Q1 2022 Karyopharm Therapeutics Inc Earnings Call

[music].

Good morning.

Unknown Executive: Good morning, and welcome to the Karyopharm Therapeutics First Quarter 2022 Earnings Conference Call. Did you need the... There will be an opportunity. Please press star then 1 on your telephone keypad.

Unknown Executive: To withdraw your question, please press star then 2. I'd now like to turn the call over to Debbie, and thank you all for joining us on today's conference call to discuss Karyopharm's First Quarter 2022 Financial Results and Recent Company Program. Today I'm joined by Richard Paulson, President and CEO, Sohanya Cheng, Chief Commercial Officer, Dr. Reshma Rangwala, Chief Medical Officer, Dr. Patricia Judson, SVP Medical Strategy, and Mike Mason, Chief Financial Officer. This morning, we issued a press release detailing Karyopharm's financial results for the first quarter of 2020.

Welcome to the carrier farm Therapeutics first quarter 2022 earnings conference call.

Unknown Executive: This release, along with a slide presentation that we will reference during today's call, is available under the events and presentations section of our website at karyopharm.org. For today's call, as seen on slide two, Richard will provide some opening remarks. Sohanya will provide a commercial update for Expovio, and then Reshma and Patricia will provide an update on the clinical development program. Mike will then provide an overview of the financial highlights from the quarter, and Richard will provide some closing remarks before opening the call-out for questions.

All participants will be unless you're normally Mount should you need assistance. Please signal a conference specialist by pressing the star key followed by DRAM.

After todays presentation, there will be an opportunity to ask questions.

To ask a question you May press Star then one on your telephone keypad to withdraw your question. Please press Star then two.

Please note this event is being recorded.

I would now like to turn the conference over to him.

Senior Vice President Investor Relations. Please go ahead.

Thank you Debbie and thank you all for joining us on today's conference call to discuss the carrier farms first quarter 2022 financial results and recent company broke that.

Today, I'm joined by Richard Paulson, President and CEO , So high a Chang Chief commercial officer don't feel rushed right wrong Wala, Chief Medical Officer Doctor Apache said, Justin SVP medical strategy, and Mike Mason Chief Financial Officer.

This morning, we issued a press release detailing.

Financial results for the first quarter 'twenty to 'twenty two.

This release, along with a slide presentation that will be well accepted during today's call.

Under the events and presentations section of our website at Canada, That's why I'm dotcom.

For today's call as seen on slide to Richard who will provide some opening remarks. So anya will provide a commercial update for export deal that regimen Petrucelli will provide an update on the clinical development program.

Mike will then provide an overview of the financial highlights from the courtyard and Richard will provide some closing remarks before opening the call up for questions.

Unknown Executive: 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 Education Reform Act of 1995, as outlined on slide 16. 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 annual report on Form 10-K, which is on file with the FCC, and 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 now rely on these forward-looking statements as representing our views as of any date subsequent to today.

Before we begin our formal comments I'll remind you that various remarks, we will make today constitute forward looking statements for purposes of the safe Harbor provision under the private Securities Litigation Reform Act of 1995 as outlined on slide three.

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 annual report on Form 10-K, which is filed with the SEC and in other filings that we may make with the FCC in the future.

Any forward looking statements represent our views as of today.

While we may elect to update these forward looking statements at some point in the future.

That's particularly disclaims 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 you know he shouldn't live we'll also be providing on this call outlook for non-GAAP R&D and SG&A expenses for 2022, we are now providing.

Unknown Executive: In addition, we will also be providing on this call an outlook for non-GAAP, R&D, and HG&A expenses for 2020. We are not providing reconciliations of these forward-looking Nungap measures because projections of stock compensation expense, which is required for such reconciliations, are not available without unreasonable evidence. I will now turn the call over to Richard. Please turn to slide 16.

Most nations off these forward looking non-GAAP measures because projections all stock compensation expense, which is required for such we called filiation are not available without unreasonable effort.

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

[laughter].

Richard Paulson: Thank you, Elhan, and good morning to everyone joining us on the call and webcast today. Q1 was another strong quarter, and I am very excited to provide an update on our plan as we continue to execute on our growth strategy through our focused commercial execution and pipeline development that we are pursuing on behalf of patients in need. On slide five, we have an overview of the key pillars that drive our underlying value and provide opportunity for what we believe will be substantial future growth.

Thank you Ann and good morning to everyone joining us on the call and webcast today.

Q1 was another strong quarter and I'm very excited to provide an update on our plan as we continue to execute on our growth strategy through our focused commercial execution and pipeline development that we are pursuing on half of patients in need.

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

First we are successfully building upon our existing multiple myeloma franchise.

Richard Paulson: First, we are successfully building upon our existing multiple myeloma franchise. This quarter, we generated strong revenues and expect to continue strong sales in 2022 through focused execution and proven commercial capabilities, creating value for both patients and shareholders. On the global regulatory front, we are expecting the European CHMP to complete its review of Selenix or its application in Second Line Plus and issue an opinion during the first half of 2022.

This quarter, we generated strong revenues and expect to continue strong sales in 2022 through focused execution and proven commercial capabilities, creating value for both patients and shareholders.

On the global regulatory front, we are expecting the European C. H M. P to complete its review of the Selinexor application in second line plus.

And issue an opinion during the first half of 2022.

Richard Paulson: Together with our global commercialization partners, we are increasingly bringing Expovio to patients worldwide. Second, we are shifting from our Multimiloma franchise to our Focused pipeline, where we continue to make strong progress. We are advancing a clinical pipeline comprised of mid- and late-stage clinical development programs that are being purposefully built and strategically focused on targeting cancers with high unmet needs, where our science enables us to make the biggest difference in the lives of patients and in areas with a high probability of success.

Together with our global commercialization partners, we are increasingly bringing exposure to patients worldwide.

Second shifting from our multiple myeloma franchise through our focused pipeline, where we continue to make strong progress we.

We are advancing our clinical pipeline comprised of mid and late stage clinical development program.

It is being purposefully built and strategically focused on targeting cancers with high unmet need where our science enables us to make the biggest difference in the lives of patients and in areas with high probability of success.

Richard Paulson: To that end, we are pursuing approval opportunities for multiple myeloma, endometrial cancer, myofibrosis, and myelodysplastic syndromes over the next two to four years. Our third pillar is our people, and we strengthened the leadership team during the first quarter.

To that end, we are pursuing approval opportunities in multiple myeloma endometrial cancer myelofibrosis and my own Myelodysplastic.

Myelodysplastic syndrome over the next two to four years.

Our third pillar is our people and we strengthened the leadership team during the first quarter.

Richard Paulson: We believe we have the right people in place who have exceptional abilities to achieve both scientific and commercial excellence while executing on our key corporate objectives. Fourth, and finally, to support our strategic and focused growth plan, we are well capitalized and expect to be able to fund our operations into early 2024. At Karyopharm, everything we do is driven by our mission to positively impact patient lives and defeat cancer. Our foundation is our science, and we are a global leader in the inhibition of nuclear export.

We believe we have the right people in place who have exceptional abilities to achieve both scientific and commercial excellence, while executing on our key corporate objectives.

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

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

Our foundation is in our science and we are the global leader in the inhibition of nuclear export.

Richard Paulson: Against this backdrop, we believe we have a strong organization that allows us to execute this year and beyond. The first quarter of 2022 was marked by several meaningful achievements, as outlined on slide six. Including continued robust commercial performance and significant progress across our pipeline. To start, we achieved total revenues of $47.7 million, which included $19.4 million from certain licensed and milestone revenues, as our footprint expands globally. Second, Expovio delivered strong year-over-year growth in the U.S. During the first quarter, it achieved $28.3 million in net product revenue, representing year-over-year growth of 30%.

Against this backdrop, we believe we have a strong organization, which allows us to execute this year and beyond.

The first quarter of 2022 was marked by several meaningful achievements.

And on slide six.

Including continued robust commercial performance and significant progress across our pipeline.

Yeah.

To start we achieved total revenues of $47 7 million, which included $19 4 million from certain license and milestone revenues.

Our footprint expands globally.

Second <unk> delivered strong year over year growth in the U S.

During the first quarter, achieving $28 3 million in net product revenue representing year over year growth of 30%.

Richard Paulson: We achieved these results through continued increasing uptake in the second through fourth lines, with strong growth in the third line and despite COVID-related headwinds experienced during January and February. For global commercialization efforts, Expovio or Nexpovio is now approved in 37 countries, the most recent of which are Mainland China, Australia, and Singapore through our partner Antigene.

We achieved these results through continued increasing uptake in the second through fourth line.

With strong growth in the third line and despite COVID-19 related headwinds experienced during January and February.

For global commercialization efforts <unk>, our <unk> is now approved in 37 countries.

The most recent of which our mainland China, Australia, and Singapore through our partner Anti-aging.

Richard Paulson: In endometrial cancer, we recently reported top-line results from a Phase III Siendo study, where Cellinexor showed especially encouraging results in the exploratory subgroup of patients with P53 wild-type tumors, improving PFS by an impressive 10 months, and we are planning to initiate a registrational phase 3 study in the second half of this year. We'll be presenting results at the upcoming ASCO 2022 Annual Meeting, including results from a subgroup, a molecular analysis from the CIANDO study, and preliminary clinical results from our Phase 1-2 study investigating Selinexor combined with Ruxolitinib in patients with treatment-naive myofibrosis.

In endometrial cancer, we recently reported topline results from the Phase III <unk> study.

Selinexor showed especially encouraging results in the exploratory subgroup of patients with P 53, wild type tumors improve.

Improving PFS by an impressive 10 months and it.

We are planning to initiate a registrational phase III study in the second half of this year.

We'll be presenting results at the upcoming <unk> 2022 annual meeting, including results from a subgroup and molecular analysis from this the Endo study.

And the preliminary clinical results from our phase one two study investigating selinexor combined with <unk> in patients with treatment naive myelofibrosis.

