Q4 2021 Karyopharm Therapeutics Inc Earnings, 2022 Financial Outlook and SIENDO Topline Results Discussion Call

Good morning, My name is Sarah and I will be your conference operator today.

Operator: Good morning. My name is Sarah, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics fourth quarter and full year 2021 financial results conference call. There will be a question and answer session following. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Sarah Connors, Vice President, Corporate Communications. Please go ahead.

At this time I would like to welcome everyone to the carrier farm Therapeutics fourth quarter and full year 2021 financial results Conference call.

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

I would now like to turn the call over to Sarah Corners, Vice President Corporate Communications. Please go ahead.

Thank you Sarah and thank you all for joining us on today's conference call to discuss the top line results from the phase III at the end of the study as well I was curious on fourth quarter and full year 2021 financial result, today I am joined by Mr. Richard Carlson, President and Chief Executive Officer, Mr. Han you Jain Chief commercial officer.

Sarah Connors: Thank you, Sarah, and thank you all for joining us on today's conference call to discuss the top line results from the Phase 3 Siendo Study, as well as Karyopharm's fourth quarter and full year 2021 financial results. Today I am joined by Mr. Richard Paulson, President and Chief Executive Officer, Ms. Sohanya Cheng, Chief Commercial Officer, Dr. Jatin Shah, Chief Medical Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Stephen Michener, Chief Business Officer, and Sharon Shackham, Chief Scientific Officer.

Dr. Jason Shah Chief Medical Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Steven Michener, Chief Business Officer, and Sharon Shack on Chief Scientific Officer earlier. This morning, we issued two press releases one announcing top line results from the Phase III study in endometrial cancer and one detailing.

Sarah Connors: Earlier this morning we issued two press releases, one announcing top line results from the Phase 3 Siendo Study in Endometrial Cancer, and one detailing Karyopharm's financial results for the fourth quarter and full year 2021. These releases, along with the slide presentation that we plan to reference during today's call, are available under the events and presentation section of 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 provisions under the Private Securities Litigation Form Act of 1995, as outlined on slide 2.

<unk> financial results for the fourth quarter and full year 2021. These releases along with a slide presentation that we plan to reference during today's call are available under the events and presentations section of our website carrier farm 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 1095 as outlined on slide. Two these include statements about our future expectations clinical developments and regulatory matters and timelines the potential.

Sarah Connors: These include statements about our future expectations, clinical developments, and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations relating to the commercialization of Expovio and Nexpovio, financial projections, and our plans and prospects. Actual results may differ materials 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.

<unk> of our products and product candidates, including our expectations relating to the commercialization of <unk> and next Silvio financial projections, and our plans and prospects actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent.

<unk> 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.

Sarah Connors: Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. If you turn to slide 3, you can see our agenda for today. I will now turn the call over to Richard. Please turn to slide 4.

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

For today I will now turn the call over to Richard Please turn to slide four.

Thank you Sarah and good morning, everyone.

Richard Paulson: Thank you, Sarah, and good morning, everyone. As we work to defeat cancer and improve patients' lives, I am very pleased to report that the Phase III Siendo Study met its primary endpoint of a statistically significant improvement in median progression-free survival compared to placebo. Delan XOR treated patients at a medium PSF of 5.7 months, compared to 3.8 months for patients on placebo. Representing an improvement of 50% [inaudible] with a hazard ratio of .70 and a p-value of 0.0486.

As we work to defeat cancer and improve patients' lives I am very pleased to report that the phase III <unk> study.

Richard Paulson: Additionally, Telenexor demonstrated sustained and long-term improvement in progression-free survival. At 12 months, there was an improvement in patients in remission from 25.8% to 35.3%. Representing a 37% increase in probability that Selenex or treated patients will be in remission compared to patients on no treatment, for today's standard of watch and wait. In this study, Stellan XR was well tolerated with no new safety signals identified and a well-discontinuation rate of 10.5% due to adverse events. Karyopharm will work with investigators in the FDA to complete a fully valuation of the T&D data. Importantly, the preliminary data also identified a pre-specified subgroup.

Its primary endpoint of a statistically significant improvement.

In medium progression free survival compared to placebo.

Selinexor treated patients had a median PFS of five seven months.

Compared to three eight months for patients on placebo.

Representing an improvement of 50%.

We've got a hazard ratio of <unk>, seven zero and a P value of 0.0 for ASIC.

Additionally, selinexor demonstrated sustained and long term improvement in progression free survival.

At 12 months, there was an improvement in patients in remission from 25, 8%.

At 35, 3%.

Representing a 37% increase in profitability.

<unk> treated patients will be in remission compared to patients on no treatment.

For today's standard of watch and wait.

In this study Selinexor was well tolerated with no new safety signals identified in a low discontinuation rate of 10, 5% due to adverse events.

Tara borrowing will work with investigators and the FDA to complete a full evaluation of the <unk> data.

Importantly, the preliminary data also identified a pre specified subgroup.

Richard Paulson: Biotype P53, known as the guardian of the genome, which achieves a statistically significant reduction in the risk of disease progression or death. In this pre-specified subgroup, currently consisting of 103 patients, The data showed an almost four-fold improvement in progression-free survival for cell and exoretry to patients, with a median progression free survival of 13.7 months, compared to 3.7 months for patients on placebo. The hazard ratio of 0.38, and a p-value of 0.0006.

<unk> P 53, known as the Guardian of the genome.

Which achieved a statistically significant reduction in the risk of disease progression or death.

And this pre specified subgroup.

Currently consisting of 103 patients.

The data showed an almost four fold improvement in progression free survival for Selinexor treat a patient.

With a median progression free survival of 13 seven months.

Compared to $3 seven months for patients on placebo.

The hazard ratio of <unk> 38.

And a P value of 0.0006.

We plan to submit a supplemental new drug application to the FDA during the first half of 'twenty two.

Richard Paulson: We plan to submit a supplemental new drug application to the FDA during the first half of 2022 and also plan to submit the detailed results from the study for presentation at upcoming medical meetings in the first half of 2022. I would like to acknowledge the exceptional work done by a lot of very dedicated individuals at both Karyopharm and at the Ciendo Clinical Trial site, and I wish to express our sincerest gratitude for everyone involved, especially the patients and their families.

And also plan to submit the detailed results from this study for presentation at upcoming medical meetings in the first half of 'twenty two.

I would like to acknowledge the exceptional work done by a lot of very dedicated individuals are both carryover.

And at this the Enzo clinical trial site.

I wish to express our sincerest gratitude for everyone involved.

Especially the patients and their families.

On slide five I will present, an overview of our five key pillars that drive our underlying value and we will provide opportunity for what we believe will be substantial future growth.

Richard Paulson: On slide five, I will present an overview of our five key pillars that drive our underlying value and will provide opportunity for what we believe will be substantial future growth. First, We are successfully building upon our existing U.S.

First.

We are successfully building upon our existing U S multiple myeloma Foundation.

Richard Paulson: Multiple Myeloma Foundation, as our lead oncology asset, Expovio, generated $29.8 million in net product revenue in the fourth quarter of 2021, representing growth of 47% year over year. For the full year 21, we generated net product revenue of 98.4 million, representing growth of 29% compared to the prior full year. We expect to continue growing sales in 22 through strong execution and proven commercial capabilities, creating value for both patients and shareholders. We are striving to become the standard of care in second line plus, host Anti-CD38 and establish Exfolio as a novel effective modality in the multiple myeloma treatment landscape. Globally, I am very pleased we have brought on board a new commercialization partner for Europe, Latin America, and other key territories with our Menorini partnership that was finalized in December.

As our lead oncology asset exposure.

Generally $29 8 million in net product revenue in the fourth quarter of 'twenty one.

Representing growth of 47% year over year.

For the full year 'twenty, one we generated net product revenue of $98 4 million.

Representing growth of 29% compared to the prior full year.

We expect to continue growing sales in 'twenty, two through strong execution and proven commercial capabilities, creating value for both patients and shareholders.

We are striving to become the standard of care in second line costs.

Most anti CD 38, and establish exposure as a novel effective modality in the multiple myeloma treatment landscape.

Globally I am very pleased that we have brought on board a new commercialization partner for Europe , Latin America, and other key territories with our mentoring any partnership that was finalized in December .

In the near term, we are expecting the European <unk> to complete its review of the Selinexor MAA in second line <unk>.

Richard Paulson: In the near term, we are expecting the European THMP to complete its review of the Selenexor MAA in second line plus, and issue an opinion during the first half of 22, with Manarini and our other global partners. We will increasingly bring Exfolio to patients worldwide. Second, as just outlined, our near-term opportunity in solid tumors took a huge step forward as Siendo met its primary endpoint with a statistically significant 50% improvement in medium progression pre-survival versus placebo.

And issue an opinion during the first half of 'twenty two.

With men or any in our other global partners, we will increasingly bring exposure to patients worldwide.

Second as just outline our near term opportunity in solid tumors took a huge step forward <unk> met its primary endpoint with a statistically significant 50% improvement in median progression free survival versus placebo.

Third we are advancing our clinical pipeline that is being purposely built and strategically focused on targeting cancers with high unmet needs.

Richard Paulson: Third, we are advancing a clinical pipeline that is being purposely built and strategically focused on targeting cancers with high-end vet needs. Where science enables us to make the biggest difference in the lives of patients in areas with high probability of success. To that end, we have rapidly initiated new Phase II trials in myodysplastic syndromes and myofibrosis, where we believe we have the potential to achieve approvals over the next three to four years.

Where our science enables us to make the biggest difference in the lives of patients and in areas with high probability of success.

To that end, we have rapidly initiated new phase II trials in Myelodysplastic syndrome and myelofibrosis.

