Karyopharm Therapeutics Inc.
Q3 2017 Earnings Call Transcript

Published: 4 Nov 2017

[Operator:]

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 Third Quarter 2017 Financial Results Conference Call. [Operator Instructions] Please be advised that this call's being recorded at the company's request. I would now like to turn over to Mr. Christopher Primiano, Senior Vice President, Operations, Business Development, General Counsel and Secretary of Karyopharm therapeutics.

[Christopher Primiano:]

Thank you, Liz, and thank you all for joining us on today's conference call to discuss Karyopharm's third quarter 2017 financial results. This is Chris Primiano, and I'm joining today by Dr. Michael Kauffman, Chief Executive Officer; Mr. Michael Falvey, Chief Financial Officer; Dr. Sharon Shacham, Founder, President and Chief Scientific Officer; and Dr. Jatin Shah, our Vice President, Clinical Strategy. On the call today, Michael Kauffman will make some introductory comments and provide a short update on the clinical development programs and plans. Then Mike Falvey will provide an overview of the third quarter of 2017 financial results. Dr. Kauffman will then discuss our key upcoming milestones and provide some summary remarks, and we'll open up the call up your questions for which Dr. Shacham and Dr. Shah and I will also be available. Earlier this morning, we issued a press detailing Karyopharm's results for the third quarter 2017. 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 provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments 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 quarterly report on Form 10-Q for the quarter ended June 30, 2017, which was filed with the SEC on August 8, 2017, and any other filings we may make with the SEC, including our quarterly report on Form 10-Q for the third quarter of 2017, which we expect to file later today. Any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent date. 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 presenting 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 site data unless otherwise specified. I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer of Karyopharm.

[Michael Kauffman:]

Thank you, Chris, and good morning, everyone. Thank you for joining us on today's call. Let me start by saying that we've had an active third quarter, and we're extremely proud of our recent progress. Of particular notice is the recent execution of an exclusive licensing transaction with Japanese oncology leader Ono Pharmaceutical Co. Ltd. for the development and commercialization of our lead SINE compound selinexor and for second-generation SINE compound eltanexor, also known as KPT-8602, for our all-human oncology indications in Japan, South Korea, Taiwan, Hong Kong and the ASEAN countries. Ono markets several blockbuster oncology drugs in Japan, including Opdivo, also known as nivolumab, and Kyprolis, which is also known as Carfilzomib. Across these 2 products, Ono has specific expertise in multiple myeloma, Hodgkin's disease and a variety of different solid tumors, making them an ideal partner to advance both selinexor and eltanexor in Japan and the other licensed territories. The transaction, which carries a total deal value of up to $193 million plus royalties, includes a onetime upfront fee of 1 - of USD 22.3 million to Karyopharm from Ono and USD 170.7 million if certain specified future development and commercial milestones are achieved by Ono. These amounts are based on the currency exchange rates on October 11, 2017, the effective date of the license agreement. Karyopharm is also eligible to receive low double-digit royalties based on future net sales of selinexor and eltanexor in the licensed territories. In exchange, Ono receives exclusive rights to develop and commercialize both compounds in the license territories at its own cost and expense. Ono will also have the ability to participate in any global clinical study of selinexor and eltanexor at their own cost and expense for patients enrolled in the licensed territories. Ono is well known and widely respected for its clinical development and commercial expertise, and this partnership provides nondilutive funding to Karyopharm as well as important validation for both selinexor and eltanexor while allowing us to remain focused on executing our late-phase selinexor trials and pursuing regulatory approvals in the U.S. and European Union. Next. We are looking forward to an exciting American Society of Hematology Annual Meeting this year. We've had more than 14 abstracts selected to the meeting, including 3 oral presentations. Amongst the selected abstracts will be 4 poster presentations featuring clinical data from the ongoing Phase 1b/2 STOMP study, evaluating the backbone of selinexor plus low-dose dexamethasone to a variety of other antimyeloma agents. The 4 STOMP presentations will include

[Michael Falvey:]

