Q4 2019 Earnings Call

[music].

Good morning, My name is sure me and I will be a conference operator today at this time I would like to welcome everyone to the Karyopharm Therapeutics fourth quarter and full year 2019 financial results Conference call.

There will be a question answer session to follow.

Please be advised that this call is being recorded at the company's look what.

I would now like to turn the call over to Mr. in car here, you'll farms, Vice President Investor and public relations. Please go ahead.

Thank you Sheree and thank you all for joining us on todays conference call to discuss carrier farms fourth quarter full year 2019 financial results and business update this busy in car and I'm joined today by Dr., Michael Kaufman, Our Chief Executive Officer, Mr., Mike Mason, Chief Financial Officer.

Mr. Christopher from Yano, Chief business Officer, and General Counsel.

Mr Perry Monaco senior Vice President sales.

The call today, Mike will provide an overview of key recent corporate developments and an update on the commercial launch of exposure you. Mike will then highlight the fourth quarter and full year 2019 financial results, we will conclude with the Q when a portion of the call.

Earlier. This morning, we issued a press release detailing care forms results for the fourth quarter and full year 2019.

This release as well as an accompanying slide presentation are available on our web site at Karyopharm dotcom.

Before we begin our formal comments I'll remind you that various remarks, we'll make today constitute forward looking statements for purposes of the safe Harbor provisions under the private Securities Litigation Reform Act of 1995. These include statements about future expectations clinical developments and regulatory matters in timelines the potential success of our products and product candidates include.

Your expectations related to the commercialization of its probably a financial projections and 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 factor sections of our most recent quarterly report on form 10-Q, which is on file with the FCC and another filings that we may make what the FCC in the future.

Any forward looking statements represent our views as of today only 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 if any date subsequent to today.

In addition, please note that any references we make to clinical trial data during todays discussion referred to interim unaudited site data unless otherwise specified.

We'll also be providing on this call non-GAAP outlook for operating expense for 2020, we can which can only be provided on a non-GAAP basis without unreasonable effort I'll now turn the call over to Dr., Michael Kaufman, Chief Executive Officer of Karyopharm.

Thank you in and good morning, everyone and for those following along with the slide presentation. Please now turn to slide number four.

2019 was a monumental year for Karyopharm marked by the accelerated approval of exposure in July.

Well, we always the first and only nuclear export inhibitor approved in the U.S. and as indicated in combination with dexamethasone for patients with heavily pretreated multiple myeloma.

Karyopharm is a rich history as an innovation driven drug development company and then 2019, we rapidly transitioned into an integrated commercial stage oncology company, while we continue to expand our commercial footprint and grow our operational capabilities, we remain ever committed to advancing innovative science and developing medicines with no.

Novel mechanism of action on behalf of patient.

And we remain optimistic as we look to the future with increasingly promising pipeline of clinical programs for both Selinexor and our other drug candidates directed in increasing spectrum of human cancers.

When the commercial Brian exposure, you'll continue to build momentum in second quarter with increased adoption from prescribing physicians. We're very pleased to report exposed wheel products sales of 17.7 million in the fourth quarter and 30.5 million for the full year 2019.

The demand for exposed deal has been driven by a broad based of health care providers, both academic and community based oncologist with over 550 unique positions or accounts, having prescribing supposed to go through the end of 29 team.

We're delighted with the early physician and patient experience with expelled meal and look forward to expanding our commercial reach in the months in years ahead.

In parallel to our commercial efforts, we continue to make additional important clinical and regulatory progress in the quarter.

Our pivotal Boston study remains on track with topline data expected before the end of April. This year. Additionally, we're very pleased to announce that at the end of 20 December 2019, we submitted a supplemental new drug application to the FDA requesting accelerated approval for Selinexor based on our sales study as a treatment for patients.

As with diffuse large b cell lymphoma. After at least two lines of therapy. If approved this would represent our second indication for Expo in a group of patients with significant unmet medical need where there are no currently approved oral drug regimens available to patients.

On the European front, the M&A as content currently reviewing the marketing authorization application, we submitted for exposure in January of last year as a new treatment in patients with heavily pretreated multiple myeloma based on the results of the phase to be storm study recently, we were granted a three month extension from the Amaze committee for medicinal products.

Our human use.

Providing karyopharm with additional time to respond to the outstanding questions related to the marketing authorization application based on this revised timeline. We now expect decision on the M&A in mid 2020.

On the development front, we plan to initiate five company sponsored clinical trials in 2020, largely in combination with other active and potentially synergistic anti cancer drugs I will highlight a few of these trials in my later remarks.

And now please turn to slide five for some additional details Onyx Bobo sales growth in 2019.

Thanks in large part to the hard work and dedication of our highly experienced commercial team. We saw 38% increase in net exposure you know sales in Q4 2019 as compared to Q3 2019 importantly, we saw an even more impressive 65% increase in the actual prescription demand in the fourth quarter, which reflects exposed Leo prescriptions.

Shipped from Karyopharm is distribution partners to individual patients and prescribing health care accounts.

We can't recall the Q3 2019 was the first quarter, we introduced exposed to go into the U.S. market and there was approximately 3 million inexplicably ourselves in that quarter that went towards building initial channel inventory at our distribution partners.

Operator: BF-WATCH TV 2021 [inaudible] Good morning. My name is Cherie, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics fourth quarter and full year 2019 financial results conference call. There will be a question and answer session following. 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. Ian Karp, Karyopharm's vice president, investor, and public relations. Please go ahead. Thank you, Cherie.

Increased fourth quarter sales were primarily driven by a combination of new patient starts and prescription refills with total prescriptions filed approaching 1400 by the end of Tony 19, we're particularly pleased with the level of prescription refills today, which we believe further validates physicians ability to effectively support their patients and help mitigate in may.

