarter ended September 30, 2017, which was filed with the SEC on November 2, 2017, and any other filings we may make with the SEC, including our annual report on Form 10-K for the year ended 2017, which we expect to file later today.

Any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent date. 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.

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

Thank you, Chris, and good morning, everyone. Thank you for joining us on today's call. Late 2017 and early 2018 were very active on advancing our clinical trials as well as on the business development front. During that time we executed 2 high value strategic transactions, one with Ono Pharmaceutical Company Limited for selinexor and eltanexor, and [enrollment of] Biogen for pipeline asset KPT-350.

In the first transaction, Ono licensed exclusive rights for the development and commercialization of our lead SINE compound, selinexor, and second generation SINE compound eltanexor for all human oncology indications in Japan, South Korea, Taiwan, Hong Kong and the ASEAN countries. This transaction which carries a total deal value of up to $193 million plus royalties brings us together with a leading oncology company and commercialization powerhouse in Japan.

Ono markets several blockbuster oncology drugs in Japan including Opdivo and Kyprolis, giving us specific expertise in multiple myeloma, Hodgkin's disease and a variety of different solid tumors, and make ideal partner to advance both selinexor and eltanexor in Japan and other licensed territories.

And the second transaction, Biogen acquired one of our pipeline assets, the oral SINE compound, KPT-350, for the treatment of certain neurological conditions including amyotrophic lateral sclerosis, ALS or Lou Gehrig's disease. For those of you who may not be familiar with KPT-350, it is a novel oral therapeutic candidate that works by inhibiting XPO1, which then results in reductions in both inflammation and neurotoxicity, and has demonstrated neuroprotective properties as demonstrated in several publications including 2, in Nature Neuroscience covering models of ALS and multiple sclerosis. This transaction which carries a total deal value of up to $217 million plus royalties (inaudible) Ono KPT-350 together with Biogen world-class capability and their expertise in the development and commercialization of products for neurological and neurodegenerative diseases. Collectively, we believe this 2 transactions provide important validation for our oral SINE compounds bringing in approximately [$32 million] in non-dilutive upfront funding. Individually, the Ono transaction is important because it allows us to remain focused on executing our [late phase] selinexor trials in the U.S. and EU, and pursuing regulatory approvals in those territories, while maximizing the global future potential of both compounds.

The Biogen transaction is significant because it may provide a new treatment modality for difficult neurological diseases, such as ALS, head trauma and others. The deal represents the execution of our broader strategy of partner, our non-core, non-oncology assets, while we focus our primary objective of pursuing regulatory approval for selinexor in the United States and Europe and transitioning towards the commercial stage enterprise.

And I'll turn to review our myeloma trials. For the ongoing Phase IIb STORM study, we remain on track to report top-line response data at the end of April. This is our most anticipated near-term data readout and milestone. We call the STORM is evaluating selinexor with low dose dexamethasone. The oral [Sel-Dex] regimen in patients with so called penta-refractory myeloma, which we believe represents a significant unmet medical need. If we continue to see the robust responses and durability that we reported at ASH 2016 and published recently in the Journal of Clinical Oncology in January. We intend to submit the full STORM data to U.S. FDA in the second half of 2018, with a request for accelerated approval for selinexor as a new treatment for patients with penta-refractory multiple myeloma.

Following submission to the FDA, we are also preparing this data set for submission to the European Medicines Agency with a request for conditional approval. Further, we believe that the addressable market size for patients with penta-refractory myeloma is approximately $500 million in the U.S.A. alone. Expanding on the use of selinexor into earlier lines of myeloma treatment, we have initiated the pivotal randomized Phase III BOSTON study. This study evaluates our oral Sel-Dex regimen in combination with Velcade compared to Velcade dex alone in patients with myeloma, who have had 1 to 3 prior lines of therapy. The 2 primary endpoints in the BOSTON study are the differences in PFS and ORR between the 2 arms, and we expect to report top line data in 2019.

