Michael Kauffman - Chief Executive Officer Sharon Shacham - Founder, President and Chief Scientific Officer Justin Renz - Executive Vice President and Chief Financial Officer Christ Primiano - Vice President of Corporate Development and General Counsel.

Michael Schmidt - Leerink Partners Brian Abrahams - Jeffries Whitney Ijem - J.P. Morgan Catherine Hu - Bank of America Merrill Lynch Michael King - JMP Securities.

Good morning. My name is Brian, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Third Quarter 2015 Financial Results Conference Call. Justin Renz, Executive Vice President, Chief Financial Officer and Treasurer of Karyopharm Therapeutics, please begin your conference..

Thank you Brian, and good morning. Welcome to the third quarter 2015 earnings call.

This is Justin Renz, I am joined today by Michael Kauffman, the Chief Executive Officer of Karyopharm will provide a brief overview of the third quarter, Sharon Shacham, our Founder, President and Chief Scientific Officer will provide an update on selinexor clinical and regulatory progress and development plans; and Christ 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 third quarter ended September 30, 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, the 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 quarterly report on Form 10-Q for the third quarter of 2015, which is on file with the SEC as of this morning 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 date subsequent to today. We are happy to take a few questions following the prepared comments.

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

Thank you, Justin, and good morning everyone. Thanks for joining us today. Before I turn the call over to Sharon, I would like to make a few introductory comments.

First, we are making strong progress advancing our oncology pipeline and are more confident than ever in the clinical potential of our lead compound selinexor to improve outcomes for patients in a number of cancer settings.

While we have a lot going on, rest assured that we are very focused on the quality execution of the most important clinical studies that will enable selinexor to get to market. We expect data in late 2016, which if positive, we will submit for regulatory approval as soon as possible.

I want to point out that our confidence is based on the broad and durable anti-tumor activity with adequate tolerability of oral selinexor that we have observed in both hematologic and solid tumor malignancies.

This broad activity is consistent with selinexor’s known mechanisms of action as a novel inhibitor of Exportin-1 or XPO1 leading to the observed reactivation of tumor suppressor proteins and reductions in various onco proteins.

More importantly, our confidence and drive are further heightened by the continued enthusiasm from the clinical community as we continue to evaluate selinexor’s activity including in combinations with other anti-cancer agents across a wide variety of difficult to treat cancers.

Between company and investigator sponsored trials, there are currently 43 active clinical studies evaluating selinexor. In fact, over 1250 patients across various hematologic and solid tumor studies have been treated with oral selinexor.

To-date, 19 patients have remained on single-agent selinexor for over 12 months with the longest for over two years without clinically significant cumulative toxicities or major organ dysfunction.

As a result, we believe selinexor’s breadth of activity and novel mechanism of action provide multiple paths to late-stage development and potential commercialization.

I am also pleased to report that we are continuing to enroll patients on schedule following the recent selinexor dose reduction in our Phase II SOPRA study in older patients with relapsed or refractory AML. We remain on track for interim data in mid-2016 and top-line data at the end of 2016.

Preliminary evaluations of tolerability based on the recent dose reductions appear promising in this population of older patients with previously treated AML. We had another selinexor milestone in this quarter with the initiation of the STOMP study or Selinexor and Backbone Treatments of multiple myeloma patients with support from Myeloma Canada.

In this multi-arm Phase 1b/2 clinical study, we are evaluating selinexor plus low-dose dexamethasone in combination with a number of backbone therapies in the multiple myeloma setting. We believe that adding selinexor and dexamethasone to these activations will provide prolonged clinical benefits.

Selinexor and low-does dexamethasone are already being combined with carfilzomib or Kyprolis in an investigator sponsored trial where promising preliminary data were presented at ASH 2014 and when we update it with additional patient data at ASH 2015.

Speaking of ASH, we look forward to presenting a range of data at the coming American Society of Hematology 2015 Meeting in Orlando, Florida on December 5 through the 8, including five oral presentations and 12 posters describing the role of both our SINE and PAK4 compounds in Oncology.

Presentations include clinical and pre-clinical data demonstrating the activity of selinexor alone and in combination with other anti-cancer agents. Sharon will briefly discuss these in more detail.

In addition, we will present pre-clinical data on KPT8602, a second-generation SINE compound and pre-clinical data on our first-in-class oral PAK4 Allosteric Modulator, KPT9274. Early pre-clinical development with KPT8602 has demonstrated the potential for a SINE compound with distinct pharmaceutical properties allowing for daily dosing.

