Q3 2021 Karyopharm Therapeutics Inc Earnings Call

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Claudia Guntek: Good morning, my name is Claudia Guntek, and I will be the conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics third quarter 2021 financial results conference call.

Good morning. My name is Carter, you can take I wouldn't be conference operator today.

This time I would like to welcome everyone to the carrier from Therapeutics third quarter 2021 financial results conference call.

Claudia Guntek: There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Jason.

He will be a question and answer session to find out.

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

I would now like to turn the call over to Jason Finkelstein Agua partners.

Jason: Thank you, Claudia. Thank you all for joining us on today's conference call to discuss Karyopharm's third quarter 2021 financial results and business updates. Today I'm joined by Richard Paul, President and Chief Executive Officer; Ms. Sohanya Cheng, Senior Vice President, Sales and Commercial Operations; Dr. Jaden Shah, Chief Medical Officer; Mr. Mike Mason, Chief Financial Officer; Mr. Stephen Michener, Chief Business Officer; and Dr. Sharon Shackham, Chief Scientific Officer. During today's call, as outlined on slide two, Richard will provide some introductory remarks, Sohanya will provide an update on our Expovio commercial progress, and Sheaton will highlight recent pipeline advances. And then Mike will discuss the third quarter, financial results, highlights, and guidance.

Thank you Claudia Toussaint you all for joining us on today's conference call to discuss carrier farms third quarter 2021 financial results and business update.

Today I'm joined by Mr. Richard Paulson, President and Chief Executive Officer, Mr. Han you Chang.

Your Vice President sales and commercial operations, Dr. <unk> Shah Chief Medical Officer, Mr. Mike Mason, Chief Financial Officer.

Mr. Stephen Michener, Chief business Officer, and Dr. Chevron Shackup Chief Scientific officer.

During today's call as outlined on slide two Richard will provide some introductory remarks, Ohio will provide an update on our commercial progress.

We will highlight recent pipeline back then and then Mike will discuss the third quarter financial results highlights and guidance.

Jason: We'll conclude with some thoughts from Richard on upcoming milestones, and then we'll move to the Q&A portion of the call. This morning, we issued a press release detailing Karyopharm's results for the third quarter of 2021. This release, along with the slide presentation that we plan to reference during today's call, is available on our website, 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 Provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide 9. These include statements about our future expectations.

We will conclude with some thoughts from Richard.

How many milestones and they will move to the Q&A portion of the call.

Earlier. This morning, we issued a press release detailing carrier Power's results for the third.

Third quarter of 2021.

It's really along with a slide presentation that we plan to reference during today's call are available on our website at carrier, Florida Dot 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 provisions under the private Securities Litigation Reform Act of 1995 as outlined on slide three.

These include statements about our future expectations clinical developments and regulatory matters and timeline.

The success of our products and product candidates, including our expectations relating to the commercialization of <unk> in Mexico, IPO financial projections, and our plans and prospects.

Jason: Clinical Developments and Regulatory Matters and Timelines. [inaudible] 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 the SEC, and other filings that we may make with the SEC. Any forward-looking statements represent our views as of today only, but we may elect to update these forward-looking statements at some point in the future.

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 the SEC and in other filings that we may make with the SEC in the future.

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

Jason: We specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I will now turn the call over to Richard Paulson. Please turn to slide four. Thank you, Jason.

Subsequent to today.

I'll now turn the call over to Richard Paulson, Please turn to slide four.

Thank you, Jason and good morning, everyone.

Richard A. Paulson: And good morning, everyone. Now, please turn to slide five. After joining as president and CEO in May and now having been in this position for a full physical quarter, I've valued the opportunity to meet and speak to many of our shareholders, customers, and investigators. From our insightful conversations, I've enjoyed the enthusiasm and the commitment to our science. With the ability to positively impact patients, work across many different types of cancers, I look forward to continuing these interactions in the future, as our future outlook for Karyopharm is rooted in three key fundamentals. First, our Execution Expovios launch.

Now please turn to slide five.

After joining as president and CEO in May and now having been in this position for a full fiscal quarter.

Value the opportunity to meet and speak to many of our shareholders customers and investigators.

From our insightful conversations I've enjoyed the enthusiasm and commitment to our science.

With the ability to positively impact patients work across many different types of cancers I look forward to continuing these interactions in the future as our future outlook for carryover arm is rooted in three key fundamentals.

First is our execution <unk> launch currently <unk> is approved in three indications in the U S and multiple myeloma and diffuse large b cell lymphoma.

Richard A. Paulson: Currently, Expovios is approved in three indications in the US, for multiple myeloma and diffuse large B-cell lymphoma. We have a tremendous opportunity in front of us to continue expanding Expovios' breadth and depth through continued head-down execution in the approved indications and advancement of key late-stage myeloma studies. We delivered strong commercial results in the third quarter with a significant increase in net product revenues compared to the second quarter of 2021, driven by an acceleration in demand growth for Expovio.

We have a tremendous opportunity in front of us to continue expanding <unk> breadth and depth through continued head down execution in the approved indications and advancement of key late stage myeloma studies.

We delivered strong commercial results in the third quarter with a significant increase in net product revenues compared to the second quarter of 2021, driven by an acceleration in demand growth for <unk>.

Richard A. Paulson: Expovio continues to move into earlier lines of therapy in multiple myeloma as a new effective modality that can become the standard of care in Second Line Plus, which Sohanya will discuss later in the call. In parallel, we will continue to build our foundation globally. We are anticipating that the European Medicine Agency's Committee for Medicinal Products for Human Use will complete the review of our next foveal marketing application as a second line plus treatment for multiple myeloma, which is expected during the first half of 2022. Second, our pipeline.

<unk> continues to move into earlier lines of therapy in multiple myeloma as a new effective modality that can become the standard of care in second line, plus which was so high on here will discuss later in the call.

In parallel we will continue to build our foundation globally.

We are anticipating that the European Medicine Agency Committee for medicinal products for human use will complete their review of our <unk> marketing application as a second line plus treatment for multiple myeloma, which is expected during the first half of 2022.

Second is our pipeline as we advance our pipeline we are actively working to prioritize our clinical development plan in Hematological malignancies, and solid tumor indications with the highest unmet need probability of success and attractive market opportunities.

Richard A. Paulson: As we advance our pipeline, we are actively working to prioritize our clinical development plan and hematological malignancies and solid tumor indications with the highest unmet need, probability of success, and attractive market opportunities. This includes our Phase 3 Siendo study evaluating selonexor and endometrial cancer, where there are no approved treatments for maintenance therapy following chemotherapy in any line of treatment. Top-line results for this study are expected by the end of this year or early next year and, if positive, will further reinforce the therapeutic potential of Salinexor in solid tumor indications.

This includes our phase III <unk> study evaluating selinexor in endometrial cancer, where there are no approved treatments for maintenance therapy, following chemotherapy and any line of treatment.

Top line results for this study are expected by the end of this year or early next year and if positive will further reinforce the therapeutic potential of selinexor in solid tumor indications.

Richard A. Paulson: We are also advancing targeted late-stage clinical studies across multiple hematological and solid tumor indications that Jayten will review later on in our call. And we look forward to hosting a Virtual Investor Day on Wednesday, December 8, to present further details on our commercial and pipeline priorities. To support our focused growth plan, we are well capitalized to fund our operations with a cash runway into the middle of 2023. Third, our people foster scientific creativity, pioneering technologies, and are dedicated to delivering Expovio to patients.

We are also advancing targeted late stage clinical studies across multiple hematological and solid tumor indications that Jason will review later on our call.

And we look forward to hosting our virtual Investor day on Wednesday December eight to present further details on our commercial and pipeline priorities.

To support our focused growth plan, we are well capitalized to fund our operations with a cash runway into the middle of 2023.

Third is our people, who foster scientific creativity pioneering technologies and are dedicated to delivering <unk> to patients.

