Karyopharm Therapeutics Inc (KPTI) 2015 Q1 法說會逐字稿

Good morning. My name is Andrew, and I will be your conference operator today. At this time I would like to welcome everyone to the Karyopharm Therapeutics first-quarter 2015 financial results conference call. Dr. Michael Kauffman, Chief Executive Officer of Karyopharm Therapeutics, please begin your conference.

Thank you and good morning. This is Michael Kauffman, the Chief Executive Officer of Karyopharm. I am here with Dr. Sharon Shacham, our Founder, President, and Chief Scientific Officer; Justin Renz, Executive Vice President and Chief Financial Officer; and Chris Primiano, our Vice President of Corporate Development and General Counsel. Welcome to the first-quarter 2015 earnings call, where we will provide a brief review of our finances followed by a clinical and regulatory update. We will then have time for questions.

Earlier today we issued a press release detailing Karyopharm's results for the first quarter ended March 31, 2015. The release is available on our website at karyopharm.com.

Various remarks we make may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments, and regulatory timelines, potential success of our product candidates, financial projections, and our plans and prospects.

Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the, quote, risk factors, end quote, section of our most recent annual report on Form 10-K, which is on file with the SEC, and in any other filings we may make with the SEC. Any forward-looking statements represent our views as of today only. We may update these statements in the future, but we disclaim any obligation to do so.

Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. Over the next 30 minutes we will provide a brief review of our financial results through the first quarter of 2015 and then provide a corporate update, including our clinical development programs and business strategy.

We are happy to take a few questions following the prepared comments. I will turn the call over to Justin to review the financials. Justin?

Thank you, Michael. Since we issued a press release earlier today outlining our first-quarter, March 31, 2015, financial results, I will just review the highlights and then speak to our cash balance and our financial guidance.

The Company reported a net loss of $26.1 million or $0.74 per share for the quarter ended March 31, 2015. That compares with a net loss of $13.7 million or $0.46 per share for the same period in 2014, including stock-based compensation expense of $3.7 million and $2.8 million for the quarters ended March 31, 2015, and 2014, respectively. Our first-quarter net cash burn from operating activities was $20.2 million.

Research and development expense was $20.8 million in the first quarter of 2015 compared to $11 million for the same period in the previous year. And general and administrative expenses were $5.4 million compared to $2.9 million for the same period in 2014. This increase in expenses is primarily related to the significantly expanded clinical development activities for our lead drug candidate, selinexor, KPT-330. And the increase in general and administrative expense resulted primarily from an increase in personnel costs, including headcount and stock-based compensation expenses, along with the cost of operating as a public company.

Cash, cash equivalents, and investments including long-term investments as of March 31, 2015, totaled $285.3 million compared to $214.8 million as of December 31, 2014. As a reminder, Karyopharm raised approximately $91 million net of expenses in a common stock follow-on offering which closed in January of 2015.

Based on current operating plans, we expect our existing cash will fund our R&D programs and operations into 2018, including moving our registration-directed clinical studies to their next data and collection points. We expect to end 2015 with a cash balance greater than $200 million.

With that, I will turn the call back over to Dr. Kauffman.

Thank you, Justin. During the first quarter, Karyopharm and its collaborators presented a comprehensive body of data across our oncology pipeline, including a total of 21 presentations at the 2015 annual meeting of the American Association of Cancer Research or AACR. Two of these were late breakers.

Sharon will tell you more about the content and importance of these data as well as our clinical progress with selinexor. In sum, the data we presented at AACR further demonstrated the role of XPO1 inhibition in a broad set of difficult-to-treat cancers with limited treatment options.

We have been granted a US patent for selinexor which will expire in 2032 absent any patent term extensions. This patent covers the composition of matter of selinexor as well as certain other compositions and related methods. Selinexor is being evaluated broadly in multiple registration-directed and other late-stage trials in patients with relapsed and/or refractory hematological and solid tumor cancers.

In addition, we received US patent allowance covering the composition of matter for KPT-350, an oral SINE compound being developed for the treatment of inflammatory and autoimmune diseases. Once issued, this patent is expected to provide patent protection for KPT-350 and pharmaceutical compositions comprised of KPT-350 into 2033. KPT-350 is expected to enter the clinic in healthy volunteers by Q1 2016.

