Q2 2024 SpringWorks Therapeutics Inc Earnings Call

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Gigi: My name is Gigi, and I will be your conference operator today. I would like to welcome everyone to the Springworks Therapeutics 2nd Quarter 2024 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's remarks, there will be a question and answer session. Please limit your questions to one.

Gigi: Good morning. My name is Gigi, and I'll be your conference operator today. I would like to welcome everyone to the Springworks Therapeutics Second Quarter 2024 Earnings Conference Call.

Speaker Change: At this time, all participants are in a listen-only mode.

Speaker Change: After the speaker's remarks, there will be a question and answer session.

Samantha Sandler: Thank you. I would now like to hand the conference over to Samantha Sandler, Senior Director of Investor Relations at Springworks Therapeutics. Samantha, you may now begin the conference.

Speaker Change: Please limit your questions to one. Thank you.

Speaker Change: I would now like to hand the conference over to Samantha Sandler, Senior Director of Investor Relations at Springworks Therapeutics. Samantha, you may now begin the conference.

Samantha Sandler: Thank you and good morning, everyone. Welcome to Springworks Therapeutics' second quarter 2024 earnings conference call. This morning, we issued a press release that outlines our financial and operational results for the second quarter. You can access the press release as well as the slides that we will be presenting today by going to the investors and media section of our website at www.springworkstx.com. Joining me today are Saqib Islam, Chief Executive Officer; Bhavesh Ashar, Chief Commercial Officer; Dr. Jim Cassidy, Chief Medical Officer; Frank Perier, Chief Financial Officer; and Dr. Badreddin Edris, Chief Operating Officer.

Samantha Sandler: Thank you and good morning everyone. Welcome to Springworks Therapeutics second quarter 2024 earnings conference call.

Speaker Change: You can access the press release as well as the slides that we will be presenting today by going to the investors and media section of our website at www.springworkstx.com.

Speaker Change: Joining me today are Saqib Islam, Chief Executive Officer, Bhavesh Ashar, Chief Commercial Officer, Dr. Jim Cassidy, Chief Medical Officer, Frank Perier, Chief Financial Officer, and Dr. Badreddin Edris, Chief Operating Officer.

Samantha Sandler: Before we begin, I would like to remind you that some of the statements made during the call today are forward-looking statements that are subject to a number of risks and uncertainties, which may cause our actual results to differ materially, including those described in our reports filed with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements, and Springworks disclaims any obligation to update such statements. I will now turn the call over to Saqib.

Speaker Change: Before we begin, I would like to remind you that some of the statements made during the call today are forward-looking statements.

Saqib Islam: Thank you, Sam, and thank you all for joining us this morning. I'm pleased to share our second quarter results and how we are delivering on our objective to make a profound impact on the lives of patients with devastating diseases. Starting with obsivio for patients with Desmond tumors, we are encouraged by the strong momentum of our U.S. In the second quarter of 2024, we reported $40.2 million in net product revenue. This robust and continued growth is driven by the transformative clinical benefits of OXIVIA.

Saqib Islam: Thank you, Sam, and thank you all for joining this morning.

Speaker Change: I'm pleased to share our second quarter results and how we are delivering on our objective to make a profound impact on the lives of patients with devastating diseases.

Speaker Change: In the second quarter of 2024, we reported $40.2 million in net product revenue.

Saqib Islam: High demand from patients and physicians across treatment settings and strong commercial execution. Since our FDA approval last November, obsivio has rapidly become the standard of care systemic therapy for patients with desmoid tumors. As Bhavesh will discuss in more detail, we are seeing steady growth in new patient starts as well as strong persistence from those who previously initiated auxiliotherapy.

Saqib Islam: Importantly, patients are reporting rapid and meaningful symptomatic relief, which is contributing to their overall improved quality of life and their enthusiasm for OXIVIO for their treatment. We are pleased with our early launch experience and believe that we have only reached a small proportion of people with desmoid tumors who can benefit from OXIVIA. Our confidence in the overall patient population has continued to increase as we have gained further insights from the launch and from emerging desmoid tumor specific claims data.

Speaker Change: We are pleased with our early launch experience and believe that we have only reached a small proportion of people with desmoid tumors who can benefit from OXIVIO.

Saqib Islam: Our conviction remains high in the opportunity we have in front of us to serve an increasing number of desmoid tumor patients. Turning to our investigational MEK inhibitor, mirtimetinib. In the second quarter, we completed our NDA submission to the FDA for the treatment of children and adults with neurofibromatosis type 1 associated plexiform neurofibromas, or NF1PN. Our NDA submission is based on positive data from our Pivotal Phase IIb RENEW trial, which supports the potential for mirtimetinib to be a best-in-class therapy for both children and adults living with these devastating lifelong

Speaker Change: Our conviction remains high in the opportunity we have in front of us to serve an increasing number of desmoid tumor patients.

Speaker Change: Turning to our investigational MEK inhibitor, mirtimetinib, in the second quarter, we completed our NDA submission to the FDA for the treatment of children and adults with neurofibromatosis type 1 associated plexiform neurofibromas, or NF1PN.

Saqib Islam: There is a substantial unmet need for the approximately 40,000 people living with NF1PN in the United States alone, 30,000 of whom are adults, and 10,000 are pediatric patients. However, challenges with administration and tolerability limit the use of currently available options for children, and there are no FDA-approved therapies for out-of-hospital care.

Saqib Islam: We look forward to working with the FDA throughout our NDA review process and to advancing our commercial preparations in anticipation of our second medicine being introduced to patients in 2025. We are also excited about the opportunities in our emerging portfolio. We have several important efforts in development to serve additional patient populations with high unmet needs, including patients with ovarian granulosa cell tumors, multiple myeloma, and MAPK mutant solid tumors. In addition, we recently began enrollment in our Phase 1 study of our investigational TEED inhibitor SW682 in hippomutant solid tumors, which represent up to 10% of cancers.

Speaker Change: We look forward to working with the FDA throughout our NDA review process and to advancing our commercial preparations in anticipation of our second medicine introduced to patients in 2025.

Speaker Change: We are also excited about the opportunities in our emerging portfolio.

