Good morning. My name is Gigi, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics first quarter 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.
Thank you, Gigi, and thank you all for joining us on today's conference call to discuss Karyopharm's first quarter 2019 financial results and business update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, our Chief Executive Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Christopher Primiano, Chief Business Officer and General Counsel, and Mr. Anand Varadan, our Chief Commercial Officer. On the call today, Michael Kauffman will provide an overview of some of our recent corporate developments. Mike Mason will provide an overview of the first quarter 2019 financial results. Dr. Kauffman will discuss our key upcoming milestones and provide some summary remarks. We will open up the call for your questions. Earlier this morning, we issued a press release detailing Karyopharm's results for the first quarter of 2019. The release is available on our website at karyopharm.com.
Before we make 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 for 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 most recent annual report on Form 10-K, 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. I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer.
Thank you, Ian, and good morning, everyone. Thank you for joining us on today's call. I will begin with a quick overview of recent company events and developments. First, in mid-March, the FDA extended the PDUFA action date for the selinexor new drug application by three months to July 6, 2019. This extension followed the FDA Oncologic Drug Advisory Committee meeting that was convened on February 26 to review data supporting our NDA, requesting accelerated approval for oral selinexor in combination with low-dose dexamethasone for patients based on the results of the single-arm phase II-B STORM study. At the conclusion of the ODAC meeting, in a vote of eight to five, the committee recommended that the FDA wait for the results from Karyopharm's randomized, open-label, phase III BOSTON study evaluating selinexor in patients with previously treated myeloma before making a final decision regarding approval.
After the conclusion of the ODAC meeting, Karyopharm continued to have productive discussions with the FDA regarding the selinexor new drug application. At the request of the FDA, Karyopharm submitted additional existing clinical information as an amendment to the NDA. Following review of these additional data, the FDA extended the PDUFA action date by three months. Since then, we have been working closely with FDA as they complete their review of the selinexor new drug application, and we remain deeply committed to bringing selinexor into the hands of physicians treating patients with refractory multiple myeloma. While the FDA will consider the recommendations of the advisory committee, the final decision regarding approval of the product is made solely by the agency and the recommendations of the advisory committee are non-binding.
As a reminder, the BOSTON study, which was fully enrolled this past January, is evaluating selinexor in combination with Velcade, also known as bortezomib, and dexamethasone, compared to dexamethasone alone in patients with myeloma who have had one to three prior lines of therapy. As progression-free survival is the primary endpoint, we expect to have top-line results from that study by the end of 2019 or into 2020, depending on the occurrence of the progression. In the recent meeting of the Data Safety Monitoring Board, no new safety signals were identified on the study, and based on the first interim analysis, the board recommended proceeding with the study as originally planned with no changes in patient numbers. As we now await the conclusion of the FDA's review, we have also been very active in preparing for the potential commercial launch of selinexor in the U.S.
In January, we hired our commercial sales force of approximately 60 sales representatives and eight nurse liaisons. Should selinexor receive FDA approval by the updated July 6 PDUFA date, our commercial team will be in an excellent position to support a successful U.S. launch. In parallel to the U.S. activities, we announced in early January that we had submitted a marketing authorization application to the European Medicines Agency, requesting conditional approval for selinexor in the same triple-class refractory myeloma indication as in the U.S. As is a customary part of the marketing application review process, we received a consolidated list of questions from the EMA in early May 2019. To provide adequate time to evaluate the application and allow us to respond to the questions and feedback, the EMA has switched the application from an accelerated review to a traditional review.
We expect to receive a decision on the application by the end of 2019. Shifting gears now to our selinexor development programs beyond myeloma. For diffuse large B-cell lymphoma, following the presentation of positive top-line results from the phase II-B SADAL study at ASH 2018 and the receipt of Fast Track designation from the FDA during the fourth quarter of 2018. We are now working towards a New Drug Application and Marketing Authorization Application submissions requesting accelerated and conditional approvals, respectively, for patients with relapsed or refractory DLBCL who have received at least two prior multi-agent therapies and who are ineligible for stem cell transplantation, including CAR T therapies.
