Q2 2022 Karyopharm Therapeutics Inc Earnings Call

[music].

Hey, Lisa good morning, and welcome to the capital Farm Therapeutics Q2, 'twenty two earnings conference call all participants will be in the listen only mode.

Unknown Executive: Good morning and welcome to the Karyopharm Therapeutics Q2-22 Earnings Conference Call.

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Please note. This event is being recorded I would now like to turn the conference over to Mr. Glenn Beck Senior Vice President Investor Relations.

Unknown Executive: I would now like to turn the conference over to Ms. Elhan Webb, Senior Vice President, Investment Relations.

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Please go ahead.

Elhan Webb: Thank you, Operator, and thank you all for joining us on today's conference call to discuss the Karyopharm Second Quarter 2022 financial results and recent company progress.

Thank you operator, and thank you all for joining us on today's conference call to discuss <unk> second quarter 2022 financial results and recent company progress today I'm joined by Mr. Richard Paulson, President and Chief Executive Officer, Mr. <unk>.

Elhan Webb: Today, I'm joined by Mr. Richard Paulson, President and Chief Executive Officer, Ms. Sohanya Cheng, Chief Commercial Officer, Dr. Reshma Rangwala, Chief Medical Officer, and Mr. Mike Mason, Chief Financial Officer.

Jay.

Chief Commercial officer, Dr duration around Wala, Chief Medical Officer, and Mr. Mike Mason Chief Financial Officer.

Elhan Webb: Earlier this morning, we issued a press release detailing Karyopharm's financial results for the second quarter 2022. This release, along with a slide presentation that we will reference during today's call, are available under the Events and Presentations section of our website at karyopharm.com.

Earlier. This morning, we issued a press release detailing carrier farms financial results for the second quarter 2022.

This release, along with a slide presentation that we will reference during today's call are available under the events and presentations section of our website at Carole Park.

Elhan Webb: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide 3.

Closing remarks before opening the call up for questions.

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

Elhan Webb: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC and in other filings that we may make with the SEC in the future.

<unk> 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 court quarterly report on Form 10-Q, which is on file with the SEC.

In other filings that we may make with the ACC in the future.

Any forward looking statements represent our views as of today all of it.

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

We specifically disclaim any obligation to do so.

Even if our views change.

Therefore, you should not rely on these forward looking statements as representing our views as of 80 days subsequent to today.

Elhan Webb: In addition, we will also be providing on this call outlook for non-GAAP R&D and SG&A expenses for 2022.

In addition, we will also be providing on this call outlook for non-GAAP , R&D and SG&A expenses for 2022.

We are not providing recalls nations of this forward looking non-GAAP measures because projections of stock compensation expense, which is required for such recalls aviation are not available without unreasonable effort.

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

Elhan Webb: We are not providing reconciliations of these forward-looking non-GAAP measures because projections of stock compensation expense, which is required for such reconciliations, are not available without unreasonable effort.

Thank you I'll hand, and good morning to everyone joining us on the call and webcast today.

Elhan Webb: I will now turn the call over to Richard.

This morning, I'm excited to provide an update on our plan as we continue to execute on our growth strategy through our focused pipeline targeting life threatening cancers.

In Q2, we saw a significant increase in total revenues compared to Q2 of 'twenty one of approximately $40 million, which includes the benefit of licensing and milestone revenue as we continue to receive new or expanded regulatory approvals globally.

With growing patient access for Selinexor across the World. We expect revenues in ex U S territories have an increasing contribution to total selinexor revenues in the future.

In addition, we are pleased to have delivered a 44% net product revenue growth year over year, despite an increasingly competitive multiple myeloma market and some continuation of COVID-19 related challenges.

I am pleased with our team's ongoing commitment to successfully execute against our key priorities.

As a global leader in the inhibition of nuclear export everything we do is driven by our mission to positively impact patient lives and defeat cancer.

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 continue to successfully build upon our existing bulk of myeloma franchise.

Second we continued to advance our focused clinical pipeline comprised of mid and late stage clinical development programs.

That is being purpose built and strategically focused on targeting cancers with high unmet need.

Our science enables us to make the biggest difference in the lives of patients.

And where we believe we will have the highest probability of success.

To that end based on compelling data signals, we are pursuing opportunities in endometrial cancer.

Hello, fibrosis and Myelodysplastic syndromes.

Collectively we believe we have the potential to achieve multiple product approvals over the next two to four years.

Our third pillar is our people.

We strengthened the leadership team during the second quarter, including the appointment of Dr duration marijuana Wala at the company's Chief Medical Officer, and the recent promotion of Stewart, Poland to Executive Vice President and Chief Development Officer.

Stuart has more than 25 years of experience in the global biotech and pharmaceutical space.

Including both clinical operations and portfolio leadership roles at Abbvie.

Amgen and Eli Lilly.

With Stuart's promotion, we consolidated the leadership structure of our R&D organization driving increased accountability and focus.

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, we believe we are well funded into early 2024.

Mike will highlight our reduced expense guidance as we initiated cost reduction initiatives in line with the evolution of our focused pipeline.

With these pillars in place we believe we have a solid foundation, allowing us to execute this year and beyond.

Elhan Webb: Please turn to slide 4.

Let's now turn to the second quarter of 2022, which was marked by several meaningful achievements as outlined on slide six including continued healthy commercial performance and significant progress across our pipeline.

Richard Paulson: Thank you, Elhan, and good morning to everyone joining us on the call and webcast today.

First we grew total revenues to $39 7 million.

Richard Paulson: This morning, I'm excited to provide an update on our plan as we continue to execute on our growth strategy through our focus pipeline targeting life-threatening cancers.

As outlined in our press release. This morning, we introduced guidance for total revenues of $155 million to $165 million.

Richard Paulson: In Q2, we saw a significant increase in total revenues compared to Q2 of 21 of approximately $40 million, which includes the benefit of licensing and milestone revenue as we continue to receive new or expanded regulatory approvals globally.

Reflecting our growing global footprint and increased.

Visibility into license and other revenues, which is becoming an increasingly important financial driver for us.

Second exposure delivered strong year over year growth in the U S. During the second quarter, achieving $29 million in net product revenue.

Compared to $20 2 million in second quarter of 2021.

We achieved these results through continued increasing uptake in second through fourth line setting despite the ongoing impacts from the pandemic and intensified competition in late line settings.

However, driven by the challenges in the first half of the year, we are updating our <unk> net revenue guidance to $120 million to $130 million.

Presenting 27% year over year growth at the midpoint.

Next carrier farm and our European partner met Irene were recently granted full approval for <unk> in combination with Bortezomib and dexamethasone for the treatment of adults who have received one prior therapy.

This new approval dramatically expands <unk> potential use in Europe .

Richard Paulson: With growing patient access for Selenexor across the world, we expect revenues in ex-U.S. territories to have an increasing contribution to total Selenexor revenues in the future.

Selinexor is now approved in 39 countries, including the recent launches in mainland, China, Australia, and South Korea through our partner <unk> and in Canada through our partner for Us.

Finally, we continue to advance our clinical pipeline in core indications in the second quarter.

For the treatment of myelofibrosis, the FDA granted orphan drug designation for Selinexor in May.

In addition, we presented encouraging initial data observed in our phase one two frontline study of Selinexor in combination with <unk> at <unk> 22, and expect to provide further myelofibrosis data in the second half of this year.

And for Mds Alpha next door was recently granted fast track designation by the FDA as a monotherapy to treat patients with relapsed or refractory intermediate high or very high risk Mds.

In addition, the European Commission granted orphan medicinal product designation to <unk> to treat patients with Mds in the EU.

Finally, we completed enrollment for the interim analysis of our relapsed refractory phase II study in Mds with the data expected to be shared in the second half of this year.

As shown on slide seven as the global leader in the inhibition of nuclear export.

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.

Multiple myeloma endometrial cancer.

Myelofibrosis and Myelodysplastic syndromes.

In addition to all of these being areas of high unmet need for patients.

Each has a significant addressable market.

As we turn now to slide eight I would like to turn the call over to Sonya for her review of the commercial performance for the quarter John you. Thank.

Thank you Richard and good morning, everyone. Since our launch we continue to focus on expanding the potential of <unk> and its benefit to patients in earlier lines.

Richard Paulson: In addition, we are pleased to have delivered 44% net product revenue growth year over year, despite an increasingly competitive multiple myeloma market and some continuation of COVID-19-related challenges.

Turning now to slide nine on our commercial highlights for the second quarter of 2022.

We grew net product revenue by 44% versus the same period last year and continued to make progress across key indicators since our second line plus launch at the beginning of 2021.

This growth was achieved despite two key challenges, namely the COVID-19 impact on new starts in January and February of 2022, which resulted in a decline on refills in the second quarter and an intensifying competitive landscape in the later lines.

Our team executed with strength to access and educate our physician community improving in person engagements with health care providers from 60% last quarter to 75% in the second quarter, resulting in a recovery of new patient starts.

We continue to make progress with our primary growth driver and what we believe is most important to patients which is the continued shift of <unk> into earlier lines and the community setting.

With over half of our patients in the second to fourth line.

As we track duration of therapy, which takes time to mature we expect to see the benefit of this early aligns shift and continued education to improve tolerability, resulting in more patients staying on therapy longer as we approach the end of the year.

Although we have seen increasing competition in the late line setting at academic centers with new approvals in ongoing trials. Our focus remains on expanding the use of exposure in the community setting where a majority of earlier line patients are treated.

Richard Paulson: I am pleased with our team's ongoing commitment to successfully execute against key priorities.

We drove growth in the community setting and increased our penetration from 64% to 67% versus the prior quarter in the top 20% of myeloma accounts, which represents about 80% of myeloma patient volume in the U S.

Richard Paulson: As a global leader in the inhibition of nuclear export, everything we do is driven by our mission to positively impact patient lives and defeat cancer.

Richard Paulson: On slide 5, 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.

Richard Paulson: First, we continue to successfully build upon our existing multiple myeloma franchise.

Richard Paulson: Second, we continue to advance our focused clinical pipeline comprised of mid- and late-stage clinical development programs that has been purposely 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 where we believe we will have the highest probability of success. To that end, based on compelling data signals, we are pursuing opportunities in endometrial cancer, myelofibrosis, and myelodysplastic syndromes.

