Q3 2020 Karyopharm Therapeutics Inc Earnings Call

Good afternoon. My name is Kate and I will be your conference operator today at this time I would like to welcome everyone to the <unk>.

Operator: Good afternoon. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics 3rd Quarter 2020 Financial Results Conference Call. There will be a question and answer session to follow. Please be advised that the call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, Karyopharm Therapeutics Senior Vice President, Investor of Public Relations. Thank you, Kate.

Karyopharm Therapeutics, So corridor 2020 financial results conference call.

There will be a question and answer session to follow please be advised that this call is being recorded by the company's request.

I would now like to turn the call over to Mr. Ian car care.

Kerry you from Therapeutics, Senior Vice President Investor and public relations.

Thank you Carrie and thank you all for joining us on today's conference call to discuss third quarter 2020 financial results.

Ian Karp: And thank you all for joining us on today's conference call to discuss Karyopharm's third quarter 2020 financial results and business updates. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer, Dr. Sharon Shackham, President and Chief Scientific Officer, Mr. Mike Mason, Chief Financial Officer, Mr. John Demery, Chief Commercial Officer, Mr. Christopher Permiano, Chief Business Officer and General Counsel, On the call today, Michael and John will provide an overview of key recent corporate developments and an update on our commercial progress, and then Mike Mason will provide an overview of the third quarter 2020 financial results. We will conclude with the Q&A portion of our call.

This is your car and I'm joined today by Dr., Michael Kauffman, Chief Executive Officer.

Sure on Shopko, President and Chief Scientific Officer, Mr., Mike Hagan Chief.

Financial Officer, Mr., John Demeritt, Chief Commercial Officer, Mr., Christopher Primiano, Chief Business Officer, and General Counsel and Dr., Jay Shah Chief Medical Officer.

On the call today, Michael Jolliffe or key recent corporate developments.

On our commercial progress and then.

First of all the above.

Third quarter 2020 financial results.

I will conclude the <unk> portion of our call.

Earlier. This afternoon, we issued a press release detailing <unk> results for the third quarter of 21.

Ian Karp: Earlier this afternoon, we issued a press release detailing Karyopharm's results for the third quarter of 2020. This release, along with this live presentation, that we plan to reference, are available on our website at karyopharm.com. 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 Provision 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 relating to the commercialization of Expovio, financial projections, and our plans and prospects. However, 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 most recent quarterly report on Form 10-Q, which is on file with Any forward-looking statements represent our views of today only.

Release, along with the slide presentation.

So we plan to reference are available on our website at Karyopharm dotcom.

We don't want to comment Oh my.

Various remarks, we make today constitute forward looking statements for purposes of the Safe Harbor provision under the private Securities Litigation Reform Act of 1995.

Statements about future expectations clinical developments and regulatory matters and timelines the potential success of course and.

<unk> product candidates, including.

Expectations relating to the commercialization of Xtremio, what else projections, and our plans and prospects.

Actual results may differ materially from these indicators.

These forward looking statements as a result of various important factors, including those discussed in the risk factor section of our most recent quarterly report on form 10-Q, which is on file with the FCC and in other filings that we may make when you have to do in the future.

These forward looking statements represent our views of today only we may elect to update these forward looking statements.

Ian Karp: 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 we're representing our views as of any date subsequent to today. In addition, please note any references we make to clinical trial data during today's discussion refer to interim, unaudited site data unless otherwise specified. I'll now turn the call over to Dr. Michael Kaufman, Chief Executive Officer. Thank you, Ian, and good afternoon, everyone.

Well in the future.

We 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 anything subsequent to today.

Additionally, please note any references we make to clinical trial data during todays discussion refer to interim alternate site data unless otherwise specified I'll now turn the call over to Dr., Michael Kauffman, Chief Executive Officer.

Thank you and good afternoon, everyone I'm pleased to report that Karyopharm is continuing to make tremendous progress so far in 2020.

Michael P. Mason: I'm pleased to report that Karyopharm has continued to make tremendous progress so far in 2020 with the achievement of numerous commercial, pipeline, and operational accomplishments, positioning us well for what we will believe to be continued and sustained future growth. As we get closer to the end of 2020 and hopefully closer to an end to the COVID-19 pandemic, we are already preparing for numerous significant opportunities for our company and the patients we serve in 2021 and beyond. Before I begin, I'd like to take a moment to briefly put into some perspective the foundational and unique approach that we are taking towards innovating cancer drug therapy. On slide four.

Cheapened up numerous commercial pipeline and operational accomplishments positioning us well for what we believe to be continued and sustained future growth.

As we get closer to the end of 2020, hopefully closer to an end of the cold, but 19 pandemic, we're already preparing for numerous significant opportunities for our company and the patients we serve 2021 and beyond before.

Before I begin I'd like to take a moment to read they put into some perspective, a foundational and unique approach that we're taking towards innovating cancer drug therapy.

Well I for.

We have highlighted five core pillars of cancer drug therapy, which are all foundational and used across tumor types often in combination gives each patient the best chance to clinical improvement.

Michael P. Mason: We've highlighted five core pillars of cancer drug therapy, which are all foundational and used across tumor types, often in combination to give each patient the best chance at clinical improvement. Expovio is the first approved anti-cancer drug whose primary activity is the activation of tumor suppressor proteins. There are about 20 of these proteins, including P53, BRCA1 and 2, RB, and the inhibitor of NF-kappa-B, which are critical parts of each cell's own natural defense mechanism to prevent the generation of cancer cells and to direct a cell which has become cancerous to commit suicide.

Bobby always the first approved anti cancer drugs, whose primary activity is the activation of tumor suppressor proteins are about 20 of these proteins, including P 53 rocket one and two RV and the inhibitor candidate, which are critical parts of each sell all natural defense mechanism to prevent the generation of cancer cells.

The director style, which had become cancerous to commit suicide, just broad anti cancer mechanism potentially relevant to any malignancy.

Michael P. Mason: This broad anti-cancer mechanism is potentially relevant to any malignant tumor. Our goal is to continue to demonstrate the impact that Expovio can have in combination with drugs from all of the other pillars in order to maximize the impact that Expovio can have on improving outcomes for a large variety of cancers. Moving to slide five, I'll focus on our near-term and medium-term goals. First and foremost, we remain committed to increasing the positive impact we are having on the lives of patients battling cancer, and this is a core principle that guides everything we do at Karyopharm. And, as you may have seen in a press release we issued this afternoon, we have just achieved another very important milestone with our announcement that the top-line results from the Phase 3 SEAL study met its primary endpoint with a significant increase in progression-free survival in patients with unrespectable, de-differentiated liposarcoma. Additionally, over the next one to two years, there are a number of key goals that will be critical for us Second, receiving the initial approval for Expovio in Europe for patients with relapsed or refractory multiple myeloma.

Our goal is to continue to demonstrate the impact that it well we are going to have in combination with dropped from all of the other pillars in order to maximize the impact, but we all can have on improving outcomes for a large variety of cancers.

Slide five I'll focus on our near term and medium term goals.

First and foremost we remain committed to increasing the positive impact we're having on the lives patients battling cancer and this is a core principle that guidance everything we do at Karyopharm.

And as you may have seen in our press release, we issued this afternoon. We have just achieved another very important milestone with our announcement of the topline results from the phase three seal study met its primary endpoint with a significant increase in progression free survival in patients with unresectable differentiated like with sarcoma.

Additionally over the next one to two years or a number of key goals that will be critical for us including.

First securing the U.S. accrual for exposed me on second line multiple myeloma, which we believe will help significantly drive total exposure you know sales higher.

Okay, receiving the initial approval for exposure in Europe for patients with relapsed or refractory multiple myeloma.

We're launching our first solid tumor indication in the U.S. based on the data just announced and for continuing to generate support of clinical data for our growing clinical portfolio, which includes <unk> Elton XR ABT nine to seven four.

Michael P. Mason: Third, launching our first solid tumor indication in the U.S. based on the data just announced. And fourth, continuing to generate supportive clinical data for our growing clinical portfolio, which includes Expovio, Eltanexor, and KPG9274. Looking a bit further out to the next three to five years, we anticipate that Expovio could be approved in multiple oncology indications across the globe, with substantial revenue contributions from ex-U.S. royalties and sales miles. This next chapter is also anticipated to bring continued expansion of our pipeline across multiple assets and finally the broad establishment of XPO1 inhibition as a core therapeutic approach in cancer treatment.

Looking a bit further out to the next three to five years, we anticipate that exposure could be approved in multiple oncology indications across the globe with substantial revenue contributions from actually was royalties and sales milestones. This next chapter is also anticipated to bring continue expansion of our pipeline across multiple assets and finally, the broadest style.

I will spend the next deal one inhibition as a core therapeutic approach in cancer treatment.

Please now turn to slide six where I'll highlight the exciting as we announced earlier this afternoon regarding our randomized phase three seal study.

Michael P. Mason: Please now turn to slide 6, where I'll highlight the exciting news we announced earlier this afternoon regarding our randomized phase 3 SEAL study. As a reminder, SEAL evaluated the efficacy and safety of single-agent expovio in patients with advanced unrespectable de-differentiated liposarcoma following two or more prior therapies. Unfortunately, there is no standard of care for patients with advanced disease, and we are thrilled to announce that the study met its primary endpoint with a significant increase in progression-free survival and a hazard ratio of 0.70 with a p-value of 0.023. We believe that these results not only represent a significant advance in the treatment of patients with D-differentiable lymphosarcoma, but we believe these data further support exspobio This is also consistent with other earlier-stage positive results from ongoing expovio studies in diseases such as endometrial cancer, GBM, melanoma, lung cancer, and others. Microsarcoma also represents an important entry point for expovio into the solid tumor treatment landscape, where nine of the top ten most common and fatal forms of cancer are solid tumors.

