Good morning. My name is Shiri and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics' Fourth Quarter and Full Year 2019 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. Please go ahead..

Thank you, Shiri and thank you all for joining us on today’s conference call to discuss Karyopharm’s fourth quarter and full year 2019 financial results and business update. This is Ian Karp and I’m joined today by Dr. Michael Kauffman, our Chief Executive Officer; Dr. Sharon Shacham, President and Chief Scientific Officer; Mr.

Mike Mason, Chief Financial Officer; Mr. Chris Primiano, Chief Business Officer and General Counsel; Mr. Perry Monaco, Senior Vice President of Sales.On the call today, Michael will provide an overview of key recent corporate developments and an update on the commercial launch of XPOVIO.

And Mike will then highlight the fourth quarter and full year 2019 financial results. We will conclude with the Q&A portion of the call.Earlier this morning, we issued a press release, detailing Karyopharm’s results for the fourth quarter and full year 2019.

These releases as well as an accompanying slide presentation are available on our website at karyopharm.com.

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.These include statements of our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations relating to the commercialization of XPOVIO, financial projections, and our plans and prospects.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those 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 any references we make to clinical trial data during today's discussion refer to interim unaudited site data, unless otherwise specified.

We will also be providing on this call, non-GAAP outlook for operating expense for 2020, which can only be provided under non-GAAP basis without unreasonable efforts.I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer of Karyopharm..

Thank you, Ian. And good morning, everyone. And for those following along with the slide presentation, please now turn to slide 4. 2019 was a monumental year for Karyopharm marked by the accelerated approval of XPOVIO in July.

XPOVIO is the first and only nuclear export inhibitor approved in the US and is indicated in combination with dexamethasone for patients with heavily pretreated multiple myeloma. Karyopharm has a rich history as an innovation driven drug development company.

And in 2019, we rapidly transition into an integrated commercial stage oncology company.While we continue to expand our commercial footprint and grow our operational capabilities, we remain ever committed to advancing innovative science and developing medicines with novel mechanisms of action on behalf of patients.

And we remain optimistic as we look to the future with increasingly promising pipeline of clinical programs for selinexor and our other drug candidates directed in an increasing spectrum of human cancers. On the commercial front, XPOVIO continue to build momentum in its second quarter with increased adoption from prescribing physicians.

We are very pleased to report XPOVIO product sales of $17.7 million in the fourth quarter and $30.5 million for the full year 2019.The demand for XPOVIO has been driven by a broad base of healthcare providers both academic and community based oncologists with over 550 unique physicians or accounts having prescribed XPOVIO through the end of 2019.

We are delighted with the early physician and patient experience with XPOVIO and look forward to expanding our commercial reach in the months and years ahead.In parallel to our commercial efforts, we continue to make additional important clinical and regulatory progress in the fourth quarter.

Our pivotal Boston study remains on track with top-line data expected before the end of April this year.

Additionally, we are very pleased to announce that at the end of December 2019, we submitted a supplemental new drug application to the FDA requesting accelerated approval for selinexor based on our SADAL study as a treatment for patients with diffuse large B-cell lymphoma after at least two lines of therapy.

If approved, this would represent our second indication for XPOVIO in a group of patients with significant unmet medical need where there are no currently approved oral drug regiments available to patients.On the European front, the EMA is currently reviewing the marketing authorization application we submitted for XPOVIO in January of last year as a new treatment of patients with heavily pretreated multiple myeloma based on the results of the Phase 2b STORM study.

Recently, we were granted a three-month extension from the EMA's committee for medicinal products for human use providing Karyopharm with additional time to respond to the outstanding questions related to the marketing authorization application. Based on this revised timeline, we now expect a decision on the MAA in mid-2020.

On the development front, we plan to initiate five company sponsored clinical trials in 2020 largely in combination with other active and potentially synergistic anti-cancer drugs. I will highlight a few of these trials in my later remarks.And now please turn to slide 5 for some additional details on XPOVIO sales growth in 2019.

Thanks in large part to the hard work and dedication of our highly experienced commercial team; we saw a 38% increase in net XPOVIO sale in Q4, 2019 as compared to Q3, 2019.

Importantly, we saw an even more impressive 65% increase in the actual prescription demand in the fourth quarter, which reflects XPOVIO prescription shift from Karyopharm's distribution partners to individual patients and prescribing healthcare accounts.

