Good morning. My name is Sherry, 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. Please be advised that this call is being recorded at the company's quest. 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, Sherry, and thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter full year 2019 financial results and business update. This is Ian Karp, and I'm joined today by Doctor. Michael Kaufman, our Chief Executive Officer Mr. Mike Mason, Chief Financial Officer Mr. Christopher Permiano, Chief Business Officer And General Counsel and Mr.
Perry Monaco, Senior Vice President 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 4th quarter and full year 2019 financial results. We will conclude with the Q and A portion of the call. Earlier this morning, we issued a press release detailing Carifarms results for the fourth quarter full year 2019.
This release, 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 about future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations related the commercialization of XBovio, 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 factor sections 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 on a non GAAP basis without unreasonable efforts. I'll now turn the call over to Doctor. Michael Kaufman, 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 number 4. 2019 was a monumental year for Karyopharm, marked by the accelerated approval of Expovio in July. Exposvio is the 1st and only nuclear export inhibitor approved in the U. S.
And is indicated in combination with dexamethasone for patients with heavily pre treated multiple myeloma. Karyopharm has a rich history as an innovation driven drug development company. And in 2019, we rapidly transitioned 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 both selinexor and our other drug candidates directed in an increasing spectrum of human cancers. On the commercial front, Exposvio continued to build momentum in its 2nd quarter with increased adoption from prescribing physicians.
We are very pleased to report Xposvio product sales $17,700,000 in the 4th quarter $30,500,000 for the full year 2019. The demand for Expevio 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 of 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 SAGL 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 regimens available to patients. On the European front, The EMA is currently reviewing the marketing authorization application we submitted for Expobio in January of last year as a new treatment for patients with heavily pretreated multiple myeloma based on the results of the Phase 2b storm study. Recently, we were granted a 3 month extension from the EMA's committee from additional 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-twenty 20.
On the development front, We plan to initiate 5 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 Expobio 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 exposure sales 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 exposure prescriptions shipped from Karyopharm's distribution partners to individual patients and prescribing healthcare accounts.
Recall recall that Q3 2019 was the first quarter we introduced Xpobio into the U. S. Market and there was approximately $3,000,000 in Xpobio sales in that quarter, that went towards building initial channel inventory at our distribution partners. Increased 4th quarter sales were primarily driven by a combination of new patient starts and prescription refills, with total prescriptions filed approaching 1400 by the end of 2019. We are particularly pleased with the level of prescription refills to date which we believe further validates physician's ability to effectively support their patients and help mitigate and manage potential side effects from Expovio 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 Expevio 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 Xpobio. We hope to build upon the strong foundation established in 2019 and further grow Expobio in the U. S.
On behalf of the patients and families looking for new and effective approaches the treatment of refractory myeloma. Please now turn to Slide 6. As excited as we are about the recent launch excess for Xpobio 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 it specifically pertains to selinexor, along with our 2nd generation sign investigational medicine elvenxor, we have decided to initiate 5 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 2 studies in diffuse large B cell lymphoma. One will be a pivotal study of selinexor or matching placebo given with the standard combination immuno chemotherapy, our GDP, to patients with at least one prior therapy and who are ineligible for high dose chemotherapy with stem cell, rescue or for CAR T. Our GDP stands for rituximab gemcitabine dexamethasone in cisplatin. The primary endpoint of this study, Study 30, Is PFS in 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 DLBCL Study 25 evaluating selinexor in combination with other commonly used and approved agents for the treatment of DLBCL. This study will inform with a variety of additional agents for the treatment of diffuse large B cell lymphoma. Next, we plan to initiate new Phase III trials to study the combination of selinexor and a variety of active anti cancer agents in patients with colon cancer non small cell lung cancer, and 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 eltonixar in patients with myelodysplastic syndromes or fracture to standard treatment, we plan to evaluate the combination of eltonixar with cetazyridine decitabine, an oral hypomethylating agent in patients with newly diagnosed MDS.