Ian Karp: And thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter and full year 2019 financial results and business updates. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, our Chief Executive Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Christopher Permiano, Chief Business Officer and General Counsel, and Mr. Perry Monaco, Senior Vice President, SAIL.

Ian Karp: On the call today, Michael will provide an overview of key recent corporate developments and an update on the commercial launch of Expovio, and Mike will then highlight the fourth quarter and full year 2019 financial results. We will conclude with the Q&A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the fourth quarter and full year 2019. This release, as well as an accompanying slide presentation, are available on our website at karyopharm.com.

And its potential side effects from exposure you know treatment.

Our launch strategy continues to position exposed to always be oral agent of choice with a clinically meaningful efficacy profile and its approved indication.

And while it's still early in our lunch cycle. The positive momentum seen to date has been highly encouraging and our conversations with prescribing physicians and patients reinforce our belief in the long term potential exposure as a future standard of care in the treatment of patients with relapsed refractory multiple myeloma.

In 2020, we expect to see increased adoption from high and moderate volume myeloma accounts as well as from first time prescribers of exposure, we hope to build upon the strong foundation established in 2019 and further grow exposure in the U.S. on behalf of the patients and families looking for new and effective approaches in the treatment refractory myeloma.

Please now turn to slide six.

As excited as we are about the recent launch success for exposure you know in patients with heavily pretreated myeloma. We're equally excited about what the future holds for Karyopharm and the additional cancer patients we hope to serve in the future.

Ian Karp: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about future expectations, clinical developments, regulatory matters, and timelines, the potential success of our products and product candidates, including our expectations related to the commercialization of Expovio, financial projections, and 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 factor sections of our most recent quarterly report on Form 10-Q, which is on file with the SEC, and in other filings that we may make with the SEC in the future.

Ian Karp: Any forward-looking statements represent our views as of today only. 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. In addition, please note that any references we make to clinical trial data during today's discussion refer to interim, unaudited site data, unless otherwise specified. We'll also be providing on this call a non-GAAP outlook for operating expense for 2020, which can only be provided on a non-GAAP basis without unreasonable effort. I'll now turn the call over to Dr. Michael Kaufman, Chief Executive Officer of Karyopharm.

We believe that our clinical pipeline has never been more robust store promising.

As it specifically pertains to Selinexor, along with our second generation assign investigational medicine, Elton X or we have decided to initiate five new key clinical trials in 2020, largely in response to our growing confidence in the potential. These agents have beyond just mild.

First we plan to initiate two studies in diffuse large b cell lymphoma.

One will be a pivotal study of selinexor or matching placebo given with the standard Commendation immuno chemotherapy, our GDP to patients with at least one prior therapy and who are ineligible for high dose chemotherapy with stem cell rescue or for car T.

Our GDP stands for Rituximab, Jim side to be indexing about the Sonus has flattened.

The primary endpoint. This study study 30 is PFS and this trial.

Following agreement with FDA is expected to serve as a confirmatory study for the accelerated approval requested in deal Bcl based on the sales study.

We also plan to initiate a second new trial, Indeed, DLP seal study 25 evaluating selinexor in combination with other commonly used at approved agents for the treatment of DLP CEO. This study will inform the clinical development of Selinexor with a variety of additional agents for the treatment of diffuse large b cell lymphoma.

Michael P. Mason: Thank you, Ian, and good morning, everyone. And for those following along with the slide presentation, please now turn to slide number four. 2019 was a monumental year for Karyopharm, marked by the accelerated approval of Expovio in July. Expovio is the first and only nuclear export inhibitor approved in the U.S. and is indicated in combination with dexamethasone for patients with heavily pretreated multiple myeloma. Karyopharm has a rich history as an innovation-driven drug development company, and in 2019, we rapidly transitioned into an integrated commercial stage oncology company. While we continue to expand our commercial footprint and grow our operational capabilities, we remain ever committed to advancing innovative science and developing medicines with novel mechanisms of action on behalf of patients. And we remain optimistic as we look to the future with an increasingly promising pipeline of clinical programs for both Felonexer and our other drug candidates directed at an increasing spectrum of human cancers. On the commercial front, Expovio continued to build momentum in its second quarter with increased adoption from prescribing physicians. We are very pleased to report Expovio product sales of $17.7 million in the fourth quarter and $30.5 million for the full year 2019.

Next we plan to initiate new phase one two trials to study the combination of Selinexor in a variety of active anti cancer agents in patients with colon cancer non small cell lung cancer in glioblastoma.

Our hope is that these studies will help guide our future development strategies for Selinexor with the ultimate goal of pursuing several additional registrational studies in the future in these indications.

Finally based on encouraging data we presented at Ash in December 2019, with single agent Elton Exar in patients with Myelodysplastic syndromes refractory to standard treatment, we plan to evaluate the combination of out to next or with set is your dean decitabine and oral hypomethylating agent in patients with newly diagnosed Mds.

Beyond our Selinexor announced an extra programs we were excited to see a new publication in the January 2020 addition of nature cancer.

At highlighted positive results in an important preclinical study of KPTV nine to seven for as a potential therapeutic agent to overcome resistant to PD, one checkpoint blockade immunotherapy.

KPTV nine to seven four is our oral first in class dual path for and Amped inhibitor currently in a phase one single agent study based on these pre clinical data in this publication.

Michael P. Mason: The demand for Expovio has been driven by a broad base of healthcare providers, both academic and community-based oncologists, with over 550 unique physicians or accounts having prescribed Expovio through the end of 2019. We are delighted with the early physician and patient experience with Expovio and look forward to expanding our commercial reach in the months and years ahead. In parallel to our commercial efforts, we continue to make additional important clinical and regulatory progress in the fourth quarter. Our pivotal Boston study remains on track, with top-line data expected before the end of April of this year.

