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Edited Transcript of KPTI earnings conference call or presentation 16-Mar-17 12:30pm GMT

Thomson Reuters StreetEvents

Q4 2016 Karyopharm Therapeutics Inc Earnings Call

Natick Mar 16, 2017 (Thomson StreetEvents) -- Edited Transcript of Karyopharm Therapeutics Inc earnings conference call or presentation Thursday, March 16, 2017 at 12:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Justin Renz

Karyopharm Therapeutics Inc. - EVP, CFO & Treasurer

* Michael Kauffman

Karyopharm Therapeutics Inc. - CEO

* Sharon Shacham

Karyopharm Therapeutics Inc. - President & Chief Scientific Officer

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Conference Call Participants

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* Michael Schmidt

Leerink Partners - Analyst

* Jenny Lee

BofA Merrill Lynch - Analyst

* Whitney Ijem

JPMorgan - Analyst

* Brian Abrahams

Jefferies - Analyst

* Arlinda Lee

Canaccord Genuity - Analyst

* Mike King

JMP Securities - Analyst

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Presentation

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Operator [1]

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Good morning, my name is Kaylee and I will be your conference operator today. At this time I would like to welcome everyone to the Karyopharm Therapeutics fourth-quarter and year-end 2016 financial results conference call.

There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the Company's request.

I would now like to turn the call over to Mr. Justin Renz, Executive Vice President, Chief Financial Officer and Treasurer of Karyopharm Therapeutics.

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Justin Renz, Karyopharm Therapeutics Inc. - EVP, CFO & Treasurer [2]

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Thank you. Good morning and welcome to the fourth-quarter and year-end 2016 earnings call.

This is Justin Renz and I am joined today by Dr. Michael Kauffman, our Chief Executive Officer; Dr. Sharon Shacham, our founder, President and Chief Scientific Officer; and Chris Primiano, our Senior Vice President of Operations, Business Development, General Counsel and Secretary. On the call today Mike will make some introductory comments, Sharon will provide a short update on the clinical development programs and plans and I will provide an overview of the fourth-quarter and year-end 2016 financial results. Michael will then provide some summary remarks, and we will open up the call for your questions for which Chris and I will also be available.

Earlier this morning we issued a press release detailing Karyopharm's results for the fourth-quarter and year-end 2016. The release is available on our website at Karyopharm.com.

Before we begin our formal comments I will remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical development and regulatory management timeline, the potential success of our product candidates, financial projections, our plans and prospects.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31, 2016 which was filed with the SEC earlier today and any other filings we may make with the SEC. Any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent date.

While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today.

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

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [3]

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Thank you, Justin, and good morning everyone. Thank you for joining us on our call today.

Before we review our 2016 progress and our 2017 plans I want to address the announcement we issued last Friday regarding the receipt of written notice from FDA placing our selinexor clinical trials on partial clinical hold. The FDA indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator's brochure and corresponding informed consent including an incomplete list of serious adverse events associated with selinexor. As of Friday, March 10, 2017 at the FDA's request we have amended the investigator brochure and updated the informed consent documents accordingly and have submitted these documents to the FDA.

Partial clinical hold is not the result of any new safety issues or deaths in patients treated with selinexor. All patients currently enrolled in our studies with stable disease or tumor shrinkage may remain on selinexor therapy, but no new patients may be enrolled during the partial clinical hold. We are working diligently with the FDA to seek the release of the partial clinical hold and resume enrollment in our various selinexor clinical trials as expeditiously as possible.

By regulation the FDA has 30 days from receipt of our submission to notify the Company as to its position. We do not believe that any of our previously disclosed enrollment rates and timelines for ongoing and planned clinical trials will change materially.

Now moving on to our developments. During 2016 we made strong progress rapidly advancing the development of oral selinexor in our lead indication relapsed and/or refractory multiple myeloma, an indication where we believe we have a path to regulatory approval. Assuming a positive outcome we intend to use the data from the recently expanded STORM and STOMP studies along with our planned BOSTON study to support accelerated approval for an oral selinexor as a potential new treatment for patients with heavily pretreated multiple myeloma.

To date 2017 has brought several significant developments, as well. In diffuse large B-cell lymphoma, our lead indication after myeloma, we announced today a path forward towards approval following a recently completed analysis of the ongoing Phase 2b SADAL study in patients with relapsed or refractory diffuse large B-cell lymphoma. Of the first 63 patients we observed a 28.4% overall response rate across both the 60 and 100 milligram treatment arms with consistent response rates across both arms but greater durability and tolerability observed in the 60 milligram arm.

We shared these data with the FDA and with their agreement have decided to amend the SADAL study protocol to become a single-arm study focusing solely on a single-agent selinexor dose at 60 milligrams twice weekly, eliminating the 100 milligram arm. We plan to expand the SADAL study this summer with the goal of adding approximately 90 additional patients and are projecting a top-line data readout to occur in mid-2018.