As a reminder, seal evaluated the efficacy and safety of single agent exposed Leo in patients with advanced on respectable Unresectable differentiated life of sarcoma, following two or more prior therapies. Unfortunately, there is no standard of care for patients with advanced disease, and we are thrilled to announce that the study met its primary endpoint for this.

Significant increase in progression free survival and a hazard ratio of 0.70 with a P value of 0.0 to three.

We believe that these results not only represent a significant advance in the treatment of patients what did your friendship for life Oh, well. We believe these data further supporting spoke he has substantial potential across multiple solid tumors, representing a major advance for the development and commercial potential of exposure to all in college you more generally.

This is also consistent with other earlier stage positive results from ongoing exposed studies in diseases, such as endometrial cancer, GBM melanoma lung cancer and others like what sarcoma also represents an important entry point breaks bogey out into the solid tumor treatment landscape, where nine of the top 10, most common and they don't want.

Cancer, our solid tumors.

We look forward to presenting the detailed ones also steel at the upcoming connective tissue oncology society or see cost annual meeting we plan to submit a new drug application than D.A.

Michael P. Mason: We look forward to presenting the detailed results of SEAL at the upcoming Connective Tissue Oncology Society, or CTOS, annual meeting. We plan to submit a new drug application, or NDA, in the first quarter of 2021, requesting the FDA approval of Expovio to treat the patient population studied in the FEAL Phase III trial. Please now turn to slide 7.

First quarter 2021, requesting the FDA approval of exposed me out to treat the patient population studied in this field phase three trial.

Please now turn to slide seven.

Our clinical strategy for exposure continues to be innovative the innovating with a purpose.

Michael P. Mason: Our clinical strategy for Exspobio continues to be innovative, to be innovating with a purpose. Specifically, our approach has been to demonstrate meaningful activity in difficult-to-treat patient populations and then to expand dramatically into earlier lines of treatment and additional tumor types, particularly in combination with other anti-cancer drugs. This strategy has been evident in our approach in both myeloma and DLV-CI, where we began with our successful STORM and SATEL studies, and it led to subsequent development in early alliance and combination settings. Similarly, now that we have seen the positive phase 3 SEAL data, we plan to follow the same path and continue with our clinical development approach and a number of important and much larger solid tumor indications, including endometrial cancer Turning to slide eight, I'll focus on other recent highlights. During the third quarter, we achieved record quarterly Expovio net sales of $21.3 million, the strongest quarter since our July 2019 launch in pentarefractory multiple myeloma. These results reflect a 15% increase compared to the second quarter of this year.

Specifically, our approach has been to demonstrate meaningful activity in difficult to treat patient populations and then to expand dramatically into earlier lines of treatment and additional tumor types, particularly in combination with other anti cancer drugs.

This strategy has been evident in our approach in both myeloma and DLP Seattle, We began with our successful starve unstable studies and its led to subsequent development in earlier lines in combination settings.

Similarly, now that we have seen a positive phase III field data, we plan to follow the same path and continue with expansion our clinical development approach and a number of important new much larger solid tumor indications, including endometrial cancer with the CNDO study.

Lung cancer, GBM melanoma, and others, which have been selected based on encouraging earlier clinical data and commercial potential.

Turning to slide eight I'll focus on other recent highlights during the third quarter, we achieved record quarterly quarterly Expo net sales of $21.3 million the strongest quarter since our July 2018 laws in penta refractory multiple myeloma.

These results reflect a 15% increase compared to the second quarter of this year. These strong results were driven by demand for exposure in both new multiple myeloma patients starts and initial prescriptions in patients with relapsed or refractory diffuse large b cell phone.

Michael P. Mason: These strong results were driven by demand for Expovio in both new multiple myeloma patient starts and initial prescriptions in patients with relapse or refractory diffuse large bead telophones. For our pipeline progress, I'll remind you that the FDA recently accepted our Supplemental New Drug application seeking approval for Expovio for the treatment of myeloma after at least one prior line of therapy and assigned a due date In addition to a decision by the FDA, we are awaiting a decision in Europe from the EMA on our MAA seeking approval of Expovio for the storm population. In addition to this field study, we also made important progress with our development programs in other solid tumors. This includes several presentations of data at ESMO in September, which showed promising results for expobio in combination with K-TRUDA for the treatment of melanoma and expobio in combination with carboplatinum and paclitaxel for the treatment of advanced or metastatic solid tumors. Finally, on the financial front, we ended the quarter with a strong cash position of approximately $304 million that we expect will be sufficient to fund our planned I'll now ask John Demery, our Chief Commercial Officer, to provide some additional details on Excovio's sales performance during the third quarter. John?

Our pipeline progress I'll remind you that the FDA recently accepted our supplemental new drug application seeking approval. For example, we opened the treatment of myeloma. After at least one prior lines of therapy and assign to produce the action date of March 19 2021.

In addition to a decision by the FDA, we are awaiting a decision in Europe from the ebay on our M&A seeking approval exposure for the storm population.

In addition to the seal study, we also made important progress with our development programs and other solid tumors. This includes several presentations of data at ESMO in September which show promising results for Expo in combination with Keytruda for the treatment of melanoma and expose exposed yelling promising combination carbo platinum and paclitaxel at that.

EBITDA that advanced or metastatic solid tumors.

Finally on the financial front, we ended the quarter with a strong cash position of approximately 304 million that we expect will be sufficient to fund our planned operations into the second half of 2022.

I'll now ask John Demeritt, our Chief commercial officer to provide some additional details wanting stelvio sales performance during the third quarter John.

Thank you Michael and good afternoon, everyone as Michael noted earlier I am proud of the commercial momentum seen during the quarter. A direct result of the dedicated Karyopharm commercial organization that continues to drive our educational initiatives forward virtually an it person where appropriate in support of our greater multiple myeloma and diffuse large b cell lymphoma.

John Demery: Thank you, Michael. Good afternoon, everyone. As Michael noted earlier, I am proud of the commercial momentum seen during the quarter, a direct result of the dedicated Karyopharm commercial organization that continues to drive our educational initiatives forward virtually and in person, where appropriate, in support of our greater multiple myeloma and diffuse large B cell lymphoma communities of patients, families, and caregivers. On slide 9, we outline results from market research that highlight the key features of expovio treatment that are responding most with healthcare providers and helping to drive the increased usage of expovio that we've now seen over the past few quarters. Specifically cited are Expovio's rapid response data, with some responses reported as early as one week, as well as the positive storm data that showed a strong objective response rate in very difficult-to-treat patient populations, which included 100% of patients being refractory to daratumumab and 57% having high-risk cytogenetics. Next, physicians noted that Expovio is the first and only FDA-approved oral XpO1 inhibitor that selectively binds to and blocks XpO1, whose overexpression in cancer cells is increasingly being recognized as a core driver of tumor growth.

Communities, the patients families and caregivers.

Slide nine we outlined results from market research that highlight the key features of exposure you have treatment that are resonating most with health care providers and helping to drive the increased usage of exposure that we've now seen over the past few quarters, specifically cited our expose rapid response data with summer spots is recorded.

Earliest one week as well as the positive storm data that showed a strong objective response rate and very difficult to treat patient populations, which included a 100% of patients being refractory to dare to move out and 57% having high risk cytogenetics.

Next physicians noted that exposure is the first and only after FDA approved oral XP or one inhibitor, but selectively binds to block Expo one who's over expression in cancer cells is increasingly being recognized as a core driver of tumor growth.

And finally, there's increasing recognition and experience that exposed me a side effect profile typically be manageable and reversible with dose modifications prophylactic treatment.

Slide 10 shows the positive increasing quarterly sales and prescription trends for exposed here. So far in 2020, the third quarter saw a 15% increase in both net sales and patient demand compared to the second quarter Importantly, we saw robust increase in new by all the patients.

John Demery: And finally, there's increasing recognition and experience that exspobio's side effect profile can typically be manageable and reversible with dose modifications and prophylactic treatment. Slide 10 shows the positive and increasing quarterly sales and prescription trends for Expovio so far in 2020. The third quarter saw a 15% increase in both net sales and patient demand compared to the second quarter.

It's in the third quarter compared to the second quarter. The majority of prescriptions for the quarter continued to comp for multiple myeloma patients that we did see important initial contributions from D.L. Bcl patience as we continue to introduce exposed to this segment of the market and build momentum in this new indication.

Slide 11 highlights the increase in new account growth for the third quarter, which jumped to 202, new accounts prescribing exposed you, bringing the total to 543, new accounts for the year New accounts secured this quarter reflect multiple myeloma and Daryl Bcl treating physicians these results.

John Demery: Importantly, we saw a robust increase in new myeloma patients starting treatment in the third quarter compared to the second quarter. The majority of prescriptions for the quarter continued to come from multiple myeloma patients, but we did see important initial contributions from DLVCL patients as we continue to introduce Expovio to this segment of the market and build momentum in this new indication. Slide 11 highlights the increase in new account growth for the third quarter, which jumped to 202 new accounts prescribing Expovio, bringing the total to 543 new accounts for the year. New accounts secured this quarter reflect multiple myeloma and DLVCL-treating physicians.

Our particularly promising as physician education in many geographies continues to be conducted the virtual web based tools due to ongoing restrictions related to the COVID-19 pandemic.

The graph on slide 12 shows the prescription refill rate for exco yellow overtime for both the first and second refill for those patients eligible for these refills. These numbers remain stable for the third quarter that are significantly higher as compared to our initial launch period.

For instance in September of 2019, which marked the first much mark the end of the first quarter that expose you know became commercially available roughly 42% of patients we're going hard to get a second prescription one year later that number stands at 60% a substantial increase these promising and increasing refill rates.

