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spk09: Good morning. My name is Claudia Gunthert, and I will be the conference operator today. At this time, I would like to welcome everyone to the CarioPharm Therapeutics Third Quarter 2021 Financial Results Conference Call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Jason Zinkelstein of Argot Partners.
spk12: Thank you, Claudia, and thank you all for joining us on today's conference call to discuss CarioFarm's third quarter of 2021 financial results and business update. Today, I'm joined by Mr. Richard Paulson, President and Chief Executive Officer, Ms. Sohanya Chang, Senior Vice President, Sales and Commercial Operations, Dr. Jayden Shah, Chief Medical Officer, Mr. Mike Mason, Chief Financial Officer, Mr. Steven Michener, Chief Business Officer, and Dr. Sharon Shackham, Chief Scientific Officer. During today's call, as outlined on slide two, Richard will provide some introductory remarks, Sohania will provide an update on our Expovio commercial progress, Jeaton will highlight recent pipeline advancements, and then Mike will discuss the third quarter financial result highlights and guidance. We'll conclude with some thoughts from Richard on upcoming milestones and then we'll move to the Q&A portion of the call. Earlier this morning, we issued a press release detailing CarioFarm's results for the third quarter of 2021. This release, along with the slide presentation that we plan to reference during today's call, are available on our website at cariofarm.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations relating to the commercialization of Expovio and Nexpovio, financial projections, and our plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, We specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I will now turn the call over to Richard Paulson. Please turn to slide four.
spk02: Thank you, Jason, and good morning, everyone. Now, please turn to slide five. After joining as President and CEO in May, and now having been in this position for a full fiscal quarter, I've valued the opportunity to meet and speak to many of our shareholders, customers, and investigators. From our insightful conversations, I've enjoyed the enthusiasm and the commitment to our science. With the ability to positively impact patients and work across many different types of cancers, I look forward to continuing these interactions in the future as our future outlook for KaryoPharm is rooted in three key fundamentals. First is our execution in Expovio's launch. Currently, Expovio is approved in three indications in the U.S., in multiple myeloma and diffused large B-cell lymphoma. We have a tremendous opportunity in front of us to continue expanding Expovio's breadth and depth through continued head-down execution in the approved indications and advancement of key late-stage myeloma studies. We delivered strong commercial results in the third quarter with a significant increase in net product revenues compared to the second quarter of 2021, driven by an acceleration in demand growth for Expovio. Expovio continues to move into earlier lines of therapy in multiple myeloma as a new effective modality that can become the standard of care in second line plus, which was Sohania we'll discuss later in the call. In parallel, we will continue to build our foundation globally. We are anticipating that the European Medicine Agency's Committee for Medicinal Products for Human Use will complete the review of our Nexpovial marketing application as a second-line plus treatment for multiple myeloma, which is expected during the first half of 2022. Second is our pipeline. As we advance our pipeline, we are actively working to prioritize our clinical development plan and hematological malignancies and solid tumor indications with the highest unmet need probability of success, and attractive market opportunities. This includes our Phase III Siendo study, Evaluating Cell and XOR in Endometrial Cancer, where there are no approved treatments for maintenance therapy following chemotherapy in any line of treatment. Top line results for this study are expected by the end of this year or early next year, and if positive, will further reinforce the therapeutic potential of Cell and XOR in solid tumor indications. We are also advancing targeted late stage clinical studies across multiple hematological and solid tumor indications that Jayton will review later on our call. And we look forward to hosting a virtual investor day on Wednesday, December 8th to present further details on our commercial and pipeline priorities. To support our focused growth plan, we are well capitalized to fund our operations with a cash runway into the middle of 2023. Third is our people, who foster scientific creativity, pioneering technologies, and are dedicated to delivering Expovio to patients. We support a culture of innovation, courage, urgency, resilience, and energy captured in our iCure values with our employees and our collaborators. I'd like to sincerely thank our team, who are focused on helping patients in need and delivering for shareholders. As we turn now to slide six, I would like to turn the call over to Sohanya Chang, our Senior Vice President of Sales and Commercial Operations, for her review of the commercial results for the quarter. Sohanya?