Following consultation with the FDA we believe that a positive outcome from the expanded SADAL study could support an accelerated approval in DLBCL. The FDA agreed that the proposed trial design and indication are appropriate for accelerated approval, though the eligibility for accelerated approval will depend upon complete trial results and available therapies at the time of regulatory action.

In addition to this update for selinexor in DLBCL, we recently announced that a late-breaking abstract highlighting data from the SADAL study was selected for presentation at AACR 2017 where we will look forward to describing in more detailed results in a poster presentation. Finally, after conducting an in-depth analysis of the Phase 2 SOPRA study evaluating selinexor and relapsed or refractory AML, or acute myeloid leukemia, we recently announced that this study was unlikely to reach statistical significance for showing superiority of overall survival on selinexor versus overall survival on physician's choice, the primary endpoint of the study, despite the higher complete response rate observed with selinexor.

While this outcome was disappointing there were important safety findings from the SOPRA trial that we believe will inform the overall ongoing selinexor development program. Of note, the 60 milligram dose of single-agent selinexor dosed twice weekly was generally well tolerated and carried no increased risk of sepsis and febrile neutropenia was substantially less than the physician's choice control arm. Given the 13% complete response rate we observed in SOPRA versus 3% on the control arm and previously reported data of selinexor in combination with other agents in AML we plan to continue AML clinical development in combination studies through investigator-sponsored trials.

With that I'd now like to turn the call over to Sharon to provide a comprehensive Karyopharm clinical update as well as an overview of key presentations and publications that occurred during the quarter. Sharon?

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Sharon Shacham, Karyopharm Therapeutics Inc. - President & Chief Scientific Officer [4]

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Thank you, Michael. As we enter 2017 a key milestone on the new horizon is the outcome upcoming commencement of our pivotal randomized Phase 3 BOSTON study. The BOSTON study is designed to evaluate selinexor in combination with Velcade, also known as bortezomib, and low-dose dexamethasone compared to Velcade and low-dose dexamethasone in patients with multiple myeloma who have had one to three prior lines of therapy.

The planned dosing regimen of 100 mgs of selinexor once weekly, 1.3 mgs [m2] Velcade subcutaneously also dosed once weekly for four of every five weeks and 40 mgs of dexamethasone weekly which is the standard low-dose dexamethasone commonly used in the treatment of myeloma. This dosing regimen is based on the market synergy observed to date in the STOMP study as well as this is the only Phase 3 study to date utilizing once weekly bortezomib dosing.

Importantly, this trial allows for patients on the Vd control arm to cross over to SVd arm following objective progression from disease. We expect the BOSTON study to enroll approximately 350 patients and accrual is projected to complete in mid-2018.

As Michael mentioned, updated clinical data from the STORM study were presented by its lead STORM investigator, Dr. Dan Vogl of the Perelman School of Medicine at the University of Pennsylvania. In his presentation Dr. Vogl highlighted clinical data demonstrating that selinexor in combination with low-dose dexamethasone achieved a robust response presentation with quad-refractory myeloma and penta-refractory myeloma which is a quad-refractory myeloma that is also refractory when anti-CD38 monoclonal antibody like DARZALEX.

Specifically an overall response rate of 21% was achieved at both all 78 evaluable patients in the study including a 21% response rate in the 48 patients with quad-refractory disease and 20% response rate in the 30 patients with penta-refractor disease. Median overall survival for patients who achieved at least a minor response was at least 11 months and has not been reached as of the date of cutoff date while patients who did not have any response had a median survival of 5.7 months, suggesting that patients responding to selinexor had a survival benefit that is approximately twice as long as nonresponders.

Grade 3 or higher cytopenia was the most common side effect and were generally not associated with clinical sequelae. There were low rates of grade 3 or higher non-(inaudible) [toxicities] with no new safety signals identified. Based on this data we are expanding the STORM study to include 122 additional patients with penta-refractory myeloma, a growing unmet medical need for which there are currently no approved therapies.

We expect to report top-line data from the extended cohort in early 2018 and assuming a positive outcome we intend to use the STORM data to support accelerated approval for selinexor myeloma.

Once at ASH the Phase 1b STOMP data were presented by principal investigator Dr. Nizar Bahlis of the Southern Alberta Cancer Research Institute. In his presentation Dr. Bahlis described the high level of durable activity observed with selinexor in combination with Velcade including in patients with diseases already (inaudible).

Specifically, selinexor in combination with Velcade and dexamethasone achieved an overall response rate of 77% across all 22 patients in the study. Amongst the seven patients disease that was not refractory to a proteasome inhibitor the response rate was 100%.