We look forward to study and KPTV nine to seven four in combination with an anti PD one monoclonal antibody in a phase one clinical study in the near future.

Needless to say, we have a lot of important clinical activities, taking place in 2020, which we believe will help us maximize the long term potential impact our investigational compounds may have in advancing cancer care for patients in need of new treatment options.

With that I'll now turn the call over to Mike Mason to review the financials, Mike. Thank you Michael since we issued a press released earlier today with the full financial results I will just focus on the highlights which begin on slide eight.

Michael P. Mason: Additionally, we are very pleased to announce that at the end of December 2019, we submitted a supplemental new drug application to the FDA requesting accelerated approval for Selinexer based on our SAGLE study as a treatment for patients with diffuse large B cell lymphoma after at least two lines of therapy. If approved, this would represent our second indication for Expovio in a group of patients with significant unmet medical need where there are no currently approved oral drug regimens available. On the European front, the EMA is currently reviewing the marketing authorization application we submitted for Expovio in January of last year as a new treatment for patients with heavily pretreated multiple myeloma, based on the results of the Phase 2b STORM study.

Net product revenue for the fourth quarter of 2019 was 17.7 billion and 30.5 million for the year ended December 31 2019.

As previously mentioned 2019 sales were driven by a combination of patient demand as well as initial channel inventory sold to our distribution partners.

We estimate that of the 30.5 million in 2019 sales approximately 26 million was driven by patient demand with the remaining approximately four and a half million driven by channel inventory, which was in line with our plan to have customers keep approximately three weeks of channel inventory.

The estimated gross to net discount for exposure in 2019 was approximately 15%.

Michael P. Mason: Recently, we were granted a three-month extension from the EMA's Committee for Medicinal Products for Human Use, providing Karyopharm with additional time to respond to the outstanding questions related to the Marketing Authorization. Based on this revised timeline, we now expect a decision on the MAA in mid-2020. On the development front, we plan to initiate five company-sponsored clinical trials in 2020, largely in combination with other active and potentially synergistic anti-cancer agents. I will highlight a few of these trials in my later remarks. And now, please turn to slide 5 for some additional details on Expovio sales growth in 2019. Thanks, in large part, to the hard work and dedication of our highly experienced commercial team, we saw a 38% increase in NetEx Mobio sales in Q4 2019 as compared to Q3.

We still project a steady state range of 15% to 20%. However, we do expect some variability from quarter to quarter.

Cost of sales were 1.4 million for the fourth quarter of 2019, and 2.4 million for the year ended December 31, 2019, [laughter] cost of sales reflect the cost of exposure units sold and third party royalties on net product revenue.

Research and development expense for the fourth quarter of 2019 was 31.6 million compared to 38.9 million for the fourth quarter of 2018.

R&D expense for the year ended December 31, 2019 was 122.3 million compared to 161.4 million for the year ended December 31, 2018, we expect our research and development expenses to increase in 2020 as compared with 2019 as we continue clinical development of selling.

Michael P. Mason: Importantly, we saw an even more impressive 65% increase in actual prescription demand in the fourth quarter, which reflects the Expovio prescription shift from Karyopharm's distribution partners to individual patients and prescribing health care accounts. Recall that Q3 2019 was the first quarter we introduced Expovio into the U.S. market, and there was approximately $3 million in Expovio sales in that quarter that went towards building initial channel inventory at our distribution partner. Increased fourth-quarter sales were primarily driven by a combination of new patient starts and prescription refills, with total prescriptions filed approaching 1,400 by the end of 2019. We are particularly pleased with the level of prescription refills to date, which we believe further validates physicians' ability to effectively support their patients and help mitigate and manage potential side effects from exspobio treatment. Our launch strategy continues to position Expovio as the oral agent of choice with a clinically meaningful efficacy profile in its approved indication. And while it is still early in our launch cycle, the positive momentum seen to date has been highly encouraging, and our conversations with prescribing physicians and patients reinforce our beliefs in the long...

So our and our lead indications as Dr. coffin previously outlined with a focus on regulatory submissions for Selinexor.

For the fourth quarter of 2019, selling general administrative expense was 28.4 million compared to 18.8 million for the fourth quarter of 2018.

For the year ended December 31, 2019, selling general administrative expense was 105.4 million compared to 48.8 million for the year ended December 31, 2018, the increase in FCD expenses compared to the prior year was due primarily to the hiring of the karyopharm commercial team and related activities to support.

The U.S. commercial launch of exposure.

We expect our Stena expenses to increase slightly in 2020 to support our expanding operating and commercial activities related to sales and marketing of exposure.

Cash cash equivalents restricted cash investments as of December 31, 2019 totaled 265.8 million compared to 330.9 million as of December 31, 2018.

The company sold approximately 30 million under its open market agreement our ATM during the fourth quarter 2019.

Michael P. Mason: [inaudible] In 2020, we expect to see increased adoption from high and moderate volume myeloma accounts, as well as from first-time prescribers of Expovio. We hope to build upon the strong foundation established in 2019 and further grow Expovio in the U.S. on behalf of patients and families looking for new and effective approaches in the treatment of refractory myeloma. Please now turn to slide 6.

Finally based on current operating plans Karyopharm expect this non-GAAP R&D and SGN expenses, which excludes stock based compensation expense for the full year 2020 to be in the range of $240 million to $260 million.

The company expects that at the cat existing cash cash equivalents and investments and the revenue it expects to generate from exposure your product sales will be sufficient to fund its planned operations until the middle of 2021, I'll now turn call back over to Michael for some concluding remarks, Michael Thank you, Mike before moving to the Q in AG, Let me highlight some of the key.

