Q4 2022 Karyopharm Therapeutics Inc Earnings Call
Good day.
Andrea and I will be your conference operator today.
At this time I would like to welcome everyone to the carry of farm therapeutics fourth quarter and full year two cell phone 22 financial results conference call.
There will be a question and answer session to follow.
Please be advised that this call is being recorded at the company's request.
I would now like to turn the call over to Al for Lamb Senior Vice President of Investor Relations.
Please go ahead.
Thank you Andrea and thank you all for joining us on today's conference call to discuss the carrier farms fourth quarter and full year 2022 financial results and recent company for all that.
We issued a press release this morning detailing our financial results for the fourth courtyard full year 2022.
This release, along with a slide presentation that we will reference during our call today are available on our website.
For today's call as seen on slide two I'm joined by Richard So Honea read my mind.
Richard will start the call with some opening remarks, so honea will provide a commercial update and rational will provide an update on our clinical development program.
Mike will then present, an overview of financial highlights from the quarter and full year 2022 and provide guidance for 2023.
George will end with some closing remarks before we open up the call 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.
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 10-Q, four which is on file with ACC and in other filings that we may make with the FCC in the future.
Any forward looking statements represent our views as of today only while we may elect to update them at some point in the future. We specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward looking statements as representing our views as of any later date. In addition.
We will also be providing on this call then I'll look for our non-GAAP R&D and SG&A expenses for 2023.
We are not providing recall affiliations off these forward looking non-GAAP measures because projections all stock compensation expense, which is required for such recall affiliation are not available without unreasonable effort.
I will now turn the call over to Richard Please turn to slide four.
Good morning, Thank you I'll hand, and thank you everyone for joining us today for carrier farms Q4, and full year 2022 earnings call.
My name is Richard Paulson, President and Chief Executive Officer of carryover.
As you can see on slide five.
Carrier farm was founded in 2008.
As an innovation and patient focused company developing first in class oral selective inhibitors of nuclear export, which target <unk> to improve patient outcomes in cancer.
Fast forwarding to carry a farm today, where we are successfully leveraging this fundamental mechanism of action to build upon our existing multi myeloma franchise anchored around our commercial drug exposure.
Which is now approved in 40 countries and continues to move into earlier lines of therapy in multiple myeloma.
With our U S exposure revenue milestone and royalty payments from our ex U S partners. We have generated 157 million total revenues in 2022 meeting our guidance range for the year.
For 2023, we are well positioned for our next phase of growth.
Where we expect to further grow our total revenue and U S exposure sales, which so Hong you and Mike will go into more detail later on.
We have a focused pipeline comprised of mid and late stage clinical development programs.
That can help patients who suffer from cancers with high unmet need.
Demonstrate efficacy at lower doses with improved Tolerability and where we believe we will have the highest probability of success.
We are conducting pivotal phase III studies in both multiple myeloma and endometrial cancer with a third pivotal phase III study in myelofibrosis.
We expect to start in the first half of 2023 pending regulatory feedback.
Through continuing a disciplined and focused approach and advancing our pipeline and a strengthened balance sheet from our recent financing which included participation by both existing stockholders and new investors, we have extended our cash runway through late 2025.
Collectively we believe we have the potential to achieve multiple product approvals over the next two to four years as we deliver our next phase of growth leveraging our proven and established commercialization and mid to late stage development capabilities as we work to generate value for patients.
And shareholders.
Yeah.
Turning now to slide six let's review some key accomplishments from our four core programs in 2022.
As we have made considerable progress across all programs.
In multiple myeloma. Despite increased competition, we grew Expo <unk> U S. Net sales by 22% in 'twenty two compared to 21.
So Hong you will go into more details on our U S sales performance in multiple myeloma in a moment.
In endometrial cancer, we are excited moving forward with a novel biomarker driven phase III study by leveraging the potential substantial benefit of Selinexor that we've observed in patients that are <unk> 53, wild type <unk>.
Our partnership with Foundation Medicine will enable us to develop a companion diagnostic.
In myelofibrosis, we are very encouraged by the preliminary results observed from our phase one study.
Crossed three relevant domains, including SVR at 35, TSS 50, and hemoglobin stabilization.
Finally in high risk relapsed refractory Mds population with a very high unmet need we completed recruitment for the interim analysis and are looking forward to seeing the overall survival data mature in our phase II study.
As we turn now to slide seven I would like to turn the call over to <unk> for her review of the commercial performance for the quarter and full year 2022, So on you.
Thank you Richard and good morning, everyone on slide eight I'm pleased to talk about the role of <unk> within an evolving multiple myeloma landscape it.
It is clear that continues to be an unmet need despite the advancement in treatment options the disease remains incurable.
If we look at the first and second lines of therapy, we typically see utilization of three major classes with increasing proportion of patients being treated with an anti CD 38 antibody.
Following that there is a need for a class, which through a novel mechanism of action.
In the second to fourth line setting there is no clear standard of care.