Richard A. Paulson: We support a culture of innovation, courage, urgency, resilience, and energy captured in our iCure values with our employees and our collaborators. I'd like to sincerely thank our team who are focused on helping patients in need and delivering for shareholders. As we turn now to slide six, I would like to turn the call over to Sohanya Cheng, our Senior Vice President of Sales and Commercial Operations, for her review of the commercial results for the quarter. Thank you.

We support our culture of innovation courage urgency resilience and energy captured in our eye care values with our employees and our collaborators I'd like to sincerely. Thank our team who are focused on helping patients in need and delivering for shareholders.

As a return now to slide six I would like to turn the call over to Sarnia Chang, our senior Vice President of sales and commercial operations for her review of the commercial results for the quarter. So Anya.

Richard A. Paulson: Thank you, Richard. And good morning, everyone. We have accelerated growth in the third quarter and continue to make strong progress across key indicators since our second line plus launch at the beginning of this year. Please now turn to slide seven. Total Expovio net product sales for the quarter were $26.7 million, a 32% increase quarter over quarter and a 25% increase year over year.

Thank you Richard and good morning, everyone.

Accelerated growth in the third quarter and continue to make strong progress across key indicators since our second line plus launch at the beginning of this year.

Please now turn to slide seven.

Total <unk> net product sales for the quarter were $26 7 million, a 32% increase quarter over quarter, and a 25% increase year over year.

Sohanya Cheng: These increases were driven by strong execution, with over 9000 prescriptions filled as of the end of the third quarter. We continue to see a positive shift from the pentarefractory setting towards earlier lines, with the most rapid growth this year in the third line, as we continue to focus our messaging on the white space in myeloma between the second and fourth lines, where using a new class of therapy could be vital for the success of patients outcomes.

These increases were driven by strong execution with over 9000 prescriptions filled as at the end of the third quarter.

We continue to see a positive shift from the penta refractory setting towards earlier lines with the most rapid growth. This year in the third line as we continue to focus our messaging on the white space in myeloma between second and fourth line we're using.

A new class of therapy could be vital to the success of patients outcomes.

We are expanding in breadth and depth of use of <unk>.

Sohanya Cheng: We are expanding the breadth and depth of use of Expovio with strong growth in the community setting. We continue to add more accounts every quarter and increase penetration at top myeloma accounts. In addition, our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product and growing confidence in utilization in earlier lines, as physicians have an increasingly positive experience with the lower dose once weekly expovial-based triplet regimen. However, while patient visits and field activity improved in the third quarter, they have not returned to pre-COVID levels.

With strong growth in the community setting.

We continue to add more accounts every quarter and increased penetration at top myeloma accounts.

In addition, our intend to prescribe data continues to show a sustained improvement in the efficacy and safety perception of the product.

And growing confidence in utilization in earlier lines as physicians have an increasingly positive experience with the lower dose once weekly <unk> based triplet regimens.

While patient visits and field activity improved in the third quarter. They have not returned to pre COVID-19 levels.

Sohanya Cheng: We will continue to monitor any further COVID impact and remain focused on strong execution and positioning Expovio as a standard of care in Second Line Plus. With the foundation we're laying now, and with a rapidly advancing myeloma pipeline, we hope to continue to drive steady growth in the near, mid, and long term. If you will now advance to slide eight, I will turn the call over to Jayden to highlight our clinical development efforts to further build our position in multiple myeloma, other hematological, and solid tumor indications. Jayden

We will continue to monitor any further COVID-19 impact and remain focused on strong execution and positioning <unk> as a standard of care in second line plus.

With the foundation were laying now and with our rapidly advancing myeloma pipeline, we hope to continue to drive steady growth in the near mid and long term.

If you will now advance to slide eight I will turn the call to Jason to highlight our clinical development efforts to further build our position in multiple myeloma other hematological and solid tumor indications.

Jason Thank you Tanya.

Jayden: Thank you, Sohanya. If you'll now please turn to slide nine. I'd first like to touch on our key regulatory advancements. As you know, our marketing authorization application in the EU has been validated and is currently under review by the CHMP. And, as Richard mentioned earlier, we expect this review to be complete during the first half of 2022. Meanwhile, we are seeing progress with bringing Selenexer to patients in need across the globe by our ex-US partners, including a new drug submission that was recently submitted by Forest Therapeutics and accepted for review by Health Canada.

If you'll now please turn to slide nine I would first like to touch on our key regulatory advancements.

As you know our marketing authorization application in the EU has been validated and is currently under review by the <unk> and as Richard mentioned earlier, we expect this review to be complete during the first half of 2022.

We are seeing progress with bringing selinexor to patients in need across the globe are ex U S partners.

Including a new drug submission that was recently submitted by Forest Therapeutics and accepted for review by Health Canada.

In addition, we saw the approval of Selinexor for the treatment of patients with multiple myeloma and <unk> in South Korea, and several new drug applications in multiple Asia Pacific markets, including China, Hong Kong, Australia, Singapore and Taiwan.

Jayden: In addition, we saw the approval of Selenexor for the treatment of patients with multiple myeloma and DLBCL in South Korea and several new drug applications in multiple Asia-Pacific markets, including China, Hong Kong, Australia, Singapore, and Taiwan, all of our partner antigenic. Turning now to slide 10, our pipeline. We are advancing our pipeline across multiple oncologic indications with a high unmet need. This is a snapshot of our clinical pipeline, including key new clinical studies that were recently initiated, including the MF34 study evaluating Selinexer in combination with Ruxolitinib in treatment naive myelofibrosis.

All of our partner Entergy.

Yes.

Turning now to slide 10 for our clinical stage programs.

We are advancing our pipeline across multiple oncologic indications with a high unmet need.

This is a snapshot of our clinical pipeline, including key new clinical studies, our recently initiated.

Including the MF 34 study evaluating selinexor in combination with <unk> in treatment naive myelofibrosis.

The male 33 studies evaluating selinexor in combination with <unk> in patients with locally advanced or metastatic melanoma.

Jayden: The MEL33 study evaluating Selenexer in combination with pembrolizumab in patients with locally advanced or metastatic melanoma. And finally, the 801 study evaluating Seltenexer in myelodysplastic syndrome. We'll provide more details on these studies in just a moment. We're actively prioritizing our pipeline and look forward to communicating our refined corporate vision and objectives at our Virtual Investor Day that's planned for December 8, 2021.

And finally, the 801 study evaluating <unk> in Myelodysplastic syndromes.

We will provide more details on these studies in just a moment.

We're actively prioritizing our pipeline and look forward to communicating our refined corporate vision and objectives at our virtual Investor Day, that's planned for December eight 2021.

Okay.

At this time the phase III <unk> study represents the next major milestone and we remain highly encouraged by the opportunity for Selinexor in patients with endometrial cancer in the maintenance study, which is outlined on slide 11.

Jayden: At this time, the Phase 3 CIANDA study represents the next major milestone, and we remain highly encouraged by the opportunity for Selenexer in patients with endometrial cancer in the maintenance study, which is outlined on slide 11. Endometrial cancer is the most common gynecological cancer in the U.S., with over 66,000 new cases in 2021. While most women are diagnosed with early stage disease and have a good prognosis after surgery alone, approximately 14,000 patients each year will present with advanced or metastatic disease. These patients are typically treated with chemotherapy for four to six cycles. And as there are no treatments approved for maintenance,

Endometrial cancer is the most common gynecological cancer in the U S with over 66000, new cases in 2021.

While most women diagnosed with early stage disease and have a good prognosis. After surgery alone approximately 14000 patients each year, who will present with advanced or metastatic disease.

These patients are typically treated with chemotherapy for four to six cycles.

And as there are no therapies approved for maintenance.

Jayden: After chemotherapy, patients are followed with close observation and a "watch and wait" approach. Unfortunately, the treatment is not curative, and there is a short remission time, typically four to six months before the disease returns. And when their disease progresses, these patients are typically treated with additional chemotherapy, immunotherapy, or targeted agents. Maintenance therapy has been a very effective strategy in multiple diseases to extend the time in remission. The concept of maintenance therapy has been very well established in gynecological malignancies with PARP inhibitors in ovarian cancer.