spk07: Thank you, Richard, and good morning, everyone. We have accelerated growth in the third quarter and continue to make strong progress across key indicators since our second LinePlus launch at the beginning of this year. Please now turn to slide seven. Total Expovio net product sales for the quarter were 26.7 million, a 32% increase quarter over quarter, and a 25% increase year over year. These increases were driven by strong execution, with over 9,000 prescriptions filled as of the end of the third quarter. We continue to see a positive shift from the Penta refractory setting towards earlier lines, with the most rapid growth this year in the third line, as we continue to focus our messaging on the white space in myeloma between second and fourth line, where using a new class of therapy could be vital for the success of patients' outcomes. We are expanding in breadth and depth of use of Expovio, with strong growth in the community setting. We continue to add more accounts every quarter and increase penetration at top myeloma accounts. In addition, our intent to prescribe data continues to show sustained improvement in the efficacy and safety perception of the product and growing confidence in utilization in earlier lines as physicians have an increasingly positive experience with the lower dose once weekly Expovio-based triplet regimen. While patient visits and field activity improved in the third quarter, they have not returned to pre-COVID levels. We will continue to monitor any further COVID impact and remain focused on strong execution and positioning Expovio as a standard of care in Second Line Plus. With the foundation we're laying now and with a rapidly advancing myeloma pipeline, we hope to continue to drive a steady growth in the near, mid, and long term. If you will now advance to slide eight, I will turn the call to Jayton to highlight our clinical development efforts to further build our position in multiple myeloma, other hematological, and solid tumor indications. Jayton?
spk05: Thank you, Sonia. If you'll now please turn to slide nine, I'd first like to touch on our key regulatory advancements. As you know, our marketing authorization application in the EU has been validated and is currently under review by the CHMP. And as Richard mentioned earlier, we expect this review to be complete during the first half of 2022. We are seeing progress with bringing Cell and XR to patients in need across the globe by our ex-US partners, including a new drug submission that was recently submitted by Forest Therapeutics and accepted for review by Health Canada. In addition, we saw the approval of Celanexor for the treatment of patients with multiple myeloma and DLBCL in South Korea and several new drug applications in multiple Asia-Pacific markets, including China, Hong Kong, Australia, Singapore, and Taiwan, all with our partner, Antigene. Turning now to slide 10 for clinical stage programs. We are advancing our pipeline across multiple oncologic indications with a high unmet need. This is a snapshot of our clinical pipeline, including key new clinical studies that were recently initiated, including the MF34 study, evaluating salinexer in combination with ruxolitinib in treatment-naive myelofibrosis. The MEL33 study, evaluating selanexer in combination with pembrolizumab in patients with locally advanced or metastatic melanoma. And finally, the 801 study, evaluating eltenexer in myelodysplastic syndromes. We'll provide more details on these studies in just a moment. We're actively prioritizing our pipeline and look forward to communicating our refined corporate vision and objectives at our Virtual Investor Day that's planned for December 8, 2021. At this time, the Phase III Sienda study represents the next major milestone, and we remain highly encouraged by the opportunity for Selinexer in patients with endometrial cancer in the maintenance study, which is outlined on slide 11. Now, endometrial cancer is the most common gynecological cancer in the U.S., with over 66,000 new cases in 2021. While most women are diagnosed with early-stage disease and have a good prognosis after surgery alone, approximately 14,000 patients each year will present with advanced or metastatic disease. These patients are typically treated with chemotherapy for four to six cycles. And as there are no therapies approved for maintenance, after chemotherapy, patients are followed with close observation and a watch and wait approach. Unfortunately, the treatment is not curative and there's a short remission time, typically four to six months before the disease returns. And when their disease progresses, these patients are typically treated with additional chemotherapy, immunotherapy, or targeted agents. Maintenance therapy has been a very effective strategy in multiple diseases to extend the time in remission. The concept of maintenance therapy has been very well established in gynecological