If we now move forward to the late line setting we see rapid advancements with the emergence of T cell redirecting therapies.
However, these medicines can be complex in terms of patient management and infrastructure needed for administration, and therefore typically localized to the academic setting.
That's the patience and the second to fourth line setting who are largely treated by community prescribers exposure continues to have a strong value proposition as an effective manageable easily combinable convenient oral therapy.
In addition, we have data to strongly support the rationale enough because you have exposure you'll use following an anti CD 38 regimen.
Furthermore, with the emergence of T cell mediated therapy.
Concept of T cell fitness is becoming increasingly critical for physicians, particularly in the academic setting.
Terry a farm is playing a leading role in exploring this topic and building a body of evidence around the effectiveness of Expo B L pre and post the T cell redirecting therapies, and we expect to see more data generated in this area through the course of the year to further bolster our positioning in multiple myeloma.
Not treatment landscape.
Turning now to slide nine and I'll commercial highlights for the fourth quarter and full year 2022.
In 2022 week real exposure net revenues by 22% versus 2021 meeting our guidance. This was primarily driven by demand growth, which included a year over year increase in both new starts and Greenfields as we continue to treat more patients with <unk>.
Oh and extend their time on therapy.
Our team executed with strength delivering 28% sales growth in the community in 'twenty two versus prior year.
Community setting remains a primary area, okay contributing to about 70% of sales in Q4.
In the academic setting, which was impacted by new competitive entrants, including one novel class of therapy, becoming commercially available in December expansion of car T site and ongoing clinical trials, we grew 7% in sales in 2022 versus 2021.
In addition, we continue to make progress across our growth drivers, including shifting into earlier lines and increasing our duration of therapy. We are.
Also continues to improve the perception of the product with clear support and advocacy for Expo deal at the podium of Kols seen at medical Congresses.
As we turn to slide 10, let's walk through the details of the progress we have made across our key growth drivers.
We have grown the proportion of patients in earlier lines with now roughly 55% of exposure of your patients in the second to fourth line driven by rapid growth in the third line.
This shift into earlier lines, we continue to see an increase in duration year over year.
Finally, we continue to expand our breadth of use as we increase the number of prescribing accounts across the U S.
With roughly 70% of accounts being in the community.
On slide 11, as we look to 'twenty to 'twenty three we remain focused on further expanding these growth drivers.
We're guiding to a U S net product revenue range of 125 to 140 million, which at the midpoint represents 10% year over year growth.
We believe this guidance range reflects solid growth in a competitive landscape that is expected to further intensify in 'twenty to 'twenty three with four potential new competitor approvals.
We anticipate Q1 sales in line with the prior quarter given ongoing pressure from increased adoption of tech badly in the academic setting and a higher G T and driven by the Medicare Donut hole reset and I are a rebate.
We will continue to execute with a well established and entrenched field team.
Bridging our broad base of prescribers in the community.
Building upon their positive experiences and further expanding their use.
We also plan to continue messaging and positioning Expo B O in the second to fourth line post anti CD 38.
In 2022 we saw the most rapid growth in the third line our focus remains on continuing to accelerate our growth in this line of therapy.
In addition in 2023, we plan to engage with key academic institutions to generate data pre and post a T cell mediated therapies.
Or are there potentially strengthening our position in the second to fourth line.
Finally, as we look to the mid and long term, we expect that the all oral phase three study of Selinexor in combination with <unk> and dexamethasone with a focus on targeting the community setting will be a key driver of future growth if approved.
We look forward to continuing to grow exposed and build out with myeloma franchise benefiting more patients in this challenging and in terrible disease.
Now I would like to turn the call over to Rachel to give an update on our clinical pipeline progress.
Thank you so Honeywell as you can see the overview of our clinical pipeline on slide 13, we have two differentiated complementary novel sine compound Selinexor and ultra next door, which are being evaluated across multiple cancers of high unmet need including myelofibrosis.
This myelodysplastic neoplasms, endometrial cancer and multiple myeloma.
Selinexor brand name exposure is our first novel X P O one inhibitor and the F. D. A approved in multiple myeloma and diffuse large b cell lymphoma. It is currently being investigated in both solid tumors and hematologic malignancies.
Okay next door is our second X P O one inhibitor and is currently being investigated in relapsed refractory Mds.
Paired to selinexor or lower blood brain barrier penetration is observed with alto next door in.
In addition, it's I see 50, a measure of potency is lower than Selinexor, which enables more continuous dosing in fact in select animal models evaluating M. D S.
<unk> X P. O. One inhibition has been shown to lead to enhanced anti tumor activity.
Turning now to slide 14, we are working to optimize the dose of selinexor across our clinical programs.
Since expose your first approval in 2019, we have utilized real world experience, coupled with observations from our own clinical trials demonstrate that lower doses of selinexor can optimize the patient benefit by improving its tolerability, which ultimately allow patients to stay on therapy longer.
And therefore improve their overall benefit.