After chemotherapy patients were followed with close observation in a watch and wait approach.

Unfortunately, the treatment is not curative and Theres a short remission time typically four to six months before the disease returns and.

And when their disease progresses. These patients are typically treated with additional chemotherapy immunotherapy or target genes targeted agents.

Yeah.

Maintenance therapy has been a very effective strategy in multiple diseases to extend the time in remission.

Concept of maintenance therapy is well established and gynecologic malignancies with PARP inhibitors in ovarian cancer yet.

Jayden: Yet there are no approved maintenance therapies for patients with endometrial cancer after chemotherapy. To put the potential opportunity for endometrial cancer in perspective, 14,000 patients each year are treated with chemotherapy and could potentially benefit from maintenance therapy, with this number estimated to grow in the future. Looking at slide 12, in our initial Phase II SIGN study, we looked at single-agent Selenixir in patients with chemotherapy-refractory disease with a high disease burden that's growing and not in remission.

Yet there are no approved maintenance therapy for patients with endometrial cancer post chemotherapy.

To put the potential opportunity in endometrial cancer and perspective.

14000 patients each year are treated with chemotherapy and could potentially benefit from maintenance therapy.

With this number is estimated to grow in the future.

Looking at Slide 12 in our initial phase two sine study.

We look at single agent Selinexor in patients with chemotherapy refractory disease with a high disease burden, that's growing and not in remission.

In this population with currently available treatments most patients either do not respond or of a transient stable disease for less than eight weeks.

Jayden: In this population, with currently available treatments, most patients either do not respond or have transient stable disease for less than eight weeks. In this patient population, we demonstrated the activity of single-agent Selenexer, with nearly one-third of patients in this refractory setting experiencing disease control, which is defined as those with a complete response, partial response, or stable disease for at least three months. In this third-line setting with chemotherapy-refractory disease, Cellinexer demonstrated a median duration of disease control of 6.3 months.

In this patient population, we demonstrated the activity of single agent Selinexor.

With nearly one third of patients in this refractory setting with disease control, which is defined as those with a complete response partial response or stable disease for less.

At least three months.

In this third line setting with chemotherapy refractory disease Selinexor demonstrated a median duration of disease control of six three months.

Jayden: This data supports the evaluation of Selenexer in earlier lines of therapy. To be clear, in contrast to sign, In this CNDO study, evaluate Selenexer in the first line setting and in a chemotherapy sensitive setting, as you see on slide 13. The Phase 3 study is evaluating the role of once-weekly, low-dose Selenexer in patients with endometrial cancer as maintenance therapy post-chemotherapy.

This data supports the evaluation of Selinexor in earlier lines of therapy.

To be clear in contrast to sign.

In the <unk> study evaluating selinexor in the first line setting.

Setting in chemotherapy sensitive setting as you see on slide 13.

The phase III studies evolving the role of once weekly low dose selinexor in patients with endometrial cancer as maintenance therapy post chemotherapy.

The <unk> study is enrolling approximately 248 patients randomized two to one to receive either 80 milligrams of Selinexor once weekly or placebo.

Jayden: The SIENDO study is enrolling approximately 248 patients, randomized 2 to 1, to receive either 80 mg of Selenixer once weekly or placebo. Eligible patients include those who have stage four or recurrent disease, who have completed a course of taxane-platinum combination chemotherapy and achieved either a partial or complete response. The primary endpoint of the trial is an improvement in progression-free survival, or PFS, as defined from the time of randomization until death or disease progression.

Eligible patients include those who have stage four or recurrent disease, who have completed the course of taxane or platinum combination chemotherapy.

<unk>, either a partial or complete response.

The primary endpoint of the trial as an improvement in progression free survival or PFS as defined from the time of randomization until death or disease progression.

In November of 2020, we announced the trial had passed as planned interim futility analysis and so the study has continued as planned.

Jayden: In November of 2020, we announced the trial had passed its planned interim futility analysis, and so the study has continued as planned. Recruitment is on track. And we expect the top-line data, which is event-driven, by the end of this year or early next year. Turning now to slide 14, we recently commenced dosing in an expanded Phase 2 study evaluating Eltenexer, our second novel oral signal compound, in patients with MDS. MDS occurs when the hematopoietic stem cells within the marrow become abnormal and create immature blood cells that are not able to function properly, which leads to a significantly low blood count.

Recruitment is on track and.

And we expect the top line data, which is event driven by the end of this year or early next year.

Okay.

Turning now to slide 14, we recently commenced dosing in an expanded phase III study evaluating <unk>, our second novel oral sine compound in patients with Mds.

MBS occurs when the hematopoietic stem cells within the marrow become abnormal and create immature blood cells that are not able to function properly.

Which leads to significantly low blood counts.

So is estimated at approximately 15000, new cases of Mds occur in the U S annually with a prevalence of approximately 60000 in the U S.

Jayden: It is estimated that approximately 15,000 new cases of MDS occur in the U.S. annually, with a prevalence of approximately 60,000 in the U.S. With an aging population and an improving awareness of the disease, this incidence is expected to increase. Hypomethylating agents, or HMAs, are the current standard of care for patients with newly diagnosed high-risk MDS. However, only 50% of patients respond, and these responses typically last less than two years. Unfortunately, HMA therapy is not curative, and all patients ultimately develop disease that's refractory to HMA therapy.

With an aging patient aging population and an improving awareness of the disease. This incidence is expected to increase.

Hypo monthly behavior to HMH or the current standard of care for patients with newly diagnosed high risk Mds.

However, only 50% of patients respond and these responses typically last less than two years.

Unfortunately, HMA therapy is not curative and all patients ultimately develop disease that is refractory to HMA therapy.

There are no class of drugs approved in HMA refractory disease.

Jayden: There is no class of drugs approved for HMA refractory disease, and the prognosis for HMA refractory diseases is poor, with a median overall survival of four to six months. There are no agents currently approved for HMA refractory disease, and the need for novel efficacious agents is critical. If you turn to slide 15, you will see that in our Phase 1 study, single-agent eltanextra showed clear single-agent activity in patients with high-risk relapsed MDS that was refractory to HMAs.

And the prognosis and HMA refractory disease is poor with a median overall survival of four to six months.

There are no agents currently approved for HMA refractory disease.

And the need for novel Efficacious agents is critical.

If you turn to slide 15, you will see in our phase one study single agent <unk> showed clear single agent activity in patients with high risk relapsed Mds that was refractory to HMH.

In that study <unk> demonstrated a 53% overall response rate.

Jayden: In that study, Eltenexor demonstrated a 53% overall response rate and a median overall survival of 9.9 months, doubling historical controls of four to six. At the recommended phase two dose of 10 milligrams, L-Tonexer monotherapy was well tolerated with a low incidence and grade of gastrointestinal events. However, exacerbation of cytopenia occurred in 20 to 40% of patients.

And a median overall survival of nine nine months doubling historical controls of four to six months.

At the recommended phase II dose of 10 milligrams <unk> mono therapy was well tolerated with a low incidence and grade of gastrointestinal events.

Exacerbation of Cytopenia as occurred in 20% to 40% of patients.

Based on a promising signal observed in the phase. One study. We are pleased to have recently initiated dosing in the phase II expansion to design of which you can see on slide 16.

Jayden: Based on a promising signal observed in the Phase 1 study, we're pleased to have recently initiated dosing in the Phase 2 expansion, the design of which you can see on slide 16. Finally, I'd like to highlight our emerging program in myelofibrosis. Turning now to slide 17. In the U.S., it's estimated that approximately 5,000 cases of myelofibrosis occur annually with a prevalence of 16,000 to 18,500 in the U.S. Currently, in myelofibrosis, there's only a single class of drugs, JAK inhibitors, which are approved and used commonly in the first line.

Finally, I'd like to highlight our emerging program in myelofibrosis.

Turning now to slide 17.

In the U S is estimated at approximately 5000 cases of myelofibrosis occur annually with a prevalence of 16 to 18500 in the U S.