We also appointed Mikael Dolsten, President of Worldwide Research and Development of Pfizer, to Karyopharm's Board of Directors. Dr. Dolsten brings significant pharmaceutical research and development expertise to Karyopharm. Drawing on over 25 years of clinical and regulatory experience, including at Pfizer, Wyeth Research, and Boehringer Engleheim, Mikael's contributions will be significant as we continue to advance our product pipeline, including selinexor for hematologic and solid tumor malignancies.

I will now turn the call over to Dr. Sharon Shacham to provide an update on our clinical development plans for selinexor and our other SINE compounds. Sharon?

Thank you, Michael. Now I will provide an update of our clinical development plans for selinexor. To date over 750 patients across various hematologic and solid tumor Karyopharm-sponsored studies have been treated with oral selinexor. Several patients have remained on-study for over 12 months, and the longest over two years.

We continue to observe broad and durable anti-tumor activity of selinexor in both hematologic and solid tumor cancers, consistent with selinexor's known mechanism of action as an inhibitor of XPO1. Selinexor's breadth of activity and novel mechanism of action provide multiple paths to potential commercialization.

Between Company- and investigator-sponsored trials, there are 41 clinical studies listed on clinicaltrials.gov related to selinexor. We plan to present highlights from some of these studies of selinexor single-agent and in combination at medical conferences during the remainder of the year, including the American Society of Clinical Oncology, or ASCO, 2015 annual meeting.

I will begin by discussing selinexor in hematological malignancies. We are actively enrolling patients in the three registration-directed clinical trials of selinexor in hematologic malignancies. The first trial, called SOPRA, of selinexor in older patients with relapsed or refractory AML, is enrolling patients older than 60 years of age who have received one prior line of therapy and who are ineligible for intensive chemotherapy and transplantation.

The second trial, called SADAL, so selinexor against diffuse aggressive lymphoma, which is enrolling patients with relapsed refractory DLBCL. And the third trial, called SIRRT, is for Selinexor in Relapsed/Refractory Richter's Transformation. Preliminary top-line data from these studies are anticipated in the second half of 2016. In addition, we have initiated a Phase 2 study in patients with relapsed or refractory peripheral and cutaneous T-cell lymphoma leukemia, based on patients' responses observed in Phase 1 study.

Our enthusiasm for initiating these studies with selinexor in hematological malignancies is supported by a single-agent activity which has been presented at medical meetings in the past several months. As Michael mentioned, preclinical data that expanded upon the understanding of selinexor activity in hematologic malignancies, including non-Hodgkin's lymphoma, acute myeloid leukemia, and multiple myeloma were presented at the 2015 AACL annual meeting -- as was a late-breaking abstract demonstrating potent anticancer effects of selinexor, both alone and in combination with chemotherapy in double- and triple-hit diffuse large B-cell lymphoma patients' cell lines. These data are consistent with selinexor's activity in our ongoing Phase 1 clinical trial in hematological malignancy.

Karyopharm also planned to initiate a single-arm trial in multiple myeloma called STORM, for selinexor treatment of refractory myeloma based on previously-reported encouraging data in heavily pretreated patients with multiple myeloma and in consultation with key opinion leaders. The study will initially enroll 80 patients whose myeloma is refractory to bortezomib, carfilzomib, lenalidomide and pomalidomide.

In addition, about 25% of the patients will have myeloma refractory to an anti-CD-38 monoclonal antibody, such as daratumumab. If the data from those 80 patients are promising, we may extend the size of the study to potentially support registration. We hope to present the initial data on the 80 patients in the first half of 2016.

On the solid tumor front, Karyopharm is actively enrolling patients in four selinexor Phase 2 solid tumor studies. The first trial, our SIGN study, is in gynecological malignancies. The second trial, our KING study, is in glioblastoma multiforme.

The third trial, our SHIP study, is in metastatic prostate cancer. And the fourth trial, STARRS study, is in squamous head and neck, lung, and esophageal cancers. We will present interim data from SIGN and KING at ASCO 2015 annual meeting.

In addition, we will present an update of our ongoing Phase 1B study in patients with locally invasive or metastatic sarcoma, including patients with liposarcoma. Based on the data we have seen in that study in patients with relapsed or progressive liposarcoma, we are planning to initiate a registration-directed study of single-agent selinexor versus control to treat liposarcoma in the second half of 2015.

