Justin Renz - EVP, CFO and Treasurer Michael Kauffman - CEO Sharon Shacham - President and Chief Scientific Officer.

Michael Schmidt - Leerink Swann Whitney Ijem - JPMorgan Catherine Hu - Bank of America Merrill Lynch Mike King - JMP Securities Arlinda Lee - Canaccord Genuity Brian Abrahams - Jefferies.

Good morning. My name is Michelle [ph] 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 2015 Financial Results Conference Call. [Operator Instructions] As a reminder, today's conference is being recorded.

I would like to introduce your host for today's conference, Mr. Justin Renz, Executive Vice President, Chief Financial Officer and Treasurer of Karyopharm Therapeutics. Mr. Renz, please go ahead..

Thank you and good morning. Welcome to the fourth quarter and full year 2015 earnings call.

This is Justin Renz, and I'm joined today by Michael Kauffman, the Chief Executive Officer of Karyopharm, who will provide a brief overview; Sharon Shacham, our Founder, President and Chief Scientific Officer, who'll provide an update on [inaudible] clinical and regulatory progress and development plans; and Chris Primiano, our Senior Vice President of Corporate Development, General Counsel and Secretary.

Earlier today we issued a press release detailing Karyopharm's results for the fourth quarter and year ended December 31, 2015. The release is available on our website at Karyopharm.com. Various remarks we'll make 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 risk factors section of our most recent quarterly report on Form 10-Q which is on file with the SEC, and 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 other date subsequent to today. We are happy to take questions following the prepared remarks.

I'll now turn the call over to Dr. Michael Kauffman, the Chief Executive Officer of Karyopharm..

STORM in multiple myeloma, where we expect phase 2b topline data at the primary endpoint of overall response rate from the first 80 patients in mid-2016. SOPRA in AML, where we expect the phase two interim analysis in late 2016 where we will make a go/no-go decision, and the topline overall survival data from this study will be available in mid-2017.

STAMP, also in multiple myeloma, where we expect phase 1b topline data in the recommended phase two dose for at least one of the regimens in late 2016. SADAL in DLBCL, where we expect phase 2b topline overall response data in early 2017.

And SCORE in multiple myeloma, which we expect to begin in the middle of this year, with phase two topline overall response data in mid-2017. On the solid tumor front, we initiated the phase 2/3 SEAL study evaluating single-agent oral selinexor in patients with advanced unresectable dedifferentiated liposarcoma after at least one systemic therapy.

This study is based on promising clinical data presented at the American Society of Clinical Oncology or ASCO 2015 Annual Meeting, in which durable stable disease and improvement in progression-free survival compared to previous chemotherapies were observed.

Topline progression-free survival data from the phase two portion of this study are expected in mid-2017.

We look forward to the presentation of additional data on our pipeline this year, including at the upcoming AACR Meeting in April in which 19 abstracts related to selinexor and our earlier-stage oncology programs have been accepted for presentation.

Finally, we are continuing to progress our non-oncology pipeline programs, including verdinexor or KPT-335, for certain viral indications, with an initial focus on influenza, and KPT-350 for neurological auto-immune and inflammatory conditions.

We may partner with a collaborator to undertake the clinical development and potential commercialization of these non-oncology programs. With that, I'll now turn the call over to Sharon to provide more details on our clinical development plans for selinexor and our pipeline of other drug candidates.

Sharon?.

Thank you, Michael. I will now provide an update on our development activities and plans, starting with selinexor and hematologic malignancies.

As Michael mentioned, we are actively enrolling patients in several later phase clinical studies evaluating the activity of selinexor in hematologic malignancies, including the STORM study in patients with multiple myeloma, the SOPRA study in older patients with relapsed/refractory acute myeloid leukemia, and the SADAL study in patients with relapsed/refractory DLBCL.

In May 2015, we initiated the phase 2b STORM clinical trial evaluating selinexor and low-dose dexamethasone in patients with heavily pre-treated multiple myeloma.

We are enrolling patients with myeloma that have been treated with and are usually refractory to bortezomib and carfilzomib, each of which is a proteasome inhibitor; lenalidomide and pomalidomide, each of which is an immunomodulatory agent or an iMiID; and disease refractory to at least proteasome inhibitor and one iMiD and has disease refractory to their most recent therapies.

In addition, as a result of the FDA approval of the anti-CD38 monoclonal antibody daratumumab last November, we're seeing to increase the proportion of patients enrolling into STORM study whose disease is also refractory to an anti-CD38 monoclonal antibody like daratumumab.