Assuming a positive outcome from the BOSTON study, we expect to be well positioned to support request for full approval for Sel-Dex with Velcade. We estimate that the market size for the sel/Vel/dex regimen in myeloma patients relapsing after at least 1 prior regimen is $1 billion to $2 billion annually. The BOSTON study was designed based on results from one of the arm, so the multi-arm Phase Ib/II STOMP study. We presented clinical results from 4 of these arms of the STOMP study at the ASH meeting in December 2017, and all of the data showed apparent benefit of combining oral selinexor with standard anti-myeloma agents. We will not go into the specifics here, but based on these exciting results, we are continuing to improve to the existing arms and expanding the STOMP study to include an arm for newly diagnosed patients for a combination with once weekly Kyprolis.

In addition to myeloma, we are developing selinexor for the treatment of diffuse large B-cell lymphoma or DLBCL. The Phase IIb SADAL study investigating oral selinexor as a single agent for the treatment of patients with relapsed or refractory DLBCL continues to accrue well, and we plan to report top line results by the end of 2018. Assuming a positive outcome, we intend to use the data from the SADAL study to support a request for accelerated approval from the FDA and conditional approval from the EMA for oral selinexor in patients with relapsed/refractory DLBCL who have received at least 2 prior lines of therapy. We believe that the addressable market size for patients with DLBCL, relapsing after 2 or more therapies is approximately $500 million annually in the United States alone.

We are frequently asked about where we see selinexor fitting into both the myeloma and DLBCL treatment landscapes, particularly in light of the CAR-T therapies, which are being explored in several malignancies. I'd first like to say that CAR-T is a very exciting new therapy for the select group of patients who are able to receive it. The first CAR-T for DLBCL, Gilead's Yescarta has received approval for patients who are relapsed after prior therapy and have medically able to safely undergo this therapy. Other CAR-T therapies are being developed in DLBCL, as well as in multiple myeloma. However, the vast majority of patients simply won't be eligible for CAR-T, because of the treatment complexities as well as the intensities of (inaudible) of regimens currently in use. CAR-T therapies are typically restricted to a highly selective group of patients usually younger than 65 years old, whose medical conditions make it likely that they can safely undergo these treatments. We believe that is an easily administered oral therapy. Selinexor represents a completely novel option for the vast majority of patients with relapsed or refractory myeloma or DLBCL, including those who are not fit enough for CAR-T therapy, and even for those whose disease relapses after CAR-T therapy.

Beyond hematologic malignancies, selinexor is also being developed in certain solid tumor indications, namely [gynecologic] where we can see some liposarcoma. An investigator sponsored Phase II-III study evaluating once weekly selinexor as a maintenance therapy versus placebo was recently initiated in patients with endometrial cancer following first or second-line chemotherapy. This multi-center study is being led by Professor Vergote of the Catholic University of Leuven, Belgium. In our most advanced solid tumor trial, the SEAL study, we are investigating single agent selinexor versus placebo in patients with previously treated advanced dedifferentiated liposarcoma. The Phase III portion of the study is underway and top line data are anticipated by the end of 2019, assuming a positive outcome of the primary endpoint of PFS, we finally used these data to support NDA and EMA filings for oral selinexor as a potential new treatment for patients with advanced dedifferentiated liposarcoma.

Moving to Eltanexor, positive Phase I/II data for eltanexor were also presented at ASH 2017. The data shows that oral eltanexor both alone or in combination with low dose dexamethasone induced responses or disease control in patients with heavily pretreated myeloma. The recommended Phase II dose was established and eltanexor has shown lower levels of fatigue and anorexia compared to selinexor. Advanced colorectal cancer, castration resistant prostate cancer, and myelodysplastic syndrome are malignancies where selinexor and XPO1 inhibition have shown clear activity where side effect, such as fatigue and anorexia were problematic. Therefore, the eltanexor study has been expanded to evaluate it in these indications and we expect to share initial data from this expansion later this year.

Before I turn the call over to Mike, I'm pleased to tell you about how we are growing our commercial growth as we plan, as we prepare for a potential NDA filings in penta-refractory in myeloma and relapse/refractory DLBCL. We have hired 3 new Vice Presidents to our commercial team, Kirk Schamp, Isabelle Mercier, and [Perry]. Kirk joined us as our Vice President of Market Access. He brings over 30 years of commercial oncology experience from his prior roles at [inside] Amgen, this includes his experience launching the Oral Cancer (inaudible) [angiopathy]. Isabelle Mercier has joined us as our Vice President of Marketing, she brings significant experience in building and leading U.S. and global commercial teams during her 23-year [career] that spends oncology marketing positions at Takeda, Sanofi, and SangStat, she lead the marketing efforts for Velcade in the U.S. and other oncology drugs, including Taxotere, Eloxatin and others.