John Demery: These results are particularly promising as physician education in many geographies continues to be conducted via virtual and web-based tools due to ongoing restrictions related to the COVID-19 pandemic. The graph on slide 12 shows the prescription refill rate for Expovio over time for both the first and second refill for those patients eligible for these refills. These numbers remain stable for the third quarter but are significantly higher as compared to our initial launch period. For instance, in September of 2019, which marked the end of the first quarter that Expovio became commercially available, roughly 42% of patients were going on to get a second treatment. One year later, that number stands at 60%, a substantial increase. These promising and increasing refill rates, coupled with an average of 2.9 treatment cycles per patient as of the end of September, further reinforce the positive feedback we've received from patients and physicians regarding their experience and usage of Expovio.

Coupled with an average of 2.9 treatment cycles per patient as of the end of September further reinforce the positive feedback we've received from patients and physicians regarding their experience and usage of Ics drove you importantly, the patient discontinuation rate due to side effects remains relatively low at 13%.

Which we believe is a testament to more and more physicians gaining comfort in helping their patients manage the side effect profile of EXPAREL via with proper prophylactic therapy dose modifications.

The third quarter of 2020 represented the first full quarter of our launch in relapsed refractory deal Bcl following approval in late June on Slide 13, we're pleased to share preliminary launch metrics for this period, which showed two thirds of prescriptions have come from community based physician.

John Demery: Importantly, the patient discontinuation rate due to side effects remains relatively low at 13%, which we believe is a testament to more and more physicians gaining comfort with helping their patients manage the side effect profile of Expovio with proper prophylactic therapy and dose modifications. The third quarter of 2020 represented the first full quarter of our launch in relapsed refractory DLBCL following approval in late June. On slide 13, we're pleased to share preliminary launch metrics for this period, which show that two-thirds of prescriptions have come from community-based physicians.

Early retail trends have been strong as well at 60%, but which matches what we've seen in the multiple myeloma space and we were able to secure a category to a NCCN compendia listing within two weeks of approval.

These efforts are translated into positive initial feedback from treating physicians and their patients based on our market research target physicians are most attracted to expose response rate as a single agent.

Oral option and the ability to treat the LBC outpatient and a completely new way.

Additionally, we've seen positive payer dynamics with no on label patient denials seen to date.

John Demery: Early retail trends have been strong as well, at 60%, which matches what we've seen in the multiple myeloma space, and we were able to secure a Category 2A NTCN Compendia listing within two weeks of approval. These efforts have translated into positive initial feedback from treating physicians and their patients. Based on our market research, target physicians are most attracted to Excovio's response rate as a single agent, oral options, and the ability to treat DLBCL patients in a completely new way. Additionally, we've seen positive payer dynamics with no unlabeled patient denials seen to date. And finally, the feedback we are hearing regarding Expovio's Thymeprofile has also been positive, with most physicians reporting that the 60mg twice weekly dose, the approved dose, being manageable for patients.

Finally, the feedback we are hearing regarding suburbia side effect profile has also been positive with most physicians reporting 60 milligrams twice weekly dose the approved dose being manageable for patients. We will continue to fully leverage the newly approved indication and the L. Bcl to access our key stakeholders educate on this new indicate.

You can also generate increasing excitement in multiple myeloma to help more patients impacted by these diseases now I'd like to turn the call back over to Michael to discuss our regulatory update and clinical development priorities. Michael. Thank you John on Slide 14, I'll provide a brief update on our key upcoming regulatory activities.

<unk> results from a Boston study served as the basis for our Sndk submitted to the FDA for the treatment of patients with multiple myeloma. After at least one prior line of therapy or a Sunday. It was accepted for filing in July with the decision expected by March 19, 2021 in Europe. We've submitted the final additional re monitoring data from the storm study requested by.

Michael P. Mason: We will continue to fully leverage the newly approved indication in DLBCL to access our key stakeholders, educate them on this new indication, and also generate increasing excitement in multiple myeloma to help more patients impacted by these diseases. Now, I'd like to turn the call back over to Michael to discuss our regulatory updates and clinical development priorities.

The M&A in September of 2019, and an October 2020, Karyopharm received a further updated list of outstanding issues or the CH empty summarizing the remaining topics for karyopharm photographs, and indicating the CH MP intensive consulted scientific advisory group for additional advice, we continue to expect a decision from CHF.

Michael P. Mason: Thank you, John. On slide 14, I'll provide a brief update on our key upcoming regulatory activities. The positive results from the Boston study served as the basis for our SNDA submitted to the FDA for the treatment of patients with multiple myeloma after at least one prior line of therapy. Our SNDA was accepted for filing in July, with a decision expected by March 19, 2021.

By the end of this year. In addition contingent upon following receipt of CHF.

Opinion, we expect to submit an M&A based on data from the Boston study before the end of 2020.

For del Bcl, we're still in the process of evaluating the optimal approach and timing of future regulatory submissions and we look forward to providing you with an update on future.

Michael P. Mason: In Europe, we submitted the final additional remonitoring data from the STORM study requested by the EMA in September of 2019, and in October 2020, Karyopharm received a further updated list of outstanding issues from the CHMP summarizing the remaining topics for Karyopharm to address and indicating the CHMP intends to consult its scientific advisory group for additional advice. We continue to expect a decision from the CHMP by the end of this year. In addition, continuing upon and following receipt of CHMP's opinion, we expect to submit an MAA based on the data from the Boston study before the end of 2020. For DLBCL, we're still in the process of evaluating the optimal approach and timing of future regulatory submissions, and we look forward to providing you with an update in the future. Please now turn to slide 15.

Please now turn to slide 15, the potential expansion of our exposure to label based on the promising Boston data results.

Represent an important turning point in the multiple myeloma treatment paradigm expose current penta refractory multiple myeloma indication is largely applicable to the approximately 6000 patients in the United States, who are treated in the fourth in later lines of therapy annually.

If approved and expanded label based on the population studied in the Boston trial, but expand expose potential impact over 30000 patients annually in the U.S. treated in the second and third line settings.

This slide highlights some of the key differences between that started in Boston populations study and data generated from these trials.

As you can see the patient studies in the Boston trial had been previously treated with far fewer therapies in the patients that storm and had disease that was far less refractory to treatment I immediately they prior therapies and storm as compared to two in the Boston study subsequently the response rate a median PFS in the Boston study was substantially higher than the storm.

Michael P. Mason: The potential expansion of our Expovio label based on the promising Boston data represents an important turning point in the multiple myeloma treatment paradigm. Expovio's current pentorefractory multimyeloma indication is largely applicable to the approximately 6,000 patients in the United States who are treated in the fourth and later lines of therapy annually. If approved, an expanded label based on the population studied in the Boston trial would expand Expovio's potential impact to over 30,000 patients annually in the U.S. treated in the second and third line settings. This slide highlights some of the key differences between the STORM in Boston population study and data generated from these trials.

Study. This was also driven by the mechanistic approach of combining two drugs with different and additive or synergistic mechanisms of action in the Boston study as exposed me out ANEXIO one inhibitor. It was given in combination with once weekly Velcade, a protease inhibitor along with standard low dose dexamethasone.

Importantly, the mean duration of treatment was 10 months in the Boston study as compared to three months in the storm study.

Michael P. Mason: As you can see, the patients studied in the Boston trial had been previously treated with far fewer therapies than the patients in STORM and had disease that was far less refractory to treatment, i.e., a median of eight prior therapies in STORM as compared to two in the Boston study. Subsequently, the response rate and median PFS seen in the Boston study were substantially higher than in the STORM study. This may be driven by the mechanistic approach of combining two drugs with different and additive or synergistic mechanisms of action in the Boston study, as Expovio, an XPO1 inhibitor, was given in combination with once weekly Velcade, a proteasome inhibitor, along with standard low-dose dexamet Importantly, the mean duration of treatment was 10 months in the Boston study as compared to three months in the Storm Center.

Lets comparison to study this T to why we believe it will be all has just begun to make an impact on the treatment paradigm in multiple myeloma. We believe the greatest utility for exposure, we have in the future will be as a combination therapy with other potent anti myeloma drugs, such as Velcade and taken only once per week instead of the currently approved dose of twice per week and.

Finally, I'd be remiss, if I didn't mention some update for a number of other exciting pipeline opportunities, we're pursuing for selinexor, which can be seen on slide 16.

In the human logic malignancy space, we expect to dose our first patient by the end of the year and our confirmatory phase three the LBC all trial, which will study selinexor in combination with Rituximab and chemotherapy regiment of Jim Decitabine Dexamethasone platinum based therapy.

Michael P. Mason: This comparison of studies is key to why we believe Expovio has just begun to make an impact on the treatment paradigm for multiple myeloma. We believe the greatest utility of Expovio in the future will be as combination therapy with other potent anti-myeloma drugs, such as Velcade, and taken only once per week instead of the currently approved dose of twice per week. And finally, I'd be remiss if I didn't mention some updates on a number of other exciting pipeline opportunities we're pursuing for SolidXR, which can be seen on slide 16. In the hematologic malignancy space, we expect to dose our first patient by the end of the year in our confirmatory phase 3 DLVCL trial, which will study felinexer in combination with rituximab and a chemotherapy regimen of gemocytabine, dexamethasone, and platinum-based therapy.

We have also recently initiated two new trials in myelofibrosis, where we have been encouraged by some smaller investigator initiated studies and we expect to begin enrollment in these new studies in 2021.

And as I mentioned earlier, we have a number of important ongoing studies in the solid tumor setting both as a single agent and in combination which follow nicely from the positive steel results, we announced today.

With that I'll turn the call over to Mike Mason to review the quarterly financials, Mike. Thank you Michael since we issued a press release earlier today with the fall financial results I will just focus on the highlights let's begin on slide 18 net product revenue for the third quarter of 2020 was 21.3 million third quarter sales were driven by patient demand from.