Speaker Change: In addition, we recently began enrollment in our Phase I study of our investigational TID inhibitor SW682 in hippomutant solid tumors, which represent up to 10% of cancers.

Saqib Islam: Finally, we have durable IP protections for our lead molecules and a robust balance sheet that we expect to fund us through profitability. I'll now hand the call to Bhavesh to discuss our progress with OXIVIO for patients with desmoid tumors. Bhavesh. Thank you.

Speaker Change: I'll now hand the call to Bhavesh to discuss our progress with Oxivio for patients with Desmoid tumors.

Bhavesh Ashar: Thank you, Saqib. I'm happy to share an update on the U.S. launch of Auxilio. Two full quarters into our launch, Auxilio is already the most prescribed systemic therapy for adults with Desmond Tumor. As Saqib highlighted, in the second quarter of 2024, we generated 40.2 million dollars in net product revenue, driven by strong demand for OXIVIO by patients and physicians across treatment sites, real-world experience of Auxilio's meaningful benefits, and focused commercial execution in delivering the first and only FDA-approved medicine to the deadly tumor community.

Bhavesh Ashar: Thank you, Saqib. I'm happy to share an update on the U.S. launch of Auxilio.

Bhavesh Ashar: Two full quarters into our launch, Auxilio is already the most prescribed systemic therapy for adults with Desmond tumors.

Bhavesh Ashar: As Saqib highlighted, in the second quarter of 2024, we generated $40.2 million in net product revenue, driven by strong demand for Auxilio by patients and physicians across treatment sites.

Bhavesh Ashar: We're seeing robust adoption with broad use aligned with our FDA-approved label, including in newly diagnosed patients and in those seeking their next line of therapy after unsatisfactory outcomes with previous interventions. Physicians at Centers of Excellence were strong early adopters of OXIVU. We're also pleased with the continued uptake amongst physicians at other academic and community centers, where we are also seeing steady new patients start. In addition, we've received consistent feedback from both patients and physicians on OXIVIO's life-altering impact.

Bhavesh Ashar: We're seeing robust adoption, with broad use aligned with our FDA-approved label, including in newly diagnosed patients and in those seeking their next line of therapy after unsatisfactory outcomes with previous interventions.

Bhavesh Ashar: We're also pleased with the continued uptake amongst physicians and other academic and community centers, where we are also seeing steady new patient starts.

Bhavesh Ashar: In addition, we've received consistent feedback from both patients and physicians on Oxivio's life-altering impact.

Bhavesh Ashar: Patients are experiencing rapid and significant symptom relief, notably pain reduction, helping them to get back to their daily life. Enhancing the patient experience with Oxidio has been an area of focus this quarter. We're pleased with the successful introduction of the 150 milligram and 100 milligram strength auxilio tablets and convenient blister packaging.

Bhavesh Ashar: Patients are experiencing rapid and significant symptom relief, notably pain reduction, helping them to get back to their daily lives.

Bhavesh Ashar: The new product format has seen strong adoption to date, validating the importance of this innovation for patients. Patients prescribed Octavio continue to have broad access to Octavio with reimbursement across payers. Commercial and government insurers are broadly reimbursing Octavio, and formal coverage policies are in place for over 90% of commercially covered lives.

Bhavesh Ashar: The new product format has seen strong adoption to date, validating the importance of this innovation for patients.

Bhavesh Ashar: Patients prescribed Octavio continue to have broad access with reimbursement across payers.

Speaker Change: Commercial and government insurers are broadly reimbursing auxilio, and formal coverage policies are in place for over 90% of commercially covered lives.

Bhavesh Ashar: Across the payer landscape, there is clear recognition of the clinical value of our medicine as an NCCN Category 1 preferred treatment. And in June, the Desmoid Tumor Working Group Guidelines were published in JAMA Oncology, highlighting auxilios incorporation into the treatment algorithm as the first and only approved drug for Desmoid tumors. In just seven months on the market, OXIVIO has become the systemic standard of care for Desmond tumors based on our analysis of prescription data, and we're excited to leverage this position of strength to reach many more patients with this disease.

Bhavesh Ashar: We've also continued to receive highly positive feedback from prescribers and patients on their experiences with obsidial. In a recent survey of 110 oncologists, 95% of observational prescribers expressed satisfaction with their experience. More than 85% of prescribers prefer it over off-label systemics, which are known to have inconsistent efficacy and tolerability challenges, further supporting Oxidio's position as a systemic therapy of choice. In addition, most physicians said that they were likely to use oxivial as a frontline treatment, indicating treatment with oxivial at the earliest opportunity for their adult patients.

Speaker Change: In addition, most physicians said that they are likely to use oxivial as a frontline treatment, indicating treatment with oxivial at the earliest opportunity for their adult patients.

Bhavesh Ashar: Further, we're hearing consistent feedback from patients of profound symptom relief on OxivIO, including patients experiencing rapid and meaningful improvements in pain within days of initiating treatment. Strength of the Real World Feedback, which is consistent with our clinical trial experience, will continue to solidify OXIVIO as the standard of care systemic treatment for patients with Desmond tumors. Turning now to the opportunity we see ahead, there are up to 1,650 newly diagnosed patients annually.

Speaker Change: The strength of the real-world feedback, which is consistent with our clinical trial experience, will continue to solidify OXIVIO as the standard of care systemic treatment for patients with Desmond tumors.

Speaker Change: Turning now to the opportunity we see ahead of us. There are up to 1,650 newly diagnosed patients annually.

Bhavesh Ashar: Our market research supports that the vast majority of physicians are likely to use oxidio as a frontline treatment, and we're already seeing uptake of oxidio as the first intervention. Our research has previously pointed to up to 7,000 actively managed patients in the U.S. each year. Our early launch results, as well as desmo-tumor-specific ICD-10 claims data, have continued to validate the size of this currently addressable patient pool, and we now view this estimate as conservative.

Speaker Change: Our research has previously pointed to up to 7,000 actively managed patients in the U.S. each year.

Bhavesh Ashar: The role of systemic therapy is continuing to increase among patients who require active treatment, with surgery being deprioritized in treatment guidelines. With Obsidio as the first choice systemic therapy, we're confident that there continues to be a substantial opportunity for growth in this patient population. In addition, there is a sizable diagnosed prevalent population of 30,000 people overall.