For the 15 patients with proteasome inhibitor response to the disease the response rate was 67%. Importantly patients with disease was not refractory to a proteasome inhibitor, were more similar to the patients that will be evaluated in the upcoming pivotal Phase 3 BOSTON study, the overall response rate was 100%.

The most commonly reported adverse event from the recommended Phase 2 dose are fatigue, nausea, anorexia and vomiting which were primarily low-grade and (inaudible). The STOMP data indicates that the combination of proteasome inhibition and selinexor are highly synergistic and the combination of selinexor with either Velcade or Kyprolis are anticipated to be highly active even against proteasome inhibitor-resistant myeloma.

A few last points regarding STOMP, enrollment is now complete in the SVd arm and we expect to report updated data later this year. In parallel we expect to initiate a new STOMP extension arm evaluating selinexor in combination with DARZALEX and low-dose dexamethasone in heavily pretreated patients with myeloma shortly. We expect to enroll 44 patients in this new arm and plan to report top-line data from this cohort in late 2017 or early 2018.

One final item from the myeloma program, Dr. Sagar Lonial, professor and chair hematology and medical oncology at Emory University, recently presented an overview of the selinexor data at the 16th International Myeloma road Show in New Delhi, India. In his oral presentation Dr. Lonial highlighted clinical data demonstrating selinexor impressive activity in combination with proteasome inhibitors and immunomodulatory drugs for the treatment of relapsed or refractory multiple myeloma.

Turning now to our development of selinexor in the DLBCL. In today's financial results press release and our 10-K filings we announced the decision, which was made in consultation with the FDA, to amend the Phase 2b SADAL study to become a single-arm study evaluating single-agent selinexor dosed at 60 mg twice weekly, eliminating the 100 mg arm.

We are making certain other protocol amendments including reduction of the 40 mg washout converted to an eight-week washout period for patients who had a response on their last therapy. As Michael mentioned, this decision is a result of our reporting to FDA the observation of the 28.4% overall response rate of both the 60 mg and 100 mg treatment arm in 63 patients with consistent response rates across both arms but greater durability and tolerability observed in the 60 mg arm.

The FDA agreed that the change to a single-arm study was reasonable and that the proposed trial design and indication appear appropriate for accelerated approval. So the availability of accelerated approval will depend on the trial results and available therapy at the time of regulatory action.

Approximately nine additional cases will be added. And we expect to announce top-line data from this completed SADAL study in mid-2018.

In addition to today's clinical and regulatory updates for selinexor on DLBCL we recently announced the selection of the top-line Phase 2b SADAL data in patients with relapsed or refractory DLBCL as a late-breaking abstract at AACR 2017. We look forward to the presentation of more detailed top-line results in a poster session taking place Tuesday, April 4, 2017.

In addition to the SADAL data, 11 other abstracts representing preclinical data from across Karyopharm's oncology pipeline were also accepted for presentation at AACR.

As Michael mentioned earlier, going forward for AML we plan to continue clinical development of selinexor through investigator-sponsored trials in multiple combination regimens including with chemotherapy given the encouraging data to date of both these settings. One area in particular where we are evaluating oral selinexor is in pediatric leukemia. During the second half of 2016 a paper describing results from the investigator-sponsored SELHEM study evaluating selinexor activity in pediatric patients with relapsed or refractory leukemia was published in the Journal of Clinical Oncology.

The paper authored by Thomas Alexander et al reported that seven out of 15 evaluable patients in this study or 47% achieved either a complete response or complete response with incomplete blood count recovery. Five of the responders were negative for minimal residual disease and two patients experienced minimal residual negative complete response in the first cycle after receiving only selinexor therapy. Going forward we plan to explore the benefit of selinexor in combination with intensive chemotherapy through investigator-sponsored Phase 2 clinical trials in pediatric patients with heavily treated leukemia.

Turning now to our selinexor program in solid tumors. Earlier this month we completed enrollment in the Phase 2 portion of the randomized SEAL study evaluating selinexor in patients with advanced liposarcoma. We expect to report top-line data from this study in mid-2017.

And in October at the 2016 ESMO Annual Meeting we reported final data from the Phase 2 SINE study evaluating selinexor for the treatment of gynecological malignancies including ovarian, endometrial and cervical cancers. We are very encouraged by the data in endometrial cancer in which nine of the 20 evaluable patients with endometrial cancer met the primary endpoint including three confirmed partial responses and six with stable disease of 12 weeks or more for a disease control rate of 45%. Based on these data and investigator-sponsored randomized double-blind Phase 3 study evaluating selinexor in patients with advanced or recurrent endometrial cancers is in development and expected to commence enrollment in late 2017.

