Good morning. My name is Otoya and I'll be your conference operator today. At this time I would like to welcome everyone to the Karyopharm Therapeutics Third Quarter 2014 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'm here with Dr. Sharon Shacham, our Founder, President and Chief Scientific Officer, Justin Renz Executive Vice President and Chief Financial Officer; and Christ Primiano, our Vice President of Corporate Development and General Counsel. Welcome to the third quarter 2014 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 third quarter 2014 results, which is available on our website at karyopharm.com. Various remarks we make will 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 most recent Annual Report on Form 10-K which is on file 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 relay 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 overview of our financial results to third quarter of 2014, and then provide a corporate update including our clinical development program and regulatory strategy. We are happy to take a few questions following the prepared comments. I will turn the call over to Justin now to review the financials.

Thank you, Michael. Since we issued a press release earlier this morning outlining our third quarter 2014 financial results, I'll just review the highlights and then speak to our cash balance and financial guidance. The company reported a net loss of $19.7 million or $0.61 per share for the quarter ended September 30, 2014 that compares with a net loss of $9.3 million or $3.66 per share for the same period in 2013. These losses include stock-based compensation expense of $2.9 million and $1.3 million for the quarters ended September 30, 2014 and 2013 respectively. For the nine months ended September 30, 2014, Karyopharm reported a net loss of $49.9 million or $1.63 per share compared to a net loss of $21.8 million or $9.11 per share for the same period in the previous year. These amounts include stock-based compensation expense of $9.7 million and $1.8 million for the nine months ended September 30, 2014 and 2013 respectively. Research and development expense was $16 million in the third quarter of 2014, compared to $7.7 million for the same period in the previous year. And general and administration expense was $3.8 million compared to $1.6 million for the same period in the prior year. For the nine months ended September 30, 2014, research and development expense was $40.1 million compared to $18.8 for the same period in the prior year. And general and administration expense was $10 million compared to $3.4 million for the same period in the prior year. This increase in expenses for both periods is primarily related to the significantly expanded clinical development activities for our lead drug candidate Selinexor KPT-330, and the increase in general and administration expenses resulted primarily from the costs of operating as a public company throughout 2014, and an increase in stock-based compensation expense. Cash and cash equivalents as of September 30, 2014, totaled $227.1 million compared to $156 million at the end of the year. Based on our current operating plans, we expect our existing cash will fund our R&D programs and operations into the second half of 2017, including moving our two registration studies in AML and Richter's to their next data inflection points. We expect to end 2014 with a cash balance of approximately $210 million. With that I'll turn the call back over to Dr. Kauffman.

Thank you, Justin. We made considerable progress this quarter including advancing our lead product candidate Selinexor, our first-in-class oral selective inhibitor of Nuclear Export or SINE compound. As you are aware Selinexor is a covalent inhibitor of Exportin-1 also called XPO1. Inhibition of XPO1 leads to the accumulation and activation of many tumor suppressor proteins such as p53, BRCA1, FOXO, and IkB; as well as to the reduction of oncoproteins such as c-Myc, NF-kB, FLT-3, and BCL2. At the present time Selinexor is the only XPO1 inhibitor in clinical development. Following our large Phase 1, 2 trials of Selinexor in a diverse set of cancers, we have now initiated two registration directed clinical studies, including one at acute myeloid leukemia, and as announced earlier today, another in Richter's Transformation. Additional registration directed studies are planned and will be discussed during the call plus we have made significant strides during accelerating Selinexor's development in hematologic cancers with high-end medical need. In addition, we also expanded our leadership team in global presence to pursue our aggressive development and commercialization strategy. We are continuing to develop Selinexor for the treatment of solid tumors as evidenced by encouraging clinical data presented from an ongoing Phase 1 clinical study of Selinexor in patients with advanced heavily pretreated solid tumors. Consistent with its broad mechanism of action, Selinexor demonstrated signs of clinical activity in hormone and chemotherapy refractory prostate cancer, head and neck squamous cell carcinomas, and gynecologic cancers. Previously we showed durable to destabilization in tumor shrinkage in patients with chemotherapy relapse sarcomas. Importantly, Selinexor has shown to have manageable and predictable side effects primarily nauseas, fatigue, and anorexia, which improve over time on treatment. On the regulatory front, we received U.S. FDA and European EMA orphan drug status for Selinexor in both AML and DLBCL. We also received U.S. patent allowance covering composition of matter of Selinexor. Once issued, this patient will provide Karyopharm with patent protection for Selinexor in pharmaceutical compositions comprising Selinexor through the middle of 2032. I'll now turn the call over to Dr. Sharon Shacham to provide an update on Selinexor clinical development plan.