These patients will also be included in the evaluation of the first cohort of 80 patients of the STORM study. We continue to enroll patients on our phase two SOPRA study of selinexor in patients 60 years of age or older with relapsed or refractory AML who are ineligible for standard intensive chemotherapy and/or transportation.

The protocol provides for an interim analysis following a defined number of events or deaths.

At that point, the study data safety monitoring board will review the results of the interim analysis and provide us with the recommendation of starting the trial for significant efficacy or futility, continuing the study as currently planned, or increasing the size of the study. We currently expect this interim analysis to occur in late 2016.

But the timing of the analysis depends on the survival of patients. The sample size of the study is designed to have 80% power to detect a 75% improvement in median overall survival with the selinexor targeting approximately 5.2 months versus the physician choice arm of approximately 3 months.

We are also continuing to enroll patients in our phase 1b multiple myeloma study STORM, where selinexor and dexamethasone are being evaluated in combination with either bortezomib, pomalidomide or linalidomide. As Michael mentioned earlier, we expect to determine our recommended phase two dose in at least one of these combinations in late 2016.

Now, moving on to the SADAL study. As we described at ASH last year, based on discussion with the FDA, we amend the protocol for the ongoing SADAL study to remove dexamethasone from the original regimen and evaluate selinexor as a single agent in patients with relapsed/refractory DLBCL.

The study is evaluating 60 mg and 100 mg twice weekly doses of selinexor, with 100 patients per arm.

At least 50% of patients on each arm of SADAL will have the GCB subtype of DLBCL, which represents a particular high unmet medical need given the lack of available therapy for patients with difficult-to-treat subtype in the relapsed/refractory setting.

The primary endpoint of this trial is overall response rate on each arm separately, with the goal of determining the more optimal dose for patients with heavily pretreated DLBCL. Turning now to single-agent selinexor in solid tumors.

We are currently conducting company-sponsored trials of single-agent selinexor in three solid tumor indications, including advanced liposarcoma, the SEAL study; gynecological malignancies, the SIGN study; and recurrent glioblastoma multiforme, the KING study.

The phase 2/3 SEAL study, which launched earlier this year, evaluating single-agent oral selinexor in patients with advanced unresectable dedifferentiated liposarcoma was initiated based on promising clinical data presented at the American Society of Clinical Oncology, ASCO, 2015 Annual Meeting, in which durable stable disease and improvement in progression-free survival compared to previous chemotherapies were observed.

Fifty patients are expected to be enrolled in the phase two portion of the study, with the potential to increase enrollment in the phase three portion following an interim analysis.

The study design, including the primary endpoint of progression-free survival, was acceptable to the FDA and will be evaluated for futility in an interim analysis of the phase two portion of this study. We plan to present updated data for -- from the SIGN and KING studies at an appropriate medical meeting this summer.

We are pleased with the growing interest in and progress with oral selinexor across a very broad area of malignancies, as evidenced by the number of investigator-sponsored trials as well as the number of our own trials.

Beyond selinexor, we are leveraging our leadership in nuclear transport and related targets with the advancement of our earlier-stage pipeline programs. In January we initiated a phase 1/2 study of oral KPT-8602, a novel second-generation small molecule SINE compound, in patients with relapsed/refractory multiple myeloma.

The study was initiated based upon preclinical studies presented at the ASH 2015 Annual Meeting, in which KPT-8602 demonstrated single-agent anti-multiple-myeloma activity, along with the potential for higher and more frequent dosing compared with selinexor. Topline data are expected in late 2016.

Finally, we also plan to initiate in May 2016 the first in-human study of our first-in-class oral dual inhibitor of PAK4 and NAMPT, KPT-9274, in patients with heavily pretreated solid tumors or lymphoma. We look forward to continuing to provide you with updated results as they become available. Now I will turn the call back to Justin..

Thank you, Sharon. Since we issued a press release earlier outlining our fourth quarter and yearend of December 31, 2015 financial results, I'll just review the highlights and then speak to our cash balance and our financial guidance.

Karyopharm reported a net loss of $118.2 million or $3.32 per share for the ended December 31, 2015, compared to a net loss of $75.8 million or $2.43 per share for the year ended December 31, 2014.

For the quarter ended December 31, 2015, we reported a net loss of $29 million or $0.81 per share, compared to a net loss of $25.9 million or $0.79 per share for the same period in 2014.

We recognized stock-based compensation expense of $17.1 million and $14.2 million for the years ended December 31, 2015 and 2014, respectively, as well as $5.4 million, that is, $4.6 million for the quarters ended December 31, 2015 and 2014, respectively.

