Karyopharm Therapeutics Inc. (KPTI) Q4 2017 Earnings Report, Transcript and Summary

Good morning. My name is Iva, 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] 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. Christopher Primiano, Chief Business Officer of Karyopharm therapeutics.

Thank you, Iva, 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 am 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 provide an overview of the fourth quarter and year-end of 2017 financial results. Dr. Kauffman will then discuss our key upcoming milestones and provide some summary remarks. We will then open the up for questions for where Sharon, Jatin and I will also be available. Earlier this morning, we issued a press 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 time lines, the potential success of our product candidates, financial projections, and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our 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 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 presenting 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 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, we're very active on advancing our clinical trials, as well as on the business development front. During that time, we executed two high value strategic transactions, one with Ono Pharmaceutical Company Limited for selinexor and selinexor and one with 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 in commercialization powerhouse in Japan. Ono market several blockbuster oncology drugs in Japan, including OPDIVO and Kyprolis, giving them specific expertise in multiple myeloma, Hodgkin's disease and a variety of different solid tumors, and making them an ideal partner to advance both selinexor and eltanexor in Japan and other licensed territories. In 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 neuro toxicity and has demonstrated neuro protective properties as demonstrated in several publications, including two in Nature Neuroscience covering models of ALS and multiple sclerosis. This transaction which carries a total deal value up to $217 million plus royalties, brings oral KPT-350 together with Biogen's world-class capabilities and their expertise in the development and commercialization of products for neurological and neurodegenerative diseases. Collectively, we believe these two transactions provide important validation for our oral SINE compounds, while 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 commercial stage enterprise. And I'll turn to review our myeloma trials. For the ongoing Phase 2b STORM study we remain on track for top-line response data at the end of April. This is our most anticipated near-term data readout and milestone. Recall that 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 in durability that we reported at ASH 2016 and published recently in the Journal Clinic of Oncology in January, we intent to submit the full STORM data to the U.S. FDA in the second half of 2018 with the request of 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 the request for conditional approval. Further, we believe that the addressable market size for patients with penta-refractory myeloma is approximately $500 million in the USA alone. Expanding on the usage selinexor or into earlier lines of myeloma treatment, we have initiated the pivotal randomize Phase 3 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 one to three prior lines of therapy. The two primary endpoints in the BOSTON study are the differences in PFS and ORR between the two 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 one prior regimen is $1 billion to $2 billion annually. The BOSTON study was designed based on results from one of the arms at our multi arm Phase 1b/2 STOMP study, representing clinical results from four 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 as well as 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 2b SADAL study investigating oral selinexor as a single agent with the treatment of patients with relapsed/refractory DLBCL continues to accrue well and we plan to report top-line results by the end of 2018. Assuming a positive outcome, we intent to use the data from the SADAL studies, for the 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 two prior lines of therapy. We believe that the addressable market size for patients with DLBCL relapsing after two or more therapies as 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 export 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 are 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 will be eligible for CAR-T because of this treatment complexities as well as the intensities of lympho [ph] regimens currently in use CAR-T therapies are typically restricted to a highly selected group of patients usually younger than 65 years old, whose medical conditions make it lightly that they can safely undergo these treatments. We believe that as an easily administered oral therapy, selinexor represents a completely novel option for the vast majority of patients with relapsed/refractory myeloma or DLBCL, including those who are not fitting up for CAR-T therapy and even for those whose disease relapses after CAR-T therapy. The un-hemologic malignancies, selinexor is also being developed in certain solid tumor indications, namely Gynecologic Malignancies and liposarcoma. And investigators sponsored Phase 2/3 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 multicenter study is being led by Professor Vergote of the Katholieke Universiteit 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 3 portion of this 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 plan to use these data to support NDA and EMA fillings for oral selinexor as a potential new treatment for patients with advanced dedifferentiated liposarcoma. Moving to eltanexor. The positive Phase 1/2 data for eltanexor were also presented at ASH 2017. The data showed that oral eltanexor both alone or in combination with dexamethasone, induced responses or disease control and patients with heavily pretreated Myeloma. The recommend the Phase 2 doses established in 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, but where side effects 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 am pleased to tell you about how we are growing our commercial group as we plan, as we prepare for a potential NDA filing in penta-refractory myeloma and relapsed/refractory DLBCL. We have hired three new Vice Presidents to our commercial team, Kirk Schamp, Isabelle Mercier and Perri Monaco [ph]. Kirk joined as our Vice President of Market Access. He brings over 30 years of commercial oncology experience from his prior roles at Ariad Insight, ASI and Amgen. This includes his experience launching the oral cancer therapy [indiscernible]. Isabelle Mercier has 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 spans oncology marketing positions at Takeda, Sanofi and Science [ph]. She led the marketing efforts for Velcade in the U.S. and other oncology drugs including taxotere, eloxatin and other. Perri Monaco has also joined as our Vice President of Sales. He built the regional sales team to support the launch of Kyprolis, and has led Amgen sales team overseeing District Manager, sales reps, and nurse educators, He has also held various sales position at Medtronic, Sanofi and AstraZeneca, We are extraordinary excited to have Kirk, Isabelle and Perri on board to help lead our efforts to prepare for the potential launch for selinexor. I'll now turn the call over to Mike. Mike?