Animal data are very encouraging and two oral presentations will cover this compound at ASH.

In addition to the presentations and posters at ASH, Karyopharm is hosting a special event in Orlando on Monday, December 7 at 8 O’clock PM Eastern Time in which we and key opinion leaders in the field of hematology oncology will discuss the significant potential for broadening the foundation for SINE-based therapy across multiple cancers.

In addition to Sharon and myself, our guest speakers will include Dr. Andrzej Jakubowiak, the Director of the Myeloma Program at the University of Chicago; Dr. Gert Ossenkoppele, Professor of Hematology at the VU University Medical Center in Amsterdam; and Dr. Jeffrey Rubnitz, Director of the Leukemia Lymphoma Division at St.

Jude Children’s Research Hospital. We expect this to be a highly engaging and informative event, which will be webcast for those who cannot attend in person. I’ll now turn the call over to Sharon to provide an update on our clinical development plans for Selinexor and our other compounds.

Sharon?.

Thank you, Michael. I will now provide an update on our Selinexor development activities and plans.

Let me also emphasize the point that Michael made, while we and our clinical investigators are conducting a large number of trials, we remain extremely focused on prioritizing our most valuable and later-stage trials and driving them towards successful outcomes.

As Michael also mentioned, based on striking pre-clinical synergy in animal models of myeloma, we recently initiated the STOMP trial in which we are evaluating Selinexor and low-dose dexamethasone in combination with other active agents in patients with previously treated multiple myeloma.

We plan to report preliminary top-line data for this study in 2017. This STOMP study complements the already ongoing investigator-sponsored trial of Selinexor plus carfilzomib and dexamethasone with updated results being presented at ASH by Dr. Jakubowiak.

We anticipate that this study will inform the design of randomized studies of selinexor added to the backbone therapies in multiple myeloma which could serve as the basis for full approval in multiple myeloma. In addition, Karyopharm is active in enrolling patients in full later-phase hematologic malignancy studies evaluating selinexor.

One in all the patients with relapsed refractory AML SOPRA study, the second in patient with relapsed refractory DLBCL SADAL study which was an excellent combination with dexamethasone in patients with refractory multiple myeloma STOMP study and the first in patient with Richter's Transformation SIRRT study.

Based on our extensive Phase 1 experience with single-agent selinexor, we believe 60 mg twice-weekly is the most appropriate dose in several settings and then all presentations supporting the selection of this dose with both efficacy and tolerability in specific indications is being presented at ASH 2015.

In patients with heavily pre-treated multiple myeloma in our STOMP study selinexor was used at 80 mg twice-weekly in combination with 20 mg of dexamethasone. In addition, we will continue to evaluate the use of 60 mg doses to 100 mg of selinexor and our ongoing SADAL study in patients with heavily pre-treated DLBCL.

As noted previously, the SOPRA study in all the patients with AML will now use the 60 mg twice-weekly dose and we look forward to reporting preliminary top-line data from this study in the fourth quarter of 2016. Moreover, our SIRRT study in patients with Richter's Transformation is evaluating the 60 mg dose of selinexor.

Finally, selinexor is being combined with a number of other anti-cancer agents and appropriate dose selections are being determined in ongoing Phase I, II studies. On the solid tumor front, Karyopharm is currently conducting a variety of single-agents in combination studies.

In addition, based on data – of dosing a Phase I study and following an FDA meeting conforming our trial design, randomized blinded placebo controlled Phase II 3 trial in liposarcoma our SEAL study is planned to commence before the end of this year.

As Michael highlighted, there continues to be significant excitement from the investigator to assist the use of selinexor in a variety of oncology settings.

Towards that end, a number of investigators sponsored or company sponsored clinical trials evaluating the potential of selinexor in combination with chemotherapy or targeted agents are currently ongoing on plan.

Of note, this past weekend, promising pre-clinical data demonstrating the anti-tumor benefit of combining selinexor with immunotherapy in aggressive melanoma models were presented at the Society for Immunotherapy of Cancer Annual Meeting in Maryland. Karyopharm researchers in collaboration with Dr.

Greg Lesinski from Ohio State University presented pre-clinical data demonstrating that the combination of selinexor with anti-PD1 or anti-PDL1 immune checkpoint inhibitors as results considerable anti-tumor and immuno-stimulating activity in two aggressive murine melanoma models.