Recall the Q3, 2019 was the first quarter we introduced XPOVIO into the US market and there was approximately $3 million in XPOVIO sales in that quarter that went towards building initial channel inventory at our distribution partners.Increased fourth quarter sales were primarily driven by a combination of new patient starts and prescription refills with total prescriptions filed approaching 1,400 by the end of 2019.

We are particularly pleased with the level of prescription refills today which we believe further validates physician's ability to effectively support their patients and help mitigate and manage potential side effects from XPOVIO treatment.

Our launch strategy continues to position XPOVIO as the oral agent of choice with a clinically meaningful efficacy profile in its approved indication.

And while it is still early in our launch cycle, the positive momentum seen to date has been highly encouraging and our conversations with prescribing physicians and patients reinforce our beliefs in the long-term potential of XPOVIO as a future standard of care in the treatment of patients with relapsed refractory multiple myeloma.In 2020, we expect to see increased adoption from high and moderate volume myeloma accounts as well as from first-time prescribers of XPOVIO.

We hope to build upon the strong foundation established in 2019 and further grow XPOVIO in the US on behalf of the patients and families looking for new and effective approaches in the treatment of refractory myeloma.Please now turn to Slide 6.

As excited as we are about the recent launch success for XPOVIO in patients with heavily pretreated myeloma, we are equally excited about what the future holds for Karyopharm and the additional cancer patients we hope to serve in the future.

We believe that our clinical pipeline has never been more robust or promising as specifically pertains to selinexor along with our second-generation sign investigational medicine eltanexor.

We have decided to initiate five new key clinical trials in 2020, largely in response to our growing confidence in the potential these agents have beyond just myeloma.First, we plan to initiate two studies in diffuse large B-cell lymphoma.

One will be a pivotal study of selinexor or matching placebo given with the standard combination in immunochemotherapy R-GDP to patients with at least one prior therapy and/or ineligible for high dose chemotherapy with stem cell, rescue or for CAR-T. R-GDP stands for rituximab, gemcitabine, dexamethasone and cisplatin.

The primary endpoint of this study 30 is PFS and this trial following agreement with FDA is expected to serve as a confirmatory study for the accelerated approval requested in DLBCL based on the SADAL study.

We also plan to initiate a second new trial in the DLBCL study 25 evaluating selinexor in combination with other commonly used and approved agents for the treatment of DLBCL.This study will inform the clinical development selinexor with a variety of additional agents for the treatment of diffuse large B-cell lymphoma.Next we plan to initiate new phase 1/2 trials to study the combination of selinexor in a variety of active anti-cancer agents in patients with colon cancer, non-small-cell lung cancer in glioblastoma.

Our hope is that these studies will help guide our future development strategies for selinexor with the ultimate goal of pursuing several additional registrational studies in the future in these indications.

Finally, based on encouraging data we presented at ASH in December 2019 with single agent eltanexor in patients with myelodysplastic syndromes refractory to standard treatment.

We plan to evaluate the combination of eltanexor with cedazuridine-decitabine, an oral hypomethylated agent in patients with newly diagnosed MDS.Beyond our selinexor and eltanexor programs, we were excited to see a new publication in the January 2020 edition of Nature Cancer that highlighted positive results from an important preclinical study of KPT-9274 as a potential therapeutic agent to overcome resistance to PD-1 checkpoint blockade immunotherapy.

KPT-9274 is our oral first in-class dual PAK4 and NAMPT inhibitor currently in a phase 1 single agent study.

Based on these preclinical data in this publication, we look forward to studying KPT-9274 in combination with an anti PD-1 monoclonal antibody in a phase 1 clinical study in the near future.Needless to say we have a lot of important clinical activities taking place in 2020, which we believe will help us maximize the long- term potential impact our investigational compounds may have in advancing cancer care for patients in need of new treatment options.With that I'll now turn the call over to Mike Mason to review the financials.

Mike?.

Thank you, Michael. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights which begin on slide 8. Net product revenue for the fourth quarter of 2019 was $17.7 million and $30.5 million for the year ended December 31, 2019.

As previously mentioned, 2019 sales were driven by a combination of patient demand as well as initial channel inventory sold to our distribution partners.

