Good morning. My name is Liz, and I will be your conference operator today. 4th Quarter and Full Year 2018 Financial Results Conference Call. I would now like to turn the call over to Mr. Ian Karp, Karyopharm's Vice President, Investor And Public Relations.
Thank you, Liz, and thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter full year 2018 financial results and business update. This is Ian Karp, and I'm joined today by Doctor. Michael Kauffman, Chief Executive Officer Mike Mason, Chief Financial Officer Doctor. Sharon Shakam, our Founder, President and Chief Scientific Officer Christopher Permiano, Chief Business Officer And General Counsel Anon Meriden, our Chief Commercial Officer Doctor. Jason Shaw, Senior Vice President of Clinical Development and Cameron Peters' Vice President of Finance.
On the call today, Michael Kaufman provide an overview of some of our recent business developments, and then the newest member of our executive team, our CFO, Mike Mason, will provide an overview of the fourth quarter and full year 2018 financial results. Doctor. Kauffman will 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 fourth quarter full year 2018.
The release is 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 provision under the Private Securities Litigation Reform Act of 1995. These include statements about future expectations, clinical development, and regulatory matters and timelines, the potential success of our product candidates, financial projections and our plans and prospects. Actual results may differ materially from those by these forward looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recently of our most recent quarterly report on Form Ten 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 our views change. Therefore, you should not rely on these forward looking statements as representing our views 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 Kaufman, our Chief Executive Officer.
Thank you, Ian, and good morning, everyone. Thank you for joining us on today's call. In addition to a productive end of 2018, it's been a busy 1st few months of 2019, and I'll focus my comments on our most recent developments. Before I begin, let me briefly welcome Mike Mason. Who joined us earlier this week as our new CFO.
We are thrilled to have him as part of the executive team. I'll tell you a bit more about Mike and his suppressive background in a few minutes. First, I'd like to discuss the FDA oncologic drug advisory committee or ODAC committee meeting that was convened on February 26, review data supporting our new drug application, requesting accelerated approval for oral selinexor for the treatment of patients with triple class refractory multiple myeloma, who received at least 3 prior therapies. In a vote of 8 to 5, the committee recommended that FDA wait to see the results from Karyopharm's randomized open label Phase III BOS study, evaluating selinexor in patients with relapsed or refractory myeloma, receiving 1 to 3 prior therapies before making a final decision regarding approval. Split committee acknowledged that the vote was a difficult one, and we were encouraged by the support from a number of the ODAC panel members.
Although FDA will consider the recommendation of the advisory committee, the final decision regarding approval of the product is made solely by the FDA. And the recommendations by the advisory committee are non binding. While we are disappointed with ODAC's recommendation to delay potential approval of selinexor. We are working with the FDA to evaluate the best path forward as they continue to review the new drug application. Caryopharm remains deeply committed to improving the outcomes of patients with cancer, including those with relapse refractory multiple myeloma.
Specifically, triple class refractory myeloma is an urgent, unmet medical need, and selinexor is the first agent to be studied in a large trial in patients with a serious condition and an estimated 3 to 5 month survival according to existing published literature. Following the ODAC vote, we are working closely with FDA through your review process of the NDA towards the assigned PDUFA date of April 6, 2019. If the FDA does decide to delay, there approval decision until the results from the BOSTON study are available. We expect to have top line results from that study by the end of 2019 at the earliest or into 2020, depending on the occurrence of progression events, which is the primary endpoint in this trial. As a reminder, the BOS study, which we announced in January, was fully enrolled, is evaluating selinexor in combination with Velcade, also known as portessment, plus low dose dexamethasone.
Compared to Velcade plus low dose dexamethasone in patients with multiple myeloma with 1 to 3 prior lines of therapy. Switching gears now to the European front, we announced in early January that we had submitted a marketing authorization application. Or MAA to the European's medicine agency requesting conditional approval for selinexor in the same triple class refractory indication as the U. S. Nexa was then granted accelerated assessment by the EMA's Committee from additional products for human use.
Let me move now to some key clinical data we presented in the fourth quarter. December, we presented updated data from the class patients with triple class refractory myeloma, all of whom had previously been treated with the 5 most commonly prescribed anti myeloma drugs. Oral cell decks achieved a 26.2 percent overall response rate, including 2 complete responses, 6 very good partial responses and 24 partial responses. The 2 CRs, stringent CRs were also negative for minimal residual disease. All responses were confirmed by an independent review committee.