malignancies with PARP inhibitors in ovarian cancer, yet there are no approved maintenance therapies for patients with endometrial cancer post chemotherapy. To put the potential opportunity in endometrial cancer in perspective, 14,000 patients each year are treated with chemotherapy and could potentially benefit from maintenance therapy with this number estimated to grow in the future. Looking at slide 12, in our initial phase two sign study, we looked at single-agent salinexer in patients with chemotherapy refractory disease with a high disease burden that's growing and not in remission. In this population, with currently available treatments, most patients either do not respond or have a transient stable disease for less than eight weeks. In this patient population, we demonstrated the activity of single-agent Selinexer with nearly one-third of patients in this refractory setting with disease control, which is defined as those with a complete response, partial response, or stable disease for at least three months. In this third line setting with chemotherapy refractory disease, Selinexor demonstrated a median duration of disease control of 6.3 months. This data supports the evaluation of Selinexor in earlier lines of therapy. To be clear, in contrast to sign, In this CNDOS study, we evaluate Selinexer in the first line setting and chemotherapy-sensitive setting, as you see on slide 13. The phase three study is evaluating the role of once-weekly low-dose Selinexer in patients with endometrial cancer as maintenance therapy post-chemotherapy. The Ciendo study is enrolling approximately 248 patients, randomized two to one, to receive either 80 milligrams of Selinexer once weekly or placebo. Eligible patients include those who have stage four or recurrent disease, who have completed a course of taxane platinum combination chemotherapy and achieved either a partial or complete response. The primary endpoint of the trial is an improvement in progression-free survival, or PFS, as defined from the time of randomization until death or disease progress. In November of 2020, we announced the trial had passed its planned interim futility analysis, and so the study has continued as planned. Recruitment is on track, and we expect the top-line data, which is event-driven, by the end of this year or early next year. Turning now to slide 14, we recently commenced dosing in an expanded phase two study, evaluating L-tenexor, our second novel oral sign compound in patients with MDS. MDS occurs when the hematopoietic stem cells within the marrow become abnormal and create immature blood cells that are not able to function properly, which leads to significantly low blood counts. It is estimated that approximately 15,000 new cases of MDS occur in the U.S. annually, with a prevalence of approximately 60,000 in the U.S. With an aging population and an improving awareness of the disease, this incidence is expected to increase. Hypomethylating agents, or HMAs, are the current standard of care for patients with newly diagnosed high-risk MDS. However, only 50% of patients respond, and these responses typically last less than two years. Unfortunately, HMA therapy is not curative, and all patients ultimately develop disease that's refractory to HMA therapy. There are no class of drugs approved in HMA refractory disease. And a prognosis in HMA refractory disease is poor, with a median overall survival of four to six months. There are no agents currently approved for HMA refractory disease, and the need for novel efficacious agents is critical. If you turn to slide 15, you will see in our phase one study, single-agent Eltenexer showed clear single-agent activity in patients with high-risk relapsed MDS that was refractory to HMAs. In that study, L-tenexor demonstrated a 53% overall response rate and a median overall survival of 9.9 months, doubling historical controls of four to six months. At the recommended phase two dose of 10 milligrams, L-tenexor monotherapy was well tolerated with a low incidence and grade of gastrointestinal events. Exacerbation of cytopenias occurred in 20 to 40% of patients. Based on a promising signal observed in the phase one study, we're pleased to have recently initiated dosing in the phase two expansion, the design of which you can see on slide 16. Finally, I'd like to highlight our emerging program in myelofibrosis. Turning now to slide 17. In the U.S., it's estimated that approximately 5,000 cases of myelofibrosis occur annually with a prevalence of 16,000 to 18,500 in the U.S. Currently, in myelofibrosis, there's only a single class of drugs, JAK inhibitors, which are approved and used commonly in the first line. Unfortunately, ruxolinib is not curative, and the disease often progresses within four years for primary responders.
spk04: There are no other class of drugs approved and relapsed to myelofibrosis, and the need for novel therapeutics is critical.