Thank you, Michael. Since we issued a 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 a $176.4 million compared to $175.5 million as of December 31, 2016. For the full year 2017, research and development expense were $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 of 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the full year's 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 increase spending on a late stage clinical trials and onetime 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 to 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 to 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 transformational year in 2018. To summarize, at the end of April we plan to provide top-line data from the Phase 2b 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 file 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 on this NDA submission with a potential submission to the EMA for conditional approval. For the pivotal Phase 3 BOSTON study, we expect to complete enrollment this year with top-line data anticipated in 2019. And for the STORM study, we look forward to presenting updated data from the Revlimid Pomalyst Velcade and Darzalex arms initial data from the Kyprolis arms at appropriate medical meetings during 2018. For our solid tumor programs, with the newly initiated Phase 2/3 investigator sponsored trial with 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 3 portion of 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 have created. We believe there are 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, operator?

[Operator Instructions] And our first question is from Mike King with JMP Securities. Your line is now open.

Good morning, guys. Thanks for taking the questions. Just actually two minor ones really, Michael can you just talk about in 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 three months, six 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 the single arm study. Our belief based on KOL interactions and so forth that a response rate in the neighborhood of 25% and a duration north of five to six months were in the five to six months range would be sufficient for an exciting new drug in lymphoma especially a single agent oral therapy.

Okay. But as far as you - I'm not trying to put words in your mouth, but we're seeing bright line or something like that in six months is not you would say is not the case?

Yeah, 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, it means that they really have no options, no one to product clinical benefit. There are certainly KOL that believe anything north of four months would be sufficient, but we'd like to shoot for 25% in five or six months and please keep in mind that our e-hub data we did the interim results.

Right.

At a response rate of 33% with a duration of response in the neighborhood of seven months or longer.

Right. Okay, great. That's helpful. Just curious do you know if any of your patients in SADAL have been able to go on to 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 two years, who are in once a week maintenance therapy and so we're able to follow these for a long time, but we haven't gotten a full follow-up data in terms of other therapies for the patients that have progressed.

Okay. Thanks for that color. 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? And what's the ultimate goal of this - is it to generate publications, is it just to 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 publication is very important. The usual inform future randomized studies as well as the publications. And I think the critical, 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 that doctors can safely combine these compounds in the events that they want to. And that's our goal. And in 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 can 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 yet, I mean the date 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 arms, so we'll have to take a limited number for randomized studies.

Okay. Thanks for taking the questions. We're looking forward to April.

Our next question is from Brian Abrahams with RBC Capital Markets. Your line is now open.

Hey, guys, thanks for taking my questions and congratulations on all the progress. I guess following up on this the STOMP questions. I guess I'm sort of wondering particularly the rationale for moving into the frontline, I guess to what degree that plan should reflect. What you are seeing coming out of the - 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 having kind of maximally convenient frontline regimen?