Academic and community based physicians with channel inventories sales.

Growing in line with actual prescription growth.

The estimated gross to net discount Fabio in third quarter was approximately 16%. We continue to expect the gross to net discounts at all between 15 and 20% for the remainder of this year.

Michael P. Mason: We have also recently initiated two new trials in myelofibrosis, where we have been encouraged by some smaller investigator-initiated studies, and we expect to begin enrollment in these new studies in 2021. And, as I mentioned earlier, we have a number of important ongoing studies in the solid tumor setting, both as a single agent and in combination, which follow nicely from the positive STIHL results we announced today. With that, I'll turn the call over to Mike Mason to review the quarterly financials. Mike?

Research and development expense for the third quarter of 2020 was 37 million compared to 26.3 million for the third quarter of 2019.

The increase in R&D expenses compared to the third quarter of 2019 was mainly attributable to COVID-19 trial activity and continued activity in our other ongoing clinical trials.

<unk> expense for the third quarter of 2020 was 30.9 million compared to 25.3 million for the third quarter of 2019, the increase the nest unit expenses compared to the prior year was primarily due to activities to support the U.S. commercialization. This phobia, including expenses related to the launch of exposure you as a treatment for patients.

Michael P. Mason: Thank you, Michael. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 18. Net product revenue for the third quarter of 2020 was $21.3 million. Third quarter sales were driven by patient demand from academic and community-based physicians, with channel inventory sales growing in line with actual prescriptions. The estimated gross net discount for Expovio in the third quarter was approximately 16%. We continue to expect the gross net discount to fall between 15% and 20% for the remainder of this year.

Collapse or refractory the LDC.

As noted on slide 19 cash cash equivalents restricted cash investments as of September 30 of 2020 totaled 304.2 million compared to 265.8 million as of December 31, 2019.

We currently project exposed deals sales to grow modestly through the remainder of 2020 based on expected catalyst with more significant growth expected. Following the potential expanded approval. This photo based on the results from the Boston said.

Michael P. Mason: Research and Development expenses for the third quarter of 2020 were $37 million compared to $26.3 million for the third quarter of 2019. The increase in R&D expenses compared to the third quarter of 2019 was mainly attributable to COVID-19 trial activity and continued activity in our other ongoing clinical trials. SG&A expense for the third quarter of 2020 was $30.9 million compared to $25.3 million for the third quarter of 2019.

Based on our current operating plans, we expect our non-GAAP R&D and that's net expenses for the full year 2020 to be in the previously projected range of 240 million to 269.

In addition, we currently expect that our existing cash cash equivalents investments and the revenue we expect to generate over your product sales will be sufficient to fund our planned operations into the second half of 2020. So I'll now turn the call back over to Michael for some concluding remarks, Michael Thank you, Mike before moving to the queue. Today, Let me highlight some of the key clinical and regulatory.

Sorry milestones that we expect for the remainder of 2020 as shown on slide 20.

As you can see we have achieved many key milestones throughout the year, but still have important goals to accomplish by the end of this year first we expect a decision from the M&A on the storm M.A. J.

Michael P. Mason: The increase in SG&A expenses compared to the prior year was primarily due to activities to support the U.S. commercialization of Expovio, including expenses related to the launch of Expovio as treatment for patients with relapsed or refractory DLD. As noted on slide 19, cash, cash equivalents, and restricted cash investments as of September 30, 2020 totaled $304.2 million compared to $265.8 million as of September 31, 2019. We currently project Expovio sales to grow modestly for the remainder of 2020 based on expected catalysts, with more significant growth expected following the potential expanded approval of Expovio based on the results from the Boston study. Based on our current operating plans, we expect our non-GAAP R&D and SG&A expenses for the full year 2020 to be in the previously projected range of $240 million to $260 million. In addition, we currently expect that our existing cash, cash requirements, and investments and the revenue we expect to generate from Expovio product sales will be sufficient to fund our planned operations in the second half of 2022. I'll now turn the call back over to Michael for some concluding remarks. Michael.

Next we plan to submit the full Boston data to the M&A before the end of the year and Jane upon following receipt of CHF would be a decision on the storm and then.

And finally, we anticipate initiating arc and former confirmatory phase three study of exposure, we own deal Bcl in support of our recent accelerated approval and of course, we'll continue to support the FDA issued a review of our San Diego based on the Boston study, where we expect a decision from the FDA on or before the PDUFA date of March 19 2021.

We appreciate your ongoing support and look forward to keeping you updated on our future progress I'll now turn the call over to the operator for questions.

Operator.

We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone if youre using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two please limit yourself to one question and one follow up.

This time, we will pause.

Charlie to assemble our roster.

Our first question is from Jonathan Chang from Sep deem, leaving go ahead.

Michael P. Mason: Thank you, Mike. Before moving to the Q&A, let me highlight some of the key clinical and regulatory milestones that we expect for the remainder of 2020, as shown on slide 20. As you can see, we have achieved many key milestones throughout the year but still have important goals to accomplish by the end of this year. First, we expect a decision from the EMA on the storm, MAA.

Hi, guys. Thanks, very much for taking my questions and congrats on the positive seal read out.

First question can you talk about the D. differentiated label sarcoma treatment landscape, how do you see this commercial opportunity and what if any read through this has on your broader thinking regarding the solid tumor opportunity for exposure.

Michael P. Mason: Next, we plan to submit the full Boston data to the EMA before the end of the year, contingent upon and following receipt of CHMP's decision on the Stormin AA. And finally, we anticipate initiating our confirmatory phase three study of Expovio and DLVCL in support of our recent accelerated approval. And, of course, we'll continue to support the FDA through the review of our SNDA based on the Boston study, where we expect a decision from the FDA on or before the PDUFA date of March 19, 2021. We appreciate your ongoing support and look forward to keeping you updated on our future progress. I'll now turn the call over to the operator for questions. Operator? We will now begin the question and answer session. To ask a question, you may press star then one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys.

Sure, let me dive and I'll give a brief brief because we don't think it will lecture on this.

But unfortunately that differentiated life of sarcoma landscape is only populated by for enteral chemotherapy cytotoxic agents I'm pretty much every patient will get anthracite Glenn I liked your my son in combination with Jim cited being or some other cytotoxic and most patients will receive a repeal in Andorra expected in Jordan.

Our treatment course beyond that there are really no other treatments that have.

Clear documented activity and are routinely use.

The exposure you know potentially could be the first oral therapy approved in this indication and Furthermore, this is the largest study of LIFO sarcoma ever performer and I believe it's the largest dedicated type of sarcoma study ever performed so so we think we can really become one of the important drugs.

You know after chemotherapy is used.

And could provide a real.

Operator: To withdraw your question, please press star then two. Please limit yourself to one question and one follow-up. At this time, we will pause momentarily to assemble our roster. Our first question is from Jonathan Chang from SVB Living. Go ahead. Hi guys, thanks very much for taking my questions and congrats on the positive SEAL readout. First question, can you talk about the de-differentiated liposarcoma treatment landscape, how you see this commercial opportunity, and what, if any, impact this has on your broader thinking regarding the solid tumor opportunity for exposed tumors? Sure. Let me dive in.

Better tolerated, we believe oral options for these patients who are heavily pre treated.

Got it I'm just one follow up question then.

On a different topic I can you provide additional color on the outstanding questions from the CHF Pea that you received in October I think you said.

Yeah, I'll turn that over to Dr. shack him to comment.

I'm, sorry, Mike I can you sound and I will follow up.

Sure sure I believe the question was.

And can we provide additional color on some of the question.

Questions from the ebay that they continue to ask us and I think as we've described previously.

Michael P. Mason: I'll be brief because we can't give a lecture on this. Unfortunately, the de-differentiated liposarcoma landscape is only populated by parenteral chemotherapy cytotoxic agents. Pretty much every patient will get anthracycline, like adriamycin, in combination with gemcitabine or some other cytotoxic, and most patients will receive aribulin and/or crevectin during their treatment course. Beyond that, there are really no other treatments that have clear documented activity and are routinely used. Expovio potentially could be the first oral therapy approved in this indication, and furthermore, this is the largest study of liposarcoma ever performed, and I believe it's the largest dedicated liposarcoma study ever performed. So we think we can really become one of the important drugs after chemotherapy is used and could provide a real... better tolerated, we believe oral option, to these patients who are heavily pre-treated. I got it.

The M&A has has requested additional information regarding some of the laboratory analyses in patients who were on the study in particular some of the responding patients than we provided notice.

To the M&A. In addition, we have provided a as the EMA has asked us to continue to justify the benefit risk we provided the Boston data in support of the storm and they application.

Yeah.

Second question very much.

Our next question is from Peter Lawson from Barclays Go ahead.

Hi, there. This is mitchell on for Peter Congratulations on that positive data and thanks for taking our question. So the first question I have is that could see all the hathaway supplemental up 4.7.

We're just wondering did the FDIC say, what would qualify as meaningful and how much you beat those expectations by.

The FDA Doesnt say that what they do the both the FDA and EMA I have provided.

Nice input.

In particular scientific advice from the EMEA and post meeting advice from the FDA.

Michael P. Mason: Just one follow-up question then on a different topic. Can you provide additional color on the outstanding questions from the CHMP that you received in October, I think you said? Yeah, I'll turn that over to Dr. Shacham to comment. I'm sorry, Michael, can you start, and I will say, Sure, sure.

Considering that this trial could potentially serve as the basis for an approval and generally that means that you have to hit the statistical.

Boundary <unk> 0.05, which we did and that the trial has to be well conducted internally consistent which we also believe it has been so we believe we've we've hit hit the.