As a result, all of our ongoing clinical trials incorporate selinexor doses X 40, or 60 milligrams once weekly, which is a quarter to less than half of the original approved doses of 80 milligrams twice weekly.
Let's now turn our attention to endometrial cancer.
On slide 16, I would like to discuss the unmet need in endometrial cancer and why we find this opportunity so exciting for women.
First endometrial cancer is the most common form of gynecologic cancer in the United States with approximately 50% of advanced or recurrent tumors classified as T. P 53 wild type.
Second the current treatment landscape for advanced or recurrent endometrial cancer consists of first line chemotherapy.
Upon completion of chemotherapy the N C C N 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%.
And Selinexor is administered orally and maintenance therapy is well established in other cancer types. We believe selinexor has the potential to offer a maintenance option in T. P 53, wild type patients and improve the overall clinical benefit for these patients.
But ask a 2022 we presented the subgroup analyses in molecular classification data from the <unk> study evaluating selinexor in endometrial cancer as a maintenance therapy.
A previously disclosed a subgroup analysis showed that patients, whose tumors where T. P 53, wild type and treated with Selinexor demonstrated a median progression free survival of 13.7 months.
<unk> to 3.7 months for patients treated with placebo.
On slide 17 are the updated P. S. Astral results in this P 53, wild type subgroup from a data cut as of November 2022.
This update now shows that the median PFS for Selinexor has increased to 28 months.
To 5.2 months for placebo with no observed change and the safety profile.
This improvement in the progression free survival highlight the potential benefit that can be achieved with selinexor in patients who are whose tumors are P. 53 wild type supports the evaluation of sine compounds in this molecular subtype and underscores the rationale for evaluating selinexor as a maintenance.
Therapy in P 53, wild type endometrial cancer in our ongoing pivotal E. C. O four two study as seen on slide 18.
This study will utilize foundation medicine's tissue based next generation sequencing test to identify patients whose tumors are P 53 wild type.
A total of 220 patients will be randomized in a one to one manner to receive either once weekly selinexor at a dose of 60 milligrams or placebo.
The study's primary endpoint is progression free survival with a key secondary endpoint of overall survival.
The study is a collaboration between Kerry and Barb and got the European network for Gynecological Oncological trial groups N G O G. The gynecology oncology group.
Topline results are expected in the second half of 'twenty 'twenty, four and could represent a paradigm shift for women with T. P 53, wild type endometrial cancer.
Let's now take a closer look at myelofibrosis.
As you can see on slide 20, there is a high unmet need for new therapies and novel mechanisms of action given that the ethical and see what the current standard of care Jakafi is limited to patients with JAK naive myelofibrosis.
<unk> 45 per cent of patients achieving SVR 35, or T. S. S 50 at week 24.
Overall survival is limited.
Key patient populations do not benefit.
The rates are substantially lower for male patients as well as patients who start on Russell, It's 15 milligrams twice a day.
The S. T. R 30 fives for both of these key patient populations is only approximately 25%.
These are both critically important given that the males comprise approximately half of myelofibrosis patients and real world evidence data suggests that the majority of patients are treated with the crux of Loopnet at 15 milligrams twice, a day or less and about a third of patients are treated with five milligrams two.
Ice today.
Selinexor has the potential to enhance multiple factors important to all patients.
<unk> decreasing screen size, improving patients' symptoms.
<unk> should have hemoglobin levels, increasing overall survival disease modification all in the context of a manageable safety profile.
As seen on slide 21 targeting X P. O one can potentially be very effective as it didn't hibbitts multiple pathways downstream for Jack including 8-K T stop.
Stack and arc this may lead to potent monotherapy activity as well as the potential synergism in combination with JAK inhibitors and other targets.
Turning now to slide 22, you can see the design of our frontline Myelofibrosis study a phase one study evaluating the combination of Selinexor in rux I'll, let Ned in patients with treatment naive myelofibrosis.
In this study we completed enrollment of the phase one portion and dosed 24 patients.
Our objective for this study are to explore the combination of Selinexor in Rockville at Nib building on the single agent activity of both compounds.
Turning to slide 23, we recently shared updated results at Ash 2022.
Based on our October data cut 92% of Evaluable patients achieved a 35% or greater spleen volume reduction at week 24 in.
In addition, 67% of Evaluable patients, which included those patients who completed their symptom evaluation forms achieved a 50% or greater reduction of their total symptom score at week 24.
And finally, 57% of transfusion independent patients who had at least eight weeks of treatment maintained.
Stable hemoglobin or improved their hemoglobin levels after last follow up.
The combination of Selinexor in boxes, and it was generally well tolerated and had a manageable safety profile with the most common reported grade three or four treatment emergent adverse events being anemia and thrombocytopenia.
The grade three four anemia rates observed with the combination of about 38% less than the 45% observed with rux.
Alone.
We plan to present updated results from this study in the first half of 2023, including a T. S. That's 50 analysis that will incorporate symptom scores collected from patients medical charts.
