Karyopharm Therapeutics Inc (KPTI) 2018 Q4 法說會逐字稿

Good morning. My name is Liz, 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 2018 Financial Results Conference Call. (Operator Instructions) 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, Liz, and thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter and full year 2018 financial results and business update. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer; Mike Mason, Chief Financial Officer; Dr. Sharon Shacham our Founder, President and Chief Scientific Officer; Christopher Primiano, Chief Business Officer and General Counsel; Anand Varadan, our Chief Commercial Officer; Dr. Jatin Shah, Senior Vice President, Clinical Development; and Cameron Peters, Vice President of Finance.

On the call today, Michael Kauffman will 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. Dr. Kauffman will discuss our key upcoming milestones and provide some summary remarks. We will then open up the call for your question.

Earlier on this morning, we issued a press release detailing Karyopharm's results for the fourth quarter and 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 harbors provision under the Private Securities Litigation Reform Act of 1995. These include statements about future expectations, clinical development and regulatory matters and time lines, the potential success of 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 recently -- 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 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, 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 to 2018, it's been a busy first 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 impressive background in a few minutes.

First, I'd like to discuss the FDA Oncologic Drugs Advisory Committee, or ODAC, committee meeting that was convened on February 26 to 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 have 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 BOSTON study, evaluating selinexor in patients with relapsed or refractory myeloma receiving 1 to 3 prior therapies before making a final decision regarding approval. The 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 nonbinding.

While we are disappointed with ODAC's recommendation to delay the 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. Karyopharm remains deeply committed to improving the outcomes of patients with cancer, including those with relapsed/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 the review process of the NDA toward the assigned PDUFA date of April 6, 2019. If the FDA does decide to delay their 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 BOSTON study, which we announced in January was fully enrolled, is evaluating selinexor in combination with Velcade, also known as bortezomib, 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 have submitted a Marketing Authorization Application, or MAA, to the European Medicines Agency requesting conditional approval for selinexor in the same triple class refractory indication as the U.S. Selinexor was then granted an accelerated assessment by the EMA's Committee for Medicinal Products for Human Use.

Let me move now to some key clinical data we presented in the fourth quarter. In December, we presented updated data from the STORM study at the American Society of Hematology 2018 Annual Meeting. For the STORM study's primary endpoint, amongst the 122 with triple class patients with triple class refractory myeloma, all of whom had previously been treated with the 5 most commonly prescribed anti-myeloma drugs, oral Sel-Dex achieved a 26.2% 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 patients with at least a minimal response from Sel-Dex 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 occurred in 27% of patients, and 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 in diffuse large B-cell lymphoma, or DLBCL. During the fourth quarter of 2018, FDA granted Fast Track designation to selinexor for the treatment of patients with DLBCL who have received at least 2 prior therapies and are not eligible for high-dose chemotherapy with stem cell rescue or CAR-T therapy. These patients were enrolled in the Phase IIb SADAL study, and this is selinexor's second Fast Track designation.

Top line data from the SADAL study were also presented at ASH. Based on the modified intent-to-treat analysis from the first 115 of 127 patients, selinexor achieved an overall response rate of 29.6, and all of these responses have been adjudicated by an independent central radiological committee. The median duration of response across responding patients was 9.2 months, and the median overall survival was 9.1 months for all patients on the study.

As of the data cut-off 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 of progressive disease were not evaluable and that was 3.2 months.

The most common treatment-related AEs were similar to STORM or gastrointestinal and constitutional symptoms along with cytopenias; most were manageable with dose modifications and/or supportive care.

We are working closely with the FDA to determine the appropriate time lines for submission of the NDA for DLBCL based on the results of the SADAL study. We are 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 as Chief Financial Officer. Mike formerly served as Vice President of Finance and Treasurer at Alnylam Pharmaceuticals, Inc., a public biopharmaceutical company. He brings over 18 years of diversified financial experience and has deep expertise in global financial operations and controls, financing transactions and supporting pharmaceutical product launches. Mike is a proven leader in our industry and his experience leading finance teams 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 and full year 2018 financial results.

Thank you, Michael. Let me first say how excited I am to be joining Karyopharm 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 $330.9 million compared to $176.4 million as of December 31, 2017, and $212.3 million as of September 30, 2018. The increase in cash was driven by the net proceeds of $166.9 million from the private offering of senior convertible notes completed on October 26, 2018. These notes have an aggregate principal amount of $172.5 million, are due in 2025 and have a 3% coupon. This offering includes -- included the full exercise of the initial purchasers' option to purchase additional notes.

Now for the full year results. License and other revenue for the year ended December 31, 2018, was $30.3 million compared to $1.6 million for the year ended December 31, 2017. The 2018 revenue was primarily related to the company's license agreements with Biogen and Ono.

R&D expense was $161.4 million compared to $107.3 million for the full year 2017. For the full year 2018, G&A expense was $48.8 million compared to $24.9 million for the full year 2017.

For the full year 2018, Karyopharm reported a net loss of $178.4 million or $3.14 per share compared to a net loss of $129 million or $2.81 per share for the full year of 2017. Net loss includes stock-based compensation expense of $17.3 million and $20.4 million for the full years 2018 and '17, respectively.

Turning now to the financials for the fourth quarter. For the fourth quarter 2018, R&D expense was $38.9 million. G&A expense for the fourth quarter of 2018 was $18.8 million.