We are working with both the FDA and EMA to determine the appropriate timelines for these submissions. We expect to have some greater clarity following the FDA's decision on our New Drug Application requesting accelerated approval for oral selinexor in myeloma. Next, I'd like to discuss some recent developments for our selinexor program in endometrial cancer, where there are currently no approved therapies for the treatment of patients in the maintenance setting following initial chemotherapy. During the first quarter, an Investigational New Drug Application was submitted and accepted by the FDA for a randomized, blinded phase II/III study titled the SIENDO study, evaluating selinexor versus placebo as a maintenance therapy in patients with advanced or recurrent endometrial cancer following their initial platinum-based treatments. The primary endpoint in the SIENDO study is progression-free survival. This study was previously an investigator-sponsored trial and has subsequently transitioned to a company-sponsored study.
We are targeting complete enrollment in this study in 2020. We've also seen further progress across a number of additional clinical programs. Two selinexor abstracts have been selected for presentation at the upcoming American Society of Clinical Oncology, or ASCO, meeting 2019 in late May and early June in Chicago. The first will be an oral presentation describing results from the phase II-B KING study evaluating single-agent selinexor in patients with recurrent glioblastoma. The second will be a poster presentation with discussion describing additional overall survival from the STORM study in patients with heavily pretreated myeloma. Finally, on the corporate front, we recently appointed Tina Clark Beam as chief compliance officer. Tina formerly served as Executive Director of Compliance and Ethics at Alexion Pharmaceuticals.
She brings to the company 21 years of healthcare industry experience. Her appointment reflects our ongoing commitment to maintaining the highest compliance and ethics standards as we transition to a commercial stage organization. With that, I'll now turn the call over to Mike Mason for an overview of the first quarter 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. As of March 31, 2019, cash equivalents, and investments, including restricted cash, totaled $265.1 million, compared to $330.9 million as of December 31, 2018. For the first quarter of 2019, license and other revenue was $0.2 million compared to $10 million for the first quarter of 2018. The revenue in 2018 was from the $10 million upfront payment for the asset sale of KPT-350 to Biogen in the first quarter of 2018. For the first quarter of 2019, research and development expense was $38 million, compared to $41.3 million for the first quarter of 2018. We expect R&D expense to decrease going forward in 2019 compared to the first quarter of 2019, largely due to reduced spend from the BOSTON and SADAL trials.
General and administrative expense for the first quarter of 2019 was $27.1 million, compared to $7.6 million for the first quarter of 2018. The increase was due primarily to the hiring of the Karyopharm commercial team and related commercial launch preparation activities to support the potential U.S. commercial launch of selinexor. Assuming a commercial launch by July, we expect G&A expenses for the remainder of 2019 on a quarterly basis to be relatively consistent with Q1 2019. For the first quarter of 2019, we reported a net loss of $66.2 million, or $1.09 per share, compared to a net loss of $38.5 million or $0.78 per share for the first quarter of 2018. Net loss includes stock-based compensation expense of $3.9 million and $4.2 million for the first quarters of 2019 and 2018, respectively.
Based on current operating plans, which assume a selinexor commercial launch by July 2019, we expect our full year operating expense to be between $200 million and $250 million, excluding stock-based compensation. Additionally, we expect that our existing cash equivalents, and investments will be sufficient to fund operations into the second half of 2020. If the FDA decides to delay its approval decision for selinexor until the BOSTON data are available, we will reevaluate our spending expectations for 2019 and update the investment community at the appropriate time. I'll now turn the call back over to Michael for concluding remarks. Michael?