Thank you, Michael. Since we issued a press reason earlier today outlining our third quarter 2017 financial results, I'll just review the highlights and then speak to our cash balance and financial guidance. Cash, cash equivalents and investments as of September 30, 2017, including restricted cash, totaled $159.4 million compared to $175.5 million as of December 31, 2016. For the third quarter of 2017, research and development expense was $25.2 million compared to $19.9 million for the same period of last year. For the third quarter of 2017, general and administrative expense was $5.8 million compared to $5.9 million for the same period last year. Karyopharm reported a net loss of $30.6 million or $0.65 per share for the third quarter of 2017 compared to a net loss of $25.4 million or $0.69 per share for the same period last year. Net loss includes stock-based compensation expense of $4.9 million and $5.6 million for the third quarters of 2017 and 2016, respectively. For financial guidance for 2017, we expect our operating cash burn, including research and development and general and administrative expenses to be approximately $95 million. Based on current operating plans, we expect that our existing cash and cash equivalents will be sufficient to fund our research and development programs and operations into 2019, including the continued clinical development of selinexor in our lead indications with a focus on filing for accelerated approval in myeloma during 2018, assuming positive data from the STORM study, and preparing a commercial infrastructure for the potential launch of selinexor in North America and Western Europe. I'll now turn the call back over to Michael Kauffman for concluding remarks. Michael?

[Michael Kauffman:]

Thank you, Mike. I'm very proud of our progress in 2017. And just before we have questions, I'd like to recap our expected milestones. For STORM, we expect top line data from penta-refractory myeloma in April 2018, which if positive, is expected to support an NDA submission in the second half of 2018 requesting accelerated approval. For SADAL, we expect top line data the second half of 2018, which if positive is expected to support an NDA submission request for accelerated approval in 2019. For Velcade and Pomalyst arms, we're presenting updated data at ASH and will also be presenting new data for Revlimid and the Darzalex combination arms at ASH 2017. For the pivotal Phase 3 BOSTON study, we expect to complete enrollments in 2018 with top line data anticipated in 2019. And for our solid-tumor programs, we're expecting executing on the Phase 3 portion of the SEAL study, and we expect to report top line data by the end of 2019. We believe we have the potential for multiple exciting catalysts on the near horizon, and we'll continue to work diligently to advance selinexor's potential as a new treatment paradigm for patients suffering from myeloma, DLBCL, liposarcoma and other neoplasms. Thank you for listening today. We'll now open the call for questions. Operator?

[Operator:]

[Operator Instructions] Our first question comes from the line of Mike King with JMP Securities. Your line is now open.

[Mike King:]

Michael, just wanted to ask about STOMP and how we should think about it kind of overlaying on the development of selinexor in multiple myeloma as those trials continue to hit, whereas their arms continue to hit their enrollment goals. How do you foresee supplementing the lead application via STORM? Are these going to be sNDAs? Will these follow BOSTON? Are they for publication purposes only? I was hoping maybe you could give us a little bit of clarity on how those arms will fill out the dossier?

[Michael Kauffman:]

Sure. Well, there are 4 arms - 4 major arms on the STOMP study. Obviously, the Velcade arm is being used today in the ongoing Phase 3 Boston study, so that'll be a - if the results are positive, that would potentially support a full approval in second-line myeloma for sel-vel-dex versus vel-dex, so that's how we will use that arm. The other arms are being investigated with the potential to support additional randomized trials in the future for full approvals, and all of those regimens are potentially useful in that regard towards a full approval. But short of that and given the time frames involved, we would anticipating - that we would anticipate filing all of them with the various NCCN guideline groups and other people compendia listings so that we can have at least compendia listings as we progress them to full approval. And I'd also remind everyone that the FDA has taken a bit of a broader view of things recently, and the dara and pom combination, which was based on - was approved, was given an accelerated approval based on the Phase I/II data that were generated in that study. So one can imagine that we might be available for some of those kinds of options once we have a full approval. Let me ask Jatin to also talk about how we can move - so how we're thinking about moving selinexor into the newly diagnosed arena as well? Jatin?