Michael P. Mason: As excited as we are about the recent launch success for Expovio in patients with heavily pretreated myeloma, we are equally excited about what the future holds for Karyopharm and the additional cancer patients we hope to serve in the future. We believe that our clinical pipeline has never been more robust or promising, as it specifically pertains to Selenexer, along with our second-generation signed investigational medicine, Eltenexer. We have decided to initiate five new key clinical trials in 2020, largely in response to our growing confidence in the potential these agents have beyond just myeloma. First, we plan to initiate two studies in diffuse R to B cell lymphoma.

Milestones, we expected 2020, which are found on slide 10.

For the pivotal phase three Boston study topline data are expected before the end of April the exact timing depends on the occurrence of progression events in the trial, we call that Boston studies evaluating the combination of once weekly Selinexor once weekly Velcade indexes zone.

In patients with multiple myeloma who've had one to three lines of therapy.

If positive these data could support regulatory submissions in 2020 in the United States in Europe for patients with multiple myeloma, who have received at least one prior therapy.

Michael P. Mason: One will be a pivotal study of cellinexor or matching placebo given with the standard combination immunokinemotherapy, RGDP, to patients with at least one prior therapy and who are ineligible for high-dose chemotherapy with stem cell rescue or for CAR-T. RGDP stands for rituximab, gemcitabine, dexamethasone, and cisplatin. The primary endpoint of this study, Study 30, is PFS, and this trial, following agreement with FDA, is expected to serve as a confirmatory study for the accelerated approval requested in DLBCL based on the fatal study. We also plan to initiate a second new trial in DLBCL, study 25, evaluating Selinexer in combination with other commonly used and approved agents for the treatment of DLBCL. This study will inform the clinical development of Selinexer with a variety of additional agents for the treatment of diffuse large B cell lymphoma.

And then later in the air we expect to following.

A regulatory decision in Europe based on our EMEA and heavily pretreated refractory myeloma.

Regulatory filings based on data from the Boston study.

Topline phase III assuming of course, those data are positive topline phase three data from the seal study and LIFO sarcoma is subsequent potential regulatory submissions based on these data.

Our regulatory decision from the FDA based on deal Bcl supplemental India as well as the potential us commercial launch of this in this indication if approved and finally the potential U.S. commercial launch for exposure in second line multiple myeloma, assuming the Boston date are positive and support FDA approval.

Clearly theres a lot to follow and we look forward to providing updates on these important milestones throughout the year.

Michael P. Mason: Next, we plan to initiate new Phase 1-2 trials to study the combination of Selinexer and a variety of active anti-cancer agents in patients with colon cancer, non-small cell lung cancer, and glioblastoma. Our hope is that these studies will help guide our future development strategies for Solanaxer with the ultimate goal of pursuing several additional registrational studies in the future based on these indicators. Finally, based on the encouraging data we presented at ASH in December 2019 with single-agent Eltenexor in patients with myelodysplastic syndromes or fracture-to-standard treatment, we plan to evaluate the combination of Eltenexor with cetazuridine and cytabine and oral hypomethylating agents in patients with newly diagnosed MDS. Beyond our Cellinexor and Elcinexor programs, we were excited to see a new publication in the January 2020 edition of Nature Cancer that highlighted positive results from an important preclinical study of KPT-9274 as a potential therapeutic agent to overcome resistance to PD-1 checkpoint blockade immunotherapy.

We appreciate your support and look forward to keeping you updated on our 2020 progress in the coming months in quarters ahead, I'll now turn the call over to the operator for questions operator.

Thank you, ladies and gentlemen, as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound.

Please standby, while we compiled the Q anyway.

My first question will come from Eric Joseph with JP Morgan.

Hey, good morning, everyone. This is the Turner on for Eric. Thank you for taking my question just a couple of quick ones from Us. So first I know you reiterated timelines for Boston, but I'm curious how do you hit a sufficient number of PFS events to trigger the final analysis sounded like you are very close at our conference about a month ago.

[noise] yeah. Thanks. Thanks for the question, we're close enough to the eventual announcement of the Boston events that were not prepared to answer any additional specifics on this we're waiting for the data come in.

When it if it does we will.

Michael P. Mason: KPT-9274 is our oral, first-in-class, dual PAC-4 and NAMP inhibitor currently in a Phase I single-agent study. Based on these preclinical data and this publication, we look forward to studying KPT-9274 in combination with an anti-PD-1 monoclonal antibody in a Phase I clinical study in the near future. Needless to say, we have a lot of important clinical activities taking place in 2020, which we believe will help us maximize the long-term potential impact our investigational compounds may have on advancing cancer care for patients in need of new treatment options.

Hi, good process properly through the IR say, the DSMB B and reviewed by FDA and then we'll make an announcement.

Okay. Thank you and then I'm just hoping can you provide any additional color on the extension you received from the M&A and deal beauty LNG, that's the nature or excuse me in penta refractory myeloma and the nature of the outstanding questions you have to answer.

Yeah. The DNA is reviewing the data you know.

Frankly line by line. These are these are normal questions.

There's a fair number of them, obviously FDA ahead of far fewer of them and we're just running through there. So they just granted us a three month longer extension to continue to to work through the list.

Michael P. Mason: With that, I'll now turn the call over to Mike Mason to review the financials. Mike? Thank you.

Michael P. Mason: Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 8. Net product revenue for the fourth quarter of 2019 was $17.7 million, and $30.5 million for the year ended December 31, 2019. As previously mentioned, 2019 sales were driven by a combination of patient demand as well as initial channel inventory sold to our distribution partners. We estimate that of the $30.5 million in 2019 sales, approximately $26 million was driven by patient demand, with the remaining approximately $4.5 million driven by channel inventory, which was in line with our plan to have customers keep approximately three weeks of channel inventory. The estimated growth to net discount for Expovio in 2019 was approximately 15%. We still project a steady state range of 15 to 20%; however, we do expect some variability from quarter to quarter.