Beyond our selinexor and eltonxor programs, we were excited to see a new publication in the January 2020 edition of Nature Cancer. That highlighted positive results in an important preclinical study of KPT-nine thousand two hundred and seventy four as a potential therapeutic agent to overcome resistant to PD1 checkpoint blockade immunotherapy. KPT-nine thousand two hundred and seventy four is our oral 1st in class dual PACT4 and NAMT inhibitor currently in a phase 1 single agent study. Based on these clinical data in this publication, we look forward to studying KPT-nine thousand two hundred and seventy four in combination with an anti PD-one 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 begin on slide 8. Net product revenue for the fourth quarter of 2019 was $17,700,000 and $30,500,000 for the year ended December 31, 2019. As previously mentioned, 2019 sales were driven by patient demand as well as initial channel inventory sold to our distribution partners. We estimate that of the $30,500,000 in 20.19 sales, approximately $26,000,000 was driven by patient demand, with the remaining approximately $4,500,000 driven by channel inventory, which was in line with our plan to have customers keep approximately 3 weeks of channel inventory.
The estimated gross to net discount for Expovio 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 were $1,400,000 for the fourth quarter of 2019 2 $400,000 for the year ended December 31, 2019. Cost of sales reflect the cost of Expevio units sold and third party royalties on net product revenue. Research and development expense for the fourth quarter of 2019 was $31,600,000 compared to $38,900,000 for the fourth quarter of 2018.
R and D expense for the year ended December 31, 2019, was $122,300,000 compared to 161 point $4,000,000 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 Doctor. Kaufman previously outlined, with a focus on regulatory submissions for selinexor. For the fourth quarter of 2019, selling, general administration expense was 28 $400,000 compared to $18,800,000 for the fourth quarter of 2018. For the year ended December 31, 2019, selling general administrative expense was $105,400,000 compared to $48,800,000 for the year ended December 31, 2018.
The increase in SG and A expenses compared to the prior year was due primarily to the hiring of the carrier from commercial team and related activities to support the U. S. Commercial launch of Expobio. We expect our SG and 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 $265,800,000 compared to $330,900,000 as of December 31, 2018.
The company sold approximately $30,000,000 under its open market agreement or ATM during the fourth quarter of 2019. Finally, based on current operating plans, KaryPharm expects its non GAAP R and D and SG and A expenses, which exclude stock based compensation expense. The full year of 2020 to be in the range of $240,000,000 to $260,000,000. The company expects that its existing cash cash of Lenten investments and the revenue it expects to generate from exposure product sales will be sufficient to fund its planned operations until the middle of 2021. I'll now turn the call back over to Michael for some concluding remarks.
Michael?
Thank you, Mike. Before moving to the Q and A, Let me highlight some of the key milestones we expect in 2020, which are found on Slide 10. For the pivotal Phase III 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. Recall that BOSTON study is evaluating the combination once weekly selinexor, once weekly Velcade and dexamethasone in patients with multiple myeloma, who've had 1 to 3 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 the 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 Phase III, assuming, of course, those data are positive, Top line Phase III 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 U. S. Commercial launch of this in this indication, if approved.
And finally, the potential U. S. 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 and look forward to keeping you updated on our 2020 progress in the coming months and quarters ahead.
I'll now turn
Our first question will come from Eric Joseph with JP Morgan.
Hey, good morning, everyone. This is Turner on for Eric. Thank you for taking my Just a couple of quick ones from us. So first, I know you 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 our conference about a month ago?
We're close enough to the eventual announcement of the Boston events that 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 mention you received from the EMA and DLBCL and just the or excuse me, in enter refractory melanoma 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's 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 3 month longer extension to continue to work through the list.
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 clinicaltrials dotgov in the not too distant future. But basically, it's a randomized blinded study, selinexor with matching placebo, evaluating with against the backbone of our GDP, which is, as I mentioned, rituximab, gemcitabine dexamethasone, the P is for cisplatinum, This is our GDP. It's a pretty standard regimen. It's the goal of the study is to really introduce a potentially more powerful backbone regimen, our GDP rather than typical bendamustrine rituxan for these patients and to use selinex or both in the induction part where the patients will get 6 cycles of the up to 6 cycles of the RGDP.