Thank you, Michael. Now I will provide an update of our clinical development plan for Selinexor. To-date over 450 patients across various hematological and solid tumor indications have been treated with oral Selinexor, with several remaining on study for over 12 months and the longest for over two years. We have observed broad and durable antitumor activity of Selinexor in both hematological and solid tumor cancers, consistent with the known mechanisms of Selinexor option. This breadth of activity and novel mechanism of production provide us with multiple paths to potential commercialization of Selinexor. In addition to our on-clinical activities, there are numerous Investigator-Sponsored Trials or IST either ongoing or planning and evaluating Selinexor alone or in combination with other therapies for hematological or solid tumor malignancy. Starting with hematological malignancies, we initiated and are actively enrolling patients in tumor registration-directed Phase 2 studies of Selinexor in hematological malignancies. The first called SOPRA or Selinexor in Older Patients with relapsed or refractory AML is enrolling patients who are ineligible for intensive chemotherapy and/or transplantation. The second is called SIRRT or Selinexor in Relapsed Refractory Richter's Transformation. We expect both of these studies to take approximately two years to complete. The SIRRT study is a single-arm Phase 2 trial designed to evaluate the safety and efficacy of Selinexor, given only to patients with Richter's Transformation whose disease has relapsed after or refectory to chemo-immunotherapy with overall response rate as the primary study endpoint. It is an open-label multi-center study and will involve approximately 50 patients in approximately 35 sites worldwide. Richter's Transformation is a rare condition in which Chronic Lymphocytic Leukemia changes into a fast growing or aggressive type of non-Hodgkin lymphoma. Approximately, 1,500 patients are diagnosed with Richter's Transformation each year in the USA with similar numbers in the European Union.…

Thank you, Sharon. Switching gears now I'll take a moment to recap the progress we've made on the corporate side during this quarter. Recently we appointed Justin Renz, as our Chief Financial Officer and Executive Vice President of Finance. Justin brings over 15 years of financial experience including EMD Serono, Coley Pharmaceuticals, CombinatoRx, and Zalicus, and is leading our Investor Relations efforts as well as our internal financial functions. On the clinical front, as you know, we are developing Selinexor in multiple countries and we anticipate a substantial number of our clinical trial patients, as well as our promotional markets to be focused in Europe. Therefore we have expanded Karyopharm's global presence with the opening of our wholly-owned European subsidiary to provide the corporate structure necessary to support Karyopharm's expanded clinical and regulatory activities in Europe. We appointed Ran Frenkel, as Executive Vice President Worldwide Clinical Development to run this subsidiary. Ran has significant experience managing global clinical operations and regulatory affairs activities within the biopharmaceutical industry. Also this quarter, the Board elected J. Scott Garland, Senior Vice President and Chief Commercial Officer at Relypsa to Karyopharm's Board of Directors. Scott brings nearly 25 years of oncology commercial leadership to Karyopharm, including experience in Genentech, Amgen, Merck, and Exelixis, and his skills and experience in leading oncology focused sales and marketing organizations within the biopharmaceutical industry would be valuable to Karyopharm as we continue to advance the Selinexor development program towards commercialization. In summary, we believe that innovation of XPO1 by oral Selinexor represents a widely applicable approach to treating neoplastic diseases. The activation of multiple tumor suppressors, coupled with the reduction in oncoproteins, are novel modes of selectively killing cancer cells with minimal effects on normal cells. Preclinical data have shown that XPO1 is a non-redundant pivotal survival pathway for cancer cells and the development of XPO1 is therefore difficult allowing for prolonged disease control over extended period. Karyopharm is continuing to execute on our clinical and regulatory development strategy as demonstrated with the significant progress made to-date in advancing the development of Selinexor, our novel oral XPO1 inhibitor product candidate. With that operator, we are ready to take questions.

Thank you. (Operator Instructions). The first question is from Yigal Nochomovitz of Oppenheimer. Your line is open.

Hi, good morning. Thanks for taking the question. I just wanted to get a better understanding of why you're opting for the switch to the flat dosing versus the megs per meter squared for DLBCL in myeloma as well as possibly other settings? Thanks.

Obviously, flat dosing is much easier to handle both for the clinicians, at the sites and for the patients. We have done an exhaustive analysis of pharmacokinetic data and we can see that the exposure of Selinexor is not dependent on the body surface area and therefore we are able to switch from body surface area based dosing to flat dosing.

Okay, great. And you briefly mentioned on the call Sharon, regarding the solid tumor plans. Could you discuss in more detail what you're thinking there in terms of where you might focus on for an approval trial?

Yes, we do have a number of options in front of us. And with the Board discussion ongoing about our plans to move ahead aggressively in both human solid, we're not ready to talk future solid tumor plans. We will update on the Phase 2 data which we're excited about next year and we're looking at the combinations as well. But we will pursue a solid tumor plan. We just haven't honed it on one or two yet since we seem to have a growing number.