Unknown Attendee: So the question was, can we provide additional color on some of the questions from the EMA that they continue to ask us? And I think, as we've described previously, the EMA has requested additional information regarding some of the laboratory analyses in patients who are on the study, in particular some of the responding patients, and we've provided that to the EMA. In addition, we've provided, as the EMA has asked us to continue to justify the benefit-risk, we've provided the Boston data in support of the STORM-MAA application. Got it.

Appropriate goal posts I should also mentioned that the hazard ratio in the phase two portion of this study was essentially identical to that in the phase three so the FDA was aware that as was the M&A and up.

They went into this phase three expecting a hazard ratio of about 0.7, which is what it was designed for.

Great. Thank you and then if you could just comment on discontinuation rate. After the seal study is that consistent with that 13% you've seen in the real world <unk> myeloma, and then now what additional data should be expected see toss beyond PFS. Thank you.

Unknown Attendee: Thank you very much. Our next question is from Peter Lawson from Barclays. Go ahead. Hi there, this is Mitchell on the computer.

Michael P. Mason: Congratulations on the positive data and thanks for taking our question. So, the first question I have is for the CO, the Hazardous Waste Reclaiming Limit for 0.7. We're just wondering, did the FDA say what would qualify as meaningful, and how much did you beat those expectations by? The FDA doesn't say that. What they do, both the FDA and the EMA have provided advice, in particular scientific advice from the EMA and post-meeting advice from the FDA, considering that this trial could potentially serve as the basis for an approval. And generally, that means that you have to hit the statistical boundary of 0.05, which we did, and that the trial has to be well conducted and internally consistent, which we also believe it has been. So we believe we've hit the appropriate goalposts.

Yeah, I can't I can't speak to the exact discontinuation rate, but I can say that it was.

These patients are not as heavily pretreated patients with Lastline myeloma and.

They also have much less systemic co morbidities that lend stage myeloma patients haven't one would expect the dropout rate therefore, we'd be.

It would be lower in addition, the dose here was lower obviously you might look at that dose being used in the seal study was more similar to the deal Bcl sales study. You also you will see a complete presentation that as far as time permits at the C costs. This will be given by our lead investigator and it should be a full dataset.

Thanks and congrats.

Your next our next question is from Murray recall from Jefferies Go ahead.

Michael P. Mason: I should also mention that the hazard ratio in the Phase 2 portion of this study was essentially identical to that in the Phase 3, so the FDA was aware of that, as was the EMA, and they went into this phase 3 expecting a hazard ratio of about 0.7, which is what it was designed for. Great, thank you. And then, if you could just comment on the discontinuation rate for the SEAL study, is that consistent with the 13% you've seen in the real world for myeloma? And then, what additional data should we expect at CTOS beyond PFS? Thank you.

Hi, everyone. Thanks for taking my questions and I'll offer my congrats on the label sarcoma data as well I'll ask a question about myeloma. So we're exposed beyond Threeq you. It also deal Bcl two can you talk about the cobot impact and for new myeloma pace.

Yeah. That's what my notes treatment are you seeing out what some of the new patients and if you can break out.

Combo preferences as well and then you mentioned the average treatment cycles per patient at 2.9, just wondering if you expect that to continue to increase in the current market opportunity in the last line setting or do you see a leveling off around a 2.9 and then when you get into the expansion would be earlier line pace.

Michael P. Mason: Yeah, I can't I can't speak to the exact discontinuation rate, but I can say that it was lower. These patients are not as heavily pre-treated as patients with last-line myeloma. They also have much less systemic comorbidities that end-stage myeloma patients have. And one would expect the dropout rate, therefore, would be lower.

And that that number could potentially go up.

Michael P. Mason: In addition, the dose here was lower. So you might look at the dose being used in the SEAL study was more similar to the DLVCL SATEL study. You'll, you'll see a complete presentation that, as far as time permits, at the CTAS. This will be given by our lead investigator, and it should be a full data set.

Well I'm already that was quite an encyclopedia of so I'll ask John Demeritt, our chief commercial officer to begin to address that and we'll keep our well keep it a little bit sharper go ahead, John if I Miss any of those keep me honest, yeah, but let me ask let me answer that thought about Boston first and are we seeing expo use with al Qaeda in earlier lines of therapy.

Michael P. Mason: Thanks and congratulations. Our next question is from Maurice Raycroft from Jeffries. Go ahead. Hi, everyone.

Currently the majority of used trucks W is and fourth line plus as indicated we obviously do expect that to move earlier whats the Boston indication in combination with Velcade is approved.

John Demery: Thanks for taking my questions, and I'll offer my congratulations on the liposarcoma data as well. I'll ask a question about myeloma. So for Expovion 3Q and also DLBCL2, can you talk about the COVID impact? And for new myeloma patients, what line of treatment are you seeing with some of the new patients? And if you can break out combo preferences as well.

You know from our market research that many of the academic and community based physicians are prescribing stelvio in combination with other drugs. So it's not just exposed the opus.

John Demery: And then you mentioned the average treatment cycles per patient at 2.9. Just wondering if you expect that to continue to increase in the current market opportunity in the last line setting, or do you see it leveling off around 2.9? And then when you get into the expansion with the earlier line patients, that number could potentially go up. Wow, Maury, that was quite an encyclopedia.

Semesters out, but they are using it primarily in that fourth line plus setting now currently where it's indicated.

Again, we do expect significant acceleration in earlier lines of usage once we get the new indication for patients with approval one prior line of therapy.

In terms of second question around the impact of the pandemic, where you think that it does still continue to have multiple effects in person visits by our sales force nurse liaison to pair teams, Turkey stakeholders continue to be impacted our data and research suggests about 15% to 20% of HCP as can be seen via in person.

John Demery: So I'll ask John Devery, our Chief Commercial Officer, to begin to address that. And we'll keep our, we'll keep it a little bit short. But go ahead, John. If I miss any of those, keep me honest.

John Demery: Yeah. So, let me ask you, let me answer the one about Boston first. And are we seeing Expovio use with Delcate in earlier lines of therapy? Currently, the majority of use for Expovio is in fourth line plus, as indicated. We obviously do expect that to move earlier once the Boston indication in combination with Delcate is approved. We do know from our market research that many academic and community-based physicians are prescribing Expovio in combination with other drugs. So it's not just Expovio plus dexamethasone, but they're using it primarily in that fourth line plus setting now, which is currently where it's indicated.

We do continue to believe it's harder to appropriately educate change behavior in a virtual environment as compared to maintaining prescribing habits like the goal of more established brands. We have done and are doing a number of initiatives to offset the impact of being virtual including increasing peer to peer education, increasing other non personal promotion.

In digital content training, our field teams on how to be more effective in the virtual environment and finally targeting some large physician networks and their EMR systems to better identify patients in the penta refractory setting since Joe the questions. What was the other question I think one was about the average duration of treatment order or the number of cycles.

John Demery: Again, we do expect significant acceleration in earlier lines of usage once we get the new indication for patients with approval for their prior line of therapy. In terms of the second question around the impact of the pandemic, we do think the pandemic does still continue to have multiple effects. In-person visits by our sales force, nurse liaisons, and paired teams to our key stakeholders continue to be impacted. Our data and research suggest that about 15 to 20% of HCPs can be seen via in-person visits. We do continue to believe it's harder to appropriately educate and change behavior in a virtual environment as compared to maintaining prescribing habits like the goal of more established brands.

And maybe what I would just say there is yeah. I mean, we're close to where we were at 2.9 through through the end of September which we're excited to be at that level you know a.

A little over a year into the launch.

I think to some extent.

As we get closer and then into the launch in the Boston population. So that number will hopefully go significantly higher because as Michael mentioned earlier, the average duration of treatment.

John Demery: We have done and are doing a number of initiatives to offset the impact of being virtual, including increasing peer-to-peer education, increasing other non-personal promotion and digital content, training our field teams on how to be more effective in the virtual environment, and finally, targeting some large physician networks and their EMR systems to better identify patients in the petro-refractory setting. So those were two of the questions. What were the other questions?

In Boston, where them the mean duration of treatment in Boston was 10 month versus three months in storm. So.

Potentially it could go a little bit higher but I think the reality is we're going to come up pretty soon to hopefully a boston approval.

And then I think patients who will be getting treatment much earlier with X Savio, hopefully, we'll stay on drug and treated for longer.

Great. Thanks, guys.

Thank you.

Next our next question is from Brian Abrams from RBC capital markets go ahead.

John Demery: I think one was about the average duration of treatment or the number of cycles. And maybe what I would just say there is, yeah, I mean, we're close to where we were at 2.9 through the end of September, which we're excited to be at that level, you know, a little bit over a year into the launch. I think to some extent, you know, as we get closer and then into the launch in the Boston population, that number will hopefully go significantly higher because, as Michael mentioned earlier, the average duration of treatment on Boston, or the mean duration of treatment in Boston, was 10 months versus three months in Storm. So potentially, it could go a little bit higher, but I think the reality is we're going to come up pretty soon to hopefully a Boston approval. And then I think patients who will be getting treatment much earlier with Expovio hopefully will stay on the drug and be treated for longer. Great.

Hey, guys. Thanks for taking my questions and congrats on the field data.

Curious how frequently ER physicians are looking to use EXPAREL beyond earlier line myeloma post the Boston presentation, but maybe can't do the access and the degree to which inclusion in the NCCN guidelines might open up earlier line access even prior to label expansion any update on timing there a timing for the Boston publication.

Yeah, well, we do expect the Boston publication to come out soon hopefully before the end of the year, but maybe sooner.

No exactly but there will be published.

Peer reviewed journal and that will hopefully facilitate an NCCN. Guideline addition, again the speed of that addition, we don't know.

There our expectation is that there are a not insignificant number of places where you can use the NCCN guidelines as a basis for insurance coverage, which is the major impediment right now to earlier line adoption. We believe that this combination of Selinexor at 12 Euro plus.