Perry has also joined as our Vice President of Sales. He built the regional sales team to support the launch of Kyprolis, and has lead Amgen sales team overseeing district manager, sales reps, and nurse educators. He also held various sales position at Onyx, Sanofi and AstraZeneca. We're extraordinarily excited to have Kirk, Isabelle and Perry on-board to help lead our efforts to prepare for the potential launch of selinexor.

I'll now turn the call over to Mike. Mike?

Thank you, Michael. Since we issued our press release earlier today outlining our full financial results, I'll just review our full year and fourth quarter 2017 financial highlights. As of December 31, 2017. Cash, cash equivalents and investments, including restricted cash totaled $176.4 million compared to $175.5 billion as of December 31, 2016. For the full year, 2017, research and development expense was $107.3 million compared to $86.9 million for the full year 2016. For the full year 2017, general and administrative expense was $24.9 million compared to $23.9 million for the full year 2016.

For the full year 2017 Karyopharm reported a net loss of $129.0 million or $2.81 per share compared to a net loss of $109.6 million or $2.92 per share for the full year 2016.

Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the full years 2017 and 2016, respectively.

Turning now to the financial results for just the fourth quarter of 2017. Research and development expense was $34.8 million compared to $20.7 million for the same period in 2016. General and administrative expense for the fourth quarter of 2017 was [$6.2 million] compared to [$6.5 million] for the same period in 2016. Comparing the fourth quarter of 2017 to the prior quarter, the third quarter of 2017, R&D expense increased by [$9.6 million] reflecting increased spending on our late-stage clinical trials and one-time payments related to our agreement with Ono. For the fourth quarter of 2017, we reported a net loss of $39.0 million or $0.80 per share compared to a net loss of $26.9 million or $0.65 per share for the fourth quarter of 2016. Net loss includes stock-based compensation expense of $4.5 million and $5.1 million for the fourth quarters of 2017 and 2016 respectively. Based on our current operating plans, we expect that our existing cash, cash equivalents and investments will be sufficient to fund our research and development programs and prepare our commercial infrastructure through at least the first quarter of 2019. Including the continued clinical development of selinexor in our lead indications. Assuming positive data from the STORM study, these plans include filing an NDA with the FDA requesting accelerated approval in myeloma during 2018, and preparing the commercial infrastructure for the potential launch of selinexor in the U.S.

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

Thank you, Mike. The last year has been one of significant achievement for Karyopharm, and we are planning for a transformational year in 2018. To summarize, at the end of April, we plan to provide top line data from the Phase IIb STORM study in multiple myeloma, if the data from STORM are positive, we plan to submit an NDA to the U.S. FDA requesting accelerated approval during the second half of 2018. We also plan to follow the NDA submission with the potential submission to the EMA for conditional approval.

For our SADAL study in DLBCL, we expect to report top line data by the end of 2018. If positive, we plan to submit an NDA to the FDA with a request for accelerated approval, and again, we plan to follow this NDA submission with the potential submission to the EMA for conditional approval.

For the pivotal Phase III BOSTON study, we expect to complete enrollment this year with top line data anticipated in 2019. And for the STOMP study, we look forward to presenting updated data from the Revlimid, Pomalyst, Velcade and Darzalex arms, an initial data from the Kyprolis arms at appropriate medical [meetings] during 2018.

For a solid tumor programs, with these newly initiated Phase II/III investigator sponsored trial of selinexor as a maintenance therapy in patients with endometrial cancer, we look forward to the investigator reporting results in the future.

And finally, we expect to report top line data from the Phase III portion of the SEAL study by the end of 2019. As we look ahead to an exciting catalyst rich 2018, we are laser focused on executing across all our clinical and corporate objectives and building on the momentum we've created. We believe there is significant opportunity for Karyopharm, and we will continue working to advance selinexor as a potential new treatment paradigm for patients suffering with myeloma, DLBCL, liposarcoma, and other malignancies.

I will now turn the call over to the operator for questions.

Thank you. (Operator Instructions) And our first question is from Mike King with JMP Securities.