Finally, we continue to make strides advancing our earlier-stage pipeline programs including KPT-8602, KPT-9274 and KPT-350. Clinical data from the Phase 1/2 evaluating KPT-8602, our second-generation SINE compound, were presented at ASH 2016 demonstrating that oral KPT-8602 was well tolerated in heavily treated patients with relapsed or refractory multiple myeloma and showed early signs of encouraging efficacy. In March 2017 we announced that an abstract highlighting preclinical data demonstrating KPT-9274's activity and synergy with doxorubicin to treat dogs with lymphoma was selected as a late-breaking poster at AACR 2017. The poster will be presented by Cheryl London from Tufts University on Wednesday, April 5, 2017.

And the Target ALS Foundation awarded a $900,000 grant to support preclinical studies of KPT-350 in ALS. The project, which is led by Karyopharm collaboration with researchers from Johns Hopkins University and the University of Florida, is studying KPT-350 in preclinical models and seeking to develop an oral suspension formulation to those patients who cannot swallow tablets.

With that I will turn the call over to Justin to discuss our financials.

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Justin Renz, Karyopharm Therapeutics Inc. - EVP, CFO & Treasurer [5]

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Thank you, Sharon. Since we issued a press release earlier today outlining our fourth-quarter and year-end 2016 financial results, I will just review the highlights and then speak to our cash balance and our financial guidance.

Cash, cash equivalents and investments as of December 31, 2016 including restricted cash totaled $175.5 million compared to $210 million as of December 31, 2015. For the quarter ended December 31, 2016, research and development expense was $20.7 million compared to $24.1 million for the quarter ended December 31, 2015. For the quarter ended December 31, 2016, general and administrative expense was $6.5 million compared to $5.3 million for the quarter ended December 31, 2015.

Karyopharm reported a net loss of $26.9 million or $0.65 per share for the quarter ended December 31, 2016 compared to a net loss of $29 million or $0.81 per share for the quarter ended December 31, 2015. Net loss includes stock-based compensation expense of $5.1 million and $5.4 million for the quarters ended December 31, 2016 and 2015 respectively.

For the year ended December 31, 2016 research and development expense was $86.9 million compared to $97.7 million for the year ended December 31, 2015. Put the year ended December 31, 2016, general and administrative expense was $23.9 million compared to $21.6 million for the year ended December 31, 2015.

We reported a net loss of $109.6 million or $2.92 per share for the year ended December 31, 2016 compared to a net loss of $118.2 million or $3.32 per share for the year ended December 31, 2015. Net loss includes stock-based compensation expense of $22.3 million and $17.1 million for the years ended December 31, 2016 and 2015 respectively.

For financial guidance Karyopharm expects its 2017 operating cash burn, including research and development and general administrative expenses, to be in the range of $85 million to $90 million. Based on our current operative plan we expect our existing cash and cash equivalents will fund our R&D programs and operations until the end of 2018 including through the top-line data readouts for the STORM and SADAL studies as well as for completion of enrollment for both the BOSTON study and the Phase 3 portion of the SEAL study.

With that I will now turn the call back over to Michael for concluding remarks. Michael?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [6]

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Thank you, Justin. Before we open the call for questions I'd just like to take a moment to recap the upcoming milestones that we are expecting this year.

First, we plan to initiate the pivotal randomized Phase 3 BOSTON study evaluating selinexor in combination with Velcade and dex in myeloma previously treated with one to three prior therapies, moving selinexor into much earlier lines of treatment. Second, we expect to report several important data readouts during this year including, one, top-line data from the Phase 2b SADAL study in patients with relapsed or refractory DLBCL, we will present it at AACR 2017 early April; second, top-line data from the randomized Phase 2 SEAL study in patients with liposarcoma, our most advanced solid tumor indication in May 2017; and, third, top-line Phase 1 safety and tolerability data for KPT-9274 also in 2017.

We are executing on our plan to expand both the STORM and SADAL studies in relapsed or refractory myeloma and DLBCL. For STORM top-line data in penta-refractory myeloma is expected to read out in early 2018 and for SADAL top-line data is expected in mid-2018.

In closing, I'd like to highlight that we continue to have a strong balance sheet which provides us the flexibility to pursue our clinical and corporate objectives through the end of 2018. We are very excited about selinexor.

We have a novel first-in-class oral therapy with broad productivity in both hematologic and solid tumors. We have learned a great deal about optimizing selinexor dosing and we are very confident in our multiple paths to approval.

Thank you for listening today and we look forward to keeping you updated on our progress. With that I'd like to open the call now for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Michael Schmidt, Leerink Partners.

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Michael Schmidt, Leerink Partners - Analyst [2]

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Hi, good morning and thanks for taking my questions. I had one regarding the SADAL trial in DLBCL.