We estimate that of the $30.5 million in 2019 sales, approximately $26 million was driven by patient demand with the remaining approximately $4.5 million driven by channel inventory which was in line with our plan to have customers keep approximately three weeks of channel inventory.The estimated growth to net discount for XPOVIO in 2019 was approximately 15%.

We still project a steady-state range of 15% to 20%, however, we do expect some variability from quarter-to-quarter. Cost of sales was $1.4. million for the fourth quarter of 2019 and $2.4 million for the year ended December 31,. 2019.

Cost of sales reflects the cost of XPOVIO units sold and third-party royalties on net product revenue.Research and development expense for the fourth quarter of 2019 was $31.6 million, compared to $38.9 million for the fourth quarter of 2018.

R&D expense for the year ended December 31, 2019 was $122.3 million compared to $161.4 million for the year ended December 31, 2018. We expect our research and development expenses to increase in 2020 as compared with 2019 as we continue clinical development of selinexor in our lead indications as Dr.

Kauffman previously outlined with a focus on regulatory submissions for selinexor.For the fourth quarter of 2019, selling, general and administration expense was $28.4 million compared to $18.8 million for the fourth quarter of 2018.

For the year ended December 31, 2019, selling, general and administrative expense was $105.4 million compared to $48.8 million for the year ended December 31, 2018.

The increase in SG&A expenses compared to the prior year was due primarily to the hiring of the Karyopharm commercial team and related activities to support the US commercial launch of XPOVIO.

We expect our SG&A expenses to increase slightly in 2020 to support our expanding operating and commercial activities related to sales and marketing of XPOVIO.Cash, cash equivalents restricted cash and investments as of December 31, 2019 totaled $265.8 million compared to $330.9 million as of December 31, 2018.

The company sold approximately $30 million under its open market agreement or ATM during the fourth quarter of 2019. Finally, based on current operating plans, Karyopharm expects its non GAAP R&D and SG&A expenses which exclude stock based compensation expense for the full year 2020 to be in the range of $240 million to $260 million.

The company expects that its existing cash, cash equivalents and investments and the revenue it expects to generate from XPOVIO product sales will be sufficient to fund its planned operations until the middle of 2021.I'll now call back over to Michael for some concluding remarks.

Michael?.

Thank you, Mike. Before moving to the Q&A, let me highlight some of the key milestones we expect in 2020 which are found on slide 10. For the pivotal Phase 3 Boston study top-line data are expected before the end of April. The exact timing depends on the occurrence of progression events in the trial.

We called it Boston studies evaluating the combination of once weekly selinexor, once weekly Velcade and dexamethasone in patients with multiple myeloma who have one to two three lines of therapy.

If positive, these data could support regulatory submissions in 2020 in the United States and Europe for patients with multiple myeloma who have received at least one prior therapy. And then later in the year, we expect to following.A regulatory decision in Europe based on our MAA and heavily pretreated refractory myeloma.

Regulatory filings based on data from the Boston study. Top-line phases 3 assuming of course those data are positive. Top line phase 3 data from the SEAL study in liposarcoma and subsequent potential regulatory submissions based on these data.

A regulatory decision from the FDA based on DLBCL supplemental NDA as well as the potential US commercial launch of this in this indication if approved.

And finally, the potential US commercial launch for XPOVIO in second-line multiple myeloma assuming the Boston data are positive and support FDA approval.Clearly, there's a lot to follow and we look forward to providing updates on these important milestones throughout the year.

We appreciate your support to look forward to keeping you updated on our 2020 progress in the coming months and quarters ahead.I'll now turn the call over to the operator for questions.

Operator?.

[Operator Instructions]Our first question will come from Eric Joseph with JP Morgan/.

Hey. Good morning, everyone. This is Tera on for Eric. Thank you for taking my questions. Just a couple quick ones from us. So first I know you've reiterated timelines for Boston, but I'm curious have you hit a sufficient number of PFS events to trigger the final analysis? Sound like you're very close at a conference about a month ago..

Yes. Thanks for the question. We're close enough to the eventual announcement of the Boston events but we're not prepared to answer any additional specifics on this. We're waiting for the data to come in. When and if it does, we will have it processed properly through the IRC, the DSMB and reviewed by FDA and then we'll make an announcement..

Okay. Thank you and then I'm just hoping can you provide any additional color on the extension you receive from the EMA and DLBCL and that made - -excuse me -- [Indiscernible] and the nature of the outstanding questions you have to answer..