We continue to see a positive shift in perception of exposed in the second to fourth line per the intend to prescribe data due to the growing confidence among our positions in using the lower dose.

Once weekly <unk> based triplet regimens with over 90% of patients now starting on a 100 milligrams weekly dose or less.

The evolution from higher to lower dose and from late two earlier line use is one that we have seen with many myeloma therapies over several years since the original launch as an exposure continues to make steady progress along this same journey.

As we look to the future potential of exposure within a rapidly evolving multiple myeloma landscape. It is clear there continues to be a high unmet need both in the near and long term.

Over the next several years, while new therapies may emerge in the fifth line plus setting and while the anti CD 38 class ship to the frontline there remains a white space in that middle section of the treatment journey, where no standard of care is established.

Setting up patients for success in that Middle section of the treatment plan may allow them to access subsequent therapies. In later lines as we see improved patient outcomes with multiple classes and lines of therapy over an ever increasing number of years.

As a new class of therapy <unk> is a convenient oral regimen that is manageable and easily combinable for a second to fourth line patients.

In the long term as the treatment paradigm evolves, we continue to build a body of evidence to further demonstrate the value of Expo <unk> and further entrench our positioning in the second to fourth line and <unk> will discuss this in further detail.

For the second half of this year my team and I remain laser focused on continuing to drive the shift into earlier lines and expanding our growth in the community with an unwavering passion to improve the lives of these patients.

With that please advance to slide 10, and I'll turn the call over to <unk> to review, our clinical pipeline progress.

Thank you <unk>, we have strategically partnered follow next door in key ex U S territories and as we look to the future on slide 11, one of our top priorities is to expand our footprint in multiple myeloma across the globe.

I've touched on by Richard carry a farm and our partners <unk> just recently obtained approval in Europe for <unk> in combination with Bortezomib and dexamethasone in patients with multiple myeloma following at least one prior therapy.

Approval follows a positive opinion granted in May 2022 by the CH M. P. Based upon results from the Phase III Boston study. In addition follow next four with recently launched in mainland China, Hong Kong and in Canada through our strategic partners.

Richard Paulson: Collectively, we believe we have the potential to achieve multiple product approvals over the next two to four years.

Richard Paulson: Our third pillar is our people.

Turning now to slide 12, I will be reviewing our focused and developmental pipeline, which has the potential to deliver a consistent and steady stream of new approvals over the next two to four years.

Richard Paulson: We strengthened the leadership team during the second quarter, including the appointment of Dr. Rayshmer Wangwala as the company's chief medical officer and the recent promotion of Stuart Poulton to executive vice president and chief development officer. Stuart has more than 25 years of experience in the global biotech and pharmaceutical space, including both clinical operations and portfolio leadership roles at AbbVie, Amgen, and Eli Lilly. With Stuart's promotion, we consolidated the leadership structure of our R&D organization, driving increased accountability and focus.

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.

And please turn to slide 13, the unmet need remains strong for new modalities like following up for to treat multiple myeloma, because physicians ability to class switch with multiple combination has driven significantly better patient outcome. The.

Richard Paulson: Fourth and finally, we believe we are well-funded into early 2024, and Mike will highlight our reduced expense guidance as we initiated cost reduction initiatives in line with the evolution of our focus pipeline.

Richard Paulson: With these pillars in place, we believe we have a solid foundation allowing us to execute this year and beyond.

Richard Paulson: Let's now turn to the second quarter of 2022, which was marked by several meaningful achievements. As outlined on slide 6, including continued healthy commercial performance and significant progress across our pipeline. First, we grew total revenues to $39.7 million.

Richard Paulson: As outlined in our press release this morning, we introduced guidance for total revenues of $155 to $165 million, reflecting our growing global footprint and increased visibility into license and other revenues, which is becoming an increasingly important financial driver for us.

The majority of patients treated in the first or second line are given an anti CD 38 based treatment regimen. Unfortunately, multiple myeloma is still considered an incurable disease due to inevitable relapse and acquired drug resistance and therefore, many of these patients disease will become refractory to or relapsed.

From an anti CD 38, pie and image treatment.

Our clinical data support the use of Selinexor in the post anti CD 38, setting. We believe this is the setting in which <unk> has the strongest spec follow NEC <unk> has an increasingly understood and manageable safety profile and while we only promote FDA approved regimen physicians have the option to.

Combined with several different backbones for the NCC guidelines.

Additionally, with the emergence of new multiple myeloma treatment, including T cell engaging therapies.

New therapies and cellular therapies, we are actively investigating the role of <unk> inhibition plays in preserving and maintaining T cell fitness, which is needed for optimal stem cell collection for patients considering cellular therapies and a robust immune environment.

We believe these data will underscore the role of <unk> inhibition in this evolving landscape and further anchor selinexor as in earlier line treatment.

You would now turn to slide 14, I would like to highlight our rapidly advancing myelofibrosis program and the current treatment landscape.

<unk> is the current standard of care for newly diagnosed myelofibrosis with only approximately 40% of patients achieving spleen volume reduction of 35% as a frontline treatment no other drug classes other than JAK inhibitors have been approved in the last 10 years.

Our first line Myelofibrosis study outlined on this slide the phase one two study evaluating the combination of <unk> and Russell at Nib in patients with treatment naive myelofibrosis.

Our goal for this study are to evaluate the efficacy and safety of <unk>. In this first line myelofibrosis patient population building on the single agent activity of both compounds.

Given the potential synergism between these two drugs, we believe that the combination of Selinexor plus rug bullet nib has the potential to improve upon multiple efficacy parameters, including maintaining or improving symptom burden.

Turning to slide 15, this study which began in mid 2021 has shown encouraging results. Thus far with preliminary phase one data recently presented at ESMO 2022, and the European Hematology Association 2020 to Congress.

These results included favorable tolerable tolerability with no dose limiting toxicities and 75% of <unk>.

<unk> patients, demonstrating a greater or equal to 35% spleen volume reduction at week 12.

50% are transfusion independent patients who had at least eight weeks of treatment maintained stable hemoglobin or improved hemoglobin levels at last follow up. In addition, all of the Evaluable <unk> patients who had been on treatment for at least 12 weeks and had complete data experienced rapid.

Reductions in their symptom scores with three of seven patients, having greater or equal to 50% reduction at week 12.

Turning to slide 16, you can see that the combination of Selinexor and <unk> was generally well tolerated and manageable in the phase one portion of the study no dose limiting toxicities were reported at either dose level of <unk> with the most common reported grade three or four adverse events.

Thrombocytopenia anemia and neutropenia.

The hematologic adverse events were reversible with dose interruptions and reductions that occurred with both <unk> and <unk> on slide 17, you can see detailed SBR 35, and TSS 50 scores of all Evaluable patients in this study.

Currently patients are being enrolled in the phase <unk> portion of the study with the last patient expected to be dosed. This month.

We expect to present updated clinical data from this study in the second half of 2022. Additionally, we continue to enroll in our previously treated myelofibrosis 035 study and we look forward to report our top line results in the second half of 2023, as we deliver a robust <unk>.

<unk> program in myelofibrosis with its novel mechanism of action.

Now as we turn to slide 18, I would like to discuss the unmet need in 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 with approximately 50% of tumors classified as P 53 wild type.

Next the current treatment landscape for advanced or recurrent endometrial cancer consists of first line chemotherapy.

Upon completion of chemotherapy, the NCC and guidelines recommend a watch and wait approach until disease progression.

This approach clearly needs improvement given that the five year survival rate in this patient population is only 17%.

Selinexor is administered orally and maintenance therapy is well established with the physicians that treat multiple types of solid tumors, including breast and ovarian cancer. We believe <unk> has the potential to offer a maintenance option that could sustain the response from chemotherapy and improve the overall clinical.

Benefit for these patients.

Presented at Astro 2022 for the subgroup analyses for molecular classification data from the <unk> study evaluating selinexor in endometrial cancer.

Preliminary analysis of exploratory subgroups of the <unk> study assessed four distinct molecular subtypes in endometrial cancer using the cancer genome Atlas one of the accepted gynecologic oncology algorithm that is used to calculate prognostic risk scores.

As previously disclosed this analysis indicated that patients whose tumors were P 53, wild type mice treated with Selinexor demonstrated a median progression free survival 13, seven months compared to $3 seven months for patients treated with placebo.

In contrast patients whose tumors were either P 53, mutant or aberrant and treated with <unk> demonstrated a median progression free survival of three seven months compared to five six months for patients treated with placebo.

These data suggest that P 53, wild type has the potential to be a robust biomarker and selinexor may provide meaningful benefit to patients with P 53, wild type endometrial cancer phase.

Based upon productive dialogue, we have had with the FDA. We have selected companion diagnostic partner and are in the process of finalizing an agreement with them. We are excited with the ongoing close collaboration with both <unk> and <unk> got and remain on track to initiate this phase III registration.

Enabling trial in the fourth quarter of this year with that I will now advance to slide 19, and turn the call over to Mike to review the second quarter financial highlights Mike. Thank you raised money since we issued a press release earlier today with the full financial results I will just focus on the highlights which begin on slide 20.

Total revenue for the second quarter of 2022.

<unk> $39 7 million compared to $22 6 million for the second quarter of 2021.

With increasing approvals and commercial launches for Selinexor globally, we expect milestone and royalty payments by our partners to deliver a larger contribution to our total revenues in the future.

Richard Paulson: Second, Expovio delivered strong year-over-year growth in the U.S. during the second quarter, achieving $29 million in net product revenue compared to $20.2 million in second quarter of 2021. We achieved these results through continued increasing uptake in second-through-fourth-line setting, despite the ongoing impacts from the pandemic and intensified competition in late-line settings.

Net product revenue from U S commercial sales <unk> for.

For the second quarter of 2022 was $29 million.

Richard Paulson: However, driven by these challenges in the first half of the year, we are updating our Expovio net revenue guidance to $120 million to $130 million, representing 27 percent year-over-year growth at the midpoint.

Richard Paulson: Next, Cariopharm and our European partner, Manarini, were recently granted full approval for Nexpovio, in combination with bortezomib and dexamethasone, for the treatment of adults who have received one prior therapy. This new approval dramatically expands Nexpovio's potential use in Europe.

Richard Paulson: Selenexor is now approved in 39 countries, including the recent launches in mainland China, Australia, and South Korea through our partner, Antigene, and in Canada through our partner, Forests.