spk05: Turning now to slide 18. In preclinical studies, inhibition of nuclear cytoplasmic transport by Selinexer or Eltenexer reduced survival of cells expressing JAK in both ruxolidib-sensitive and resistant cells. These data led to an investigator-sponsored Phase II study evaluating once-weekly low-dose Selinexer in patients with ruxolitinib-resistant myelofibrosis. The data from this investigator-sponsored Phase II study has been submitted to ASH 2021 for potential presentation during the fourth quarter. On slide 19, you can see the study design for a new company-sponsored randomized multicenter Phase II study, which is expected to start also during the fourth quarter. We look forward to updating you on the progress of this and all of our important studies at our Virtual Investor Day. With that, I'll now advance to slide 20 and turn the call over to Mike Mason to review the quarterly financials. Mike?
spk02: Thank you, Jayden. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 21. Total revenue for the third quarter of 2021 was $37.7 million compared to $21.3 million for the third quarter of 2020. Net product revenue for the third quarter of 2021 was $26.7 million compared to $21.3 million for the third quarter of 2020 from U.S. commercial sales of Expovio. The estimated gross to net discount for Expovio in the third quarter was 15%, which was on the lower end of our expected range of 15% to 20%. and we continue to expect to be in that 15% to 20% range for the full year 2021. We recognized $11 million of license and other revenue for the three months ended September 30, 2021, including $9.8 million in milestone payments from antigen following the July 2021 approval of Selinexor for the treatment of patients with multiple myeloma and DLBCL in South Korea, and $1.2 million of revenue associated with named patient programs. R&D expenses for the third quarter of 2021 were $45.8 million compared to $37 million for the third quarter of 2020. The increase in R&D expenses, as previously stated on our Q2 call, was primarily attributable to the $7.4 million asset purchase of new medicines in the third quarter of 2021. SG&A expenses for the third quarter of 2021 were $35.1 million, compared to $31 million for the third quarter of 2020. The increase in SG&A expenses compared to the third quarter of 2020 was due primarily to an increase in personnel costs, primarily related to an increase in headcount and compensation costs. Cash, cash equivalents, restricted cash and investments, as of September 30, 2021, totaled $209.3 million, compared to $276.7 million as of December 31, 2020. Based on our current operating plans, we expect that our non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense for the full year 2021, to be in the range of $270 to $290 million. We expect that our existing cash, cash equivalents, and investments, as well as the revenue we expect to generate from Expovio product sales and other license revenues, will be sufficient to fund our planned operations into the middle of 2023. I'll now flip to slide 22 and turn the call over to Richard for some final thoughts. Richard? Thank you, Mike. We are building off a very strong first nine months of the year, and as we move into the fourth quarter and beyond, there are a number of key near-term catalysts and milestones for us to deliver on as we continue to strengthen our organization and deliver for patients with high unmet needs, as outlined on slide 23. In multiple myeloma, our focus remains on the continued enhancement and strong execution for our commercial organization to secure increased expovo sales in the second line plus treatment setting. We are awaiting the completion of the review of the MAA package in the EU based on the data from the phase three Boston study. We plan to initiate our phase three study of XPD in multiple myeloma later this year. an all-oral combination that would allow us to further build in the multiple myeloma landscape. From our solid tumor programs, we expect top-line data from the Phase III Siendo study in endometrial cancer later this year or early next year, a market opportunity where there are no approved drugs in the maintenance setting following chemotherapy in any line of treatment. We have additional cell and XOR data in various hematological indications submitted to ASH 2021, and we look forward to announcing our selected abstracts tomorrow, Thursday, November 4th. Lastly, we plan to host a virtual investor day on December 8th to review our strategic imperatives and pipeline priorities to support our continued evolution as a company. To close, we're excited to continue delivering for patients who are fighting cancer across the world. I look forward to updating the investment community on our continued progress in the months and quarters ahead, And with that, I would now like to ask the operator to open the call up to the question and answer portion of today's call. Operator?
spk09: Thank you very much. To ask a question, you may press star, then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. The first question comes from from Jefferies. Please go ahead.