Yes.

Currently.

<unk> in myelofibrosis, Theres only a single class of drugs JAK inhibitors, which are approved and used commonly in the first line.

Unfortunately, <unk> is not curative and the disease often progresses within four years for primary responders.

Jayden: Unfortunately, ruxolidinib is not curative, and the disease often progresses within four years for primary responders. There are no other classes of drugs approved for relapsed myelofibrosis, and the need for novel therapeutics is critical. ......... Turning now to slide 18. In preclinical studies, inhibition of nuclear cytoplasmic transport by Selenexer or Eltenexer reduced survival of cells expressing JAK in both ruxolinib-sensitive and resistant cells.

There are no other class of drugs approved in relapsed myelofibrosis and the need for novel Therapeutics is critical.

Turning now to slide 18.

In preclinical studies inhibition of nuclear cytoplasmic transport by Selinexor or <unk> reduced survival of cells, expressing Jack and both <unk> sensitive and resistant cells.

These data led to an investigator sponsored phase II study evaluating once weekly low dose selinexor.

Jayden: These data led to an investigator-sponsored Phase 2 study evaluating once-weekly low-dose Selinexer in patients with ruxolipnib-resistant myelofibrosis. The data from this investigator-sponsored Phase 2 study have been submitted to ASH 2021 for potential presentations during the fourth quarter. On slide 19, you can see the study design for a new company-sponsored randomized multicenter phase 2 study, which is expected to start during the fourth quarter. We look forward to updating you on the progress of this and all of our important studies at our Virtual Investor Day. With that, I'll now advance to slide 20 and turn the call over to Mike Mason to review the quarterly financials.

Patients with Russ Russel Loopnet resistant myelofibrosis.

The data from this investigator sponsored phase II study has been submitted to ash 2021 for potential presentation during the fourth quarter.

On Slide 19, you can see the study design for a new company sponsored randomized multicenter phase II study, which is expected to start also during the fourth quarter.

We look forward to updating you on the progress of this and all of our important studies at our virtual Investor day.

With that I will now advance to slide 20, and turn the call over to Mike Mason to review the quarterly financials Mike.

Michael P. Mason: Thank you, Jay. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 21. Total revenue for the third quarter of 2021 was $37.7 million, compared to $21.3 million for the third quarter of 2020. Net product revenue for the third quarter of 2021 was $26.7 million, compared to $21.3 million for the third quarter of 2020 from US commercial sales of Expovio. The estimated growth to net discount for Expovio in the third quarter was 15%, which was on the lower end of our expected range of 15 to 20%.

Thank you Jamie.

Since we issued a press release earlier today with the full financial results I will just focus on the highlights which begin on slide 21 total revenue for the third quarter of 2021 was $37 7 million compared to $21 3 million for the third quarter of 2020.

Net product revenue for the third quarter of 2021 was $26 7 million compared to $21 3 million for the third quarter of 2020 from U S commercial sales of exposure.

The estimated gross to net discount for <unk> in the third quarter was 15%, which was on the lower end of our expected range of 15% to 20%.

Michael P. Mason: And we continue to expect to be in that 15 to 20% range for the full year 2021. We recognized $11 million of license and other revenue for the three months ended September 30, 2021, including $9.8 million in milestone payments from Antigen following the July 2021 approval of Cellinexor for the treatment of patients with multiple myeloma and DLBCL in South Korea, and $1.2 million of revenue associated with the Named Patient Program. R&D expenses for the third quarter of 2021 were $45.8 million, compared to $37 million for the third quarter of 2020.

And we continue to expect to be in that 15% to 20% range for the full year 2021.

We recognized $11 million of license and other revenue for the three months ended September 32021.

$9 8 million in milestone payments from <unk>. Following the July 2021 approval of Selinexor for the treatment of patients with multiple myeloma and <unk> in South Korea, and $1 2 million of revenue associated with named patient programs.

R&D expenses for the third quarter of 2021 were $45 8 million compared to $37 million for the third quarter of 2012.

Michael P. Mason: The increase in R&D expenses, as previously stated on our Q2 call, was primarily attributable to the $7.4 million asset purchase of new medicines in the third quarter of 2021. SG&A expenses for the third quarter of 2021 were $35.1 million compared to $31 million for the third quarter of 2020. The increase in SG&A expenses compared to the third quarter of 2020 is due primarily to an increase in personnel costs, primarily related to an increase in hit count and compensation costs.

The increase in R&D expenses as previously stated on our Q2 call.

Was primarily attributable to the $7 4 million asset purchase of new medicines in the third quarter of 2021.

SG&A expenses for the third quarter of 2021 were $35 1 million compared to 31 million for the third quarter of 2020.

The increase in SG&A expenses compared to the third quarter of 2020, due primarily to an increase in personal personnel costs, primarily related to an increase in head count and compensation costs.

Richard A. Paulson: Cash, cash equivalents, and restricted cash investments, as of September 30, 2021, totaled $209.3 million, compared to $276.7 million as of December 31, 2020. Based on our current operating plans, we expect that our non-GAAP R&D and SG&E expenses, which excludes stock-based compensation expense for the full year 2021, to be in the range of $270 to $290 million. We expect that our existing cash, cash equivalents, and investments, as well as the revenue we expect to generate from Expovio product sales and other licensed revenues, will be sufficient to fund our planned operations into the middle of 2023. I'll now flip to slide 22 and turn the call over to Richard for some final thoughts. Richard?

Cash cash equivalents restricted cash and investments as of September 32021 totaled $209 3 million compared to $276 7 million as of December 31, 2020.

Based on our current operating plans, we expect our non-GAAP R&D and SG&A expenses, which excludes stock based compensation expense for the full year of 2021 to be in the range of $270 million to $290 million, we expect that our existing cash cash equivalents and investments as well as the revenue we expect to generate from <unk> product sales and other license.

<unk> will be sufficient to fund our planned operations into the middle of 2023.

I'll now flip to slide 'twenty, two and turn the call over to Richard for some final thoughts Richard.

Richard A. Paulson: Thank you, Mike. We are building off a very strong first nine months of the year, and as we move into the fourth quarter and beyond, there are a number of key near-term catalysts and milestones for us to deliver on as we continue to strengthen our organization and deliver for patients with high unmet needs, as outlined on slide 23. In multiple myeloma, our focus remains on the continued enhancement and strong execution of our commercial organization to secure increased expovial sales in the second line plus treatment setting.

Thank you Mike.

We are building off a very strong first nine months of the year and as we move into the fourth quarter and beyond there are a number of key near term catalysts and milestones for us to deliver on as we continue to strengthen our organization and deliver for patients with high unmet needs as outlined on slide 23.

In multiple myeloma, our focus remains on the continued enhancement and strong execution for our commercial organization.

To secure increased <unk> sales in the second line plus treatment setting.

We are awaiting the completion of the review of the MAA package in the EU based on the data from the Phase III Boston study.

Richard A. Paulson: We are awaiting the completion of the MAA package in the EU based on the data from the Phase 3 Boston study. We plan to initiate our Phase III study of XPD in multiple myeloma later this year, an oral combination that would allow us to further build in the multiple myeloma landscape. From our solid tumor programs, we expect top-line data from the Phase 3 Siendo study in endometrial cancer later this year or early next year.

We plan to initiate our phase III study of SPD in multiple myeloma later this year, an all oral combination that would allow us to further build in the multiple myeloma landscape.

From our solid tumor programs, we expect topline data from the phase III <unk> study in endometrial cancer later this year or early next year.

Richard A. Paulson: A market opportunity where there are no approved drugs in the maintenance setting following chemotherapy in any line of treatment. We have additional Cellinexor data and various hematological indications submitted to ASH 2021. And we look forward to announcing our selected abstracts tomorrow, Thursday, November 4th. Lastly, we plan to host a virtual investor day on December 8 to review our strategic imperatives and pipeline priorities to support our continued evolution as a company. To close, we're excited to continue delivering medicine for patients who are fighting cancer across the world.