Paired to $20 2 million for the second quarter of 2021, representing a 44% increase year over year.

Richard Paulson: Finally, we continue to advance our clinical pipeline in core indications in the second quarter.

Richard Paulson: For the treatment of myofibrosis, the FDA granted orphan drug designation for Selenexor in May. In addition, we presented encouraging initial data observed in our Phase I-II front-line study of Selenexor, in combination with ruxolitinib, at ASCO 22, and expect to provide further myofibrosis data in the second half of this year.

Richard Paulson: And for MDS, Eltenexor was recently granted Fast-Track designation by the FDA, as a monotherapy to treat patients with relapsed or refractory intermediate high- or very high-risk MDS. In addition, the European Commission granted orphan medicinal product designation to Eltenexor to treat patients with MDS in the EU.

Richard Paulson: Finally, we completed enrollment for the interim analysis of our relapsed refractory Phase II study in MDS, with the data expected to be shared in the second half of this year.

Richard Paulson: In addition to all of these being areas of high unmet need for patients, each has a significant addressable market.

Gross to net discount for <unk> in the second quarter was 17%, we expect growth to that discount to be in the 15% to 20% range for the full year 2022.

Richard Paulson: As shown on slide 7, as the global leader in the innovation of nuclear export, 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.

Richard Paulson: Multiple Myeloma, Endometrial Cancer, Myelofibrosis, and Myelodysplastic Syndrome.

We recognized $10 7 million of license and milestone revenue in the second quarter of 2022, which.

Which includes $6 5 million earned in reimbursement of development expenses from the mentoring any group and $1 5 million related to milestone earned from our partner Force Therapeutics.

R&D expenses for the second quarter of 2022 were $44 3 million compared to $34 million for the second quarter of 2021.

Our results. This quarter included a one time $3 8 million severance related stock compensation charge.

We 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 second quarter of 2022, or 37 3 million compared to $36 5 million for the second quarter of 2021.

The increase in SG&A expenses was due to a one time $3 5 million severance related stock compensation charge in the second quarter.

Cash cash equivalents restricted cash and investments as of June 30 of 2022 totaled $172 6 million compared to $235 6 million as of December 31, 2021.

Based on our current operating plan.

<unk> guidance for full year 2022.

It is as follows.

Total revenue in the range of $155 million to $165 million.

<unk> net product revenue of $120 million to $130 million.

Reflecting a decrease of approximately $15 million versus our prior guidance.

non-GAAP, R&D and SG&A expenses, which excludes stock based compensation expense.

To be in the range of $250 million to 265.

Including approximately $5 million of severance related expenses.

Reflecting a decrease of approximately $15 million versus our prior guidance.

We initiated cost reduction initiatives in the second quarter that will accelerate in the second half of 2022.

Including stopping certain signal seeking programs, such as our lung and colorectal cancer studies.

In addition, we are optimizing our R&D and G&A infrastructure by eliminating roles as we continue to align the organization with our prioritized programs.

These efforts will reduce overall compensation costs.

<unk>, 10% in the second half of 2022 compared to the first half of the year.

Through these enhanced efforts, we expect these savings will build through 2023 sustaining our cash runway.

We project that our existing cash cash equivalents and investments as well as the revenue we expect to generate from <unk> product sales and license revenues, including a $20 million cash payment from antigen that we expect to receive near the end of the year related to a milestone that we previously recognized will be sufficient.

To fund our planned operations into early 2024.

Richard Paulson: 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.

Let's move to slide 21, and turn the call back to Richard for some final thoughts.

Thanks, Mike and as you've heard from the team we continue to maintain momentum with a number of key near term catalysts and corporate milestones for us to deliver on as outlined on slide 22, as we continue to strive each day for patients with high unmet needs.

In closing I would like to thank all of our teams that carryover arm and our investigators as we work everyday to positively impact the lives of patients with cancer.

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

Thank you.

We will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad.

If you are using a speakerphone please pick up your handset before pressing the keys.

Your question is from Scott.

Please press Star then two at this time, we will pause momentarily.

<unk>.

First question is from the line of.

Great.

With Jefferies. Please go ahead.

Hi, This is Kevin <unk> on for Maury, Thanks for taking my questions.

First question for myeloma.

Myeloma can you say what percentage of second quarter, New patient starts were earlier line and then should we think of this number of shifting higher from the roughly 50% split with increased academic competition. Thanks.

Sohanya Cheng: Sohanya?

Yeah. Thanks, Kevin for the question I'll turn to us for that so on yes, yes, hi, there Kevin Thanks for the question. So yes, we have seen.

Sohanya Cheng: Thank you, Richard, and good morning, everyone.

Sohanya Cheng: Since our launch, we continue to focus on expanding the potential of Explovio and its benefit to patients in earlier lines.

Improvement in that shift into earlier lines.

We're now well over 50% of our patients are now in the second to fourth line.

As for the community as we know a majority of these patients are treated.

Earlier line patients are treated in the community and we see that over 65% of our business comes from the community and we continue to increase our breadth and depth in the community.

Great. Thank you and then just one im sorry.

Go ahead Kevin.

Just one on myelofibrosis. So could you just talk more about what we can expect from the totality of data and.

In the second half of next year in terms of.

The number of patients or follow up for both mono.

Monotherapy and combo therapy, and then how are you thinking about how that's going to inform your path forward in myelofibrosis.

Now I'll turn to our ratio when you talk to that Kevin.

Thanks, Ron.

Hi, Kevin Thanks for the question. So we're very excited to present, some updated myelofibrosis data in the second half of 2022, we're going to be focused on focusing on the zero three for studying the 034 study is in the treatment naive population in which we are evaluating the efficacy and safety.

Selinexor in combination with Jakafi or <unk>.

As you likely know this study is a phase one followed by a randomized phase two and we anticipate that we will be providing updated efficacy and safety from the phase one portion of the trial. So this will include patients that were enrolled as part of the dose escalation as well as pay.

<unk> that were enrolled as part of the expansion phase.

In total we are anticipating approximately 21 patients to be included in this cohort and this is going to be additional follow up as compared to what we presented at <unk> as well as at <unk> 2022.

By and large the data sets that we are going to be providing are going to be similar to <unk> 2022 with focus on SVR TSS 15 anemia data and also updated safety and Tolerability data as well.

Great. Thank you.

Thanks, Kevin.

Thank you.

Next question comes from the line of Peter Lawson with Barclays. Please go ahead.

Great. Thanks, Thanks for the update with changing guidance just wonder if you could walk through the any changes in how you're thinking about particular growth drivers for <unk>.

For this year and next year Richard.

Yeah sure sure Peter maybe I'll just kick it off and then I'll turn it to so heartening because I think as John had mentioned, we did face some headwinds in Q2.

Sohanya Cheng: Turning now to slide 9, on our commercial highlights for the second quarter of 2022, we grew net product revenue by 44% versus the same period last year, and continued to make progress across key indicators since our second line plus launch at the beginning of 2021. This growth was achieved despite two key challenges, namely the COVID impact on new starts in January and February of 2022, which resulted in a decline on refills in the second quarter, and an intensifying competitive landscape in the later lines.

We're confident in our revised guidance moving forward as we do believe there is very strong opportunity for growth, especially in that second to fourth line in the community setting. So I guess, Tom I'll turn it to you to talk to some of the growth drivers you see moving forward.

Peter and the first half of the year, we recognize that we face headwinds driven by.

Two things one was the refills were down in the second quarter due to the Covid impact on reducing new patient starts in January and February and secondly, the intensified competition in the academic centers in the later lines due to a new approvals as well as clinical trials ramping up post COVID-19 and our revised guidance.

<unk> reflects these headwinds.

As we think about looking ahead, the midpoint of the updated guidance range is $125 million, which represents 27% growth year over year for 2022, and we believe there continues to be significant opportunity for long term growth as we think about the second half.

Of this year and beyond our team is laser focused in two areas number one accelerating growth in the second to fourth line to offset erosion in late lines from late line competition, and secondly to expand further into the community where a majority of the earlier.

<unk> patients are treated and we've community physicians prefer a convenient oral regimen, that's manageable easily combinable postpone anti CD 38, as we think about growth drivers for.

So the second half of the year. There are several we see continued positive momentum in these areas number one new patients start the recovery in the second quarter of the year as oncology patient visits are normalizing post COVID-19.

Sohanya Cheng: Our team executed with strength to access and educate our physician community, improving in-person engagements with healthcare providers from 60% last quarter to 75% in the second quarter, resulting in a recovery of new patient starts.

Sohanya Cheng: We continue to make progress with our primary growth driver and what we believe is most important to patients, which is the continued shift of Explovio into earlier lines and the community setting, with over half of our patients in the second to fourth line.

Secondly, as I mentioned, we are seeing this continued positive shift in use of exposure in the second to fourth line over half of our patients are in this setting we're seeing higher growth in the community. This is a key area of focus for us increased penetration in the top 20% of the myeloma accounts.

The majority of which are community accounts.

Seeing the continued improvement in the perception and building our confidence in the community and most importantly, as we think about tailwind for the second half of this year with Colby access restrictions coming down.

Sohanya Cheng: As we track duration of therapy, which takes time to mature, we expect to see the benefit of this earlier line shift and continued education to improve tolerability, resulting in more patients staying on therapy longer as we approach the end of the year.

The engagements of our field based representatives with healthcare providers is increasing significantly so we've moved to over 75% of interactions being live and this is critical for us in a competitive space to drive education at this early stage of the launch.

And for these reasons, we feel confident about our growth trajectory for the second half of this year and beyond.

Thank you and then what percentage of revenues is coming from the academic settings.

Sohanya Cheng: Although we have seen increasing competition in the late line setting at academic centers with new approvals and ongoing trials, our focus remains on expanding the use of Explovio in the community setting, where a majority of earlier line patients are treated. We drove growth in the community setting and increased our penetration from 64% to 67% versus the prior quarter in the top 20% of myeloma accounts, which represents about 80% of myeloma patient volume in the U.S.

Yes, so about 65% of our business is coming from the community and the remainder is coming from the academic setting and our focus remains on expanding further into the community.

Okay. Thank you and then.

I guess the question just for Mike just thinking about costs for the second half, we said 10% reduction.

<unk> costs in the second half how does that.

Change as we think about 'twenty three as well.

Yes, so thanks Peter.