I guess I'm a little bit surprised to see the enrollment of only 63 patients. And I guess my question is, number one, are those equally distributed in the two arms, the low dose and the high dose, and maybe can you comment on also enrollment speed?

My impression was I thought you anticipated to complete enrolling of the study early this year. Thank you.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [3]

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Thanks, Michael. It is a one-to-one randomization between the two arms. Obviously, this will collapse into a single-arm study following the good discussions with the FDA.

Keep in mind also that the enrollment is much further along than the 63 but we had to have PET scans and CAT scans completed in order to present the data. So there's significantly more patients than the numbers you saw. They are one-to-one.

One of the challenges we've had with this disease is that patients that are seen in university hospitals, which is where we conduct most of our trials, tend to be the ones that are in real trouble. Those are the ones that are progressing actively on chemotherapy. And what I think we've all learned in DLBCL, and I think this is true across the board for all the different therapies, is with patients that are actively progressing on chemotherapy are very, very difficult to treat.

And a single-agent oral therapy and, frankly, multiagent chemotherapy can't control things, it's very unlikely that a single agent can control things. So we've made sure that we select the patients whose disease is at least stabilized. And those tend to be patients that are often seen in the community setting and which, so we have had a bit of a challenge on the recruitment.

Now that all said, analyzing our data and updating we are going to loosen the inclusion criteria a little bit because what we recognize is that patients that do have a stabilized disease or tumor shrinkage can often have a shorter washout period. The 14-week washout period was to ensure that the residual effects of multiagent chemotherapy were over. And what we've done is now short that to eight weeks for patients who have had at least had a partial response on their most recent therapy.

We think this will pick up, the response rate. And I think also investigators, and we are very excited about these data and you will see the details of those data.

So we believe that the results here, these are central radiologically reviewed, independently confirmed responses in this disease and we have some very durable responses. So I think there's a lot of excitement now about this trial with these results out and that should tick up recruitment, as well.

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Michael Schmidt, Leerink Partners - Analyst [4]

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So the 28% response rate, I assume it's in evaluable patients, not enrolled patients, correct?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [5]

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Sorry, can you repeat the question?

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Michael Schmidt, Leerink Partners - Analyst [6]

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The response rate, the 28%, I assume that figure is based on the evaluable patients, not an ITT analysis, correct?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [7]

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No, that's an ITT -- this is a Phase 2 study for potential accelerated approval. And all patients, to be clear, all patients were progressing on study entry and, in order to be eligible for the study, but they just had to have a washout period. This is all patients in the study.

The FDA does not accept evaluable patients as a way in Phase 2 accelerated approval. It's anybody who got a single dose of the drug.

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Michael Schmidt, Leerink Partners - Analyst [8]

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Understood. Thank you.

And a question I guess on the AML trial. Obviously, that was a very difficult indication in general to the trials in, I guess my impression was that based on the Phase 1 data of the rationale in AML for selinexor was pretty strong.

And I guess my question is how do you interpret those results and what read-through is there to the other indications that are being pursued with the drug just based on a mechanism -- mechanistic interpretation? Thank you.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [9]

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Sure. Well I think, as you said, this is one of the most difficult if not the most difficult disease in the hematologic malignancy space. It's a disease which, frankly, in the US has no approved drugs.

This is the elderly population that is not eligible for chemotherapy. So nothing has made it yet, nothing showed a benefit.

I think we were actually very excited to see a 13% CR/CRI rate which shows the drug is clearly very active. This is against the 3% CR/CRI rate in the controller. So we know we have very good activity of the drug.

We also know that the patients that did achieve CR, and they usually do that in the first one to two cycles, do much better than the overall population on either arm of the study. So that was clearly a benefit for that 13%, the 13% of patients.

We think the only real read-through that you can garner given how difficult the syndication is and the age of the patients is really on the safety side. And I think what we were all very excited to see was that it's very clear that we do not have a sepsis issue with this drug at all. It's a 60 milligram twice weekly dose, the rate of sepsis was the same on the selinexor arm and on the control arm.

In fact, the rate of sepsis was below 6%. It was actually 4.9%, putting it in a very good number for patients with AML who get sepsis a lot unfortunately.

The second really important finding was that the rate of febrile neutropenia was substantially less on the patients with selinexor as compared to the control arm. It was more than 2 times below what the control arm showed. So, again, the drug has a very nice safety profile even in patients that are as sick and as elderly and have as many comorbid conditions as the patients in this AML study.

So we've confirmed that 60 milligrams is an extremely good dose in all indications, and we are moving ahead with that in most of the indications. I should say just in passing you will note that the myeloma dose is 80 milligrams twice a week. That's in combination with dexamethasone, which can help mitigate some of the nausea and fatigue that we see with selinexor.