Yes. The EMA is reviewing the data, frankly line by line these are normal questions. There are a fair number of them obviously FDA had far fewer of them. And we're just running through this so they just granted us a three month longer extension to continue to work through the list..

Our next question will come from Maury Raycroft from Jefferies..

Hi, everyone. Good morning and congrats on the updates today. I had a question on the confirmatory DLBCL trial.

Could you provide more specifics on the design including the number of patients and expectations on PFS?.

Yes. I can't give you a final number, but it'll go up on clinical trials.gov in the not-too-distant future. But basically it's a randomized blinded study selinexor with matching placebo evaluating with --against a backbone of R- GDP which is as I mentioned rituximab, gemcitabine, dexamethasone, and p is cisplatin.

This is R-GDP at a pretty standard regimen.

It's --the goal of the study is to really introduce a potentially more powerful backbone regimen R- GDP rather than typical [Indiscernible] for these patients and to use selinexor both in the induction part where the patients will get six cycles of the -- up to six cycles of the R-GDP and then they can continue selinexor indefinitely following response either PR or CR.

So this will be one of the first kinds of these studies in second third line DLBCL to look at an adoption and maintenance in a second third line..

Got it. That's helpful.

And then a second question is just if you can provide any additional perspective into the pair make shifting more towards commercial and then anything else that you're seeing from use in the commercial setting with combo use that you can providing perspective on?.

So Perry will handle that..

Yes. So with regards to combo, while we can't break out specifically how much XPOVIO is being used in combination with other anti myeloma drugs. We do know from our own market research that many academic and community based physician are prescribing XPOVIO in combination with other drugs.

Our commercial team will of course only focus on clinical data that's within XPOVIO approved FDA label. However, as I'm sure you know there's quite a bit of data from combination studies and they've been presented at medical meetings and have been published including most recently at the 2019 ASH conference.

And we do get many unsolicited inquiries to our medical affairs department for information about combination data.With regards to the pair make, I think the pair make remains pretty much consistent with what we had expected prior to our approval.

And I don't think we really expect that to change as the patient population for myeloma is somewhat of an elderly patient population..

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

Hey, guys. It's [Indiscernible] on for Brian. Thanks for taking the questions and congrats on the progress. Two quick ones for me.

First, it sounds like the demand and the refill rate has continued to be strong here, wondering so you have a sense for average time on therapy now, now that we're a greater than six months into the launch compared to what you might have expected from the clinical trial data? And if there's any real-world upside there? And then second question just briefly following up on a prior question.

Is there any sense that the given the timelines the EMA approval would be at all contingent on what you see from Boston? Thanks..

So, Perry, I'll handle the first question..

Yes. So with regards to timeline therapy, it's still a little early to tell. We are very encouraged obviously with those refill rates. We're seeing our discontinuation rates due to side effects to be lower than what was reported in STORM. So these are very good early indicators, but again I know we're six months but it's still too early.

We've got some good persistency there though..

Yes. And regarding the question to be clear the MAA application that's being reviewed right now is based on STORM for patients with triple class refractory disease and at least three prior regimens. There's no explicit connection between the two.

It does so happen that it's highly likely that there will be Boston data available during this three-month extension. How and if the MAA chooses to use those data will be up to them..

Our next question comes from Michael Ulz with Baird..

Hey, guys. Thanks for taking the question and congrats as well as on all the progress. I just had a question on the Boston study and top-line data you're expecting before the end of April here.

Can you just give us a sense of what you plan to release in the top-line results? For example should we expect PFS? Will that include hazard ratio maybe a p-value? And then should we expect any color on safety? Thanks..

Thanks Mike. Yes, I think you hit the main elements that we're intending and part of this is contingent upon agreement with various convention and important meeting discussions to make sure that we can bring the data out in a fulsome way in front of the academic and treating communities.

But our hope is to present medium progression-free survival potentially with a hazard ratio and a p-value and then to make some general comments on safety.

I think as most people are aware this study is --we're aware of all the safety events on the trial and we continue to see that there are no new safety signals as of last week when we reviewed this. And there are no -- there is no imbalance of deaths against the selinexor as we've seen in some recent other trials.

So we're very confident that on the safety side the drug is performing in the way expected..