And then they can continue selinexor indefinitely. Following a response either PR or CR. So this will be one of the first kinds of these studies in 2nd, 3rd line DLBCL to look at an induction and maintenance in the 2nd, 3rd line.
Got it. That's helpful. And then second question is just if you can provide any additional perspective, into the payer mix shifting more towards commercial. And then anything else that you're seeing from, use in the setting with combo use that you can provide any perspective on?
So, Perry, I'll 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 physicians are prescribing Xpovio in combination with other drugs Our commercial team will of course only focus on clinical data that's within Xpovio's 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 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 payer mix, I think the payer mix 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.
Got it. Thanks for taking my questions.
Yes.
Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets.
Hey guys, you got Owen on for Brian. Thanks for taking the questions and congrats on the progress. 2 quick ones for me. First, it sounds like the demand and the refill rate has continued to be strong here. Wondering if you have a sense for average time on therapy now now that we're greater than 6 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 time on 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 6 months, but it's still too early. We've got some good persistency there though.
Yes. And regarding the question, To be clear, the M and A application that's being reviewed right now is based on storm for patients with penta refractory, sorry, triple class refractory disease and at least 3 prior regimens. There's no explicit connection between the 2. It does so happen that it's highly likely that there will be Boston data available during this 3 month extension. How?
And if the MAA chooses to use those data, we'll be up to them.
Our next question comes from Mike Alts with Baird.
Hey guys. Thanks for taking the question and congrats as well as on all the progress. 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? 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 median 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 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 arm as was seen in some recent other trials. So we're very confident that on safety side, the drug is performing in the way expected.
Thank you. Our next question comes from Ed White with H. C. Wainwright.
So,
regarding the sales force, are you rightsized right now if the Boston data is positive or will you be adding more sales people? And then also I just wanted to get your thoughts on the strategy and if there'll be people needed for, DLBCL provided you get approval for that indication as well?
Perry, I'll handle that. Yes. So, thanks for the question. So, when we sized originally, we sized with DLBCL in mind. And so, we 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 sized for the Boston indication as well.
Great. Thank you. And then just on, the EMA, wondering if you can narrow the timeline of the MA submission for DLBCL. If you can say early, middle or late 2020, And then also does the multiple myeloma extension have any pick impact at all on your thoughts about the DLBCL submission in Europe? Thank you.
Sure.
The plan on the DLBCL submission in Europe is is going to be the timing will likely coincide probably more with the Boston submission in Europe. It just easier for us to handle the 2 submissions together. So we'll be thinking about that, but we haven't made a final decision on that.
Okay, great. Thank you.
Comes from Jonathan Chang with SVB Leerink.
Good morning and thanks for taking my questions. First question, you indicated that ASH plans to evaluate the FPD 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'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.
Got it. And secondly, can you talk about the rationale for evaluating the selinexor combination studies in colorect 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 1st in human in patients with advanced. Solid tumor malignancies. There were, there were, I believe, 6 different partial responses there. These are these were resist confirmed partial responses across the smattering of diseases.
One of the PRs was in metastatic colorectal cancer KRAS mutant, one of them, to a couple of them were actually in melanoma. 1 was in, I believe, in pancreatic cancer and 1 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 in actually in liposarcoma, the phase 3 readout, which we expect to be mid this year.
But got back to the colorectal in lung, there's a given the single agent activity in colorectal that we reported, 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 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-1s have shown minimal activity in microsatellite stable colorectal cancer. And so the goal will be to combine these 2 agents that show minimal activity separately PD-1s to work. And then obviously to complement the AXPO mechanism of selinexor with the immunotherapy.
I should say there's an ongoing study at MD Anderson looking at selinexor in combination with Keytruda and nivo, 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 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 RAS mutant lung cancer. And docetaxel is a standard of care second line agent.
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 expovial 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 and some very important solid tumors. And we're looking forward to announcing some data this year and next in that regard.
Got it. Thank you.
Thank you. Speakers, I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Mr. Michael Kaufman, for any further remarks.
Hi, thanks very much and thanks everybody for for joining us today. I think we're going to see a great year coming. And we look forward to you 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.