Where we believe we have the potential to achieve approvals over the next three to four years.

Our fourth pillar is our people and we have the right people in place along with a strong leadership team with an exceptional ability to achieve both scientific and commercial excellence and executing on our key corporate objectives.

Richard Paulson: Our fourth pillar is our people, and we have the right people in place, along with a strong leadership team, with an exceptional ability to achieve both scientific and commercial excellence in executing on our key corporate objectives.

Richard Paulson: [inaudible] Most recently, we bolster our team even further with the promotion of Sohanya Cheng, the Chief Commercial Officer, and the addition of Peter Honig to the Board of Directors. Fifth and finally, to support our Strategic and Focus Growth Plan, we are well-capitalized funder operations into early 2024. At Karyopharm, everything we do is driven by our mission to positively impact patients' lives and defeat cancer. Our foundation is in our side, and we are the global leader with our first-in-class sign technology.

Most recently, we bolstered our team even further with the promotion of <unk> to Chief Commercial Officer, and the addition of Peter <unk> to the board of directors.

Fifth and finally to support our strategic and focused growth plan, we are well capitalized to fund our operations into early 2024.

At carrier farm everything we do is driven by our mission to positively impact patients lives and defeat cancer.

Our foundation is in our sight.

And we are the global leader with our first in class Science technology.

Richard Paulson: Against this backdrop, we believe we have a strong organization which allows us to begin 2022 primed to support patients and deliver for shareholders this year and beyond. Turning now to slide six. Driven by our vision, our innovation, as well as our scope and range of data, we are focused on our core program. Multiple Myeloma, Endometrial Cancer, Myofibrosis, and Myodysplastic Syndrome. As we now turn to slide seven, I would like to turn the call over to Sohanya for her to review the commercial results for the quarter. Sohanya?

Against this backdrop, we believe we are a strong organization, which allows us to begin 2022, Brian to support patients and deliver for shareholders This year and beyond.

Turning now to slide six.

Driven by our vision, our innovation as well as our scope and range of data we are focused on our core program.

Multiple myeloma endometrial cancer.

Fibrosis.

Ill dysplastic syndrome.

As we now turn to slide seven I would like to turn the call over to Sondra for her to review the commercial results for the quarter Joanna.

Thank you Richard and good morning, everyone.

Sohanya Cheng: Thank you, Richard, and good morning, everyone. As Richard mentioned, we have maintained strong growth in the fourth quarter and continue to make excellent progress across key indicators since our second line plus launch at the beginning of 2021. Please now turn to slide 8.

Richard mentioned, we have maintained strong growth in the fourth quarter and continue to make excellent progress across key indicators since our second line plus launch at the beginning of 2021.

Please now turn to slide eight.

On this slide we show how we have rapidly evolved opioid dosing in three important ways over the past two years to improve efficacy and patient experience.

Sohanya Cheng: On this slide, we show how we have rapidly evolved exfobio dosing in three important ways over the past two years to improve efficacy and the patient experience. On the left, from a high dose administered at 160 milligrams per week to lower doses of 60 to 100 milligrams, in the center from twice weekly to once weekly dose, and on the right, evolving from a doublet in later lines to triplets in earlier lines.

Hello.

From a high dose administered at 160 milligrams per week.

Lower doses of 60 to 100 milligrams.

In the center from twice weekly to once weekly dosing and on the right.

<unk> all been from a doublet in later line two triplets.

Triplets in earlier lines.

Wireless <unk> in combination with Velcade is the approved indication and the only indication we promote to explore <unk> in combination with <unk>, Derek Tim or Matt and Carfilzomib.

Sohanya Cheng: While its foveo in combination with Valcade is the approved indication and the only indication we promote to, its foveo in combination with Tomo Lidemite, Derritam Amman, and Carfels Amiff are also included as part of the MCCN guidelines for the treatment of second-line plus months, This evolution is an important part of the drug's life cycle, and we have worked rapidly to explore different doses and combinations as we continue to expand the breadth and depth of Exsovio's life cycle. Turning now to slide nine, it is clear that over the last few quarters, we positively changed the growth trajectory and continue to make steady progress across key indicators.

So included as part of the <unk> guidelines for the treatment of second line plus multiple myeloma.

This evolution is an important part of the drug's lifecycle and we have worked rapidly to explore different doses and combinations as we continue to expand the breadth and depth of external views lifecycle.

Turning now to slide nine it is clear that over the last few quarters, we positively change the growth trajectory and continue to make steady progress across key indicators.

We continue to see a positive shift from the penta refractory setting.

Sohanya Cheng: We continue to see a positive shift from the penta refractory setting towards earlier light, with the most rapid growth this year in the third line, as we continue to focus our messaging on exfovio as a new class of therapy in the white space of second to fourth line in the myeloma treatment journey. We are also expanding in the breadth and depth of use of Expovio with strong growth in the community setting.

It's early aligned.

With the most rapid growth this year in the third line as we continue to focus on messaging on <unk> as a new class of therapy in the white space.

Second to fourth line in the myeloma treatment journey.

We are also expanding in the breadth and depth of use of <unk> with strong growth in the community setting.

Sohanya Cheng: We continue to add more accounts every quarter and increase penetration at Tough Myeloma Care. 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 early alliance, as physicians have an increasingly positive experience with the lower-dose once-weekly expovio-based triplet regimen. While we continue to see the impact of COVID on oncology patient visits compared to pre-COVID baseline, our field team achieved a high level of live engagements with physicians in the fourth quarter. As we've all observed in January, the Omicron variant has added pressure on the health care system and our access to providers.

We continue to add more accounts every quarter and increased 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 <unk> based triplet regimens.

While we.

Continue to see the impact of Covid on oncology patient visits compared to pre COVID-19 baseline.

Our field team achieved a high level of live engagement with physicians in the fourth quarter.

As we've all observed in January the Omicron barrier has added pressure on the health care system and our access to providers.

Jatin Shah: We will continue to adapt to this and remain focused on strong execution and positioning expovio as a standard of care in Second Line Plus. Building on our momentum in 2021 and with a rapidly advancing mahaloma pipeline, we expect to continue to drive steady growth in the near, mid and long term. If you'll advance to slide 10, I will now turn the call to Jason to discuss the positive update from a phase 3 C-endo study evaluating Selinexor in patients with endometrial cancer. Thank you, Sohanya.

We will continue to adapt to this and remain focused on strong execution and positioning <unk> as a standard of care in second line plus.

Building on our momentum in 2021 and with a rapidly advancing myeloma pipeline, we expect to continue to drive steady growth in the near mid and long term.

If you'll advance to slide 10, I will now turn the call to Jason to discuss the positive updates from our phase III study evaluating selinexor in patients with endometrial cancer.

<unk>.

Okay.

Thank you Sonya.

Jatin Shah: First, I would like to send a thank you to our teams, the CNDO investigators, our lead global investigator and steering committee chair, Dr. Vergoot from the University of Leuven Cancer Institute in Belgium, and the lead U.S. principal investigator, Dr. Vicky Macker from Memorial Sloan Kettering, as well as our partners, the European Network for Gynecologic Oncology Trials and the GOG Foundation, and of course the patients who participated at the end of the trial and their families. Now, please turn to slide 11, where I'll recap the positive P&O results covered by Richard. I am very pleased to report the Phase III Siendo results demonstrate spallanexer significantly extends remission in patients with advanced or recurrent endometrial cancer.

First I would like to send a thank you to our teams the <unk> investigators are.

Jatin Shah: Delanextro treated patients had a median progression free survival of 5.7 months compared to 3.8 months for patients on placebo, representing an improvement of 50%, hazard ratio of 0.70 with a p-value of 0.0486, representing a 30% reduction in the risk of death, disease progression, or death. In addition, Selenexor demonstrated a sustained and long-term benefit in progression-free survival as seen at 12 months with a 37% increase in the probability that a Selenexor-treated patient will be in remission compared to patients on no treatment for today's current standard of care of watch and wait. In this study, Thalanexrin was well tolerated with no safety signal, no new safety signals identified, and a low discontinuation rate of 10.5% due to adverse events...

Lead global investigator and steering Committee chair, Dr. <unk> and the University of Louisville move in Cancer Institute in Belgium.

Jatin Shah: Additionally, the preliminary data also identified Wild Type T53, again known as a guardian of the genome, in a pre-specified subgroup. We achieved a statistically significant reduction in the risk of disease progression or death. In this pre-specified subgroup of patients with wild-type T53, currently consisting of 103 patients, the data showed an almost four-fold improvement in progression-free survival for Stelin X-ray-treated patients, with a median progression-free survival of 13.7 months, compared to 3.7 months for patients on placebo, with a hazard ratio of Inhibition of XPO1 by Selenexor leads to the nuclear accumulation of P53, which is a well-established tumor suppressor protein, which we believe allows P53 to carry out its function again because Selenexor inhibits XPO1.

And the lead U S principal investigator Dr. Vicki Makar from Memorial Sloan Kettering.

Jatin Shah: So why is this top line data so significant? because there is no current treatment to extend their time intermission for patients in the maintenance setting, which is simply unacceptable. As you can see on slide 12, endometrial cancer is the most common gynecological cancer with significant unmet need for patients with advanced disease. It is projected there will be nearly 66,000 new cases in the U.S. and more than 130,000 new cases in Europe in 2022.

Jatin Shah: The current treatment landscape consists of first line treatment with chemotherapy, typically a taxane plus a platinum, where response rates can be as high as 67%. However, following a response from chemotherapy with no available treatments, the NCCN guidelines recommend a watch and wait approach until disease progresses. The prognosis is poor with this approach, with progression typically within four months for those who have responded to chemotherapy.