John Demery: Thank you, guys. Thank you. Our next question is from Brian Abrahams from RBC Capital Markets. Go ahead.

Michael P. Mason: Hey, guys, thanks for taking my questions and congrats on the SEAL data. I'm curious how frequently physicians are looking to use Expovio and earlier line myeloma post the Boston presentation but maybe can't due to access and the degree to which inclusion in NCCN guidelines might open up earlier line access even prior to label expansion. Any update on timing there or timing for the Boston publication? Yeah, well, we do expect the Boston publication to come out soon, hopefully before the end of the year, but, Unknown Attendee, Detlef Winckelmann, Reshma Rangwala, Elhan Webb, Sohanya Cheng, Karyopharm Therapeutics Inc. And then, just as a follow-up, you mentioned some of the continued multiple effects that the pandemic is having.

Plus velcade Dex once a week is actually the simplest of all of the regimens for relapse refractory myeloma patients with one prior therapy, and therefore could be really beneficial to folks so.

We're hopeful that we can facilitate access was the FCC and guidelines come out and then of course ultimately to the FDA approval.

Got it and then and then just as a follow up.

You mentioned some of the continued multiple effects that the pandemic is having a looking forward I guess in the near to medium term, but I'm curious your expectations for how the second or even third wave of cobot that we're seeing may impact near term use an uptake I guess I'm wondering if you'd expect continued challenges to physician and patient engagement or Conversely.

If you may be able to take advantage of some of the.

Michael P. Mason: Looking forward, I guess, in the near to medium term, I'm curious about your expectations for how the second or even third wave of COVID that we're seeing may impact near-term use and uptake. I guess I'm wondering if you would expect continued challenges to physician and patient engagement, or conversely, if you may be able to take advantage of some of the benefits of oral administration and perhaps fewer facilities available for the administration of CAR T and DLVCL. Thanks.

The benefits of the oral administration, and perhaps fewer facilities the facilities available for administration of car T and deal Bcl. Thanks.

So I think the answer to your question is yes, there are opportunities and there are challenges in the current coverage situation. Obviously for many patients an oral therapy as preferred particularly is less visits during the time of peak pandemic.

In fact, I think it is also as you mentioned more difficult to engage physicians in person. We have tried to offset that and are continuing to do more and more to offset in terms of some of the digital non personal promotion initiatives that I just mentioned earlier.

Michael P. Mason: So I think the answer to your question is yes, there are opportunities and challenges in the current COVID situation, obviously, for many patients, and oral therapy is preferred, particularly with fewer visits during the time of peak pandemic impact. I think it is also, as you mentioned, more difficult to engage physicians in person. We have tried to offset that and are continuing to do more and more to offset it in terms of some of the digital non-personnel promotion initiatives that I just mentioned earlier. Our next question is from Eric Joseph from J.P. Morgan. Go ahead.

Our next question is from Eric Joseph from JP Morgan go ahead.

Hi, good afternoon, and basically my question.

First in relation to the ceiling the LIFO sarcoma opportunity I'm curious to get a sense of whether you see an opportunity to advance our next or earlier.

Up in the treatment paradigm for Michael.

Michael P. Mason: Hi, good afternoon, and thanks for taking the question. First, in relation to the seal and the liposarcoma opportunity, I'm curious to get a sense of whether you see an opportunity to advance LNX or earlier in the treatment paradigm for liposarcoma, either as an alternative to chemo or as maintenance, and whether that's strategically of interest. And then I have a follow-up on Xplovio. Although liposarcoma is a relatively small population, the de-differentiated type in around 2,000 patients per year, it's obviously an important disease and needs addressable therapy. There's been a good bit of interest from various groups, given the SEAL data, which of course they've just heard about, and we expect to continue additional studies in earlier lines, probably with outside groups, if you will. Part of that is because we want to focus our internal resources on some of the larger tumor groups that we're showing activity in. Our C-endo study is ongoing.

Oh, sorry, cromer, either as an alternative chemo or add convenience and whether that strategically adventurous and then I have a.

A follow up on the suburbia.

Paul I'll go to life with sarcoma as a relatively small population that differentiated type and around 2000 patients per year its.

It's obviously, an important disease and needs addressable therapy.

There has been a good bit of interest from from various groups given the sale data which of course, they've just heard about and we expect to continue additional studies in earlier lines, probably with outside groups. If you will pardon.

Part of that is because we want to focus our internal resources and some of the larger tumor groups that were that were showing activity.

Our CNDO study is ongoing that too for those who don't recall. This is a phase three randomized blinded study a once weekly selinexor versus matching placebo in patients with.

Michael P. Mason: For those who don't recall, this is a phase three randomized blinded study of once-weekly Selenexor versus matching placebo in patients with endothelial cancer who receive frontline chemotherapy, typically a platinum taxol couplet, have at least a partial response, which is approximately 80% of these patients, and then right now, there's no maintenance therapy for those folks, unfortunately, and we know that essentially all of So we're conducting the endo study in the maintenance setting after first-line chemotherapy in that group, and that's a big focus; that study's ongoing. We expect data within, before the end of next year, and that's a fairly substantial population with a big unmet medical need. So that'll be our next big focus in solid tumors, and then, of course, you heard about some of the earlier data at ESMO that we mentioned and some of the other places in GBM where we've shown clear single-agent activity, which we intend to pursue.

And just nearly all cancer, who received frontline chemotherapy typically a plot platinum taxol couplet and then.

I have at least a partial response, which is approximately 80% of these patients and.

And then right now there is no maintenance therapy for those folks Unfortunately, and we know that essentially all of them will relapse, So where we're conducting CNDO study in the maintenance setting after first line chemotherapy in that group on and that's a big focus that studies ongoing we expect data within before the end of next year and that's a fairly substantial.

Well sized population for the big unmet medical needs, so that will be our next.

Big focus in solid tumors and that of course, you heard about some of the earlier data at ESMO that we mentioned in some of the other places in GBM, where we show clear single agent activity, which we intend to pursue so we're going to try to move at all fronts, but we'll take advantage of our credo with the NC I and other external groups that have shown interest to move in.

The sarcoma area.

Michael P. Mason: So we're going to try to move on all fronts, but we'll take advantage of our credit with the NCI and other external groups that have shown an interest in moving in the sarcoma area. Got it, that's helpful. And maybe just a question on the Expovio commercial, if I could, it sounds like you have pretty good visibility on where demand is coming from between myeloma and DLBCL. I'm wondering if you could just unpack how much demand, how much script demand was actually coming from DLBCL.

Got it that's helpful. Maybe just a question on exposure your commercial if I could it sounds like you have pretty good visibility on where demand is coming from between myeloma and Bcl I'm wondering if you could just unpack.

How much demand how much strip strip demand is actually coming from you or bcl and.

Im also just trying to.

Just square some of the conservative.

Michael P. Mason: And I'm also just trying to just square some of the conservative expectation in terms of growth for the balance of the year. Do you, I guess, how much of a growth opportunity you see in third line DLBCL? You know, are you seeing any kind of competition from other agents in the community setting? How much of a growth opportunity does the third line, DOBC, I'll sort of represent in your term. So to address the first question, for competitive reasons, we don't break out sales separately between multiple myeloma and DLBCL. What we can tell you is that the majority of prescriptions in the third quarter came from multiple myeloma, but DLBCL patients were an important contributor that we believe will continue to grow over time.

Expectation in terms of growth for the balance of the year.

Do you I guess, how much of a growth opportunity do you see in third line deep deal Bcl.

Are you seeing kind of competition from other.

Agents in the community setting how much of a growth opportunity does.

Third line.

You'll be sheltered represent near term.

And so to address the first question for competitive reasons, we don't breakout sales separately between multiple myeloma and Vito, but we can tell you is that the majority of prescriptions in the third quarter came from multiple myeloma. The Yelp Bcl patients were an important contributor that we believe will continue to grow over time.

Yes, and just in terms of the competitive landscape in growth moving forward I mean, I think we've mentioned a few you know I think we've been.

Michael P. Mason: Yeah, and just in terms of the competitive landscape and growth moving forward, I mean, I think we've mentioned a few, you know. I think we've been as transparent as we possibly can be, which is that we're certainly quite pleased that we grew 15% quarter over quarter this quarter. The myeloma metrics continue to look good. And obviously, we're starting to get contributions from DLBCL. And we, you know, we balance that with we're still in the midst of a COVID pandemic, which does create some challenges. And as you mentioned, obviously, there are some new competitive entrants, particularly in the DLBCL space. But we also have a number of catalysts that we're expecting, and we'll see when those come in, including publication of the Boston data we talked about, NCCN guidelines we talked about, and the actual DLBCL launch gaining momentum. So, you know, all of those create sort of pushes and pulls.

As transparent as we possibly can be which is we're certainly quite pleased that we grew 15% quarter over quarter. This quarter myeloma metrics continue to look good and obviously, we're starting to get contribution NGL Bcl and we we balanced that with we're still in the midst of a covert endemic which which does create some challenges as you.

Mentioned, obviously there are some some new competitive entrance, particularly on the Yelp DLP shelf space, but.

But we also have a number of of catalysts that we're hoping that we're expecting that we'll see when those come and including publication of Boston data, we talked about NCCN guidelines, we talked about and the actual DLT launch on gaining momentum. So it all goes create sort of pushes and pulls I think ultimately we can.

Taking a look to keep our eye on the Boston submission and working with the FDA and that piece as well as in Europe, because we know that that clearly the biggest driver of growth in the near term is going to be upon a boston approval and our ability to sell into the second line multiple myeloma. So those are really the things that we think drive growth over the next three to five.