This will enable a robust assessment of the symptom improvement observed with the combination of Selinexor in Rockville at Nab from the majority of patients enrolled in this phase one study.
As you can see on slide 24, 92% of Evaluable patients at week, 24 achieved an SCR, a 35% or greater than 100% of evaluable patients achieved any degree of spleen volume reduction.
The data on slide Slide 25, our new subgroup analysis from the phase one portion of the old three four study.
Specifically, we identified seven patients is Russell at Nib was reduced to five milligram do decide opinion is a cycle, one or two and who remained on this dose for the duration of their treatment.
We are interested in this subgroup given that quote long term maintenance at five milligrams twice daily has not shown responses and quote us.
Noted in the Russell at Nib prescribing information.
Despite this reduction to sub therapeutic doses of rux Alit nib.
All patients dosed with Selinexor in combination with rux for Lytton, an experienced reductions in their spleen and improvements in their symptoms with all five patients who were assessed at week 24 experienced a greater or equal to 35% reduction in spleen volume.
These data suggest that selinexor may potentially have monotherapy activity in treatment naive patients and underscores the potential of X P. O. One it's a fundamental mechanism in myelofibrosis, there could be leveraged both as monotherapy and in combination.
Turning to slide 26 based on the observations from the old three fourth study coupled with the need to develop effective therapies and the broadest population of JAK naive myelofibrosis.
We're optimizing our development plans to maximize the benefit observed in this population we anticipate having defined this plan at the first half of 2023.
Now turning to old Kinect four and M D.
As you can see on slide 28, approximately 15000 people in the United States are expected to have been diagnosed with intermediate to higher risk Mds in 2022.
HMA is of the current standard of care for newly diagnosed higher risk Mds patients.
Prognosis and HMA refractory disease is poor with the median overall survival of 46 months and there are currently no approved therapies for HMA refractory Mds.
On Slide 29, you can see the design of our phase two study of Ultra next door and relapsed refractory high risk Mds in this phase one portion of the study single agent <unk> four demonstrated promising activity among patients with HMA refractory M. D S. Specifically.
Specifically, a median overall survival of approximately 10 months was observed.
We have completed enrollment of a planned interim analysis in our phase two study and expect to report efficacy and safety results in the first half of 2023 with that I will now hand, it over to Mike.
I hope everyone is having a lovely morning, and thank you raised about turning to our financials. Since we issued a press release earlier today with the full financial results I will just focus on the highlights which begin on slide 31 total revenue for the fourth quarter of 2022 was $33 6 million compared to 120.
$6 3 million for the fourth quarter of 2021.
In line with our guidance for the year total revenue for the full year of 2022 was $157 1 million compared to $209 8 million for the full year of 2021.
As a reminder, in the fourth quarter of 2021, we recognized $96 5 million of license and other revenue, including the upfront payment of 75 million from battery.
Net product revenue from U S commercial sales of <unk> for the fourth quarter of 2022 was $31 1 million compared to $29 8 million for the fourth quarter of 2021.
Net product revenue from U S commercial sales of exposure for the full year 2022 was $120 4 million meeting our guidance for the year compared to $98 4 million for the full year 2021, representing a 22% increase year over year the.
The gross to net discount for <unk> in the fourth quarter of 2022 was 21% and for the full year of 2022 was 19%.
We expect the gross to net discount to be in the 20% to 25% range for the full year 2023.
R&D expenses for the fourth quarter of 2022 were $30 9 million compared to 44 million for the fourth quarter of 2021.
$148 7 million for the full year 2022, compared to $160 8 million for the full year 2021. The decrease in R&D expenses was primarily attributable to decreased clinical trial and related costs due to the prioritization of our core programs in our clinical pipeline during 2022.
In 2023, as we continue to make progress with our clinical pipeline, we expect R&D expense to remain relatively consistent including the costs from three pivotal clinical studies two of which are ongoing and one additional plan to initiate in the first half of 2023.
The increased costs from advancing these pivotal programs will be mostly offset by the cost saving measures. We initiated in 2022, which included in overall head count reduction and continued focus on our prioritized pipeline.
SG&A expenses for the fourth quarter of 2022 were $34 6 million consistent with the fourth quarter of 2021.
SG&A expenses for the full year 2020 to $445 4 million compared to $143 8 million for the full year 2021.
In 2023, we expect our SG&A expenses to increase to slightly increase in line with increased inflation and cost of it.
On a non-GAAP basis, which excludes stock based compensation, our total R&D and SG&A expenses in 2022 or $259 million in line with our guidance for the year.
Cash cash equivalents restricted cash and investments as of December 31, 2022 totaled $279 7 million. Following successful completion of $165 million private placement in December compared to $235 6 million as of December 31, 2021.
As a reminder, we expect to receive $22 million in cash payments for managing this quarter related to previously earned and recognized milestones.
Based on our current operating plans we are expecting.
Total revenue of $160 million to $175 million for 2023, consisting of U S exposure your on net product revenue and license royalty and milestone revenue expected to be earned from our partners primarily met or any entity we.