As well as our partners the European network for Gynecological oncology trials, and the Doj Foundation and of course, the patients who participated in this the end of the trial and their families.

Now please turn to slide 11 for a recap of the positive <unk> results covered by Richard.

Jatin Shah: Now let me turn the call back to Sohanya's talk in more detail about the market opportunity and patient cell next to her patients cell next to her can benefit if a clue, Thank you, Jason. We have a meaningful market opportunity in front of us. Turning to slide 13, while most of the 66,000 cases in the US are diagnosed with early stage disease and have a good prognosis after surgery alone. A approximately 14,000 patients each year in the US will present with advanced or recurrent disease.

I am very pleased to report the phase III <unk> results demonstrate <unk>.

Jatin Shah: [inaudible] of those patients. Up to 67% of those treated with chemotherapy will respond. Translating to approximately 9,000 patients being eligible to benefit from Selenexor in the maintenance therapy in the front line. Further driving and enhancing that opportunity are several factors.

<unk> significantly extends remission in patients with advanced recurrent endometrial cancer.

Selinexor treated patients had a median progression free survival of five seven months compared to three eight months for patients on placebo.

Sohanya Cheng: First, maintenance therapy is already well established with physicians that treat multiple solid tumors, including breast and ovarian cancer. Second, progression free survival of 5.7 months demonstrated by Selenexor in Ciendo is superior to the watch and weight approach used today. Third, patients are treated until progression in the maintenance setting. And of course, selling next door is an oral medicine, that is well positioned to be the first and only treatment post chemotherapy in the maintenance setting that has the potential to extend time in response and remission.

Representing an improvement of 50%.

Hazard ratio of <unk>, seven zero with a P value of zero.

0.0486.

Representing a 30% reduction in the risk of that disease progression or death.

In addition, selinexor demonstrated sustained and long term benefit in progression free survival.

As seen at 12 months with a 37% increase in probability of Selinexor treated patient, we will be in remission compared to patients on no treatments for today's current standard of care of watch and wait.

In this study.

So next one was well tolerated with no safety signals no new safety signals identified.

And a low discontinuation rate of 10, 5% due to adverse events.

Additionally, the preliminary data also identified in a pre specified subgroup wild.

Wild type P 53, again known as a guardian of genome.

We achieved a statistically significant reduction in the risk of disease progression or death.

In this pre specified subgroup of patients with wild type <unk> three currently consisting of 103 patients.

The data showed almost four fold improvement in progression free survival for <unk> treated patients.

The median progression free survival of 13 seven months.

Compared to $3 seven months for patients on placebo.

With a hazard ratio of 0.38, and the P value of 0.0006.

Inhibition of <unk> leads to new kilo accumulation of <unk> 53, which is a well established tumor suppressor proteins.

Which we believe allows <unk> to carry out its function again, because selinexor inhibits <unk>.

So why is this topline data is so significant.

Because there is no current treatment to extend their time inhibition for patients in the maintenance setting which is simply unacceptable.

As you can see on slide 12, endometrial cancer is the most common gynecologic cancer with significant unmet need for patients with advanced disease.

Sohanya Cheng: And finally, Karyopharm has an established and strong commercial and medical affairs footprint, which is rapidly engaging in preparing for a potential launch. In summary, as we turn to slide 14, we believe Cellynector has the potential to become an exciting new standard of care for women with advanced or recurrent endometrial cancer. This belief is driven by powerful faith-free results.

This projected there'll be nearly 66000, new cases in the U S and more than a 130000, new cases in Europe in 2022.

The current treatment landscape consists of first line treatment with chemotherapy typically a taxane plus the platinum where response rates can be as high as 67%.

However, following a response from chemotherapy with no available treatments. The NCC guidelines recommend a watch and wait approach until disease progresses.

The prognosis is poor with this approach with progression typically within four months for those who have responded to chemotherapy.

Now, let me turn the call back to <unk> to talk in more detail about the market opportunity and patients selinexor.

<unk> Selinexor can benefit if approved.

Thank you Jason.

Sohanya Cheng: A dire unmet need in the maintenance setting and a significant market opportunity. In short, a paradigm shift for patients living with advanced endometrial cancer. Turning to slide 15, I'd like to now turn the call back to Jason to discuss highlights from some of our other core programs. Thank you, Sohanya.

We have a meaningful market opportunity in front of us.

Turning to slide 13, while most of the 66000 cases in the U S diagnosed with early stage disease and have a good prognosis after surgery alone.

Proximately 14000 patients each year in the U S will present with advanced or recurrent disease.

Of those patients.

Up to 67% of those treated with chemotherapy will respond.

Leading to approximately 9000 patients being eligible to benefit from selling next door in a maintenance therapy in the frontline.

Further driving and enhancing that opportunity or several factors.

May.

Maintenance therapy is already well established with physicians that treat multiple solid tumors, including breast and ovarian cancer.

Second progression free survival of five seven months demonstrated by selling next or in the Endo is superior to the watch and wait approach used today.

Third.

<unk> are treated until progression in the maintenance setting.

For Selinexor is an oral medicine that is well positioned to be the first and only treatment post chemotherapy in the maintenance setting that has the potential to extend time in response and remission.

And finally carrier farm has been established and strong commercial and medical affairs footprint, which is rapidly engaging and preparing for a potential launch.

In summary, as we turn to slide 14, we believe Selinexor has the potential to become an exciting new standard of care for women with advanced recurrent endometrial cancer.

This belief is driven by powerful phase III results.

Dire unmet need in the maintenance setting and a significant market opportunity.

In short a paradigm shift for patients living with advanced endometrial cancer.

Turning to slide 15, I'd like to now turn the call back to Jason to discuss highlights from some of our other core programs.

Thank you so turning to slide 16, we will now turn to our other core programs, which are focused on blood cancers.

Jatin Shah: Turning to slide 16, we'll now turn to our other core programs, which are focused on blood cancer. We are confident in our programs with a proven track record with robust clinical data. Salinexer has demonstrated strong response rates, both as a single agent and in combination in many hematologic indications, first in myeloma and diffuse large B cell lymphoma, and more recently in myelofibrosis and myelodysplastic syndrome.

We are confident in our programs with a proven track record with robust clinical data.

Selinexor has demonstrated strong response with both as a single agent and in combination in many hematologic indications.

First in myeloma and diffuse large b cell lymphoma.

And more recently in myelofibrosis.

Myelodysplastic syndromes.

Single agent activity is one of the key factors in predicting positive phase III results and regulatory approvals and so next year has been no exception.

Jatin Shah: Single Asian Activity is one of the key factors in predicting positive phase three results and regulatory approvals, and cell indexer has been no exception. In multiple myeloma, there's an increasing use, at least 80% and growing, in the first two lines of an anti-CD38-based therapy, who has limited data in one to four lines of therapy from trials of how to manage patients whose disease progresses after an anti-CD38-based treatment. This is where we have focused and generated data with Selenexor-based combinations that include pomalidomide, carfilzomib, and bortezomib with a goal of solving that data gap.

In multiple myeloma.

Creasing use at least 80% and growing in the first two lines of an anti CD 38 based therapy.

There is limited data in one to four lines of therapy from trials with how to manage patients whose disease progresses. After an anti CD 38. These treatment.

This is where we are focused and generated data with selinexor based combinations that include <unk> carfilzomib and bortezomib with a goal of solving that data gap.

As you can see on slide 17.

Jatin Shah: As you can see on slide 17, the design of our Phase 3 SPD study continues to fill this data gap and further evaluates and entrenches Selenexor-based combinations host in anti-CD38. This study will compare the triplet regimen of elotuzumab, amalidomide, and dexamethasone, or EPD, versus SPD.

Design of our phase III SPD study continues to fill this data gap and further evaluate and entrenches <unk> based combinations boosting anti CD 38.

This study will compare the triplet regimen of <unk>, <unk> and dexamethasone for <unk>.

Versus SPD.

Jatin Shah: This will be our global study that is expected to recruit up to 280 patients who received one to four prior lines of therapy. We expect to dose the first patient during the first quarter of 2022 and top line data is expected in 2024, if approved, the SPD triplet with a second all oral triplet combination. Approved in relapsed or fractured multiple myeloma....

This will be a global study is expected to up to 280 patients who received one to four prior lines of therapy.

We expect to dose the first patient during the first quarter of 2022 and top line data is expected in 2024.

If approved the SPD triplet with the second oral triplet combination.

In relapsed refractory multiple myeloma.

Yeah.

Jatin Shah: Turning now to the Expovio regulatory expansion beyond the U.S. on slide 18. We continue to see increased access to Selenepser worldwide through regulatory filings made by both Karyopharm and our global strategic partner. In Europe, the marketing authorization application based on clinical data from the Phase 3 Boston study has been validated and is currently under review by the CHM team. We expect this review to be completed during the first half of 2022. Our partner, Antigen, received conditional approval for expovial for relapsed multiple myeloma in China.

Turning now to the exposure of regulatory expansion beyond the U S on slide 18.

We continue to see increased access to sell and that's a worldwide through regulatory filings made by Booth carrier farm and our global strategic partners.

In Europe , the marketing authorization application based on clinical data from the Phase III Boston study has been validated.

Is currently under review by the CH empty.

We expect this review to be completed during the first half of 2022.

Our partner antigen received conditional approval for <unk> for relapsed multiple myeloma in China.

Jatin Shah: There are also new drug submissions or applications for SBD submitted or on file in Canada and multiple Asia Pacific markets through our strategic partners. We look forward to keeping you updated on those approvals as they happen. Now turning to slide 19, we review myelofibrosis. We believe Selenexor has the potential to improve outcomes for patients with JAK inhibitor refractory disease. As seen on slide 20, there are approximately 5,000 patients per year in the U.S. diagnosed with myelofibrosis. A disease that's characterized by significant anemia, weakness, fatigue, and splenic enlargement.