Just actually 2 minor one's really. Michael, could you just talk about SADAL, what if there is any FDA standard or requirement or soft guideline for the amount of follow-up in terms of time, is it 3 months, 6 months or is it just left to whatever the patient population would suggest. And then I have a separate study for myeloma.

Sure. Quick answer on the first one. As always the FDA indicates that any trial results will be a review issue, and that's of course true especially in a single-arm study. Our belief based on KOL interactions and so forth is that the response rate in the neighborhood of 25%, and a duration north of 5 to 6 months -- in the 5-month to 6-month range would be sufficient for an exciting new drug in lymphoma, especially a single agent oral therapy.

But as far as you -- [I'm not trying to working out] but we see a bright line or something like that at 6 months is not -- you would say is not the case?

Yes. I don't think there is a red line in the sand at all, I think it's -- again as the FDA likes to say, it's a risk benefit issue, it's a review issue and considering these patients really have zero standard of care. Our patients are not eligible for any kind of transplantation including CAR-T, means if they really have no options known to produce clinical benefit, there are certainly KOL that believe anything north of 4 months would be sufficient. But we like to [shoot] for 25% and 5 or 6 months, and please keep in mind that our EHA data, we did the interim results at a response rate of [33%] with a duration of response in the neighborhood of 7 months or longer.

Just curious, have you -- do you know if any of your patients in SADAL have been able to go onto CAR-T therapy?

We don't know that at this time.

Okay.

We do know that we have several patients on SADAL, who are in complete response now for more than 2 years, who are -- and once a week maintenance therapy. And so we're able to follow these for a long time, but we haven't gotten the full follow update in terms of other therapies for the patients that have progressed.

And then just to myeloma for a second. On STOMP, what's the ultimate objective, you've got multiple arms going on, obviously it's going to be very interesting to see how selinexor plays with all the other approved therapies, what's the ultimate goal of -- is it to generate publications or is it just gain experience with safety, what comments can you make on that? Thanks.

Yes. It has several goals, including the ones that you mentioned, I mean certainly publications is very important. These will inform future randomized studies as well as the publications. And I think the critical point is that when myeloma drugs, and this is true of all of the drugs in myeloma, when myeloma drugs are available in the market, doctors have their own opinions and their own desires given their patient specific needs on how to use the drugs, either alone or in combinations. And unfortunately companies have little control over that, but one of the most important things is to provide information so the doctors can safely combine these compounds in the event that they want to, and that's our goal. And part of that, as I mentioned we're even looking at an arm now with newly diagnosed patients, where selinexor combination with Revlimid, we are going to study because this provides an all oral option, which for a lot of patients, particularly elderly patients is a highly desirable kind of a therapy.

When do you think we could see the first randomized study grow out of STOMP?

Well, keep in mind that BOSTON is already ongoing with the Velcade arm. In terms of our future studies we are not [certain], and I mean the data are still maturing, obviously all of the combinations look interesting in terms of appearing to have higher response rates than any of the single agents and better durability, but we need to let the data mature. We're excited about many of the arm, so we'll have to pick a limited number for randomized studies.

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

Hi, guys. Thanks for taking my questions, and congratulations on the progress. I guess, following up on the STOMP questions, I guess, I'm sort of wondering particularly the rationale for moving into the front line, I guess to what degree that plan should reflects what you're seeing coming out of the more mature lenalidomide combination data, and to what degree is that sort of based on clinical efficacy data versus the concept of pairing these oral drugs and having a kind of a [maximally] convenient front line regimen?

Yes. I'd make one statement and turn it over to Jatin. I think it's a combination of the 2 things that you said. We're very aware that combinations of many front line regimen, such as Velcade-dex, Kyprolis, [Rev-Dex], and probably more recently or soon to come is the [Dara] front line with Revlimid, but all of them involve injections. And we see a real desire for patients, especially certain patients that can avoid having your skin punctured and try to minimize their visits to the clinic or to the hospital. Jatin, do you want to add anything?

Yes. Though I agree, I think absolutely, when we look at the vast majority of our myeloma patients, there's going to be [both the ages sadly] some of the patients who have difficult time coming into clinics having all-oral regimen, because we keep these patients still in this phase for high-risk myeloma potentially. So there's a number of patients I think that all-oral regimen could be effective.