Okay, great. Thank you.

Thank you. My next question will come from where you see calls with Jefferies.

Hi, everyone. Good morning, and congrats on the updates today.

I had a question on that confirmatory.

Ill provide more specifics on the design, including the number of patients and expectations on PFS.

Yes.

Can't give me a final number but it will go up on clinical trials that govern the not too distant future, but basically it's a randomized blinded study.

Selinexor with matching placebo.

Evaluating.

With against a backbone of our GDP, which is as I mentioned rituximab, Jim side to be index and methods out of the Tias for assist platinum.

This is our GDP at a pretty standard regimen.

Michael P. Mason: Cost of sales was $1.4 million for the fourth quarter of 2019 and $2.4 million for the year ended December 31, 2019. Cost of sales reflects the cost of Expovio units sold and third-party royalties on net product revenue. Research and development expense for the fourth quarter of 2019 was $31.6 million compared to $38.9 million for the fourth quarter of 2018. R&D expense for the year ended December 31, 2019 was $122.3 million compared to $161.4 million for the year ended December 31, 2018. We expect our research and development expenses to increase in 2020 as compared with 2019 as we continue clinical development of Selenaxor in our lead indications, as Dr. Kaufman previously outlined, with a focus on regulatory submissions for Selenaxor.

The goal of this study is to really introduce a potentially more powerful backbone regimen.

GDP rather than typical bend, a must junior toxin for these patients and to use selinexor. Both in the induction part where the patients will get six cycles of the up to six cycles of the our GDP.

And then they can continue selinexor indefinitely following response, either PR CR.

So this will be one of the first kinds of these studies in second third line deal Bcl two to look at a induction and maintenance in the second third line.

Got it that's helpful. And then my second question is just if you can provide any additional perspective.

To the payer mix shifting more towards commercial and than anything else that you're seeing from.

Michael P. Mason: For the fourth quarter of 2019, selling general administration expense was $28.4 million compared to $18.8 million for the fourth quarter of 2018. For the year ended December 31, 2019, selling general administration expense was $105.4 million compared to $48.8 million for the year ended December 31, 2018. The increase in SG&A expenses compared to the prior year was due primarily to the hiring of the Karyopharm commercial team and related activities to support the U.S. commercial launch of Expovia. We expect our SG&A expenses to increase slightly in 2020 to support our expanding operating and commercial activities related to sales and marketing of Expovia. Cash equivalents and restricted cash investments as of December 31, 2019 totaled $265.8 million compared to $330.9 million as of December 31, 2018.

Using the commercial setting with combo use the you can provide any perspective on.

So Perry I'll handle that.

Yes, so with regards to combo.

While we can't break out specifically, how much exposure was being used in combination with other anti myeloma drugs.

We do know from our own Mark market research that many academic and community based physicians are prescribing Expo in combination with other drugs.

Our commercial team will of course only focus on clinical data that's within expose approved FDA label.

However, as I'm sure you know, there's quite a bit of data from combination studies and they've been presented at medical meetings and.

And have been published including most recently at the 2019 Ash Conference and we do get many unsolicited inquiries to our medical Affairs Department for information about combination data with regards to the payer mix I think the payer mix remains pretty much consistent with what we had expected.

Prior to our approval and I don't think we really expect that to change.

Michael P. Mason: The company sold approximately $30 million under its Open Market Agreement, or ATM, during the fourth quarter of 2019. Finally, based on current operating plans, Karyopharm expects its non-GAS, R&D, and SG&A expenses, which exclude stock-based compensation expense, for the full year 2020 to be in the range of $240 to $260 million. The company expects that its existing cash, cash equivalents, and investments, and the revenue it expects to generate from Expovio product sales, will be sufficient to fund its planned operations until the middle of 2021.

The patient population for myeloma is somewhat of an elderly patient population.

Got it thanks for taking my questions yes.

Thank you. Our next question comes from Brian Abrahams with RBC capital markets.

Yeah.

Hey, guys you going on for Brian Thank for taking the questions and congrats on the progress.

Two quick ones for me first it sounds like the demand and the refill rate has continued to be strong here wondering if you have a sense for for average time on therapy now now that were greater than six months into the launch.

Michael P. Mason: I'll now call back over to Michael for some concluding remarks. Thank you, Mike.

Paired to what you might have expected from the clinical trial data and if there's any real world. The upside there and then second question just briefly following up on a prior question is there any sense that the given the timelines the may approval would be at all contingent on what you see from Boston. Thanks.

Michael P. Mason: Thank you, Mike. Before moving to the Q&A, let me highlight some of the key milestones we expect in 2020, which are found on slide 10. For the Pivotal Phase III Boston Study, top-line data are expected before the end of April. The exact timing depends on the occurrence of progression events in the trial. Recall that the Boston Study is evaluating the combination of once-weekly Selinexer, once-weekly Velcane, and dexamethasone in patients with multiple myeloma who have had one to three lines of therapy. If positive, these data could support regulatory submissions in 2020 in the United States and Europe for patients with multiple myeloma who have received at least one prior therapy. And then later in the year, we expect the following. A regulatory decision in Europe based on our MAA and heavily pre-treated refractive myeloma

So Perry I'll handle the first question, yes, so with regards to time on therapy, it's still a little early to tell we are very encouraged obviously with those refill rates, we're seeing our discontinuation rates due to side effects to be lower than what was reported in storms. So these are very good early indicators.

But again I know were six months, but it's still too early we've got some some good persistency there though.

Yeah and regarding the is that question.