Research and development expense was $97.7 million for the year ended December 31, 2015, compared to $60.1 million for the year ended December 31, 2014. For the quarter ended December 31, 2015, R&D expense was $24.1 million, compared to $20.0 million for the same period last year.

General and administrative expense was $21.6 million for the year ended December 31, 2015, compared to $15.9 million for the year ended December 31, 2014. For the quarter ended December 31, 2015, general and administrative expense was $5.3 million, compared to $5.9 million for the same period in 2014.

Our increase in expenditures is primarily related to the significant expanded clinical development activities for our lead drug candidate selinexor which Sharon just highlighted. Regarding cash utilization, we had cash burn from operations plus fixed asset additions of $21.2 million in the fourth quarter and $95.8 million year to date 2015.

Cash, cash equivalents and investments as of December 31, 2015, including restricted cash totaled $210.0 million compared to $214.8 million at the end of 2014. We expect to end 2016 with a cash balance greater than $120 million.

Based on our current operating plans, we expect our existing cash will fund our R&D programs and operations into the middle of 2018 including moving the SOPRA, SADAL, STORM and SEAL studies, our four ongoing later phase clinical trials and once commenced, the SCORE study to their next data inflection point.

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

Thank you, Justin. In summary, over the past year we continued to expand our leadership position in the development of oral SINE-based therapies for selinexor clinical advancements across a number of hematologic and solid tumor indications and the presentation of encouraging data on our early stage oncology pipeline programs.

This broad and aggressive oncology clinical development program is continuing in 2016 with both Company and investigator sponsored trials underway or planned to evaluate selinexor as a single agent and in combination with other existing and emerging oncology therapies.

We are looking forward to sharing several key clinical data readouts throughout the remainder of this year and into 2017.

Finally, to reiterate my opening remarks, our primary focus is to execute our most advanced studies enabling Karyopharm to potentially commercialize selinexor as expeditiously as possible while also understanding how to maximize selinexor to benefit the greatest number of patients in the longer term. With that, we are ready to take questions.

Operator?.

[Operator Instructions] Our first question comes from the line of Michael Schmidt with Leerink. Your line is open, please go ahead..

Good morning and thanks for taking my questions. I had a couple. One on the SOPRA trial, it looks like the interim analysis is now pushed out by six months or so.

What is behind that?.

As you know, this is an event driven trial and the preliminary read is although accrual is right on target and we are very excited about it, it is actually doing very well, the events are coming in a bit slower than we originally planned so we just moved that guidance a little bit..

Great, understood.

On the SADAL study in DLBCL, I may have missed that but what percentage of patients are you now looking for to have been relapsed from CD38 antibodies?.

In the SADAL study, you mean probably you mean the STORM study in melanoma?.

I am sorry, yes, correct..

At least 25% of the patients will be exposed to a CD38 antibody..

Okay, great.

And then lastly, just a question on your SADAL study, DLBCL, the recent protocol amendment, Michael, can you remind me I think you built in a period of 12 weeks after a patient relapses from the prior therapy? Is that correct?.

Yes, it is a period of 14 weeks or 98 days for a complete washout from a systemic multi-agent therapy regimen..

I guess my question is like how does that affect enrollment or how likely is it that a patient who is progressing from prior therapy can actually wait 14 weeks before going on to the next therapy?.

So the patients we are targeting now and based on our Phase 1 analyses and some of the early Phase 2 results, if a patient is actively progressing on four or five drugs with Rituximab, they are suffering significant side effects and it is very difficult to get them under control with a single agent oral therapy.

So the patients we're primarily looking at are those people that are having a relapse after a complete remission or a very good partial response..

Okay.

I guess what percentage of patients fall into that category DLBCL typically?.

Yes, we would say about 40% of patients DLBCL and recognizing obviously that would slow down accrual that is why we push the timing on that and we stand by the current timing that we said. We also opened the trial again based on some further analysis of the data in all of the Phase 1.

We added patients who have DLBCL that has transformed from a low grade lymphoma such as follicular lymphoma into the study.

So while we decrease the potential patients, we added in the transformed DLBCL and we also opened it up to patients who had a minimum two priors to a maximum of five prior therapies and that also opened it up a bit compared to the prior regimen..

Okay, great. Thanks for taking my questions..

Thank you. And our next question comes from the line of Whitney Ijem with JPMorgan. Your line is open, please go ahead..

Good morning. So just going back to a question around commercialization, you mentioned you are looking to start building out infrastructure in both the U.S. and E.U. And as I recall earlier this year you had kind of indicated that you were looking to partner in the E.U. and you didn't see a need to build out infrastructure there at this point.

So I guess it seems like there has been a change of thinking there.

Can you give us any color on that?.