spk08: Hey, everyone, and congrats on the update today. Thanks for taking my questions. So I was just wondering if you can talk more about what you're seeing in the third-line setting. What are the most common treatments that patients are coming off of before getting Expovio? And in that third-line setting, is it the Boston regimen that's being used, or what else can you say about the combo preferences?
spk02: Sure. Thanks, Maury. Maybe I'll turn to Sohania to answer that.
spk07: Yeah, thanks, Richard. As you heard earlier, we're seeing an acceleration in the shift from later lines into earlier lines. And our syndicated data indicate the strongest growth this year is in the third line setting. In terms of patient proportions, we see an approaching 50-50 split between patients in the second to fourth line and patients in the fifth line plus setting. In terms of the overall treatment paradigm, most patients are treated with an IMID, a proteasome inhibitor, or an anti-CD38 in the first or second line. In the later lines, we see several new competitors or classes in the mix. We believe we are strongly positioned in that middle section of second to fourth line where a class switch to an exposio-based regimen could be vital for the success of the patient. We're also highly effective in subgroups of patient types such as high-risk, elderly, and renal dysfunction. As we continue to look into the future, we expect to see the sustained shift in the line of therapy from the later lines, from the original penta-refractory indications to earlier lines in line with our Boston data, which launched at the beginning of this year.
spk02: Does that address your question, Maury?
spk08: Yeah, that's helpful. Maybe one quick follow-up. In the last couple of quarters, you guys have reported metrics on refill rate. Just, and I'm not seeing it in this update, just wondering if you can comment a little bit on what you're seeing with refill rate.
spk07: Yeah, absolutely, Maury. So we are still in the early stages of the launch of the second line plus indication since the beginning of this year, and this data is still maturing. We do have preliminary data that shows that more patients are staying on therapy longer, and this is driven by two factors, the shift into earlier lines as well as better side effect management. As we evolve into earlier lines, we expect to see the duration increase driven by that shift into earlier lines and in line with our targeting positioning. However, we cannot definitively guide to a specific duration number at this time since we're in a dynamic phase of our transition into earlier lines of use and in an early stage of the launch, so we need to let that data mature.
spk08: Okay, okay, makes sense. Congrats again, and thanks for taking my question.
spk03: Thanks, Laurie.
spk09: Thank you. The next question comes from Peter Lawson from Barclays. Please go ahead, Peter.
spk13: Peter, I'm sorry to interrupt.
spk09: If you don't mind just speaking up a bit, because we cannot hear you. Your line is quite low.
spk13: Yeah, I'll pick up my headset. Congratulations on the quarter. And the drivers in 3Q, kind of what will continue into 4Q? How should we think about that? And, you know, kind of what's left to accelerate revenue growth in 4Q and into 2022? Thank you.
spk02: Thanks, Peter. We will turn to Sonia on that.
spk07: Yeah, thanks for the question, Peter. So we saw significant demand growth this quarter, contributing to 32% quarter-over-quarter revenue growth, and we feel very confident in our sustained growth. This was driven by strong execution and the new positioning we introduced in the second quarter in that white space of second to fourth line. Now, in terms of drivers, there's three key indicators. Number one is the acceleration of that shift into earlier lines. And as I mentioned, our syndicated data is indicating that strongest growth this year in the third line, as well as that shift from the Expobio-based doublet regimen to the once weekly triplet base regimen in line with our Boston indication. And we expect to continue to see a shift in that line of therapy. The second driver is that expansion in the breadth and depth of use of Expobio. We're adding more accounts every quarter and we're increasing our penetration at the top myeloma accounts. The most significant growth that we saw was in the community setting and we expect to continue to see that in the future as well. Lastly, In terms of the qualitative market research as well as customer feedback that we're getting, we see a sustained improvement in the overall product perception and a growing confidence amongst physicians in managing this product with our new lower-dose, once-weekly, Expovio-based triplet regimen. So as I mentioned, we are still in the early stages of the second line plus launch, and we won't be giving sequential growth guidance, but we remain confident in our ongoing efforts to drive increasing use in earlier lines, growth position confidence in ExpoVO, and remain focused on very strong execution.
spk13: Great. Thank you. Were there any one-timers in the quarter that we should be thinking about as we kind of grow revenues off of Q3?