And there are also new drug submissions were applications, where SPD submitted or on file in Canada, and multiple Asia Pacific markets.

Through our strategic partners.

Look forward to keeping you updated on those approvals as they happen.

Now turning to slide 19.

And we review Myelofibrosis, we believe <unk> has the potential to improve outcomes for patients with JAK inhibitor refractory disease.

And as seen on slide 20, there are approximately 5000 patients per year in the U S diagnosed with myelofibrosis.

The disease is characterized by significant anemia weakness fatigue and splenic enlargement.

Only class of drugs approved in myelofibrosis are JAK inhibitors.

Jatin Shah: The only class of drugs approved in myelofibrosis are JAK inhibitors. Unfortunately, these are not curative and 60% of patients do not respond. Among the 40% of patients who do respond initially, the response lasts at most four years. There is no other class of drugs approved when survival is short, typically less than 14 months for those patients once a JAK inhibitor stops working.

Unfortunately, these are not curative and 60% of patients do not respond.

Among the 40% of patients who do respond initially to response last at most four years.

There is no other class of drugs approved and survival is short typically less than 14 months for those patients once a JAK inhibitor stops working.

It is in this setting with promising data with once weekly low dose selinexor.

Jatin Shah: It is in this setting we have promising data with once weekly low dose telonexer. Turning now to slide 21, recent data that were reported at ASH 2021 show that for patients on study for at least 24 weeks, 40% of patients achieved an SVR35, and 60% of patients achieved SVR25. These are very compelling results in this patient population. As you can see on slide 22, the median duration of treatment was 11 months with a range of 2.8 to 28.8 months. On slide 23, you can see that among patients with anemia or transfusion dependence at screening, defined as a hemoglobin less than 10 grams per deciliter.

Turning now to slide 21, recent data that we reported at Ash 2021 show that for patients on study for at least 24 weeks.

40% of patients achieved an <unk> 35.

And 60% of patients achieved SVR 25.

These are very compelling results in this patient population.

As you can see on slide 22, the median duration of treatment was 11 months with a range of $2 eight to 28 eight months.

On slide 23.

You can see that among patients with anemia or transfusion dependence at screening.

Find has a hemoglobin less than 10 grams per deciliter.

50% of the patients achieved either an improvement in their hemoglobin levels.

Jatin Shah: 50% of patients achieved either an improvement in their hemoglobin levels or became transfusion independent as of the time of this data readout. Looking at slide 24, based on all these data. We have rapidly moved into a global randomized phase two trial that's recruiting patients with at least six months of prior jack inhibition and randomize them to once weekly low-dose Selenexer for physician's choice. 112 patients are expected to be enrolled, and the first patient was dosed in late 2021.

Became transfusion independent.

At the time of this data readout.

Looking at Slide 24 based on all of these data.

We are rapidly moving to a global randomized phase III trial, that's recruiting patients with at least six months prior JAK inhibition and randomize them to once weekly low dose selinexor for physicians choice.

112 patients are expected to be enrolled in the first patient was dosed in late 2021.

Jatin Shah: Top line data from this trial is expected during the second half of 2023. Turning now to slide 25 with our program in MDS and our second novel compound. We believe Eltenexor has the potential to improve outcomes in patients with hypomethylated refractory MDS. On slide 26, we show that approximately 15,000 patients are diagnosed each year in the U.S. with intermediate to high-risk MDS who need therapy. Again, currently the only class of drugs that are approved are hypomethylating agents.

Topline data from this trial is expected during the second half of 2023.

Turning now to slide 25, with our program in Mds and our second novel compound. We believe <unk> has the potential to improve outcomes in patients with hypo <unk> agent refractory Mds.

On slide 26, we show that approximately 15000 patients are diagnosed each year in the U S with intermediate to high risk Mds, who need therapy.

Again currently the only class of drugs that are approved or hypo <unk> living agents.

Jatin Shah: Once the disease progresses on HMA, there are no other approved therapies and survival is very short, along the line of four to six months. There's a clear, high, unmet need and an opportunity to improve outcomes for patients with MDS that's refractory to HMAs. Turning to slide 27, our Phase 1 study of single-agent L-Connectors showed clear activity in patients with MDS refractory to HMAs. In that study, LTIN-XR demonstrated a 53% overall response rate and a median overall survival of 9.9 months, doubling historical controls of four to six months.

Once the disease progresses on HMA or no other approved therapies and survival is very short along the line of four to six months.

There is a clear high unmet need and an opportunity to improve outcomes for patients with Mds that is refractory to hma's.

Turning to slide 27, our phase one study of single agent <unk> issued clear activity in patients with Mds refractory to HMH.

That study <unk> demonstrated a 53% overall response rate and a median overall survival of nine nine months doubling historical controls of four to six months.

In addition, new results reported at Ash 2021.

Jatin Shah: In addition, new results for the report of ASH 2021, demonstrate that the response rates also correlated to improved overall survival. The median overall survival for patients with a complete response was nearly 12 months compared to three months for patients with progressive disease, a hazard ratio of 0.23. Based on this promising signal observed in the phase one study on slide 28, shows our ongoing phase two expansion that we've initiated in 2021. The top line data is expected in 2023.

Demonstrated response rates also correlated to improve overall survival.

The median overall survival for patients with a complete response with nearly 12 months compared to three months for patients with progressive disease, a hazard ratio of 0.0 to three.

Based on this promising signal observed in the phase one study on slide 28.

<unk> is our ongoing phase II expansion and we've initiated in 2021 top line data is expected from 2023.

Also of note just a few weeks ago, the FDA granted orphan drug designation for <unk> for the treatment of Mds.

Jatin Shah: Also of note, just a few weeks ago, the FDA granted Orphan Drug Designation for Eltinexor for the treatment of MDS. We believe this designation reinforces Eltenex's potential to improve clinical outcomes for patients with HMA refractory MDS. With that, now I'll advance to slide 29 and turn the call over to Mike Mason to review the strategic partnerships driving our global footprint, as well as our quarterly and full-year financials.

We believe this designation reinforces <unk> has potential to improve clinical outcomes for patients with HMA refractory Mds.

With that now ill advance to slide 29, and turn the call over to Mike Mason to review the strategic partnerships driving our global footprint as well as our quarterly and full year financials Mike.

Mike Mason: Thank you, Jayden. Turning now to slide 30, our business development activities continue to focus on leveraging strategic partners to support commercialization outside the United States. As Richard mentioned earlier, in December 2021, we signed an exclusive license agreement with the Menorini Group, whereby Menorini will develop and commercialize mixophobia in the EU, the UK, and Latin America, among other territories.

Thank you Jason turning now to slide 13, our business development activities continue to focus on leveraging strategic partners to support commercialization outside the United States.

As Richard mentioned earlier in December 2021, we signed an exclusive license agreement with the memory group, whereby <unk> will develop and commercialize <unk> in the EU the U K and Latin America among other territory.

Mike Mason: In exchange, Karyopharm receives an upfront payment of $75 million and is eligible to receive an additional $202.5 million in future milestones based on regulatory and sales performance, plus tiered double-digit royalties on that, Manarini is a strong EU-based partner with over $4 billion in annual revenue. They operate in over 140 countries and have a deep commitment to developing treatment addressing oncologic and hematologic disease. This deal adds to the growing global footprint, bringing Expovio to patients worldwide with partners Forest in Canada, Neopharm Israel, and Antigen in Asia Pacific.

In exchange dairy farmers sees an upfront payment of $75 million and is eligible to receive an additional $202 $5 million in future milestone based on regulatory and sales performance plus tiered double digit royalties on that.

<unk> has a strong base for the strong EU based partner with over $4 billion in annual revenue the operating over 140 countries and have a deep commitment to developing treatments addressing oncologic and hemo hematologic diseases.

Deal adds to the growing global footprint, bringing <unk> to patients worldwide with partners for Us and Canada, Nufarm, Israel and antigen in Asia Pacific.

Mike Mason: With Antigen, Karyopharm recorded $19.5 million in milestone revenue from Antigen in the fourth quarter of 2021, with cash payment expected one year from the anniversary of their launch. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights to begin on slide 31. Total revenue for the fourth quarter of 2021 was $126.3 million, compared to $35.1 million for the fourth quarter of 2020.

With antigen tariff arm recorded $19 5 million in milestone revenue from <unk> in the fourth quarter 2021 with cash payment expected one year from the anniversary of the launch.

Turning to our financials since we issued a press release earlier today with the full financial results I will just focus on the highlights on slide 31.

Mike Mason: Net product revenue, from U.S. Commercial Sales of Expovio for the fourth quarter of 2021 was $29.8 million compared to $20.2 million for the fourth quarter of 2020, representing a 47% increase year-over-year. The estimated growth to net discount for Expovio in the fourth quarter was 15%.

Total revenue for the for the fourth quarter of 2021 was $126 3 million compared to $35 1 million for the fourth quarter of 2012.

Net product revenue.

From U S commercial sales of exposure for the fourth quarter of 2021 was $29 8 million compared to $20 2 million for the fourth quarter of 2020, representing a 47% increase year over year.

The estimated gross to net discount for <unk> in the fourth quarter was 15%, we expect gross to net discounts to be in the 15% to 20% range for the full year of 2022.

We recognized $96 5 million of license and other revenue in the fourth quarter of 2021, including the upfront payment of $75 million.