Richard Paulson: And last but not least, on the corporate front, we recently strengthened the leadership team with Dr. Reshma Rangwala joining us as Chief Medical Officer. We are delighted to have her join the team, and we believe that her extensive experience developing and executing clinical strategies for novel oncology therapeutics, as well as engaging regulators and the medical community at all stages of development, will be of immeasurable value as we accelerate our four core programs in clinical development, as shown on slide seven.

And last but not weak on the corporate front, we recently strengthened the leadership team without duration malware ran wala, joining us as chief Medical Officer.

We are delighted to have her joined the team and we believe that her extensive experience.

Eloping and executing clinical strategies for novel oncology therapeutics, as well as engaging regulators and the medical community at all stages of development will be a immeasurable value as we accelerate our four core programs in clinical development as shown on slide seven.

Richard Paulson: Our drive, vision, and innovation, along with the scope and range of data generated to date, have led us to focus on our four core programs shown here. Multmyeloma, Endometrial Cancer, Myofibrosis, and Myodesplastic Syndrome, along with all of these being areas of high unmet need for patients. Each has a significant addressable market.

Our drive vision and innovation, along with the scope and range of data generated to date have led us to focus on our four core programs showing here.

Multiple myeloma endometrial cancer, myelofibrosis and Myelodysplastic syndromes.

Along with all of these being areas of high unmet need for patients each.

Each has a significant addressable market.

Sohanya Cheng: The key focus of today's call will be our endometrial cancer and myofibrosis program. As we turn now to slide 8, I would like to turn the call over to Sohanya for her review of the commercial performance for the quarter. Okay, Sohanya?

A key focus of today's call will be our endometrial cancer and myelofibrosis programs.

As we turn now to slide eight I would like to turn the call over to Sanya for her review of the commercial performance for the quarter. So on yes.

Sohanya Cheng: Thank you, Richard, and good morning, everyone. Since our launch, we continue to focus on expanding the potential of Expovio and its benefit to patients in early alignment. Slide nine shows how we have evolved from our original approval of XD based on the STORM study to gaining FDA approval for the XBD regimen based on our BOSTON study and now to initiating a phase three study with selinexor, pomalidomide, and dexamethasone, an all oral triplet combination, which Reshma will expand on later.

Thank you Richard and good morning, everyone. Since our launch we continue to focus on expanding the potential of ex OBO and its benefits to patients in earlier lines.

Slide nine shows how we have evolved from a original approval of X D. Based on the storm study to gaining FDA approval for the X V. D regimen based on our Boston study and now to initiating a phase three study with Selinexor Palmer, let it might and dexamethasone and all.

Oral triplet combination, which raised my will expand on later.

Sohanya Cheng: In this process, we have evolved from twice weekly to once weekly, from higher to lower doses, from a doublet to triplet, expanded into earlier lines with multiple combinations, and improved the overall patient experience. And we've achieved all of this during challenging times with the ebbs and flows of COVID. The team has done outstanding work to adapt quickly, focus on head-down execution, and continue to drive strong results.

In this process, we have evolved from twice weekly to once weekly from higher to lower doses from a doublets and triplets expanded into earlier lines with multiple combination and improve the overall patient experience.

And we've achieved all of this during challenging time with the ebbs and flows of Covid.

The team has done outstanding work to adapt quickly.

On head down execution and continue to drive strong results.

Sohanya Cheng: Turning now to slide 10, our commercial highlights for the first quarter of 2022. It's rewarding to continue to see patients being treated in earlier lines and staying on therapy longer. Despite the impact of COVID in the first quarter of this year, we grew net product revenue by 30% versus the same period last year and continue to make excellent progress across key indicators since our second line plus launch at the beginning of 2021. In addition, inventory levels were consistent with the last quarter.

Turning now to slide 10 on our commercial highlights for the first quarter of 2022.

It's rewarding to continue to see patients being treated in earlier lines and staying on therapy longer despite the impact of Covid in the first quarter of this year. We grew net product revenue by 30% versus the same period last year and continued to make excellent progress across.

Ross key indicators since our second line plus launch at the beginning of 2021.

In addition inventory levels were consistent with the last quarter.

Sohanya Cheng: The environment was particularly challenging with the surge of COVID in January and February, which impacted oncology patient visits and new starts, as well as our access to healthcare providers. However, we did see a recovery in March, with patient visits starting to normalize, our new starts growing, and our access to physicians improving. We continue to make strong progress with our primary growth driver and what we believe is most important to patients, which is the positive shift in earlier lines from the pentarefractory setting, with the strongest growth in the third line, as we continue to focus our messaging on expovio as a new class of therapy in the white space of the second to fourth line in the myeloma treatment journey.

The environment was particularly challenging with the surge of Covid in January and February which impacted oncology patient visits and new starts as well as our access to health care providers.

We did see a recovery in March with patient visits starting to normalize our new starts growing and our access to positions improving.

We continue to make strong progress with our primary growth driver and what we believe is most important to patients which is the positive shift in earlier lines from the penta refractory setting with the strongest growth in the third line as we continue to focus our messaging on Expo will be O.

As a new class of therapy in the white space, a second to fourth line in the myeloma treatment journey.

Sohanya Cheng: This shift into earlier lines, as well as continued education to improve tolerability, has resulted in more patients staying on therapy longer. We are also expanding the breadth and depth of the use of Expovio with strong growth in the community setting.

This shifts into earlier lines as well as continued education to improve Tolerability has resulted in more patient.

Hang on therapy longer.

We are also expanding in the breadth and depth of use of Expo deal with strong growth in the community setting.

Sohanya Cheng: While we continue to grow our breadth by adding more accounts every quarter and penetrating more top myeloma accounts, as we progress through our launch phase, our focus is now on growing depth with our core customer base by increasing new patient starts and driving the shift into earlier lines where patients are more likely to stay on therapy longer, thus generating more refills in the future. We believe the beneficial impact on patients and growing confidence among our physicians in using the lower-dose once-weekly exfobio-based triplet regimen are seen in the data.

While we continue to grow our breath by adding more accounts every quarter and kind of trading and more top myeloma accounts.

As we progressed through our launch phase our focus is now on growing depth with our core customer base by increasing new patient starts and driving the shift into earlier lines, where patients are more likely to stay on therapy longer thus generating more refills in the future.

We believe the beneficial impact to patients and growing confidence among our positions in using the lower dose once weekly <unk> based triplet regimens.

<unk> seen in the data.

Sohanya Cheng: Our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product in the third line. We remain confident about guidance we provided for 2022 net product revenue of $135 to $145 million.

Our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product in the third line.

We remain confident about guidance, we provided for 2022 net product revenue of 135 to 145 million, we see strong and consistent momentum across all our growth drivers.

Sohanya Cheng: We see strong and consistent momentum across all our growth drivers, increasing confidence amongst physicians in using Expovio, and we have a field team that is laser-focused and committed to bringing Expovio to more patients in the second to fourth line. With regard to COVID, we continue to see the environment normalizing, and we'll monitor and adapt as things evolve. The unmet need remains strong for new modalities like Expovio because in multiple myeloma, physicians' ability to cross-switch with multiple combinations has driven significantly better patient outcomes.

Increasing confidence amongst physicians in using ex mobile and we have a field team that is laser focused and committed to bringing <unk> to more patients in the second to fourth line.

With regards to Covid, we continue to see the environment, normalizing and well monitor and adapt as things evolve.

The unmet need remains strong for new modalities like exposed yo because in multiple myeloma physicians ability to clock switch with multiple combination has driven significantly better patient outcome.

Sohanya Cheng: A majority of treated patients in the first to second line are exposed to an anti-CD38 therapy. Many of these patients' diseases will become refractory to or relapse from an anti-CD38 treatment. We believe this is where Exfovio is a strong fit in the second-to-fourth line.

A majority of treated patients in the first to second line are exposed to an anti CD 38 therapy. Many of these patients disease will become refractory to or relapsed from anti CD 38 treatment.

We believe this is where exposure is a strong fit in the second to fourth line. It is a novel class of therapy with robust efficacy and with a breadth of data and the post anti CD 38, setting it has a well understood and manageable safety profile and while we only promote FTE.

Sohanya Cheng: It is a novel class of therapy with robust efficacy and with breadth of data in the post-anti-CD38 setting. It has a well-understood and manageable safety profile, and while we only promote FDA-approved regimens, physicians have the option to combine it with several different backbones per the NCCN guidelines. Building on our momentum in 2021 and early this year, and with a rapidly advancing myeloma pipeline, we expect to continue to drive steady growth in the near, mid, and long term. With that, please advance to slide 11, and I'll turn the call over to Reshma and Patricia to review our clinical pipeline progress. Thank you, Sohanya.

<unk> regimens physicians have the option to combine with several different backbones for the NCC and guidelines.

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

With that please advance to slide 11, and I'll turn the call over to Ray Smart and Patricia to review, our clinical pipeline progress.

Thank you Tanya it's great to be here today, just under three weeks after I joined to carry a farm as Chief Medical Officer.

Reshma Rangwala: It's great to be here today, just under three weeks after I joined Karyopharm as chief medical officer. Before discussing our pipeline, I'd like to take a moment to introduce myself. I'm a medical oncologist with more than a decade of experience in oncology drug development, both at large pharmaceutical companies and at smaller developmental stage companies. Prior to joining Karyopharm in mid-April, I spent 10 years in roles with increasing responsibility at three life science companies, including Aerovive, GenMab, and Merck.

Before discussing our pipeline I'd like to take a moment to introduce myself I'm, a medical oncologist with more than a decade of experience in oncology drug development, both at large pharmaceutical companies and that smaller developmental stage companies.

Prior to joining carry a farm in mid April I spent 10 years in roles with increasing responsibility at three life science companies, including Arabize Genmab and Merck during my career in the industry I participated in the development of multiple oncology drugs with varying varying mechanisms of actions, including.

Reshma Rangwala: During my career in industry, I've participated in the development of multiple oncology drugs with varying mechanisms of action, including immuno-oncology agents and antibody drug conjugates across all phases of drug development, from IND filings for phase 1 to designing and implementing registrational studies leading to successful first approvals as well as additional major indications. In addition, I have participated in the development of companion diagnostics, including a PD-L1 IHC I can see that both Selenexor and Elconexor have significant potential for battling an array of cancer types, and I am thrilled to join the Karyopharm team at such an exciting and pivotal time in the company's growth.