spk02: No. No one-time impact in the quarter.
spk13: Perfect. Thank you so much. Thanks for taking the questions.
spk03: Thanks, Peter.
spk09: Thank you. The next question comes from David Lieberwitz from Morgan Stanley. Please go ahead, David.
spk11: Thank you very much for taking my question. Given that there's so much shift in the treatment paradigm for multiple myeloma, where are Does Velcade, the Velcade combination actually end up, I guess, being most predominant? Will it be in the second line or the third line, given that where Darzalex has been increasing its use? And beyond that, was there any inventory shifts or anything in the quarter on the wholesaler side?
spk02: Maybe I'll just start with Mike to talk on the inventory side, and then I can turn to Sohania to talk about the utilization in that second or fourth line, David. Sure. On the inventory side, it was a minor drawdown in inventory in the quarter, but as you remember from last quarter, we had about a $2 million shift, so it was a minor impact on the quarter. So we expect inventory to not have a meaningful impact on quarterly revenue going forward. Mm-hmm.
spk07: And as far as your treatment paradigm question, most patients, as you mentioned, are treated with an anti-CD38 or IMID or a PI in the first and second line. So following that, and prior to the later line therapies, there is that significant unmet need where we are seeing the most rapid growth in both second and third line for expovio. Now, our sales and marketing teams will, of course, only promote to the FDA-approved Expobio combination with bortezomib and dexamethasone, and we're continuing to see a rise in that triplet regimen in the third-line and second-line setting. However, NCCN also has other regimens on board, Expobio in combination with pomalidomide and dexamethasone, and Expobio in combination with daratumumab and dexamethasone. And as I mentioned, we only promote to the Expobio combination in our FDA label, but we're seeing that positive shift from the doublet late-line setting towards that triplet setting in earlier lines in line with our Boston indication.
spk02: And Jaden, maybe just want to expand on that from your perspective.
spk05: Yeah, absolutely. I mean, I think from the treatment paradigm perspective, we're seeing increased using a CD38-based therapy in that first and second line, as Sohania mentioned. And so, you know, these patients are either getting an IMID plus the CD38 or a PI plus the CD38. As they progress on that, those therapies, then coming into third line, it starts really leveraging two principles that we're very comfortable with in myeloma, which is class switching. And so if they're on an IMID-based therapy, then switching to a PI-based therapy such as Velcade becomes attractive and is based on kind of sound reasoning for the last 20 years of class switching. So I think that there's a strong degree of comfort around Velcade-based therapies in the community for many years. And so, as Sonia mentioned, there's multiple options now for expogio-based therapy for what the physicians want to do, and they have that optionality.
spk11: Thank you for that. And shifting over to Altenexer, has Selenexer been studied previously in MDS, if you could remind us, and what was the experience, and how would Altenexer differ? Sure.
spk05: Great question. So Selinexer has been evaluated in MDS previously. There was a phase one study, phase one, two study done with Dr. Klimek out of Memorial Sloan Kettering. There they showed a proof of concept with activity with single agent Selinexer in that setting in relapsed MDS with a response rate greater than 30%. So there is that proof of concept now with both Selanexer and Eltenexer in MDS that provides that body of data and the confidence around signed compounds in MDS.
spk11: And the decision, I guess, to move with Eltenexer in this population, was it based on the tolerability?
spk05: Yes, as we looked at the totality of the data, there are differences with Eltenexer with the ability to give low-dose continuous Eltenexer for five days in a row. we saw better activity in our early data with Eltenexer. When you look at the totality of data with Selenexer and Eltenexer, we made the decision to really develop Eltenexer in MDS and in myeloid and limited seas.
spk11: Got it. Thank you very much for taking my questions. Congrats on the quarter. Thank you.
spk09: Thank you. The next question comes from Brian Abrams from RBC Capital Markets. Please go ahead, Brian.