Mike Mason: We expect growth to net discounts to be in the 15 to 20% range for the full year 2022. We recognize 96.5 million of license and other revenue in the fourth quarter of 2021, including the upfront payment of $75 million from venerated, R&D expenses for the fourth quarter of 2021 were $44 million compared to $37.2 million for the fourth quarter of 2020. FG&A expenses for the fourth quarter of 2021 were $34.6 million compared to $33.9 million for the fourth quarter of 2020. Cash, cash equivalents, restricted cash, and investments as of December 31, 2021 totaled $235.6 million compared to $276.7 million as of December 31, 2020.

R&D expenses for the fourth quarter of 2021 or $44 million compared to $37 2 million for the fourth quarter of 2020.

SG&A expenses for the fourth quarter of 2021 were $34 6 million compared to $33 9 million for the quarter.

Cash cash equivalents restricted cash and investments as of December 31, 2021 totaled $235 6 million compared to $276 7 million as of December 31, 2020.

Based on our current operating plan, we are expecting net product revenue of $135 million to $145 million for 2022, reflecting approximately 40% growth compared to 2021.

Richard Paulson: Based on our current operating plan, we are expecting net product revenue of $135 to $145 million for 2022, reflecting approximately 40% growth compared to 2021, non-GAAP R&D and SG&A expenses, which excludes stock-based comp expense to be in the range of $265 to $280 million for the full year of 2022. And finally, 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 early 2021. I'll now flip to slide 32 and turn the call over to Richard for some final thoughts. Richard.

non-GAAP , R&D and SG&A expenses, which excludes stock based comp expense to be in the range of $2 $65 million to $280 million for the full year of 2022, and finally that our existing cash cash equivalents and investments as well as the revenue we expect to generate from <unk> product sales and other license revenue will be sufficient to fund our planned.

Since early 2024.

I'll now flip to slide 32, and turn the call over to Richard for some final thoughts Richard.

Richard Paulson: Thanks, bye. 2021 was a very strong year for Karyopharm and I'm excited about our future, especially following the positive phase 3 scandal study, plus our progressing and focused pipeline. We are maintaining strong momentum with a number of key near-term catalysts and corporate milestones for us to deliver on as we continue to deliver for patients. With high end met needs and strength in our organization as outlined on slide 33. For the multiple myeloma program, we expect to leverage our commercial capabilities, striving to become the standard of care in second-line plus post-NT CD38 and increase U.S. expovial sales throughout the year, to dose the first patient in our Phase 3 study evaluating selonexor, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma in the first quarter and receive a decision from the CHMP and EMA on our MAA requesting approval for selonexor, fortesimib, and dexamethasone in patients with multiple myeloma following at least one prior therapy in the first half of 2022.

Thanks, Mike.

101 was a very strong year for <unk> and are excited about our future, especially following the positive phase III agenda study plus are progressing and focus pipeline.

We are maintaining strong momentum with a number of key near term catalysts and corporate milestones for us to deliver on as we continue to deliver for patients with high unmet need.

And strengthen our organization as outlined on slide 33.

For the multiple myeloma program, we expect to leverage our commercial capabilities striving to become the standard of care in second line plus post anti CD 38, and increased U S. <unk> sales throughout the year.

To dose the first patient in our phase III study evaluating selinexor.

And next methadone in patients with relapsed or refractory multiple myeloma in the first quarter and receive a decision from the <unk> and EMA on our MAA requesting approval for Selinexor Bortezomib and dexamethasone in patients with multiple myeloma following at least one prior therapy and the first half of 2002.

'twenty two.

For the endometrial cancer program, we plan to submit the detailed results from this study for presentation at upcoming medical meetings in the first half of 'twenty two.

Richard Paulson: For the Endometrial Cancer Program, we plan to submit the detailed results from the study for presentation at upcoming medical meetings in the first half of 2022, to plan to submit a supplemental new drug application to the FDA during the first half of 2022. And finally, we plan to conduct pre-launch activities in anticipation of a potential approval and launch in the first half of 2023.

We plan to submit a supplemental new drug application to the FDA during the first half of 'twenty two.

And finally, we plan to conduct prelaunch activities in anticipation of a potential approval and launch in the first half of 'twenty three.

For the Myelofibrosis program, we expect to report top line phase one data in combination with JAK inhibition and treatment naive myelofibrosis during the second half of 'twenty two.

Richard Paulson: For the myofibrosis program, we expect to report top-line Phase I data in combination with JAK inhibition and treatment-naive myofibrosis during the second half of 2022, and report top line phase 2 data in previously treated myofibrosis during the second half of 23. And finally, for the MDS program, we expect to report Preliminary Phase I AltenAxor data in combination with an HMA in Frontline MDS in 2022, and report top-line Phase II data in HMA Refractory MDS in the first half of 2023. In closing, I would like to give a heartfelt thank you to our teams, especially all the dedicated people who served to move the Shando trial forward during COVID and deliver our data rapidly.

And report top line phase II data and previously treated myelofibrosis during the second half of 'twenty three.

And finally for the Mds program.

Expect to report preliminary phase <unk> data in combination with an HMA and frontline Mds in 'twenty two and.

Report top line phase II data and HMA refractory Mds in the first half of 'twenty three.

In closing I would like to give a heartfelt. Thank you to our teams.

Actually all of the dedicated people who served to move the agenda trial forward during COVID-19 and deliver our data rapidly.

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. Thank you. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the key.

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

With that I would now ask the operator to open the call up for <unk>.

And answer portion of today's call operator.

Thank you we will now begin the question and answer session.

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 mckeith.

To withdraw your question. Please press Star then two.

Operator: To withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Maurice Raycroft with Jeffries. Please go ahead.

At this time, we will pause momentarily to assemble our roster.

Our first question comes from Maury Raycroft with Jefferies. Please go ahead.

Hi, good morning, everyone and congrats on the update today and thanks for taking my questions.

Maurice Raycroft: Hi, good morning, everyone, and congrats on the updates today. Thanks for taking my questions. I'll start off with myeloma guidance. Can you tell us what's going into your assumption of 145 to 155 million in the 40% growth for expoVO in 2022? What proportion of earlier line patients are you assuming? And is there anything built into your assumptions under ability?

I'll start off with myeloma guidance.

Can you tell us what's going into your assumption of $145 million to $155 million and the 40% growth for <unk> in 2022, while proportion of earlier line patients are you assuming and is there anything built into your assumptions on durability.

Thanks Laurie.

Richard Paulson: Thanks, Maury. Just to correct that our guidance is 135 to 145 for the year. And maybe I'll let Sohanya talk to what's going into that, that guidance. Sohanya?

Just to correct that our guidance is $1 35 to $1 45 for the year.

And maybe I'll, let <unk> talk to whats going into that to give that guidance. So anya.

Great. Thanks, Marty for the question. So yes, we feel very confident about the annual guidance of 135 to 145, which is roughly 40% growth year over year and it's in line with many best in class launches in the multiple myeloma space.

Sohanya Cheng: Great, thanks, Maury, for the question. So, yeah, we feel very confident about the annual guidance of 135 to 145, which is roughly 40% growth year over year, and it's in line with many best in class launches in the multiple myeloma space. As far as growth drivers, we look at what drove growth in 2021, and it was strong execution and the new positioning in the white space of second to fourth mind, and we'll continue to focus in these areas. There are three key growth drivers. The 1st is the continued shift into earlier lines. Where we anticipate seeing the most continued rapid growth in the 3rd line. In fact, in 2021.

As far as growth driver as we look at what drove growth in 2021, and it was strong execution and the new positioning and the white space. The second to fourth line and we will continue to focus on these areas. There are three key growth drivers. The first is the continued shift into earlier line, where we are.

<unk> being the most continued rapid growth in the third line in fact in 2021.

Sohanya Cheng: Exscobio was the fastest-growing multiple myeloma product in the third line, and we anticipate continuing to see this shift into earlier lines. We're approaching roughly about half of our patients now in the second to fourth line, and then the remaining half in the fifth line plus. The second growth driver is the continued expansion in the breadth and depth of use of the product.

<unk> was the fastest growing multiple myeloma product in the third line and we anticipate anticipate continuing to see the shift into earlier lines. We.

We are approaching roughly about half of our patients now in that second to fourth line and then the remaining half in that first line plus.

The second growth driver is the continued expansion in the breadth and depth of use of the product. So we continue to add more accounts.

Sohanya Cheng: So we continue to add more accounts as well as increase our penetration at our top myeloma accounts. The third growth driver is to continue to move the needle on our intent to prescribe data and the perception of the product. And as the community is building confidence in our use of our new lower dose, once weekly exfovio based triplet regimen, that shift will continue to happen. So those are the kind of the key ingredients driving growth and part of the guidance for next year. Got it. That's really helpful.

As well as increase our penetration at our top myeloma accounts.

The third growth driver is to continue to move the needle on I intend to prescribe data and the perception of the product and as the communities building confidence in our use of our new lower dose once weekly <unk> based triplet regimen that shift will continue to happen. So those are the kind of the key ingredients driving growth.

And part of the guidance for next year.

Got it that's really helpful.

Sohanya Cheng: And I also wanted to ask a question on CNDO. So if you can talk more about the proportion of endometrial maintenance, that is wild type P53, and how does that population fit into your regulatory and commercial strategy? Yeah, thanks so much for that, Maury.

Also wanted to ask a question on <unk>. So.

If you could talk more about the proportion of endometrial maintenance that is a wild type <unk> three and how does that population fit into your regulatory and commercial strategy.

Yes, thanks, so much for them already so when you look at patients with P 53, Wild type <unk>.