[Jatin Shah:]

So maybe I think I'll highlight just a couple other medically relevant kind of takes on that. And I think one is the fact that we're able to combine selinexor with all the other kind of therapeutics in the myeloma space, including carfilzomib, as shown previously, and now with both Imetelstat and daratumumab. So I think this is especially relevant for the treating community, moving forward in that we're having high response rate so we connote that in our pomalidomide arm, for example, we saw high activity both from len refractory pom naive patients, which is very similar to what we see with pom-dara-dex. Also, I think this is data that's very promising moving forward that we can combine it with all the other therapeutics and move them into various other lines. And then I think this also sets us up to move into earlier lines of therapy, realizing - including early diagnosed as Michael referred to as Revlimid is more commonly used in that front-line therapy setting as well, so now that we're able to combine with lenalidomide or Revlimid, we'll be exploring moving that into the front-line therapy both for transplant eligible and ineligible patients into those - find some opportunities there.

[Operator:]

Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.

[Unidentified Analyst:]

This is Rick on for Brian. Congrats on the STOMP updates and the ASH abstracts, and we're looking forward to seeing the complete data. Compared to the last cutoff for STOMP, the overall response rates among PI-refractory patients appears to have come down a bit. Could you talk about any of the differences in the PI-resistant population recruited later in the study? Remind us of the dosing in these patients and whether anything in your baseline characteristics may have led to the slower response.

[Michael Kauffman:]

Yes. I'll jump in first, and then turn it over to Sharon for additional follow-up since Jatin recently joined us. So one of the things that happens when you get good results in these trials is you start to get sicker and sicker patients, and we definitely had more patients that have Kyprolis refractory myeloma as opposed to simply Velcade refractory myeloma. And so these are sicker patients that have moved into the Velcade refractory arm. And we're actually quite excited because these patients are PI refractory arm. These patients should have a response rate on once-weekly Velcade close to zero, and that's really important to remember. These patients are refractory to full-dose proteasome inhibitors so giving them half a dose of Velcade is not going to induce a response. And we're actually quite excited about this. And in fact, these data continue to support one of our secondary endpoints in the BOSTON study, which you - which look at the response on SVd for patients that crossed over from the Velcade dex arm that have directly refractory disease. And if that arm is positive with significant response rate, we would file for that as an additional potential indication from the BOSTON study. I'll turn it over to Jatin or Sharon, if you have anything to add.

[Sharon Shacham:]

No. I think Michael has described it correctly. We saw more of the quad or even [indiscernible] refractory patient, some coming into the second part of both - of the SVd arm once we opened the expansion.

[Michael Kauffman:]

Thank you. One of the highlights - just to add quickly, is that even the PFS shown in that arm is quite substantial at about 9 months, which is pretty good for a Velcade refractory population, where again, you'd see minimal response rate at all and an expected PFS on Velcade of maybe 1 or 2 months.

[Sharon Shacham:]

Yes. And I think it's - the depths of the response didn't change much and the [DOR] as well as - very promising. So in overall, the activity of the SVd combination still looks great.

[Operator:]

Our next question comes from the line of Arlinda Lee with Canaccord. Your line is now open.

[Arlinda Lee:]

On 9274, how do you guys think about that development of the concept of your exo inhibitors? And then, I guess, maybe more focusing on SADAL and DLBCL, how many extra patients due to enroll in the expansion cohort? What do you think there hurdle would be for an accelerated approval? And maybe a little bit more detail on whether you think you might be able to file in, I guess, '19 now.

[Michael Kauffman:]

Yes. So let me answer the second part, and I'll turn it over to - 9274 question to Dr. Shacham. The SADAL sign-ons are what we said before, the data - the top line data from the final cohort of 130 patients will be available in the second half of next year, and we will file as expeditiously as we can after that - after those data come out. So that really hasn't changed. We had 30 patients at the 60-milligram dose initially, and we're adding approximately 100 more patients to that group, which is ongoing and improving nicely, so we're happy...