Yes, I'll read one statement and turn it over to Jatin. I think it's a combination of the two things that you said, we're very aware that combinations of many frontline regimens such as Velcade Dex, Kyprolis rev-dex and probably more recently or soon to come the dara frontline, with Revlimid but all of them involve injections. And we see a real desire for patients especially certain patients that can avoid having their skin punctured and try to minimize their visits to the clinical or to the hospital. Jatin, you want to add anything?

Yeah, though I agree I think absolutely when we look at that the vast majority of our myeloma patients, they're going to be [indiscernible] we have difficult time coming into clinics and having all oral regimen because they keep these patients, put them to space for high risk myeloma potentially, so there is number of patient I think that all oral regimen would be effective.

Great, and then can you…

I just to remind everyone that Brian, just to add to that that the exits [indiscernible] plus Revlimid frontline work is ongoing and again, I think Takeda believe there is a firm 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 the totally new mechanism.

Great. And then on the BOSTON study, wondering if you could provide any color on enrollment there in particular, the receptivity that you are seeing to use of that regimen and the weekly Velcade, the with vel-dex control arm impact of having a cross-over on enrollment in that study and some of the patient characteristics who are coming in?

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

Yeah, absolutely. So, I think first and foremost our enrollment is going well, it's on track. And so thus, I think that's promising where we're at right now and we're attract for enrollment. And I think that probably reflects a number of things that are still in need for novel therapies and there is still the use of Bortezomib in that 1 to 2 lines of therapy. And so, this trial is enrolling well globally, including North America. So, I think that's promising. And then the two about the patient characteristics. So, these are patients and I think that are well-positioned. Because we look in the vast majority of patients getting therapy upfront in the frontline therapy. And so, these patients come off at either complete their transplant in eligible patients who are getting the majority of, getting rev-based therapy for an existing to PI-based therapy where Bortezomib is appealing not only typically during the clinics. And so, this is the well-positioned in our sense. And those are patients that we're seeing come on study. The other patients are those that they have gone offer transplant and that have maintenance and again progressing on that who come to a PI-based regimen. Those who do get Bortezomib upfront usually don't get - until progression. And so, they may have had Bortezomib based therapy as part of the reduction therapy and then continue on or take a treatment free at all and come on to the study. And so those are the patients that we're seeing come on to the study.

That's very helpful, Thanks, Jatin. And then maybe one more question and I'll hop back in the queue. I guess the 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 at the clinical programs expand versus growth in G&A as some of the additional groundwork is laid for and for commercial preparation with consideration to as kind of the run rate exiting fourth quarter. How should we think about 2018 looking? Thanks.

Sure. 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 continue to see that through the course of 2018, as we get into the later stage and clinical trials particularly the BOSTON trial which is in combination with Velcade. And it's a sizable trial, we'll expect to see a growth in expenses there. Likewise, over the course of last year we did build up our regulatory safety and quality capabilities, but as we move forward, we're filing the NDA with the FDA. We'd expect to see that spending increase. And lastly on the G&A front, we have put in some important administrative capabilities to ensure that we can support an organization that's larger and moving into commercial stage. So, we'll continue to see growth there. On the commercial side, we've noted our plans for this year is to develop the high-level infrastructure. And Michael referred to three important hires that we've made since our call. So that's a sign that we are getting the infrastructure in place to support a launch. But as we think it make sense to hold off and 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.

Thanks, Mike. Very helpful. Thanks, everyone.

Our next question is from Arlinda Lee with Canaccord. Your line is now open.

Hi, guys. Thanks for taking my questions. The BOSTON enrollment, can you provide additional color on maybe what the geographical split is deployed. And then maybe your thoughts on launching selinexor or ex-U.S. yourself versus maybe seeking a partnership. And then lastly on the STORM data that expect later this next month. Are we going to get both a response rate and durability indication of durability? Thanks.

Hi, Arlinda, this is Michael. Thanks. Quickly on the last question, you'll get response rate and you'll either get median duration of response or if there are a lot 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. This you also get a comment about safety if there are any new safety signals then we don't anticipate at this time. On the BOSTON study I'll just quickly remind everyone that most of the Phase 3 studies in myeloma come ex-U.S., the Darzalex studies both Polyst and Castor [ph] had about 93% ex-U.S. the participation and that's because Phase 3s are not just don't approve well in the U.S. U.S. patients tend 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.