Finishing up on this solid tumor update, in addition to the hematological cancer data we presented at the AACR, we also presented preclinical data on selinexor's activity in solid tumor at that meeting, including a late-breaking abstract describing the synergistic activity of selinexor in combination with olaparib, an approved PARP inhibitor in models of triple negative breast cancer. These data continue to support further investigation of selinexor across a range of solid tumors, both alone and in combination with other therapies.

Currently there are a number of investigator-sponsored and Company-sponsored trials, ongoing or planned, evaluating the potential of selinexor in combination with other chemotherapy or targeted agents in both hematologic and solid tumor cancers. Some of the key studies with this preliminary data expected within the next year include the following: selinexor with carfilzomib and dexamethasone in multiple myeloma -- we presented preliminary evidence of antitumor activity with this combination at last year's ASH meeting.

Selinexor with bortezomib and dexamethasone in multiple myeloma in transplant induction has already begun. In addition, a study of selinexor in combination with bortezomib and dexamethasone in patients with at least one prior therapy with myeloma is not refractory to bortezomib is expected to begin in the second half of 2015.

Selinexor with pomalidomide and dexamethasone in multiple myeloma, which we anticipate will begin in the second half of 2015; selinexor and rituximab, in combination with various chemotherapeutic and novel agents in non-Hodgkin's lymphoma, including DLBCL, which we anticipate will begin in the second half of 2015. Importantly, the results of this study will be used to design a phase 3 randomized confirmatory study in patients with relapsed-refractory DLBCL.

Selinexor with ibrutinib in CLL and non-Hodgkin's lymphoma, which we expect to begin shortly; selinexor with decitabine in AML, which began in 2014; selinexor with carboplatin and paclitaxel in patients with relapsed or refractory ovarian or endometrial cancer, which has recently begun; additional combination studies in both solid and hematologic malignancies have commenced or will begin shortly. A full list of ongoing and pending studies is available at clinicaltrials.gov.

Although our late program is focused broadly on oncology, XPO1, the target of our SINE compounds including selinexor, is relevant in several other diseases' settings. For example, all strains of influenza A and B viruses, regardless of species of origin, require XPO1 in order to complete their lifecycle.

XPO1 inhibition with SINE compounds potently inhibits influenza replication in vitro and in vivo. In particular, administration of verdinexor, also called KPT-335, and all-SINE compound closely related to selinexor, has shown reduction in viral titers, reduced cytokine levels, and improved survival in both murine and ferret influenza models.

Based on these results, a Phase 1 healthy volunteer study of verdinexor is expected to be initiated in the second quarter of 2015. Based on the results of this study, we may move to evaluate activity of verdinexor as an antiviral agent. This is just another exciting example of the breadth of opportunity for SINE compounds to help patients with limited treatment options.

I will turn the call back to Michael now to provide a brief summary before we take questions.

Thank you, Sharon. In summary, our broad selinexor development program continues in 2015 with plans to initiate additional potential registration-directed studies for selinexor in multiple myeloma and liposarcoma. We look forward to the presentation of selinexor clinical data updates in both solid and hematologic tumors at upcoming medical conferences later this year, including the presentation of selinexor single-agent solid tumor data at the upcoming 2015 ASCO annual meeting, being held May 29 through June 2, 2015, in Chicago. Data to be presented include Phase 2 clinical updates in both gynecological cancers and recurrent glioblastoma as well as Phase 1B clinical data in advanced sarcomas and Phase 1 clinical data in Asian patients with advanced solid and hematologic cancers. All of these data are with single-agent selinexor. Finally, we anticipate that additional SINE compounds for non-oncology indications will enter the clinic over the next year.

With that, operator, we are ready to take questions.

(Operator Instructions) Mike King from JMP Securities.

Congrats on all the progress. A couple questions -- regarding the combination study that you mentioned in the formal remarks, Sharon, both in myeloma as well as the other heme malignancies, I just want to be clear that all of those are going to be under a corporate IND rather than structured as ISTs? Or is there some mix of corporate and ISTs in there?

It's a mix of corporate and ISTs. The combination of selinexor with pomalidomide in myeloma will be a Company-sponsored study. One of the combinations -- selinexor with Velcade in patients that are not resistant or refractory to bortezomib -- is also a Company-sponsored study. And this study, investigating the combination of selinexor, rituximab and several chemotherapies in non-Hodgkin's lymphoma will also be a sponsored study. The rest of the studies are mostly ISTs.