Immuno oncology agents and antibody drug conjugates across all phases of drug development from I N D filings for phase ones to designing and implementing Registrational studies, leading to successful first approvals as well as additional major indications. In addition, I have participated in it development.

With companion diagnostics, including a PD L. One I H C.

I can see that both selinexor and <unk> has significant potential for battling an array of cancer types.

I'm thrilled to join the carry a farm team at such an exciting and pivotal time in the company's gross I'm impressed with the team and the science of S. P O one inhibition.

Reshma Rangwala: I'm impressed with both the team and the science of SP01 inhibition. I am excited to see the potential of these treatments for patients that are being evaluated in our four core programs. Now, turning to slide 12, I will be reviewing our clinical development pipeline from our four-core program. As we look to the future on slide 13, one of our top priorities is to expand our footprints in multiple myeloma, both in the U.S. and across the globe. We have strategically partnered with Selenexor in key ex-U.S. territories.

I'm excited to realize the potential of these therapies for patients that are being evaluated in our four core programs.

Now turning to slide 12, I'll be reviewing our clinical developmental pipeline from our four core programs.

As we look to the future on slide 13, one of our top priorities is to expand our footprint in multiple myeloma, both in the U S and across the globe. We have strategically partnered selinexor in key ex U S territories.

Reshma Rangwala: Our partner, Antigen, recently obtained approvals, which include conditional and full approvals for Expovio in mainland China, Australia, and Singapore. For Europe, the application requesting approval for Selenexor in patients with multiple myeloma following at least one prior therapy has been validated and is currently under review by the CHMP. The outcome of the CHMP review is expected by the end of the first half of 2022.

Our partner Anthony Jin recently obtained approvals, which include conditional and pull approvals brookstone P O in mainland, China, Australia, and Singapore for Europe , the application requesting approval for Selinexor in patients with multiple myeloma following at least one prior therapy has been.

Alidade It and it's currently under review by the C. H M. P C.

The outcome of the C. H M. P review is expected by the end of the first half of 2022.

There are also pending marketing approval applications for second line, plus multiple myeloma submitted or on file in Canada, and other Asia Pacific markets through our strategic partners.

Reshma Rangwala: Second Line Plus Multiple Myeloma is submitted or on file in Canada and other Asia-Pacific markets through our strategic partners. Turning now to slide 14 and some updates from our developmental pipeline, I'll start with multiple myeloma.

Turning now to slide 14, and some updates from our developmental pipeline.

I'll start first with multiple myeloma. In addition to the work so hanya and her team are doing on the commercial front in the U S and the work our global partners are doing on the regulatory front.

Reshma Rangwala: In addition to the work Sohanya and her team are doing on the commercial front in the U.S. and the work our global partners are doing on the regulatory front, we are also working to obtain additional clinical data in order to expand to additional multiple myeloma patient populations where Selenexor may provide benefits. To that end, we are initiating a global, registration-enabling, randomized phase 3 study in the first half of 2022 that is designed to evaluate the SPD triplet regimen in patients with multiple myeloma, following at least one prior line of therapy, including an anti-CD38-based regimen. SPD will be an all-oral regimen, which is highly desirable with this patient population, with over half of the patients in second line being on an oral-containing regimen.

We are also working to obtain additional clinical data in order to expand into additional multiple myeloma patient populations, where selinexor may provide benefit to.

To that end, we are initiating a global registration, enabling randomized phase III study in the first half of 'twenty 'twenty. Two that is designed to evaluate the SPD triplet regimen in patients with multiple myeloma. Following at least one prior line of therapy, including an anti CD 38 base.

Regimen.

S. P D will be an all oral regimen, which is highly desirable with this patient population with over half of the patients in second line being in an oral containing regimen.

Reshma Rangwala: This is building on our STOMP data, which showed robust efficacy and good tolerability. And it's paired with the well-established backbone of pomalidomide, which is widely used in earlier lines. As you can see from our study design, SPD will be evaluated against the triplet combination of elotuzumab, pomalidomide, and low-dose dexamethasone, or EPD. I will now turn the call over to Patricia to review the Endometrial Cancer and Myelofibrosis programs, which begin on slide 15.

<unk> is building on our stomp data, which showed robust efficacy and good tolerability and it's paired with a well established backbone upon melitta mine, which is widely used in earlier lines.

As you can see from our study design S. P. D will be evaluated against the triplet combination of either choose a mab Palmer <unk> and low dose dexamethasone or E. P D.

I will now turn the call over to Patricia who reviewed the endometrial cancer in myelofibrosis programs, which begin on slide 15.

Thank you very small so first I'll provide an overview of the unmet need in endometrial cancer and why we find our upcoming opportunities so exciting for patients.

Reshma Rangwala: Thank you, Reshma. First, I'll provide an overview of the unmet need for endometrial cancer and why we find our upcoming opportunities so exciting for patients. Endometrial cancer is the most common form of gynecologic cancer in the United States.

And the mutual cancer is the most common form of banner collage of cancer in the United States.

Patricia Judson: Unlike other solid tumors, endometrial cancer mortality continues to increase. Of the 14,000 patients diagnosed with advanced or recurrent endometrial cancer each year in the US, approximately 50% have P53 wild-type tumors. The current landscape for advanced or recurrent endometrial cancer consists of first-line chemotherapy, where response rates are approximately 70%. However, following responses to chemotherapy, there are no effective treatments available, and the NCCN guidelines recommend a watch and wait approach until disease progression. This approach clearly needs improvement because the five-year survival is only 17%. However, as Selenexor is administered orally, and maintenance therapy is well-established with physicians that treat multiple types of solid tumors, including breast and ovarian cancer.

Unlike other solid tumors endometrial cancer mortality continues to increase.

Of the 14000 patients diagnosed with advanced or recurrent endometrial cancer each year in the U S. Approximately 50% have P 53 wild type tumors.

The current landscape for advanced or recurrent endometrial cancer consist of first line chemotherapy, where response rates were approximately 70%.

However, following responses to chemotherapy there are no effective treatments available and the NCC and guidelines recommend a watch and wait approach until disease progression.

This approach clearly means improvement because the five year survival is only 17%.

And Selinexor is administered orally and maintenance therapy is well established with physicians that treat multiple types of solid tumors, including breast and ovarian cancer.

Patricia Judson: We believe Selenexor has the potential to offer these patients a new maintenance option that could sustain the response from chemotherapy and help keep cancer from returning for longer. As you know, we recently reported results from the Phase 3 Siendo study. A subset in this study, which is shown on slide 16, demonstrated single-agent Selenexor to have an impressive 10-month improvement in median PFS in a pre-specified exploratory subgroup of 103 patients who had T53 wild-type endometrial cancer. All the patients in this study were diagnosed with advanced or recurrent endometrial cancer.

We believe Selinexor has the potential to offer these patients a new maintenance option that could sustain the response from chemotherapy and help keep cancer from returning for longer.

As you know, we recently reported results from our phase III D&O study.

Ah subsets in this study which is shown on slide 16.

Demonstrated single agent Selinexor to have an impressive 10 month improvement in median PFS in a prespecified exploratory subgroup of 103 patients who had P 53, wild type endometrial cancer.

The patients in this study were diagnosed with advanced or recurrent endometrial cancer. They were treated with frontline chemotherapy and had either a partial or complete response to chemotherapy.

Patricia Judson: They were treated with frontline chemotherapy and had either a partial or complete response to chemotherapy. In patients with P53 wild-type disease, the Selenexor-treated patients achieved a median progression-free survival of 13.7 months, compared to just 3.7 months in the placebo-treated patients. Based on these exciting data, we are partnering with opinion leaders, the Gynecologic Oncology Group, and the European Network for Gynecologic Oncology Trials, or NGOT, to initiate a registration-enabling Phase III study, which we plan to initiate during the second half of 2022. Now, I would now like to highlight our rapidly advancing myelofibrosis program and the current treatment landscape. If you turn to slide 17, please.

In patients with Pes fifty-three, while take disease. The selinexor treated patients achieved a median progression free survival of 13.7 months compared to just 3.7 months in the placebo treated patients.

Based on these exciting data we are partnering with opinion leaders the gynecologic oncology group.

In the European network for Gynecological oncology trials are and got to initiate a registration enabling phase III study, which we plan to initiate during the second half of 'twenty to 'twenty two.

I would now like to highlight our rapidly advancing myelofibrosis program and the current treatment landscape.

Patricia Judson: Therefore, ruxolitinib is the current standard of care for newly diagnosed myelofibrosis. However, approximately 40% of patients respond to frontline treatment, leaving 60% of patients requiring subsequent therapy. For patients who respond initially to rexalitinib, the response rates can be up to four years. However, once patients stop responding, the expected median survival is approximately 14 months, and the five-year survival rate is only 18%. There are no other drug classes other than JAK inhibitors currently approved or that have been approved in the last 10 years.

If you turn to slide 17 please.

So it looks a little Nick is the current standard of care for newly diagnosed myelofibrosis.

However, approximately 40% of patients respond to frontline treatment, leading 60% of patients requiring subsequent therapy.

For patients who respond initially to rux a witness the response rates can be up to four years.

Once patients stop responding the expected median survival is approximately 14 months.

The five year survival rate is only 18%.

There are no other drug classes other than the JAK inhibitors currently approved or has been approved in the last 10 years.

On Slide 18, I'll review this strong single agent data that we generated in our phase two essential study, which looked at single agent Selinexor in patients after a JAK one inhibitor.

Patricia Judson: On slide 18, I will review the strong single-agent data that we generated in our phase two essential study, which looked at single-agent Selenexor in patients after a JAK1-2 inhibitor. 40% of patients in this study achieved a spleen volume reduction of 35% or greater following at least 24 weeks of treatment. The two-year probability of survival was 92%.

40% of patients in this study achieved the spleen volume reduction of 35% or greater following at least 24 weeks of treatment.