Yes, if we spoke differently than before, there really hasn't been.

There are certain things that regardless of whether we partner or I should say when we partner in the EU because we do intend to partner in the EU that we need to have some of our own infrastructure in place and we do in fact have a site in Munich, Germany which is primarily clinical and operations and we are just going to build that out a little bit, not a significant number of hires, to include MSLs and the like, medical science liaison and the like in the EU.

But the plan is that there are many companies that do a really good job marketing in Europe so we will be partnering at the appropriate time to handle that..

Got it.

And then just on 2016 R&D, I guess you gave the cash guidance for year-end but is there any color you can give us on the shape of R&D spend or maybe first half versus second half kind of weighted R&D spend this year?.

Hi, this is Justin, Whitney. Our R&D expense overall we expect to be somewhat less than prior year excluding obviously stock-based compensation. But we would expect our expense to be relatively ratable throughout the year perhaps going up toward the end of the year as we get the SCORE study enrolling in the middle of the year..

Great, thanks for taking the questions..

Thank you. And our next question comes from the line of Catherine Hu with Bank of America. Your line is open, please go ahead..

Thanks for taking my questions. How much of an update will we get from the SIGN and KING studies in midyear, like how many patients, etcetera? And then for the interim rate for the STORM midyear, what kind of level of detail will we get with those results and what are you thinking is the bar for you to expand the study? Thanks..

On the KING and SIGN, we will give a full update including when we expect the study to be completed and what is the current response rate that we are seeing at the conference midyear.

The other question was on SOPRA update?.

STORM..

On STORM? As we mentioned several other times, we expect to have the study complete enrollment in mid-2016 and followed by the topline data towards the end of --.

Right.

What level of detail will you be giving in that interim read?.

We will provide response rate and also plans whether we are completing the study, expanding it, etc..

Thank you. And our next question comes from the line of Mike King with JMP Securities. Your line is open, please go ahead..

Good morning, guys. Thanks for taking my question. Most of my questions have been answered, just a couple of quick ones. Was wondering, do you know if Dr.

Jakubowiak has any intentions of updating his study results or have we seen his final results?.

His study is still ongoing and I am sure there will be more updates towards the end of the year..

Okay, great. And then just wondering is there any plan for combination therapies in solid tumors? So far all the solid tumors studies have been single agent selinexor.

Is there any thought to combination therapies in solid tumors?.

Yes, this is available on clinicaltrials.gov and you will see that we have several studies evaluating selinexor in combination in solid tumor, there are studies at Memorial Sloan-Kettering by Vicky Makker looking at combination of selinexor with carbotaxel and there is currently an eight-arm study of selinexor in combination with different chemotherapies..

Okay.

And do you expect any of those results this year?.

Some, yes..

Some, okay. And then finally just on STORM, have used seen -- you mentioned earlier that you are looking for about 25% of those patients to be relapsed from anti-CD38 antibodies.

Can you tell us if you have seen that level of relapse or anything about the pace of enrollment in patients that have relapsed from anti-CD38 antibodies?.

Yes, the protocol requires that at least 25% of the patients will be and we have no problem in enrolling into this study. We are meeting all of our expectations in terms of enrollment. So this population exists and definitely need new therapies..

Okay, great. Thanks for taking the questions..

Thank you. And our next question comes from the line of Arlinda Lee with Canaccord. Your line is open, please go ahead..

On STORM, sorry to get back to this like everyone else but we noticed on clinicaltrials.gov that you changed the terminology from quad refractory to quad experience. And I am wondering how that kind of factors into your updated guidance and discussions with regulatory agencies and maybe what we can expect on that front going forward? Thank you..

So the vast majority of the patients on the study or at least quad-refractory and some are penta-refractory as you mentioned earlier. We opened the definition for quad exposed mostly due to the recommendation issues with very elderly -- some of these patients have nine or ten trial therapies.

Some of them are not in the center but they are being treated right now. And to allow patients that were treated with Velcade but with no documentation, we opened the extension but we are doing our best to make sure that we understand whether these patients were relapsed or refractory to each one of these four, five drugs..

And then maybe just a follow-up. So I guess in terms of regulatory discussions, is there a difference with between the refractory and the experience with the regulatory agencies or do you think the documentary evidence that you collected should be sufficient? Thanks..

I am sure the commendation will be key to prove that the patients refractory to at least the four drug and some of the five drug and we will discuss it with the agency at the appropriate time..

Okay, great. And then on SADAL, can you update us on what the net effect of the enrollment criteria changes had on the overall patient population? Thank you..