Jatin Shah: So when we look at patients with p53 wild type, that's approximately 50% of patients with advanced endometrial cancer, who have this. And we looked at within our study, approximately 50% as well in our study have wild type p52. So consistent with what we see in a broader patient population. I think the second question comes to the regulatory kind of path forward of that.

Approximately 50% of patients with advanced endometrial cancer, who have this.

We look at within our study approximately 50% as well in our study have wild type <unk>, so consistent with what we see in a broader patient population.

I think the second question comes to the regulatory path forward with that so I think I want to be very clear to remind folks that we have a positive phase III study for the overall patient population. So we have ongoing discussions with the agency and we'll continue to have that to the sweet part of that discussion.

Jatin Shah: So I think I want to be very clear and remind folks that we have a positive phase three study for the overall patient population. So we have ongoing discussions with the agency and we'll continue to have that. So this will be part of that discussion for the final label negotiation. Got it.

The final label negotiations.

Got it.

Jatin Shah: And also, for the 103 patients, so that number with the wild type P53, is that a two to one ratio too, for this study? Or can you say more about how many patients were in the treatment arm versus placebo? And just clarifying, does that number represent the number of events?

Also for the 103 patients so.

That number with the wild type <unk> 53 is that a two to one ratio to for this study.

Can you say more about.

How many patients were in the treatment arm versus placebo and just clarifying does that number represents the number of events or is.

The PFS for the P 53 population is still maturing.

Yes, so those 103 patients I would say.

Jatin Shah: Or is the PFS for the P53 population still maturing? Yeah, so those 103 patients, I would say the final top line results are based on 104 patients and same thing for the subgroup analysis. So that itself is fixed.

The final top line results are based on the 104 patients and same thing for the subgroup analysis. So that itself is fixed.

And so we will present the full data set at.

Jatin Shah: And so we'll present the full data set at the major medical meeting. Got it. Okay, congrats again, and thanks for taking my, Thanks, Marty. Our next question comes from Peter Lawson with Barclays. Please go ahead. Hey, thanks for taking my question. And congratulations. On the on the Ciendo study, just, As we think about the P53 subgroup, is that something you'd push in the label or are you going for a broader label? maintenance setting and interview.

Major medical meeting.

Got it okay. Congrats again and thanks for taking my question.

Thanks Mark.

Our next question comes from Peter Lawson with Barclays. Please go ahead.

Peter Lawson: Yeah, thanks, Peter. I think I think as we just touched on, you know, that the overall study, obviously, as we've shared, it's positive and has a, you know, positive statistical significant improvement in patients, in the maintenance setting. And so when we look at this area right now, you know, there are no other approved therapies for these patients.

Hey, Thanks for taking my question.

Congratulation to them.

The.

The <unk> study.

Yeah.

As we think about.

P 53 separate.

Something youll push in the label you're going for a broader label.

Maintenance testing and introduce you okay.

Yeah. Thanks, Peter I think I think as we just touched on.

The overall study, obviously and as we've shared is positive and is a.

Positive statistical significant improvement in patients.

In the maintenance setting and so when we look at this area right now there are no other approved therapies for these patients.

Jatin Shah: So as we look at that, you know, we need to understand the full data set as we continue to do the analysis on this and we'll engage with the FDA, you know, over the near term to work on reviewing the data and determining what the final label will be. Gotcha. And will we get a, P53 mutant breakout for whether it's PFS or hazard ratio. Yeah, absolutely. So we'll provide the full data set as we present at a major medical meeting. Got you.

As we look at that we need to understand that the full dataset as we continue to do the analysis on this and we will engage with the FDA.

Over the near term to work on are reviewing the data and determining what the final label Lily.

Got you.

Get a.

<unk> three mutant breakout for whether it's PFS hazard ratio.

Yeah, absolutely we will provide the full datasets.

As we presented at a major medical meeting.

Got you okay. Thanks for taking the question.

Our next question comes from Michael <unk> with Morgan Stanley . Please go ahead.

Peter Lawson: Okay. Thanks for taking the question. Our next question comes from Mike Old with Morgan Stanley. Please go ahead. Hey, guys.

Hey, guys. Thanks for taking the question just a follow up on <unk> 2022 guidance and just just thinking about the quarterly progression here should.

Mike Old: Thanks for taking the question. Just to follow up on Expovio 2022 guidance. Just thinking about the quarterly progression here, should we consider maybe any seasonality in one cue or continued maybe pressure from Omicron that persists in one cue? Sohanya, do you want to take that?

Should we consider maybe any seasonality in one Q4 continued may be pressure from home across.

That persist in <unk>. Thanks.

And so I need to want to take that.

Yes.

Sohanya Cheng: Yep. Thanks for the question, Mike. So we are not disclosing quarterly guidance.

For the question Mike. So we are not disclosing quarterly guidance, we've provided the annual guidance of about $135 million to $145 million as far as quarterly seasonality given the variances we've seen the market in the different quarter to your point, we will focus on year over year performance moving forward.

Sohanya Cheng: We've provided the annual guidance of the 135 to 145 million as far as quarterly seasonality, given the variances, we've seen the market in the different quarters. To your point, we will focus on year over year performance moving forward for that order. And again, we feel positive about the annual guidance we've given to answer your question on Omicron variant. So, in Q4 and 2021, we did see the impact of COVID on oncology patient visits compared to pre COVID baselines.

That quarter.

And again, we feel positive about the annual guidance we've given.

Answer your question on Omicron Varian so.

Sohanya Cheng: However, in January, the Omicron variant has now added pressure on the healthcare system and our access to providers. But we continue to leverage a very nimble and patient centric sales force and strong digital and commercial capabilities and we continue to see strong across our key growth drivers. So we remain laser focused on strong execution and positioning as standard of care and the second line plus. Got it.

Q4, and 2021, we did see the impact of Covid on oncology patient visits compared to pre COVID-19 baseline.

However in January the Omicron theory has now added pressure on the health care system, and our access to proprietary but we.

We continue to leverage a very nimble and patient centric salesforce and strong digital and commercial capabilities and we continue to see strong across our key key growth drivers. So we remain laser focused on strong execution and positioning <unk> as the standard of care in second line.

Class.

Got it thank you.

Our next question comes from Brian Abrahams with RBC. Please go ahead.

Sohanya Cheng: Thank you. Our next question comes from Brian Abrams with RBC. Please go ahead. Hi, this is Steve on behalf of Brian.

Hi, This is Steve on for Brian Congrats on the progress and thanks for taking our question, but curious do you plan to revisit any other indications in the sign study to look for a possible effect of P 53 in ovarian or cervical cancer, maybe as a follow up are there any differences in the adverse event profile between the wild type population and the overall population. Thank you.

Brian Abrams: Congratulations on the progress and thanks for taking our question. We're curious, do you plan to revisit any other indications in the assigned study to look for a possible effect of P53, say in ovarian or cervical cancer? And maybe, as a follow-up, were there any differences in the adverse event profile between the wild-type P53 population and the overall population?

Yes, so im sorry. The first question was on adverse event profile and so I think we can comment is that we don't expect to see any differences right and the biology between those two patient populations and we will provide that full data set as we move along with key though.

Jatin Shah: Yes, I'm sorry, the first question was on adverse event profile. And so I think what we can comment is that we don't expect to see any differences right in the biology between those two patient populations, and we'll provide that full data set as we move along. What's key, though, is that what you need is something that's well tolerated in the maintenance setting.

What you need is something that's well tolerated in the maintenance setting and the biggest indicator is at 10, 5% discontinuation rate, which is very low in that setting and really speaks to the tolerability of once weekly low dose selinexor in the maintenance setting.

Jatin Shah: And the biggest indicator is that 10.5% discontinuation rate, which is very low in that setting, and really speaks to the tolerability of once weekly low dose Selenexer in the maintenance setting. Can you repeat your first question for me? Because I'm looking at other indications of time, with the science that were in the science study.

Could you repeat your first question for me.

As I'm looking at other indications in time.

With the signs that we are in the same study.

Jatin Shah: Yeah, so looking at ovarian cancer and endometrial and cervical cancer. So those are the two other histologies in the signed study ovarian and endometrial. So we're clearly committed to gynecologic malignancies, and we'll have further discussions. But again, our four key programs is going to be myelofibrosis, MDS, myeloma, and endometrial cancer, and we'll continue to build upon this platform. So great.

Yes, so looking at the ovarian cancer and endometrial and cervical cancer. So those are the two other histology in the sign study ovarian endometrial. So we're clearly committed to going to a closet malignancies and we'll have further discussions.

Again, our four key programs is going to be myelofibrosis, Mds myeloma endometrial cancer and will continue to build upon this platform. So.

Great. Thanks.

Our next question comes from Eric Joseph with Jpmorgan. Please go ahead.

Eric Joseph: Our next question comes from Eric Joseph with J.P. Morgan. Please go ahead. Hi, good morning.

Hi, good morning, Thanks for taking the questions.

I'm curious as it relates to <unk>.

Eric Joseph: Thanks for taking the questions. I'm curious, as it relates to Siendo, I'm curious whether you've taken a preliminary look at OS trend, appreciating that it's not, you know, a primary, it's going to be a secondary point here, just wondering whether it might be a gating factor to an SNDA submission, and whether OS might be part of the overall package that you would submit to FDA. And then, Secondly, as it relates to the primary implant analysis of PFS, does the statistical analysis plan make any distinction between intent-to-treat and a per-protocol treatment population? And if so, what population is reflected in this top-line data set?

I'm curious, whether you've taken a preliminary look at OS trend.

Appreciating that its not a primary is going to be a secondary endpoints here I'm just wondering whether.

It might be a gating factor to it.

The NDA submission.

And whatever.

<unk> might be part of the overall package that you could submit to FDA.