Okay, thank you for the clarification. And then just wondering if, Justin, you could walk us through the spend, the R&D spend. I don't expect you to give us quarter by quarter, but shouldn't we think about increasing R&D spend as the year progresses, since you guys will be starting a number of important registration-directed study with lots of patients and attendant costs?

Yes, Michael. So, as you suggested, our Q1 burn was approximately $20 million. And I think it's fair to ramp that up gradually over the course of the year, for a burn target this year in the $95 million range, plus or minus $5 million, depending on our enrollment.

Okay, great. And then just one more quick question and I'll jump back in the queue, and that is with regard to STORM. Are you guys going to push ahead aggressively on the combination studies irrespective of the outcome of the STORM's in the first 80-patient cohort? Or will that analysis drive another strategic decision sometime in 2016 regarding the further development of selinexor in myeloma? Thank you.

The combination of selinexor or with pomalidomide or with Velcade will be run in parallel to the STORM study. So we will push this selinexor with dex in the STORM study and then separately the combination separate -- in parallel. In addition to this, keep in mind that we also have the study of carfilzomib and selinexor and dex that was already initiated.

Michael Schmidt, Leerink Partners.

For the KING and SIGN studies, how many patients have you treated in those by now? And could you help us frame expectations a little bit going into ASCO here?

So the SIGN study actually includes three different diseases -- ovarian, endometrial, and cervical. Each one of them has at least 20 patients per cohort. And the results of that will be presented at ASCO. The KING study has now over 20 patients across the surgical arm and the treatment arm. And again, we will present results from this study very soon.

Okay. And are those two studies -- are the patients in those studies basically -- are they very late-stage or salvage-type patients, similar to the studies that we've seen so far in the hematological settings?

Yes, so these are -- in the SIGN study these are very heavily pretreated patients, especially in ovarian. There are more options in ovarian compared to endometrial disease or cervical cancer. In the KING studies, these patients have to come after temozolomide and radiation. And they may have received at least these two and potentially others.

I see. Great, thanks. I thought the ACR data in triple negative breast cancer was pretty interesting. Could you -- I may have missed it on the call. What are your plans there for potential clinical studies?

We are, based on the results that we presented showing the synergy with the PARP inhibitor, we are looking -- we are considering opening a study in combination of selinexor with PARP in either breast cancer or ovarian cancer.

Okay, great. Thanks so much, and have a good ASCO coming up. Thanks.

Arlinda Lee from MLV.

Given the emerging data that you guys are putting out on other indications that are non-oncology, I'm curious about your prioritization between oncology and non-oncology -- and, as well, within oncology. Thanks.

Yes, let me be very clear about our priorities. Our number-one priority is the registration-directed studies for selinexor. That's across the Company, across all indications. So the majority of the Company resources and personnel effort are in the registration-directed studies, because our primary goal is to get selinexor to the patients who need them -- need it.

The secondary priority is to further clarify the breadth of selinexor activity, both alone and, I think more broadly, even, in combination with lots of other drugs. We've instituted a large IST mechanism to drive that, since it's cost prohibitive to do it all as Company-sponsored.

However, we and our Board have agreed that there is significant value that we could unleash, taking advantage of well-described biology involving XPO1. We have utilized compounds that have different pharmacokinetic and toxicologic data to try to take advantage. For instance, the KPT-335 in influenza has shown significant inhibition of influenza virus replication in both mouse and ferret models, and we want to push ahead with that. It was much more potent than some of our other SINE compounds.

And we have had KPT-350 being developed for autoimmune and inflammatory diseases. And that was the subject of a recent Nature Medicine publication as well, where we showed both anti-inflammatory and neuroprotective activity. So each of our SINE compounds is of interest and could serve in significant unmet medical needs, but the priority is on selinexor.

Great. Thank you very much.

(Operator Instructions) And that looks like all the questions that we have in the queue for today. So I'd like to turn the call back over to management for closing remarks.

Thank you very much. That concludes our first-quarter 2015 conference call. Thank you all for participating, and we hope to see you at our ASCO event in the next few weeks. Have a good day, everyone.

Ladies and gentlemen, thank you again for your participation in today's conference. This now concludes the program, and you may all disconnect your telephone lines. Everyone have a great day.