Yeah Arlinda, so as we've said assuming positive data from STORM. We plan 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 launches in Europe. And then of course we have Ono to support the commercial launch in Japan and in the other territories that the agreement covers.

Okay, great. Thank you very much.

Our next question is from Maury Raycroft with Jeffries. Your line is now open.

Hi. Good morning and thanks for taking my questions. 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?

Hi, Maury. It's very tough to model all of those possibilities and again practice are always that there is a review issue and there's 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 one of the study we show that patients who had at least the 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 the 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 would point out that we did get a 21% response in quad-refractory, 20% response in first part and we hope to do that again, and to remind you folks that daratumumab's response rate in the quad-refractory population which is near to the population we can find was also 21%. And we're seeing about the same response rate after daratumumab, so this suggest at least us and to the doctors that are participating on this study that selinexor can provide a benefit to these patients.

Got it. Thank you. And just to clarify, will it be possible to get a 12 months duration of response rate the same point?

You mean the 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.

Okay. 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 had serving for accelerated approval, the two cases, the two important cases they approved were Velcade and Darzalex. And at the time, Velcade of course was the first proteasome inhibitor and novelty are very important, Darzalex being of course the first CD30 antibody. So, we're excited to be the first XPO1 inhibitor and I think very importantly and perhaps you appreciate even more than FDA, we're the first oral therapy in this class. And oral therapy matters, and you can 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 in our favor and we will do the best we can to convince the EMA that this drug deserves to be available to patients in Europe.

Got it. Thank you very much.

Our next question is from Ed White with H.C. Wainwright & Company. Your line is now open.

Hi guys, thanks for taking my question. And congratulations on hiring the three VPs. So, just a question on that you had mentioned that the sales force won't be higher until around approval time, if you could just maybe give us a little hint on the size for the sales force going forward, and how we are 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 understood as Michael has talked about there's been a number of launches of therapies in the last five or six years, so the call pattern is fairly well understood, and the influencers are. And based on the extensive work that we've done to map out our commercial strategy in the U.S. we think the sales force of approximately 70 sales reps is about the right size to have a successful launch and we certainly want to make that 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 made the right investments over the course of 2017 in terms of developing the right commercial leadership within our organization and setting out our execution plans, the final step that we can take before launches to actually pull the trigger of hiring the sales force, and based on our current timetables which is looking at a launch in the earlier 2019 we think comfortably we can hire the sales force early next year.

Okay, great, thanks for taking my question.

Our next question is from Eric Joseph with JPMorgan. Your line is now open.

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 can kind of be a bit more specific about whether kind of the past registration with the EMA is kind of partner independent and whether you are partnering discussions or kind of the data and more focused on the STORM readout or whether they've all been contingent on a progress on - with SADAL on the DLBCL front. And then just also just kind of thinking about the commercial landscape and Michael just wondering if you could kind of elaborate on your comments, earlier there if you talk little about the propensity for medical versus transplant in that setting and, yeah only with this.

Okay, so let me try to tackle these somewhat complicated questions, and I'll start, and the Chris can come in and 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 in 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 their abattoirs and so on and working for the process in Europe is one that we are comfortable with and I'll turn it over to Chris and 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 partner and sort of the interplay between the registration process and our partnering discussions, so I would sort of think of those as to parallel tracks where we're continuing the regulatory process with EMA and data dependent, we'll prepare the appropriate fillings. Well, the partnership discussions proceed in parallel and I suspect that two pads would intersect in a timely fashion. So, the registration is not dependent on a partner.

Great. And then you asked a little bit about the using 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 STORM right now penta-refractory myeloma patients on to STORM coming from Europe and France, Greece and other places, the UK 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. And I just add one more thing and there is 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.

Got it. Thanks. Maybe just one follow-up, can you kind of say anything any updates on the timings to the start of the Phase 3 confirmatory study in DLBCL? Thanks.