And then.

Secondly, as it relates to that.

The primary endpoint analysis of PFS.

A statistical analysis plan make any distinction between intend to treat and the per protocol.

<unk> and <unk>.

So.

What population as is reflected in the top line data set.

Yes, absolutely so number one no overall survival is not a gating factor the submission of the SBA.

Jatin Shah: Yeah, absolutely. So number one, no, overall survival is not a gating factor to submission of the SNDA. Number two, too early with too few events with overall survival events to make any conclusions. And number three for the primary PFS per the statistical analysis plan agreed and reviewed by the FDA. It is primary is progression free survival by investigator on an intended treat. And that's the data that we have presented. Okay, great.

Two.

Too early with too few events with overall survival events.

To make any conclusions.

And number three for the primary PFS further statistical analysis plan.

Viewed by the FDA. It is primary is progression free survival by investigator on an intent to treat in that study that we presented.

Okay great.

Jatin Shah: And perhaps if I could follow up just one, Expovia question, commercial questions related to the guidance, and also for acute performance. Can you just comment on how patients that were new to brand trended in fourth quarter compared to third quarter, and as part of the guidance for this year, how should we be thinking about that metric, new to brand, trending sequentially? Thanks, Eric. Maybe I'll turn that to you, Sohanya.

And perhaps if I could follow up just one.

<unk> will be a question commercial questions related to the guidance.

And also for key performance can you just comment on how.

Patients that were new to brand trended in the fourth quarter compared to third quarter and as part of the guidance for this year.

How should we be thinking about that metric new to brand.

<unk> sequentially.

Thanks, Eric maybe I'll turn that to use on here.

Yes, Thanks, Eric So we continue to show strong new patient starts.

Sohanya Cheng: Yeah, thanks, Eric. So we continue to show strong new patient starts. And we also showed improvement in our refill rate with patients staying on therapy longer because of the early aligned shifts. I think as we move into 2022, you know, those three key growth drivers of the early aligned shifts, the increase in the breadth and depth of use, and the improvement in our intent to prescribe data should all contribute towards increased momentum with our new patients, as well as our refill rate. Okay, okay.

And we also showed improvement in our refill rate with patients staying on therapy longer because of the early align chip.

As we move into 2022, those three key growth drivers of the earlier lines due to the increase in the breadth and depth of use and the improvement and I intend to prescribe data should all contribute towards increased momentum with our new patients as well as our refill.

Great.

Okay. Okay, alright, thanks for taking the question guys.

Sohanya Cheng: All right. Thanks for taking the questions, guys. Our next question comes from Jonathan Chang with SVB Learing. Please go ahead. Hi, guys.

Thanks.

Our next question comes from Jonathan Chang with SBB Leerink. Please go ahead.

Hi, guys. Thanks for taking my questions and congrats on <unk>.

Jonathan Chang: Thanks for taking my questions and congrats on CIENDO. First question, what is your strategy for commercial success in CIENDO? Are there lessons learned from the multiple myeloma and DLBCL experience that are applicable here? And second question, can you provide any color around the duration of treatment that you're seeing in multiple myeloma? And are you seeing a difference in duration between earlier line versus the PENTER? Myeloma Treatment Center. Thank you. Thanks Jonathan. Maybe I'll take the first question.

First question what is your strategy for commercial successful tender are there lessons learned from the multiple myeloma and <unk> experienced that are applicable here and second question can provide any color around the duration of treatment that you are seeing in multiple myeloma and <unk>.

Are you seeing a difference in duration between earlier line versus the pentair.

Optimum myeloma treatment.

Yes.

Yeah, Hi, thanks, Thanks, Jonathan maybe I'll take the first question.

Richard Paulson: So I think, again, when you look at the Siendo patient population, obviously we're still going to be engaging very much with regards to our action and our plans forward. I think, you know, this is very different than multiple myeloma because there are currently no approved therapies in a maintenance setting. So we have the potential to be the first and only therapy. We believe, again, this by itself is a real significant market opportunity because I think as Sohanya talked to, there's an incidence of 14,000 patients in frontline with about 67% responding to chemotherapy. So those numbers obviously are different than the multiple myeloma markets in the different areas.

Again, when you when you look at the <unk> patient population, obviously, we're still going to be engaging very much with regards to our action in our plans forward I think this is very different in multiple myeloma.

Because there are currently no approved therapies in the maintenance setting. So we have the potential to be the first and only therapy.

We believe this by itself is a real significant market opportunity because I think Sean you talked to.

Entrance or 14000 patients in frontline with about 67% responding to chemotherapy.

So those numbers, obviously are different than the most myeloma markets and in different areas. So now in the maintenance setting the different series you really treating through progression.

Richard Paulson: So now in the maintenance setting, the difference here is you're really treating through progression. And as we have shared in here, in the medium PFS for the total population, it's 5.7 months. But also in that P53 wild-type population, it's 13.7 months. We've shown through that, with a discontinuation rate of 10.5%, it's really been well tolerated for those 13 months. So, you know, as we know, in our study, approximately 50% of the wild type P53 patients are in the study, and that's, you know, the, T53 status is a very known and actionable mutation as part of the kind of standard evaluation and workup for when people are looking at their patients.

And as we have shared in.

And here in the median PFS for the total population.

It's $5 seven months, but also in that 253 wild type population is $13 seven months.

We've shown through that with the discontinuation rate of 10, 5% and it's really been well tolerated for those 13 months. So.

As we know in our study approximately 50% of the wildfire P 53.

Patients are in the study.

<unk>.

P 53 status is a very known and actionable mutations as part of the kind of standard evaluation work up for when people are looking at their patients.

Richard Paulson: So as we move forward, you know, we need to continue to do more work on this, but it's well understood. Well-documented, well-measured, and physicians, I think, and patients are really looking for moving away from the watch and wait and being able to move to treat their cancer and obviously extend their time in remission. So, you know, I'm very excited about it and also kind of a very different opportunity.

So as we move forward, we need to continue our work on this but it's well understood.

Well documented well measured and physicians I think and patients are really looking for moving away from the watch and wait and being able to move to treat their cancer and obviously extend their time information. So we're very excited about it and then also kind of a very different opportunity and then the last point I would close with on that is and here we are taking.

Richard Paulson: And then the last point I would close with on that is, in here, we're taking our established teams, you know, which are well-established, which are delivering, you know, excellent results, and are going to be able to move forward rapidly and engage, you know, with, with healthcare practitioners, you know, following the potential approval and a label. And for the second part of the question, maybe I'll turn to Sohanya to talk overall about what we're seeing in terms of, you know, evolution for patients being on therapy. Unknown Speaker 1. Thank you. Unknown Speaker 2.

Our established team and which are well established which are delivering excellent results.

And we're going to be able to move forward rapidly and engage with health care practitioners.

Following the potential approval and a label and for the second part of the question, maybe I'll turn to <unk> to talk.

Overall, though what we're seeing in terms of evolution for patients being on therapy.

Yes, most of our operating multiple myeloma.

Thanks, Richard So so multiple myeloma duration therapy, so preliminary data.

Sohanya Cheng: Thanks, Richard. So, so multiple myeloma duration therapy. So preliminary data is showing more patients are staying on therapy longer. And again, that's driven by a shift into early align and better side effect management. Now, it's important to remember this data is still maturing. We're still in the early stage of our second line plus launch.

Showing more patients are staying on therapy longer and again, that's driven by a shift into earlier lines and better side effect management now it's important to remember this data is still maturing we're still in the early stage of our second line plus launch so we cannot definitively guide to duration.

At this time.

Sohanya Cheng: So we cannot definitively guide to duration at this time. And we're also in that dynamic phase of our transition into earlier lines of use. But as we evolve into earlier lines, and we are now approaching that 5050 split between second to fourth line and fifth line plus in our patient population. With our greatest growth happening in our 3rd line, we, we will continue to see these patients in earlier line stay on therapy longer. Got it.

And we're also in that dynamic phase of our transition into earlier lines of abuse.

As we evolve into earlier lines and we are now approaching that 50 50 split between second to fourth line and first line plus in a patient population with a greatest thrills happening in our third line.

We will continue to see these patients in earlier lines.

Cherokee longer.

Got it thanks for taking my questions.

Okay.

Our next question comes from Ed White with H C. Wainwright. Please go ahead.

Sohanya Cheng: Thanks for taking the question. Thank you. Our next question comes from Ed White with H.C. Wainwright. Please go ahead. Good morning.

Good morning, Thanks for taking my questions.

Ed White: Thanks for taking my question. Can you discuss, perhaps, the use of, The prescribing under the label with Velcade versus what you're seeing with the other drugs under the NCCN guidelines. How is that breaking out and how is the growth been under with the NCCN guidelines? Great. Do you want to take that?

Can you discuss perhaps.

The used.

The.

Prescribing under the label with Velcade versus what Youre seeing with the other drugs under the NCC and guidelines how is that breaking out.

The gross spend under with the NCC and guideline.

Great and do you want to take that.

Yes.

Sohanya Cheng: Yes. So, expovio-based triplet use as an overall trend is rising significantly. And to break it down, 60% or so of the data that we see of expovio-based triplets are in combination with Velcade and DESS. And again, this is our approved indication. It's the only triplet regimen we promote.

Yes.

So <unk> based triplet youth as an overall trend that is rising significantly and you break it down 60% or so from the data that we see of exposure based triplets are exposed via combination.

<unk> with Velcade and Jeff and again this is our approved indication and the only triplet regimen, we promote too but we also know to your point there are other combinations with <unk>, Carfilzomib and Dara, Tim or Matt on the CCN guidelines, today's that remaining 40% or so of that triplet youth.