Thank you, Mike. Before moving to the Q&A, I'd like to provide an overview of our key upcoming milestones. For our first selinexor NDA, we continue to work collaboratively with the Food and Drug Administration towards the July 6, 2019 PDUFA date and prepare for a potential commercial launch by mid-year. We are continuing to work closely with the EMA in support of our MAA, requesting conditional approval for selinexor in patients with triple-class refractory myeloma, with an expected decision by the end of 2019. For our next potential indication in relapsed or refractory DLBCL, we plan to submit an NDA to the FDA with a request for accelerated approval and will be working with the FDA over the coming months to determine the most appropriate timing for submission. We also plan to submit an MAA with a request for conditional approval for oral selinexor in this patient population.
For the pivotal phase III BOSTON study, enrollment was completed in January, and top-line data are expected by the end of 2019 or into 2020, depending on the occurrence of progression events on the trial. These data could support regulatory submissions in 2020 in second-line myeloma. The various arms of the phase I-B/II STOMP study continue in myeloma, and we look forward to presenting updates from the various combination arms at future medical meetings. Finally, we will continue to progress our solid tumor programs in liposarcoma and endometrial cancer. In closing, I'd just like to say that we remain deeply committed to working with the patients, physicians, regulators, and the overall myeloma community with the goal of bringing selinexor to the market as a new treatment option for patients who are in dire need of novel therapies to treat their highly refractory disease.
I'll now turn the call over to the operator for questions. Operator?
Ladies and gentlemen, at this time, if you have a question, please press the Star and the number 1 key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question is from Brian Abrahams from RBC Capital Markets. Your line is now open.
Hi. Thanks very much for taking my questions. My first question, what efficacy data would you be able to provide to the FDA in the ongoing BOSTON study, without compromising the integrity of that trial? What mechanisms and processes might be in place to do that? I'm curious what degree of maturity of data would be available, just based on the trajectory of enrollment, which I know completed in January, ahead of the July PDUFA, then I have a follow-up.
Yeah. Point 1 and very important is that the FDA has specifically asked us not to disclose what data they requested and what data they reviewed in their review of the application. Separately and independently of that, what we have said is that our Data Safety Monitoring Board, which meets periodically throughout the trial, did review and go through the first interim analysis, which includes both a safety review, including an analysis of fatalities on each arm of the trial. In addition, certain efficacy data, which is assembled by a third party, and for which we are blinded as a company. Based on the safety review, they found no new safety findings and no concerns about any potential imbalances on the trial.
On the efficacy side, what we know is that the DSMB did not recommend any alteration to the sizing of the trial, and they did not indicate that the trial was futile, so that the trial is proceeding along the lines for which it was originally designed.
Can you provide any more details on sort of the parameters around that interim with respect to what the bar might've been for futility or for resizing?
We don't disclose those data, but what you can glean from the statistical parameters in the study is that we're looking for approximately a 30% improvement in the overall progression-free survival in the study, and that's the primary endpoint. As you know, the key secondary endpoint is the overall response rate.
That's really helpful. One more from me, if I could. Wondering if you could give us any more detail on how the EMA review process is going and maybe just qualitatively the nature of their questions. Were they sort of asking some of the same questions and for some of the same data that FDA was, or might we think about European processes of being a bit different, just given the way they look at and their preference for oral drugs in this disease? Hop back into queue. Thanks.
Yeah. I think it's safe to say that generally speaking, there are no surprise questions at all from the Europeans. They largely follow the FDA's questions. Just given the size of this application and the times coming back, we'll be able to turn this around in a timeframe that gives us an answer by the end of the year.
Really helpful. Thanks again, Michael.
Pleasure.
Thank you. Our next question is from Maury Raycroft from Jefferies. Your line is now open.
Hi, guys. This is Mitchell on for Maury. Thank you for taking our questions. I wanted to ask if you're able to give any kind of context around what the FDA was looking for. Is it more on the safety side or the efficacy side as well?