I just remind everyone that, Brian, just to add to that that the ixazomib plus Revlimid frontline work is ongoing. And again I think it shows that the Takeda believes there's unmet need for an all-oral regimen, and we are providing a different opportunity now with not using a proteasome inhibitor, but instead combining with a totally new mechanism.

And then on the BOSTON Study, wondering if you could provide any color on enrollment there, in particular the receptivity that you're seeing to use of that regimen, weekly Velcade, the val-dex control arm impact of having a crossover on enrollment in that study in some of the patient characteristics that -- of who are coming in?

So before I turn it to Jatin, I'll just remind folks that this study is sell val-dex versus Valdex, the Velcade dex arm has twice-weekly Velcade and the sell val-dex is all given once weekly. So it's potentially a more convenient arm to be on and we do allow crossover for patients on val-dex who progress can crossover to SVd, it's in patients with 1 to 3 prior therapies. Jatin, you want to comment on some of the patient characteristics and how approvals going?

I think first and foremost, is going well, is on track, robust. So I think that's promising we're at right now and we're on track for enrollment. And I think that propably reflects a number of things that they're still in need for novel therapies and they're still the use of Bortezomib and at 1 to 3 lines of therapy and so this trial is enrolling well globally including North America. So I think that's promising. #2, about the patient characteristics, and so these are patients, I think, that are well positioned, because we look in the vast majority of patients getting in mid-week therapy upfront in the frontline therapy. And so these patients come off that either to your transplant ineligible patients who are getting the majority of them are getting (inaudible) based therapy transitioning to a PI-based therapy with bortezomib is appealing not only typically do in the clinics. And so this is well positioned in that sense and those are the patients that we're seeing come on study. The other patients are those that they have gone on for transplant and then they have maintenance and again progressing on that and come up to a PI-based regimen. Those who do get bortezomib upfront, usually don't get bortezomib until progression and so they may have had bortezomib-based therapy as part of the induction therapy and then continue on or take a treatment for enrollment, come onto to the study. And so those are the patients that we are seeing come onto the study.

And then maybe one more question, I'll hop back in the queue. I guess a question for Mike. As we think about the breakdown of operating expenses for 2018, what's the right way to think about the balance between growth of R&D as the clinical programs expand versus growth in G&A, as some of the additional groundwork is laid for commercial preparation with consideration to kind of the run rate exiting fourth quarter, how should we think about 2018 looking? Thanks.

And I think if you look at how we grew expenses over the course of 2017, almost all of the growth, if not all of the growth, came on the R&D side. I think you'll -- we'll continue to see that through the course of 2018 as we get into the later stage clinical trials, particularly the Boston trial, which is in combination with Velcade, and it's a sizable trial, we will start to see a growth in expenses there. Likewise in -- over the course of last year, we did build up our regulatory, safety and quality capabilities. But as we move forward with filing the NDA with the FDA, we'd expect to see that spending increase. And lastly, on the G&A side, we have put in some important administrative capabilities to ensure that we can support an organization that is larger and moving into commercial stage. So we'll continue to see growth there. On the commercial side, we noted our plans for this year is to develop the high-level infrastructure and [Michael] referred to 3 important hires that we've made since our last call. So that's a sign that we are getting the infrastructure in place to support a launch. But as we think it makes sense to hold off on actually hiring the sales force, which is where you see the bulk of the commercial spend coming on that will come much closer to launch.

Our next question is from Arlinda Lee with Canaccord.

The BOSTON enrollment, can you provide additional color on maybe what the geographical split is deployed, and then maybe your thoughts on launching selinexor ex-US yourself versus maybe seeking a partnership? And then lastly on the storm data that expected later this month -- next month. Are we going to get both a response rate and a durability -- indication of durability? Thanks.

Hi, Arlinda. It's Michael. Thanks. Quickly on the last question, you'll get a response rate and you will either get median duration of response or if there are lots of patients who remain on study and there maybe, you'll get a median duration of follow-up, which can provide a pretty good guide to the DOR. You're also going to comment about safety, if there any new safety signals and we don't anticipate any at this time. On the BOSTON study, I'll just quickly remind everyone that most of the Phase III studies in myeloma come ex-US. The Darzalex studies, both [Paulette and Castor] had about 93% ex-U. S participation and that's because Phase IIIs are not just on accrue while in the U.S. -- U.S. patients tend to want to be on single-arm studies and they have lots of options here. So we expect to be a similar guide that way, that kind of breakdown has had zero effect on FDA's review of the data and that's partly because the myeloma treatment paradigms in these countries that do participate are essentially are similar to the U.S. and so the patients are representative. And then on the last question, I'll turn it over to Chris Primiano, our Chief Business Officer.