But to your probability of survival was 92%.

Patricia Judson: To put these data into context, currently available therapies in a similar patient population lead to spleen volume reductions of 35% or greater in approximately 15% of patients. Furthermore, in the essential trial, we observed positive impacts on hemoglobin levels. Including 50% of patients achieving either improved hemoglobin levels or transfusion independence. The hemoglobin increased by at least 2 grams per deciliter in 67% of patients. Again, contrast this with other agencies, in which anemia often worsens on therapy. In this study, Selenexor was generally well-tolerated, with a median treatment duration of 11 months and a range of 2.8 to an impressive 28.8.

To put these data into context currently available therapies in a similar patient population b to spleen volume reductions of 35% or greater in approximately 15% of patients.

Furthermore, an essential trial, we observed positive impacts on hemoglobin levels, including 50% of patients achieving either improved hemoglobin levels or transfusion independence.

The hemoglobin increased by at least two grams per deciliter and 67% of patients.

Again contrast, this with other agents.

Which anemia, often worsens on therapy.

In this study Selinexor was generally well tolerated with a median treatment duration of 11 months and a range of 2.8 to an impressive 28.8 months.

The Central study is small and has early data, but you can see why we are excited about the potential of our two ongoing studies.

Patricia Judson: The essential study is small and has early data, but you can see why we are excited about the potential of our two ongoing studies. We believe that Selenexor, as a novel class of therapy, has the potential to improve outcomes for patients with multiple possible benefits, including Durable Spleen Volume Reduction, Improvement in Anemia Status, and the Potential to Decrease Symptom Burden by Decreasing the Inflammatory Cytokine Profile and Disease Modification.

We believe that Selinexor as a novel class of therapy has the potential to improve outcomes for patients with multiple possible benefits, including durable spleen volume reduction improvement in anemia status.

The potential to decrease symptom burden by decreasing the inflammatory cytokine profile and disease modification.

Turning now to slide 19, we have our most advanced myelofibrosis study the ongoing phase two MF 035 study.

Patricia Judson: Turning now to slide 19, we have our most advanced myelofibrosis study, the ongoing Phase 2 MS-035 Study, which is a randomized, open-label study evaluating single-agent Selenexor versus Physician Choice Therapy in patients with myelofibrosis who have had at least six months of prior treatment with a JAK1-2 inhibitor. The primary objective of this study is to assess SVR35, and key secondary endpoints include TSS50, overall response rate, overall survival, anemia response, impacts on symptom burden, and safety.

Which is a randomized open label study evaluating single agent Selinexor versus just physician choice therapy.

In patients with myelofibrosis, who have had at least six months of prior treatment with a JAK one two inhibitor.

The primary objective of this study is to assess the SVR 35, and key secondary endpoints include T. S. F. 50, overall response rate overall survival anemia response.

Impacts on symptom burden and safety.

Patricia Judson: We dosed our first patient in this study last year and expect to report top-line data during the second half of 2020. Turning now to slide 20. So this is our frontline myelofibrosis study, a Phase 1-2 study evaluating the combination of selonexor and rexalitinib in patients with treatment-naive myelofibrosis.

We dosed our first patient in this study last year and expect to report topline data during the second half of 2023.

Turning now to slide 22.

This is our first line myelofibrosis study.

Our phase one two study evaluating the combination of Selinexor and rock fill it.

In patients with treatment naive myelofibrosis.

Patricia Judson: Our goals for this study are to explore the combination of selenexa and ruxolitinib, building on the single agent activity of both compounds. Given the potential synergism between these two drugs, we believe that the combination of selenium rock has the potential to improve upon efficacy parameters while maintaining or improving symptom burden. This study began in mid-2021, and we're excited to be presenting the preliminary phase one data at the upcoming ASCO 2022 annual meeting. With that, I'm now going to advance to slide 21 and turn the call over to Mike to review the first quarter financial highlights.

Our goals for this study are to explore the combination of Selinexor and Russell letting them.

Building on the single agent activity of both compounds.

Given the potential synergism between these two drugs, we believe that the combination of Celean rocks.

The potential to improve upon efficacy parameters, while maintaining or improving symptom burden.

This study began in mid 2021, and we're excited to be presenting the preliminary phase one data at the upcoming <unk> 2022 annual meeting.

With that I'm now going to advance to slide 21, and turn the call over to Mike to review the first quarter financial highlights Mike.

Michael Mason: Thank you, Patricia. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which began on slide 22. Total revenue for the first quarter of 2022 was $47.7 million, compared to $23.3 million for the first quarter of 2021. Net product revenue from US commercial sales of Expovio for the first quarter of 2022 was $28.3 million, compared to $21.7 million for the first quarter of 2021, representing a 30% increase year over year. The estimated growth in the discount for Expovio in the first quarter was 19%.

Thank you Patricia since we issued a press release earlier today with the full financial results.

Just focus on the highlights which begin on slide 22.

Total revenue for the first quarter of 2022 was $47 7 million.

Compared to $23 3 million for the first quarter of 2021.

Net product revenue from U S commercial sales of exposure for the first quarter of 2022 was $28 3 million compared to $21 7 million for the first quarter of 2021, representing a 30% increase year over year.

The estimated gross to net discount for <unk> in the first quarter was 19% we.

Michael Mason: We expect growth to net discount to be in the 15 to 20% range for the full year 2020. We recognize $19.4 million of license and milestone revenue in the first quarter of 2022, which is inclusive of $8.6 million related to milestones earned in connection with our license agreements with Antigen and Prometico and $7.1 million earned in reimbursement of development expenses from Mentory. As a reminder, as part of the agreement that we announced in December, Manarini reimburses us for 25% of all expenses. We incur expenses for the global development of Selenexor not to exceed $15 million. R&D expenses for the first quarter of 2022 were $42.1 million, compared to $37.1 million for the first quarter.

We expect gross to net discount to be in the 15% to 20% range for the full year 2022.

We recognized $19 4 million of license and milestone revenue in the first quarter of 2022, which is inclusive of $8 6 million related to milestones earned in connection with our license agreements with entergy and per Medica, and $7 1 million earned in reimbursement of development expenses from the memory group.

As a reminder, as part of the agreement that we announced in December mentoring. He reimburses us for 25% of all expenses that we incur for the global development of Selinexor not to exceed $15 million per year.

R&D expenses for the first quarter of 2022 were $42 1 million compared to $37 1 million for the first quarter or 2021.

Michael Mason: This increase is primarily attributable to higher clinical trial expenses. Startup Costs for the Phase 3, We do expect our 2022 non-GAAP R&D expenses to decrease by approximately 10% compared to 2021, with the majority of the decrease expected in the second half. SG&A expenses for the first quarter of 2022 were $38.8 million, compared to $37.7 million for the first quarter.

This increase was primarily attributable to higher clinical trial expenses, including startup costs for the phase III SPD study.

We do expect our 2022 non-GAAP R&D expense to decrease by approximately 10% compared to 2021 with the majority of the decrease expected in the second half of 2022.

SG&A expenses for the first quarter of 2022 were $38 8 million compared to $37 7 million for the first quarter of 2021.

Michael Mason: Cash, Cash Equivalents, Restricted Cash, and Investments, as of March 31, 2022. Total $207 million compared to $235.6 million as of December 31, 2021. Based on our current operating plans, we continue to expect 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 compensation, to continue to be in the range of $265 to $280 million for the full year of 2022.

Cash cash equivalents restricted cash and investments.

At March 31, 'twenty two.

Totaled $207 million compared to $235 6 million as of December 31, 2021.

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

non-GAAP, R&D and SG&A expenses, which excludes stock based compensation expense to continue to be in the range of $265 million to $280 million for the full year of 2022.

Michael Mason: Certain previously expected launch preparation costs for endometrial cancer, which were included in our SG&A guidance, were shifted to R&D for the new Siendo. Therefore, we expect non-GAAP R&D expenses to decrease by approximately 10%, asked to serve as our reporting contractors for the next 6 months, trial compared to 2021, with most of the decrease expected to occur in the second half of 2022.

Certain previously expected launch preparation costs for endometrial cancer, which were included in our SG&A guidance were shifted to R&D for the new <unk> two study.

We expect non-GAAP R&D expense to decrease by approximately 10%, including the cost of the <unk> two trial compared to 2021 with most of the decrease is expected to occur in the second half of 2022.

Michael Mason: And finally, that our existing CASH, CASH for Co-Inference, as well as the revenue we expect to generate from Expovio product sales and other licensed revenues. Unknown Operator, I'll now flip to slide 23 and turn the call back.

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 revenues will be sufficient to fund our planned operations into early 2024.

I'll now flip to slide 23, and turn the call back for Richard.

Richard Paulson: Thanks, Mike. We believe that we are well positioned for a strong 2022, both on the commercial front as well as with the advancement of our clinical program. We continue to maintain strong momentum with a number of key near-term catalysts and corporate milestones for us to deliver on, as outlined on slide 24, as we continue to strive each day for patients with high unmet needs. The key upcoming milestones we are focused on over the near term, in addition to our continued focus on driving commercial performance, are to dose the first patient in our phase three study evaluating the all-oral SPD triplet in patients with relapsed or refractory multiple myeloma by the end of the first half of 2022, and receive a decision from the CHMP on our application requesting approval for selonexor, bort For the Endometrial Cancer Program, we will be presenting subgroup and molecular analysis data from the Siendo Study in an oral presentation at ASCO 22.

Thanks, Mike.

We believe that we are well positioned for a strong 2022, both on the commercial front as well as with the advancement of our clinical programs. We continue to maintain strong momentum with a number of key near term catalysts and corporate milestones for us to deliver on.

As outlined on slide 24, as we continued to strive each day for patients with high unmet needs.

The key upcoming milestones we are focused on over the near term. In addition to our continued focus on driving commercial performance.

Our to dose the first patient in our phase III study evaluating the all oral SPD triplet in patients with relapsed or refractory multiple myeloma by the end of the first half of 2022.

And receive a decision from the C. H M. P on our application requesting approval for Selinexor Bortezomib and dexamethasone in patients with multiple myeloma. Following at least one prior therapy also during the first half of 2022.