We expect U S exposure net product revenue of 100, and twenty-five John or $40 million.
non-GAAP, R&D and SG&A expenses, which excludes stock based compensation expense to be in the range of $260 million to $280 million for the full year of 2023.
And finally that our existing cash cash equivalents and investments as well as the revenue we expect to generate from <unk> product sales and other license revenues will be sufficient to fund our planned operations into late 2025.
I'll now flip to slide 32, and turn the call over to Richard for some final thoughts Richard.
Thank you Mike.
We are focused on maintaining momentum as we deliver on our next phase of growth with a number of key near term catalysts and corporate milestones as you see on slide 33.
Our people continue to strive each day for patients with high unmet needs as we work to generate value for patients and shareholders.
Thank you again for joining us today, and I would now like to ask the operator to open the call up to the question and answer portion of today's call.
Operator.
We will now begin the question and answer session.
To ask a question you May press Star then one on your telephone keypad.
If you are using a speakerphone please pick up your handset before pressing the keys.
To withdraw your question. Please press Star then two.
At this time, we will pause momentarily to assemble the roster.
Okay.
And our first question will come from Peter Lawson of Barclays. Please go ahead.
Great. Thanks, so much thanks for taking my questions just on I guess.
Attention data readout of the phase two.
N D S.
Data for Alto next so that it looks like it's now first half as well.
Once you kind of.
Where should we expect to see the data and how much do we expect to see.
Yeah, Thanks, Peter I'll turn to a duration maybe talk to that.
Yeah. Thank you. Thank you Peter Great question. So you know the timing of the M. D. S and her interim analysis is very much dependent upon the overall survival data.
Data and I say that partly because very high unmet need patient population and it's very hard to treat relapsed refractory patient population. We know from the published literature that overall survival for these patients is less than a year at only four to six months, so being able to identify a re.
Robust overall survival signal allows us to identify the best path forward. So you know at this point.
So following the OS data it looks like it is going to occur in the first half this year, but again hard to project you know as we continue following these patients survival.
We'll be opportunistic in terms of how we present those data whether it's out of medical Congress or through some kind of a company for them but.
You know the way I look at it this is only a good thing for our patients.
Thank you and then just as we think about Selinexor use.
With B C M, a therapies or head of B C may surface, just kind of walk through kind of the potential impact or benefit you had from gsk's blend, but being withdrawn and then if you're seeing sort of makes it would be a news ahead of so.
They used to be CMA therapies.
Yeah, Peter maybe I'll turn to so on you touched on the first part of that and then I'll I'll aberrational kind of close it was an interesting data.
T cell fitness Sarnia.
Great. Thanks, Thanks, Peter for the question. So let me let me talk about the blend Rep question first blend Rep was used primarily in late line patients.
And as you know with exposure we are focused in that second to fourth line setting.
Secondly, GSK continued their compassionate use programs so that current patients on.
Glenn Beck could continue on having said that now we're starting to see pockets of opportunity around the country, where some of the blended up opportunities in the late line academic setting are starting to materialize with new starts on exposure.
Switching gears to kind of overall competitive landscape in the T cell mediated therapies in the B C class and the role of Expo B O. So taking a step back and when you look at this class.
The primarily all the entrance in the class have been coming into the late line setting in the academic center. When you look at our performance in 2022, we agree with over 20% year over year for the full year, but in the academic setting despite increased competition.
With obesity, UBC and me as well as the car T. We grew 7% year over year. This is an important space because exposed youll continues to have a strong value proposition in the academic space, we already see physicians using it in certain.
Accounts, primarily as a runway leading up to a T cell therapy and secondarily. We also see some explosive you'll use post T cell therapy in the academic setting.
Now as we generate more T cell fitness data they should further strengthen our positioning in the academic setting.
My final point is that as we know these complex therapies can be very difficult for certain types of patients to access for example, the elderly patients and rural patients.
Which constitute a majority of multiple myeloma patients so that will be our target population for us in the academic setting.
Now as we continue to generate more data on this T cell fitness story I'd love to call on <unk> to elaborate on some of the exciting work that we've got planned ahead for this year.
Yeah. Thank you so hernia so.
We are looking at the T cell fitness story, largely because physicians are very interested in the T cell fitness story is they really want to know what agents that they can prescribe to their patients.
Going to negatively impact their ability to get some kind of immunotherapy later in line, including car T is this.
This is very important for them because they know from experience that a certain class of drugs, including the alkylating agents like fight toxin and mouth land kill dividing cells, including T cells, which ultimately caused damage to negatively impact our patients apheresis collection.
You know given the minimal slots given that you know getting a slot for these patients on car T.
It's so difficult again, they want to have confidence that if they can prescribe selinexor to their patients. It is not going to again negatively impacted their ability to get one of those therapy is what we are doing is looking across multiple different datasets, including preclinical data leveraging our own translational data as well as looking at real.