Okay, great. And if I could just squeeze in one more you mentioned the European subsidiary which you started is that any sort of signal that you may interested in commercializing Selinexor independently in EU or is that just a basis for further partnering discussions potentially down the road across the pond?

I think, as we've said our plan is to move aggressively from a regulatory point of view and the major Western, well including Western European venues. We have great interactions with FDA, EMA, health Canada and the like to-date. And we want to -- per the Board's recommendation, we want to keep all of our options open regarding commercialization if it makes sense for us to do it on our own, we will do it, or direct it on our own, we will do it in Europe as well. We feel we can move expeditiously without large company processes here. So we are definitely keeping our options open.

Thank you. And the next question is from Steve Byrne of Bank of America. Your line is open.

Hi. Just regarding the dose do I understand correctly that in both the Richter's and the DLBCL studies that you're planning that you're going for the 60mg/m2 dose maybe it's 60 mg flat dose, I'm not sure I heard that right. But can you just talk a little bit about why you thought that dose was intolerable in the multiple myeloma patients and do you have a concern about that dose moving forward?

So just to clarify in both the DLBCL and in the Richter study we are looking at the dose of 60mg/m2 that is equivalent to a dose of 100 mg flat dose. In the DLBCL we will also evaluated a lower dose of 60mg that is equivalent to roughly to 35mg/m2. In the myeloma, we will follow-up with a dose of 45mg/m2, which is more or less about 80 mg flat dose. And at ASH we will report the results of both the 45mg/m2 as well as the 60mg/m2 based on basis as we mentioned we made our decision to move forward with 45mg/m2. Patients stayed on that dose for a long period of time and the side effects profile at this dose of 45mg/m2 is very manageable.

And Sharon, how do you think about the dose of Dexamethasone that you mentioned in the DLBCL study that I think you said 8mg to 12mg twice weekly. Do you view that as a therapeutic dose or more of prophylactic dose?

The dose of dexamethasone in the DLBCL study is a prophylactic or supportive care dose mostly to help mitigating potential nausea and anorexia and fatigue. And we found it to be very helpful in the ongoing Phase 1 study.

And what do you think about the merits of raising that dose and including dexamethasone in the Richter study?

In the Richter study we will also have a similar dose of dexamethasone as supportive care the 8 to 12 dose. And in future study we might look to increasing the dose of dexamethasone in combination with other chemotherapies and Selinexor to look at the potential synergy lymphoma.

And just lastly what do you view as a response rate in the Richter study that you would view as a hurdle for approval?

We are looking for a response rate that is over 20%.

Thank you. The next question is from Mike King of JMP Securities. Your line is open.

Well thanks for taking my question and congrats on the progress throughout the year guys. I had a couple of quick follow-ups of your trials. Just wondering with regard to SIRRT versus I'm sorry if I'm getting my nomenclature mixed up its SIRRT versus SADAL, SADAL is the DLBCL study or is that AML?

DLBCL.

Okay. In SIRRT and SADAL, how does one keep the two patient populations separate from one another. Is Richter -- the presentation of Richter is so clear that one can determine that this is in fact Richter's and not a new case of aggressive lymphoma? I mean, I know it's a transformed form of CLL. But is it clear in the clinic that is actually Richter's versus aggressive lymphoma?

Yes so in the third study the patient has to come up with aggressive lymphoma that is rising after CLL and has to be concerned by histology. In the SADAL study, the DLBCL study we are looking at patients with denovo DLBCL. So and again the disease will be confirmed by histology as well as the subtype of DLBCL. So it is a varied population.

Right. Okay. And are there going to be overlapping sites in both of those studies?

Several.

I'm sorry.

Yes, several.

Yes, okay. And then with regard to AML, can you guys talk about how you will account for possible compounding by transplant. I can't imagine that this population is one that heavily going to go to transplant but just in the case that you do get clear marrow, are patients going to go to transplant and if so how do you count for that in the statistics?

The patient that are going into the SOPRA study, the AML study are not -- could have not received candidate for transplantation in the past. Even if they were treated with high dose induction chemotherapy they were not able to go to transplantation, even if they achieved complete response in that setting. So the likelihood of these patients to go to transplantation after treatment with Selinexor is very small. We will have an in interim data analysis after 50% of the events and at that point if we need to adjust our statistics to a console if we will see transplantation then we will do that at this point.

Sharon, can you guys say what your expectation is there. Is it single-digit percent that might go to transplant or?

Yes, single-digit, as mostly because they were not eligible for transplantation coming in.

Okay, right. And then finally I just wanted to ask you guys if you have considered applying for breakthrough therapy designation you seem like you've got robust data set 450 patients plus et cetera. Is BTD contemplated for Selinexor in any of these indications?

Of course we are contemplating that and several other regulatory strategies and so mostly that will take place somewhere between 2015.