For the endometrial cancer program, where appropriate we will be presenting subgroup and molecular analysis data from the <unk> study in an oral presentation at <unk> 22.

We are also planning to initiate a new registration, enabling phase III study in P 53, wild type tumors during the second half of 'twenty two.

Richard Paulson: We are also planning to initiate a new registration-enabling phase 3 study in P53 wild-type tumors during the second half of 22. For the myofibrosis program, we look forward to presenting top-line Phase I selenectar data in combination with JAK inhibition in treatment of naive myofibrosis, also at ASCO. And finally, for the MDS program, we expect to report preliminary phase one eltanexor data in combination with a hypomethylating agent in frontline MDS during the second half of 2022.

For the Myelofibrosis program, we look forward to presenting top line phase one selinexor data in combination with JAK inhibition in treatment naive myelofibrosis also would ask about 'twenty two.

And finally for the Mds program, we expect to report preliminary phase one alpha and XR data in combination with a hyper method of ending agent in frontline Mds during the second half of 2022.

Richard Paulson: In closing, I would like to give a heartfelt thank you to all our teams at Karyopharm and our investigators as we work every day to positively impact the lives of patients with cancer. We would also like to thank our shareholders for your ongoing support and look forward to keeping you updated on our continued progress. It's an exciting time for the company, and we are all diligently working to create value for all of our many stakeholders. With that, I would now like to ask the operator to open the call up to the question and answer portion of today's call. Operator?

In closing I would like to give a heartfelt. Thank you to all of our teams that carry a farm and our investigators as we work everyday to positively impact the lives of patients with cancer.

We would also like to thank our shareholders for your ongoing support and look forward to keeping you updated on our continued progress. It's an exciting time for the company and we are all diligently working to create value for all of our many stakeholders with that I would now like to ask the operator to open the call up to the question and answer portion of today's call.

Operator.

We will now begin the question and answer session to ask a question you May press.

Operator: We will now begin the question and answer session. If you have 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 button for more information.

Star then one on your telephone keypad, if you are using a speaker phone. Please.

Pick up your handset before pressing the team.

To withdraw your question. Please press Star then two.

Operator: Thank you. Thank you. Thorden, [inaudible] At this time, we will pause momentarily to assemble our. This question comes from Maury Raycroft.

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, and thanks for taking my questions first one is on myelofibrosis with the upcoming data at <unk> can you talk about how many patients or what kind of follow up we might see at <unk> and maybe talk more about how you are looking for Selinexor plus rux for this combo to differentiate from some of the other.

Maurice Raycroft: Hi, good morning, and thanks for taking my questions. The first one is on myelofibrosis and the upcoming data at ASCO. Can you talk about how many patients or what kind of follow-up we might see at ASCO and maybe talk more about how you're looking for Selenaxor plus Rux for this combo to differentiate it from some of the other Rux combos in the clinic? Thanks, Memorial. For the first part of that, I'll pass it over to Patricia to talk about what we expect to see at Asco and also what we expect to see in combining Rucks with talent extortion in the front line mile fibrosis. So, Patricia? Patricia?

<unk> combos in the clinic.

Yeah. Thanks Mario.

First part of that deal I'll pass it over to Patricia to talk about what we expect to see it at school and also what we expect to see in combining <unk> with that with Selinexor in their front line myelofibrosis. So Patricia.

Patricia Judson: Yeah, thanks. So we're really excited about the preliminary data that we're going to be reporting at ASCO in about a month. So this is going to be the Phase 1 portion of the ongoing Phase 1-2 trial that is obviously looking at Selenexor in combination with Ruxolitinib in patients with treatment-naive myelofibrosis. And obviously, we'll share more details when the ASCO abstracts are released on May 26. What we're hoping to see with this combination, so anytime you combine two agents with strong single agent activity, we look to improve on the efficacy and still have a tolerable side effect profile.

Yeah. Thanks, So we're really excited about the preliminary data that we're gonna be reporting at <unk> in about a month. So this is gonna be the phase one portion of the ongoing phase one two trial that obviously is looking at selinexor in combination with rux or letting them in patients with treatment.

Ive myelofibrosis, so obviously, we'll share more details when the <unk> abstracts are released on May 26.

What we're hoping to see with this combination.

So anytime you combine two agents with strong single agent activity, we look to improve on the efficacy and still have a tolerable side effect.

Profile.

Patricia Judson: So as I reviewed during the presentation, you know, in the essential trial with monotherapy, Selen XOR, we saw really durable spleen responses; 40% of patients achieved an FV35 at 24 weeks or greater. In the Ruxolitinib trial, 40% of patients achieved SVR35. Therefore, the combination should be higher than this.

So as I reviewed during the presentation you know in the essential trial with monotherapy Selinexor, we saw really durable spleen responses, 40% of patients achieved an F 35 at 24 weeks or greater.

And rux, a litany of trial of 40% of patients achieved S. E. R 35 mm therefore, the combination should be higher than that.

Yeah.

Sohanya Cheng: Got it. That's really helpful. And I also wanted to ask a question about myeloma too. So for the proportion of patients being prescribed in early versus later lines, it seems like that's been at about 50-50 for a few quarters now. Are you seeing this start to shift more toward earlier lines? And can we learn more about it this year over the next couple of quarterly episodes? Yeah, thanks, Maurie. I'll turn to Sohanya to take you through that.

Got it that's really helpful and also wanted to ask a question about <unk>.

Myeloma too so for a proportion of patients being prescribed and early versus later lines. It seems like that's been at about 50 50 for a few quarters. Now are you seeing this start to shift more toward earlier lines and can we learn more about that this year over the next couple of quarterly updates.

Yeah, Thanks, Mario I'll turn for Tucson into to take you through that.

Sohanya Cheng: Thanks, Maurie, for the question. So yes, we continue to see that steady shift into the second to fourth line. And we see now greater than 50% of our patients now in the second to fourth line versus the fifth line plus. And the good news is that patients are seeing the benefit here and are staying on therapy longer. So we're seeing an increasing proportion of patients, for example, staying on four cycles or greater. And you're seeing this benefit because of the earlier line shift, primarily. And we'll continue to update you on that as we move forward more during the year. Okay, okay. Very good.

Thanks, Barry for the question. So yes, we continue to see that steady shift into the second to fourth line and we see now greater than 50% of our patients now in that second to fourth line versus the first line plus and that.

The good news is the pace and start seeing the benefit here and I'm staying on therapy longer. So we're seeing an increasing proportion of patients. For example, staying on four cycles are greater and you're seeing that benefit because of the earlier lines chef primarily.

And what we'll continue to update on that as we move forward Marty during the year.

Okay. Okay very good thanks for taking my questions.

Thank you.

The next question is from Peter Larson with Barclays. Please go ahead.

Operator: Thanks for taking my questions. Thank you. This next question is from Peter Larson with Barker. Unknown Speaker.

Hey, Thanks for taking my questions.

Peter Lawson: Thanks for taking my questions. I guess the first one's just around the impact of COVID. Is there any way?

I guess the first one is just around the impact of Covid anyway, Hey, Richard Mike to kind of break out the impact of Covid in the first couple of months of the quarter.

Richard Paulson: Richard or Mike to kind of break out the impact of the code. Yeah, thanks. Thanks, Peter. I'll let Sohanya do that because it's pretty clear as she looks at some of the numbers. Sohanya?

Yeah. Thanks, Thanks, Peter I'll, let I'll, let dawn you do that because it's a it's pretty clear she looks at some of the numbers. So on yeah yeah.

Sohanya Cheng: Yeah, thanks, Peter. So, you know, overall, when you think about, you know, COVID's impact, there are a couple of different facets, right? So, a particularly challenging environment in Q1.

Thanks, Peter So overall when you think about Covid impact there is.

A couple of different facets, right, so, particularly challenging environment in Q1, but when you look at January and February in particular, we see the data shows that Kobe head up to.

Separately, a 10% negative impact on oncology patient visits in Q1 of 2022.

Sohanya Cheng: But when you look at January and February, in particular, the data shows that COVID had up to approximately a 10% negative impact on oncology patient visits in Q1 of 2022. Now, that, in turn, impacted on new patient starts in that January to February period. The second component in terms of COVID impact is field activity and access to physicians, and this was impeded in that January to February period, including our proportion of live engagement.

That in turn impacted on new patient starts in that January and February period. The second component in terms of Covid impact is field activity and access to physicians and this was impeded in that January and February period.

Including our our proportion of live engagement and as you know in the initial stages of a launch it's critical to have this time in front of customers. However in March we saw the trends improved improving both in the marketplace. We're seeing signs of patients returning back to the clinic, but more importantly.

Sohanya Cheng: And as you know, in the initial stages of a launch, it's critical to have this time in front of customers. However, in March, we saw the trends improving in the marketplace. We're seeing signs of patients returning to the clinic, but more importantly, our access to physicians improved in March with over 60% of our engagement being live. Also, we grew our new starts in March as well.

Our access to physicians improved in March with over 60% of our engagement being light.

We grew our new start up.

In March as well if you take a step back and look at our growth drivers Holistically, we sustained improvement across all our growth drivers. So we continue to see that positive shift in earlier line, which gives us that duration benefit we continue to increase our breadth.

Sohanya Cheng: If you take a step back and look at our growth drivers holistically, we have sustained improvement across all our growth drivers. So, we continue to see that positive shift in earlier lines, which gives us that duration benefit. We continue to increase our breadth, but more importantly, our depth of use of Expovio, and we have also improved our perception of intent to prescribe data. Thank you; it is encouraging to see. The Revenue Guidance Reiterated. What factors should we be thinking about that could help? We accelerate quarter over quarter growth and also drive higher. Unknown Speaker.

But more importantly, our death abuse of exposure and we also improved our perception or the intent to prescribe data.

Thank you and then.

It is encouraging to see the revenue guidance reiterated.

What factors should we be thinking about that help reaccelerate quarter over quarter growth and also drive higher.

Year over year growth and.