We do expect our cost reduction initiatives that were introduced in the second quarter to accelerate in the second half of 'twenty two.

Cost savings from certain signal seeking program such a study.

Studies in lung and colorectal cancer that we terminated in addition to personnel related reduction to optimizing our R&D and G&A infrastructure.

Eliminating certain roles, we look to align the organization with our core programs. So this overall will reduce compensation costs.

By approximately 10% in the second half of 'twenty two.

Not necessarily providing guidance for next year, but our cost reduction initiatives that are focused pipeline. We do expect our cost savings will increase not only in the second half of the year, but we'll build into 2023 sustaining our cash runway into early 2024.

Okay. Thanks rich.

Thanks Peter.

Thank you.

Next question comes from the line of Mike <unk>.

With Morgan Stanley . Please go ahead.

Hey, guys. Thanks for taking the question.

Sohanya Cheng: We continue to see a positive shift in perception of Explovio in the second to fourth line per the intent to prescribe data due to the growing confidence among our physicians in using the lower dose once weekly Explovio-based triplet regimen, with over 90% of patients now starting on 100 milligrams weekly dose or less.

For <unk> in terms of physician perception can you maybe talk about how that's evolved over the past year or two.

Just curious trying to get a sense of the progress you've made there so far and then looking forward.

What's the opportunity to continue to.

Improve that thanks.

Yeah, Thanks, Mike I will turn to us to talk to that thanks, Mike.

Sohanya Cheng: The evolution from higher to lower dose and from late to earlier line use is one that we have seen with many myeloma therapies over several years since their original launches, and Explovio continues to make steady progress along this same journey.

Perception evolves with a product evolution and our product has been through an incredible evolution in the past 18 months from late lines to earlier like high dose to almost half the dose plus with the right supportive care and so we've seen perception shift in a positive direction.

Sohanya Cheng: As we look to the future potential of exfovio within a rapidly evolving multiple myeloma landscape, it is clear there continues to be a high unmet need, both in the near and long term. Over the next several years, while new therapies may emerge in the fifth line plus setting, and while the anti-CD38 class shifts to the front line, there remains a white space in that middle section of the treatment journey where no standard of care is established.

Sohanya Cheng: Setting up patients for success in that middle section of the treatment plan may allow them to access subsequent therapies in later lines, as we see improved patient outcomes with multiple classes and lines of therapy over an ever increasing number of years.

And over time, and they intend to prescribe data as well as anecdotal feedback that we get from physicians on a daily basis, particularly in the community setting we're seeing an increase in their likelihood to prescribe in the second to fourth line as well as a positive perception of the product both in <unk>.

Sohanya Cheng: As a new class of therapy, exfovio is a convenient oral regimen that is manageable and easily combinable for second to fourth line patients.

Sohanya Cheng: In the long term, as the treatment paradigm evolves, we continue to build a body of evidence to further demonstrate the value of exfovio and further entrench our positioning in the second to fourth line, and Reshma will discuss this in further detail.

Sohanya Cheng: For the second half of this year, my team and I remain laser focused on continuing to drive the shift into earlier lines and expanding our growth in the community with an unwavering passion to improve the lives of these patients.

Efficacy and safety, what our data is also showing that more than 90%.

Patients are being started on 100 milligrams or less so this is great progress as we've seen the evolution of our dosing as we think about moving forward and improving our perception.

The key is to continue to educate our physicians or nurses or support staff on the importance of the right dose dose reductions and supportive care and live engagements are critical both between the field representative and the health care provider as well as physician to physician.

Year to peer education, so as I mentioned earlier as Covid restrictions are coming down and our live engagements are increasing this education will be key to continuing to drive an improvement in our perception moving forward.

Got it thank you.

Sohanya Cheng: With that, please advance to slide 10, and I'll turn the call over to Reshma to review our clinical pipeline progress.

Thanks, Mike.

Okay.

Reshma Rangwala: Thank you, Sohanya.

Thank you.

Next question comes from the line of clean Queasy.

Please go ahead.

Thanks, Good morning, and thanks for taking my questions.

Should we be thinking about that the COVID-19 impact from <unk> has now fully cycled through or should we be expecting some pressure on the second half of this year and in Europe can you.

Just talk about how soon you think that could be a meaningful contributor to your top line and remind us what your economics are there. Please.

Reshma Rangwala: We have strategically partnered Selenexor in key ex-U.S. territories, and as we look to the future on slide 11, one of our top priorities is to expand our footprint in multiple myeloma across the globe.

Yeah sure. Thanks for the question is maybe for the first part.

Reshma Rangwala: As touched on by Richard, Cariopharm and our partners, Menorini, just recently obtained approval in Europe for nexpovio in combination with bortezomib and dexamethasone in patients with multiple myeloma following at least one prior therapy. The approval follows a positive opinion granted in May 2022 by the CHMP based upon results from the Phase III Boston study.

I will turn to <unk> to talk about the COVID-19 impact from from Q1, and how that evolves because it does evolve.

Over time, it becomes reduced as we move forward.

And then for the second part I will turn to Mike to talk kind of about the economics.

Reshma Rangwala: In addition, Selenexor was recently launched in mainline China, Hong Kong, and in Canada through our strategic partners.

In Europe, so saw any maybe kick off the first part yes. So the COVID-19 impact we breakdown into two fronts. One is oncology patient visits and that impact that that has on our new patient starts and refills.

Reshma Rangwala: Turning now to slide 12, I will be reviewing our focused developmental pipeline, which has the potential to deliver a consistent and steady stream of new approvals over the next two to four years.

Reshma Rangwala: As you turn to slide 13, the unmet need remains strong for new modalities like Selenexor to treat multiple myeloma because physicians' ability to class switch with multiple combinations has driven significantly better patient outcomes.

Reshma Rangwala: The majority of patients treated in the first to second line are given an anti-CD38 based treatment regimen.

Reshma Rangwala: Unfortunately, multiple myeloma is still considered an incurable disease due to inevitable relapse and acquired drug resistance, and therefore many of these patients' disease will become refractory to or relapse from an anti-CD38, PI, and IMID treatment.

Reshma Rangwala: Our clinical data support the use of Selenexor in the post-anti-CD38 setting. We believe this is the setting in which Selenexor has the strongest fit.

Reshma Rangwala: Selenexor has an increasingly understood and manageable safety profile, and while we only promote FDA-approved regimens, physicians have the option to combine with several different backbones per the MCCN guidelines.

Reshma Rangwala: Additionally, with the emergence of new multiple myeloma treatments, including T-cell engaging, therapies, immunotherapies, and cellular therapies, we are actively investigating the role XPO1 inhibition plays in preserving and maintaining T-cell fitness, which is needed for optimal stem cell collection for patients considering cellular therapies and a robust immune environment.

Reshma Rangwala: We believe these data will underscore the role of XPO1 inhibition in this evolving landscape, and further anchor Selenexor as an earlier line treatment.

Reshma Rangwala: If you would now turn to slide 14, I would like to highlight our rapidly advancing myelofibrosis, program and the current treatment landscape. Ruxolitinib is the current standard of care for newly diagnosed myelofibrosis, with only, approximately 40% of patients achieving a spleen volume reduction of 35% as a frontline treatment.

Reshma Rangwala: No other drug classes, other than JAK inhibitors, have been approved in the last 10 years.

And we felt that we went through the peak of it in January and February with Omicron, where we saw patient visits come down by up to 10%, which impacted on new starts and in turn our refills. So we feel that is reflected in our lowering of our guidance I think the second impact of Covid is access.

To physicians.

And what we're seeing is a trend to returning to normal.

Not at 100% of live access, but we're around 70, 75% or so.

And so as we think about moving forward.

Signs that we see are continually continued improving signs, we obviously don't have a crystal ball to predict.

Any changes in.

Colgate fluctuations over the course of the year, but the trends that we're seeing.

Bolt on oncology patient visit side as well as the access to physicians are both improving.

And Mike do you I'll take the second part we're talking about the European launches that kind of as they evolve over the next 12 months to 24 months sure yes. Thanks.

<unk>.

Thank you and just a refresher on our mentoring and deals that we announced back in December of 2021 and includes about $200 million in future milestone plus tiered double digit royalties on next on net sales.

<unk> expect first commercial launch in Germany in the second half of this year.

As Richard mentioned this launch will evolve over the next 12 months.

Pricing and reimbursement discussions interval with each country.

Great. Thank you and if I can ask.

In myelofibrosis.

We saw some encouraging early data I believe at 12 weeks at <unk>. The update in the second half will that include 24 week data and can you talk about how you expect that data mature from 12 to 24 weeks for both SBR 35 in TFS Betsy.

Yes, maybe I'll.

Duration me to talk about that and again as you remember kind of looking even from our earlier data on deepening over time I think is an important perspective to look at that ratio.

Absolutely Hi, Colleen and thanks for the question.

Yes.

We absolutely will provide 24 week data for the.

The dataset that we anticipate to provide in the second half of 2022 is going to include more patients. So more patients that were enrolled as part of the phase <unk>. In addition to the data already presented from the Phase Iia.

But also more mature data, we will see is that 12 week as well as 24 week in a subgroup of those patients and as Richard Richard just alluded, we keep going back to the essential data via central data as an investigator initiated trial that is evaluating.

Evaluating selinexor as a monotherapy or primarily in our relapsed or pre treated patient population and what we saw in those data were quite intriguing in that patients who stayed on therapy over time, we saw that their responses deepened over time. So we do anticipate a similar kind of.

And on as we evaluate selinexor in combination with <unk> now in our first line population specifically that theyre.

<unk>.

<unk> potentially could deepen over time, so yes, we're looking forward to presenting those data soon.

Great. Thanks for taking my questions.

Thanks Colin.

Yes.

Thank you.

Reshma Rangwala: Our frontline myelofibrosis study, outlined on this slide, is a Phase I-II study evaluating, the combination of Selenexor and Ruxolitinib in patients with treatment-naive myelofibrosis.

Next question comes from the line of Brian Abrahams.

RBC capital markets. Please go ahead.

Great. Thanks. This is Steve on for Brian . Thanks for taking our question could you share any thoughts on how increasing competition in myelofibrosis, including with <unk>. So this is a matter of fact.