To be clear the M&A application, that's being reviewed right now is based on storm for patients with penta refractory sorry, Triple class refractory disease and at least three prior regimens.

Michael P. Mason: Regulatory filings based on data from the Boston study, and top line phase three, assuming, of course, those data are positive. Top-line phase three data from the SEAL study in liposarcoma and subsequent potential regulatory submissions based on these data. A regulatory decision from the FDA based on the DLBCL supplemental NDA, as well as the potential U.S. commercial launch in this indication, if approved. And finally, the potential U.S. commercial launch for Expovio in second-line multiple myeloma, assuming the Boston data are positive and support FDA approval. Clearly, there's a lot to follow, and we look forward to providing updates on these important milestones throughout the year. We appreciate your support and look forward to keeping you updated on our 2020 progress in the coming months and quarters ahead. I'll now turn the call over to the operator for questions. Operator?

There's no explicit connection between the two it does sell happened that it's highly likely that there will be Boston data available. During this three month extension, how and if the M.A. chooses to use those data will be up to them.

Got it thanks guys.

Thank you again, ladies and gentlemen, if you have a question at this time. Please press. The Star then one key our next question comes from Mike Ohmes with Bank.

Hey, guys. Thanks for taking the question and congrats as well as on all the progress.

Just had a question on the on the Boston study and a topline data you're expecting before the end of April here can you just give us a sense of what what do you plan to release in the in the topline results for example.

Operator: Thank you. Ladies and gentlemen, as a reminder to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A list. Our first question will come from Eric Joseph of J.P. Morgan.

Should we expect PFS will that include hazard ratio, maybe a P value and then should we expect any color on safety. Thanks.

Thanks, Mike Yeah, I think you hit the main elements that we're intending on part of this is contingent upon agreement with various act.

Unknown Speaker: Hey, good morning everyone. This is Turner on for Eric.

Convention and.

Important meeting discussions to make sure that we can bring the data out unfold in a fulsome way in front of the.

Academic and treating communities, but our hope is to present median progression free survival.

Michael P. Mason: Thank you for taking my question. Just a couple quick ones from us. First, I know you've reiterated the timelines for Boston, but I'm curious, have you hit a sufficient number of PFS events to trigger the final analysis? Sounded like you were very close at our conference about a month ago.

Potentially with the hazard ratio and a P value and then to make some general comments on safety I think is as most people are aware. This study is.

Michael P. Mason: Yeah, thanks for the question. We're close enough to the eventual announcement about the Boston events that we're not prepared to answer any additional specifics on this. We're waiting for the data to come in. When and if it does, we will have it processed properly through the IRC, the DSMB, and reviewed by FDA, and then we will make an announcement.

We are aware of all the safety events on the trial in wheat, we continue to see that there are no new safety signals as of.

Last week, when we review this.

And there are no.

There is no imbalance of deaths against the Selinexor arm.

Michael P. Mason: Okay, thank you. And then I'm just hoping, can you provide any additional color on the extension you received from the EMA and DLPTL and just the nature of the outstanding questions you have to answer?

As was seen in some recent other trials. So we're very confident that on the safety side. The drug is performing in the way expected.

Great. Thank you.

Michael P. Mason: Yeah, the EMA is reviewing the data, you know. Frankly, line by line, these are normal questions. There's a fair number of them. Obviously, FDA had far fewer of them, and we're just running through this, so they just granted us a three-month extension to continue to work through the list.

Thank you. Our next question comes from Ed weight with H.C. Wainwright.

Good morning, Thanks for taking my question.

So.

Regarding the Salesforce are you right size right now if the Boston data is positive or will you be adding more.

Unknown Speaker: Okay, great. Thank you.

Salespeople and then also I just wanted to get your thoughts on.

Operator: Thank you. Our next question will come from Maurice Raycroft with Jeffreys. Hi everyone. Good morning and congratulations on the updates today. I had a question about the confirmatory DLBCL file. Can you provide more specifics on the design, including the number of patients and expectations for PFS?

This strategy and if there will be additional people needed for Dl Bcl.

If I did you get approval it for that indication as well.

Harry I'll handle that yes. So thanks for the question. So when we sized originally we size with Dl Bcl in mind and so we don't feel like that will require us to add any people. We do look at this stuff on a regular basis and while the Boston indication does give us a greater patient population that we.

Michael P. Mason: Yeah, I can't give you a final number, but it'll go up on clinicaltrials.gov in the not too distant future. But basically, it's a randomized blinded study of Selenexor with matching placebo, evaluating the backbone of RGDP, which is, as I mentioned, rituximab, gemcitabine, dexamethasone, and the P is for cis This is RGDP, it's a pretty standard regimen. The goal of the study is to really introduce a potentially more powerful backbone regimen, RGDP, rather than typical bendamustrine rituxan for these patients and to use Selenaxer both in the induction part, where the patients will get six cycles of RGDP or up to six cycles of RGDP, and then they can continue Selenaxer indefinitely So this will be one of the first kinds of these studies in second, third line DLBCL to look at induction and maintenance in the second and third line.

Conserve the customer base that treats multiple myeloma redone remains the same so we believe we're right sized for the Boston indication as well.

Great. Thank you.

Then just on.

The I may I'm, just wondering if you can narrow the timeline of the m- submission for deal Bcl.

If you can say early middle or late 2020, and then also does the multiple myeloma extension have any pick impact at all on your thoughts about the DLT Bcl submission in Europe.

Thank you.

Sure.

The plan on the deal Bcl submission in Europe is going to be a that the timing will likely coincide probably more with the Boston submission in Europe. It just.

Easier for us to handle the two submissions together, so we'll be will be thinking about that but we haven't made a final decision on that.

Okay, great. Thank you.