World evidence to really assess whether selinexor can maintain that immune environment and therefore maximize the benefit that they can achieve with one of those newer immunotherapies.
Great. Thank you just finally, Mike sort of anything you can say around the 2023 revenue growth is that so in terms of volume and pricing would be great. Thank you.
And maybe I'll turn to someone you on that Sonya.
Okay. Thanks for the question. So so different components kind of going into the guidance first of all we feel confident in delivering within our guidance range as we look at the different levers going into the guidance, it's really a balance between demand growth from expansion in the <unk>.
Unity and shift into earlier lines, and that's balanced with increased pressure in the academic settings from new competition coming in 2023.
A few viewpoint from the tail winds just increased use in the academic side.
The community setting we grew 28% year over year of last year. This continues to remain our primary area of focus I think the interesting thing as we mature with this drug is we have now built a very strong base of prescribers and we will continue to drive down there we also.
We continue to shift into earlier lines. So these factors will help to drive demand here.
The only thing I would add to that Peter is we did guide.
Gross to net will be higher in 2023 versus 2022. So we expect the range to be somewhere in the 20% to 25% were in 2022 were around 19.
Thanks, so much.
Thanks Peter.
The next question comes from Maury Raycroft of Jefferies. Please go ahead.
Hi, good morning, and congrats on the progress and thanks for taking my questions I was going to ask about multiple myeloma with some of the data that youre seeing in the third line setting I guess are you breaking out that percentage from the 55% total and can you talk about what exactly the treatment paradigm is that youre seeing prior to third.
And I guess, how well defined is that frontline and second line treatment in the paradigm.
Yeah, Thanks, Martin I'll get Tony to talk to that Sonya.
Yeah. Thanks, Mark for the question. So our most rapid area of growth within the second to fourth line bucket is in the third line that is a large contributing factor to that nice upward trend that we're seeing in the second to fourth line and as you know, we now see a 55% of our patients.
In that bucket little hard given that the data that we see to break down exact numbers by line of therapy, but we know that third line is a contributing factor in in 2023 our focus will remain on accelerating our growth in the third line that's switching to the dynamics in the in the first and second line.
We see the use of the the major three classes upfront, but primarily the trend that we're seeing is an increase in the use of the anti CD 38 antibody in the first and the second line.
As a result that unmet need is growing four in effective manageable treatment following and anti CD 38, and that is where we have actively generating data to demonstrate the rationale and efficacy of Expo Bill immediately following an anti C. D 30.
Eight.
Got it that's helpful and is this third line setting is this aligning with your community uptake data and do you expect this to be a key driver behind your fees or future growth expectations in the community setting.
Absolutely at least.
See the again the most rapid growth in the third line the community as you know when they start off prescribing the drug they see these community physicians see a variety of patients across tumor types. So when they start up any new therapy. They can come across a couple of initial hurdles with it.
Mobile given that the tying in to the launch that we are they cross a lot of these initial hurdles and now it's really about moving them into earlier lines and continuing to build the confidence that they already have from some of those initial experiences.
Got it makes sense and I was going to ask one question on myelofibrosis too I'm. Just wondering if you can give any granularity on timing for the additional data a recommended phase two dose in the phase three start up dates in the first half of 'twenty three and what do you need to see from the 40 make data to go forward with that dose or what are your latest thoughts on dosing.
<unk> for that study.
Yeah.
Yeah restaurant do you want to capture that one.
Yeah, absolutely and thanks for the question. So their next update is going to occur sometime in the first half of 'twenty to 'twenty three the update again is just going to include the patients. The 24 patients that were enrolled as part of the phase one. So all of these patients again were treated with the combination of Selinexor and rock solid node.
And they're all treatment naive patient population and we're following all of them for maturities. So the key time point that we wanted to assess their S. V. R. T. S has 50 hemoglobin and safety is specifically going to be at that 24 week and beyond and so as we.
Continue to follow these patients it's going to help guide them the optimal timing of when we can provide that update again across those key efficacy as well as safety endpoints as well as additional data, including translational data.
An important sub group data as well in terms of how we identify the recommended phase two dose we're gonna look across multiple parameters. So it's going to be about the efficacy of gun that we specifically see at the week 24 of course that important safety profile, but we also need to.
Incorporate pharmacodynamic data too so you know.
Stay tuned for the update again, it'll it'll occur in the first half of this year.
Okay. Thanks for taking my questions.
Thanks Martin.
The next question comes from Chris Raymond of Piper Sandler. Please go ahead.
Oh. Good morning. This is no coker bruski on for Chris. Thanks for taking the questions. Maybe just just to for US. The first I'm just for the pivotal phase III frontline study in Myelofibrosis I guess can you just provide some more color around the regulatory feedback.
You're waiting for in order to initiate that study and then I guess second just with endometrial cancer I know that you guys have indicated that you'll present updated subgroup results from Canada. This year, maybe can you just help frame what updated data, we should expect to see and there's a particular venue or venues that we should maybe think about it as a good fit for the update.
Yeah.