Reshma Rangwala: Our goals for this study are to evaluate the efficacy and safety of Selenexor and Ruxolitinib, in this first-line myelofibrosis patient population, building on the single-agent activity of both compounds. Given the potential synergism between these two drugs, we believe that the combination, of Selenexor plus Ruxolitinib has the potential to improve upon multiple efficacy parameters, including maintaining or improving symptom burden.

While recruitment moving forward and any thinking on that might affect your timeline assumptions for the next day.

Yeah, Thanks, Steve I'll turn it duration for that but I think as we've been talking to you we reduced our overall recruitment moving forward well, but are you. If I may want to talk to that yes, absolutely and again. Thank you for the question.

Reshma Rangwala: Turning to slide 15, this study, which began in mid-2021, has shown encouraging results, thus far, with preliminary Phase I data recently presented at ASCO 2022 and the European Hematology, Association 2022 Congress. These results included favorable tolerability with no dose-limiting toxicities and 75% of, the evaluable patients demonstrating a greater or equal to 35% spleen volume reduction at, Week 12. Fifty percent of transfusion-independent patients who had at least eight weeks of treatment, maintained stable hemoglobin or improved hemoglobin levels at last follow-up.

There's a lot of interest coming out of <unk>, and especially <unk> with a 034 study that dataset with small as you know again, we will have an opportunity to present updated data in the second half of this year, but those initial data again were very encouraging given the fact that we saw some very robust responses in terms.

Reshma Rangwala: In addition, all of the evaluable seven patients who had been on treatment for at least 12, weeks and had complete data experienced rapid reductions in their symptom scores, with three of seven patients having greater or equal to 50% reduction at Week 12.

Reshma Rangwala: Turning to slide 16, you can see that the combination of Selenexor and Ruxolitinib was, generally well-tolerated and manageable.

Reshma Rangwala: On slide 17, you can see detailed SBR35 and TSS50 scores of all evaluable patients in, this study.

Reshma Rangwala: In the Phase Ia portion of the study, no dose-limiting toxicities were reported at either dose level, of Selenexor, with the most common reported Grade III to IV adverse events being thrombocytopenia, anemia, and neutropenia. The hematologic adverse events were reversible, with dose interruptions and reductions that, occurred with both ruxolitinib and selenoxor.

Reshma Rangwala: Currently, patients are being enrolled in the Phase 1b portion of the study, with the, last patient expected to be dosed this month.

Reshma Rangwala: We expect to present updated clinical data from this study in the second half of 2022.

Reshma Rangwala: Additionally, we continue to enroll in our previously treated myelofibrosis 035 study, and we look forward to report our top-line results in the second half of 2023, as we deliver a robust development program in myelofibrosis with this novel mechanism of action.

Reshma Rangwala: Now as we turn to slide 18, I would like to discuss the unmet need in endometrial cancer, and why we find our upcoming opportunity so exciting for patients.

Reshma Rangwala: First, endometrial cancer is the most common form of gynecologic cancer in the United States, with approximately 50 percent of tumors classified as P53 wild type.

Reshma Rangwala: Next, the current treatment landscape for advanced or recurrent endometrial cancer consists, of first-line chemotherapy.

Reshma Rangwala: Upon completion of chemotherapy, the NCCN guidelines recommend a watch-and-wait approach, until disease progression.

Reshma Rangwala: Based upon productive dialogue we have had with the FDA, we have selected a companion, diagnostic partner and are in the process of finalizing an agreement with them.

Reshma Rangwala: This approach clearly needs improvement, given that the five-year survival rate in this patient, population is only 17 percent.

Reshma Rangwala: We are excited with the ongoing close collaboration with both GOG and NGOT and remain on track, to initiate this Phase III registration-enabling trial in the fourth quarter of this year.

Reshma Rangwala: Acellin exul is administered orally, and maintenance therapy is well-established for the physicians, that treat multiple types of solid tumors, including breast and ovarian cancer. We believe acellin exul has the potential to offer a maintenance option that could sustain, the response from chemotherapy and improve the overall clinical benefit for these patients.

Reshma Rangwala: Presented at ASCO 2022 were the subgroup analyses and molecular classification data from the, CANDIS study evaluating acellin exul in endometrial cancer. A preliminary analysis of exploratory subgroups of the CANDIS study assessed four distinct, molecular subtypes in endometrial cancer using the Cancer Genome Atlas, one of the accepted gynecologic oncology algorithms that is used to calculate prognostic risk scores. As previously disclosed, this analysis indicated that patients whose tumors were P53 wild type, treated with acellin exul demonstrated a median progression-free survival of 13.7 months compared to 3.7 months for patients treated with placebo.

Reshma Rangwala: In contrast, patients whose tumors were either P53 mutant or aberrant and treated with acellin, exul demonstrated a median progression-free survival of 3.7 months compared to 5.6 months for patients treated with placebo.

Reshma Rangwala: These data suggest that P53 wild type has the potential to be a robust biomarker and, acellin exul may provide meaningful benefit to patients with P53 wild type endometrial cancer.

The SPR as well as intriguing data around TSS 50, as well as the anemia. So this this really as sort of has a halo effect I will say with the investigators to it is a competitive space, especially because that myelofibrosis patient population is is rare with that said I think there is a lot of interest.

In being able to participate in these clinical trials. So we do anticipate.

Enrollment to continue and we Havent changed we don't we don't anticipate any changes in our data available availability and in terms of Readouts.

Okay.

Great. Thanks for the color.

Reshma Rangwala: With that, I will now advance to slide 19 and turn the call over to Mike to review the

Thanks, Steve.

Thank you.

Next question comes from the line of Amit.

Joseph.

J P. Morgan. Please go ahead.

Michael Mason: second quarter financial highlights.

Hi, good morning, Thanks for taking the questions.

Michael Mason: Mike?

First one on Ghana.

Commercial.

Michael Mason: Thank you, Reshma.

I'm curious, whether you're seeing any tension with.

Michael Mason: Since we issued a press release earlier today with the full financial results, I will just, focus on the highlights which begin on slide 20.

Michael Mason: Total revenue for the second quarter of 2022 was $39.7 million compared to $22.6 million, for the second quarter of 2021.

Michael Mason: With increasing approvals and commercial launches for Selenex or globally, we expect milestone, and royalty payments by our partners to deliver a larger contribution to our total revenues in the future.

Michael Mason: Net product revenue from U.S. commercial sales of Expovio for the second quarter of 2022, was $29 million compared to $20.2 million for the second quarter of 2021, representing a 44% increase year over year.

<unk>.

The expansion of anti CD 38 years in earlier lines.

From the J&J results, we saw impressive growth of <unk> given the introduction of the sub Q formulation I'm, just wondering whether there youre kind of seeing a competitive dynamic.

Also whether you have a sense of.

<unk> uptake today in the.

Among patients who prior therapy with 90 638 to the extent that Doug.

Doug with expansion today, Mike.

Represent a windfall.

Subsequent years.

And then also just kind of drilling down a little bit further on the uptake that youre seeing today by line of therapy do you have a sense.

Could you just sort of weak.

Thanks, Bill good uptake within that.

Second to fourth line setting.

So that sort of weighted.

Core towards sport blend versus second one thanks.

Yes, Thanks, Eric maybe I'll break the question up.

A couple of parts the first part I'll turn to <unk> to talk about.

Michael Mason: The growth to net discount for Expovio in the second quarter was 17%. We expect growth to net discount to be in the 15 to 20% range for the full year of 2022.

Michael Mason: We recognize $10.7 million of license and milestone revenue in the second quarter of, 2022, which includes $6.5 million earned in reimbursement of development expenses from the Mentorini Group and $1.5 million related to milestones earned from our partner Forrest, Therapeutics.

Michael Mason: R&D expenses for the second quarter of 2022 were $44.3 million compared to $34 million, for the second quarter of 2021. Our results this quarter included a one-time $3.8 million severance related stock compensation, charge.

Michael Mason: We 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.

Michael Mason: Based on our current operating plans, Carrier Farms' guidance for full year 2022 is as follows. Total revenue in the range of $155 million to $165 million, Expovio net product revenue, of $120 million to $130 million, reflecting a decrease of approximately $15 million versus our prior guidance, and non-GAAP R&D and SG&A expenses, which excludes stock-based compensation , including approximately $5 million of severance related expenses, reflecting a decrease of, approximately $15 million versus our prior guidance.

As we're seeing increasing use of <unk> in earlier lines of <unk>, what that means for us.

Michael Mason: SG&A expenses for the second quarter of 2022 were $37.3 million compared to $36.5 million, for the second quarter of 2021. The increase in SG&A expenses was due to a one-time $3.5 million severance related stock, compensation charge in the second quarter.

Michael Mason: We initiated cost reduction initiatives in the second quarter that will accelerate in, the second half of 2022, including stopping certain signal-seeking programs such as our lung and colorectal cancer studies.

Michael Mason: Cash, cash equivalents, restricted cash, and investments as of June 30, 2022, totaled $172.6, million compared to $235.6 million as of December 31, 2021.

Michael Mason: In addition, we are optimizing our R&D and G&A infrastructure by eliminating roles as, we continue to align the organization with our prioritized programs. These efforts will reduce overall compensation costs by approximately 10 percent in the second, half of 2022 compared to the first half of the year. Through these enhanced efforts, we expect these savings will build through 2023, sustaining, our cash runway.

Michael Mason: We project that our existing cash, cash equivalents, and investments, as well as the revenue we, expect to generate from Expovio product sales and license revenues, including a $20 million cash payment from Antigen that we expect to receive near the end of the year related to a milestone that we previously recognized, will be sufficient to fund our planned operations into early 2024.

And also I think within that.

We talked to how we're seeing our evolution between that second to fourth line in terms of lines of therapy, where the greatest brokers.

And then also been turning to integration that I talked to some of our our data it really.

<unk> hundred 30, <unk> and how.

<unk> a novel New class.

Positive for patients both FTC 38, So let me take the first part and then over to rich great. Thanks, Eric. So yes, we're seeing a continued increase in the use of anti CD 38 in the front line, which in turn continues to leave that unmet need open in that middle section of the treatment journey beats.

Richard Paulson: Let's move to slide 21 and turn the call back to Richard for some final thoughts.

Richard Paulson: Thanks, Mike.

Richard Paulson: And as you've heard from the team, we continue to maintain momentum with a number of key, near-term catalysts and corporate milestones for us to deliver on, as outlined on slide, 22, as we continue to strive each day for patients with high unmet needs.