Median overall survival across the study was 8.6 months and median overall survival in the approximately 40% of with at least a minimal response on Celldex was 15.6 months compared to a median survival of 1.7 months in patients whose disease progressed or was not evaluable. The most common adverse events included thrombocytopenia, nausea, vomiting, fatigue, and decreased appetite. AEs were generally predictable and manageable with dose adjustments and or supportive care. Treatment emergent adverse events leading to treatment discontinuation of 27% of patients these were considered by the treating investigator to be treatment related in 18% of patients. Major organ toxicities were not prominent in this study and safety results were consistent with those previously reported from Part 1 of the STORM study and from other selinexor studies.
Other key myeloma abstracts presented at ASH included updated clinical data from the Daratumumab and pomalidomide arms of the Phase Ib stomp study. These data continue to show strong efficacy and manageable tolerability. Turning now to our selinexor development program diffuse large B cell lymphoma or D LBCL during the fourth quarter of 2018 FDA granted Fast Track designation to selinexor for the treatment of patients with DLBCL who received at least 2 prior therapy and are not eligible for high dose chemotherapy with stem cell rescue or CAR T therapy. These patients were enrolled in a Phase 2b SADAL study, this is selinexor2nd fast track designation. Top line data from SADAL study were also presented at ASH, based on the modified intent to treat analysis from the first 115 patients, selinexor achieved an overall response rate 29.6, and all of these responses had been adjudicated by an independent central radiological committee.
Median duration of response across responding patient was 9.2 months, and the median overall survival was 9.1 months for all patients on the study. As of the data cutoff date, median survival for patients with at least a complete or partial response was 29.7 months, as compared to median survival for patients whose best response was progressive disease were not evaluable, and that was 3.2 months. Most common treatment related AEs were similar to STORM or gastrointestinal and constitutional symptoms, along with cytopenias, a were manageable with dose modifications and or supportive care. We are working closely with the FDA to determine the appropriate timelines for mission of the NDA for DLBCL based on the results of the sales study. We're also planning to submit an MAA in Europe with a request for conditional approval in the same indication.
Next, for a quick update on the commercial front, given the upcoming advisory committee meeting. Our plan is to continue to work towards the April 6 PDUFA date and assess the ongoing investment in our U. S. Commercial capabilities, following our discussions with the FDA to evaluate the best path forward for selinexor. And finally, on the corporate front, earlier this week, we announced the appointment of Michael P.
Mason, Chief Financial Officer. Mike formerly served as Vice President of Finance And Treasurer at Alnylam Pharmaceuticals Incorporated, a public biopharmaceutical company. He brings over 18 years of diversified financial experience has deep expertise in global financial operations and controls, financing transactions and supporting pharmaceutical product launch Mike is a proven leader in our industry and is an experienced leading finance team through significant organizational growth will be a valuable addition to Karyopharm. I'll now turn the call over to Mike to provide an overview of the fourth quarter full year 2018 financial results.
Thank you, Michael. Let me first say how excited I am to be joining Carrier farm at such an important time in the company's history, and I look forward to contributing to its future success. As of December 31, 2018, cash, cash equivalents and investments, including restricted cash, totaled $330,900,000, compared to $176,400,000 as of December 31, 2017 $212,300,000 as of September 30, 2018. The increase in cash was 2018. These notes have an aggregate principal amount of $172,500,000 are due in 2025 and have a 3% coupon.
This offer included the full exercise of the initial purchasers option to purchase additional notes. Now for the full year results, license and other for the year ended December 31, 2018 was $30,300,000 compared to $1,600,000 for the year ended December 31. 2017. The 2018 revenue was primarily related to the company's license agreements with Biogen and Pona. R and D expense was $161,400,000 compared to $107,300,000 for the full year 2017.
For the full year 2018, G and A expense was $48,800,000 compared to $24,900,000 for the full year 2017. For the full year of 2018, Karyopharm reported a net loss of $178,400,000 or $3.14 per share compared to a net loss of $29,000,000 or $2.81 per share for the full year of 2017. Net loss includes stock based compensation expense of $17,300,000 and $20,400,000 for the full year 2018 2017, respectively. Turning now to the financials for the 4th quarter. The fourth quarter of 2018, R and D expense was $38,900,000.
G and A expense for the fourth quarter of 2018 was $18,800,000. For the fourth quarter of 2018, we reported a net loss of $58,200,000 or $0.96 per share compared to a net loss of $39,000,000 or $0.80 per share for the fourth quarter of 2018. Net loss includes stock based compensation expense of $3,900,000 4.6 dollars for the 4th quarters in 20 18 and 'seventeen, respectively. Based on our current operating plans, we expect that our existing cash cash equivalents and investments will be sufficient to fund operations into the second half of twenty twenty, which currently assumes the commercial launch of selinexor the U. S.
In the second quarter of 2019. If the FDA decides to delay its approval, vision for selinexor until the Boston data is available, we will reevaluate our spending expectations for 2019. I'll now turn the call back over to Michael Kaufman for concluding remarks. Michael?