Importantly, from a mechanistic perspective, when added to an anti-PDL1 antibody, selinexor increased the number of NK cells and help kill lymphocyte and increased T-cell activation all compared with anti-PDL1 alone.

Based on this oncology and pre-clinical data, we look forward to investigating the activity of selinexor with immune checkpoint inhibitors in the clinic in the near future.

Based on promising pre-clinical data for KPT8602, our second SINE compound which will be reported at ASH 2015, we have filed an Investigational New Drug or IND application with the Food and Drug Administration for KPT8602. Pending agency review, we plan to initiate clinical study with KPT8602 in multiple myeloma in early 2016.

As Michael mentioned, we have seen some early oncology and pre-clinical signals with KPT8602 indicating that this may have a tolerability profile that could potential enable increased or more frequent dosing.

And finally, we also plan to file an IND for our Oral PAK4 Allosteric Modulator, KPT9274 and pending agency review initiate clinical development in patients with heavily pre-treated solid tumors or lymphoma in the first half of 2016.

So, as you have heard, we are quite pleased with the growing interest and progress with oral selinexor across a very broad array of malignancies. In addition, we look forward to evaluating the activity of our early-stage oncology compound including KPT8602 and KPT9274.

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 today outlining our third quarter ended September 30, 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 $30.4 million or $0.85 per share for the quarter ended September 30, 2015 that compares with a net loss of $19.7 million or $0.61 per share for the same period in 2014. We recognized stock-based compensation expense of $3.5 million and $2.9 million for the quarters ended September 30, 2015 and 2014 respectively.

Our third quarter net cash burn from operating activities was approximately $25.3 million.

Research and development expense was $25.9 million in the third quarter of 2015, compared to $16 million for the same period in the prior year while general and administrative expenses were $4.8 million in the third quarter of 2015, compared to $3.8 million for the third quarter of last year.

Our increase in expenditures is primarily related to the significantly expanded clinical development activities for our lead drug candidate Selinexor KPT-330, which Sharon just highlighted. As Michael mentioned earlier, by December, we expect to have over 40 actively enrolling clinical studies including 10 Phase IIs.

Cash, cash equivalents, and investments, as of September 30, 2015, totaled $230.2 million, compared to $256 million at the end of June. We expect to end 2015 with a cash balance greater than $200 million.

Based on current operating plans, we expect our existing cash will fund our R&D programs and operations well into 2018, including moving our later-phase clinical studies to their data points. I'll now turn the call back over to Dr. Michael to provide a brief summary before we take some questions. .

Thank you, Justin. In summary, this has clearly been a very productive period for Karyopharm. Many of the ongoing selinexor clinical studies are enrolling at a brisk rate while new studies, primarily in combination with other anti-cancer agents continue to ramp up and come online.

We are looking forward to sharing additional data on our pipeline of first-in-class oncology therapeutics at the upcoming ASH Meeting in early December including selinexor activity in combination regimens across hematologic malignancies and continuing to execute against our many development goals during the remainder of the year.

To reiterate, our primary focus is to execute our most advanced studies enabling Karyopharm to commercialize selinexor while also understanding how to maximize selinexor to benefit the greatest number of patients. With that, operator, we are ready to take questions.

Operator?.

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

Hi, good morning and thanks for taking my questions.

On the AML SOPRA study, I was wondering, if there are any additional insights from the first 100 patients that you treated at the high-dose that drug gained and whether you had any plans to present any of that data?.

Yes, the totality of the data from SOPRA will presented when the trial has completed. Given that this is potentially a registration trial. It’s a randomized trial as you know with the survival endpoint. It’s totally inappropriate and certainly not appreciated by regulators to present AML data.

But we are happy very, very – with very, very preliminary observations, we are happy with what we’ve seen so far with the dose reduction and we remain on track with the timelines that we discussed during the call. .

Okay, great. And then, on the upcoming ASH Conference, I was wondering if you have some more color on the multiple myeloma trial particular, if any additional information on how many patients might be included in that dataset? And also can you remind us what the bar and sort of that combination in the last case, in multiple myeloma? Thank you. .

Yes, as you know, there were eight patients presented in the abstract, all of whom are extremely heavily pre-treated really had gone through available agents and where refractory proteasome inhibitors and in almost all cases, quite refractory to carfilzomib in their most recent or nearly most recent therapy.