Our market opportunity, where there are no approved drugs in the maintenance setting following chemotherapy and any line of treatment.

We have additional selinexor data and various hematological indications submitted to ash 2021.

And we look forward to announcing our socket abstracts Tomorrow Thursday November for us.

Lastly, we plan to host a virtual Investor day on December 8th to review of our strategic imperatives and pipeline priorities to support our continued evolution as a company.

To close we're excited to continue delivering for patients who are fighting cancer across the world.

Richard A. Paulson: I look forward to updating the investment community on our continued progress in the months and quarters ahead. And with that, I would now like to ask the operator to open the call up to the question and answer portion of today's call. Operator?

I look forward to updating the investment community on our continued progress in the months and quarters ahead.

And with that I would now like to ask the operator to open the call up to the question and answer portion of today's call operator.

Thank you very much to ask a question you May Press Star then one on your telephone keypad. If you are using speaker phone. Please pickup your handset before pressing the keys.

Operator: Thank you very much. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the key. To withdraw your question, please press star again. The first question comes from Maurice Raycroft from Jeffries. Please go ahead.

Withdraw your question Keith.

Thank you.

Next question comes from <unk> cost from Jefferies. Please go ahead.

Maurice Thomas Raycroft: Hey, everyone. And congrats on the update today. Thanks for taking my questions. I was just wondering if you could talk more about what you're seeing in the third line setting. What are the most common treatments that patients are coming off of before getting Expovio? And in that third line setting, is it the Boston regimen that's being used? Or what else can you say about the combo preparation? Thanks, Maurie. Maybe I'll turn to Sohanya to answer that.

Hi, everyone and congrats on the update today. Thanks for taking my question. So I was just wondering if you can talk more about what youre seeing in the third line setting what are the most common treatment that patients are coming off of before getting <unk> and in that third line setting is that the Boston regimen, that's being used or what.

Can you say about the combo preferences.

Sure. Thanks, Marc maybe I'll turn this on and to answer that yes. Thanks, Richard as you as you heard earlier, we're seeing an acceleration in that shift from later lines into earlier lines and our syndicated data indicate the strongest growth. This year is in the third line setting.

Richard A. Paulson: Yeah, thanks, Richard. As you heard earlier, we're seeing an acceleration in the shift from later lines into earlier lines. And our syndicated data indicates the strongest growth this year is in the third-line setting. In terms of patient proportions, we see an approaching 50-50 split between patients in the second-to-fourth line and patients in the fifth-line-plus setting. In terms of the overall treatment paradigm, most patients are treated with an IMID, a proteasome inhibitor, or an anti-CD38 antibody as the first or second line.

In terms of patient proportions, we see an approaching 50 50 split between patients in the second to fourth line.

And patients in the fifth line plus setting in terms of the overall treatment paradigm. Most patients are treated with an image a proteasome inhibitor or an anti CD 38 in the first or second line.

Sohanya Cheng: In the later lines, we see several new competitors or classes in the mix. We believe we are strongly positioned in that middle section of the second to fourth line, where a class switch to an expovial-based regimen could be vital for the success of the patient. We're also highly effective in subgroups of patient types such as high risk, elderly, and renal dysfunction. As we continue to look into the future, we expect to see a sustained shift in the line of therapy from later lines, from the original pentarefractory indications to earlier lines, in line with our Boston data, which launched at the beginning of this year. Answer your question, Maury. Yeah, that's helpful.

In the later lines, we see several new competitors all classes in the mix.

We believe we are strongly positioned in that middle section second to fourth line, where a class switch to an <unk> based regimen could be vital for the success of the patient.

We are also highly effective in subgroups of patient types, such as high risk elderly and renal dysfunction.

As we continue to look into the future, we expect to see that sustained shift in the line of therapy from the later lines from the original penta refractory indication to earlier lines in line with our Boston data, which launched at the beginning of this year.

That address your question Maury.

That's helpful and maybe one quick follow up.

Maurice Thomas Raycroft: And maybe one quick follow-up. In the last couple quarters, you guys have reported metrics on refill rate. Just in case I'm not seeing in this update, just wondering if you could comment a little bit on what you're seeing with refill rate. Yeah, absolutely, Maury.

In the last couple of quarters, you guys have reported metrics on repo rate.

And I am not seeing in this update just wondering if you can comment a little bit on what youre seeing with the refill rate.

Absolutely Maury. So we are still in the early stages of the launch of the second line plus indication since the beginning of this year and this data is still maturing we do have preliminary data that shows that more patients are staying on therapy longer and this is driven by two <unk>.

Sohanya Cheng: So we are still in the early stages of the launch of the second line plus indication since the beginning of this year, and this data is still maturing. We do have preliminary data that shows that more patients are staying on therapy longer, and this is driven by two factors, the shift into earlier lines, as well as better side effect management. As we evolve into earlier lines, we expect to see the duration increase driven by that shift into earlier lines and in line with our targeting positioning.

Factors the shift into earlier lines as well as better side effect management as we evolve into early aligns we expect to see that duration increase driven by that shift into earlier lines and in line with our targeting positioning.

Sohanya Cheng: However, we cannot definitively guide to a specific duration number at this time since we're in a dynamic phase of our transition into earlier lines of use and in an early stage of the launch. So we need to let that data mature.

However, we cannot definitively guide to a specific duration number at this time since we're in a dynamic phase of our transition into earlier lines of use and in an early stage of the launch so we need to let the data mature.

Okay. Okay. It makes sense and congrats again and thanks for taking my question.

Maurice Thomas Raycroft: Okay, okay, it makes sense. Congratulations again and thanks for taking my question.

Operator: Thank you. The next question comes from Peter Lawson from Barclays. Please go ahead, Peter.

Peter Richard Lawson: Thanks very much.

Operator: Peter, I'm sorry to interrupt, if you don't mind.

Unknown Speaker: Unknown Speaker. Your line is quite low.

Unknown Speaker: Unknown Speaker. Yeah. Congratulations on the quarter and the drivers in the three queues. Kind of what will continue into 4Q? How should we think about that? And kind of what's left to accelerate revenue growth in 4Q and beyond.

Peter Richard Lawson: Sure. Thanks, Peter. Maybe we'll turn to Sohanya on that.

Sohanya Cheng: Yeah, thanks for the question, Peter. So we saw significant demand growth this quarter, contributing to 32% quarter-over-quarter revenue growth, and we feel very confident in our sustained growth. This was driven by strong execution and the new positioning we introduced in the second quarter in that white space between second to fourth line. Now, in terms of drivers, there are three key indicators. Number one is the acceleration of that shift into earlier lines.

We introduced in the second quarter in that White space of second to fourth line now.

Now in terms of drivers there's the three key indicators number one is the acceleration of that shift into earlier lines and as I mentioned are syndicated data is indicating the strongest growth. This year in the third line as well as that shift from <unk> based doublet regimen with too.

Sohanya Cheng: And as I mentioned, our syndicated data is indicating the strongest growth this year in the third line, as well as that shift from the expovial-based doublet regimen to the once-weekly triplet-based regimen in line with our Boston indication. And we expect to continue to see this shift in that line of therapy. The second driver is an expansion in the breadth and depth of use of expovial. We're adding more accounts every quarter, and we're increasing our penetration at the top myeloma accounts.

Once weekly triplet base regimen in line with our Boston indication and we expect to continue to see a shift in that lineup therapy. The second driver is that expansion in the breadth and depth of use.

Of <unk>, we're adding more accounts every quarter and we're increasing our penetration at the top of myeloma accounts. The most significant growth that we saw within the community setting and we expect to continue to see that in the future as well lastly.

Sohanya Cheng: The most significant growth that we saw was in the community setting, and we expect to continue to see that in the future as well. Lastly... In terms of the qualitative market research as well as customer feedback that we're getting, we see a sustained improvement in the overall product perception and a growing confidence among physicians in managing this product with our new lower-dose once-weekly expovio-based triplet regimen. So, as I mentioned, we are still in the early stages of the second line plus launch, and we won't be giving sequential growth guidance, but we remain confident in our ongoing efforts to drive increasing use in earlier lines, grow position confidence and expovio, and remain focused on very strong execution.