Thank you, Mike. Before moving to the Q And A, I'd like to provide an overview of our upcoming milestones. For our first selinexor NDA, we'll continue to work collaborative with the FDA towards the April 6, 2019 PDUFA date. If the FDA delays their decision until BOSTA study results are available, we'll adjust our plans accordingly as we await the results from that Boston study. We are working with EMA in support of our medicine's authorization request, condition requesting conditional approval for selinexor in patients with triple class refractory myeloma and the potential for an opinion from CHMP as early as third quarter.
For our next potential indication in relapsed or refractory deal CTL, we plan to submit an NDA to the FDA with a request for accelerated approval, and we'll work closely with the FDA to determine the appropriate timeline. We also plan to submit an MAA in Europe with a request for conditional approval for oral selinexor in this patient population, and we'll provide an update on the timing of that when we know more. For the pivotal phase 3 BOSTON study, enrollment is now complete and top line data are expected at the earliest by the end of 2019 or into 2020, depending on myeloma. For the Stump study in myeloma, we look forward to presenting updates from the various combination arms of future medical meetings. Finally, regarding development in solid tumors, our ongoing Phase III study in liposarcoma and the SIENDO study in endometrial cancer continue to enroll patients in top line data from both studies are expected in 2020.
In closing, I'd like to sincerely thank the carrier farm employees who tirelessly helped us prepare for this week as well as all the patients and physicians who supported us at Odac. We are deeply committed to working with patients, physicians in the myeloma community. The goal of selinexor becoming a new treatment alternative for those patients with no other options of known clinical benefit. I'll now turn the call over to the operator for questions.
You.
Our first question comes from the line of Maury Raycroft with Jefferies. Your line is now open.
First question is on the BOSTON study. I'm wondering if you have a sense of the discontinuation rates between the two arms and if there's any general differences between the two arms? And then in the control arm, if a doctor wants to dose reduce Velcade to one time per week, do those patients stay on study? And if this is happening, do you have a sense of what proportion has experienced this?
Yes, thank you. I'll send that question over to Doctor. Shaw.
No, thank you for that question. So, first of all, so there's 2 points there. One is that the patient of the physicians can dose reduce the Velcade to once weekly per protocol, if they're running to side effects or adverse events. So that is permitted. They can say I'm study just as they would, per their product label.
And then regarding discontinuations, the study is blinded and it's followed by the DSMB the DSMBs met now three times and there's been no safety signals that are the reason to change the conduct of the study.
Okay. And Go ahead, Maury. One more. Yes.
And I guess just thinking about scenarios, if the April 6th PDUFA does not lead to approval for last line myeloma, what are next steps if the Boston PFS benefit with selinexor is similar to the control, but the safety is better with the combo versus twice weekly Velcade?
Yes, I'll take that. Maury, that scenario is just too tough to come. Think about really we'd have to look at all the data and figure out the next steps. From there. I'd just remind folks that the data from which this study, the BOSTON study was designed, came from the phase 1 study focusing nineteen patients with who would have met criteria for the Boston study.
And, the median PFS was over 15 months with a median response over sorry, the response rate was over 80% compared to the historical controls with Belcade with median PFS of about 9 months and ORR around 60% to 63%. So hopefully those numbers will continue to be shown the BOSTON study and should lead to a successful study.
Our next question comes from the line of Arlinda Lee with Canaccord Genuity. Your line is now open.
Hi guys, thanks for taking my questions. I had a few kind of on on Boston, what you think FDA is looking for from that? You have guided to year end top line data. When might we see then the PFS data And then secondly, on SADAL, can you maybe update us, on your discussions with, FDA on that? Could you trial for accelerated with SADAL if FDA is looking for a BOSTON based study results for myeloma?
Thanks.
Yes. When we say top line data at the end of the year or early next year for BOSTON, we refer to PFS data and that would also include secondary endpoint of ORR. As far as the SADAL filing timelines, we're working closely with FDA to holistically across all of our entire Selinexor program to determine the optimal timing for everything come in so that FDA is sufficiently convinced for the activity of the drug.
Okay. Thank you.
Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.
Hi guys. Thanks for taking the questions. This is Owen on for Brian. Just a couple of quick ones from me. First, it seems like at the panel, there was some positive commentary at times on selinexor's single agent affecting DLBCL.
I'm wondering if you think they might have any similar terms with the single arm trial regarding the safety assessment. And then also on safety, you mentioned a number of the methods you're exploring to the toxicity profile? And should we expect that these might be implemented in future studies like solid tumor studies and that we might see a better AE profile there? Thanks.
That there were some supporting voices on the panel, of course. And in fact, the myeloma expert on the panel was quite supportive. I think the other one consideration separately on SADAL is there's no dexamethasone at all in that study. It's a lower dose, these patients, because of the lack of available therapy DLBCLD patients are substantially less heavily pretreated with a median of 3 prior therapies versus 7. In a storm.