Michael P. Mason: I think ultimately, you know, we continue to keep our eye on the Boston submission and work with the FDA on that piece, and as well as in Europe, because we know that clearly the biggest driver of growth in the near term is going to be a Boston approval and our ability to fail into second line multiple myeloma. So those are really the things that we think will drive growth over the next, you know, three to six to nine months, and we look forward to, you know, keeping abreast of all those. Okay, I got it.

Six to nine months and and we look forward to keeping abreast of all those things.

Okay got it thanks for taking the questions.

Our next question is from David Lebowitz from Morgan Stanley Go ahead.

Thank you very much for taking my question given that prescription demand increased from 12% to 15%.

Michael P. Mason: Thanks for taking the question. Our next question is from David Lebowitz from Morgan Stanley. Go ahead. Thank you very much. Unknown Speaker Given that prescription demand increased from 12, and similar between the two quarters, how is the cadence of those prescriptions relative? And what dynamics, I guess, are at play?

From second quarter to third quarter.

Sales growth ultimately stayed pretty similar between the two quarters or how is the cadence of those prescriptions relative to sales over the quarter.

And what dynamics I guess are at play, causing the conversions.

John Demery: Yeah, I think if the cadence is, you know, on a quarterly basis, I mean, on a monthly basis. Yeah, that's not something that we typically disclose, you know, on a monthly basis. I think in terms of where the scripts are coming from, certainly in DELVCL, they're largely coming from community-based physicians, which is a little bit different than I think some of the early uptake we saw in multiple myeloma, which was coming from both, you know, large academic sites as well as some community-based sites as well. I think that was your question. If I missed it, John, I don't know if you want to add anything. I thought that was the question as well.

Yes, I think your question if the cadence as you know on a quarter I mean on a monthly basis, yeah, that's not something that we typically disclose.

On a on a monthly basis I think in terms of.

Where the scripts are coming from certainly India, we see out there, they're largely coming from the from the community based physicians.

Which is little bit different than I think some of the early uptake we saw in multiple myeloma, which was coming from both large.

A large academic sites as well as some community based sites as well I think that was your question if I missed it John I don't know if you want to add.

I thought that was the question as well.

And with respect to the label sarcoma data given I guess.

Michael P. Mason: And with respect to the liposarcoma data, given, how does that, I guess, give you confidence? Well, I think I've said before, There are similarities and differences, and every tumor type is different. The fact that virtually there are really no very effective drugs for liposarcoma, and thankfully, we have aribulin approved, anthracyclines are generally approved, and trabectadine, but these are, you know, chemotherapies that are essentially all cytotoxic agents. These are large tumors. They're difficult for drugs to access, and the fact that we could show a real benefit in a third line, you know, a very difficult population, following at least two chemotherapies, we think is very important for reading to other solid tumors. These data show that exfovio clearly penetrates large masses.

Specifics regarding that tumor type.

How does that get you I guess give you confidence going forward with respect to other solid tumors.

Well I think I have said before.

You know there are similarities and differences in every tumor type is different the fact that virtually there are really no very effective drugs in line plus our call then and thankfully we have a regulator approved anthracyclines or generally approved.

And Tribeca, then, but but these are chemo therapies that are essentially all cytotoxic agents.

It's these are large tumors.

They're difficult for drugs to access and the fact that we could show a real benefit was in the third line varied.

Very difficult population following at least to chemotherapy is we think is is very important for reading to other solid tumors. This these data show that exposure clearly penetrates large masses. They can go in it can slow tumor growth, we'll see about some responses, perhaps which are quite unusual in this tumor, particularly in the sector.

Michael P. Mason: It can go in; it can slow tumor growth. We'll see some responses, perhaps, which are quite unusual in this tumor, particularly in the second and third line setting, especially for a non-cytotoxic agent, and hopefully, this gives those patients an oral option, but it does speak to the fact that this drug can penetrate into solid tumors, particularly connective tissue, which tends to be more difficult, so its positive results are always beneficial in cancer. This represents our third disease type and is quite different from the hematologic disorders that we've talked about before. We think this provides a great foundation. It also helps solidify some of the early data we've seen in combination that's been reported from the ESMO Place study and other studies. Thanks, Francis.

The third line setting, especially for another set of toxic agent and and hopefully this gives those patients that oral option, but it does speak to the fact that this drug can penetrate into solid tumors, particularly connective tissue, which tend to be more difficult. So it's positive results are always beneficial in cancer. This represents our third disease type.

And quite different from the human logic disorders.

Disorders that we've talked about before we think this provides a great foundation. It also helps solidify some of the early data we've seen in combination that's been reported from the ESMO play.

Place and other studies.

Hi, Thanks for answering my question.

Our next question is from Mike Oh from Baird go ahead.

Michael P. Mason: Our next question is from Mike Alts from Baird. Go ahead. Hi guys, thanks for taking the question and congrats on all the progress as well. I just had a follow-up on an earlier question related to the SEAL data, just wondering if you could maybe comment a little bit further on the safety profile you were seeing there beyond the discontinuation rate and maybe how that compares to the label, just trying to get a sense if there's anything notably different. I have a quick follow-up. Sure, what we can say is kind of what we said in our press release is that we see a, you know, a safety profile that's consistent with what you've seen before, qualitatively. Quantitatively, it tends to be substantially less, particularly on the cytopenias. Remember, these patients are coming in with only two prior cytotoxic therapy. There's not a lot of marrow suppression. They don't have disease in their bone marrow.

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

I just had a follow up on an earlier question related to the steel data just wondering if you maybe comment a little bit further on the safety profile you are seeing there beyond discontinuation rate and maybe how that compares to the label I'm just trying to get a sense, if there's anything notably different different there that we should be looking for and I have a quick follow up.

Sure. What we can say is kind of what we said in our press is that we see a let's.

A safety profile that is consistent with what you've seen before qualitatively Kwan.

Quantitatively, it's it tends to be substantially less particularly on the Cytopenias remember these patients are coming in with with only two prior cytotoxic therapy. So not a lot of marrow suppression. They don't have disease in their bone marrow bottom.

Bottom line is they have a much healthier marrow then the kinds of myeloma patients that we've treated even on Boston, even as compared to Boston. So you expect a lot less cytopenias, which is what we saw and frankly unfortunately, because these tumors are in the abdomen and can often compressed G.I. structures and the like the patients often come in with baseline nausea.

Michael P. Mason: Bottom line is they have a much healthier marrow than the kinds of myeloma patients that we've treated, even in Boston, even as compared to Boston. So, you expect a lot less cytopenias, which is what we saw. And frankly, unfortunately, because these tumors are in the abdomen and can often compress GI structures and the like, these patients often come in with baseline nausea, fullness, and abdominal pain, which may or may not get better or worse on expovia.

And fullness abdominal pain.

Which you know, which which may or may not get get better or worse Onyx folio, so expect higher baseline levels of nausea, but basically this looks like selinexor with outside opinion.

Michael P. Mason: So, expect higher baseline levels of nausea. But basically, this looks like cell annexure with cytopenias. Gotcha. That's helpful.

Got you that that's helpful and then.

Just a quick follow up you mentioned a couple couple other opportunities in solid tumors and this liposarcoma kind of gives you more confidence there maybe you could just talk a little bit about timeline for some of these other tumor types or your strategy.

Michael P. Mason: And then, This is just a quick follow-up. You mentioned a couple of other opportunities in solid tumors, and this liposarcoma kind of gives you more confidence there. Maybe you could just talk a little bit about timelines for some of these other tumor types or your strategies for some of these tumor types. Thanks.

And some of these tumor types. Thanks.

Yeah, I think in 2021, we're going to be elaborating. Some some additional studies, we already have ongoing phase one combination study of.

Michael P. Mason: I think in 2021, we're going to be elaborating some additional studies. We already have ongoing a phase one combination study of felinexer plus dosetaxel phase one, two, I should say, with Steli plus dosetaxel based on some not yet public data from an investigator-sponsored trial by the Atomic Group. This is in patients with non-small cell lung cancer, both KRAS mutant and KRAS wild type previously treated non-small cell lung cancer, where we were seeing some interesting things, and we want to recapitulate that in the company's hands. We have studies ongoing in GBM where we have announced and will continue to update on a single agent, approximately 10% bonafide response rate in temozolomide radiation relapsed or refractory GBM patients that have a dire prognosis.

Well next surplus Ddos attacks on phase one two I should say was selling plus ddos attacks all based on so.

Not yet public data from an investigator sponsored trial by the atomic group on this isn't patients non small cell lung, both K Ras mutants and K Ras Wild type previously treated non small cell lung cancer.

Where are we were seeing some interesting things and we want to recapitulate that the company's hands. We have studies ongoing in GBM, where we have announced and will continue to update on a single agent approximately 10%.

Bonafide response rate in a temozolomide radiation relapsed or refractory GBM patients that have a dire prognosis.

We have we have data with a bunch of different solid tumors with.

Michael P. Mason: We have data with a bunch of different solid tumors in combination with platinum and taxol, including in patients who've already seen platinum and or taxol. And we'll be moving on some of these both internally and again through our NCI collaboration going forward more in 2021 on those. Lastly, we think these are very exciting data, and our investigators are quite excited about the potential combination with K-TRUDA. You know, amongst nine patients with untreated melanoma, we saw a 55 percent response rate, including two CRs, in that initial study. And importantly, there were no major auto-inflammatory side effects reported, which is quite distinct from similar multi immune modifier combinations. And if we're able to combine it with K-Trut in melanoma, that opens up possibilities in other tumors. But importantly, it may open up those possibilities in melanoma and other tumors without the major auto-inflammatory side effects that some of the sort of, you know, Avivo plus Yerba Boy types of combinations can deliver.

In combination with platinum taxol, including in patients, who have already seen platinum and or taxol.

And we'll be moving on some of these both internally and again through our NCR collaboration going forward more in 2021 on those.

Lastly.