Richard Paulson: In closing, I would like to thank all of our teams at Kareo Farm and our investigators, as we work every day to positively impact the lives of patients with cancer.

Second to fourth line, where there is no clear standard of care.

And <unk> has proven data post anti CD 38.

We only promote to approved regimen, which is a combination with bortezomib, but the mtc on guidelines also has other triplet regimens of <unk> in combination with <unk> carfilzomib as well as Dara, Tim or Matt to answer your second question of what about prior therapies.

That don't include an anti CD 38 backbone will if it included a <unk>.

<unk> backbone there is optionality to combined with a different backbone and exposure to occur the mtc and guidelines and overall as we take a step back.

Richard Paulson: 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.

Unknown Executive: Operator?

The continued white space in the second to fourth line is critical for a couple of different reasons. There is no clear standard of care, but also it sets up patients for a potentially successful outcome and accessibility to potential late line therapy as they emerge.

Unknown Executive: Thank you.

And I just want I just want to piggyback on what is <unk> two I mean from the R&D perspective, there are growing data to suggest from a clinical perspective that treating patients post CD 38 increases their efficacy. So the sequent to really as an important phenomenon. We also have growing.

Preclinical data, but also suggest that treating patients post CBE 38, with Selinexor Mei Mei.

Improved efficacy as well so this again treating with <unk> post CD 38 really is very efficacious for these patients.

Great.

Thanks.

As a follow up here on the Opex guidance.

Okay.

Inclusive of both the lower spend for this year and as you look at 'twenty three.

Really just your runway guidance.

Early 2020 for I guess, how should we be thinking about.

Any impact to the pace of enrollment.

The randomized studies the phase III.

Either endometrial cancer or myeloma either.

Prioritization of enrollment that will need to take place there.

The runway guidance. Thanks.

Alright.

We obviously take assumptions in all our trials and what enrollment will be so you could see lumpiness in quarters for sure.

A higher than normal in quarter versus the next but.

What's in our forecast in our base plan is a prioritized program driving that.

Okay.

Thanks for taking the questions.

Thanks, Eric.

We're just coming out of kind of top of the hour.

Two more questions.

Thank you.

Next question comes from the line of Ed White.

Etsy Greenway.

Greenway. Please go ahead.

Unknown Executive: We will now begin the question-and-answer session.

Unknown Executive: To ask a question, you may press star, then one on your telephone keypad.

Good morning, Thanks for taking my questions.

I'm just wondering if you have any visibility into the mix of the current regiments being used.

In particular.

<unk> combo.

It's not approved because as the NCS.

CCM guidelines.

So I'm just wondering what.

What's the percentage of the oral oral regimen is right now and how important the.

The combination trial is to the company, if youre already penetrating that market.

The second question is just on Ela next door.

Can you give us an update there I know that.

These two studies ongoing you're expecting.

Data in the first half of 'twenty three.

You can tell us about enrollment or any other updates you can give us. Thank you.

Unknown Executive: If you are using a speakerphone, please pick up your handset before pressing the keys.

Unknown Executive: To withdraw your questions from the press, please press star, then two.

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

Thanks, Ed for the first part of that question alternatives. So on.

The second part we're going to talk duration, because we have moved up.

Yes. Thanks. Thanks for the question. So we from the data that we see and we don't have full visibility to into a 100% of our regimen data, but from the data we see overall triplet use trend is growing over time.

Half of that use it.

<unk> is <unk> half of our overall uses exposure based triplets now the triplets are broken down into a variety of regimens.

Which include primarily X V D. Our approved indication and then a couple of other indication a couple of other regimens as well the combination with <unk> as well as the combination with Kyprolis as you mentioned on the end CCN guidelines.

As I mentioned, it's about half of our UCITS triplets of which there is a split.

With a majority of those three regimens up there and the triplet.

And in terms of <unk> and we're currently evaluating <unk> in patients with Myelodysplastic syndrome. Mds syndrome, we have two cohorts one is a relapsed refractory patient population another as a first line in which we are combining <unk> with HMA inhibitors, which as you know our standard of care in this page.

<unk> population, we're very excited to be presenting data in the second half of 2022 from the relapsed refractory phase two patient population and this is from a preplanned interim analysis.

That is fully enrolled at this point.

Great. Thank you.

Okay.

Okay.

Let's take one more question operator, sorry at the top of the hour.

Thank you.

Next question is from the line of Jonathan Chang.

Unknown Executive: First question is from the line of Maury Raycroft with Jeffries.

FCB Securities. Please go ahead.

Unknown Attendee: Please go ahead.

Unknown Attendee: Hi.

Unknown Attendee: This is Kevin Strang on for Maury.

Hey, guys. Thanks for squeezing us in <unk> on for Jonathan just wanted to ask what could the Registrational strategy and in myelofibrosis look like and how are you thinking about pursuing the frontline breasted relapse opportunity like consistent either or could you pursue both.

Unknown Attendee: Thanks for taking my questions.

Unknown Attendee: First question for myeloma, can you say what percentage of second quarter new patient starts, were earlier line?

Yes, no. Thanks, Thanks for the question overall.

Unknown Attendee: And then, should we think of this number as shifting higher from the roughly 50% split, with increased academic competition?

I'll touch on our overall, but then we want to turn duration or talk to it overall approaching both Israeli important for us because there is opportunities to really build a nice franchise in.

The myelofibrosis area in terms of those relapsed patients or in combination in the frontline. So maybe you can talk and expand on that yes, absolutely I mean, we've got a robust clinical development program in myelofibrosis covering both the first line as well as the relapsed refractory patient population in the first line setting we are evaluating.

Unknown Attendee: Thanks.

Sohanya Cheng: Thanks, Kevin.

Sohanya Cheng: For the question, I'll turn to Suhanya for that.

Sohanya Cheng: Suhanya?

Sohanya Cheng: Yeah.

<unk> saw an export in combination with Jakafi and we anticipate that combination versus rux alone again in that first line patient population in the relapsed setting there really is no standard of care in that relapsed setting we are likely going to evaluate selinexor versus physicians choice.

Chemotherapy.

Both trials are currently enrolling.

And likely anticipate that the second the relapsed refractory patient population would read out with readout first but again both trials are on track.

Sohanya Cheng: Hi there, Kevin.

Sohanya Cheng: Thanks for the question.

Sohanya Cheng: Yes, we've seen an improvement in that shift into earlier lines.

Sohanya Cheng: And we're now well over 50% of our patients are now in the second to fourth line.

Sohanya Cheng: As for the community, as we know, a majority of these patients are treated, the earlier, line patients are treated in the community.

Thank you.

Sohanya Cheng: And we see that over 65% of our business comes from the community.

Thanks for the question.

Thank you.

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

Thank you operator, and thank you to everyone for joining us on the call today.

Sohanya Cheng: And we continue to increase our breadth and depth in the community.

Sohanya Cheng: Great, thank you.

Excited to continue moving forward and focusing on our key priorities and continuing to focus on delivering for patients over the rest of this year that concludes our call.

Unknown Attendee: And there's just one on, sorry.

Unknown Attendee: Go ahead, Kevin.

Unknown Attendee: Oh, just one on myelofibrosis.

Richard Paulson: Thank you, operator, and thank you to everyone for joining us on the call today.

Unknown Attendee: So could you just talk more about what we can expect from the totality of data in the, second half of next year in terms of number of patients or follow up for both monotherapy and combo therapy?

Richard Paulson: We're excited to continue moving forward and focusing on our key priorities and continuing, to focus on delivering for patients over the rest of this year.

Unknown Attendee: And then how are you thinking about how that's going to inform your path forward in myelofibrosis?

Unknown Attendee: Thanks.

Richard Paulson: Okay, I'll turn to Reshma to talk to that, Kevin.

Richard Paulson: That concludes our call.

Reshma Rangwala: Reshma?

Reshma Rangwala: Hi, Kevin.

Reshma Rangwala: Yeah, thanks for the question.

Reshma Rangwala: So we're very excited to present some updated, myelofibrosis data in the second half of 2022. We're going to be focusing on the 034 study. The 034 study is in the treatment-naive population in which we are evaluating the efficacy and, safety of Selenexor in combination with Jakafi or Ruxolitinib.

Reshma Rangwala: As you likely know, this study is a Phase I followed by a randomized Phase II, and we anticipate that we will be providing updated efficacy and safety from the Phase I portion of the trial. So this will include patients that were enrolled as part of the dose escalation as well as patients that were enrolled as part of the expansion phase.

Reshma Rangwala: In total, we are anticipating approximately 21 patients to be included in this cohort, and this is going to be additional follow-up, as compared to what we presented at EHA as well as at ASCO 2022.

Unknown Executive: Goodbye.

Reshma Rangwala: By and large, the datasets that we are going to be providing are going to be similar to ASCO 2022, with focus on, SVR, TSS50, anemia data, and also updated safety and tolerability data as well.

Goodbye. Thank you.

Unknown Executive: Thank you.

Unknown Attendee: Great.

Unknown Executive: The conference has now concluded.

Unknown Attendee: Thank you.

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

Unknown Executive: Thank you for attending today's presentation.

Unknown Attendee: Thanks, Kevin.

Unknown Executive: You may now disconnect.

Unknown Attendee: Thank you.

Unknown Executive: Next question comes from the line of Peter Lawson with Barclays.

Unknown Executive: Please go ahead.

Unknown Attendee: Great.

Unknown Attendee: Thanks.

Unknown Attendee: Thanks for the update.

Unknown Attendee: With changing guidance, I wonder if you could walk, through any changes in how you're thinking about particular growth drivers for this year and next year, Richard?

Richard Paulson: Yeah, sure, Peter.

Richard Paulson: I'll just kick it off, and then I'll turn it to Suhanya, because, I think, as Suhanya mentioned, you know, we did face some headwinds in Q2.

Richard Paulson: We are confident in our revised guidance moving forward.

Richard Paulson: You know, as we do believe, there's very strong opportunity for growth, especially in that second to fourth line in the community setting.

Richard Paulson: So maybe, Suhanya, I'll turn it to you to talk to some of the growth drivers you see, moving forward.

Sohanya Cheng: Yeah.

Sohanya Cheng: Thanks, Peter.