[Sharon Shacham:]

So about the 9274, it's in Phase 1 in solid tumors and lymphoma. And we also - the science around NAMPT inhibition is very different, and that's the one extra one inhibitor indication based on the inhibition of NAMPT and PAK4. We are looking for biomarkers and specific indications and also looking at the combination that we will follow up immediately as we will identify the recommended Phase 2 dose of the single agent in KPT-9274.

[Operator:]

Our next question comes from the line of Maury Raycroft with Jefferies. Your line is now open.

[Maury Raycroft:]

So following up on the STOMP SVd combo PR refractory patients. I'm wondering if those patients were mostly twice-weekly Velcade? Or was it more of a split between once- and twice-weekly dosing? And if patients are on once weekly and they start to respond, can they be stepped up to twice weekly to maintain the response?

[Sharon Shacham:]

So the vast majority of patients on STOMP received selinexor once weekly. It's only 3 patients that received - sorry but only once weekly. Only 3 patients received bortezomib twice weekly. And that's the already - there is cognitions at - and so in the penta-refractory, it's almost all the patient received both only once weekly. In the protocol what we allow is for patients that are receiving 100 once weekly, if they tolerate well and they didn't reach the PR, then we allowed them to receive selinexor twice weekly. And some patients we did that. But we are not moving from once weekly, both of them move to twice weekly bortezomib because as we said, bortezomib is helping enhance the deep activity of selinexor in this patient, and we don't need more than once-weekly bortezomib to achieve that. We will just get more thrombocytopenia and that obviously related to Velcade.

[Maury Raycroft:]

And along those lines of selinexor helping resensitize patients to Velcade in the refractory setting, I'm wondering for the pom - Pomalyst plus selinexor combo data where you show the overall response rate of 29% in refractory patients. Do you think selinexor is helping resensitize in those patients too? Or is something else going on?

[Sharon Shacham:]

Can you please repeat which patients?

[Maury Raycroft:]

The STOMP pom plus selinexor in the refractory patient. The pom plus Revlimid refractory.

[Sharon Shacham:]

So it's hard to say and we are following it closely, there is definitely a patient that would see pom in the past and now pom refractory and had a response. And the response rate there is more than what we would see in STOMP, so single agents that are excel. So you might think that there is some synergy there even in the pom refractory, but as we identify the recommended dose and move to extension, we will be able to answer this question in more detail.

[Maury Raycroft:]

And last question is based on the selinexor plus Darzalex combo. Can we expect to see some additional patients at the meeting?

[Sharon Shacham:]

Of course.

[Maury Raycroft:]

Any estimate as to how many?

[Sharon Shacham:]

It's a ongoing Phase 1 study, so there's 3 plus 3 design. And so it will be more patients than what you see now.

[Operator:]

Our next question comes from the line of Michael Schmidt with Leerink. Your line is now open.

[Michael Schmidt:]

I just had a couple follow-ups regarding the multimyeloma combination with Velcade. How does the patient population differ? Any expectation between the BOSTON trial and the STOMP Velcade arm? Does the BOSTON trial exclude prior Velcade? Or does it include, for example, patients that received Velcade previously.

[Sharon Shacham:]

No. They can receive Velcade at once. In the past, they actually can receive any proteasome inhibitor in the past. They may need to be proteasome inhibitor. They cannot be refractory to a proteasome inhibitor, and then it be 6 months from the last proteasome inhibitor.

[Michael Schmidt:]

I'm just trying to get a sense of, I guess, what would expectations be in the BOSTON trial, for example, how the arm val-dex will perform. And I guess, what would you expect for the once-weekly dex dosing alone in those types of patients?

[Sharon Shacham:]

Once-weekly dex dosing alone?

[Michael Schmidt:]

Yes. I guess, how much is that - if you're - if not all patients are refractory to Velcade, how much contribution would you expect from the once-weekly dex in Boston in the treatment arm relative to selinexor? And then, what expectations for the twice-weekly val-dex control arm in the study for efficacy?