Michael P. Mason: Got it. That's helpful. And then the second question is just if you can provide any additional perspective on the pair makes shifting more towards commercial, and then anything else that you're seeing from using the commercial setting with combo use that you can provide any perspective on.

Thank you Sir your next question comes from Jonathan Chang with SVB Ling.

Good morning, and thanks for taking my questions.

First question you indicated at Ash plans to evaluate that the tripling that phase three study.

Perry Monaco: So Perry will handle that.

Perry Monaco: Yeah, so with regard to combo, we can't break out specifically how much Expovio is being used in combination with other anti-myeloma drugs. But we do know from our own market research that many academic and community-based physicians are prescribing Expovio in combination with other drugs. Our commercial team will, of course, only focus on clinical data that's within Expovio's approved FDA label. However, as I'm sure you know, there's quite a bit of data from combination studies, and they've been presented at medical meetings, and we do get many unsolicited inquiries to our Medical Affairs Department for information about combination data. With regard to the payer mix, I think the payer mix remains pretty much consistent with what we had expected prior to our approval, and I don't think we really expect that to change, as the patient population for myeloma is somewhat of an elderly population.

That's still the plan.

Yeah, we're still considering in SPD study, we just haven't market first start date given the other.

Trials, which which we think are critically important and.

Equal or or potentially even higher medical values. So we'll we'll we'll keep updating you on that but theres a lot of interest in this trip, let it exactly which venue will be using to have it evaluated.

Well the dependence on some new information going forward, but we tend to go forward with it we just haven't figured out the venue yet.

Got it.

And secondly can you talk about the rationale for evaluating the Selinexor combination studies in colorectal lung cancer.

Yes, sure you may recall, although it was a very long time ago.

It seems.

Several years ago, we publish the phase one results of single agent Selinexor in first in human in patients with advanced.

Solid tumor malignancies, there were no where I believe six different partial responses. There. These are these were recently confirmed partial responses across a smattering of diseases.

Unknown Speaker: Got it. Thanks for taking my questions. Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets.

Operator: Hey guys, we've got Owen on for Brian. Thanks for taking the questions and congratulations on the progress. Two quick ones for me. First, it sounds like demand and the refill rate have continued to be strong here. I'm wondering if you have a sense for average time on therapy now, now that we're greater than six months into the launch, compared to what you might have expected from the clinical trial data, and if there's any real world upside there. And then, second question, just briefly following up on a prior question, is there any sense that, given the timelines, the EMA approval would be at all contingent on what you see from Boston? Thanks.

One of the PR solution in metastatic colorectal cancer K Ras mutant a one of them.

A couple of them, we're actually in melanoma, one was and I believe in pancreatic cancer and one in ovarian cancer. So there was in a couple of others.

So there is some single agent activity of this drug in solid tumors and you'll you'll see the first activity and actually in light of sarcoma into phase three read out, which we expect to be mid this year, but got back to.

The colorectal lung.

There's there's a.

Unknown Speaker: So, Kary will handle the first question. Yeah.

Given the single agent activity and colorectal that we reported in there were a number of stable disease patients and we've also followed that up with some additional data from Asian patients with colorectal.

Unknown Speaker: In regards to time on therapy, it's still a little early to tell. We are very encouraged, obviously, with those refill rates. We're seeing our discontinuation rates due to side effects are lower than what was reported in STORM. So these are very good early indicators. But again, I know we're six months, but it's still too early. We've got some good persistency there, though.

Finally, with K Ras mutant colorectal disease that showed that that selinexor can induce tumor shrinkage I'm not typically in the PR range, but but certainly shrinking tumors with some durability. So there is some single agent activity in colorectal.

Michael P. Mason: Regarding the question, to be clear, the MA application that's being reviewed right now is based on STORM for patients with triple class refractory disease and at least three prior regimens. But there's no explicit connection between the two. It does so happen that it's highly likely that there will be Boston data available during this three-month extension. However, how and if the MAA chooses to use those data will be up to them. Got it. Thanks, guys.

Obviously, the PD ones have shown minimal activity in microsatellite stable colorectal cancer and so the goal will be to combined these two ages that show minimal activity separately in an attempt.

To generate sufficient neo antigens to get the PD ones to work and then obviously to complement the X.P.L. mechanism of Selinexor with the immunotherapy I should say there is an ongoing study at MD Anderson looking looking at Selinexor in combination with.

Keytruda and digital and.

Unknown Speaker: Thank you. Again, ladies and gentlemen, if you have a question at this time, please press the star and then one key. Our next question comes from Mike Almswith Baird.

And Nivo.

And then we've established a safety these combinations and we look forward to presenting some combination data and they're not too distant future and in those indications across several solid tumors.

Operator: Hey guys, thanks for taking the question and congratulations as well on all the progress. I just had a question on the Boston study and top-line data you're expecting before the end of April here. Can you just give us a sense of what you plan to release in the top-line results? For example, should we expect PFS, will that include a hazard ratio, maybe a P-value, and then should we expect any color on safety?

So we know that we can do these combinations safely and we want to expand this into colorectal, which is a big unmet need now given the minimal activity of.

Unknown Speaker: Thanks.

Of new drugs in colorectal cancer.

On the lung cancer side, there was a nature medicine publication of.

The mechanism of action of Selinexor in lung cancer, particularly in Ras mutant lung cancer.

Michael P. Mason: Thanks Mike. Yeah, I think you hit the main elements that we're intending, and part of this is contingent upon agreement with various conventions and important meeting discussions to make sure that we can bring the data out in full in a fulsome way in front of the academic and treating communities. But our hope is to present median progression-free survival, potentially with a hazard ratio and a p-value, and then to make some general comments on safety. I think, as most people are aware, this study is, we're aware of all the safety events on the trial, and we continue to see that there are no new safety signals as of last week when we reviewed this, and there is no There is no imbalance of deaths against the cellinex So we're very confident that on the safety side, the drug is performing in the way expected. Great, thank you.