Speaker Change: The role of systemic therapy is continuing to increase among patients who require active treatment, with surgery being deprioritized in treatment guidelines.

Speaker Change: In addition, there is a sizable diagnosed prevalent population of 30,000 people overall.

Bhavesh Ashar: We know that the majority of desmoid tumor patients receive active intervention over the course of their disease, and hence a meaningful proportion of these patients who are currently on the sidelines could potentially be addressed with a new treatment option. We have seen robust adoption to date and continue to have strong confidence in the sizable opportunity ahead of us to continue serving adults with desmode tumors at all stages of treatment. Our success thus far positions us well for continued momentum in the second half of the year and beyond. We are gratified to have earned the advocacy of Desmo Tumor experts through their collaboration in the DEFY study, as well as engagement following the approval of OXReveal. Our commercial efforts aim to amplify their voices to educate and improve outcomes for patients.

Speaker Change: We have seen robust adoption to date and continue to have strong conviction in the sizable opportunity ahead of us to continue serving adults with desmal tumors at all stages of treatment.

Speaker Change: Our commercial efforts aim to amplify their voices to educate and improve outcomes for patients.

Bhavesh Ashar: This comes in the form of providing opportunities for these leaders to educate the broader desmo tumor community, including physicians, nurses, advocates, patients, and caregivers on guideline recommended treatment approaches. Importantly, this includes education on the role of systemic therapy, the limitations of surgical intervention, and the availability of Oxevio as an FDA-approved and NCCN Category 1 preferred treatment option. Education and peer-to-peer information and experience sharing are critical avenues to increasing awareness of observance and will continue to support increased breadth and depth of practice.

Speaker Change: This comes in the form of providing opportunities for these leaders to educate the broader desmo-tumor community, including physicians, nurses, advocates, patients, and caregivers, on guideline-recommended treatment approaches.

Speaker Change: Education and peer-to-peer information and experience sharing are critical avenues to increasing awareness of observio and will continue to support increased breadth and depth of prescribing.

Bhavesh Ashar: Continuing to address the needs of patients also remains paramount, and we're highly focused on supporting positive experiences with absenteeism. In mid-May, we successfully introduced our 150 milligram and 100 milligram strength tablets in convenient blister packaging. This new product format was developed as an innovation for patients to increase convenience and adherence by reducing daily pill intake and simplifying morning and evening dosing. We have seen a strong transition to this new format during the second quarter and expect this transition to continue over the next three months.

Speaker Change: Continuing to address the needs of patients also remains paramount, and we're highly focused on supporting positive experiences with obsidial.

Speaker Change: This new product format was developed as an innovation for patients to increase convenience and adherence by reducing the daily pill intake and simplifying morning and evening dosing.

Speaker Change: We have seen a strong transition to this new format through the second quarter and expect this transition to continue over the next three months.

Bhavesh Ashar: Additionally, we're expanding our educational resources and delivering best-in-class patient services through Springworks Care Connections, which further support the treatment journey with Axivio. We also continue to generate data to support the strong clinical profile of OXIVIO and are advancing our efforts to expand OXIVIO into additional geographies. In the second quarter, we presented additional data from our Phase 3 DEFY trial at ASCO that reinforced the robust efficacy and manageable safety profile of oxidio, including in hard-to-treat subgroups, such as patients with characteristics associated with poor prognosis and those with APC mutations, which can be a more aggressive form of the disease.

Speaker Change: Additionally, we're expanding our educational resources and delivering best-in-class patient services through Springworks Care Connections.

Speaker Change: We also continue to generate data to support the strong clinical profile of OXIVIO and are advancing our efforts to expand OXIVIO into additional geographies.

Speaker Change: In the second quarter, we presented additional data from our Phase 3 to 5 trial at ASCO.

Bhavesh Ashar: In an oral presentation at ASCO, the file was also showcased as one of the most comprehensive assessments of ovarian function in an oncology clinical trial to date and a best practice for evaluating a drug's effect on ovarian function, Future Cancer Trials in Accordance with ASCO Guidelines. This analysis included updated data on investigator-reported resolution of ovarian toxicity in Defy, which further supported the transient nature of ovarian toxicity in both the majority of patients who stay on oxidative therapy and all those who stop treatment for any reason. Turning to upcoming milestones.

Speaker Change: for future cancer trials in accordance with ASCO guidelines.

Speaker Change: This analysis included updated data on investigator-reported resolution of ovarian toxicity in DEFY, which further supported the transient nature of ovarian toxicity in both the majority of patients who stay on oxidative therapy and all those who stop treatment for any reason.

James Cassidy: We're working closely with European regulators as they review our marketing authorization application, and we are excited by the potential to receive approval from the European Commission in 2025. We also look forward to sharing long-term follow-up data from DeFi at a medical conference before the end of the year. In our Phase I and Phase II studies, patients remained on Oxidil for a median of over four years, and at the time of the phase three defied trial data cutoff, median treatment duration was approaching two years.

Speaker Change: Turning to upcoming milestones, we're working closely with European regulators as they review our marketing authorization application, and we're excited by the potential to receive approval from the European Commission in 2025.

Speaker Change: We also look forward to sharing long-term follow-up data from DEFI at a medical conference before the end of the year.

James Cassidy: With these long-term follow-up data from DEFI, we plan to provide an update on the continued anti-tumor activity and overall clinical benefit provided by Obsidio for longer durations of treatment. The ability for patients to stay on therapy is critical given the persistent morbidities associated with this disease. And we believe these longer-term results from DEFY will further support the potential for extended treatment duration. I'll now turn over to Dr. Jim Cassidy, our Chief Medical Officer, to discuss the progress we're making with our MEK inhibitor, metamidinib, for children and adults with NF1PM. Jim.

Speaker Change: With these long-term follow-up data from DEFI, we plan to provide an update on the continued anti-tumor activity and overall clinical benefit provided by El Cidio with longer durations of treatment.

Speaker Change: The ability for patients to stay on therapy is critical given the persistent morbidities associated with this disease, and we believe these longer-term results from DEFY will further support the potential for extended treatment durations.