Hey, Arlinda. So as we've said, assuming positive data from STORM, we planned to file an NDA later this year in the U.S. and then a possible launch in 2019 with filings with the EMA sort of following in short order behind that. And so as you can imagine, we wouldn't expect to be a fully integrated global pharmaceutical company by 2019. So our plan is to keep moving those regulatory filings forward to the extent applicable based on the data from STORM outside the U.S. in particular in the EMA and to look for a partner to support the commercial launch in Europe and then of course we have Ono to support the commercial launch in Japan and in the other territories if their agreement covers.

Our next question is from Maury Raycroft with Jefferies.

First for STORM, I'm wondering if overall response rate comes in below expectations, can you talk about how duration of response and potentially OS could influence the total data package in the go-forward path?

Yes. Hi, Maury. It's very tough to model all of those possibilities and again (inaudible) always says this is a review issue and it's the totality of the data, as you said. But a lot of this has to do with what the survival looks like for these patients, both the responders and non-responders, you may recall. In part 1 of the study, we show that patients who had at least a minimal response, which represented about 33% of the population that we had had a survival -- median survival of about twice as long as the patients who did not respond. I'm suggesting that response was associated with a benefit and importantly that patients --

unfortunately the patients who don't respond to Selinexor really don't have any good options available. So that as you intimated that survival result will be important to go there. And I also point out that we did get a 21% response and quite refractory 20% response in the first part and we hope to do that again and to remind folks that daratumumab's response rate in the quite refractory population which is as near to the population we can find was also 21%. And we're seeing about the same response rate after daratumumab. So this suggests at least to us and to the doctors that are participating on this study that selinexor can provide a benefit to these patients.

And just to clarify, will it be possible to get a 12-month duration of response rate, [a standpoint]?

You mean a number of patients that are responding for 12 months?

Yes.

I don't think we'll have one for this, but in the future we may.

And then last question is just, if expectations for an accelerated path for STORM are different for the FDA or EMA?

That's a very tough one to call, I mean, historically EMA has been a bit more conservative about single-arm studies, but they [are] serving for accelerated approval, the 2 cases, the 2 important cases they approved were Velcade and Darzalex, and at the time Velcade of course was the first proteasome inhibitor and novelty is very important. Darzalex being of course the first CD38 antibody. So we're excited to be the first XPO1 inhibitor, and I think very importantly and perhaps Europe appreciates it's even more than FDA. We're the first oral therapy in this class, and oral therapy matters, and you could see that again with the use of Ninlaro, and you think about again the patients that we have on study, average age is about 70, and we keep emphasizing this that these older patients really tend to not want to come into the doctors and do not want to have many blood tests and so on. So we think that all these things are in our favor and we'll do the best we can convincing the EMA that this drug deserves to be available to patients in Europe.

Our next question is from Ed White with H.C. Wainwright and Co.

Hi, guys. Thanks for taking my question, and congratulations on hiring the 3 VPs. So just a question on that, you had mentioned that the sales force won't be hired until around approval time, if you could just maybe give us a little hint on the size of the sales force going forward, and how you're going to be ramping them up, it sounds like in 2019?

Sure, Ed. So -- the market for multiple myeloma in the U.S. is pretty well understood, as Michael has talked about, there's been a number of launches of therapies in the last 5 or 6 years, so the call pattern is fairly well understood and the influences are. And based on the extensive work that we've done to map out our commercial strategy in the U.S., we think sales force of approximately 70 sales reps is about the right size to have a successful launch, and we certainly want to make those kinds of investments to make sure that selinexor gets off to a great start. Likewise, looking at the success of past launches, we know that if we make the right investments over the course of 2018 in terms of developing the right commercial leadership within our organizations and setting out our execution plans, the final step that we can take before launch is to actually pull the trigger on hiring the sales force. And based on our current timetables, which is looking at a launch in early 2019, we think comfortably we can hire the sales force early next year.