And dose of taxable is a standard of care second line agent. So we've had an investigator sponsored trial that's been ongoing in this we are.

Encouraged by what we've seen to the point in that study of Expo Vo plus dose taxol to make that into a company sponsored trial and we expect to have some updates for that trial later this year as well so theres good preclinical and clinical evidence for the activity of these regimens now in some very important in solid tumors and were looking for.

Our two announcing some data this year in next in the in that regard.

Got it thank you.

Thank you speakers im showing no further questions in the queue. At this time I would now like to turn the call back over to Mr., Michael Kaufman for any further Mike.

Hi, Thanks, very much and thanks, everybody for.

For joining us today, I think we're going to see a great year coming and I will look forward to you to updating on all the progress have a great day.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.

Unknown Speaker: Thank you. Our next question comes from Ed White with HC Wainwright.

[music].

Operator: Morning, thanks for taking my question. Regarding the sales force, are you at the right size right now if the Boston data is positive, or will you be adding more sales people? And then also, I just wanted to get your thoughts on the strategy and if there will be additional people needed for DLBCL provided you get approval for that indication as well.

Perry Monaco: Yes, Perry will handle that.

Perry Monaco: So thanks for the question. When we sized it originally, we sized it with DL-BCL in mind. And so we don't feel like that will require us to add any people. We do look at this stuff on a regular basis. And while the Boston indication does give us a greater patient population that we can serve, the customer base that treats multiple myeloma remains the same. So we believe we're right sized for the Boston indication as well.

Unknown Speaker: Great, thank you. And then just on the EMA, I'm just wondering if you can narrow the timeline for the EMA submission for DLBCL, if you can say early, middle, or late 2020. And then also, does the multiple myeloma extension have any impact at all on your thoughts about DLBCL submission in Europe? Thank you.

Michael P. Mason: Sure. The plan for the DLVCL submission in Europe is going to be that the timing will likely coincide more with the Boston submission in Europe. It's going to be easier for us to handle the two submissions together, so we'll be thinking about that, but we haven't made a final decision on that.

Unknown Speaker: Okay, great. Thank you.

Operator: Thank you, and our next question comes from Jonathan Cheng with SVB Learing.

Unknown Speaker: Good morning, and thanks for taking my questions.

Unknown Speaker: First question...

Michael P. Mason: You indicated that ASH plans to evaluate the SPD triplet in a phase 3 study. Is that still the plan?

Michael P. Mason: Yeah, we're still considering an SPD study. We just haven't marked it for a start date given the other trials, which we think are critically important and of equal or potentially even higher medical value. So we'll keep updating you on that, but there's a lot of interest in this triplet, and exactly which venue we'll be using to have it evaluated will depend on some new information going forward. But we intend to go forward with it. We just haven't figured out the venue yet.

Michael P. Mason: Got it. And secondly, can you talk about the rationale for evaluating the cell and extra combination studies in colorectal and lung? Yeah, sure.

Michael P. Mason: You may recall, though, it was a very long time ago. Several years ago, we published the phase one results of single-agent Selenectar in first-in-human studies in patients with advanced Solid Tumor Malignancies. There were, I believe, six different partial responses there. These were resistance-confirmed partial responses across a smattering of diseases. One of the PRs was in metastatic colorectal cancer, a KRAS mutant. One of them, and a couple of them were actually in melanoma.

Michael P. Mason: One was in, I believe, pancreatic cancer, and one in ovarian cancer, and a couple of others. So there is some single-agent activity of this drug in solid tumors, and you'll see the first activity actually in liposarcoma in the Phase III readout, which we expect to be mid-this year. But back to colorectal and lung, there's a significant amount of Given the single agent activity in colorectal that we reported, and there were a number of stable disease patients, and we've also followed that up with some additional data from Asian patients with colorectal cancer, particularly with KRAS mutant colorectal disease, that showed that Selenixer can induce tumor shrinkage, not typically in the PR range, but certainly shrink Obviously, the PD1s have shown minimal activity in microsatellite-stable colorectal cancer, and so the goal will be to combine these two agents that show minimal activity separately in an attempt to generate sufficient neoantigens to get the PD1s to work, and then, obviously, to complement the XPO mechanism of Selenixer with immunotherapy.

Michael P. Mason: I should say there's an ongoing study at MD Anderson looking at Selenixer in combination with Keytruda and Nevo. And we've established the safety of these combinations, and we look forward to presenting some combination data in the not-too-distant future for those indications across several solid tumors. So we know that we can do these combinations safely, and we want to expand this into colorectal cancer, which is a big unmet need now, given the minimal activity of new drugs in colorectal cancer. On the lung cancer side, there was a Nature Medicine publication of the mechanism of action of Soanexer in lung cancer, particularly in RAS mutant lung cancer. And docetaxel is a standard-of-care second-line agent, so we've had an investigator-sponsored trial that's been ongoing with this.

Michael P. Mason: We are encouraged by what we've seen to the point in that study of Expovio plus docetaxel to make that into a company-sponsored trial, and we expect to have some updates for that trial later this year as well. So there's good preclinical and some clinical evidence for the activity of these regimens now in some very important solid tumors, and we're looking forward to announcing some data this year and next in that regard. Got it. Thank you.

Operator: Thank you. Speakers, I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Mr. Michael Koffman for any further remarks.

Michael P. Mason: Hi, thanks very much, and thanks, everybody, for joining us today. I think we're going to see a great year ahead, and we'll look forward to you updating us on all the progress. Have a great day.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

Unknown Speaker: BF-WATCH TV 2021

Unknown Speaker: transcript Emily Beynon BF-WATCH TV 2021