For the fourth quarter of 2018, we reported a net loss of $58.2 million or $0.96 per share compared to a net loss of $39 million or $0.80 per share for the fourth quarter of 2018. Net loss includes stock-based compensation expense of $3.9 million and $4.6 million for the fourth quarters in 2018 and '17, 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 2020, which currently assumes the commercial launch of selinexor in the U.S. in the second quarter of 2019. If the FDA decides to delay its approval decision 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 Kauffman for concluding remarks. Michael?

Thank you, Mike. Before moving to the Q&A, I'd like to provide an overview of our upcoming milestones. For our first selinexor NDA, we'll continue to work collaboratively with the FDA towards the April 6, 2019 PDUFA date. If the FDA delays their decision until BOSTON 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 medicines authorization request, requesting conditional approval for selinexor in patients with triple class refractory myeloma and the potential for an opinion from CHMP as early as the third quarter.

For our next exponential indication in relapsed or refractory DLBCL, 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 time line.

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 III 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 the occurrence of PFS events in the trial. If positive, these data could support regulatory submissions in 2020 in second-line multiple myeloma.

For the STOMP study in multiple myeloma, we look forward to presenting updates from the various combination arms at 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, and top line data from both studies are expected in 2020.

In closing, I'd like to sincerely thank the Karyopharm 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 and the myeloma community with 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.

(Operator Instructions) Our first question comes from the line of Maury Raycroft with Jefferies.

First question is on the BOSTON study. I'm wondering if you have a sense of the discontinuation rates between the 2 arms and if there's any general differences between the 2 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 turn that question over to Dr. Shah.

No, thank you for that question. So first of all, so there's 2 points there. One is that patients -- the physicians can dose reduce to Velcade to once weekly per protocol if they run into side effects or adverse events. So that is permitted, and they can stay on the 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 DSMB has met now 3 times and there's been no safety signals, none that have arisen 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 6 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 I study focusing on 19 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 Velcade with median PFS of about 9 months and ORR around 60% to 63%. So hopefully, those numbers will continue to be shown in the BOSTON study and should lead to a successful study.

Our next question come from the line of Arlinda Lee with Canaccord Genuity.

I had a few kind of on BOSTON and what you think FDA is looking for from that. You had 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 file for accelerated with SADAL if FDA is looking for a BOSTON-based study results for myeloma?

Yes. Let me take top line data. At the end of the year or early next year for BOSTON, we refer to PFS data. And I would also include secondary endpoint of ORR. As far as the SADAL filing time lines, we're working closely with FDA to -- holistically across all of our entire selinexor program to determine the optimal timing for everything to come in so that FDA is sufficiently convinced for the activity of the drug.

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

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 effect in DLBCL. Wondering if you think they might have any similar concerns 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 manage 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?

Yes. I guess, quickly, a couple of very fast points 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 therapies in DLBCL, these patients are substantially less heavily pretreated with a median of 3 prior therapies versus 7 in 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 in STORM.

(Operator Instructions) Our next question comes from the line of Eric Joseph with JP Morgan.

Just a couple from us mostly on BOSTON. Wondering if you could just 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 for folks on the selinexor -- patients on the selinexor arm.

Certainly. I'll just take it quickly top line because we've not privy to all of the data. But the DSMB has reviewed all that, as Jatin mentioned, and the study has continued to proceed unaltered from the initial. This is a global study. It 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 of this nature, including the daratumumab study where less than 10% of the 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 come from the line of Jonathan Chang with SVB Leerink.

First question, what is your view on sepsis and infections in the STORM and, ultimately, BOSTON patient population and how they're determined to be treatment-related or treatment-emergent?

Yes. So let me just quickly answer the second one, and I'll turn it over to Jatin to talk about sepsis and pneumonia to 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 sponsors' opinion of any of these events. And when we say related or not, this is absolutely due to the treating physician who is there looking at the patient and taking care of the patient. Jatin, can you take on the sepsis and pneumonia in myeloma?

Yes, absolutely. So the challenge always is that these patients with myeloma are extremely immunocompromised, and that's the #1 cause of death in these patients, unfortunately, is infection and sepsis as the myeloma progresses. And for these patients on the STORM study specifically, and including myeloma in general, that is indeed the #1 cause of gross 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 ODAC that they can be very difficult to differentiate from an attribution perspective and is often attributed to (inaudible).

Maybe comment on the BOSTON study, so what we're aware of or...

Yes. So again, I think from the -- on the BOSTON study with the DSMB, they have reviewed the data and there has been no difference that they have noted between the 2 arms. And so they would let this study continue on.

Great. Thanks.

Great. That's helpful. Maybe just one more question here. What is your view on the contribution of dex to the STORM development?

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 view. The contribution of low-dose dexamethasone in patients who had 7 prior lines of therapy, including 6 prior lines of glucocorticoid-containing therapy is essentially 0. Single-agent low-dose dexamethasone cannot induce responses in patients that entered the study on -- the STORM study.

Our next question comes from the line of Ying Huang with Bank of America Merrill Lynch.

This is Alec on for Ying. Just 2 from me. How does the review process look if the FDA were to postpone approval until the BOSTON readout? Would the approval decision be made in both penta-refractory and in patients who have received 1 of 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 might be possible, but it's really premature to address that.

Okay. And my next question is on financing. So given the second half 2020 cash guide, which includes the commercial revenues of selinexor in 2Q '19. 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 deal close would you be considering at that time?

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 be delayed. So we will not be seeking cash this year.

And that concludes today's question-and-answer session. I'd like to turn the call back to Michael Kauffman for closing remarks.

Yes. Thank you very much. I again want to reiterate my thanks to all the patients, physicians and myeloma advocacy groups and all of the others including the Karyopharm team, 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 are 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.