spk00: Hi, hello. This is Leonid on for Brian. Thanks for taking our question. I actually wanted to stay with Elton Exor for a moment. So, you know, I'm curious what you guys are thinking about in terms of the regulatory and clinical bar in MDS for Elton Exor, kind of what you're hoping to see and, you know, how you're seeing this landscape evolve right now. I mean, is there potential for this to be a registrational trial given the unmet need? I'm just curious on your thoughts there. Thanks.
spk05: Yeah, great question. And so, as you know, this field of MDS is rapidly evolving, but what's clear is this, right? HMA therapies are the standard of care and first line. All the other drugs in development, and there are no other drugs other than HMAs right now that are approved in MDS. Number two, when you look at all the other kind of study drugs that are being evaluated in MDS, those are all being evaluated in newly diagnosed MDS. So the field is actually not evolving in the relapsed refractory space. There are no drugs approved in the relapsed refractory space, and there's really limited to no therapies being developed in that relapsed space. So when you look at most of the other studies, they're all in newly diagnosed space. So that really leaves a very clear unmet need and an opportunity in the relapsed space, and that's where we see a clear signal with L-Snex here in that setting. And so as you look at the field in the relapsed refractory space, the field is not evolving as quickly as you would anticipate.
spk02: And then I think maybe, Jayden, just expand on a look at the evolution of the data and with the study, you know, how we would look at, you know, positively engaging with regards to the FDA based on the outcomes. I think if our data continues to hold up, it's obviously a big impact for patients and positive for them.
spk05: Yeah, absolutely. There's a clear unmet medical need there. And when we look at the response rates that we see with Eltenexer, I think if we continue to see response rates in this range, then these would be positive.
spk04: and we'll have discussions with the agency at that point in time.
spk00: Got it. Thank you.
spk03: Thanks.
spk09: Thank you. The next question comes from Eric Joseph from JPMorgan. Please go ahead, Eric.
spk01: Hi. Good morning. This is Hannah on for Eric. Thanks for taking the questions. Just a few from us. So first, looking more closely at the new patient starts, are you able to see if there's any physician stickiness Meaning, are you seeing any formerly prescribing physicians now prescribing exposure for their patients in earlier lines, or are the majority of earlier line scripts coming from new prescribers?
spk07: Yeah, thanks for the question. We're seeing a new patient starts and that's driven by an expansion in both the breadth and depth of use. So there's new prescribers coming on board and trying Expovio for the first time as well as we're growing in depth. So there's prescribers that had used Expobio in the original later line indications, and we're now seeing them growing in confidence in using it in earlier lines. So we're seeing that shift into second and third line.
spk03: Does that address your question, Hannah?
spk01: Yes, that addresses it. And then moving towards just your recently initiated Phase II trial in combination with Pembrolizumab for melanoma, just where and how do you see this combination fitting into the indication of the current treatment?
spk02: I'll turn to Jayton on that.
spk05: Yeah, no, absolutely. So, great question around that. So, we've seen some activity now as presented by the MD Anderson group looking at selenets or imprimolizumab in patients with disease that's refractory to checkpoints. And based on the kind of early promising signals there, we're continuing to really confirm the signal there for what the activity that we see with this combination specifically in checkpoint refractory disease. And the field is evolving there, especially in checkpoint-naive patients. I think there's still a clear unmet need and opportunity in patients with checkpoint refractory disease. And we're evaluating both those patients who have primary refractory disease or those who have a response and then become refractory, as those have two different biologies.
spk04: And based on the data, that will inform or guide us in terms of the next steps.
spk03: Great. Thanks for taking the questions. Thanks, Anna.
spk09: Thank you. The next question comes from Jonathan Cheng from SVB Lyrics. Please go ahead, Jonathan.
spk06: Good morning, and thanks for taking my questions. First question, can you remind me what data you have available that gives you color into what lines of treatment and combinations Expofio is being utilized in?
spk07: Yeah, as you know, it's very difficult to get an accurate picture of lines of therapy, but we do have syndicated data from payer claims data that gives us good coverage on our patients that indicate that shift in line of therapy.
spk06: Got it. And second question, and this is a higher level question. Can you talk about how you're thinking about moving towards being a cash flow positive company in the future, both on the revenue and expense side, and how we should be thinking about your strategy in relation to your cash runways?