Sohanya Cheng: And, you know, the first half of the year, we recognized that we faced, headwinds driven by two things. One was the refills were down in the second quarter due to the COVID impact on reducing new patient starts in January and February.

Sohanya Cheng: And secondly, the intensified competition in the academic centers in the later lines due to new approvals, as well as clinical trials ramping up post-COVID.

Sohanya Cheng: And our revised guidance reflects these headwinds.

Sohanya Cheng: As we think about looking ahead, the midpoint of the updated guidance range is 125 million, which represents 27% growth year-over-year for 2022.

Sohanya Cheng: And we believe there continues to be significant opportunity for long-term growth.

Sohanya Cheng: As we think about the second half of this year and beyond, our team is laser-focused in two areas.

Sohanya Cheng: Number one, accelerating growth in the second to fourth line to offset erosion in late lines from late-line competition.

Sohanya Cheng: And secondly, to expand further into the community where a majority of the earlier-line patients are treated and these community physicians prefer a convenient oral regimen that's manageable, easily combinable post and anti-CD38.

Sohanya Cheng: As we think about growth drivers, For the second half of the year, there are several we see continued positive momentum, in these areas.

Sohanya Cheng: Number one, new patients start recovery in the second quarter of the year as oncology, patient visits are normalizing post-COVID.

Sohanya Cheng: Secondly, as I mentioned, we're seeing this continued positive shift in use of expovial, in the second to fourth line.

Sohanya Cheng: Over half of our patients are in this setting.

Sohanya Cheng: We're seeing higher growth in the community.

Sohanya Cheng: This is a key area of focus for us, increased penetration in the top 20% of the myeloma, accounts, a majority of which are community accounts.

Sohanya Cheng: We're seeing the continued improvement in the perception and building of confidence, in the community.

Sohanya Cheng: And most importantly, as we think about tailwind for the second half of this year, with COVID, access restrictions coming down, our live engagements of our field-based representatives with healthcare providers is increasing significantly. So we've moved to over 75% of our interactions being live.

Sohanya Cheng: And this is critical for us in a competitive space to drive education at this early stage, of the launch.

Sohanya Cheng: And for these reasons, we feel confident about our growth trajectory for the second half, of this year and beyond.

Sohanya Cheng: Thank you.

Unknown Attendee: And then what percentage of revenues is coming from the academic settings?

Sohanya Cheng: Yeah, so about 65% of our business is coming from the community and the remainder is coming, from the academic setting.

Sohanya Cheng: And our focus remains on expanding further into the community.

Sohanya Cheng: Thank you.

Unknown Attendee: And then I guess a question just for Mike, just thinking about costs for the second half, of what you said, a 10% reduction in costs in the second half.

Michael Mason: How does that change as we think about 23 as well?

Michael Mason: Yeah, so thanks, Peter.

Michael Mason: We do expect a cost reduction initiative that we introduced in the second quarter to accelerate, in the second half of 22.

Michael Mason: The cost savings from certain signal-seeking programs, such as studies in lung and colorectal, cancer that we terminated, in addition to personnel-related reductions to optimizing our R&D and G&A infrastructure by eliminating certain roles, we look to align the organization with our core program.

Michael Mason: So this overall will reduce compensation costs by approximately 10% in the second half of, 22. We're not necessarily providing guidance for next year, but our cost reduction initiatives, in our focus pipeline, we do expect our cost savings will increase, not only in the second half of the year, but will build into 2023, sustaining our cash run rate into early 2024.

Unknown Attendee: Okay.

Unknown Attendee: Thanks so much.

Unknown Attendee: Thanks, Peter.

Unknown Executive: Thank you.

Unknown Executive: Next question comes from the line of Mike Walsh with Morgan Stanley.

Unknown Attendee: Please go ahead.

Unknown Attendee: Hey, guys.

Unknown Attendee: Thanks for taking the question.

Unknown Attendee: For Expovio, in terms of physician perception, can you maybe talk about how that's evolved, over the past year or two?

Unknown Attendee: Just curious, trying to get a sense of the progress you've made there so far, and then looking forward, what's the opportunity to continue to improve that?

Unknown Attendee: Thanks.

Richard Paulson: Yeah, thanks, Mike.

Sohanya Cheng: I'll turn to Sohanya to talk to that.

Sohanya Cheng: Thanks, Mike.

Sohanya Cheng: Perception evolves with a product's evolution, and a product has been through an incredible evolution in the past 18 months, from late lines to early lines, high dose to almost half the dose, plus with the right supportive care. And so we've seen perception shift in a positive direction over time.

Sohanya Cheng: In the intent to prescribe data as well as anecdotal feedback that we get from physicians, on a daily basis, particularly in the community setting, we're seeing an increase in their likelihood to prescribe in the second to fourth line, as well as a positive perception of the product, both in efficacy and safety.

Sohanya Cheng: What our data is also showing, that more than 90% of our patients are being started on 100 milligrams or less.

Sohanya Cheng: So this is great progress as we've seen the evolution of our dosing.

Sohanya Cheng: As we think about moving forward and improving our perception, the key is to continue to educate our physicians, our nurses, our support staff on the importance of the right dose, dose reductions, and supportive care.

Sohanya Cheng: And live engagements are critical, both between the field representative and the healthcare provider, as well as physician-to-physician, peer-to-peer education.

Sohanya Cheng: So as I mentioned earlier, as COVID restrictions are coming down, and our live engagements are increasing, this education will be key to continuing to drive an improvement in our perception moving forward.

Unknown Attendee: Got it.

Unknown Attendee: Thank you.

Unknown Attendee: Thanks, Mike.

Unknown Attendee: Thank you.

Unknown Executive: Next question comes from the line of Colleen Cousy with Baird.

Unknown Executive: Please go, Baird.

Unknown Attendee: Thanks.

Unknown Attendee: Good morning, and thanks for taking our questions.

Unknown Attendee: So should we be thinking about that the COVID-19 impact from 1Q has now fully cycled through, or should we be expecting some pressure still in the second half of this year?

Unknown Attendee: And in Europe, can you just talk about how soon you think that could be a meaningful contributor to your top line, and remind us what your economics are there, please?

Richard Paulson: Yeah, sure, Colleen.

Unknown Attendee: Thanks for the question.

Richard Paulson: Colleen, thanks for the question.

Richard Paulson: Maybe for the first part, I'll turn to Sohani to talk about the COVID-19 impact from Q1, and how that evolved, because it does evolve over time and becomes reduced as we move forward.

Sohanya Cheng: And then for the second part, I will turn to Mike to talk kind of about the economics in Europe.

Michael Mason: So, Sohani, maybe kick off the first part.

Sohanya Cheng: Yeah, so the COVID impact, we break down into two fronts. One is oncology patient visits and the impact that that has on our new patient starts and refills. And we felt that we went through the peak of it in January and February with Omicron, where we saw patient visits come down by up to 10%, which impacted our new starts and, in turn, our refills.

Sohanya Cheng: So we feel that is reflected in our lowering of our guidance.

Sohanya Cheng: I think the second impact of COVID is access to physicians.

Sohanya Cheng: And what we're seeing is a trend to returning to normal. We are not at 100% of live access, but we are around 70%, 75% or so.

Sohanya Cheng: And so as we think about moving forward, the signs that we see are continued improving signs.

Sohanya Cheng: We obviously don't have a crystal ball to predict any changes in COVID fluctuations over the course of the year, but the trends that we're seeing both on the oncology patient visit site as well as the access to our physicians are both improving.

Sohanya Cheng: And Mike, do you want to take the second part, where you talk about the European launch as, it kind of, as they evolve over the next, you know, 12 to 24 months?

Michael Mason: Sure.

Michael Mason: Yeah.

Michael Mason: Thanks. And just, you know, just a refresher on our Menorini deal, so that we announced back in, December of 2021, it includes about $200 million in future milestone plus tiered double-digit royalties on next, on net sales.

Michael Mason: So Menorini expects first commercial launch in Germany in the second half of the, of this, year.

Michael Mason: And they'll, as Richard mentioned, this launch will evolve over the next 12 months as pricing, and reimbursement discussions, you know, evolve with each country.

Unknown Attendee: Great.

Unknown Attendee: Thank you.

Unknown Attendee: And if I can ask a follow-up on myelofibrosis, you know, we saw some encouraging early data, I believe at 12 weeks at ASCO.

Unknown Attendee: The update in the second half, will that include 24-week data, and can you talk about how you, expect that data mature from 12 to 24 weeks for both SBR35 and TSS50?

Richard Paulson: Yeah.

Reshma Rangwala: Maybe I'll turn to Reishma to talk about that.

Reshma Rangwala: And again, as you remember, kind of looking even from our earlier data on deepening over, time, I think is an important perspective to look at, Reishma.

Reshma Rangwala: Yeah, absolutely.

Reshma Rangwala: Hi, Colleen.

Reshma Rangwala: Thanks for the question.

Reshma Rangwala: So yes, we absolutely will provide 24-week data.

Reshma Rangwala: So the data set that we anticipate to provide in the second half of 2022 is going to include, more patients. So more patients that were enrolled as part of the Phase 1B, in addition to the data already, presented from the Phase 1A, but also more mature data.

Reshma Rangwala: So we'll see the 12-week as well as 24-week in a subgroup of those patients.

Reshma Rangwala: And as Richard just alluded, you know, we keep going back to the essential data. The essential data is an investigator-initiated trial that was evaluating Selenexor as a monotherapy, primarily in our relapsed or pretreated patient population.

Reshma Rangwala: And what we saw in those data were quite intriguing in that patients who stayed on therapy over, time, we saw that their responses deepened over time.

Reshma Rangwala: So we do anticipate a similar kind of phenomenon as we evaluate Selenexor in combination with, ruxolitinib now in a first-line population, specifically that their, you know, SVR potentially could deepen over time.

Reshma Rangwala: So yeah, we're looking forward to presenting those data soon.

Unknown Attendee: Great.

Unknown Attendee: Thanks for taking our questions.

Unknown Attendee: Thanks, Colleen.

Unknown Attendee: Thank you.

Unknown Executive: Our next question comes from the line of Brian Abrams with RBC Capital Market.

Unknown Executive: Please go ahead.

Unknown Attendee: Great.

Unknown Attendee: Thanks.

Unknown Attendee: This is Steve.

Unknown Attendee: I'm for Brian.

Unknown Attendee: Thanks for taking our question.