The FDA was quite responsive to us after the conclusion of the ODAC meeting. I think one of the lines that I'm happy to share with you that they said was that they not only look at the total vote, but they look at the content of the comments in the votes. I think there were several members of the ODAC committee that seemed to understand myeloma in great detail and had some comments that seemed to resonate with the FDA regarding the selinexor efficacy on safety data. I think the FDA was just looking for additional reassurance that some of these comments were correct. I will add that the underlying theme with what was ongoing at the time regarding venetoclax in its phase III with venetoclax/Velcade dex versus Velcade dex, FDA was continuing to conduct its own analyses throughout our review process and during our ODAC process.
About two weeks after ODAC, FDA released a clinical hold or implemented a clinical hold on venetoclax, and I think there's just been a heightened sensitivity around both efficacy and safety in myeloma, and FDA was doing its appropriate due diligence on all new drugs being developed in this area.
Okay. Thank you. That's helpful. Are you able to say if they requested any additional data beyond BOSTON, or is it limited just to that?
I can't speak to any of the data that, specifically what they requested. It was a very wholesome review of the entire data set, and again, with the backdrop of venetoclax and other results in myeloma, they were doing their appropriate diligence to make sure that they understood fully the behavior of our compound.
Okay. Thank you.
Thank you. Our next question's from Jonathan Chang from SVB Leerink. Your line is now open.
Hi, guys. This is David Roche on for Jonathan. Thanks for taking our question. First question, could you help set investor expectations on the KING data coming at ASCO, since it's been a while since we've seen those?
Yeah. To put it in perspective, the KING study was conducted in patients with previously treated and progressive glioblastoma multiforme, that is GBM, which is a type of glioma. These patients really have no known treatment options of benefit. This was a single-agent selinexor study, which included a dose-finding component, et cetera. What we're looking for is both responses and disease stabilization, and those will be reported at ASCO in the oral presentation.
Great. Thank you. Could you provide any further context on the EMA decision specifically to switch from the accelerated review to traditional? Do you expect the EMA's decision by the end of 2019, regardless of what happens in the interim?
We think that the EMA certainly watch ODAC very carefully, they had their own set of questions. As I mentioned before, this was a large application. This is one of the largest safety databases, with over 1,000 patients treated with hematologic malignancies in the safety database for selinexor. This is much bigger than most other accelerated approval safety databases in myeloma or other diseases. I think it's the large amount of data, it's the diversity of diseases, it's a large number of questions, a lot of which are very similar to what the FDA has answered. We weren't surprised at all, just the size of the data package.
Great. Then regarding timing?
We think the Europeans are pretty good about making sure that they stay on their timelines. Remember that the EMA process does depend on the company's ability to return information in a timely fashion. Part of the extension here was because they had a large number of questions, none of which were unexpected, but they wanted to make sure that the company had plenty of time to return the answers.
Great. Thank you. That's helpful.
Thank you. Our next question is from Arlinda Lee from Canaccord. Your line is now open.
Hey, good morning. It's Ben on for Arlinda. Thanks for taking my question. Many of them have been answered, but I'm just wondering if you could provide a little bit of additional color on FDA discussions and maybe questions since the panel. Was there anything that in your mind stood out that might have caught the FDA's attention to, as far as questions or concerns or comments made by any of the panel members that might have made them take another look as it were?
Yeah, look, we can all dance around this. The FDA is taking another look, or we wouldn't have had the 3-month PDUFA extension. I think that there was unfortunately, and this has been the trend, it's difficult to get myeloma doctors on the panel who haven't worked with companies, so are not conflicted. Dr. Clifton Mo was the sole myeloma expert on the panel, and certainly from our perspective, he did an excellent job summarizing the six or seven major FDA concerns and really doing a nice job allaying those concerns, at least in his mind, why this drug had extraordinary activity and deserved accelerated approval in his mind, based on what the FDA presented and based on what Karyopharm presented.