spk02: I think maybe I'll just start off, and obviously as we look moving forward, you know, a number of catalysts. First is just continuing to drive our breadth and depth in multiple myeloma and continuing to grow in multiple myeloma. And obviously, you know, moving forward, I think with our Siendo study, as we're talking to that being very near term. And I think also as you've heard from Jayton in that opportunity, you know, right now that's an opportunity which has a very different uptake then you see in multiple myeloma a much more rapid uptake because there is no approved therapy for patients in this setting. And obviously there's a big incidence population which would benefit pretty rapidly from having an improvement in the setting of actually having more time to extend in remission when you're looking at endometrial cancer patients. And then continuing to build on that, obviously with bringing our other new indications forward. So driving our revenue growth, is key. And I think also making sure, as we talked to, that we're very focused in terms of where we invest in terms of having the highest impact for patients and the highest probability of success. And then on top of that, I'll let Mike talk to it, but, you know, you've heard some of the talk about our partner revenue and different areas that we're adding in terms of, you know, evolving our cash runway. Mike? Sure. Yeah, that's a good summary. Just to add, I think obviously on the inflow side, you know, we Our goal with Europe, with potential approval in the first half of 2022, is to be commercially ready there, potentially with a partner. So that's certainly one source of capital coming in outside of traditional revenues or financing. We also have $40 million remaining on our healthcare royalty financing agreement as another tool in our belt. And as Richard said, and we'll give a lot more color to this in our R&D day in about a month on how we really focus on
spk03: Prioritizing our investments in our pipeline. Got it. Thank you.
spk09: Thank you. The next question comes from Colleen Cassie from Bayard. Please go ahead, Colleen.
spk10: Great. Thanks so much for taking your questions and congrats on the quarter. For the top line growth that you saw in 3Q, are you able to comment on between longer duration and new patients, what was more of a driver in 3Q and looking forward where you see the bigger opportunity for growth, whether it's adding new patients or prolonging the duration.
spk02: Thanks, Colleen. I'll just start at a high level and then turn it to Sahan. But again, I think it's a combination of both. As you heard Sonia talk to, we're going to continue to drive the breadth and depth as we move into earlier lines of therapy, which we've done very well in this quarter with the greatest growth being through the year in that third line setting. And as we move up into earlier lines, patients have a greater duration of therapy. So it's both in terms of bringing new patients on board in the earlier lines. and having a greater duration of therapy through the patient obviously benefiting in the earlier lines. So Anya, anything you want to add to that?
spk07: No, I think that's a great summary, Richard, yeah.
spk02: Does that address your question, Colleen?
spk10: Yes, it does, thank you. And on the impact from COVID that you saw in 3Q, can you just put that into context versus what you saw in 2Q and what your expectations are for that in the coming quarters?
spk02: Sure, I'll turn to So Anya on that.
spk07: Yeah, so we saw an increase in 3Q field activity and an increasing proportion of our visits being in person versus virtual, but we have not returned to pre-COVID levels. Similar trend on patient visits. While there's a gradual increase over time in patient visits, that also has not returned to pre-COVID levels. At KaryoPharm, we have a nimble, dedicated, very patient-centric team that is able to reach our prescribers to ensure they have the right education. We've also strengthened our digital capabilities to complement field efforts. So we are entirely focused on strong execution. We have to actively monitor the COVID impact and adjust our engagements as needed, but we remain focused on strong execution. Great. Thanks so much for taking our questions.
spk02: Thanks, Colleen.
spk09: Thank you. Thank you. We have no further questions at this time. I would like to hand back to Richard to conclude. Thank you.
spk02: Thank you, operator, and thank you again to everyone for joining our call today. Looking forward to continue to update you on our success as we continue to bring Expovio to more patients, not only in multiple myeloma, but also in other key hematological indications and solid tumors, you know, with a high unmet need. where we can make a significant impact to positively impact the lives of cancer patients. Thank you for joining us today, and have a great day.
spk09: Thank you very much, sir. You may now disconnect your lines.
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