And the reason for that higher dose in myeloma is because patients that have penta-refractory disease are extremely, have extremely aggressive myeloma. And we wanted to use a higher dose to try to get the best response rate that we could in order to get the disease under control. And then we can continue on the therapy at that dose or they can drop it a little bit.

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Michael Schmidt, Leerink Partners - Analyst [10]

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Good, thank you, Michael.

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Operator [11]

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Ying Huang, Bank of America Merrill Lynch.

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Jenny Lee, BofA Merrill Lynch - Analyst [12]

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Hi, this is [Jenny Lee] on for Ying Huang. Thank you so much for taking our question.

We were just wondering a little bit about the durability of response to the Phase 2 SADAL data. If you could give us any color on the durability.

And then also what was driving the durability and tolerability in the lower dose arm versus the higher dose? Is that driven by toxicity or compliance issues as well as dropout rates?

Then, lastly, are these responses seen in both GCB and non-GCB DLBCL patients? Thank you.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [13]

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Right. So I can't give you a lot of color here. I should mention that we actually got a special SEC exemption from the AACR to even put out the top-line response rate data.

So we are really, we've really got a nice result from them to allow us to talk to you about this today. And, obviously, we wanted to announce the path forward which the FDA has agreed with to move forward.

I would just remind folks that ibrutinib's CLL study for accelerated approval tested 840 milligram, the high dose, against 420, the lower dose. They had identical response rates on both arms and they had a lot more toxicity on the 840 arm, virtually very similar to what we are seeing here. We decided to go to the FDA and get them to look at the data and then discuss with us the possibility of ending the 100 milligram arm at this point which they agreed with.

So we do have better durability. I can't give you much more than that, but suffice it to say these are durable responses similar to what we saw in Phase 1.

And I will also tell you that without giving any numbers that we do see responses in both GCB and in the non-GCB cohorts. But that's all I can say now. You will have to wait until Tuesday at AACR.

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Jenny Lee, BofA Merrill Lynch - Analyst [14]

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Okay, great. Thank you.

And just a quick one for the 8602 molecule, will be see any more data in 2017? Thank you.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [15]

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Yes, we probably will have an update on 8602 later in the year, towards the end of the year at some kind of hematology meeting.

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Jenny Lee, BofA Merrill Lynch - Analyst [16]

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Great, thank you.

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Operator [17]

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Whitney Ijem, JPMorgan.

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Whitney Ijem, JPMorgan - Analyst [18]

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Hi, guys. Thanks for taking the question.

First, just to follow up on the last one on durability in the SADAL study, understand that you can't comment on what you actually saw. But can you remind us what you were looking for, what the threshold for clinical meaningfulness was in your mind?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [19]

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Yes, after discussion with many experts response rates north of 20% in this disease, which I remind everyone doesn't have any approved therapy since rituximab was approved in 2006, and that approval was first-line DLBCL in combination with CHOP, there hasn't been any other approval in DLBCL. For the patients we are treating who are ineligible for transplant and unlikely to benefit from more intensive chemotherapy, there are no therapies that we are aware of that are on the horizon.

Obviously, CAR-T is going after this indication. But those patients are all chemotherapy eligible and all transplant eligible, and they are highly hand selected. This is really a group of patients that we are treating that are in extremely ill health and have very limited treatment options.

In terms of durability, what we've said is, again, talking to experts, if a single oral agent can deliver more than four months of durability that's considered very good in this population because otherwise the patients are going to be getting intravenous chemotherapies and many of them will have failed already some of the oral options that are not labeled. And so there's really not much to give them. So 20% ORR in north of four months was what we were looking for.

I also point out that these responses as well as being ITT population were also central radiologically reviewed. These are not the investigator-assessed responses or hours, these are, per protocol these are the actual responses. And that was the primary endpoint of the protocol was the overall response rate by central radiological review.

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Whitney Ijem, JPMorgan - Analyst [20]

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Got it. And then in the SEAL study, can you just remind us after we get the top-line data from the Phase 2 midyear, what are the next steps or timelines around the Phase 3 portion?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [21]

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So this is a -- to be clear, the protocol is a combined Phase 2/3 study that has been agreed to by FDA and EMA in meetings with both of those regulatory bodies. This is a study of selinexor 60 milligrams twice a week randomized against placebo. It's a blinded study and we will have, obviously, the results in a side effect profile in this population.

Once the Phase 2 is completed as it has we will move into the Phase 3 portion if the Phase 2 looks good. And that will be a 2 to 1 randomization with additional patients, the actual numbers to be determined by the results of the Phase 2. So we will be updating all of that in the middle of the year and moving ahead towards the Phase 3 in the second half of the year.

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Whitney Ijem, JPMorgan - Analyst [22]

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Great, thanks for taking the questions.

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Operator [23]

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Brian Abrahams, Jefferies.

