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 Care E. O. Farm 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, Caryopharm's Vice President, Investor And Public Relations.
Thank you, Gigi, and thank you all for joining us on today's conference call to discuss Carrieopharm's first quarter 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 Primiano, Chief Business Officer And General Counsel and Mr.
Anan Meriden, our Chief Commercial Officer. On the call today, Michael Kaufman will provide an overview of some of our recent corporate developments. Then, Mike Mason will provide an overview of the first quarter 2019 financial results. Doctor. Kaufman will then discuss our key upcoming milestones and provide some summary remarks.
We will then 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 another filing 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 Doctor. Michael Kaufmann, Chief Executive Officer.
Thank you, Ann, and good morning, everyone. Thank you for joining us on today's call. I will begin with a quick overview for the selinexor new drug application by 3 months to July 6, 2019. This extension followed the FDA oncology drug advisory committee meaning 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 2b storm study. At the conclusion of the ODAC meeting in a vote of 8 to 5, 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, Carrier Farm continued to have productive discussions with the FDA regarding the selinexor new drug application. At the request of the FDA, Caryopharm submitted additional existing clinical information as an amendment to the MDA. Following review of these additional data, The FDA extended the PDUFA action date by 3 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 Vortezma and dexamethasone, complicated dexamethasone alone. In patients with myeloma who have had 1 to 3 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 United States. In January, we hired our commercial sales force of approximately sales representative and 8 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 successful United States launch. In parallel to the U. S.
Activities, 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 United States. 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 AMA has switched the application from an accelerated review a traditional review. We expect to receive a decision For diffuse large B cell lymphoma, following a presentation of positive top line results from the Phase 2b SADAL study in 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 requiring accelerated and conditional approvals, requesting accelerated and conditional approvals, respectively. For patients with relapsed or refractory DLBCL who have received at least 2 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 and 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 twothree 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 2 selinexor abstracts have been selected for presentation of the upcoming American Society of Clinical Oncology or ASCO meeting 2019 in late May early June in Chicago. The first will be an oral presentation describing results from the Phase 2b 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. And finally, on the corporate front, we recently appointed Tina Clark Beaman as Chief Compliance Officer. Tina formally served as Executive Director of Compliance And at Alexion Pharmaceuticals. She brings to the company 21 years of health care industry experience and 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 some highlights. As of March 31, 2019, cash, cash equivalents and investments, including restricted cash, totaled $265,100,000 compared to $330,900,000 as of December 31, 2018. For the first quarter of 2019, license and other revenue was $200,000, compared to $10,000,000 for the first quarter of 2018. The revenue in 2018 was from the $10,000,000 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 $38,000,000 compared $41,300,000 for the first quarter of 2018. We expect R and 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 $27,100,000 compared to $7,600,000 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 and A expenses for the remainder of 2019, on a quarterly basis to We reported a net loss of $66,200,000 or $1.09 per share compared to a net loss of $38,500,000 or $0.78 per share for the first quarter of 2018.
Net loss includes stock based compensation expense of 3,900,000 and $4,200,000 for the first quarters of 2019 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 to be between $200,000,000 $215,000,000 excluding stock based compensation Additionally, We expect that our existing cash, cash equivalents and investments will be sufficient to fund operations into the second half
of twenty twenty.
If the FDA decides to delay its approval decision for selinexor until the Austin 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 Reynolds?
Thank you, Mike. Before moving to the Q And 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 midyear. 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 than we 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 we'll be working with the FDA over the coming months to determine the most appropriate timing for submission. We also plan to submit an with a request for conditional approval for oral selinexor in this patient population. For the pivotal Phase III BOSTON study, enrollment is completed 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. If positive, These data could support regulatory submissions in 2020 in 2nd line myeloma. Next, the various arms of the phase 1btwo stomp study continuing in myeloma and we look forward to presenting updates from the various combination arms at future medical meetings And finally, we will continue to progress our solid tumor forward presenting updates from the various combination arms at future medical meetings.
And 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.
And our first question is from Brian Abrahams from RBC Capital Markets.
My first question, what efficacy data would you be able to provide to the FDA and the BOSTON study, ongoing BOSTON study without compromising the integrity of that trial? And what mechanisms and processes might be in place to do that? And I'm curious I guess 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?
And then I had a follow-up.
Yes. So point 1 and very important is the FDA has specifically asked us not to close what data they requested and what data they reviewed in their review of the application. Separately, 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 the safety review, including an analysis of fatalities on each arm of the trial. And in addition, certain efficacy data, which is assembled by a third party, and is we are 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. And on the efficacy side, What we know is that the DSMB did not recommend any alteration to the sizing of the trial, suggesting that, and they did not indicate that trial is 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 have 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. And as you know, the key secondary endpoint is the overall response rate.
That's really helpful. One more for me, if I could. I'm 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 that and some of the same data that FDA was or might we think about the European processes a bit different just given the way they look at and their preference for oral drugs in this disease.
Yes. I think it's safe to say that generally speaking, the, there are no surprise questions at all. From the Europeans. They largely follow the FDA's questions. And just given the size of this application and the times coming back, we'll be able to turn this around in the timeframe that gives us an answer by the end of the year.
Really helpful. Thanks again, Michael.
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. So I wanted to ask, if you're able to give any kind context around the 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. And I think there were several members of the ODAC committee that seemed to understand myeloma in in great detail and had some comments that seem to resonate with the FDA regarding the selinexor efficacy and safety data. I think the FDA was just looking for additional reassurance, that some of these comments were correct. And I will add that the underlying theme, with the 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.