We saw very exciting data and our investigators are quite excited about the potential combination with keytruda.

You know amongst nine patients with untreated melanoma, we saw 55% response rate, including to see ours in that initial study and importantly, there were no major auto inflammatory side effects recorded which is quite distinct from a similar multi immune modify.

Fire combinations and if were able to combine with keytruda in melanoma that opens up possibilities in other tumors, but importantly, it may open up those possibilities in melanoma and other tumors without the major auto inflammatory side effects that some of the sort of opdivo plus yervoy types of combinations can deliver.

Okay, great. Thank you.

Unknown Attendee: Okay, great. Thank you. Our next question is from Ed Wright from H.C. Wainwright. Go ahead.

Our next question is from Ed White from H.C. Wainwright go ahead.

John Demery: Congratulations on the SEAL data and just a couple of questions on solid tumors. So I know you mentioned the GBM study and the phase one, two trial; the first patient was enrolled in June with this large 400 patient trial. I'm just wondering how the enrollment is going in that. Has it been impacted by the pandemic?

Hi, congratulations on the field data and just a couple of questions on solid tumors.

So I think you had mentioned the GBM study and the phase one two trial the first patients enrolled in June.

With this large 400 patient trial.

Im just wondering how the enrollment is going in that it has been impacted by the pandemic.

John Demery: When can we see data? And then the second question is, what are your thoughts on the launch strategy for solid tumors? So liposarcoma is small. What is your strategy for hiring a sales force?

When can we see data.

And then second question is just what are your thoughts on the launch strategy in solid tumors, so like with sarcoma small.

What is your strategy for hiring a sales force how many people and how do you build up in solid tumors. Thanks.

John Demery: How many people and how do you build it up in solid tumors? Thanks. Sure.

Sure. So when asked Dr shock them to take the first question about the accrual on the GBM study.

Unknown Attendee: So I'm going to ask Dr. Shackham to take the first question about accrual in the GBM study. The study has three arms, including two arms in patients with GBM that are newly diagnosed and then another arm looking at patients with relapsed refractory disease. And enrollment is going well in all arms. It's a 3 plus 3 design.

Sure.

Hi, the study is to be on.

Including 2008.

Gentlemen, you keep them that done nearly diagnosed and and then another I'm looking at things sentiment that we not.

Talk to me this is and enrollment is going well and all the parts they design.

And we don't see any impact from the cooling it said none enrollment for this study the sites on gauge and the.

Unknown Attendee: And we don't see any impact from the Corona study on enrollment for this study. The sites are engaged, and the study is moving forward. Maybe just quickly on the solid tumor side of things, I think certainly within the life of sarcoma, the vast majority of patients in the US will be treated, and all sarcomas are treated at centers of excellence across the US. There's probably about 90 or so of them total, and then you can narrow that down to probably 30 or so that are seeing the lion's share of patients here in the US.

I studied moving forward.

[laughter].

Yeah, maybe just quickly on the the solid tumor side of things I think certainly within the light Michael Sarcone space. The vast majority of patients in the us will be treated and for with all sarcoma are treated at centers of excellence across the U.S., there's probably about nine years sold them total and then you can narrow that down to probably.

30, or so that are seeing the.

Lions share of patient journey U.S. Betsy.

Thats something we could we could certainly do from a commercial standpoint with a handful of folks whether those are you know medical science liaisons or sales reps or a combination, but that's certainly a fairly straightforward call point at these centers of excellence as you start to get out too.

John Demery: That's something we could certainly do from a commercial standpoint with a handful of folks, whether those are medical science liaisons or sales reps or a combination. But that's certainly a fairly straightforward call point at the centers of excellence. As you start to get out to the endometrial cancer study, the endo study, knock on wood, should that study be positive? That's obviously a much larger solid tumor indication. These patients are seen at a very significantly large number of sites. We'd have to take a look at what that commercial model looks like and make a decision.

The endometrial cancer study the Endo study knock on what should that study the positive that's obviously a much larger solid tumor indication.

These patients are seeing that vastly a significant number of sites. So we'd have to take a look at what that commercial model looks like and make a decision, but certainly that would be a a terrific.

Michael P. Mason: But certainly, that would be a terrific issue to have to think about how we would commercialize an endometrial cancer drug. And we have a follow-up from Peter Lawson from Barclays.

Terrific just you'd have to think about how we would commercialize and mutual cancer.

I'm good how question and we have a follow up from Peter Lawson from Barclays Go ahead.

Hey, Thanks for taking my question just congrats on the silicone mandates are and will.

Michael P. Mason: Hey, thanks for taking my question. I just want to congratulate you on the psychoma data, and will you be able to submit that to the EU, or would you need a different trial, and how should we think about the patient? that you can initially treat with using that data as a label.

Will you be able to submit that to the you would you need to.

The different trial and how should we think about the patient.

You can initially treat.

With it using that data as a as a label.

Michael P. Mason: Well, this trial did receive positive expert advice from the EU's scientific advice group, from their scientific advice group, so it was discussed with them. It was approved with them, and we do believe it could serve for approval in the EU.

Well. This this trial did receive positive expert advice from the EU scientific from their scientific advice group. So its been discussed it was discussed with them. It was approved with them and we do believe it could serve for approval in the EU. The on label indication there would be patience with differentiated life of sarcoma.

Michael P. Mason: The on label indication would be patients with de-differentiated liposarcoma that have received two prior systemic therapies and at least two buyers. And what number of patients, because there are around, what, 2,000? Patients. That's what we'd be thinking about.

That have received two prior systemic therapies.

And at least one prior systemic and what number of patients you visit <unk> <unk> 2000.

Patients will that's a way yeah, we'd be thinking about okay.

Michael P. Mason: Okay. Yeah. And then on endometrial, is that the next data after sarcoma, or what should we think about as the next solid tumor data? Well, in terms of randomized phase 3 data, yeah, I can say, with a little tongue in cheek, it's hard. These are huge trials.

And then on the endometrial is done the next data up to <unk>, what should we think about the next solid tumor deal in terms of it in terms of randomized phase three day.

I can say with a little tongue in cheek. Its hard to these are huge trial that started to conduct a lot of that especially the company our size, but yes that is the next one and that should be out by the end of next year.

Michael P. Mason: It's hard to conduct a lot of them, especially with a company our size, but yes, that is the next one, and that should be out by the end of next year. There will be updates during the year with other combinations, including in both hematologic and solid tumors, as well as potentially data within the next year, say, in myelofibrosis and other areas.

So any updates starting the year with other combinations, including in both hematologic and solid tumors as well as potentially data within the next year say in myelofibrosis and other areas.

Got you, Okay, and then just on multiple myeloma deal Bcl, you got a sense of the duration of treatment.

John Demery: Thank you. And then just on multiple myeloma, DRBCL, do you get a sense of the duration of treatment for multiple myeloma or DLBCL? Well, I mean, across our specialty pharmacy network, it's about three, three months on average per patient. Now again, you know, DLBCL just, just started.

In multiple more liberal.

Bcm.

Yeah, well I mean, we're at quarter end about I mean across our specialty pharmacy that where it gets about three three months on average per patient now again, you know the LTL Bcl just just starting so those patients are not at three yet and you know you'll have paid.

John Demery: So those patients are not at three yet. And you know, you'll have patients out for, you know, 10-12 months, some longer, and you'll have patients that, you know, don't get a response after one or two months. But the average right now is about three months. And it's been climbing. Someone asked an earlier question, you know, how much higher can it go?

Just out for you know 10 12 months some longer and you are patients that don't get a response after one or two months, but certainly the the average right now is about three months and it's been climbing.

Someone asked earlier question you know how how much higher can it go Oh, we think it probably could go a little bit higher.

John Demery: We think it probably could go a little bit higher, but it probably can go substantially higher once we, if and when we get the Boston indication, because those patients in the second and third line obviously stay on the drug for much longer periods of time. And just a final question just around guideline changes: when do you think that happens? I assume you mean for myeloma. The way it works procedurally is that you have to have a publication.

But it probably can go substantially higher once we if and when we get the Boston indication because those patients in the second and third line, obviously stay on drug for much longer periods of time.

Great. Thank you and just the final question just around.

Guideline changes when do you think that happened.

I assume you mean for myeloma.

The way it works procedurally is you have to ever a publication, we believe that publication will be out before the end of the year there will be a publication in a peer reviewed journal coming out with.

Michael P. Mason: We believe that publication will be out before the end of the year. There will be a publication in a peer-reviewed journal coming out. That will be submitted to the NCCN committee, and they will determine the timing of when if and when they add the regimen to their recommendation. Could that be year-end, or do you think that kind of...

That will be submitted to the NCCN committee and they will determine the timing of when if and when they add the regimen to their recommendations.

Could that be yearend to do things like kind of naturally with it really depends on the publication it could be it depends on the publication timing of the timing of the NCCN Committee. In addition to Boston publication, we will be submitting the other single arm.

Michael P. Mason: Potentially, it really depends on the publication. It could be, it depends on the publication timing and the timing of the NCCN committee. In addition to the Boston publication, we will be submitting the other single arm studies, particularly daratumumab, Kyprolis, and Pamela, and those could potentially follow, but all of this is dependent, of course, on publication in the NCC and adjudication.

Study results, particularly with with Daratumumab Kyprolis.

And Pomalyst.

And those could potentially follow but all of this depends upon of course publication NCCN adjudication.

Great. Okay. Thanks much thanks.

Michael P. Mason: Great. Okay. Thank you so much. Thank you. Well, thank you, everybody. Appreciate your following us, and we look forward to talking to you again in the near future. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Well. Thank you everybody I appreciate your following with US and we look forward to talking to you again in the near future Fest.

The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

It is for the local.

Test of English as a foreign.

Operator: Test of English as a pharmacist