Operator: Thank you. What are the factors there, and how should we think that is kind of playing out? Yeah, thank you, Peter. I'll turn that over to Sohanya in a minute. But, as you know, there's obviously those dynamics that happen Q over Q. So, obviously, we're focusing on reiterating our guidance and achieving that range of about 40% growth over the year. I think Sohanya's talked about some of those headwinds we faced already in Q1. But I'll turn to Sohanya to kind of take you through why we have the confidence to deliver on that for the full year. Great

What are the factors there and how should we think of that kind of playing out through the year.

Thank you.

Yes. Thank you Peter I'll turn it over to Tom in a minute, but as you know, there's obviously those dynamics that happened Q over Q, so focusing obviously on reiterating our guidance and achieving that that range of about 40% growth over the year I think Don you talked about some of those headwinds we faced already in Q1, but I'll turn it so I need to kind of take through.

Why we have the confidence to deliver on that for the full year great. Thanks, Peter So first of all 30% year over year of net product revenue growth I feel extremely good about in it given the backdrop.

Sohanya Cheng: Thanks, Peter. So first of all, 30% year over year net product revenue growth, I feel extremely good about it given the backdrop of the significant COVID impact we experienced, particularly in the January and February phases. In terms of moving forward, and the growth drivers, they remain the three key growth drivers where we've seen sustained improvement. So our focus for the rest of this year is to accelerate that earlier line shift. And we've seen our most rapid growth on the third line.

The significant COVID-19 impact, we experienced particularly in the January February phase in terms of moving forward and the growth drivers. They remain the three key growth drivers, where we've seen sustained improvement. So our focus for the rest of this year is to accelerate that earlier.

Sohanya Cheng: And our focus is to continue to accelerate that third line growth. And as I mentioned earlier, you see, as a result, the benefit on duration when these patients move into earlier lines. The second area of focus is we talked about breadth and depth. But as we evolve through our launch phase, our focus becomes accelerating depth. So to give you an example of depth and increase in the use of Expovio with our core customer base, if you look at our top 20 Expovio accounts, which include a lot of the major community networks, and they contribute to about a third of the business, we saw almost 50% revenue growth. So for the rest of this year, with access improving to our physicians, driving depth will be a critical success factor. And finally, improving the perception of the product.

Shift and we've seen on most of rapid growth in the third line and our focus is to continue to accelerate that third line growth and as I mentioned earlier you see as a result, the benefit on duration when these patients move into earlier line.

Second area of focus as we've talked about breadth and depth, but as we evolve through launch phase our focus becomes accelerating death. So to give you. An example of deaths and increase in the use of exposure with our core customer base. If you look at our top 20 exposure Youre count.

Which include a lot of the major community networks and they contribute about a third of the business. We saw almost 50% revenue growth. So for the rest of this year with the access improving to our physicians driving deaths will be a critical success factor and finally, improving the process.

Sohanya Cheng: We've seen continued sustained improvement over the course of the year, and we plan to continue to do that in terms of improving perceptions of both efficacy as well as safety. And then, as Richard pointed out, there can be quarter over quarter fluctuations. Typically, they're in Q4, Q1, you see some seasonality dynamics, some buying pattern dynamics in Q4.

And of the products, we've seen continued sustained improvement over the course of the year and we plan to continue to do that in terms of improving perception of both the efficacy as well as the safety and then in terms of Richard pointed out that there can be quarter over quarter fluctuations typically they're in queue.

For Q1, you see some seasonality dynamics I'm buying pattern dynamics in Q4, but when you think about Q2 and moving forward, we anticipate the marketplace normalizing in terms of patient flow and obviously, excluding any potential future COVID-19 impact so I feel confident.

Sohanya Cheng: But when you think about Q2 and moving forward, we anticipate the marketplace normalizing in terms of patient flow, obviously excluding any potential future COVID impact. So I feel confident about our annual guidance of 135 to 145 million. Are there any clues from the scripts or the access? Flow for April as well. How did that get better over months?

About our annual guidance of 135 to 145 million.

Are there any clues from.

In the script or the access or patient flow for April as well how did that did that get better as of March.

So final question, yes, well I think what will come we'll comment on that as we get into Q2 I think we just wanted to focus on Q1 now because it takes a while obviously over that data to mature and see what it looks like.

Operator: [inaudible] I think we'll comment on that as we get into Q2. I think we just want to focus on Q1 now because it takes a while, obviously, for that data to mature and see what it looks like. Thanks, Peter.

Got you okay. Thank you so much.

Thanks Peter.

Operator: The next question is from Mike Oltz with Morgan. Hey guys, thanks for taking the question. Unknown Speaker Just given that you're seeing some impact of COVID on the commercial side.

The next question is from Michael Moore.

Organ Stanley. Please go ahead.

Hey, guys. Thanks for taking the question.

Just given that you are seeing some impact of COVID-19 on the commercial side I'm just curious if you're seeing any impact on the enrollment side, specifically for your phase two MF and Mds studies.

Operator: I'm just curious if you're seeing any impact on the enrollment side, specifically for your Phase II MF and MDS studies. Yeah, thanks, Mike. I'll hit that at a high level, and then I'll turn it over to Reshma.

Richard Paulson: But I think, as we all experienced in the environment, in January and February, you know, a number of staff were out across our clinical trial sites. So that did affect some of our startup times. It did affect some of the access in different areas. And Reshma, maybe you want to expand on that a little bit? Yeah, we see that.

Yeah. Thanks, Mike.

I get that at a high level, and then I'll turn it over to duration.

But.

Because we all experienced in the environment.

In January and February you know a number of staff were out across our clinical trial sites, so that didn't affect to some of our startups.

It affects some of the access in different areas and a ratio maybe you wanted to expand on that a little bit.

Yeah, we see that and thank you for the question I mean, we see some of the challenges with Covid.

Reshma Rangwala: Thank you for the question. I mean, we see some of the challenges with COVID in our clinical trials as well. We've had issues with sort of resources, ability to get to sites, and challenges in opening up the sites, you know, at our facilities.

In our clinical trials as well we've had your issues with them sort of resources the ability to get to sites challenges in opening up the sites you know at our facilities.

With that said you know hopefully we should be you know seeing that seeing a turnaround and you know continued enrollment and potentially expanded enrollment in all of our studies.

Reshma Rangwala: You know, with that said, hopefully, we should be seeing a turnaround and continued enrollment and potentially expanded enrollment in all of our studies. Got it. That's helpful. And maybe just one more question for me and a follow-up on just the MF data. I'm inspecting at ASCO.

Got it that's helpful and maybe just one more question for me and a follow up just on the MF data.

Are you expecting at Pasco next month.

In terms of the bar when we think about the data you mentioned, 40% is kind of what what to expect for rux in combination you should be above that but.

Operator: In terms of the bar, when we think about the data you mentioned, 40% is kind of, downloaded from www. AllSubs.org. As you think about moving this program forward in the future, what... Unknown Speaker Yeah, what's meaningfully above, say, 40%, you know, is it 10 percentage points, is it more than that, or, We'll write some color there. Yeah, thanks, Michael. I'll turn to Patricia to talk about that, but I think there's a number of areas that Patricia would talk about. One obvious factor is the overall response rate.

As you think about moving this program forward in the future what.

Yeah, what's meaningfully above 40% is it.

Is it 10 percentage points is it more than that or just you know.

Provide some color there that'd be helpful. Thanks.

Patricia Judson: The other is also looking at the symptom burden across patients and looking to reduce kind of the other symptom burden, as well as some of the side effect profiles. Patricia, maybe you can expand on that back to Mike. [inaudible] Yeah, thanks, Mike, for the question. So, you know, when we talk to the KOLs, they believe that if we can see a response rate of anything better than 40%, that would be a really good bar to reach.

Yeah, Thanks, Mike I'll turn to Patricia to talk to that but I think theres a number of areas that Patricia what type of on one is obviously, though the overall response rate. The other is also looking at the symptom burden across patients and.

Looking to reduce kind of the other symptom burden as well as kind of some of the side effect profile. So Patricia maybe you can expand on that back to Mike.

Yeah. Thanks, Mike for the question. So you know when we talk to the Kols. They believe that if we can see a response rate anything better than 40%, but that would be really a good bar to reach.

Patricia Judson: You know, one of the things that we have noted with Selenexor is that we improve on multiple fronts. So screen volume reduction, symptom improvement, improvement in anemia, and potential disease modification with a reduction in bone marrow fibrosis. And it's interesting, even though Selenexor has a side effect of anemia, we note that with continued use in these myelofibrosis programs, the anemia actually decreases over time.

You know one of the things that we have noted with Selinexor is that we improve on multiple fronts. So spleen volume reduction symptom improvement improvement in anemia.

And potential disease modification with the reduction in bone marrow fibrosis.

And it's interesting even though selinexor has a side effect of the new yeah. We note that with continued use and these myelofibrosis program that the anemia actually decreases over time, so we're hoping that perhaps.

Operator: So we're hoping that perhaps the combination of RUX plus Selenexor may actually decrease some of the anemia. But, as you said, we're looking forward to the ASCO post. Great, thank you. Thanks Mike. This question is from Colleen Kusy. Hi, good morning.

Perhaps a combination of rux, plus selinexor may actually decrease some of the anemia.

Right.

Said, where we're looking forward to the ESCO poster.

Great. Thank you.

Thanks, Mike question.

Next question is from Colin can see with Baird. Please go ahead.

Hi, good morning, Thanks for taking our questions. So.

Colleen Kusy: Thanks for asking your questions. So in the Phase 1 study for mild fibrosis that you'll have at ASCO, is there anything that we should keep in mind in terms of the patient selection for that trial, especially when comparing to other MS studies? Yeah, I'll turn to Patricia for that.

So in the.

Phase one study for myelofibrosis that you'll have to ask though is there anything that we should keep in mind in terms of the patient selection for that trial, especially when comparing to other studies.

Now I'll turn to to Patricia for that.

Patricia.

Yeah. So this is a.

Patricia Judson: Yeah, so this is phase one, they're naive to JAK1,2 inhibitors. So this is just frontline treatment. They are required to have a platelet count of over 100,000, and other than that, they're just frontline MS patients.