Jim Cassidy: I'll now turn over to Dr. Jim Cassidy, our Chief Medical Officer, to discuss the progress we're making with our MEK inhibitor, metamidinib, for children and adults with NF1PN.

James Cassidy: Thanks, Bhavesh. I'm glad to provide an update on our progress developing murdermethanib as a potentially best-in-class therapy for patients with NF1PN, which is a highly morbid and lifelong disease that affects both children and adults. There is a significant opportunity to improve outcomes for these patients. There are approximately 100,000 people in the United States living with NF1. These individuals have a 30 to 50 percent lifetime risk of developing plexiform neurofibromas, which are tumors that grow along peripheral nerve sheaths and can cause severe disfigurement, pain, and functional impairment.

Jim Cassidy: Jim?

Jim Cassidy: Thanks Bhavesh, I'm glad to provide an update on our progress developing Mirdamethanib as a potentially best-in-class therapy for patients with NF1PN, which is a highly morbid and lifelong disease that affects both children and adults.

Speaker Change: It's that.

Speaker Change: There are approximately 100,000 people in the United States living with NF1. These individuals have a 30-50% lifetime risk of developing plexiform neurofibromas, which are tumors that grow along peripheral nerve sheaths and can cause severe disfigurement, pain and functional impairment.

James Cassidy: We estimate that there are approximately 40,000 patients with NF1pn in the U.S. today, the majority of whom are adults who currently do not have an approved therapy. As there is no specific demographic data for this disease, we estimate that there are a proportionate number of people living with NF1PN outside of the United States as well. While systemic therapies are the treatment of choice, and MEK inhibitors have been clinically validated as a class in this indication, there are no formal treatment guidelines.

Speaker Change: We estimate that there are approximately 40,000 patients with NF1PN in the US today, the majority of whom are adults who currently do not have an approved therapy.

Speaker Change: As there is no specific demographic meaning for this disease, we estimate that there are a proportionate number of people living with NF1PM outside of the United States as well.

James Cassidy: And our market research shows that only a small portion of NF1PN patients have been treated with targeted therapy. We have done considerable work to understand the disease state, the current treatment paradigm, and physician and patient preferences. And taken as a whole, our research supports that patients are in need of new options. This is illustrated by a highly fragmented treatment landscape with significant use of off-label therapies, even in pediatric patients for whom there is no approved medicine.

James Cassidy: People living with NF1p have substantial needs that are not met by current options, and bringing a new systemic therapy could allow many more patients to be treated. As we'll discuss, the positive results from our pivotal C2b renewal trial support MEDNUMED's potential to be a first-in-class therapy for adults with NF1PN and a best-in-class option for paediatric patients. The new results were presented at three medical conferences in the second quarter, including during an oral session at ASCO.

Speaker Change: As we'll discuss, the positive results from our pivotal C2b Renew trial support NIRDNIMED's potential to be a first-in-class therapy for adults with NF1PN and a best-in-class option for pediatric patients.

Speaker Change: The new results were presented at three medical conferences in the second quarter, including during an oral session at ASCO.

James Cassidy: These presentations are improving awareness and building enthusiasm for positive results amongst the physician community. The FSC data across both adult and paediatric cohorts in Renew showed significant reductions in the size of PN tumors, with robust objective response rates confirmed by blinded independent central review. In addition, we saw very deep responses that have not been seen before in published studies of this disease.

Speaker Change: In addition, we saw very deep responses that have not been seen before in published studies of this disease.

James Cassidy: The majority of patients with a confirmed objective response experienced a tumor reduction of greater than 50 percent, and reductions of up to 90 percent were seen in both cohorts. This is particularly significant when you consider the hard-to-treat patients that were enrolled in our study. Importantly, physician feedback suggests that these are unprecedented data and have the potential to be a meaningful differentiator. In both children and adults, NMD demonstrated a manageable safety profile with low rates of grade 3 adverse events and low discontinuation rates due to adverse events.

Speaker Change: The majority of patients with a confirmed objective response experienced a tumor reduction of greater than 50% and reductions of up to 90% were seen in both cohorts.

Speaker Change: This is particularly significant when you consider the hard-to-treat patients that were enrolled in our study.

Speaker Change: Importantly, physician feedback suggests that these are unprecedented data and have the potential to be a meaningful differentiator.

Speaker Change: In both children and adults, the method demonstrated a manageable safety profile with low rates of grade 3 adverse events and low discontinuation rates due to AEs.

James Cassidy: We believe Merrimetanib's tolerability profile supports the potential for extended treatment duration, which is important in a chronic disease like NF1PN where there are high rates of recurrence after stopping therapy. In renew, across both cohorts, the median time on treatment was approaching two years, and some patients were on myrmidonet therapy for nearly four years at the time of the primary analysis.

Speaker Change: We believe Mirdamethamib's tolerability profile supports the potential for extended treatment duration.

Speaker Change: In Renew, across both cohorts, the median time on treatment was approaching two years, with some patients on modern med-net therapy for nearly four years at the time of the primary analysis.

James Cassidy: Nearly all patients that completed the treatment phase continued on therapy in the long-term follow-up portion of the study. The potential for modern medicine to enhance patient quality of life is also very meaningful. Pain is a common symptom in NF1PN, and current clinical practice recommendations indicate that this is a critical factor in treatment initiation decisions. Further, in many cases, the primary goal of treatment is improvement of pain-associated morbidity. Pain was the most commonly reported baseline disability in the RENEW trial.

Speaker Change: Nearly all patients that completed the treatment phase continued on therapy in the long-term follow-up portion of the study.

Speaker Change: The potential for modern medicine to enhance patient quality of life is also very meaningful.

James Cassidy: So it's significant that both adults and children, including those with the most ability to take in pain, supported early, sustained, and clinically significant reductions in pain severity and pain interference over the course of metamethamphetamine treatment. In Renew, children and caregiver reports were highly positive in this regard, with maximum acceptability scores for ease of swallowing and willingness to continue to take the dispersible tablet.

Speaker Change: In Renew, children and caregiver reports were highly positive in this regard, with maximum acceptability scores for ease of swallowing and willingness to continue to take the dispersible tablet.

