Good morning. My name is Carmen, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics' Third Quarter 2018 Financial Results Conference Call. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, Karyopharm's Vice President, Investor and Public Relations. You may begin.

Thank you, Carmen, and thank you all for joining us on today's conference call to discuss Karyopharm's third quarter 2018 financial results and business update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, our Chief Executive Officer; Mr. Mike Falvey, Chief Financial Officer; Dr. Sharon Shacham, our Founder, President and Chief Scientific Officer; Mr. Chris Primiano, our Chief Business Officer; and Mr. Anand Varadan, our Chief Commercial Officer. On the call today, Michael Kauffman will make some introductory comments. Then Mike Falvey will provide an overview of the third quarter 2018 financial results. Dr. Kauffman will then discuss our key upcoming milestones and provide some summary remarks. We will then open up the call for questions, for which Sharon, Mike, Chris, Anand and I will also be available. Earlier this morning, we issued a press release detailing Karyopharm's results for the third quarter of 2018. The release is available on our Web site at karyopharm.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of 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 most recent Quarterly Report on Form 10-Q, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. In addition, please note that the 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, our Chief Executive Officer.

Thank you, Ian, and good morning, everyone. Thank you for joining us on today's call. Over the past few months, we have continued to make great progress towards bringing oral selinexor, our lead product candidate to patients with refractory forms of cancer. In fact, just yesterday, we announced that the FDA has granted Fast Track designation to selinexor for the treatment of patients with diffuse large B-cell lymphoma who have received at least two prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or CAR-T therapy. Of course, this Fast Track designation marks selinexor’s second such distinction following the Fast Track designation granted earlier this year for patients with penta-refractory multiple myeloma. Regarding myeloma, we are particularly encouraged that the FDA has now assigned a Priority Review for our new drug application seeking accelerated approval for selinexor as a new treatment for patients with penta-refractory multiple myeloma and has set an action date of April 6, 2019 under PDUFA, the Prescription Drug User-Fee Act. The filing of Karyopharm’s first NDA is a significant milestone for both selinexor and our entire company. If approved, we believe that selinexor’s novel mechanism of action, oral administration and compelling clinical profile will make it a meaningful treatment option for patients with higher refractory multiple myeloma. We are also actively working towards submission of a Marketing Authorization Application to the European Medicines Agency with a request for conditional approval for selinexor in this same penta-refractory indication in the first quarter of 2019. These NDA and MAA packages are supported by positive results from Part 2 of the Phase 2b STORM study evaluating twice weekly oral selinexor plus low dose dexamethasone or Sel-Dex in patients with penta-refractory myeloma. To put the current level of unmet medical need in perspective for these patients…

Thank you, Michael. Since we issued a press release earlier today outlining our full financial results, I'll just review our third quarter 2018 financial highlights. As of September 30, 2018, cash, cash equivalents and investments, including restricted cash, totaled $212.3 million compared to $176.4 million as of December 31, 2017. On October 26, 2018, we completed a private offering of a $172.5 million aggregate principal amount of 3% convertible senior notes due in 2025. This offering included the full exercise of the initial purchasers’ option to purchase additional notes. After deducting the initial purchasers’ discounts and commissions and other estimated offering expenses, the net proceeds are $166.9 million. For the third quarter 2018, research and development expense was $36.4 million compared to $25.2 million for the same period in 2017. General and administrative expense for the third quarter 2018 was $13.0 million compared to $5.8 million for the same period in 2017. Comparing the third quarter of 2018 to the prior quarter, the second quarter of 2018, R&D decreased by $8.3 million. This quarter’s clinical trial spend was below trend while the second quarter spending was above trend. General and administrative expense increased $3.5 million from the prior quarter, primarily because of increased spending on our commercial launch. For the third quarter of 2018, we reported a net loss of $48.1 million, or $0.79 per share, compared to a net loss of $30.6 million, or $0.65 per share, for the third quarter of 2017. Net loss includes stock-based compensation expense of $4.8 million and $4.9 million for the third quarters of 2018 and 2017, respectively. Karyopharm expects its operating cash burn, including research and development and general and administrative expenses, for the year ended December 31, 2018 to be in the range of $175 million to $185 million. Following our private placement of convertible senior notes during October of 2018, and based on our current operating plans, we expect that our existing cash, cash equivalents and investments will be sufficient to fund operations into the second quarter of 2020. If selinexor receives FDA approval, cash generated from product sales could extend this runway even further. Our current operating plans include the continued clinical development of selinexor in our lead indications and on preparing the commercial infrastructure and hiring a sales force for the potential launch of selinexor in the United States. I’ll now turn the call back over to Michael Kauffman for concluding remarks. Michael?

Thanks, Mike. Before I review our upcoming milestones and move to the Q&A, I’d like to take a moment to formally welcome our newest member of our Board of Directors, Dr. Carsten Thiel. Dr. Thiel currently serves as Chief Executive Officer of Abeona Therapeutics and brings extensive experience in leadership positions with leading innovative and commercially successful life science companies including Alexion, Amgen and Roche. We believe his strategic insight and operational expertise commercializing medicines in international markets will be invaluable as we prepare to bring oral selinexor to patients across the globe and maximize its full commercial potential. Moving on now to our upcoming milestones. For our first selinexor NDA, we look forward to an FDA decision by April 6, 2019. And if approved, we expect to be well positioned to commercially launch selinexor as a new treatment for penta-refractory myeloma very shortly after approval. Additional data from the Phase 2b STORM studies supporting this NDA will be presented at this year’s ASH meeting in December. For our SADAL study in DLBCL, we also expect to report top line data at ASH in December which if positive could support a regulatory submission in the first half of 2019. For the pivotal Phase 3 BOSTON study we expect to complete enrollment by the end of this year with top line data expected by the end of 2019. And if positive, could support a regulatory submission in 2020 in second line multiple myeloma. In Q1 2019, we plan to submit a MAA to the EMA for conditional approval for selinexor in patients with penta-refractory myeloma. For the STOMP study in multiple myeloma, we look forward to presenting updates for the combination arms with Darzalex and Pomalyst at ASH and expect to provide additional updates from the other arms of the study at future medical meetings. Finally, regarding development in solid tumors, our ongoing Phase 3 SEAL study in liposarcoma and SIENDO study in endometrial cancer continue to actively enroll patients and top line data are expected by the end of 2019 to 2020, respectively. In closing, I would just like to take a moment to express my thanks to the entire Karyopharm team for all their hard work getting the first selinexor NDA filed. This was one of our most important milestones and brings us one giant step closer to achieving our goal of bringing this important new medicine to patients battling myeloma. We are committed to working closely with the FDA during the entire review process and if the FDA grants our request for accelerated approval, oral selinexor could be available to patients in the first half of 2019. I’ll now turn the call over to the operator for questions. Operator?

Thank you. [Operator Instructions]. Our first question comes from Jonathan Chang with Leerink Partners. Please go ahead.

Good morning. Thanks for taking my questions. First question, looking ahead to ASH, what do you see as the efficacy benchmark for the SADAL study and how do you see the positioning of selinexor versus CAR-T in the third line DLBCL setting?

First of all, let’s be clear. We’re not positioning against CAR-T at all. These are extraordinarily different therapies. There are two CAR-T products that are approved in the third line setting. And for patients that are eligible for CAR-T and want to consider that, that’s a great option. Our study specifically excluded patients who are eligible for high dose chemotherapy and any sort of transplantation which would include CAR-T and our Fast Track designation specifically set for patients who are not eligible for any kind of transplant, including CAR-T. So these are very different therapies. There are currently no small molecule drugs approved at all in the treatment of diffuse large B-cell therapy and the only drug that’s approved in that is rituximab which is approved only in first line as an add-on therapy to R-CHOP chemotherapy combination and similar combinations. So we believe the benchmark in this huge unmet medical need is pretty similar to that which we described for myeloma which was a response rate above 20% so that one in five patients or better would show a partial or complete response and a duration of response that five months or longer would be sufficient. And I’ll just close by reminding everyone that the interim data that were presented at EHA, at the European Hematology Association meeting, showed in 30 patients a response rate of approximately 30% with the duration of response longer than seven months. So we believe that if we’re in that kind of a range, this drug could get over the goal line for DLBCL.

Great. Thank you. Second question, how do you view the commercial opportunity for selinexor in the penta-refractory multiple myeloma setting? How are you thinking about expectations as it pertains to what a launch trajectory could look like?

Yes, I’m going to send that question over to Anand Varadan, our Chief Commercial Officer. Anand?

Great. Thank you for the question. So in the market research that we’ve been doing recently, what we’ve found is very much aligned with what – how Michael portrayed in this prepared remarks. There is a significant unmet need in these patients who don’t have any other options after they fail these prior therapies. And in that setting, the reaction to the – especially the efficacy that selinexor demonstrated in the STORM study is very encouraging to these clinicians, especially for those patients who are able to achieve a response. So in that sense, I can relate from research that having sort of validated that there is a commercial opportunity that’s driven by the unmet need in that marketplace. And the uptick trajectory is something that we’re going to spend some time really trying to understand more fully. But I think that the fact that there is a level of demand in that level of unmet need gives us encouragement in terms of the overall opportunity there and also obviously the potential benefits for the patients.

Great. Thanks very much and congrats on the progress.

Thank you.

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead.

Hi. Thanks for taking my questions. Congrats on all the progress and congrats too on your five-year anniversary as a public company. I guess my first question is on the recent announcement of Fast Track status. Can you give us any sense of I guess what type of data and I guess what type of elements the FDA was looking at to guide their decision to grant Fast Track status?

Yes, it’s a pretty standard review. FDA needs to be apprised of all available data that are present at the time with the submission. So FDA has been updated on the progress of the study and the results to date that we’ve presented. But I don’t want to say a lot more than that, but I can assure you that FDA is up to date on all of our available data.

Okay, got it. Understood. And then as you approach an MAA submission, can you give us any updates on how European regulators might view the bar in myeloma, any similarities or differences versus FDA and where you stand with respect to your views on commercialization outside of the U.S.?

Yes, so I’ll start and then I’ll again turn it over to Chris and then Anand on the commercialization front. We’ve certainly met with a variety of different countries to potentially bring selinexor to approval in Europe. And frankly they see the unmet medical need very similar to the way the FDA viewed it, which is that patients whose disease is refractory to the three major classes of anti-myeloma medicines, names IMiDs, proteasome inhibitors and Darzalex, really are in dire straits with the very short expected survival and novel therapies particularly those with completely new mechanism of action are very much welcomed. So they were very excited about the data and we expect to work closely with the Europeans to move that through the process. With that said, let me move it over to Chris and then potentially Anand.

Sure. This is Chris Primiano, Chief Business Officer. We’re continuing to explore potential partnerships to maximize the potential of selinexor in the European market and we’ll certainly provide more information on that when appropriate. We haven’t set a specific timeline or structure. As I think I’ve said before, ultimately we’ll only move forward with a partner who shares our vision and sense of urgency. And of course we’d only pursue a collaboration that maximizes the full commercial and financial potential of a novel first-in-class compound like selinexor. Right now, as Michael described, our focus is on the regulatory approval of selinexor in Europe based on the MAA that we plan to submit to the EMA in the first quarter of next year. And I’d also add that as our enthusiasm regarding the commercial potential for selinexor increases, we’re also evaluating the potential to commercialize selinexor on our own in select European countries.

Great. That’s really helpful. Thank you.

Thanks.

Thank you. Our next question comes from Maury Raycroft with Jefferies. Your line is open.

Hi. Good morning and congrats on the progress. First question is just on DLBCL. So there are several investigator led trials in lymphoma that are ongoing assessing selinexor in combos and I think you’ve mentioned before that those could inform a confirmatory trial in DLBCL. Can you go over how the story will come together and what plans and timelines are for a confirmatory study?

Sure. So we’re exploring a variety of different options for a combination of selinexor with various – generally with chemotherapy because currently, as I mentioned, those are pretty much the standard of care in the treatment of DLBCL. We are considering combinations with ICE chemotherapy in the second line setting. We’ll be looking at things like bendamustine as well as a selinexor plus benda and usually plus rituximab versus chemo with rituximab or similar types of design. We’re conducting studies also in combination with ibrutinib which is ongoing and including DLBCL and with Vel-Dex [ph] as well. So there are a variety of different options here. And if I had to be a betting man today and this is completely preliminary, I would bet it would be selinexor or placebo against the backbone of chemo plus Rituxan.

Got it. And will some of the investigator led data, will that be at --?

Those two discussions that we will have with the FDA that we didn’t have yet.

Okay. And then also for the SADAL study, so I think you – 50-50 split between the GCB and the non-GCB populations. And I don’t think you broke out the durability for the two populations in the EHA 2017 data. Is that something that we should be focused on for the ASH update or I don’t know how important it is for the durability differences between those two populations?

Yes. So as you intimated, we do include at least 50% of patients with GCB and this is really partly unmet medical need discussion to ensure that we’re getting an adequate representation of patients with that subtype of DLBCL. As some of you are aware, the response to chemotherapy for the GCB patients is superior to that for ABC, so there tend to be fewer of them. But it means that the subsequent response is to either chemo or novel agents tend to be a lot worst for the GCB subset, in some ways making it a higher unmet medical need. We do intend to provide full data that are available to us at the time of the presentation at ASH, so I would definitely look for that. But in the past as you’re aware, both the response rate has certainly been similar in the two populations which is consistent with selinexor’s broad mechanism of action. And we would anticipate that there’s shouldn’t be extraordinary differences in the duration but hope to provide similar – supportive data at ASH.

Thank you. Our next question comes from Eric Joseph with JPMorgan. Please go ahead.

Hi. Good morning and thanks for taking the questions. For selinexor in STORM, I’m wondering if you have any greater visibility on the likelihood of a ODAC panel and how the team is preparing in anticipation, what specific issues the agency might be interested in relative to some of the other [indiscernible] that you’ve seen to-date? And with the SADAL study in DLBCL, I’m wondering how you’re viewing selinexor relatively positioned at some of the developing monoclonal antibody for seeing specifically more 208 [ph] and daratumumab, and sort of whether their clinical potential is impacting how you’re thinking about the third line relapsed/refractory DLBCL commercial opportunity? Thanks.

Yes, so simple answer on the first part. We don’t have any more insight beyond what we disclosed publicly that FDA has said that there may be an ODAC panel which is the standard positioning for FDA on any new molecule for STORM. So I can’t give you any more update on that at all. On the second part, I can say that we really need to remember that selinexor is not only a novel therapy but the mechanism of action which is to activate tumor suppressor proteins by forcing them to stay in the cell nucleus and do their job. And also to reduce the levels of onco proteins such as c-myc and bcl-2, which are both relevant especially in DLBCL. But this is really an opportunity to bring a new oral therapy to combine with many of the available therapies. You’ve already seen our combinations in myeloma and across the board with IMiDs, proteasome inhibitors and Darzalex, the preliminary data suggest that there is strong additive of our synergistic activity. And particularly with Darzalex, there will be an update at ASH which is a monoclonal issue, no. So we see – actually the advent of new monoclonals in myeloma and in DLBCL and frankly in other diseases where we’ll be studying selinexor. And the real boon to our mechanism where we can come in and activate tumor suppressors, the monoclonals do their job killing cells which usually involves a p53 or a similar type of tumor suppressor step and we expect to see – or we might see additive or synergistic activity in a lot of these combinations. And taking an oral pill while you’re getting your antibody infusion is really simple. So it doesn’t add a lot of burden to the daily life of the patient.

Got it. Thanks for taking the questions.

Thank you. Our next question comes from Michael Ulz with Baird. Please go ahead.

Hi, guys. Thanks for taking the questions. I guess just at the upcoming ASH meeting you mentioned you’re presenting some additional data from STOMP in combo with Darzalex and Pomalyst. So I’m just curious if you can talk about your combination strategy in multiple myeloma going forward sort of beyond Velcade and next steps there and timelines and maybe how you’re thinking about prioritizing potential other combinations? Thanks.

Yes, thanks very much for the question, Mike. Yes, this is part of a very – much, much larger discussion about whether we push deeply into myeloma where we already have an ongoing Phase 3 in second line myeloma in combination with Velcade. We will be coming up with Phase 1/2 data in first line myeloma in combination with Revlimid, the all oral selinexor, Revlimid and dex regimen. And in later lines in combination with Darzalex where we’ve seen very nice response rates in patients whose disease is double refractory. We’re also working in myeloma with the major cooperative groups in the U.S. and outside of the U.S. because doing some of these trials in myeloma has become very complicated. And we’re actively working inside to determine how much Karyopharm will directly run, cooperative groups will run and also how broadly we want to move. As you know, we’re moving into DLBCL. We have trials in solid tumors ongoing including our SEAL study in liposarcoma, our SIENDO study in uterine cancer and our study in glioblastoma multiforme in the KING study and additional investigator-sponsor trials in other types of cancer, in particularly solid tumors. In addition, we’re starting our second generation compound eltanexor in prostate and colon cancers as well as in myelodysplastic syndrome. So we have a great deal going on and the mechanism of action of both selinexor and the second generation SINE eltanexor have really led themselves broadly across multiple types of cancers. And as an ongoing process here and just the change in time and new data come out, we’ll be determining how deeply we move to registrational trials in myeloma or do we go more broadly into different types of cancer.

Got it. Thanks, guys.

Thank you. Our next question comes from Konstantinos Aprilakis with JMP Securities. Please go ahead.

Hi, guys. This is Simon on for Konstantinos. Thanks for taking the questions. Just curious on the safety front in DLBCL versus penta-refractory multiple myeloma, obviously both indications with relatively frail patients. Just curious if you’ve seen the same kind of trend or heard about it from your study physicians where there’s kind of a learning curve, a lot of the side effects are kind of constitutional symptoms. I think you’ve said in the past that your study physicians kind of learn to mitigate or address these symptoms before they even occur. I’m just curious if you’ve seen the same kind of trend in the DLBCL patients that you have with penta-refractory multiple myeloma?

Yes, so very good. Keep in mind that patients in the STORM study had an average of seven prior regimens and six years or six and a half years of disease. So these are extremely heavily pretreated patients. And they’ve received some of the best drugs available in all of hematology chronologic drugs. So it’s a very, very frail population. Unfortunately because of the slower drug development in DLBCL, we’re getting patients with three – a median of three prior regimens in our interim. We’re not giving them dex because we don’t need to and also because dex is not a standard of care for treatments in lymphoma the way it is for myeloma. And we’re also using a lower dose of selinexor in the patients with DLBCL. So the patients enrolled in the SADAL are less frail and have less issues, had less prior therapies than patients in the myeloma study. They’re receiving a dose that’s 25% lower. And while the physicians do have somewhat of a learning curve with selinexor as they do frankly for all new drugs, we definitely see a dose response on side effects and they do appear to be fewer side effects in the SADAL population than in the STORM population. And qualitatively – I’d just add that qualitatively the side effects are similar.

Okay. Thank you.

Thank you so much. Our next question comes from Ed White with H.C. Wainwright. Please go ahead.

Hi, guys. Thanks for taking my questions. So first just quickly on the commercialization in the U.S., how should we be thinking about the hiring of the sales force, the size? And if you said January – is January going to be the full bolus of sales people or will you be ramping up throughout the year? And then I have a follow-up question.

Great. So I’ll turn it over to Anand.

Sure. Thanks. What we’re targeting is a group of around 70 in the field and the timing for that – the recruiting for that is ongoing. And we’re planning to have them onboard would be in January is what we’re doing. So we already have our full group of sales managers. We’ve had excellent response from the sales community for opportunities with Karyopharm. We’re going through that process now and we’ll have those folks onboard and being training in that timeframe.

Okay, great. Thank you. And then just on the endometrial cancer side, so what is the company’s plans there? I know that’s an investigated-sponsor trial in Phase 3, so will the company follow up with their own – with your own Phase 3 or how should we be thinking about moving forward in endometrial?

Yes, it’s too early to say exactly what our plans are with endometrial. It’s a good study. It’s ongoing. It’s a big unmet medical need in the maintenance setting. There are currently no maintenance agents approved in uterine cancer and people unfortunately generally do relapse after chemotherapy. So we’re assessing that and – it’s part of the earlier question that was asked as part of the more global question about how deep do we go in myeloma and lymphoma and other diseases versus how broad.

Okay. Thanks, Michael. And then just I was wondering if you can give us an update on eltanexor in colorectal and the other indications as well. When should we plan to see more data?

So we are very close to finish the Phase 1 of eltanexor. We presented some of the earlier results in ESMO this year and we’ll continue to present data on the other indications going forward in this study, including the prostate in the upcoming conferences in 2019. And in 2019 we also will decide on the next steps with eltanexor and which indication we are going to develop it.

Okay. Thank you.

Thank you. Our last question comes from Ying Huang with Bank of America Merrill Lynch. Please go ahead.

Hi, guys. This is Alec [ph] on for Ying. Thanks for taking our questions. A couple on the SADAL trial. Are there any major differences you noticed between the responders and non-responders that you can point to explaining the differential response? And at ASH, should we expect more than 32 patients for efficacy in the 60 mg arms since the abstract was submitted?

So for your first question, this is a very good question and we are working by ourselves and with many, many collaborators to identify biomarkers for response. We don’t have them yet and there is – we are planning to share some of this result in meetings in 2019. For your second question, as we mentioned in the [indiscernible], we will provide to update it as we can at ASH.

Okay. And on the BOSTON trial, that’s almost fully enrolled at this point. I was wondering if you’ve got any sense at physician comfort with selinexor in penta-refractory versus using in earlier lines of therapy and what do they sort of see as the biggest value add in the earlier lines of therapy? Thanks.

Yes, this gets back a little bit to the question with addition of selinexor to other agents. The exciting thing about the Sel-Vel-Dex regimen is that it’s a one a week regimen. And to our knowledge it’s the only Phase 3 or the first Phase 3 study that uses an experimental arm involving once weekly Velcade keeping in mind that subcutaneous Velcade does require a physician office visit. So reducing the number of office visits, there’s a substantial burden reduction on patients, many of whom are elderly. Secondly, again, people are coming in to get an injection, they generally have to be checked, their standard vital signs and all. And taking a pill while you’re getting your Velcade injection doesn’t add a lot of time or effort for the patient. So it’s a very nice simple regimen to use. The Sel-Vel-Dex Phase 1/2 paper has been published and that’s in blood recently. So that’s available online. And I’ll just close by saying that if we can deliver the kinds of efficacy that we saw in the Phase 1/2 and this Phase 3 where we also had a much lower rate of neuropathy with Sel-Vel-Dex as compared to standard Vel-Dex, this could be a real improvement. Selinexor itself is only given once a week in these combinations. And the dose of 100 milligrams once a week which is used is about 60% lower than the weekly dose used in the STORM study in much sicker patients. So the combination of a reduced dose of once weekly dosing in a much, much healthier population of patients mean that selinexor as part of SVd and other combination regimens is considered well tolerated by most physicians and we haven’t seen significant pushback on that even in our global Phase 3 study.

Thank you. Ladies and gentlemen, this concludes our Q&A session for today. I will like to turn the call back to Michael Kauffman, Chief Executive Officer, for his final remarks.

Thank you, everybody, for joining this call. And I want to just also thank again all of the patients, their caregivers and their families who participate in our studies as well as clinical investigators for helping move this exciting new potential oral medicine forward and towards approval next year. Thanks all and we look forward to seeing many of you at ASH. Have a good day. Bye-bye.

With that, ladies and gentlemen, we thank you for participating in today’s conference. This concludes the program. You may all disconnect. Have a wonderful day.