Our next question is from Eric Joseph with JP Morgan.

Hi, guys. Congrats on the progress, and thanks for taking the questions. I just had a follow-up on EU registration strategy here. Just wanted you could kind of be a bit more specific about whether kind of the path to registration with EMA is kind of partnering dependent, and whether your partnering discussions are kind of to date have more focused on the STORM readout or whether they have all been contingent on progress on -- with [Fed] on the DLBCL front. And then just also -- just kind of thinking about the commercial landscape in the EU. Michael, just wonder if you could kind of elaborate on your comments earlier there, maybe talk a little about the propensity for medical versus -- medical treatment versus transplant in that setting, and I'll leave it there.

Okay. So let me try to tackle these somewhat complicated questions. And I'll start and then Chris can comment also in the partnering discussions. We feel very comfortable with the regulators in EU as well as other venues, Health Canada and so on, as well as FDA. And you've seen that because all of our trials are currently being conducted in U.S., Canada, Europe and frankly many other countries. And obviously all of these protocols and plans have to be approved by the governing regulatory bodies in each of those countries. So we've had scientific advice from the EMA on all of the different relevant trials here, STORM, SADAL and BOSTON. So getting it approved there and talking to the repertoires and so on and working through the process in Europe is one that we are comfortable with. And I'll turn it over to Chris now to talk a little bit about the partnering. Thank you.

Yes. Sure. And so I think your question was whether the registration process in Europe is dependent on partnering and sort of interplay between the registration for us and our partnering discussion. So I would sort of think of those as 2 parallel tracks. We're continuing a regulatory process with EMA and data [dependable], we'll prepare the appropriate filings, while the partnership discussions proceed in parallel and I suspect that those 2 paths would intersect in a timely fashion, so that the registration is not dependent on partner.

And then you asked a little bit about the use of selinexor in the context of Europe, alluding to the fact that they might be a little bit more excited about transplants over there. I think it's a fair statement that the academic institutions, particularly in France are excited about single transplants and even sometimes double transplants, and we see that in some of our patients. But as you recall, unfortunately, none of the current therapies including double transplant are curative. And therefore we are enrolling patients actively on to STORM right now, penta-refractory myeloma patients on to STORM coming from Europe, in France, Greece and other places, U.K. and so on. So we don't see this as a major issue, we think the number of patients in fact in Europe is at least equal to the number of patients available in the U.S. with penta-refractory disease and both populations are growing. I just add one more thing and that's there's about 120,000 to 130,000 patients currently with myeloma in the U.S. now. And the number of penta-refractory patients is growing, because the use of daratumumab is growing. And we expect these numbers to increase substantially at least, because the number of new patients is about 30,000 per year, and unfortunately there is still about 12,000 deaths per year. So there is a net gain of about close to 20,000 patients per year in U.S. and Europe for this disease.

Maybe just one follow-up, can you kind of say anything, any updates on the timing to the start of a Phase III confirmatory study in DLBCL? Thanks.

Yes. Sure. So unlike in myeloma where there's sort of an unwritten expectation from the FDA, it may be unwritten, but it's not generally unspoken. And we've talked to them, they expected in myeloma to have your Phase III ongoing at the time you'd be submitting an accelerated approval which we do at the BOSTON study. In DLBCL and other lymphomas, the requirement for having the confirmatory study ongoing at the time of even submission for accelerated approval just has not been pushed, and we do have several investigator-sponsored trials in lymphoma and DLBCL ongoing, including combination with (inaudible) and second-line therapy as [appraisal] to transplant or to try to eliminate the need for a transplant and also with various gemcitabine combinations and oxaliplatin combinations with the French group, and with some novel agents as well. So we do have a pretty robust program that's designed to determine what is the best combination strategy for DLBCL, and we've discussed those potentials with FDA, but we've not yet committed to one and neither require some more follow-up data late this year or into even mid to late next year.

Our next question is from Mara Goldstein with Cantor Fitzgerald.

Hi. Good morning. Can you hear me?

Yes, we can.

Great. This is (inaudible) in for Mara. So our question is around SADAL study, and the expectations for the data there, and also you would need to show to the regulators with accelerated approval?