Six of those eight patients showed a response that is a PR or better. One of the patients had a minor response which means at least a 25% reduction and one patient was not evaluable remains in the denominator.

We expect to have a few more patients in this study and assuming the data continue to show the robust and durable activity that we’ve seen so far. We are thinking about our plans to move ahead with such a combination in the future and we hope to update those plans at ASH. .

And so, you mentioned the new – I guess, BASKET trial in multiple myeloma looking at different, a variety of different combinations, the STOMP trial, I guess, would you wait for that data to commend for – looking at additional combinations or it sounded like we have some richer setting might be in patients who move ahead with the registration trial prior to – or aside from that study coming in?.

One of the underlying strategic beliefs that we have and based on the broad activity of this drug is that, the reactivation of tumor suppressor protein is generally applicable to nearly any combination therapy, that is, we should provide at least additive and possibly synergistic activity, given what we’ve seen so far with Kyprolis and assuming that those data hold up, we think this is a very compelling combination that we may move ahead with.

That said, obviously, we want to explore further, particularly with the image compounds, both REVLIMID and Pomalyst and we will be looking at those. But this is, these are additional options we believe.

We do believe that the data with proteasome inhibitors which we’ve seen clinically and by the way, it’s consistent with what we saw pre-clinically is quite compelling and deserves further attention. So I don’t think it will be an either/or. .

Okay, great. Thank you so much. .

Thank you. Our next question comes from the line of Brian Abrahams with Jeffries. Your line is now open. Please go ahead..

Hi, thanks for taking my question. I wanted to follow-up a little bit more on sort of the multiple myeloma go-forward path and prioritization.

I guess, I am wondering, Mike, do you still expect single-agent selinexor in highly refractory myeloma patients could be a first approval based on the STORM study perhaps expanding that out? Or is the focus really now more on getting more information about combinations and then doing a full registrational study with any particularly promising combos?.

Yes, again, I think, our approach is a really a dual-pronged one, as you allude to.

It should be clear that the STORM study would be designed if it did show sufficient activity and we don’t know what that is, we don’t know, we all know what the previous bar at FDA was, this would be an initial approach in myeloma, but this will be an for an accelerated approval based on the surrogate end-point of response rate.

Either way, we still need to have a full approval strategy to confirm such an approval and in addition, as you are all aware, Europe tends not to appreciate single-arm studies terribly and generally require randomized studies.

So, we believe that combination studies with in the randomized setting would serve for both for full approval in the US, as well as in Europe. Again, STORM could serve potentially for accelerated approval here and we are continuing to press on with that study as well. .

Got it.

And then, you mentioned, some thoughts around accommodations with checkpoint inhibitors and some of the pre-clinical data that you are seeing and we know you are looking at Richter’s, I think there was some very early promising data for the PD1s in that indication in the ASH abstract, just sort of wondering what you are thinking in terms of potential checkpoint combos, are you thinking more along the lines of solid tumor settings or might you think about some of the malignancies as well there?.

So, for the Phase I question, we will – probably we will follow-up in the solid tumor – the PD1 and PDA is already approved. The PD1 inhibitors are already are full and then, once we have the recommended Phase II dose of Selinexor in combination with PD1 inhibitor, then we can evaluate it in a range of indications including hematological indications.

.

Got it. And then, just one last question on 8602, it sounds like that’s progressing pretty well.

Just wondering if you could talk anymore specifically about some of the differences there, that could enable – that you alluded to earlier that could enable a wider therapeutic window? Is it of different manner by which it hits the target or is it more a matter of the PKPD profile of that versus Selinexor that could have differentiated clinical properties.

Thanks..

We will present a lot of it at the oral presentation of 8602 at ASH, but, in general, 8602 is more reversible, still concurrently to XPO1 similar to Selinexor, but it’s more reversible than Selinexor. And in addition to that, it has lower or significantly lower brain penetration which might allow for more frequent dosing. .

Thanks. .

Thank you. Our next question comes from the line of Whitney Ijem with J.P. Morgan. Your line is now open. Please go ahead. .

Can you hear me? I was on mute. Thanks for taking the questions.

I guess, in terms of what we will see for SOPRA in the interim data versus the top-line next year, I mean, will be getting sort of efficacy and safety data in an interim look? Or what should we be expecting there in terms of the differences between those two read outs?.

The interim analysis will include both efficacy and tolerability data. It’s about 50% of the events in the study. .