Yeah, Thanks, Yeah, I'll turn to two.
I'm, sorry about that jumped the gun there hum, but great question. So in terms of the next steps for the Myelofibrosis program again, it's going to be that data that I just mentioned in the previous question the efficacy the safety.
The pharmacodynamics the dose and then of course, you know just getting alignment from the FDA on the design and statistical analysis plan for the phase three.
So that meeting is going to occur sometime in the first half. This year and then we look forward to presenting the trial design along with the updated data again in the first half of this year, but you know I will say you know we've got a lot of other precedents out there in terms of this first line states.
Looking at a combination versus rux, a lytton Ed is likely something that we are going to pursue as well and we're going to focus on the endpoints that are relevant to the patient population, specifically SVR 35, as well as the T. S has 50, a week 24, but also look at important aspects, including hemoglobin <unk>.
<unk> and then of course that the safety profile as well.
In terms of endometrial cancer. So you know an important update that we presented on this earnings call was a recent update on the PFS result from the Sandoz subgroup. So based upon in November 2022 cut we analyze the progression free survival.
Specifically in those piece of fifty-three wild type patients, which comprised approximately 50% of all endometrial cancer and very encouraged by the updated results. What we've now seen that median progression free survival for the Selinexor arm has increased from 13.7 months.
To now 20.8 months, the placebo arm by and large it stayed the same and the most recent updates show. The median PFS is 5.2 for placebo. So very very very encouraged by the now quadrupling in that median PFS observed before the selinexor.
Treated patients we continue to follow all of these patients and.
We'll update P. S. US also looking at overall survival two as those events accrue, we'll look to present the updated data.
Great. Thank you.
Thanks Nicole.
The next question comes from Mike <unk> of Morgan Stanley . Please go ahead.
Good morning, and thanks for taking the question.
Maybe just one on the myelofibrosis strategy.
Based on some of the data you highlighted in your prepared remarks are you thinking about potentially moving mono therapy.
Frontline myelofibrosis.
And then maybe secondly can you just give us your current thinking on the strategy in second line at this point thanks.
Thank you. Thank you, Mike I'm going to wait for Richard but I'm Gonna go ahead and get them Theyre a great question. So our focus right now is absolutely the combination of Selinexor in rocks of Loopnet largely based upon the very compelled.
<unk> results that we continue to see from the phase one portion of the O. Three fourths study I'm. So looking forward to interacting with the FDA and then initiating that trial in the first half this year.
With that said, though there are some very important learnings from the phase one portion that suggests that suggest that selinexor really is a fundamental mechanism within myelofibrosis across the patient populations and it affords us an opportunity to really maximize the development of Selinexor.
In this important patient population, whether it's looking at monotherapy novel combinations et cetera, but that is something that we want to define in the future. Our focus right now is absolutely the combination of Selinexor and Rockville at Nib.
Great. Thank you.
Thanks, Mike.
Yeah.
Our next question comes from Brian Abrahams of RBC. Please go ahead.
Hi, This is Joe on for Brian . Thanks for taking my question I have two so first one on the the Alto next door are what you would like to demonstrate a from the interim data and also if you could tell us a little more about sort of like the latest data cut you saw in the.
Endometrial cancer, and how that shapes your expectation in the the new phase three data in terms of a bed with a PFS and a D O S.
Yeah.
Yeah. Thanks, Thanks, Joe I'll turn it over a duration for both of those.
Oh, absolutely. So you know as I mentioned earlier right I mean, that's relapsed refractory Knight will actually say the patients that were enrolled as part of the stage one and also in the phase two are the hardest to treat patient population I mean in fact these are these primary HMA refractory patient population.
Survival is extremely short unfortunately in this patient population with published data, indicating median survival of only four to six months, we're very highly encouraged by the phase one data that we presented at Ash 'twenty two specifically the median overall survival of those patients treated with Alto next door.
<unk> was approximately 10 months.
With that improvement in overall survival that again, we hope to see as part of this phase two it will allow us to best determine the registration path with alternate with Alto next door in this patient population.
In terms of the endometrial cancer.
Cancer again, very encouraged by the updated PFS result.
That we've observed from the November 'twenty two cut a median PFS for the solar next door patient population has increased from 13.7 months to now 20.8 months and overall survival is still immature and so we're continuing to follow those survival data, but these data are very.
Much informed our current phase three trial E. C. O four two and are encouraged by the benefit that these patients can achieve in this E. C O four two trial.
Super helpful. Thank you.
Yeah.
The next question comes from Eric Joseph of Jpmorgan. Please go ahead.
Hi, good morning, Thanks for taking the questions just a couple of other endometrial cancer.
One around the PFS update ratio can you just talk about how closely duration on treatment lines up with the.
Extended benefit on PFS.
And then secondly, I'd be interested to get a sense of how site participation or the regional mix of patient enrollment will.
<unk>.
Kind of line up between the E. C O four two study and an experienced and Sandra thanks.
Yeah. Thank you Eric Great question. So as we look at the updated P. S. A b.