James Cassidy: The totality of the new data reinforces our belief that MIRMA-MECNIM can address strong desire amongst both physicians and patients for a new therapy that offers robust tumor and symptomatic control, a manageable safety profile, and a convenient dosing regimen, all of which we expect will enable patients to remain on therapy for an extended period of time. Looking ahead, we are making meaningful progress advancing the method towards potential regulatory approval in 2025. Nodometinib has been granted Orphan Drug designation by both the FDA and the European Commission, and the FDA also granted Fast-Track and Rare Pediatric Disease designations for NF1PN.

Speaker Change: The totality of the new data reinforces our belief that Mimumetnu can address strong desire amongst both physicians and patients.

James Cassidy: We completed our NDA submission to the AFT at the end of June, and we anticipate announcing our PDUFA date in the coming weeks. We're also on track to complete the submission of our European marketing authorisation within this half. In addition, new results will continue to be showcased at upcoming medical congresses, and we expect the results to be published in a peer-reviewed journal later this year. Now, Frank Perier, our Chief Financial Officer, will discuss our second quarter financial results. Frank.

Speaker Change: We completed our NDA submission to the AFTA at the end of June , and we anticipate announcing our PDUFA date in the coming weeks.

Speaker Change: And now, Frank Perier, our Chief Financial Officer, will discuss our second quarter financial results. Frank?

Francis Perier: I'll now summarize a few highlights from our second quarter 2024 financial results. Starting with revenues, we recorded $40.2 million of Oxivio Net Product Revenue in the second quarter. This brings our 2024 year-to-date OXIVIO net product revenue to $61.2 million. Our total operating expenses increased compared to the second quarter and the first half of 2023, driven by commercial activities to support the U.S. launch of Oxibio and the anticipated U.S. launch of Myriad Medinib in both adults and children with NF1P.

Frank Perier: This brings our 2024 Year-to-Date OXIVIO Net Product Revenue to $61.2 million.

Francis Perier: We have a strong balance sheet supporting our clear path to profitability, with $522 million in cash, cash equivalents, and marketable securities as of the end of the second quarter. Lastly, we have a durable operating plan designed to fund multiple global product launches and enable the continued investment in expansion opportunities across our pipeline. With that, I'll hand the call back over to Saqib.

Frank Perier: Lastly, we have a durable operating plan designed to fund multiple global product launches and to enable the continued investment and expansion opportunities across our pipeline.

Frank Perier: With that, I'll hand the call back over to Saqib.

Saqib Islam: As we discussed this morning, we are very pleased with the continued strong momentum of our U.S. launch of Oncivio for adults with Desmond tumors and are working with urgency to bring miradomentinib to children and adults with NF1PM. In parallel with these commercial efforts, we are enthusiastic about our emerging portfolio.

Saqib Islam: Thank you, Frank. As we've discussed this morning, we are very pleased with the continued strong momentum of our U.S. launch of OXIVIO for adults with Desmond tumors and are working with urgency to bring miradomentinib to children and adults with NF1PN.

Saqib Islam: In parallel with these commercial efforts, we are enthusiastic about our emerging portfolio.

Saqib Islam: Nirogastrostat is being studied in a phase two trial in ovarian granulosa cell tumors, which is fully enrolled. These tumors account for approximately 5% of all ovarian cancers, and like desmoid tumors, this is a meaningful patient population for which there are no FDA-approved therapies. In multiple myeloma, we've established clinical proof of concept for nirengastastat in combination settings with several BCMA-directed agents and are continuing to collaborate with a number of industry and academic partners to further this strategy.

Saqib Islam: Nirogastastat is being studied in a Phase II trial in ovarian granulosa cell tumors, which is fully enrolled. These tumors account for approximately 5% of all ovarian cancers. And like desmoid tumors, this is a meaningful patient population for which there are no FDA-approved therapies.

Saqib Islam: In multiple myeloma, we've established clinical proof of concept for nirengastastat in combination settings with several BCMA-directed agents and are continuing to collaborate with a number of industry and academic partners to further this strategy.

Saqib Islam: We're also pursuing expansion opportunities for mirror dimentives in several monotherapy and combination therapy settings. Promising data from a Phase I-II study of myrtimetinib in pediatric low-grade glioma were recently presented at the International Symposium on Pediatric Neuro-Oncology Meeting, and several combination studies are currently ongoing, including a trial with MAP-cures for nirafenib in advanced solid Brimboracinib is also being explored as a monotherapy in adults with a BRAF mutant solid tumor.

Saqib Islam: We're also pursuing expansion opportunities for Myrtimetinib in several monotherapy and combination therapy settings.

Saqib Islam: Promising data from a Phase I-II study of myrtimetinib in pediatric low-grade glioma were recently presented at the International Symposium on Pediatric Neuro-Oncology Meeting.

Saqib Islam: Brinvarafinib is also being explored as a monotherapy in adults with RAF mutant solid tumors and we're looking to confirm the efficacy signal we reported last year in the dose escalation study in several ongoing dose expansion cohorts.

Saqib Islam: And we're looking to confirm the efficacy signal we reported last year in the dose escalation study in several ongoing dose expansion cohorts. Additionally, SW682, our oral Tead inhibitor, is now in the clinic. This program is designed to treat tumors with hippo pathway mutations, which can occur in up to 10% of cancers, including mesothelioma and head and neck cancer. We believe that there is a meaningful opportunity with SW682 for Springworks to develop a novel medicine for these cancers.

Saqib Islam: Additionally, SW682, our oral Tead inhibitor, is now in the clinic.

Saqib Islam: Lastly, we are also advancing several internally discovered preclinical stage programs, and we look forward to sharing more about these efforts as they progress. To close, we are very pleased with our accomplishments in the first half of this year and have multiple milestones and data readouts ahead that we look forward to sharing. These include long-term follow-up data from our DEFY trial, which we believe will support the benefits of extended treatment durations with Oxivio in Desmoid 2.

Saqib Islam: These include long-term follow-up data from our DEFY trial, which we believe will support the benefits of extended treatment durations with Oxivio in desmoid tumors.