Sohanya Cheng: But we also know, to your point, there are other combinations with pomalidomide, carfilzomib, and daratumumab on the NCCN guidelines. So, there's that remaining 40% or so of that triplet use from the data that we see where it's those other combinations, but an overall rapid rise in that trend from doublets to triplets. Great, thanks for taking my question. Our next question comes from Arlinda Lee with Canna Gorge, please go ahead.

The data that we see where.

Those other combinations, but in overall rapid rise in that trend from Dublin two triplet.

Great. Thanks for taking my question.

Our next question comes from Arlinda Lee with Canaccord. Please go ahead.

Alright, Thanks for taking my question.

Arlinda Lee: Thanks for taking my questions. I guess I have another one on the duration. Can you please comment on the duration of the webinar?

I guess I have another one on <unk>.

Duration can you comment maybe on the.

Arlinda Lee: on the duration of treatment is that is that contributing. On the growth and sales, is it from improved duration versus what proportion can you help us understand? , and the C&O side, can you remind us when you initially started the trial, what were kind of the ongoing regulatory discussions then and maybe what FDA was looking for? Michael Jackson, Do any of you want to talk to the first part?

The duration of treatment is that.

Is that.

Contributing.

On the growth in sales as it.

Improved duration versus.

What proportion can you help us understand.

And credit duration versus new patients and then on the C&I side can you remind us when you initially started the trial.

Kind of the ongoing regulatory discussions been and maybe what FDA is looking for them and.

And how you're thinking about that thank you.

Good morning, Joe I'll talk to the first part.

Yes, thanks, Thanks Arlinda.

Sohanya Cheng: Yes, thanks. Thanks, Arlinda. So, you know, again, the earlier line shift, right, it's got two drivers here.

Again, the earlier line ship right.

It's got to drive various tier one is there is a larger addressable population in the earlier lines.

And hence exposure.

<unk> remains a focus for us to establish in that second to fourth line setting but in addition, the growth driver is as these patients move into earlier lines. They do stay on therapy longer. So our second line patients will stay on therapy longer than a fourth line patients so preliminary data.

Sohanya Cheng: One is there's a larger addressable population in the earlier line. And hence, exposure, that remains a focus for us to establish in the second to fourth line settings. But in addition, the growth driver is, as these patients move into earlier lines, they do stay on therapy longer. So a second line patient will stay on therapy longer than a fourth line patient. So, preliminary data is showing that more patients are gradually staying on therapy longer, and that's driven primarily by that shift into earlier line. But also the better side effect management.

Is showing that more patients are gradually staying on therapy longer and thats, driven primarily by that shift into earlier lines, but also the better side effect management.

Sohanya Cheng: Again, data is still maturing. We're still a year into our Boston launch, and so we can't definitely guide to mean duration. Also, that we are still in that dynamic phase into the earlier line shift, but we're seeing kind of good progress as that earlier line shift happens with those patients staying on therapy longer. And Jade, maybe you can just address the second part of Orlinda's question.

Again data is still maturing, we're still a year into our Boston launch and so we definitely guide to mean duration also that we're still in that dynamic phase into the earlier lines shift that we're seeing kind of good progress.

Is that earlier line chip happens with those patients staying on therapy longer.

And Jay maybe you can just address the second part of our lenders question, Yes, absolutely. We are engaged with the agency throughout the entire lifecycle of the trial from the beginning and continuously.

Jatin Shah: Yeah, absolutely. So, you know, we're engaged with the agency throughout the entire lifecycle of the trial, from the beginning to the end. And the one key point from the regulatory discussions is that it's clear that the primary endpoint is progression-free survival by investigator, an intent to treat that has not changed.

One key point from a regulatory discussions as it's clear that the primary endpoint is progression free survival by investigator.

Jatin Shah: And that's where we report positive phase three results from CIENDO. Thank you. Again, if you'd like to ask a question, please press star, then 1. Our next question is a follow-up from Peter Lawson with Barclays. Please go ahead.

Intent to treat and that has not changed.

And Thats, what would result reported positive phase III results from <unk>.

Okay.

Okay, and if you'd like to ask a question. Please press Star then one.

Our next question is a follow up from Peter Lawson with Barclays. Please go ahead.

Peter Lawson: Thanks for the follow-up. Just on the wild-type P53 population, does that make you rethink in any way the use in endometrial in the sense of... Potential use in earlier line or combinations, etc. Yeah, great question.

Thanks for the follow up.

Just on the Wild type <unk> population does that make you rethink in any way the Houston engine material and defensive.

Potential use of nearly in line or combinations et cetera.

Yes, great question, Thanks for that period.

Jatin Shah: Thanks for that, Peter. Obviously, we share the same excitement around p53, as well as the entire population. We'll dive more into this with additional data analyses with our investigators and the agency for future trials. Thank you. Thank you. Just maybe a question on the P&L. What was the stock option expense in 2021?

We share the same excitement around <unk> 53, as well as the entire population who will dive more into this and with additional data analyses with our investigators and the agencies.

For future trials.

Got you.

The.

Peter Lawson: I'm just trying to back out the guidance. Price, do you want to manage that? Sure. Our dot-comp expense was just about $30 million.

Just maybe a question on the P&L just the what was the stock option expense in 2021, I'm just trying to back out the guidance.

I just want to manage that.

Sure.

Stock comp expense.

About $30 million.

Perfect. Thank you.

<unk>.

Mike Mason: Thank you! Just on the P53 mutant population, are you going to break that out or just wait for a conference? And would you have to break that out on the label as well for the P53 mutant population? And we'll break, it'll be broken out at a conference as the data is presented. And then I think, as we said, we have to engage with the FDA and look at the totality of the data and determine the outcome as we look at that in a later date. How should we think about pricing in the, in the endometrial population. It's the same.

Just on the on the $2 53.

Mutant population.

To.

Break that out or just wait for a conference.

And would that be would you have to break down the label as well.

<unk> three mutant population.

We'll break it'll be broken out at a conference.

Data is presented and then I think as we said we have to engage with the FDA and looked at the totality of the data and determine the outcome as we look at that in the label.

Okay.

Should we think about pricing in the.

In the interim <unk> population.

And this is the same.

Richard Paulson: I mean, our products already on the market, so it's going to be remaining at the same price. I think that the key thing, again, to look at is, in a maintenance setting, patients are really treating themselves through progression. So, you know, with physicians and patients, they want to, you know, extend the time in remission, and I think that's where it's really important looking at those medium TFS we talked to, but also looking at the real importance that over that long tail.

Our products are already on the market. So it's going to be remaining at the same price I think the key thing again to look at it as maintenance setting patients are willing treating themselves through progression.

So with physicians and patients who want to.

And extended diamond in remission.

And I think thats, where its really important looking at those.

Median PFS, we talked to but also looking at.

Two the real importance that over over that long tail.

Richard Paulson: When you're seeing that, you know, about 35% of patients are still in remission one year after starting therapy, I think that'll be very important when you look at the duration of therapy. And as we've talked to, you know, we see with the discontinuation, it's been very well tolerated, you know, for a long period of time. And for instance, the 13 months that we see in the wild-type P53 population.

And what are you seeing that above 35% of patients are still in remission at one year after starting therapy and kind of a very important when you look at the duration of therapy and as we've talked to.

See what the discontinuation.

Been very well tolerated.

The long period of time for instance, in the 13 months that we see in the.

Wild type <unk> population. So all of those factors will obviously look at the total total value of the market, but from a pricing perspective, we're at the same price we're already in the market.

Richard Paulson: So all those factors will obviously look at, you know, the total value of the market. But from a pricing perspective, you know, we're at the same price we're already in the market. Okay, thank you. And then just a final question on the guidance. I know you're not doing quarterly guidance, but are there any headwinds or tailwinds that we should be thinking about year-over-year? when we're kind of doing the model. Sohanya, do you want to take that one?

Got you okay. Thank you.

Final question on the guidance.

Quarterly guidance, but are there any headwinds or <unk> that we should be thinking about year over year.

When we're kind of doing the model.

So Andrew I'll take that one.

Peter Lawson: Yeah, I think that the tailwinds are really the key, you know, growth drivers, where we continue to sustain our momentum. As far as headwinds, you know, I think the wildcard continues to remain the impact of Omicron variant. But as I mentioned earlier, we are adapting to it, and we've got strong commercial digital capabilities, and we'll see how that evolves. But our focus remains on strong execution and positioning Expovio as the standard of care in Second Line Plus.

Yes, I think I think the tailwind, but really the key growth drivers, where we continue to sustain our momentum as far as headwinds.

The wildcard continues to remain the impact of omicron variant, but as I mentioned earlier, we are adapting to it and we've got strong commercial digital capabilities.

And we'll see how that evolves, but our focus remains on <unk>.

Long execution and positioning <unk> as the standard of care in second line plus.

Okay. Thanks, so much thanks for taking all the questions.

Sohanya Cheng: Okay, thanks so much. Thanks for taking all the questions. This concludes our question and answer session. I would like to turn the conference back over to Richard Paulson for any closing remarks. Thank you, Operator, and thank you for all of our participants today in the call. With that, again, we look forward to being able to share ongoing progress as we're moving forward with our pipeline and now working forward to continue to focus on trying to defeat cancer and benefit patients' lives who are fighting cancer. So thank you very much, Operator. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

This concludes our question and answer session I would like to turn the conference back over to Richard Carlson for any closing remarks.

Thank you operator, and thank you for all of our participants today on the call.

With that again, we look forward to being able to share ongoing progress.

And we're moving forward with our pipeline and are working forward to continue to focus on trying to defeat cancer benefit patients lives who are fighting cancers. So thank you very much operator.

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