So about 50% of the patients that are being treated with second-line in DLBCL respond to it [inaudible] etcetera. But even those responders, the vast majority of them then progress and need third or fourth line. These are the patients that we are targeting right now.

So it did reduce the amount of patients that we can have to about 40% but we expanded -- from only de novo DLBCL to transform which is a significant number of patients that actually the disease is quite tough and we allowed more prior therapies and we added more sites to the study so overall we are feeling comfortable with our projections for the data to complete the enrollment by early 2017..

Okay, thank you..

Thank you. And our next question comes from the line of Brian Abrahams with Jefferies. Your line is open, please go ahead..

Hey, guys. Thanks very much for taking my questions. First, on STORM in myeloma, I am just wondering I guess building on a prior question if you could talk a little bit more about what your bar will be for expanding that study versus focusing more on building out the database in combos.

Obviously at that time you are going to have STAMP, you will have started the SCORE study.

How do you I guess broadly speaking think about balancing potential speed to market as a monotherapy versus dedicating more resources or allocating more resources toward these combos where you could have potentially have even broader commercial opportunity?.

As we mentioned a little bit at ASH, we are very encouraged by the results we are seeing from the combination of selinexor with carfilzomib and the enrollment so far into the STORM study.

The preclinical data for looking at this combination are robust so we are definitely going to pursue the combination of selinexor with other agents in multiple myeloma in later stage studies including the Score.

We think that based on the results as we will observe on the STORM study we will decide and following interactions with the agencies on the next step about expanding this study. Remind us the ultimate object for the submission and other submissions of that kind where around 120 is the minimum for regulatory submissions..

Got it.

And then on the SADAL study as you have further refined the patient population there as you have discussed, I guess when we see the overall dataset and I guess how do you incorporate some of those patients who were enrolled pre-amendment versus those who have been enrolled post the amendment? Will there be sort of one dataset in totality or will you be presenting data in two different buckets and how will that be I guess managed from a regulatory standpoint in terms of the totality of that dataset? Thanks..

So for safety purposes, we will evaluate the entire population before and after the amendment of course and we will do separate safety analysis for each of the population. For efficacy, the protocol clearly states that only patients with outcomes that were enrolled after the amendment will be used for the efficacy analysis..

Got it. That is very helpful. And then I guess last, a question on verdinexor. You've talked a little bit more about potentially looking at that in influenza.

Given the potential breadth of activity and the interaction with the host proteins versus the virus itself, I'm sort of wondering if you are thinking about that as potentially optimal for pandemic strains where there might be less concern -- or because you might have less concern about resistance development there given the mechanism? And if you have kind of outlined the development plan there if that is primarily going to be something you look to out-license? Thanks..

So pre-clinically we tested verdinexor in many of the strains including many of the pandemic strains and it has a very broad activity. It was actually active across all of them. In terms of the development plan, we have done the Phase 1 study in healthy volunteers to enable us to look at the safety of selinexor in healthy volunteers.

Following that there will be probably a need to look at other populations like elderly so we can decide on the development path in in-patients, severe influenza versus the general population and once we complete those special populations, we will decide on the next steps..

Makes sense. Thanks so much for taking my questions..

This will probably -- we will not do by ourselves but by collaborating with a partner..

Great, thank you..

Thank you. [Operator Instructions] We have a follow-up question from the line of Michael Schmidt with Leerink. Your line is open, please go ahead..

Hey guys. Thanks. I had a follow-up but that has been answered by now. Thank you so much..

I'm showing no further questions at this time and I would like to turn the conference back over to Mr. Michael Kauffman for any closing remarks..

Thank you, operator, and thanks to everybody on the call. In closing, we made significant progress in 2015 in advancing our therapeutic pipeline and we entered 2016 well-positioned to achieve a number of value creating milestones.

We are the first company to enter clinical development within an oral XPO-1 inhibitor for the treatment of cancer and other major diseases. Our lead drug candidates are first-in-class oral SINE compounds, selective inhibitors of nuclear export that have a novel unique and broadly applicable mechanism of action.

We own global rights to all of our compounds in our pipeline with patents running until at least 2032. We expect data from our four ongoing later phase clinical trials, the SOPRA, STORM, SADAL and SEAL studies and the upcoming SCORE study over the next six to 18 months.

Our management team has a track record of success in oncology drug development, regulatory approval and commercialization with Velcade and Kyprolis.

And finally, we are well capitalized with over $210 million in cash as of December 31, 2015 which we believe is sufficient to take us through the middle of 2018 and several important inflection points for selinexor. Thank you for participating and we look forward to seeing many of you at our upcoming medical and investor conferences.

Have a good day, everyone..

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program and you may all disconnect. Everyone have a great day..