In terms of the qualitative market research as well as customer feedback that we're getting we see a sustained improvement in the overall product perception and a growing confidence amongst physicians in managing this product with our new lower dose once weekly <unk>.

Triplet regimen.

So as I mentioned, we are still in the early stages of the second line plus launch and we won't be giving sequential growth guidance, but we remain confident in our ongoing efforts to.

Drive increasing Houston earlier lines Grove position confidence in <unk> and remain focused on very strong execution.

Peter Richard Lawson: Great, thank you. Just, were there any one-timer items in that in the quarter that we should be thinking about as we kind of grow revenues off of Q3?

Just.

A one times and the cool too that we should be thinking about it.

Grew revenues or.

Two three.

No no no no one time inbox in the quarter.

Sohanya Cheng: No, no, no one-time impacts in the quarter.

Peter Richard Lawson: Perfect. Thank you so much. Thanks for taking the questions.

Perfect. Thank you so much thanks for taking the course.

Hi, Peter.

Operator: Thank you. The next question comes from David Liebowitz from Morgan Stanley. Please go ahead, David.

The next question comes from David Leibowitz for Morgan Stanley He's Gonna hate David.

David Liebowitz: Thank you very much for taking my question. Given that there's so much shift in the treatment paradigm for multiple myeloma, where does Velcade, the Velcade combination actually end up, I guess, being most predominant? Will it be in the second line or the third line, given that Darzalex has been increasing its use? And beyond that, were there any inventory shifts or anything in the quarter on the wholesaler side? And maybe I'll just start with Mike to talk about the inventory side.

Oh, Thank you very much for taking my question given that there's so much shift and the treatment paradigm for multiple myeloma, where does velcade.

The Velcade combination actually.

And I guess being most predominant will be in the second line or the third line.

Given that where.

Darzalex has been increasing its use.

And beyond that was there any inventory shifts or anything in the quarter on the wholesaler side.

Michael P. Mason: And then I can turn to Sohanya to talk about, you know, the utilization in that second or fourth line, David. Sure, on the inventory side, it was a minor drawdown in inventory in the quarter. But you know, as you remember, from last quarter, we had about a $2 million shift. So it had a minor impact on the quarter.

Yeah, maybe I'll just start with with Mike you talk on the inventory side and then they can turn this on you to talk about.

<unk> in that second to the fourth time David.

Sure on the inventory side.

Was a minor drawdown in inventory in the quarter.

You remember from last quarter waited about a $2 million shift.

There was a minor impact on the corner. So we expect inventory and I'll have a meaningful impact on quarterly revenue you're going forward.

Sohanya Cheng: So we expect inventory to not have a meaningful impact on quarterly revenue going forward. And as far as your treatment paradigm question, most patients, as you mentioned, are treated with an anti-CD38 or IMID or a PI in the first and second line. So following that, and prior to the later-line therapies, there is that significant unmet need where we are seeing the most rapid growth in both second and third lines for expovio.

Mhm.

And as far as your treatment paradigm question.

Most patients as you mentioned are treated with an anti CD 38 or.

RPI in the first and second line so following that and prior to the later Aline therapies. There is that significant unmet need where we are seeing the most rapid growth in both second and third line for exposure Yo.

Sohanya Cheng: Now, our sales and marketing teams will, of course, only promote the FDA-approved expovio combination with bortezomib and dexamethasone, and we're continuing to see a rise in that triplet regimen in the third line and second line setting. However, NCCN also has other regimens on board, expovio in combination with pomalidomide and dexamethasone, and expovio in combination And as I mentioned, we only promote the expovio combination in our FDA label, but we're seeing that positive shift from the doublet late-line setting towards that triplet setting in earlier lines in line with our Boston indication. Jayden, maybe I just want to expand on that from your perspective. Yeah, absolutely.

Now our sales and marketing team will off course, only promote to the FDA approved exposure Yo combination with Bortezomib and dexamethasone and we're continuing to see a rise in that triplet regimens in in the third line and second Lions setting.

However in CCN also has other regiments on board.

<unk> in combination with palm of Littermate and dexamethasone in <unk> in combination with Derek <unk> and dexamethasone and as I mentioned, we only promote to the X maybe a combination in our FTE label, but we are seeing that positive shift from the doublet late.

Lines setting towards that triplet setting in earlier lines in line with our box indication Andrew maybe just wanted to expand on that from your perspective, yeah, absolutely domestic from the treatment paradigm perspective, you were assume increase using a few 30 degrees therapy and the first and second line is so hard you mentioned.

Jayden: I mean, from the treatment paradigm perspective, you know, we're seeing an increase using a CD38-based therapy in that first and second line, as Sohania mentioned. And so, you know, these patients are either getting an IMID plus a CD38 or a PI plus a CD38. As they progress on that, those treatments, then coming into third line, it starts really leveraging two principles that we're very comfortable with in myeloma, which is class switching.

So.

These patients are either getting them to move closer to <unk> or a PR processing. The 30th is a progress on that.

Those therapies been coming into third line and starts really leveraging two principles that were very comfortable within myeloma, which is class switching.

Jayden: And so if they're on an IMID-based therapy, then switching to a PI-based therapy, such as Velcade, becomes attractive, and is based on sound reasoning for the last 20 years of class switching. So I think that there's a strong degree of comfort around Velcade-based therapies in the community for many years. And so, as Sohanya mentioned, there are multiple options now for expovial-based therapy for what physicians want to do, and they have that option. Thank you for that.

Corona image based therapy.

Switching to a ti based therapies, such as Velcade bitch.

Becomes attractive.

Based on kind of sound reasoning for the last 20 years from class switching so I think that there's a strong degree of comfort around velcade based therapies in the community for many years and so and as long as I mentioned, there's multiple options now Brooks bouillabaise therapy for what the physicians want to do and then how 'bout optionality.

Thank you for that and shifting over to our <unk>. Our has has selinexor with the study previously and M. D. S. If you could remind us and what was the experience and how would the ultimate Ultimate X R differ.

Jayden: And shifting over to Alpinexor, has Selenexor been studied previously in MDS, if you could remind us, and what was the experience? And how would Altenexer differ? Great question.

Great question, So selinexor has been evaluated.

Jayden: So Selenexer has been evaluated in MDS previously. There was a phase one study, phase one, and phase two study done with Dr. Klimek out of Memorial Sloan-Kettering. There, they showed a proof of concept with activity with single agent Selenexer in that setting and relapsed MDS with a response rate greater than 30%. So there is that proof of concept now with both Selenexer and Eltenexer in MDS that provides that body of research. So that's the data and the confidence around signed compounds in MDS. And the decision, I guess, to move with Elton X, sir, in this population, was it based on tolerability?

<unk> previously there was a phase one study fees one to study.

Done.

Dr. Klimek other memorial Sloan Kettering, they're they showed a proof of concept activity with single agent. So an extra in that setting and relapsed mus the.

The responsory greater than 30%. So there is a proof of concept now with both Selinexor and Elton mixer and Mds that provides a body of data and the confidence around San compounds in mgs.

And the decision I guess to move with the <unk> population was based on the.

Jayden: Yeah, so as we looked at the totality of the data, there are differences with Eltenexor where with the ability to give low dose continuous Eltenexor for five days in a row. We saw better activity in our early data with EltsinExer. When you look at the totality of data with SelenExer and EltsinExer, we made the decision to really develop EltsinExer in MDS, in myeloid, and livid. Got it. Thank you very much for taking my questions. Congratulations on the quarter.

Tolerability.

Yeah, So as we looked at the totality of the data.

Our differences with else next or where.

With the ability to give low dose continuous elton extra for five days in a row.

You saw better activity earlier in the early data with <unk>.

You look at the totality of data with Selinexor <unk>, we we made the decision to really develop ultra mixer.

And yes and <unk>.

Got it. Thank you very much for taking my questions and congrats on the corner.

Thank you thanks.