Do you feel you have an adequate data set now to do that to apply for BTD?

Yes, the guidance we've discussed is actually the FDA and given the orphan drug designations we've already received. As Sharon mentioned there is other things like fast track designation that are actually more relevant but yes, we do think we have sufficient data we just got to prioritize the fast track things to be the most pressing one next.

Thank you. And the next question is from Michael Schmidt of Leerink. Your line is open.

Good morning. Thanks for taking my questions. I wanted to follow-up on the multiple myeloma study result so far. Can you help us to benchmark the duration of response that you've seen so far to that of other drugs in late stage multiple myeloma?

Yes, a lot of data will be presented at the ASH next month. But based on that we already published several of these patients have stayed on the current dose of 45mg/m2 with dexamethasone for over four and six months is doable responses.

Okay. And how does that compare to pomalidomide or carfilzomib for instance?

So pomalidomide plus dex or carfilzomib both had a PFS of four months and that's the benchmark that we're comparing our data to.

Okay.

Now, many of our patient in the study as we already reported at ER and other meetings are coming up carfilzomib up and some of them or up pomalidomide plus dex or for both.

Yes, okay. And then I guess I saw a poster ad ASH from you guys on the thrombocytopenia side effect of the drug. And I was wondering what your thoughts on how that side effect might affect the combinability of Selinexor with other drugs; it might have potential overlapping toxicities?

So the effect of Selinexor on thrombocytopenia is unique. Basically, Selinexor as we reported in the aspects Selinexor cause rest of the stem cells and delayed maturation of megakaryocytes and therefore -- and (inaudible) platelets, which is different from the mechanisms of thrombocytopenia. For example, that is induced by protozome inhibitors. We are paying much attention to the potential overlapping toxicity of thrombocytopenia with other drugs and we will advance this by using and by tricking the schedule of Selinexor when combined with other drugs.

Great. So when do you think we'll see the first -- the next Selinexor combination study data? Will you have something at ASH already or will that be a sort of 2015 data point?

So as you may have seen there is an up thought on the combination of Selinexor and carfilzomib from the University of Chicago. The PI on this study is Richard Kubiak and he mentioned in his post that he will show some very early clinical data in the -- in his post.

Thank you. And the next question is from David Nierengarten of Wedbush Securities. Your line is open.

Hey. Thanks for taking my question. And just a couple quick ones. Have you spoken with FDA on what would be an acceptable overall response rate for the Richter's study, potentially for registration?

FDA approved the protocol and allowed us to initiate the study but we have not discussed it with FDA directly the response rate that is needed for approval of the next one in Richter's transformation based on this study. There is an interim data analysis in this study and at that point we will discuss it with FDA.

Okay. And thanks for that. And then, quickly on the esophageal head, neck and gynecologic cancers. Will you be looking at patients according to HPV status or other viral infections in conjunction with your overall response rate inputs? Are you be -- are there three paths stratified or is that something you might be looking at otherwise?

Certainly. We will look at the HPV status. As you may know, our patient is HPV, usually have 363 well types with Selinexor-close nuclear localization and reactivation of 363 in these patients. So this is a population that is of large interest to us and all patients with head and neck and esophageal cancers will have a biopsy to determine HPV status in a central lab.

Thank you. And the next question is from Arlinda Lee of MLV. Your line is open.

Hi guys. Thanks for taking my question. I had two. One, on the timing for the SADAL trial, you said that there was -- it was going to take about two years for both SIRRT and SOPRA. Is that going to be the same for SADAL or might that take a little longer?

It's about two years.

It's about two years for SADAL?

Well, it is study as well, yes.

Okay. Thank you. And then, mechanistically it seems that there is rationale for Selinexor and squamous lung cancer. Might we see data for that and after next year and -- I mean, I know you don't want to talk about necessarily your plans for the solid tumors but might we get an update in lung cancer and then about your regulatory strategy forward around that?

Well, we want you to continue to come to our earnings call so you have to -- hopefully.

Thank you. (Operator Instructions). The next question is from Mike King of JMP Securities. Your line is open.

Hi guys. Just a quick follow-up. Can you say roughly speaking what the average time on therapy will be shown at ASH for both myeloma and DLBCL?

It's -- whatever is mentioned in the abstract and then the data will presented at ASH and we can discuss it at that point.

Thank you. (Operator Instructions). And there are no further questions at this time. I'd like to turn the call back over to Dr. Kauffman for close remarks.

Well that concludes our third quarter 2014 conference call. Thank you all for participating. We look forward to providing additional clinical updates for Selinexor in both hematologic and solid tumors at the upcoming medical meetings, including a clinical update to coincide with the ASH meeting in early December. Have a good day everybody.

Thank you. Ladies and gentlemen, this concludes today's program. You may now disconnect. Good day.