Saqib Islam: It also includes initial data from our phase two trial of nirogasistat in ovarian granulosa cell tumors, and we expect the full results of the renewed trial to be published in a peer-reviewed journal. Our focus for the remainder of the year will be to continue building on OXIVIO's momentum in the U.S. while working to bring this medicine to patients in Europe and other geographies, to advance our regulatory and commercial preparations for mirtimetinib in anticipation of serving patients with NF1PN in the US and Europe, and to progress our diversified emerging portfolio in an efficient manner.

Saqib Islam: It also includes initial data from our Phase II trial of nirogascicet in ovarian granulosa cell tumors. And we expect the full renewed trial results to be published in a peer-reviewed journal.

Saqib Islam: We are confident that our strong foundation will support our continued success as we deliver on our mission to change the lives of people suffering from devastating diseases. As always, I would like to thank the patients and investigators who participated in our clinical trials, our patient advocacy partners and collaborators, and our team of spring workers. We're now happy to take questions. Operator.

Saqib Islam: We are confident that our strong foundation will support our continued success as we deliver on our mission to change the lives of people suffering from devastating diseases.

Saqib Islam: As always, I would like to thank the patients and investigators who participated in our clinical trials, our patient advocacy partners and collaborators, and our team of Springworkers. We're now happy to take questions.

Unknown Executive: Thank you. We will now open the call for questions. To ask a question, please press star 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. As a reminder, please limit yourself to one question each. Please stand by while we compile the Q&A roster. Our first question will come from Anupam Rama at J.P. Morgan.

Speaker Change: Thank you. We will now open the call for questions. To ask a question, please press star 1 1 on your telephone and wait for your name to be announced.

Speaker Change: To withdraw your question, please press star 1 1 again. As a reminder, please limit yourself to one question each.

Speaker Change: Please stand by while we compile the Q&A roster.

Unknown Executive: Yeah, so thanks, Anupam. On the repeat versus new, obviously, we saw a good number of new prescribers in the initial months of the launch. As you'd expect, we've started to see repos coming in at a regular pace from these initial starts, but supported by continued new patient starts from new patients being acquired in the second quarter as well. As you would expect, the total proportion of business coming from existing patients versus new patient starts is increasing over time, and so that's a positive development.

Speaker Change: Our first question will come from Anupam Rama at J.P. Morgan.

Anupam Rama: Hey guys, congrats on all the progress.

Anupam Rama: Just a quick one from me. What are you seeing from both new prescribers and repeat prescribers for obsivio and in the early innings, the wait-and-watch population that's coming in to seek treatment for obsivio? Thanks so much.

Anupam Rama: Thanks Anupam, Bhavesh, I'll let you...

Anupam Rama: Yeah.

Speaker Change: So thanks Anupam. On the repeat versus new, obviously we saw a good amount of new prescribers in the initial months of the launch. As you'd expect, we've started to see refills coming in at a regular pace from these initial starts, but supported by continued new patient starts.

Speaker Change: from new patients being acquired in the second quarter as well.

Speaker Change: As you'd expect, the total proportion of business coming from

Unknown Executive: From a wait-and-watch perspective, we do know, obviously, that the proportion of the DT patient population is under active surveillance at any point in time. However, we do know that over 90 percent of these patients receive some active intervention during the course of their disease. Now, with the availability of the first and only FDA-approved treatment, the opportunity ahead of us, and supported by treatment guidelines that favor systemic therapy, supported by the positive experiences that patients and physicians are seeing with Obsivio in the early innings of the launch, the opportunity ahead of us is to try and drive faster treatment for these patients under active surveillance. And so we do expect the proportion of active surveillance patients to be dropping.

Speaker Change: However, we do know that over 90% of these patients receive some active intervention during the course of their disease. Now, with the availability of the first and only FDA approved treatment, the opportunity ahead of us

Speaker Change: And supported by treatment guidelines which favor systemic therapy, supported by the positive experiences that patients and physicians are seeing.

Speaker Change: without civil in the early innings of the launch.

Speaker Change: The opportunity ahead of us is to try and drive faster treatment for these patients under active surveillance. And so we do expect the proportion of active surveillance patients to be dropping over time.

Speaker Change: Thank you. One moment for our next question.

Unknown Executive: Thank you. One moment for our next question. Our next question comes from the line of Yaron Werber from TD Cowan.

Speaker Change: Our next question comes in the line of Yaron Werber from TD Cowen.

Unknown Executive: Great, thanks for taking my question. Congratulations also on a nice quarter. Maybe I have kind of a couple of interrelated questions.

Unknown Executive: One, can you just give us a sense of inventories for the quarter for Exivio? And then, secondly, just to follow on Anupam's question, one would imagine that the academic centers are probably the early adopters, and they're moving kind of quickly as patients are coming in to use Exivio. What are you seeing in the community? Maybe just give us a little bit of a sense of the breadth of usage, thank you

Yaron Werber: One would imagine that the academic centers are probably the early adopters and they're moving kind of quickly as patients are coming in to use OXIVIO. What are you seeing in the community? Maybe just give us a little bit of sense of kind of the breadth of usage. Thank you.

Unknown Executive: Bhavesh, I'll turn to you again for that. Yeah, thank you. So from an inventory standpoint, the overall impact of inventory in the second quarter was minimal. The stocking levels were generally aligned with the demand that we're seeing. And similar to prior quarters, inventory was not a key driver of performance this quarter.

Yaron Werber: Bhavesh, I'll turn to you again for that. Yeah, thank you.

Speaker Change: So from an inventory standpoint, the overall impact of inventory in the second quarter was minimal. The stocking levels were generally aligned with the demand that we're seeing, and similar to prior quarters, inventory was not a key driver of performance this quarter.

Unknown Executive: From a community dynamic perspective, first of all, I'll say that, as we said in our prepared comments, there is a deeper pool of patients overall than we originally estimated. And we started to break into this aggregate pool of patients that is up to greater than 7,000 actively managed patients. We are, as you highlighted, pleased with the update in the Centers of Excellence. We saw breadth of prescribing in the early months of launch.

Speaker Change: There is a deeper pool of patients overall than we originally estimated and we started to break into this aggregate pool of patients that are of greater than 7,000 actively managed patients.