Unknown Attendee: Can you share any thoughts on how increasing competition in myelofibrosis, including with, combo rux studies, might affect trial recruitment moving forward, and any thinking on how that might affect your timeline assumptions for the next steps?

Unknown Attendee: Thanks.

Richard Paulson: Yeah, thanks, Steve.

Reshma Rangwala: I'll turn to Ray Schmidt for that, but as we've been talking to, we do see our overall, recruitment moving forward well, but Ray Schmidt may want to talk to that.

Reshma Rangwala: Yeah, absolutely.

Reshma Rangwala: And again, thank you for the question.

Reshma Rangwala: You know, there's a lot of interest coming out of ASCO and especially EHA with the 034, study.

Reshma Rangwala: That data set was small.

Reshma Rangwala: As you know, again, we will have an opportunity to present updated data in the second half, of this year, but those initial data, again, were very encouraging, given the fact that we saw some very robust responses in terms of the SBR, as well as intriguing data around, TSS50, as well as anemia.

Reshma Rangwala: So this really has, you know, sort of has a halo effect, I will say, with the investigators, too.

Reshma Rangwala: It is a competitive space, especially because that myelofibrosis patient population is rare. With that said, I think there is a lot of interest in being able to participate in these, clinical trials.

Reshma Rangwala: So we do anticipate enrollment to continue, and we haven't changed.

Reshma Rangwala: We don't anticipate any changes in our data availability in terms of readouts.

Unknown Attendee: Great.

Unknown Attendee: Thanks for the question.

Unknown Executive: Next question comes from the line of Eric Joseph, J.P. Morgan, please go ahead.

Unknown Attendee: Hi, good morning, thanks for taking the questions.

Unknown Attendee: First one on an expo commercial.

Unknown Attendee: I'm curious to know whether you're seeing any tension with the expansion of anti-CD38 use in earlier lines.

Unknown Attendee: From the J&J results, you know, we saw impressive growth of Darzalex given the introduction of the sub-Q formulation.

Unknown Attendee: I'm just wondering whether there you're kind of seeing a competitive dynamic.

Unknown Attendee: And also, whether you have a sense of expo view uptake today in the, among patients whose prior therapy was an anti-CD38, to the extent that Darzalex expansion today might, you know, represent a windfall in subsequent years.

Unknown Attendee: And then also just kind of drilling down a little bit further on the uptake that you're seeing today by line of therapy.

Unknown Attendee: Do you have a sense of, or could you sort of weight expo view uptake within that second to fourth line setting, so that it's sort of weighted more towards fourth line versus second line?

Unknown Attendee: Thanks.

Richard Paulson: Yeah, thanks, Eric.

Richard Paulson: Maybe I'll break the question up in a couple parts.

Sohanya Cheng: I think the first part I'll turn to Sohanya to talk about, you know, increasing use of anti-CD38s in the earlier line, Darzalex, what that means for us.

Sohanya Cheng: And also I think within that, you know, Sohanya can probably talk to how we're seeing our evolution between that second to fourth line in terms of lines of therapy, where the greatest growth is.

Reshma Rangwala: And then I'll also then turn to Indra Reshman to talk to some of our data, really, post-anti-CD38s and how, you know, having a novel new class is really positive for patients post-anti-CD38.

Richard Paulson: So, Sohanya, maybe take the first part and then over to Reshman.

Sohanya Cheng: Great.

Sohanya Cheng: Thanks, Eric.

Sohanya Cheng: So, yes, we're seeing a continued increase in the use of anti-CD38s in the front line, which in turn continues to leave that unmet need open in that middle section of the treatment journey between second to fourth line, where there is no clear standard of care.

Sohanya Cheng: And Expovio has proven data post-anti-CD38.

Sohanya Cheng: We only promote to approved regimen, which is a combination with bortezomib, but the NCCN guidelines also has other triplet regimens of Expovio in combination with pomalidomide, carfilzomib, as well as daratumumab to answer your second question of, what about prior therapies that don't include an anti-CD38 backbone?

Sohanya Cheng: Well, if it included a PI or an IMID backbone, there's optionality to combine with a different backbone in Expovio per the NCCN guidelines.

Sohanya Cheng: And overall, as we take a step back, the continued white space in that second to fourth line is critical for a couple of different reasons.

Sohanya Cheng: There is no clear standard of care, but also it sets up patients for potentially successful outcome and accessibility to potential late-line therapies as they emerge.

Reshma Rangwala: And I just want to piggyback on what Sohanya said too, I mean from the R&D perspective, there are growing data to suggest from a clinical perspective that treating patients post-CD38 increases their efficacy.

Reshma Rangwala: So the sequence really is an important phenomenon.

Reshma Rangwala: We also have growing preclinical data that also suggests that treating patients post-CD38, with Selenexor may improve efficacy as well.

Reshma Rangwala: So this, again, treating with Selenexor post-CD38 really is very efficacious for these patients.

Unknown Attendee: Great, and just as a follow-up here on the OPEX guidance, inclusive of both the lower, expense for this year, and as you look at 23, and really just your runway guidance into early 2024, I guess, how should we be thinking about any impact to the pace of enrollment of the randomized studies, the phase 3 in either endometrial cancer or myeloma, is there any prioritization of enrollment that will need to take place there in order to stay within the runway guidance?

Richard Paulson: Thanks.

Richard Paulson: No, we obviously take assumptions in all our trials of what enrollment will be.

Richard Paulson: So you could see lumpiness in quarters, for sure, if it has a higher enrollment in quarter, versus the next, but no, what's in our forecast and our base plan is our prioritized program driving that forward.

Unknown Attendee: Okay.

Unknown Attendee: Thanks for taking the questions.

Unknown Attendee: Thanks, Eric.

Unknown Executive: We're just coming up kind of top of the hour, I think one or two more questions.

Unknown Executive: Thank you.

Unknown Executive: The next question comes from the line of Ed White with HC Brainwright.

Unknown Executive: Please go ahead.

Unknown Attendee: Good morning.

Unknown Attendee: Thanks for taking my questions.

Unknown Attendee: I'm just wondering if you have any visibility into the mix of the current regiments being, used, in particular, the pomelos combo, you know, while it's not approved, it has the, NCCN guidelines.

Unknown Attendee: So I'm just wondering what, you know, what the percentage of the oral regimen is right, now and how important the combination trial is to the company if you're already penetrating that market.

Unknown Attendee: And then the second question is just on LNX, or can you give us an update there?

Unknown Attendee: I know the phase two study is ongoing.

Unknown Attendee: You're expecting data in the first half of 23, but if there's anything you can tell us, about enrollment or any other updates you can give us.

Unknown Attendee: Thank you.

Richard Paulson: Thanks, Ed.

Sohanya Cheng: For the first part of that question, I'll turn to Sohanya.

Reshma Rangwala: And for the second part, we're going to talk to Reshma because we have moved up that a, little bit.

Sohanya Cheng: Sohanya?

Sohanya Cheng: Yep.

Sohanya Cheng: Thanks, Ed, for the question.

Sohanya Cheng: So from the data that we see, and we don't have full visibility into 100% of our regimen, data, but from the data we see, overall triplet use trend is growing over time.

Sohanya Cheng: And about half of that use is expovio.

Sohanya Cheng: Half of our overall use is expovio-based triplets.

Sohanya Cheng: Now, the triplets are broken down into a variety of regimens, which include primarily XVD, our approved indication, and then a couple of other regimens as well, the combination with pomalidomide as well as the combination with Kyprolis, as you mentioned, on the NCCN guidelines.

Sohanya Cheng: So as I mentioned, it's about half of our use is triplets, of which there is a split, with a majority of those three regimens up there in the triplets.

Sohanya Cheng: And in terms of Eltenexor, we're currently evaluating Eltenexor in patients with myelodysplastic, syndrome, MDS syndrome.

Reshma Rangwala: We have two cohorts.

Reshma Rangwala: One is a relapsed refractory patient population, another is a first line in which we are combining, Eltenexor with HMA inhibitors, which as you know are standard of care in this patient population.

Reshma Rangwala: We're very excited to be presenting data in the second half of 2022 from the relapsed, refractory phase two patient population. And this is from a pre-planned interim analysis that is fully enrolled at this point.

Unknown Attendee: Great.

Unknown Attendee: Thank you.

Unknown Attendee: Thanks, Ed.

Unknown Executive: We'll just take one more question, operator, toward the top of the hour.

Unknown Executive: Thank you.

Unknown Executive: This question is from the line of Jonathan Cheng with SVB Securities.

Unknown Attendee: Please go ahead.

Unknown Attendee: Hey, guys.

Unknown Attendee: Thanks for squeezing us in.

Unknown Attendee: This is Faisal Khurshid on for Jonathan.

Unknown Attendee: I just wanted to ask, what could the registrational strategy in a myelofibrosis look like?

Richard Paulson: And how are you thinking about pursuing the front line versus the relapsed opportunity, like a distant either or, or could you pursue both?

Unknown Attendee: Yeah, no, thanks for the question.

Richard Paulson: I mean, overall, I think, and I'll touch on it overall, but then we want to turn to, Raishman to talk to it.

Richard Paulson: And overall, approaching both is really important for us.

Richard Paulson: I think there's opportunities to really build a nice franchise in the myelofibrosis area, in terms of those relapsed patients or, you know, in combination up in the front line.

Reshma Rangwala: Raishman, maybe you can talk and expand on that.

Reshma Rangwala: Yeah, absolutely.

Reshma Rangwala: I mean, we've got a robust clinical development program in myelofibrosis covering both the, first line as well as the relapsed refractory patient population.

Reshma Rangwala: In the first line setting, we are evaluating Selenexor in combination with Jakafi, and, we anticipate that combination versus Ruxolone, again, in that first line patient population.

Reshma Rangwala: In the relapsed setting, there really is no standard of care. In that relapsed setting, we are likely going to evaluate Selenexor versus Physician's Choice, Chemotherapy. Both trials are currently enrolling and likely anticipate that the second, the relapsed refractory, patient population would read out first.

Reshma Rangwala: But again, both trials are on track.

Unknown Attendee: Thank you.

Unknown Attendee: Thanks for the question.

Unknown Executive: Thank you.

Unknown Executive: This concludes our question and answer session.

Richard Paulson: I would like to turn the conference back over to Mr. Richard Paulsen for any closing comments.