And because of the lower dose, the relatively healthier patients, although all these patients are suffering from many conditions, The side effect profile, as you've seen, is significantly reduced compared to the patients who are receiving 7 prior therapies. Storm.
Great. Thanks.
Our next question comes from the line of Eric Joseph with JPMorgan. Your line is now open.
Hey guys, thanks for taking the questions. Just a couple from us mostly on Boston. Wondering if you could remind us on the geographic breakdown of recruitment in the study. And whether at this point you have any visibility on dose modification, dose reduction, or, folks on the cell and patients on the cell and next harm? Thanks.
Certainly. I'll just take it quickly top line because we're not privy to all of the data. But the DSMB has reviewed all of that. It's Dayton mentioned, and the study has continued to, to proceed unaltered from the initial. This is a global study includes essentially patients from all continents.
And, we see good recruitment from all of those places. There are a limited number of patients from the U. S, which is absolutely consistent with prior studies, have this nature, including the umab study where less than 10% of patients come from the U. S. So we're seeing what we expect to see across the world.
And that study did accrue a bit faster than we anticipated.
Our next question comes from the line of Jonathan Chang with B. Larry. Your line is now open.
Good morning. Thanks for taking my questions. First question, what is your view on sepsis and infections in the storm and ultimately Boston patient populations and how they're determined to be treatment related or treatment emergent?
Yes. So let me, let me just
quickly answer the second one and then I'll turn it over to Jaden to talk about sepsis and pneumonia. The extent we're aware of those on Boston. The assessment of relatedness, both at ODAC and in any of our trials is really by the treating investigator. It has nothing to do with the sponsor's opinion of any of these events. So when we say related or not, This is absolutely due to the treating physician who's there looking at the patient and taking care of the patient.
Jaden, can you take on the sepsis and pneumonia myeloma?
Yes, absolutely. So the challenge is always is that these patients with myeloma are extremely compromised and that's the number one cause of death in these patients, unfortunately, is infection in sepsis. As the myeloma progresses. So for these patients on the storm study specifically, including myeloma in general, that is indeed the number one cause of both morbidity and mortality. And that can become difficult to isolate between and all the many events that we saw were non neutropenic as well, which is important So as even our DSMB number noted at the Odax that it can be very difficult to differentiate, from an attribution perspective,
Maybe comment on the BOSTON study? So what we're aware of?
Yes. So again, I think from on the BOSTA study, with the DSMB, they have reviewed the data and there has been no difference that they've noted, between the two arms. And so they've let this study continue on.
Great. Thanks.
Great. That's helpful. Maybe just one more question. What is your view on the contribution of Dex to the strong results? Thank you.
Yes, I'll take that.
We have a very strong view, which is supported by all of the investigators. And frankly, we have not met anyone in the myeloma community that has taken a contrarian the contribution of low dose dexamethasone in patients who've had 7 prior lines of therapy include including 6 prior lines of glucocorticoid containing therapy is essentially 0. Not induce responses in patients that entered the study on the STORM study.
Our next question comes from the line of Yang Wong with Bank of America Merrill Lynch. Your line is now open.
Hey, guys. This is Alec on for Ying. Thanks for taking our questions. Just two from me. How does the review process look at the FDA where to postpone approval until the Boston readout, would the approval decision be made in both penta refractory and in patients have received 1 to 3 lines of prior therapy as in the BOSTON study?
Just trying to think in terms of the initial addressable market, if it were to be approved in that instance.
We can't really speak to the options. I think what you suggested is definitely an option. And, the way the FDA worded the question would suggest that be possible, but it's really premature to address that.
Okay. Thanks. And my next question is on finance So given the second half twenty twenty cash guide, which includes the commercial revenues of selinexor in 2Q 2019, If the approval were to be delayed, where do you think that would leave you cash wise? And if you did need to seek additional financing towards the end of the year, what vehicles would you be considering at that time? Thanks.
We will take a very, appropriate focused look at our situation and ensure that we have more than 2 years of cash, at our disposal should the decision to postpone the approval of selinexor So we will not be seeking cash this year.
Great. Thank you.
And that concludes today's question and answer session. I'd like to turn the call back to Michael Kaufman for closing remarks.
Yeah, thank you very much. I again, want to reiterate my thanks to all the patient's physicians and, myeloma advocacy groups and all of the others, including the Karyopharm who supported us at ODAC. And, we really are working hard with the FDA to come to a good conclusion, but We will see this and, we're also looking forward to the results of the BOSTON study. Thanks everybody for spending time with us today. Bye bye.
Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program and you may now disconnect. Everyone, have a great day.