Phase one there are naive to JAK one inhibitors.

So this is just a frontline treatments they are required to have.

Uh huh.

Platelet counts of over 100000.

And other than that they're just the the the frontline MF patients.

Operator: Does that answer your question? Yes, that's helpful. Thank you. And then just in terms of how you're thinking about development in the frontline setting versus the second line setting, and kind of how you've decided on the treatment, the patient population for the second line setting, kind of understand there are some differences in whether these patients are really rux refractory or just, you know, Jack experience. So can you talk about patient selection for the second line setting, please? Yes, thank you, Colleen. I think we'll turn to Patricia to expand on that.

Is that answer your question.

Yes, that's helpful. Thank you.

And then just in terms of how youre thinking about development in the frontline setting versus the the second line setting and kind of how you decided the treatment the patient population for the second line setting kind of understand theirs.

Some differences and whether these patients are really rocks refractory or just you know Jack experience. So can you talk about the the patient selection.

For the second line setting.

Yes, I can tell me how that works and we turned to Patricia to expand on that.

Patricia Judson: All right, thank you. So in the 035 study, which is the second line study, as you know, 40% of patients respond to frontline treatment with RUX, leaving 60% of patients looking for options. There are no other classes of treatment other than JAK inhibitors.

Alright. Thank you so in the 035 study, which is the second line study as.

As you know 40% of patients respond to a frontline treatment with rux, leaving 60% of patients looking for options and there are no other classes of treatment other than the JAK inhibitors, and so you know, there's a significant potential to increase responses and improve survival in these patients.

Patricia Judson: And so, you know, there's a significant potential to increase responses and improve survival in these patients. With a new class of drugs, we feel like this could really help the patients and give them more options. And I think, Colleen, to add to that, we're truly looking for patients who are kind of rux refractory with at least 20 to 24 weeks or six months of exposure to a JAK inhibitor. Okay, great.

With a new class of drugs, we feel like this could really help the patients and give them more options.

And I think calling to add on that where we're truly looking for patients who are kind of rux refractory with at least 2024 weeks or six months exposure to a JAK inhibitor.

Operator: Thank you. And as a quick follow-on, as you've done more work on p53 wild type, are there any other tumor types that you think might make sense to pursue based on the signal that you're seeing in endometrial? Yeah, that's a great question.

Okay, great. Thank you and as a quick follow on as you've done more work on P. 53, Wild type <unk> are there any other tumor types that you think might make sense to pursue based on the signals that you're seeing in endometrial.

Reshma Rangwala: We're continuing to do work on that, obviously, with our development team. And maybe you want to expand on that, Reshma? Yeah, absolutely. I mean, you know, P53, the exploratory subgroup from the Sando trial, really did show impressive results. I mean, these are very preliminary results, but impressive results, again, in that exploratory subgroup. We're continuing to look at P53 across multiple tumors, including our hematologic malignancies, as well as other solid tumors, and hope to look at the potential for P53 wild type as a potential subgroup across an array of cancers.

Yeah, that's a great great question, we're continuing to do work on that obviously with her with her development team and maybe do you want to expand on that ratio.

Yeah, absolutely I mean, you know P 53 of the exploratory subgroup from the Sandoz trial really did show impressive results. I mean, these are very preliminary but you know impressive results again in that exploratory subgroup were continuing to look at P 53 across multiple two or tumors, including.

Our hematologic malignancies as well as other solid tumors.

And hope to look at you know the potential for P 53 wild type.

As a potential subgroup across an array of cancers with that said, we also know that there are multiple tumor suppressors that you know we can be looking at so you know we are looking at P 53, but really across the board to best identify potential markers that we can.

Reshma Rangwala: You know, with that said, we also know that there are multiple tumor suppressors that, you know, we can be looking at. So, we are looking at P53, but really across the board to best identify potential markers that we can pursue across a range of different tumor types and patient populations.

Pursue across a range of different tumor types in patient populations.

Operator: Great, thanks for your question. Thanks, Colleen. The next question is from Brian Abrahams. RBC, Capitol Marks, Hi, this is Joe. I'm for Brian.

Great. Thanks for taking our questions.

Thanks Colin.

Our next question is from Brian Abrahams with RBC capital markets. Please go ahead.

Hi, This is Joe on for Brian . Thanks for taking our question can you talk a little bit about.

Operator: Thanks for taking our question. Can you talk a little bit about the RUX combo study in MF? So for the patient-choice arm, can physicians choose some of the newer JAK inhibitors that are recently approved or that may be approved? How do you see this impacting potential responses across the arms?

The Rux combo study and an N F and so for the patients actually signed a kinder physicians choose some of the newer JAK inhibitors.

Then our recently approved there and that May be approved how do you see how do you see this impacting the potential responses across the arms and <unk> for.

Patricia Judson: And for the monotherapy use for psilonexor, how do you see the post-RUX landscape evolving, and where can psilocybin fit in? Sure, maybe I'll turn to Patricia to talk about those two parts.

For the monotherapy use recently next door and how do you see the post rux landscape evolving and work in Salt Lake City. Thank you.

Sure, maybe I'll turn to to Patricia to talk to those two those two parts Patricia.

Yes, so the frontline.

Patricia Judson: Yeah, so the frontline trial in treatment naive patients is looking at ruxolitinib plus selenixor versus ruxolitinib single agent. So in that one, physicians don't choose the JAK inhibitor. In the other trial, 035, which is the second line, that one is selenixor versus physician's choice. And physicians can choose to either reuse ruxolitinib or they can choose any of the other treatments that are currently available, so chemotherapy, fedratinib, androgens, interferon, anything that is available for them. And then, you know, as far as the treatment landscape is concerned, obviously, there have been a couple of approvals. Pacritinib has been approved for patients who have platelet counts less than 50.

File in treatment naive is looking at Rex.

Selinexor versus Russell at mid single agent. So in that one the physicians don't choose the JAK inhibitor in the.

The.

Other trial 035, which is second line that one is selinexor versus physicians choice.

And the physicians can choose to either reuse Russell at nib or they can choose any of the other treatments that are currently available so chemotherapy.

Nib androgens interferon anything that is available for them.

And then you know as far as the treatment landscape, obviously theres been a couple of approvals.

Patrick Nib was approved for patients who have platelet counts less than 50, we knows that.

Patricia Judson: We know that there was just an acquisition of Momolitinib, which is, of course, another JAK inhibitor. Again, you know, we're pretty excited about Selenexor as it gives patients a new mechanism of action outside of the JAK inhibitor population. And I think, Joe, building on that, what's really important is looking for the response rates in those refractory MF and giving, as Patricia just touched on, the end, you know, if you can have an application to agent, which is a different class, starting to really give patients more opportunity for multiple classes, which we've seen a huge benefit from, obviously, in multiple myeloma over the last decade or so. Thank you. Thanks, from Eric, Morgan. Please go ahead. Hi, good morning.

There was just an acquisition.

Letting them, which is of course, another JAK inhibitor.

And you know, we're pretty excited about selinexor as it gives patients a new mechanism of action.

Outside of the JAK inhibitor population.

Yeah.

And I think Joe building on that what's really important is looking for the response rates in those refractory MF and giving them. The best Patricia just touched on yes, you can have an efficacious agent, which is a different class starting to really give patients more opportunity for multiple classes, which we've seen the huge benefit obviously in multiple myeloma over the last the last decade or so.

No.

Alright that was very helpful. Thank you.

Thanks.

The next question is from Eric Joseph with JP Morgan. Please go ahead.

Operator: Thanks for taking the questions. Just coming back to the COVID commercial impact, does it make sense that COVID would impact new starts for the quarter? Also, is it also your sense that this headwind impacted prescription refills as well?

Hi, good morning, Thanks for taking the questions just coming back to the commercial impacts.

If it makes sense that COVID-19 would impact new starts for the quarter is it also your sense that.

This headwind is impacted.

Prescription refills as well I'm, just trying to reconcile sort of where the impact was experienced Steven.

Eric Joseph: I'm just trying to reconcile sort of where the impact was experienced given the sort of steady 50-50 mix between earlier and late line. And to what extent, I guess, was there any shift in gross to net given the typical coverage gap on the side of payers that we see in the first quarter? Yeah, thanks, Eric. I'll turn to Sohanya for that to touch on the refill, and then I can have Mike talk to the shift Q over Q on the GTN.

Sort of a steady 50 50 mix between earlier in late line.

And.

To what extent I guess was there any shifting.

Gross to net given the cyclical.

The coverage gap on the set of players.

We see in first quarter.

Yeah, Thanks, Erik I'll turn to Tucson here for that to touch on that on the retail and then I can talk to the the shift Q over Q on the GTS.

Sohanya Cheng: Thanks, Eric, for the question. So overall, if you compare quarter over quarter demand units, we maintain demand units despite the COVID impact and the seasonality impact. So if we're breaking it down to new starts versus refills, the new starts were impacted, particularly in January and February by COVID. However, we did see a growth in new starts again in March, but overall, COVID did have an impact on new starts because, from the data that we see, oncology patient visits were impacted negatively by about 10% in January and February.

Thanks, Larry for the question. So overall, if you compare quarter over quarter demand unit, we maintain demand units, despite COVID-19 impact and the seasonality impact by breaking it down to new starts versus refills.

New starts were impacted particularly in January and February by Covid in January and February. However, we did see a growth in new starts again in March but overall COVID-19 did have an impact on new starts because oncology patient visit but the data that we see where impact.

Negatively by about 10% in January and February now if you take a look at our refills, we actually continue to improve our refill rates and Boston launch and the patients are showing signs of staying on therapy longer, particularly in the early aligned.

Sohanya Cheng: Now, if you take a look at our refill rates, we actually continue to improve our refill rates since the Boston launch, and patients are showing signs of staying on therapy longer, particularly in the earlier lines. And as I mentioned before, for example, we see this increasing proportion of patients in four cycles or more.

Sohanya Cheng: So we're making good progress overall, despite the COVID impact early this year. And Mike, do you want to touch on the GTN from Q4 to Q1? Sure.