In particular, he indicated this was the most heavily pretreated population ever studied in any trial, it was the most aggressive myeloma that has been reported on to date. He indicated that while the drug certainly had more dose reductions than most of the other drugs in myeloma, the fact that this was a patient population that was so heavily pretreated really was not surprising, and given the comorbid conditions of these patients, both because of their myeloma and because of their accumulated toxicities from other drugs. Finally, also because they're older patients with lots of other diseases, he wasn't surprised by that, and he said as an oncologist that he could easily handle these dose reductions.
I think he allayed some concerns that our serious adverse event rate was higher with this drug, and he indicated that in his mind it was similar to the other small molecules that are already approved in earlier stage myeloma patients. He indicated that the kinds of infections that we're seeing in our trial are unfortunately no different than what is seen in essentially all other myeloma trials. It's just the nature of this disease and the immunocompromise from myeloma. I think they listened to him a lot. I think they listened to Dr. Harrington on the statistics side, who was pretty convinced that this compound had clear single-agent activity, even though it's used with low-dose dexamethasone. I think they have been convinced by the panel and by additional data provided, that the low-dose dexamethasone is contributing little or nothing to the actual ORR in the study.
Okay. That's very helpful. Thank you very much.
Thank you. As a reminder, ladies and gentlemen, if you have a question, please press the star then the number one key on your touch tone telephone. Our next question is from Eric Joseph from JPMorgan. Your line is now open.
Hey, everyone. This is Turner on for Eric. A couple questions from us. Michael, I think you previously cited mature duration of response as a gaining factor to SADAL filing. How should we be thinking about the level of sensitivity around DOR that we initially saw reported at ASH in 2018, given the number of censored events? Then second part to that, what would be viewed as clinically meaningful or data that you could file on with respect to DOR and PFS, looking towards the first half 2020 submission?
Sure. Good points. Remember that in an accelerated approval, response rate and duration of response are important. There have been no small molecule drugs approved in DLBCL period. The small molecule drugs that are sometimes used, such as REVLIMID and to some extent ibrutinib, are mainly restricted to the ABC subtype of the disease, and unfortunately have single-agent durations of response that are in the four-month range, which are not considered in lymphoma, are not considered durable. I would comment on the side that in myeloma, four months in a refractory population is considered quite important. In lymphoma, typically they're looking for at least six months durations of response, and we consider that our goal for this study, and they're looking for response rates that are above the 20%-25% rate in these patients who have no other options. I think those are the bases.
I think we will update in the future, I hope, on the SADAL results, because you're correct that one of the reasons the FDA asked us to just hold on the application until we had mature data was because of the number of censored events on the DOR. We want to make sure we cross that six-month line with the vast majority of patients already having crossed that line, as opposed to being early on. We'll have to wait and see in terms of public disclosure of data, but we are excited, and we remain confident that these kinds of durations that are north of seven months for our drug with response rates in the high 20s-30% are real and will hold up, and that we'll be able to submit the application.
Could we potentially anticipate some data sometime this year, maybe at EHA or ASH?
We could potentially anticipate that, yes.
Okay. One last one from us. SIENDO is now a company-sponsored trial, which requires obviously a certain amount of investment. Has this bearing impact on the P&L that hasn't been incorporated into prior guidance? I'm just kind of curious, how has your thinking changed with respect to the probability of success and the indication to convert to a company-sponsored trial versus an IST?
Yeah, I'll just start, and then I'll turn it over to Mike for the budgetary question. I think we're increasingly excited about the potential for this drug in that indication, and we want to move it faster than is possible with an investigator-sponsored trial. That was the reason for what was done. The lead investigator is still Ignace Vergote in Europe, and he's been a huge supporter of this program and will continue to be. Let me turn it to Mike.
Sure. Yes. The cost for that program for SIENDO are in the expense guidance that we gave this morning, which is again between $200 million and $250 million of OpEx for 2019.