David Liebowitz: Thank you. The next question comes from Brian Abrams from RBC Capital Markets. Please go ahead, Brian.

The next question comes from Brian Abraham some RBC capital markets keeps going to hate Brian.

Operator: Hello, this is Leonid on behalf of Brian. Thanks for taking our question. I actually wanted to stay with Elton Exxer for a moment.

Hi, Hello. This is leeann it on for Brian Thanks for taking my question.

Actually I wanted to stay with <unk> for a moment. So I'm curious what you guys are thinking about in terms of the regulatory clinical bar and MTS for Elton XOR kind of what you're hoping to see and how you are seeing this landscape of all right. Now I mean is there potential for this to be a registrational trials given the unmet need I am just curious on your thoughts there. Thanks.

Leonid: So, you know, I'm curious what you guys are thinking about in terms of the regulatory and clinical bar for MDS for Elton Exxer, kind of what you're hoping to see and, you know, how you're seeing this landscape evolve right now. I mean, is there potential for this to be a registrational trial given the unmet need? I'm just curious about your thoughts there. Thanks.

Yeah, a great question.

Jayden: Yeah, great question. And so, you know, as you know, this field of MDS is rapidly evolving. But what's clear is this, right, HMA therapies are the standard of care and first line, all the other drugs in development, and there are no other drugs other than HMA based HMAs right now that are approved in MDS. Number two, when you look at all the other kinds of study drugs that are being evaluated in MDS.

Until you as you know this field of Mds's rapidly evolving, but what's clear is this right HMA therapies are the standard of care and first line.

All the other drugs in development and there are no other drugs other than HMA Baster Hma's right now that are approved and Mds.

Number two and you look at all the other kind of study drugs that are being evaluated in Mds.

Jayden: Those are all being evaluated in newly diagnosed MDS, so the field is actually not evolving in the relapse refractory space. There are no drugs approved in the relapse-refractory space, and there's really limited to no therapies being developed in that relapse space. So we look at most of the other studies; they're all in the newly diagnosed space. So that really leaves a very clear unmet need and an opportunity in the relapse space, and that's where we see a clear signal with Eltsinexor in that setting. And so, as you look at the field, you know, in the relapse refractor space, the field is not evolving as quickly as you'd anticipate.

Those are all being evaluated in newly diagnosed mds through the field is actually not evolving in the relapsed refractory space. There are new drugs approved in the relapsed refractory space and there's really limited to new therapies being developed in that regard. So we look at the other most of the other studies or all of the newly diagnosed so that really leaves them very clear unmet.

Need an opportunity in the rehab space and that's what we see a clear signal and belts next year in that setting.

And so as you look at the field in the relapsed refractory speaks to field is not evolving as quickly as you'd anticipate.

Jayden: And then I think maybe Jayden, just expand on it, look at the evolution of the data and with the study, you know, how we would look at, you know, positively engaging with the FDA based on the outcomes. I think if our data continues to hold up, it's obviously a big impact for patients, and good for them. Yeah, absolutely. There is a clear unmet medical need there. And when we look at the response rates that we see with L-Connexer, I think if we continue to see response rates in this range, then that would be positive, and we'll have discussions with the agency at that point in time.

And then I think maybe just expand on it to look at the evolution of the data and with the study how we would look at positively engaging with regards to the FDA based on the outcomes or image of our data continues to hold up it's obviously, a big impact provisions and positive for them.

Sure. It is clear on medical neither and let me look at the response rates that we see without mixer.

I think if we continue to see response rates in this range then these would be positive.

And we will have discussions with the agency at that point in time.

Operator: Thank you. The next question comes from Eric Joseph from J.P. Morgan. Please go ahead, Eric.

Got it thank you.

Alright.

And the next question comes from Eric Joseph from K P.

He's going to hate Inc.

Eric William Joseph: Hi, good morning. This is Hannah On for AIR.

Hi, Good morning is is Hannah Eric Thanks for taking my questions just to keep from us.

Hannah: Thanks for taking the questions. Just a few from us. So first, looking more closely at the new patient starts, are you able to see if there's any physician stickiness? Meaning, like, are you seeing any former prescribing physicians now prescribing exposures for their patients in earlier lines? Or are the majority of earlier line scripts coming from new prescribers?

First looking more closely at.

New patient starts are you able to see if there's any physician stickiness.

Like are you seeing any formerly prescribing physician now describing exposure to their patients and airlines are the majority of those airlines scripts coming from new prescribers.

Yeah. Thanks for the question.

Sohanya Cheng: Yeah, thanks for the question. We're seeing continued growth in new patient starts, and that's driven by an expansion in both the breadth and depth of use. So there are new prescribers coming on board and trying Expovio for the first time, as well as us growing in depth. So there are prescribers that have used Expovio in the original later line indications, and we're now seeing them growing in confidence in using it in earlier lines. So we're seeing that shift into the second and third line. Does that address your question?

We're seeing.

Continued growth in new patient starts and that's driven by an expansion in both the breadth and depth abuse. So there is new prescribers coming on board.

And trying exposed view for the first time as well as we're growing in depth. So there's pre.

Prescribers that had used <unk> in the original later line indications and we're now seeing them growing in confidence in using it in earlier lines. So we're seeing that shift into.

And third line.

That address your question.

Yeah, and then moving towards Sir very recently.

Jayden: Yes, that addresses it. And then moving towards just your recently initiated Phase 2 trial in combination with Pembrolizumab for melanoma, just where and how do you see this combination fitting into the indication for the current treatment?

A few trial combination.

Or a melanoma, just where and how do you see this combination fitting into a vindication undercurrent too much okay.

Jayden: I'll turn to Jayden on that. Yeah, no, absolutely. So great question around that.

I'll turn to Jason on that.

Yeah, absolutely so great question around that so we've seen some activity now is presented by.

Jayden: So we've seen some activity now presented by the MD Anderson group looking at Selinex or infimbolizumab in patients with disease that's refractory to checkpoints. And based on the early promising signals there, we're continuing to really confirm the signal there for the activity that we see with this combination specifically in checkpoint refractory disease. And the field is evolving there, especially in checkpoint-naive patients. But I think there's still a clear unmet need and opportunity in patients with checkpoint refractory disease.

The MD Anderson group looking at Selinexor informed blues in patients with the disease, that's refractory to checkpoints and based on come early promising signals there were continuing to really.

Really confirm the signal there for what the activity that we see with this combination specifically in checkpoint refractory disease.

Field of evolving there, especially in checkpoint naive patients.

I think there's still a clear unmet need an opportunity in patients who checkpoint refractory disease and reevaluating both those patients who have primary refractory disease or those who have a response from them become refractory as those are two different biologies and based on the data about two former got us in terms of the next steps.

Jayden: And we're evaluating both those patients who have primary refractory disease or those who have a response and then become refractory, as those have two different biologies. And based on the data, that will inform or guide us in terms of the next steps.

Great. Thanks for taking my question.

And China.

The next question comes from Jonathan Cheng from if need be.

Hannah: Great, thanks for taking the question.

Operator: Thank you. The next question comes from Jonathan Cheng from SVB, Lyrics. Please go ahead, Jonathan.

Inc. Tuesday, he Jonathan.

Good morning, and thanks for taking my questions. First question can you remind me what data you have available on that gives you color into what lines of treatment and combinations exposures being utilized room.

Jonathan Cheng: Good morning, and thanks for taking my question. First question, can you remind me what data you have available that gives you color into what lines of treatment and combinations of drugs are being utilized? Yeah, as you know, it's very difficult to get an accurate picture of lines of therapy. But we do have syndicated data from payer claims data that gives us good coverage on our patients that indicate that shift in line of therapy. I got it.

Yeah as you know, it's very difficult to get an accurate picture of lines of therapy, but we do have.

Syndicated data from from her claims data that gives us.

Good coverage on our patients that indicate that shift.

In lineup therapy.