Yes, sure. So, unlike in myeloma where there is sort of an unwritten expectation from the FDA, it's maybe unwritten but it's not generally unspoken. And we've talked to them, they expected in myeloma to have the Phase 3 ongoing at the time you'd be submitting an accelerated approval which we do the BOSTON study. In DLBCL and other lymphomas, the requirement for having the confirmatory study ongoing at the time of these and submission for accelerated approval just does not being pushed. And we do have several investigators sponsor trials in lymphoma and DLBCL ongoing including combination with rise and second line therapy as a prelude to transplant or to try to eliminate the need for a transplant. And also, with various gemcitabine combinations and oxy [ph] 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 that'll require some more follow-up data in late this year or into even mid to late next year.

Great, thanks for taking all the questions guys. I am looking forward to the end of April.

As are we. Thank you.

The next question is from Mara Goldstein with Cantor Fitzgerald. Your line is now open.

Hi, good morning. Can you hear me?

Yes, we can.

Great, this is Elena [ph] for Mara. So, our question is around payroll study and the expectations for the data there. And also, when you would need to show to the regulators with April rate is approval?

Yes, there is currently no precedent in DLBCL for a small molecule or a biologic therapy. There is obviously CAR-T precedent which is a basically a combination 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 a regulator are looking forward to the fact that we have been 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 that are extremely durable. So, there is 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 five months or better, five to six months or better. And I again remind everyone that we had a 33% response rate at the interim with a duration of response of seven months at least or better at EHA last year. So, we are excited about this study. We'll have the data the top-line data by the end of the year with the expectation to file on this in 2019.

It sounds great. Thank you.

Thank you. And our next question is from Ming [ph] with Bank of America. Your line is now open.

Hey guys. This is Jenny [ph] on for Ming. Thanks again for taking our question. I guess we just had one basically just on the commercial preparedness for selinexor. So, you said that you're hiring 70 reps. I guess kind of what kind of education process that you guys are thinking through. Are you going to need any KOLs or MSLs to kind of get behind to swing some of the influencers especially those who might not be using the drug in practice? And then also, in practice based on your conversations with KOLs. What are they currently using in the penta-refractory multiple myeloma population. Thank so much.

Yeah. This is Michael and I'll just turn it over to Jatin who will be heavily involved in a lot of the education of the sales reps. This penta-refractory population is to our knowledge, unprecedented in large Phase 2 trials. And it represents a population of patients that have failed, and 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 as when patients come into our study. We have seen, and you have seen from part one, deep responses very good partial responses which represent 90% reduction. And you see some durability with this single oral agent with really, we believe represents an advanced potentially for this unmet medical need. There are core side effects to our agents 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 will be to educate physicians and be as 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 that the plans.

Thanks, Michael. You specifically referring to how we educate the physicians?

Yeah.

Yeah. So, I think it's really multi-pronged approach. I think it probably have unusual that have some - with the new class of drugs. There really is a learning curve how to learn, how to use these drugs and we saw this and experiment with really proteasome inhibitors with Bortezomib with checkpoint inhibitor and with TKI. And so, I think it's going to be the similar type of approach. And so, there is going to be couple of important points, one is managing the nurses, because the nurses are the really the first line, they're managing the lot of the patient symptoms. And so, having an aggressive plan in place to work with the nurses that are going to be managing some of the symptoms and how to manage some of these symptoms. And number two, when we look at our experience so far in the trials, we seen that there really is a learning curve. So, it has the sites that have more patients on as they go through from the Phase 1 experience with early selinexor or have gone through STORM. We see that these sites get used to how to get these drugs and there is really a learning curve, so it has more patients on then they really get much more comfortable to managing those site effects. And so, we've seen that now in the clinics in the trials that I think we'll see the same thing in the clinics as well. And then speaking really to the education around the efficacy. So, this was 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 tend to be very quick. And so, learning how to manage that that with the early kind of dosing and then dose modifications as patients gone. So that's going to be key as well where we can do dose eruptions and dose modifications and educate the physicians how to manage that through the process will be important as well. So, we'll have a plan in place to talk to patients and physicians about that. Does that answer your question?

Yeah.

[Operator Instructions] And I am 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.