Mentioned before for example, we see this increasing proportion of patients in four cycles are more so we're making making good progress overall, despite the COVID-19 impact or at least this year.

And Mike do you want to touch on the G. T N from Q4 to Q1.

Michael Mason: Q1 GTN, as we mentioned in the call, was right around 19% versus Q4 GTN, which was around 15%, you know, typical higher in Q1 versus See every year, and we did a guide on the call that we expected to be somewhere. Okay, okay, that's very helpful. And maybe just a follow-up question on MM031. I guess as that study gets underway this year, does this patient enrollment there present all ahead into, you know, your commercial guidance for Expovia for the full year, and then on the cost side related to that trial, you know, given the lifecycle opportunity for both you and your partners, antigen and minerating, I'm wondering to what extent it might be contributing to the cost associated with conducting that study Thanks. Thanks, Derek.

Sure Q.

Q1 G T N as I mentioned in the call. It was right around 19% versus Q4 G. T. N was around 15%. So typical higher in Q1 versus in Q4 that you see every year and we did guide on the call that we expect to be somewhere between 15 and 20% for the full year 2022.

Okay. Okay, that's very helpful and maybe just.

A follow up question on <unk>.

And then <unk> one.

That study gets underway this year does that.

Yeah.

Patient enrollment there.

Not at all a headwind too.

Sure.

Commercial guidance for exposure for the full year and then on the cost side related to that trial given.

The lifecycle opportunity for both you and your partners.

Energy to Missouri, I'm wondering to what extent that might be considered it too.

Uh huh.

Costs associated with conducting that study.

Richard Paulson: No, I think when you look at that study, you know, in combination with POMILUS, you know, we're running that study in the U.S. and in Europe, and so we don't see it having any impact on our commercial performance. And then I think moving forward, as we're expecting to see that data, you know, the top line in 2024, working to gain approval, pending the data in 25, you know, having the opportunity for an all oral, and having that opportunity, as you know, the study is having patients having to be exposed to anti-CD38 up front.

Yeah. Thanks, Eric I think when you when you look at the study in combination with almost.

We're running that study in the U S and in Europe , and so we don't see it having any impact on our commercial performance.

And then I think moving forward as we're expecting to see that data.

The top line in 2024.

Working to gain approval of pending the data and 25.

Any opportunity for an oral.

And having that opportunity as you know the study is having patients having to be exposed to anti CD 38 upfront. So I think as we see the continued shift with increasing number of patients in the first two lines being treated with anti CD 38 two.

Richard Paulson: So, I think, as we see the continued shift with an increasing number of patients in the first two lines being treated with anti-CD38, to be able to really have the combination for an efficacious all oral, I think will drive significant value for us and for patients and for our partners as we move forward. Okay, thanks for taking the questions. Thanks, Eric. The next question is from Ed White with H. C. Wainwright. Please go ahead. Good morning.

To be able to really have the combination of for an efficacious oral I think will drive significant value for us and for patients and for our partners as we move forward.

Okay. Thanks for taking my questions.

Thanks, Eric.

The next question.

Austin is from endpoint with H C. Wainwright. Please go ahead.

Edward White: Thanks for taking my questions. Can you give us your thoughts on off-label use right now with Pomelask and the other combinations, you know, the ones that perhaps are in the NCCN guidelines? And also, you mentioned that virtual versus in-person detailing is improving in March; I believe you mentioned 60% were in-person. Can you just give us some of the historical numbers for that? How low did it go in January and February?

Good morning, Thanks for taking my questions.

Can you give us your thoughts on off label use right now with homeland and the other combinations you know the ones that are perhaps on mute and CCN guidelines.

And then also you had mentioned that a virtual versus in person detailing is improving in March I believe you mentioned, 60% were in person can you just give us some of the historical numbers that how low did it go in January and February and what was the comparison.

To the fourth quarter of last year.

And then is there a noticeable difference.

In accounts that are virtual versus in person detailing are you seeing a bigger penetration and prescriptions. Thank you.

Sohanya Cheng: And what was the comparison to the fourth quarter of last year? And then, is there a noticeable difference between accounts that are virtual versus in-person detailing? Are you seeing a bigger penetration in prescriptions? Thank you. Thanks, Ed. We'll add those three questions together, and we'll get Sohanya to run through them. Sohanya?

Thanks, Ed well add those three questions together and we'll get to the one you to run through them. So on yes, Hi, Ed.

Sohanya Cheng: Hi Ed. Thanks for the questions. I'll take that in three parts.

Thanks for the question so I'll take that in three parts. So first of all I'm looking at just the mix of regimens and and the utilization so.

Sohanya Cheng: So, first of all, looking at just the mix of regimens and the utilization. So, just, you know, looking at the data. Right? We don't have full visibility into all of the Expovio data, and there can be fluctuations quarter over quarter. But from what we are seeing since the launch of Boston, there is an overall increase in the use of triplets versus doublets. Now, triplet use is kind of split between XVD and the other regimens. We do see the use of other regimens, including Expovio in combination with pomalidomide, daratimumab, and kyprolis.

Looking at the data right, we don't have full visibility into all of the exposure of your data and there can be fluctuation quarter over quarter, but from what we have seen since the launch of Boston. There is an overall increase in the use of triplet versus the doublet now that's tripling youth it's kind of.

Between X V D and and the other regimens, we do see us.

The regimens, including Expo via combination with <unk> and Kyprolis now all four triplets are on the N. P. C. N guidelines. However, we only promote to the X V D regimen.

Sohanya Cheng: Now, all four triplets are on the NCCN guidelines. However, we only promote to the XVD regimen. And it's really a physician's discretion on how they and which regimen that they choose based on the prior therapy. Moving to your next question on just live visits versus virtual, so to date, we're roughly at our live visits are about 60%. In the January and February months, we saw drops to as low as 30 to 40%, given the increased restrictions and impact from the surge in COVID.

And it's really a physician's discretion on how they and which regimen that they choose based on the prior therapy.

Moving to your next question.

Just live visits birthdays, a virtual so to date, we're roughly our lives visits are about 60%.

In the January February months, Ah, we thought dropped to as low as 30% to 40%.

Given that the increased restrictions and any impact from the surge in COVID-19.

Sohanya Cheng: In Q4, we saw roughly the mid-50s, an even split between virtual versus in-person. So overall, I would say outside of the surge in COVID, we're seeing a return to pre-COVID levels in terms of live engagement. As far as effectiveness of live versus virtual, I believe both are equally effective.

In Q4, we saw roughly in the mid fifties, even split between virtual versus in person. So overall I would say outside of the surge in Covid, we're seeing a return to pre COVID-19 levels.

In terms of live engagement as far as effectiveness of life versus virtual.

Sohanya Cheng: It's always great to be in front of a customer live, but the team has truly adapted, our resources have adapted digitally, and we have really optimized our virtual channels as well as our live. So both channels end up being quite effective, but our preference as a field team is always to get in front of the customer in person, which is particularly effective at this stage of our launch.

I think both Bill I believe both are equally effective it's always great to be in front of a customer life. However, the team has truly adapted our resources have adopted digitally.

We have really optimized our virtual channels as well as in our lives. So both channels end up being quite effective but our preference is our field team is always to get in front of the customer in person, which is particularly effective in this stage of our launch so we continue to want to see.

Operator: So we continue to want to see those live engagements improve. I think we have time for one more question, operator. The next question is from Jonathan. SBB.

Those live engagements improve.

I think we have time for one more question operator.

Our next question is from Jonathan Chang with SBB Securities. Please go ahead.

Operator: Hi guys, this is Scott Salon on Jonathan's behalf. I just wanted to ask, could you describe what the endometrial cancer new study design might look like and sort of how you think about this study relative to others ongoing in the line of, Yes, thanks. I think for that, I'll turn it over to Patricia to talk about the potential study design. As you know, we're still engaging with the FDA, so it's still at a high level. And then maybe what we're seeing in the environment overall moving forward, Patricia. Yeah, thanks for the question.

Hi, guys. This is Scott on for Jonathan just wanted to ask could you describe what the endometrial cancer. The new study design might look like and sort of how you think about this study relative to others ongoing underlying skin.

Yeah. Thanks, I think before that I will turn it over to Patricia to talk to the potential study design as you know, we're still engaging with the FDA. So it's still a high level.

And then maybe what we're seeing in the environment overall moving forward Patricia.

Yeah. Thanks for the question. So as Richard said, we've really worked with and got G. O G and the steering committee to kind of design an appropriate clinical trial, we have a meeting scheduled with the FDA to discuss the study we know that it's gonna be a randomized placebo controlled trials.

Patricia Judson: So, as Richard said, you know, we've really worked with NGAT, GOG, and the steering committee to kind of design an appropriate clinical trial. We have a meeting scheduled with the FDA to discuss the study. We know that it's going to be a randomized placebo-controlled trial, and it will be maintenance therapy for patients with P53 wild-type endometrial cancer who've responded to chemotherapy. Obviously, we'll give more details on the study design when we initiate the study in the second half of this year. And then, as far as the landscape is concerned, There are a lot of studies that are ongoing in endometrial cancer, and we're waiting for those to mature and see how they read out.

And it would be maintenance therapy for patients with P 63, wild type and.

Endometrial cancer, who have responded to chemotherapy.

Hum.

Obviously, we'll give more details on the study design when we initiate the study in the second half of this year.

And then as far as on them.

The landscape.

The you know Theres a lot of studies that are ongoing in endometrial cancer, and we're waiting for those to mature and see how they read out.

Got it thank you.

Yeah.

Richard Paulson: Shalom. So with that, I think we're out of time. Oh, I'm sorry. Thank you, Operator. I'd like to thank everyone for joining today's call, and have a great day, everyone. The conference was now in progress. Thank you for attending today's presentation. You may now disconnect.

Sure.

So with that as Greg Let me answer session.

Oh I'm sorry.

Thank you operator, I'd like to thank everyone for joining today's call and have a great day everyone.

Yeah.

The conference has now ended.

Thank you for attending today's presentation you may now disconnect.