Sohanya Cheng: And second question, and this is a higher level question. Can you talk about how you're thinking about moving towards being a cashflow-positive company in the future, both on the revenue and expense side, and how we should be thinking about your strategy in relation to your cashflow? I think maybe I'll just start off. I mean, obviously, as we look forward, you know, a number of catalysts. First, it's just continuing to drive our breadth and depth in multiple myeloma and continuing to grow in multiple myeloma.

Got it and second question and this is a higher level of question.

Can you talk about how you're thinking about moving towards being a cash flow positive company in the future.

Both on the revenue and expense side, and how we should be thinking about your strategy in relation to your cash runway.

Yeah, I think maybe I'll just start off and obviously as as we look moving forward a number of catalyst first suggest engineering to drive or breadth and depth of multiple myeloma.

Continuing to grow in multiple myeloma, and obviously moving forward I think with our agenda study as we're talking to that being very near term and I think also as you've heard from Jason and that opportunity right now that's an opportunity which has a very different.

Sohanya Cheng: And obviously, you know, moving forward, I think, with our CNDL study, as we're talking about that being very near term. And I think also, as you've heard from Jayden about that opportunity, right now, that's an opportunity that has a very different uptake than you see in multiple myeloma, a much more rapid uptake, because there is no approved therapy for patients in this setting. And obviously, there's a big incidence population which would benefit, you know, pretty rapidly from having an improvement in the setting of actually having, you know, more time to go into remission when you're looking at endometrial cancer patients.

Jake then you see in multiple myeloma.

Much more rapid uptake because there is no approved therapy.

For patients in the setting and obviously there is a big incidents population, which would benefit pretty rapidly from from having improvement in the setting of actually having more time to extend in remission. When are you looking at endometrial cancer patients and then continuing to build on that obviously was bringing are there new and.

Richard A. Paulson: And then continuing, you know, to build on that, obviously, with bringing, you know, other new indications forward. So, driving our revenue growth is key. And I think also making sure, as we talked, that we're very focused in terms of where we invest, in terms of having the highest impact for patients and the highest probability of success. Yeah, that's a good summary. Just to add, obviously, on the inflow side, you know, our goal with Europe, where we have potential approval in the first half of 2022, is to be commercially ready there, potentially with a partner.

Locations forward so.

Driving our revenue growth.

And I think also making sure as we talk to you that we're very focused in terms of where reinvest in terms of having the highest impact for patients.

Highest probability of success.

And then on top of that make torture, but you've heard some of the talk about our partner.

Revenue in different areas that we're adding in terms of evolving our cash runway Mike sure.

Good summary, and just to add I think obviously on the inflow side.

We are goal with Europe potential approval in the first half of 2022 is to be commercially ready, they're potentially with a partner. So that's certainly one source of.

Richard A. Paulson: So, that's certainly one source of capital coming in outside of traditional revenues or financing. We also have $40 million remaining on our healthcare royalty finance agreement as another tool in our belt. And as Richard said, and we'll give a lot more color to this in our R&D day in about a month, on how we really focus on prioritizing our investments in our pipeline. Got it. Thank you.

Capital coming in outside of traditional.

Revenues are financing, we also have $40 million remaining on our healthcare royalty financing agreement as another tool in our belt and as Richard said and we will give a lot more color of this in our R&D day in about a month on how we really focus on prior to prioritizing our investments in our pipeline.

Got it thank you.

Michael P. Mason: Thank you. The next question comes from Colleen Kusy from Baird. Please go ahead, Colleen.

The next question comes from cutting Cassie from bad teeth cleaned.

Operator: Great. Thanks so much for taking our questions and congrats on the quarter.

Great. Thanks, and you are taking our questions and congrats on the corner.

Colleen Margaret Kusy: For the top-line growth that you saw in 3Q, are you able to comment on... Unknown Speaker Between longer duration and new patients, what was more of a driver in 3Q and, looking forward, where you see the bigger opportunity for growth, whether it's

For the top line growth that you saw in three Q are you able to comment on.

A tween.

Longer duration of new patients what was more of a driver and <unk> and looking forward, where you see the bigger opportunity for growth whether it's great.

Colleen Margaret Kusy: prolonging the No, thanks, thanks, Colleen. I'll just start at a high level, but then turn it to Sohanya.

Adding new patients or.

Prolonging the duration.

Yes, no. Thanks, Thanks, Colino I'll just started at a high level, but and then turn it to Sonic but again I think it's a combination of both.

Richard A. Paulson: But again, I think it's a combination of both, you know, as you heard Sohanya talk about. We're going to continue to drive breadth and depth as we move into earlier lines of therapy, which we did very well in this quarter with the greatest growth being through the year in that third line setting. And as we move up into earlier lines, patients have a greater duration of therapy. So it's both in terms of bringing new patients on board in the earlier lines and having a greater duration of therapy, with the patient, obviously benefiting from the earlier lines.

As you heard John you talk to her we're going to continue to drive the breath and depth as we move into earlier lines of therapy, which we've done very well in this quarter with the greatest growth.

And through the year in that third line setting.

And as we move up into earlier lines patients ever greater duration of therapy. So it's both in terms of bringing new patients on board and earlier lines and having a greater duration of therapy through through the patients.

Obviously benefiting and the earlier lines and so on anything you want to add to that I think that's a great summary, Richard.

Richard A. Paulson: Sohanya, anything you want to add to that? No, I think that's a great summary, Richard. Does that address your question, Colleen? Yes, it does. Thank you. And on the impact from COVID that you saw in 3Q, can you put that into context versus what you saw in 2Q and what your expectations are for that in the coming quarter? I'll turn to Sohanya on that.

The address address your question coin.

Yes. It does thank you and on the impact from Covid that you saw in three Q can you just put that in the context versus what you saw in two Q and what your expectations after that in the coming quarters.

Sure the alternatives on Umf, yes, so we saw an increase in.

Three Q field activity and an increasing proportion of our visit as being in person versus virtual but we have not returned to pre COVID-19 levels similar trend on patient visit.

Sohanya Cheng: Yeah, so we saw an increase in 3Q field activity and an increasing proportion of our visits being in person versus virtual, but we have not returned to pre-COVID levels. Similar trend on patient visits. While there's been a gradual increase over time in patient visits, that also has not returned to pre-COVID levels. At Karyopharm, we have a nimble, dedicated, patient-centric team that is able to reach our prescribers to ensure they have the right education.

While there is a gradual increase over time.

Patient visits that also has not returned to pre COVID-19 levels.

Carry a farm we have a nimble dedicated very patient centric team that is able to reach our prescribers to ensure they have the right education. We've also strengthened our digital capabilities to complement field efforts.

Sohanya Cheng: We've also strengthened our digital capabilities to complement field efforts. So we are entirely focused on strong execution. We have to actively monitor the COVID impact and adjust our engagements as needed, but we remain focused on strong execution. Great, thanks so much for taking our questions.

So we are entirely focused on strong execution.

We have to actively monitor the COVID-19 impact and adjust our engagement is needed, but we remain focused on strong execution.

Great. Thanks, so much for taking our questions.

Thanks for calling in queue.

Operator: Thank you. We have no further questions at this time. I would like to hand you over to Richard, to conclude.

Thank you we have known for the Christians at this time I would like to hand back to <unk> to compute thank you.

Richard A. Paulson: Thank you, operator, and thank you again to everyone for joining our call today. I look forward to continuing to update you on our success as we continue to bring Expovio to more patients, not only in multiple myeloma but also in other key hematological indications and solid tumors, you know, with a high unmet need where we can make a significant impact to positively impact the lives of cancer patients. Thank you for joining us today and have a great day. Thank you very much, Sarah.

So thank you operator, and thank you again to everyone for joining our call today looking forward to continue to update you on our success as we continue to bring <unk> to more patients. They are not only of multiple myeloma, but also in other key hematological indications in solid tumors with a high unmet needs or we can make a significant impact.

To positively impact the lives of cancer patients. Thank you for joining us today and have a great day.

Thank you very much said you may now disconnect your lines.

Goodbye.

[noise].

Operator: Thank you very much, sir. You may now disconnect your line.

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