Yes. There is currently no precedent in DLBCL for a small molecule or a biologic therapy. There's obviously CAR-T precedent which is basically a combination of cellular therapy with induction with heavy doses of chemotherapy. But there is no precedent in DLBCL for accelerated approval. And we've been excited, and frankly I think the regulators are looking forward to the fact that we have an oral therapy as a single agent, which has shown durable responses in both the GCB and in the ABC subtypes, unlike many of the other oral therapies. And furthermore that we have some complete responses, and even some partial responses they are extremely durable. And so, there's a lot of properties of this molecule, which are potentially very exciting. We believe that the numbers we'd like to see as a response rate somewhere around the 25% mark for partial response or better and a duration of response that's 5 months or better -- 5 to 6 months or better. And [I] again remind everyone that we had a 33% response rate at the interim with a duration of responses of 7 months at least or better at EHA last year. So we're excited about the study. We'll have the data -- the top line data by the end of the year with expectation to file on this in 2019.

Thank you. And our next question is from Ying Huang with Bank of America.

This is [Jenny] on for Ying. Thanks again for taking my question. I guess we just had one basically, just on the commercial preparedness for selinexor, as you said that you are hiring 70 reps, I guess, kind of what kind of education process that you guys thinking through, are you going to need any KOLs or MSLs to kind of get the high [displaying] some of the influencers, especially those who may not be using the drug in process. And then also in practice based on your conversations of KOLs, what are they currently using in the penta-refractory multiple myeloma population? Thanks so much.

Yes. This is Michael, and I'll just turn it over to Jatin, who will be heavily involved in lot of the education out of the sales reps. This penta-refractory population is to our knowledge, unprecedented in large Phase II trials, and it represents a population of patients that have failed, their disease has progressed following, frankly some of the best drugs we have in all of hematologic cancers. And we've been impressed with how aggressive this tumor is when patients come into our study. We have seen and you have seen from Part 1, deep response is very good, partial responses which represent 90% reduction, and you've seen some durability with this single oral agent, which really we believe represents an advanced potentially for this unmet medical need. There are core side effects to our agent as there are from all of them the nausea, anorexia, fatigue and low platelets are the most prominent ones, and the good news is that we have learned how to deal with them, and our key would be to educate physicians and the other sales reps, as well as medical science liaisons and nurse practitioner educators and so on in our sales group. So I'll turn it over to Jatin now to talk a little bit more about the plans.

Well. Thanks, Michael. Specifically referring to how we will educate the physicians?

Yes.

So, I think it's really a multipoint approach. I think if you have a new drug that hits the market with a new class of drugs, you really is a learning curve, how to learn, how to use these drugs and we saw the same experience with proteasome inhibitors with carfilzomib with checkpoint inhibitor with [TKI's]. And so, I think it's going to be a similar type of approach, and so there is going to be a couple of important points. One is managing the nurses, because the nurses are the really the first line, they're managing lot of the patient's symptoms, and so we'll have aggressive plan in place to work with the nurses that are managing some of the symptoms, how to manage some of these symptoms. #2, when we look at our experience so far on the trials, we've seen that there really is a learning curve, so as the sites that have more patients on, as I go to from the Phase I experience with early selinexor and on through (inaudible) STORM, we see that the sites get used to how to give these drugs and [naturally] learning curve, so as they had more patients on then they really get much more comfortable managing those side effects. And so we've seen that now in the clinics, in the trials, and I think obviously the same thing in the clinics as well. And then speaking really to the education around the efficacy, this is really I think -- something we'll see when we're talking to patients or physicians about the activity that we expect to see, these responders that we see are tend to be very quick. And so learning how to manage that would be early kind of dosing and then dose modifications as patients go, and that's going to be key as well, where we can do dose drops and then dose modifications and educating the physicians how to manage that through the process will be important as well, as well the plan in place to talk to patients and physicians about that. Did I answer your question?

Great. Yes.

(Operator Instructions) And I'm showing no further questions. I would now like to turn the call back to Dr. Michael Kauffman, CEO, for any further remarks.

Sure. Thanks everybody for joining today's call, and have a great day. And we'll be talking to you soon. Bye-bye.

Ladies and gentlemen, thank you for participating in today's conference. You may now disconnect. Everyone, have a great day.