Speaker Change: We're, as you highlighted, we're pleased with the update in the Centers of Excellence. We saw breadth of prescribing in the early months of launch. We saw depth of prescribing in the second quarter.

Unknown Executive: We saw depth of prescribing in the second quarter. Specifically, addressing your question about community, we've started to see good adoption in the community centers, where we continue to drive breadth, but we still have an opportunity, right? With the broad pool of patients, we have an opportunity both to continue to drive breadth of prescribing and also those who experience, who do prescribe Oxivio, to drive depth of prescribing. Now, I'll highlight a couple of things in that regard.

Unknown Executive: First of all, our ability to be in the right place at the right time for these community clinics has been significantly enhanced by the availability of DesmoTumor-specific ICD-10 codes. And so we're able to direct our sales team to be in those clinics when a patient is available for treatment. And then secondly, the educational efforts that we're driving both around the availability of Oxibio as the first and only treatment option for DesmoTumor patients, but also treatment guidelines that do favor systemic therapy, give us confidence in the ability for us to penetrate that community sector.

Speaker Change: by the availability of the desmo-tumor specific ICD-10 codes. And so we're able to direct our sales team to be in those clinics when a patient is available for treatment.

Speaker Change: And then secondly, the educational efforts that we're driving, both...

Speaker Change: Treatment Option for Desmond Tumor Patients, but also treatment guidelines which do favor systemic therapy gives us confidence in the ability for us to drive depth in that community segment as well.

Unknown Executive: Thank you. One moment for our next question. Our next question comes from the line of Corinne Johnson from Goldman Sachs.

Unknown Executive: Good morning, guys. I guess you've talked a little bit about having some more visibility into this patient population, given the ICD-10 codes, and potentially, as you kind of move to these blister packs in the forward, I guess, as you look at that, where have you identified the pockets where you see kind of the greatest opportunity for near and intermediate term growth? And what are you doing tactically to reach that patient population and keep them on therapy?

Speaker Change: Good morning, guys. I guess you've talked a little bit about having more visibility on this patient population, given the ICD-10 codes, and potentially as you kind of move to these blister packs in the forward. I guess, as you look at that, where have you identified the pockets where you see the greatest opportunity for near and intermediate-term growth? And what are you doing tactically to reach that patient population and keep them on therapy? And then I did want to ask also on Myrna Madnib, maybe with the launch next year, where do you see kind of like the low-hanging fruit with respect to initial adoption?

Unknown Executive: And then I did want to ask you also about Myrna Madnib, maybe with the launch next year, where you see kind of like the low hanging fruit with respect to additional initial adoption, and how should we think about the trajectory of the early launch compared to what you've accomplished here with Exibio?

Speaker Change: And how should we think about the trajectory of the early launch compared to what you've accomplished here with Exibio?

Unknown Executive: Thanks, Corinne, for the series of questions, but we're going to try and answer all of them, I think as we think of Mere Demand News. We view that opportunity as quite meaningful. And as I think of Lohing and Truth, you know, I think we're very comfortable saying that this is an opportunity that is actually at least as large as what we see in test point tumors. And that's driven by a number of factors.

Speaker Change: Thanks, Corinne, for the series of questions, but we're going to try and answer all of them. I think as we think of...

Speaker Change: Myrna Matnew

Speaker Change: We view that opportunity as actually quite meaningful, and as I think of Lowing and Truth, you know, I think we're

Myrna Matnew: Very comfortable saying that this is an opportunity that is actually at least as large as what we see in test point tumors.

Unknown Executive: One, by the size of the patient population, right? We talked about 40,000 patients in the US and a proportionate number outside the US. And a third of those are, excuse me, a quarter of those are pediatric, and three quarters of those are adults. So, the opportunity for us to have a best in class treatment for pediatric patients and a first in class treatment for adults, we think gives us a meaningful target. Second, the physicians in this space, even in the pediatric setting, believe that their patients are not being served as broadly as they could be.

Myrna Matnew: And that's driven by a number of factors, one, by the size of the patient population, right? We talked about 40,000 patients in the U.S. and a proportionate number outside the U.S.

Myrna Matnew: Second, the physicians in this space actually themselves, even in the pediatric setting, believe that their patients are not being served as broadly as they could be. And so we think there's an opportunity there.

Unknown Executive: And so we think there's an opportunity there. And third, you can use Cosalugo revenues, which now run at a rate just in the pediatric setting of about 500 million dollars annually, as a proxy for the opportunity just in that one quarter of the market. And, you know, as you know, we're filing for both adults, and so we think the opportunity, you know, beyond, I think, low hanging fruit implies that it's all easy. None of it is. But you've got a medicine that people are waiting for an opportunity that is sizable, and data that we believe supports a potentially best in class profile for this disease.

Myrna Matnew: implies that it's all easy, none of it is, but you've got...

Myrna Matnew: A Medicine.

Unknown Executive: Yeah, no, I just reiterate a couple of points. First and foremost, we're fortunate to have, with Oxivio, to be in a position of delivering a drug with transformative benefit to desmotumor patients, right? That is the foundation for the high awareness we have, the high satisfaction that we shared in the prepared comments, as well as the strong preference that we see amongst prescribers and patients, supported by broad access by the payer community.

Myrna Matnew: That is the foundation for the high awareness we have, the high satisfaction that we shared in the prepared comments, as well as the strong preference that we see amongst prescribers and patients, supported by broad access.

Unknown Executive: So with just seven months on the market, we've become the systemic standard of care and the most prescribed systemic therapy for adult patients with desmotumors. And so the opportunity for us is to continue to drive depth within the Centers of Excellence, as well as drive depth and breadth in the community segment. As I mentioned before, with the large pool of 7,000, more than 7,000 actively managed patients, we do see that we have a significant opportunity ahead of us to see continued growth for us.

Myrna Matnew: by the payer community. So with just seven months on the market, we've become the systemic standard of care, and the most prescribed systemic therapy for adult patients with desmoid tumors. And so the opportunity for us is to continue to drive depth within the

Unknown Executive: One moment for our next question. Our next question comes from the line of Peter Lawson from Barclays.

Myrna Matnew: Thank you.