And about 2 weeks after ODAC, FDA released clinical hold or put on an implemented clinical all in venetoclax. And I think there's just been a heightened sensitivity around, both efficacy and safety and myeloma. FDA was doing its appropriate due diligence on all new drugs being developed in this area.
Okay. Thank you. That's helpful. And then, are you able to say if they requested any additional data beyond Boston or is it limited just to that?
No, I can't speak to any of the data that specifically what they requested. But 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.
Our next question is from Jonathan Chang from SVB Leerink. Your line is now open.
Hi, guys. This is David Ruch 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?
Yes. To put it in person, the King, the King study was conducted in patients with, previously treated and progressive globlastoma multiforme. That is GBM, which is a type of or glioma. And these patients really have no known treatment of benefit. This was a single agent selinexor study, which included a dose finding component, etcetera.
And 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. And could you provide any further context on the EMA decision specifically to switch from the accelerated review to traditional? And 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, but 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 1000 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.
So 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.
So we weren't surprised at all just the size of the data package.
Great. And then regarding timing?
Yes, we think the Europeans are pretty 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. So part of the extension here was because they wanted that they had a large number of questions, none of, again, none of which were unexpected, but 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.
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 some color on FDA discussions and maybe questions since the panel. Was there anything that stuck 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 that might then might have them made them take another look as it works?
Yes. 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 or the companies.
And so we're not conflicted. Doctor. Clifton Mo was the sole myeloma expert on the panel. And certainly from our perspective, he did an excellent job summarizing the 6 or 7 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 what based on what Karyopharm presented.
In particular, he indicated this was the most heavily pretreated population ever studied in any trial and 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 co morbid conditions of these patients, both because of their myeloma and because of their accumulated toxicities from other drugs, finally, and also because they're older patients with lots of other diseases, he wasn't surprised by that. And he said it's 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.
The other small molecules that are already approved in earlier stage myeloma patients. And 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 immunocompromised from myeloma. Think they listen to him a lot. I think they listen to Doctor.
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. And 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.
And our next question is from Eric Joseph from JP Morgan. Your line is now open.
Hey, everyone. This is Turner on for Eric. A couple of questions from us. I think Michael, I think you previously cited mature duration of bonds as a gating factor to SADAL filing. How should we be thinking about the level of sensitivity around DUR that we initially saw reported at ASH in 20 18 given the number of censored events?
And 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 twenty twenty submission?
Sure. Good. Good points. Remember that an accelerated approval, response rate and duration of response are important. There have been no drugs, no small molecule drugs approved in DLBCL period.
And 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 of response that are in the 4 month range, which are not considered in lymphoma are not considered durable. I would comment on the side that in myeloma 4 months in a refractory population is considered quite important. In lymphoma, they're looking for typically they're looking for at least 6 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% to 25% rate in these patients who have no other options.
So I think those are the bases. I think we will update in the future, I hope, on the SADO 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 6 month line with the vast majority of patients already having crossed that line as opposed to being early on. So 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 7 months for our drug with response rates in the high 20s to 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. Okay.
And then one last one from us. Siento is now a company sponsored trial, which cars, obviously a certain amount of investment has this bearing impact on the P and L that hasn't been incorporated into prior guidance. And I'm just kind of curious how has your thinking changed with respect to the probability of success and indication to convert to company sponsored trial versus an IST?
Yes, 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. So that was the reason for for what was done that the lead investigator is still in his for Goat 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. And yes, so the costs for that program for Cielo are in the expense guidance that we gave this morning, which is again between 2 $215,000,000 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 star contrast to ovarian cancer where PARP inhibitors have been important and life extending therapies in the maintenance setting. So we're looking to do that We as you know, our drug has a broad mechanism of action, so we don't have any particular genotype specified for uterine cancer. But following initial platinum taxal therapy, our drug would come in as maintenance therapy for those patients, which is the vast majority who receive, who obtain at least a partial response or a complete response to their initial therapy.
We think that we estimate the size of these markets are well north of 500,000,000 and could be as high worldwide as $1,000,000,000. So these are 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.
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's contingent upon approval in multiple myeloma given they are quite different diseases? And SADAL like STORM is a single arm study.
So I guess how do you plan to frame the NDA given the FDA's preference for randomized controlled studies?
Yes. 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.
We'll verify that. So it's virtually impossible to design a study that, has an appropriate control arm. People have tried in the past. And they've even tried sort of dealer's choice or position choice control arms and they just don't accrue, and there's little interest. So 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, 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. So 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. So, what they're really reviewing is the efficacy data from the SADAL study and any updated data from ongoing trials that we would provide. And so 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. But We are thinking that if we have good discussions with FDA and move forward with the myeloma approval, they would be open to independent SADAL NDA, which will come in before the BOSTON data.
Okay, great. Thank you. And as you're sort of in a holding period here waiting for the approval in 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 and A expense for the rest of the year?
Thanks.
Yes. This is Mike. I'm going to turn it over to Anand Veritan, our Chief Commercial Officer, Anand.
Yes. Thank you for the question. So the, our first of all, our full field organization is hired and in place and trained to the extent that's school on the disease state and in terms of the customer base and the like. And they've also now, we're using this timeframe before for approval to engage with the customers in an appropriate way. So 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 signed 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 these, 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 are the kinds of labels that we might be able to anticipate for selinexor when it's approved as well. So we can be in the strongest possible posture to have a strong ramp for the commercial uptake after approval.
At this time, I am showing no further questions. I would like to turn the call back over to Michael Kaufman 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.