Our next question comes from Ed White with H.C. Wainwright..

Good morning. Thanks for taking my question.

So regarding the salesforce are you right size right now if the Boston data is positive or will you be adding more sales people? And then also I just wanted to your thoughts on the strategy and if there'll be additional people needed for DLBCL provided you get approval for that indication as well?.

Yes. So, Perry will handle that..

Yes. So thanks for the question. So when we sized originally we sized with DLBCL in mind. And so we don't feel like that will require us to add any people. We do look at this stuff on a regular basis and while the Boston indication does give us a greater patient population that we can serve.

The customer base that treats multiple myeloma remains the same. So we believe we're right size for the Boston indication as well..

Great. Thank you. And then just on the EMA. I'm just wondering if you can narrow the timeline of the EMA submission for DLBCL. If you can say early middle or late 2020. And then also does the multiple myeloma extension have any impact at all on your thoughts about the DLBCL submission in Europe? Thank you..

Sure. The plan on the DLBCL submission in Europe is going to be that the timing will likely coincide probably more with the Boston submission in Europe. It's just easier for us to handle the two submissions together. So we'll be thinking about that but we haven't made a final decision on that..

Our next question comes from Jonathan Chang with SVV Leerink..

Good morning. And thanks for taking my questions. First question, you indicated at ASH plans to evaluate the SPD triplet in a phase 3 study.

Is that still the plan?.

Yes. We're still considering an SPD study. We just haven't marked it for a start date given the other trials which we think are critically important and of equal or potentially even higher medical value.

So we will -- we'll keep updating you on that, but there's a lot of interest in this triplet and exactly which venue we'll be using to have it evaluated will depend on some new information going forward. But we tend to go forward with it. We just haven't figured out the venue yet..

And secondly, can you about the rationale for evaluating the selinexor combination studies in colorectal and lung cancer?.

Yes. Sure. You may recall although it was a very long time ago, it seems several years ago we published the phase 1 results of single agent selinexor in first in human in patients with advanced solid tumor malignancies. There were I believe six different partial responses there.

These were resist confirmed partial responses across a smattering of diseases. One of the PRS was in metastatic colorectal cancer, KRAS mutant one of them a couple of them are actually in melanoma; one was in I believe in pancreatic cancer and one in ovarian cancer.

So there was -- and then a couple of others.So there is some single agent activity of this drug in solid tumors and you'll see the first activity and actually in liposarcoma in the phase 3 readout which we expect to be mid this year.

But got back to the colorectal and lung, there's a given the single agent activity in colorectal that we reported and there were a number of stable disease patients, and we've also followed that up with some additional data from Asian patients with colorectal particularly with KRAS mutant colorectal disease that show that that selinexor can induce tumor shrinkage not typically in the PR range, but certainly shrinking tumors with some durability.

So there is some single agent activity in colorectal. Obviously, the PD-1 have shown minimal activity in microsatellite stable colorectal cancer.

And so the goal will be to combine these two agents that show minimal activity separately in an attempt to generate sufficient neo antigens to get the PD-1 to work and then obviously to complement the XPOVIO mechanism of selinexor with the immunotherapy.I should say there's an ongoing study at MD Anderson looking at selinexor in combination with [Indiscernible] and then we've established the safety of these combinations and we look forward to presenting some combination data in the not-too-distant future and in those indications across several solid tumors.

So we know that we can do these combinations safely and we want to expand this into colorectal which is a big unmet need now given the minimal activity of new drugs in colorectal cancer.On the lung cancer side, there was a Nature Medicine publication of the mechanism of action of selinexor in lung cancer particularly in KRAS mutant lung cancer and docetaxel is a standard of care second line agents.

So we've had an investigator sponsored trial that's been ongoing. In this we are encouraged by what we've seen to the point in that study of XPOVIO plus docetaxel to make that into a company sponsored trial and we expect to have some updates for that trial later this year as well.

So there's good preclinical and some clinical evidence for the activity of these regimens now in some very important solid tumors. And we're looking forward to announcing some data this year and next in that regard.End of Q&A.

Thank you. Speakers, I'm showing no further questions in the queue at this time. I'd now like to turn the call back over to Michael Kauffman for any further remarks..

Hi. Thanks very much and thanks everybody for joining us today. I think we are going to see a great year coming. And we look forward to updating on all the progress. Have a great day..

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