Unknown Executive: Yeah, thanks for the question, Peter. I think, you know, we aren't seeing any, you know, exceptional discontinuations. It's what we've expected from the DEFY study. And I think that gives us confidence going into, you know, not just the third quarter but the fourth quarter as well. So I think that the trend holds well, and as Bhavesh highlighted, we think the patient pool is actually deeper than what we had originally estimated.

Speaker Change: Great. Thanks. Thanks for taking the questions. Thanks for the update as well, and congrats on the progress. The first question is really just about the patient trends, how they've been looking month after month.

Speaker Change: Yeah, thanks for the question, Peter. I think, you know, we aren't seeing any, you know, exceptional discontinuations. It's what we've what we would have expected from the DEFY study. And I think that gives us

Speaker Change: Confidence going into, you know, not just the third quarter, but the fourth quarter as well.

Unknown Executive: And I think that portends well for the aggregate opportunity here. Fundamentally, what we are perhaps most excited about is the feedback that we're getting. You've got patients seeing deep, immediate, and persistent benefits in their pain, which is causing them to want to get on therapy and want to stay on therapy. So we believe that the opportunity here continues to be sizeable.

Speaker Change: Subs by www.zeoranger.co.uk

Unknown Executive: Our next question comes from the line of Michael Schmidt from Guggenheim. Hey guys, good morning, and congrats on

Speaker Change: Our next question comes from the line of Michael Schmidt from Guggenheim.

Unknown Executive: Hey guys, good morning and congratulations on a strong second quarter result. Just a follow-up on Oxivio, as we think about the third quarter here coming up, some other products sometimes experience seasonality over the summer months. Is that something you may expect as well with Oxivio? And then a follow-up on Mirdametnib, as we think about the launch next year, obviously, you have a product on the market already. Do you expect initial switching from Koselugo over to Mirdametnib, or would you expect a predominantly penetration into the currently untreated patients with NFS as we think about that next year?

Unknown Executive: Thanks so much.

Speaker Change: Is that something you may expect as well with OXIVIO?

Speaker Change: And then a follow-up on Murder, Madness as we think about the launch next year.

Speaker Change: Obviously, you have already a product on the market. Do you expect initial switching from COSELUGO over to MRDA MedNib, or would you expect predominantly penetration into currently untreated patients with NF1?

Unknown Executive: Yeah, I don't think that we're immune to seasonality, like we see in many other products. So, you know, I would expect to see some seasonality in the summer months, but obviously, as we've said from the outset, we think the pool is deep, and we think the opportunity is significant.

Speaker Change: So, you know, I would expect to see some seasonality in the summer months.

Speaker Change: But obviously, you know, as we've said, you know, from the outset, we think the pool is deep, and we think the opportunity is significant. Badreddin? Yeah, so with respect to our opportunity within NF1PN for myriad of maintenance, I'll remind you that our NDA filing is for both pediatric and adult patients, the latter of whom represent three-quarters of the market and do not have.

Unknown Executive: Yeah, so with respect to our opportunity within NF1PN for mirror-dependent, I'll remind you that our NDA filing is for both pediatric and adult patients, the latter of whom represent three quarters of the market and do not have unapproved therapy. So we think there's quite a bit of white space there with respect to being able to serve patients who are previously untreated. Within the pediatric population, I think there will certainly be some patients who have been treated experienced over the years that are seeking their next line of therapy.

Badreddin Idrees: White Space there with respect to being able to serve patients who are previously untreated within the pediatric population I think there will certainly be some patients who have been

Unknown Executive: But our market research shows that that market is minimally penetrated as well with respect to systemic therapy, so we think there are a significant number of pediatric patients who are also looking for their first systemic therapy option when mirror-dependent becomes available.

Badreddin Idrees: treatment experience over the years that are seeking their next line of therapy. But our market research shows that that market is minimally penetrated as well with respect to systemic therapy. So we think there's a significant number of pediatric patients who are also looking for their first systemic therapy option when Myriad Abandonment becomes available.

Unknown Executive: One moment for our next question. Our last question will come from the line of Alec Stranahan from Bank of America.

Unknown Executive: Hey guys, thanks for taking my question and congrats from us on the strong print. Any framing you can provide around the focus of the longer-term follow-up data from DeFi later this year? And maybe one quick one if I can sneak it in. Is your expectation that you will receive an accelerated review from Mirta Metnib? Just to clarify, thank you.

Speaker Change: Hey guys, thanks for taking my question and congrats from us on the strong print.

Unknown Executive: Sure, so with respect to the longer-term follow-up data, Alec, I'll remind you that at the time of our primary analysis, the median time on treatment for patients that were randomized to the nirogasistat arm was just under two years, and the majority of those patients were still remaining on therapy. And so, what we hope to be able to share an update on later this year is certainly a more mature median time on treatment figure for nirogasistat-treated patients, as well as the trends that we see in terms of responses, how they evolve over time, and the benefits that we are seeing with a longer-dated data cut on patient-reported outcomes as well.

Speaker Change: Thank you, Alec. I'll turn it back to you.

Speaker Change: Sure. So with respect to the longer term follow up data, Alec, I'll remind you that at the time of our

Speaker Change: primary analysis, the median time on treatment for patients that were randomized to the nirogasistat arm was just under two years, and the majority of those patients were remaining on therapy. And so what we hope to be able to share an update on later this year is certainly a more mature median time on treatment figure for nirogasistat-treated patients, as well as the trends that we see in terms of

Speaker Change: Responses, how they evolve over time.

Unknown Executive: So that's what we're gearing up to be able to share. And I'll remind you that in phase one and phase two, our median time on treatment was over four years in each of those studies. So there's the opportunity to really present longer term.

Unknown Executive: Thank you. With respect to any expectations on review timing and review designations for the mere demented filing, we have not given any guidance on that topic. We'll be in a position to receive the PDUFA date from FDA about 60 days from filing, so that'll be some time in place.

Unknown Executive: Thank you. This concludes today's call. Thank you for joining. You may now disconnect. Thank you. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?? ?? ?? ?? ??

Speaker Change: Thank you. This concludes today's call. Thank you for joining. You may now disconnect.

Speaker Change: All the Best..

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