Got it, and then, as we think about your cash burn guidance, I guess, I assume STOMP and COR included in that, as you look to bring 8602 in the PAK4 inhibitor into the clinic, I guess, are those trials included or how should we be thinking about how that may change looking towards next year?.

Sure, they - both are included in the burn guidance for next year, yes. .

Great. Thanks for taking the questions..

Thank you. Our next question comes from the line of Catherine Hu with Bank of America. Your line is now open. Please go ahead. .

Good morning. Thanks for taking my question.

On 8602, given the improved safety profile, should we think of that agent be used more in combinations going forward versus selinexor? And then, also, on the R&D, not given guidance for next year, but should we expect a step-up next year or a lot of these new – given a lot of these new studies are starting and it will be pretty minimal? And then just lastly, given you’ve shown some very encouraging data for disorders to reduce AEs, do you think there is more room to produce to dose particularly when using the combination regimens? Thanks.

.

Hi, Catherine, just I’ll speak to the guidance first. So, our R&D expenditures estimates for 2016 will be slightly less than 2015, in 2015 as we’ve just discussed today, we had a lot of activities in terms of getting studies up and running, as well as we put some of our treasure towards CMC and those costs will all be reduced in 2016.

So we will be able to accommodate getting 9274 and 8602 going well in 2016 as well as continuing the various clinical studies of selinexor with an overall reduced burn. .

Great. The dosing we will let Sharon just briefly discuss it, but this will be covered at ASH in an oral presentation. .

So, we have an oral presentation at the ASH about the recommended Phase II dose and we will present a lot of data there to show that the dose of selinexor, single-agent is 60 mg and it has – its optimal tolerability as well as efficacy.

In combination, we are evaluating a range of doses, usually at 60 mg or just below it and some of these are already reported at ASH and more will be reported in future meetings. .

And then, lastly, the question on 8602, just to caution, let’s not get too far ahead of ourselves. We don’t have any data yet in human.

So, we’ll have to wait and see how that profile of the drug plays out whether the reverse of this slightly improved reversibility or more reversibility will have any effect on efficacy or not and then the tolerability around the brain barriers. So we will assess this.

We chose multiple myeloma, because the readout is so quick and then, we will be able to plan for how we use selinexor and then 8602 in different indications. So we’ll have to wait on that. .

Great, thanks much. .

Thank you. [Operator Instructions] Our next question comes from the line of Michael King with JMP Securities. Your line is now open. Please go ahead..

Good morning guys. Thanks for taking the question. I apologize if these have – if you’ve addressed these in the formal remarks. I’ve been kind of hopping on to a bunch of different calls this morning.

But, two questions, first is, just on, PAK4, when do you expect to have the first molecule in humans? And then, I want to say, it was yesterday at the Triple Meeting, John Byrd from Ohio State talked about, I guess, it’s an IST that’s looking at selinexor in combination with Ibrutinib and just wonder if you might address the goals and expectations for that study? Thanks.

.

So, for your second question, this is a study, a study that John Byrd referred to is an investigator sponsored study that is being conducted at Ohio State and in the Utah. And it’s looking at a combination of selinexor with Ibrutinib. We will evaluate in two different populations in CLL and separately in patients with non-Hodgkin's lymphoma.

The goal will be to identify a recommended Phase II dose for selinexor and then to do an expansion on both – in both indications. .

Would these be high-risk patients in CLL, Sharon?.

You can imagine that most of the patients – some of these patients – these patients have not been treated with Ibrutinib before. So they are coming at the relevant early stage and we are not separating high-risk to not high-risk in the dose escalation part of the study.

In the extension, we will of course collectivize all of them and we will look at the activity of selinexor in high-risk patients and not. .

Okay, and on PAK4?.

Can you remind me the question?.

Well, the timing..

Oh, the timing. .

And the impacts were..

It will be towards the end of Q1, early Q2. This is when we are planning to initiate a Phase I study in patients with solid tumors and lymphoma or lymphoma. .

Okay, great. Thanks for taking the questions..

Thank you. There are no additional questions. I will now turn the call back to Dr. Michael Kauffman, Chief Executive Officer of Karyopharm for closing comments..

Thank you very much. Again, we appreciate everybody’s time this morning and that concludes our 2015 third quarter conference call. Have a good day everyone. .

Ladies and gentlemen, this does conclude today’ program. You may all disconnect. Everyone have a wonderful day..