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Brian Abrahams, Jefferies - Analyst [24]

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Hey, thanks for taking my questions. And congratulations on the initial SADAL data. A question on SADAL and then a question on the partial clinical hold.

I was wondering if you could expand a little bit more on the implications of the shorter washout in the study expansion on tolerability. Your level of confidence that eight weeks will be sufficient time for blood counts to be restored, and is there the potential for this to ultimately actually evolve into a less stable population being enrolled in the study that could maybe enhance the enrollment rate but decrease the overall response rates that we should be looking at for the next 90 patients?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [25]

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Yes, so, obviously, we want to maintain this robust response rate because we think it meets criteria. And you all have an update on the durability, particularly in the 60 milligram arm and the AACR results are presented. The washout period was thought about a lot and a re-analysis and having many more eyes looking at the Phase 1 data as well.

Keep in mind that the washout moving down to eight weeks applies to patients who had at least a partial response or a complete response in their most recent therapy. So they have a reduced tumor burden.

In addition, we do have hematologic requirements for baseline counts coming into the study. So if the patients don't have sufficient washout that will be reflected in their cytopenia. And we will make sure that they have to spend a little more time recovering before they can enter the study.

I will point out that, again, you will see some update on some of this at AACR. But not surprisingly patients that are severely anemic coming into the study don't fare as well. And so we will be able to make sure that doesn't happen in the second part of the study.

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Brian Abrahams, Jefferies - Analyst [26]

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Got it. And then in your 10-K it indicates that the FDA has also asked that you submit completed narrative summaries of safety reporting events.

I'm just wondering, was this in response to the inadvertent omission related to the investigator brochure questions or specific to any new safety concerns amongst regulators? And have you addressed this piece of the request yet?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [27]

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Yes, yes. We've had a complete response to the FDA. It was part of that table being left out inadvertently and they wanted to see all the main narratives along with replacement of the table so that they didn't just get a table but they got the data supporting it. (multiple speakers) there is nothing new qualitatively on safety at all.

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Brian Abrahams, Jefferies - Analyst [28]

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Got it. Very helpful.

I guess just one more on the partial hold. Have you received any FDA feedback following your submission that might give, provide a sense of potential timeline whether this would likely be within the 30-day window sooner, could get extended? Any color there?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [29]

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We can't give you any timeline at all. What we what we can say is they are definitely reviewing it.

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Brian Abrahams, Jefferies - Analyst [30]

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Okay. Thanks very much, Michael.

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Operator [31]

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(Operator Instructions) Arlinda Lee, Canaccord Genuity.

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Arlinda Lee, Canaccord Genuity - Analyst [32]

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Hi guys, thanks for taking my question. Maybe a couple more on SADAL first.

Could you provide additional color on if you are planning to enroll in the expansion cohort, also one-to-one GCB versus non-GCB? And also I think the last time you changed the enrollment criteria you guys mentioned that with the 14 weeks you guys had mentioned a proportion, what proportion of the addressable DLBCL population that could represent. Could you maybe provide an update now that you are decreasing that requirement? Thanks.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [33]

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Sure. It's still, it's a little bit funny. The GCB has to be at least 50%.

It could be 75%, it turns out it's basically around 50%. So you will see the data for GCB and that will continue forward. And that's basically a sense that GCB is under treatable now, there is just fewer options.

Obviously, there is no FDA-approved options for ABC or GCB in the third-line setting. But GCB has a sense because ibrutinib and Revlimid don't have real activity in the GCB setting. That's the first part.

What we can say is for the patients, this does increase the numbers back towards more of the population of say 30% to 40% of DLBCL patients who progress after two lines of therapy. Once the patient relapses after RICE chemotherapy plus or minus a transplant or gets GemOx in the second line if they can't tolerate the intensive R-ICE chemotherapy, there is really not a very good prognosis at all. And, frankly, the CORAL study results, which I think of many of you are familiar with that we are all looking at, really tells you that the survival of these patients is less than a year.

So for anybody who is not eligible for a transplant we can address most of those patients with the more open label now. Because, frankly, getting responses in this disease with multiagent chemotherapy is possible. It's just that they tend not to be durable.

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Arlinda Lee, Canaccord Genuity - Analyst [34]

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Okay, great. And then I guess on this administrative issue with FDA, maybe it seems like it's something that you can't screw up. And so I'm curious about the back-story to this.

Were there any antecedent minor issues that you guys had been warned on? My understanding is that the IB in these forms have to be updated at least annually. How did this happen?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [35]

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Look, mea culpa, and what can I say? It should not happen. The IB version 5.0 and 4.0 and 3.0 and 2.0, all of the IBs had, those were the IBs and they are done annually as a matter of course, as our ours, they all had this particular assay table which is an appendix in the document.