See if we can.
C N increase going from 13 to 28, we also see a proportional increase in that duration of therapy to them. So that duration is driving progression free survival benefit in that patient population, we're going to continue to follow not only the duration, but the PFS and OS.
In this trial.
In terms of site activation.
There's a lot of activity that is happening within E. C O four to one of the benefits that we can leverage is actually our experience with the C. N dough, we had approximately 100 sites as part of the Sandoz trial that included sites you know from the G O G and got with U C. O four two we can Ida.
Jennifer this highest performing sites and incorporate them into the E. C. O four two trial as well as add additional sites I say that because in the C and D. E. C. O. Four two trial, we're actually looking to activate approximately 140 sites in the U S and Europe .
Okay got it and maybe just a follow up if I could on myelofibrosis.
Yeah.
I know thats starting to phase III trial is depending is pending.
Regulatory feedback I guess I'm wondering if there's any reason to think that the phase III trial design.
Sure.
She may not rich I guess is the manifest to trial a good proxy for how the.
The phase III design with them with that sort of extra should book. Thanks.
Yeah, Yeah. Good question I mean.
Yeah, right I think we know and first line on SVR and T. O says 50 are the key end points about the physicians are interested in but also the regulatory agencies are interested in them. So we know those are going to be the end point in which we design our trial.
It's gonna be you know relatively simple comparison right just comparing the efficacy and safety of the combination of salary plus rocks to rux alone. So you know this is this is gonna be a very traditional trial, but optimizes our ability to demonstrate the benefit that patients can achieve.
With the combination compared to rux alone.
Great. Thanks for taking the questions.
Thank you Eric.
The next question comes from Ed White of H C. Wainwright. Please go ahead.
Good morning, Thanks for taking my questions.
You had mentioned several times that the Youre seeing an increase in the duration on therapy in the sector.
Second to fourth line patients I'm, just wondering if perhaps you can quantify that and perhaps give us.
An indication of what you're seeing in the fourth quarter of this year versus the fourth quarter of last year.
Yeah, so I need to want to take that one.
Yeah. Thanks for the question so on duration when we look at a year over year and it takes time for this data to mature we do see an upward trend in our duration year over year and this is really driven by two factors the increase in the proportion of patients in earlier lines, who are staying on therapy longer.
But also it's driven by effective management of these patients with dose adjustments and supportive care now as the data matures, we see an increase in proportion of patients reaching cycles, three four and five in 2022 versus 2021 in the outer edge.
End of the range is as you know patients you know, there's a broad range of patients staying on therapy on the out end of the range. We do see patients Onyx OBO over two years of therapy and overtime positions are getting increasingly confident in managing these patients.
Okay, great. Thank you for taking my question.
Thanks, Ed.
The next question comes from Jonathan Chang of <unk>.
Securities. Please go ahead.
Hey, guys. This is Matt on for Jonathan Thanks for taking my question just a couple initially on the myelofibrosis update in the first half can we expect to see any week 48, SCR 35 data there and then also for the TSS 50 by chart review I was wondering if you could elaborate on how that may or may not differ from how that data is typically collected.
And then second question I was just wondering how do the late stage combination trials in treatment naive myelofibrosis influence your trial design or are you thinking on that opportunity. Thanks.
Yeah, Thanks, Matt I'll turn to duration for those.
Yeah.
Yeah. So let me talk about the TSA. The T. S has 50 data. So we will have an opportunity to present additional TSS 50 data at the next update them largely because ah patient filled out forms from a symptom perspective physicians also collected the same.
Data in their medical charts. So we can use these two platforms I E. The forms as well as the medical chart data to really provide a comprehensive overview of the T. S. That's 50 that has been achieved in the combination to look forward to presenting that additional data in the first half.
This year.
In terms of the week 48 data yeah, absolutely. So we've got multiple patients that are staying on therapy. You know some patients are coming in you know they've been dosed for approximately a year or so.
Being able to provide the durability data, it's going to be an opportunity again for us in the first half of of of this year.
In terms of the the other competitor.
Trials within the first one space.
Yeah.
By and large I mean look forward to seeing those data, but I don't think that they're necessarily influencing our decision about the design you know as I mentioned previously this is really a very traditional phase three where you want to be able to demonstrate the benefit that can be achieved with the combination as compared to rux alone. So it is really good.
Going to be a very traditional it's three a combination with rux alone focusing on that SVR N T. S. That's 50.
Thanks for taking my questions.
Okay.
Thanks, Matt.
This concludes our question and answer session.
I'd like to turn the conference back over to Richard Paulson for any closing remarks.
Thank you operator, and thank you everyone for joining us on today's call and once again a huge thank you to all of our teams and our people across the organization as each and every person at carrier farmers working every day to say how can we improve the lives of patients suffering from cancer and we look forward to sharing an update with you here in the near future.
The conference has now concluded. Thank you for attending today's presentation and you may now disconnect.
Yeah.
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Mhm.
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