[Sharon Shacham:]

So for the vel-dex, we are following the same design that was used in the Vd versus Kd study, in the ENDEAVOR study, and we took the PFS from that study, so it's 9.3 months, I believe. For the SVd arm, we are expecting the population should be similar to the STOMP study, maybe a little bit earlier line. So we expect - based on our statistical assumptions, we will have similar results to as the Vd combination but - so to get into the 80% response rate area but using only once weekly Vd, so to have better already and minimal neuropathy.

[Michael Schmidt:]

And question - just bigger-picture for [indiscernible], you guys still thinking about the Ono deal in Asia. I think in the past, you've, I think - coming in around potentially partnering selinexor in Europe as well, but then I think I heard you say today that you think about rolling out commercially in Europe yourself. Just wondering how you think about European commercially patient at this point.

[Christopher Primiano:]

Yes. So, Michael. This is Chris Primiano. So when it comes to Europe. I think that we're unlikely to be a sort of fully integrated pharmaceutical company at the point that we would expect to and hope to be launching selinexor, so that a partner may be the right choice for us in Europe. But it's not the best choice strategically to just expect that the right partnership is going to be formed at the time that we would like to have it. So we're continuing to prepare to build that commercial infrastructure and to do the right things to set the groundwork to commercialize in a way other than with a partner if necessary, but we certainly view a partner as an appropriate avenue for commercializing selinexor in Europe.

[Operator:]

Our next question comes from the line of Mara Goldstein with Cantor Fitzgerald. Your line is now open.

[Mara Goldstein:]

Just to follow up on that last question. What would be the timing for a regulatory then submission in the EU if you do not have a partner at the time that you're ready to make that submission?

[Sharon Shacham:]

Michael?

[Michael Kauffman:]

Which - yes, which submission, sorry, are you speaking about?

[Sharon Shacham:]

The European...

[Mara Goldstein:]

For Europe. For your first - yes...

[Michael Kauffman:]

Yes, so there's a couple of points. One is that both STORM and SADAL are being conducted in Europe as well as in the U.S. Both of those are obviously single-arm trials and would be potentially submitted for conditional approval in Europe. The timing for them would be a bit after the U.S. submissions would be made and pending scientific advice discussions, including the results into Europe, so we could be in Europe in mid-'19 with the STORM plan. BOSTON would be about a year later-or-so.

[Mara Goldstein:]

And then, just - can you just remind us on 8602, what would your anticipation be of the clinical differentiation between 8602 and selinexor?

[Michael Kauffman:]

Sharon will take that.

[Sharon Shacham:]

So just a reminder, 8602 is another - is a second-generation next SINE inhibitor with minimal well penetration, and what we see and reported in the abstract that it has still marked activity but improved tolerability. And - but its activity is taking a different course. What we believe is, obviously, for all the diseases that are related with - to brain tumors or that there is a chance for brain metastasis, selinexor will be developing in these indications of course him and solid tumors. In addition, selinexor seems to be a better partner for the immunotherapy drug as it allows for the immune system - it doesn't arrest the immune system with the once-weekly dosing if we are using in combination. For other combinations with the mark's profile in terms of tolerability of 8602, we will develop it in combination with other drugs that have a very good tolerability profile in indication - in solid tumors and potentially some indication on this space?

[Operator:]

[Operator Instructions] Our next question comes from the line of David Nierengarten with Wedbush. Your line is now open.

[David Nierengarten:]

I just had a - maybe an earlier-stage question on selinexor. Have you looked at combinations at preclinically? And with any of the BCMA antibodies or constructs - anticipating future drug development there on that side?

[Sharon Shacham:]

We haven't done those combinations yet, but we are looking to look into do them.

[Operator:]

I'm showing no further questions in queue at this time. I'd like to turn the call back over to Dr. Kauffman for any closing remarks.

[Michael Kauffman:]

Just want to thank you listening to today's call, and we apologize for slight interrupt. We look forward to seeing many of you at ASH at our data presentations - events. Details for that event will be going out shortly and have a good day. Bye, bye.

[Operator:]

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.