This is not an FDA requirement but because we had it in all the previous ones they expected to see it in the next one. And as you can imagine anybody whose job is to audit things and look at things would be concerned if suddenly this important table is left out. And this represented a change in our why we did things differently this time.

So they simply said you had it in all your previous versions, you need to have it in this one. And that's all I really want to say about it. We blew it, we should have had it and we fixed it pretty expeditiously and we are very comfortable with the drug and there is nothing hidden or dramatic here.

We've treated 1,900-plus patients with selinexor plus or minus combinations including some really intensive chemotherapy combinations. And there's just not anything really exciting or new coming out of our safety profile at all. In fact, going down to the 60 milligram twice a week dose is a very nice dose.

And I think it will be very interesting especially to look at the SEAL data against placebo, which is a blinded study, and will be interested to see how selinexor performs in the lipo population just as a way of looking at side effects from a less heavily pretreated cancer group. But there's nothing dramatic here. This was a major bureaucratic or administrative oversight on our part and FDA picked it up and, frankly, we fixed it.

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Arlinda Lee, Canaccord Genuity - Analyst [36]

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Okay, thanks very much, guys.

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Operator [37]

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Mike King, JMP Securities.

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Mike King, JMP Securities - Analyst [38]

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Good morning guys. Thanks for taking the questions.

Since Arlinda started the discussion again about the recently updated investigator brochure, I just wondered if you could comment about perhaps some, if there is any time lost in terms of recirculation of IBs and whether there are any studies or study sites that need to go back to IRBs and whether any of that will delay enrollment in any of the studies?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [39]

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The IBs go over to and get adopted in. The informed consents go in a two-step process.

One is a verbal communication with the folks and then that is followed by the signing of the new informed consent. But this is all done and FDA recognizes this. They are not trying to interrupt the dosing of any patient currently on the trial.

This is a very important but administrative issue that needs to be fixed and so there is a verbal communication with the patient. There is a parallel expedited review with all the IRBs, but none of the patients are going to stop therapy because they are waiting to sign a new form.

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Mike King, JMP Securities - Analyst [40]

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No, I understand that. But do they have to, so you are saying that no one has to be re-consented, Michael, this is just going to affect new consents?

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Sharon Shacham, Karyopharm Therapeutics Inc. - President & Chief Scientific Officer [41]

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So patients that are staying on the drug per the FDA guidance including all the patients with stable disease or better will have to be re-consented. And we are working with the sites to do that according to the guidelines we have got with FDA and that will not delay the patients that are on study from receiving drugs.

On the other in terms of enrollment in any delays it will have as a minimal we will work with the sites to increase enrollment. We will add sites to admit it and we will maintain all our projections for complete enrollment and data released this year and next year.

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Mike King, JMP Securities - Analyst [42]

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Okay, great. That's all I will ask about that. And then just on, again, I'm sure you can't comment and whether it matters here or not I don't know, but whether you can say anything about in SADAL whether there were any complete responses seen?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [43]

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Yes, I don't want to say a lot about it, Mike, but I think you will see the data look very similar. The response rate in the Phase 1 was 30% and I think what you are seeing in the Phase 2 is similar results.

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Mike King, JMP Securities - Analyst [44]

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Okay. And then I just wanted to also ask, on the other arms of STORM you gave the update on the Velcade arm, but just wondering can you update us on the other complementary studies like arms like with carfilzomib and pom and Rev?

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [45]

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Sure. Just to be clear, so STOMP (multiple speakers) so Velcade finished accrual. Pom is finishing accrual at a target dose and Revlimid is --

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Sharon Shacham, Karyopharm Therapeutics Inc. - President & Chief Scientific Officer [46]

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So pom is finishing the Phase 1 portion and it will move into expansion very soon and Revlimid is a little bit behind pomalidomide. Carfilzomib is not part of the STOMP study. It is part of (multiple speakers)

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Mike King, JMP Securities - Analyst [47]

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Right, IST, yes.

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Sharon Shacham, Karyopharm Therapeutics Inc. - President & Chief Scientific Officer [48]

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So the (inaudible). And the results from that study are essentially done and we presented them at ASH. We are looking to potentially amend the study and maybe include a once weekly Carfilzomib and once weekly selinexor and this will be later this year.

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Mike King, JMP Securities - Analyst [49]

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Great. Thanks very much.

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Operator [50]

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I am showing no further questions at this time. I'd like to turn the call back to Dr. Kauffman for closing remarks.

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Michael Kauffman, Karyopharm Therapeutics Inc. - CEO [51]

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Thank you all again for your interest in Karyopharm and for participating in our call today. We look forward to seeing many of you at our medical investor conferences throughout the year and have a great day everybody. Thank you.

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Operator [52]

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