Okay, great. Thank you.
Just to add to that quickly, I think it's important to take any of these, especially these new programs, in the context of what potential market size we're looking at. There are currently no maintenance therapies available, approved at least, for patients with endometrial cancer. This is in stark contrast to ovarian cancer, where PARP inhibitors have been important and life-extending therapies in the maintenance setting. We're looking to do that. As you know, our drug has a broad mechanism of action, we don't have any particular genotype specified for uterine cancer. Following initial platinum Taxol therapy, our drug would come in as maintenance therapy for those patients, which is the vast majority who obtain at least a partial response or a complete response to their initial therapy.
We estimate the size of these markets are well north of $500 million, and could be as high worldwide as $1 billion. This is a substantial market with a substantial unmet medical need.
Thank you. Our next question is from Ying Huang from Bank of America Merrill Lynch. Your line is now open.
Hey, guys. This is Alec on for Ying. Thanks for taking our question. My first is on selinexor and DLBCL. Do you view the NDA submission in DLBCL as contingent upon approval in multiple myeloma, given they are quite different diseases? SADAL, like STORM, it's a single-arm study. I guess, how do you plan to frame the NDA, given the FDA's preference for randomized control studies?
Yeah, let me start with the second question. The difficulty in DLBCL is that for patients who are not eligible for transplant or those that have progressed following either transplant or CAR T therapy, there are no approved therapies, and there's frankly no standard of care, and a quick look at the NCCN guidelines will verify that. It's virtually impossible to design a study that has an appropriate control arm. People have tried in the past. They've even tried dealer's choice or physician's choice control arms, and they just don't accrue, and there's little interest. We designed the SADAL study with the goal to show single agent selinexor activity, which in and of itself is a very important demonstration.
The reason for us giving a little bit of a wait and see on the exact SADAL filing is because we don't want to end up in a situation where we have another ODAC around a single-arm trial in DLBCL like we did in myeloma. We want to work with the FDA, and we are working with the FDA to make sure that we're all on the same page as they review this. I should mention about 80% of the NDA for SADAL has already been reviewed by FDA in terms of safety data. What they're really reviewing is the efficacy data from the SADAL study and any updated data from ongoing trials that we would provide. We want to make sure we're completely walking together with FDA, and not end up with a difficult ODAC.
If we do have to delay it until the BOSTON top line data are available, we could. We are thinking that if we have good discussions with FDA and move forward with the myeloma approval, they would be open to an independent SADAL NDA, which would come in before the BOSTON data.
Okay, great. Thank you. As you're sort of in a holding period here, waiting for the approval on multiple myeloma, how are you managing the prior commercial ramp? Mostly, I guess, I'm wondering how you're utilizing the sales team right now, and if the PDUFA were to be delayed further, how do you plan to manage G&A expense for the rest of the year? Thanks.
Yeah. This is Michael. I'm going to turn it over to Anand Varadan, our Chief Commercial Officer. Anand?
Yeah, thank you for the question. First of all, our full field organization is hired and in place and trained to the extent that's possible on the disease state and in terms of the customer base and the like. We're using this timeframe before approval to engage with the customers in an appropriate way. To educate them, for example, around the mechanism of disease, they have materials in order to do that and to really make sure that they understand the role of SINE technology and around nuclear export as it plays a role within cancer, because that's a new area in terms of mechanism that's not necessarily familiar to this customer base.
They're also using this time to really profile the customers and to try to understand what the movement of patients are through their various practices, where they're likely to be given the label that we would anticipate or the kinds of labels that we might be able to anticipate for selinexor when it's approved as well. We can be in the strongest possible posture to have a strong ramp for the commercial uptake after approval.
Thank you. At this time, I am showing no further questions. I would like to turn the call back over to Michael Kauffman for closing remarks.
Just to say thank you everybody, again, for joining today's call, and have a great day. Bye-bye.
Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect.