Q2 2024 Day One Biopharmaceuticals Inc Earnings Call

July 30, 2024

Later, we will conduct a question and answer session. Please be advised that this conference call is being recorded I would now like to turn the call over to Joey Perone Senior Vice President of Finance and Investor Relations. Thank you you may begin.

Operator: Participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please be advised that this conference call is being recorded. I would now like to turn the call over to Joey Perrone, Senior Vice President of Finance and Investor Relations. Thank you. You may begin.

Speaker Change: Thank you Hello, everyone and good morning.

Joey Perrone: Thank you. Hello, everyone, and good morning. Welcome to Day One's Q2 2024 Financial and Operating Results Conference Call. Earlier this morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release and the slides to accompany this conference call on the Investors and Media section of our website at www.dayonebio.com. An audio webcast with the corresponding slides is also available on our website. Before we get started, I'd like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements as outlined on slide 2. Actual events and results could differ materially from those expressed or implied by any forward-looking statement.

Speaker Change: Welcome to day, one second quarter, 2024 financial and operating results conference call.

Speaker Change: Earlier. This morning, we issued a press release press release, which outlines the topics we plan to discuss today you can access the press release and the slides to accompany this conference call on the investors and media section of our website at Www Dot day, one buyout dot com, an audio webcast with a corresponding slides is also available.

Speaker Change: <unk> on our website.

Before we get started I'd like to remind everyone that some of the statements that we make on this call and information presented in this slide deck include forward looking statements is outlined on slide two.

Speaker Change: Actual events and results could differ materially from those expressed or implied by any forward looking statements.

Speaker Change: We encourage you to review the various risks uncertainties and other factors included in our most recent filings with the SEC.

Joey Perrone: We encourage you to review the various risks, uncertainties, and other factors included in our most recent filings with the SEC and any other future filings that we may make with the SEC. These forward-looking statements are based on our current estimates and various assumptions and reflect management's intentions, beliefs, and expectations about future events, strategies, competition, products, and product candidates, operating plans, and performance. You are cautioned not to place any undue reliance on these forward-looking statements, and except as required by law, Day One disclaims any obligation to update such statements. Today, I'm joined by Dr. Jeremy Bender, Chief Executive Officer, Lauren Merendino, Chief Commercial Officer, Dr. Samuel Blackman, Co-founder and Head of R&D, and Charles York, Chief Operating and Financial Officer. I will now turn the call over to Jeremy.

Speaker Change: The other future filings that we may make with the SEC.

Speaker Change: These forward looking statements are based on our current estimates and various assumptions and reflect management's intentions beliefs and expectations about future events strategies competition products and product candidates.

Speaker Change: Operating plans and performance you are cautioned not to place any undue reliance on these forward looking statements.

Speaker Change: And except as required by law. They wanted to disclaims any obligation to update such statements.

Speaker Change: Today I'm joined by Dr. Jeremy Bender, Chief Executive Officer, Laurie <unk>, Chief Commercial officer, Dr. Sam low Blackman co founder and head of R&D, and Charles Horn, Chief operating and financial Officer, I will now turn the call over to Jeremy.

Jeremy Bender: Thank you Joey and thanks to all of you for joining this call.

Jeremy Bender: Thank you, Joey, and thanks to all of you for joining this call. This is the first time we are reporting earnings with a new medicine on the market. We had an outstanding Q2 on multiple fronts, and we are excited to tell you about our progress building Day One. 2024 has been an extraordinary year for us. I'm so proud of the Day One team, each of whom have been tightly focused on our mission and on executing on our priorities, specifically launching OJEMDA and advancing and expanding our pipeline of targeted therapeutics for people of all ages. Day One was created to address the innovation gap between pediatric and adult patients living with cancer and other life-threatening diseases.

Speaker Change: This is the first time, we're reporting earnings with a new medicine on the market.

Speaker Change: We had an outstanding second quarter on multiple fronts and we are excited to tell you about our progress building day one.

Speaker Change: 2024 has been an extraordinary year for us.

Speaker Change: I'm so proud of the day, one team each of whom have been tightly focused on our mission and on executing on our priorities.

Speaker Change: Specifically launching of agenda, and advancing and expanding our pipeline of targeted therapeutics for people of all ages.

Speaker Change: Day, one was created to address the innovation gap between pediatric and adult patients living with cancer and other life threatening diseases.

Speaker Change: In April 2020 for the U S food and drug administration approved <unk> the brand name for <unk> for the treatment of relapsed or refractory pediatric low grade glioma or <unk> in patients six months of age and older harboring BRAF fusion rearrangement or BRAF <unk> 600.

Jeremy Bender: In April 2024, the US Food and Drug Administration approved OJEMDA, the brand name for tovorafenib, for the treatment of relapsed or refractory pediatric low-grade glioma, or PLGG, in patients six months of age and older harboring a BRAF fusion rearrangement or BRAF V600 mutation. With this achievement, Day One became a commercial company. Our team, including clinical, regulatory, manufacturing, medical, and commercial, was well prepared to launch our first new medicine. As you will see from our Q2 earnings, we are beginning to see those efforts yield results. The interest in OJEMDA we have observed post-approval demonstrates the significant need that exists for new medicines for PLGG patients. PLGG is the most common brain tumor in children. Until OJEMDA's approval, no approved therapies were available for the majority of patients in the relapsed refractory setting, and there has been no clear standard of care for these patients.

Speaker Change: Mutation.

Speaker Change: With this achievement day, one became a commercial company.

Speaker Change: Our team, including clinical regulatory manufacturing medical and commercial was well prepared to launch our first new medicine.

Speaker Change: As you will see from our Q2 earnings we are beginning to see those efforts yield results the.

Speaker Change: The interest in our agenda, we have observed post approval demonstrates the significant need that exists for new medicines for <unk> patients.

Speaker Change: <unk> is the most common brain tumor in children.

Jim: Hello, Jim This approval no approved therapies were available for the majority of patients in the relapsed refractory setting and there has been no clear standard of care for these patients.

Jim: Our early launch progress suggests that physicians and families are excited to have agenda as a treatment option for this chronic.

Jeremy Bender: Our early launch progress suggests that physicians and families are excited to have OJEMDA as a treatment option for this chronic and relentless disease. I'm excited to announce very strong early results from our launch. Our net revenue for Q2 was $8.2 million. As Lauren will discuss in more detail, significant new patient starts and the rapid transition of expanded access patients to OJEMDA drove these results and set us on a path to future growth. Day One's long-term success will require continued value creation through execution of the commercial opportunity for OJEMDA in relapsed refractory PLGG and through progress advancing our broader pipeline. Our global frontline PLGG trial, FIREFLY-2, continues to enroll and is now open at 100 sites.

Jim: <unk> disease.

Jim: I am excited to announce very strong early results from our launch our.

Speaker Change: Our net revenue for Q2 was $8 $2 million.

Speaker Change: As Laurie will discuss in more detail Cigna.

Laurie: Significant new patient starts and the rapid transition of expanded access patients to agenda drove these results and set us on a path to future growth.

Laurie: <unk> long term success will require continued value creation through execution of the commercial opportunity for agenda in relapsed refractory <unk> and through progress advancing our broader pipeline.

Laurie: Our global frontline <unk> trial Firefly two continues to enroll and is now open at 100 sites.

Laurie: The opportunity to demonstrate clinical benefit for <unk> in frontline <unk> is a critical next step for the program.

Jeremy Bender: The opportunity to demonstrate clinical benefit for tovorafenib in frontline PLGG is a critical next step for the program and for our goal to bring new medicines to patients. We also expanded our pipeline in Q2 with an exciting new program. In June, we in-licensed DAY301, a potential first-in-class clinical-stage antibody drug conjugate targeting PTK7. Our experienced clinical and regulatory team will develop DAY301 in adult and pediatric solid tumor patients. The DAY301 IND has been cleared by the FDA, and we are on track to dose the first patient in our Phase 1 trial of DAY301 in adults by the end of this year or early next year. Finally, we have significantly strengthened our financial position throughout 2024. In May, we brought in approximately $100 million in net cash through the sale of a priority review voucher.

Laurie: And for our goal to bring new medicines to patients.

Laurie: We also expanded our pipeline in the second quarter with an exciting new program.

Laurie: In June we in licensed <unk> hundred one a potential first in class clinical stage antibody drug conjugate targeting PTK seven.

Laurie: Our experienced clinical and regulatory team will develop day 301 in adult and pediatric solid tumor patients.

Laurie: <unk> hundred one IND has been cleared by the FDA and we are on track to dose the first patient in our phase one trial of <unk> hundred one in adults by the end of this year or early next year.

Laurie: Finally, we have significantly strengthened our financial position throughout 2024.

Laurie: In May we brought in approximately $100 million and net cash through the sale of our priority review voucher.

Laurie: Last week, we established an ex U S partnership for agenda with Ipsen that includes approximately $111 million in upfront payments and this morning, we announced an oversubscribed private placement financing providing day, one with an additional $175 million.

Jeremy Bender: Last week, we established an ex-US partnership for OJEMDA with Ipsen that includes approximately $111 million in upfront payments. This morning, we announced an oversubscribed private placement financing providing Day One with an additional $175 million. We have ample capital to fund our growth and our program investments, and we look forward to continued future progress and updates throughout 2024 and beyond. I'll now turn the call over to Lauren.

Laurie: We have ample capital to fund our growth and our program investments and we look forward to continued future progress updates throughout 2024 and beyond.

Laurie: I'll now turn the call over to Lauren.

Lauren: Thank you Jeremy.

Lauren: While it's still very early days of gender launch is off to an extremely strong start.

Lauren Merendino: Thank you, Jeremy. While it's still very early days, OJEMDA launch is off to an extremely strong start. Our pre-launch planning prepared us to move quickly to generate considerable new patient demand, transition our EAP patients rapidly, and enable a favorable response from payers. These three drivers resulted in strong revenue for the first two months of launch, and I'm pleased to share some of the details of our performance. As Jeremy mentioned, in Q2, we delivered $8.2 million in net product revenue, about $6 million of which is patient demand. The remainder is specialty pharmacy inventory. This performance is a testament to the dedication of our cross-functional team and to excellent execution across the board. One example of this is getting our product packaged into the channel and shipping to patients just 11 business days post-approval.

Lauren: Our prelaunch planning prepared us to move quickly to generate considerable new patient demand.

Lauren: Transition, our EAP patients rapidly and.

Lauren: And enable a favorable response from payers.

Speaker Change: These three drivers resulted in strong revenue for the first two months of launch and I am pleased to share some of the details of our performance.

Speaker Change: As Jeremy mentioned in Q2, we delivered $8 2 million in net product revenue about $6 million of which is patient demand.

Jeremy Bender: The remainder is specialty pharmacy inventory.

Jeremy Bender: This performance is a testament to the dedication of our cross functional team and excellent execution across the board.

Jeremy Bender: One example of this is getting our product package into the channel and shipping to patients just 11 business days post approval.

Speaker Change: From a commercial perspective, we moved quickly to communicate our approval with live engagements with over 90% of our.

Lauren Merendino: From a commercial perspective, we moved quickly to communicate our approval with live engagements with over 90% of our 200 target accounts. On these calls, we ensured that prescribers were aware of our approval, familiar with OJEMDA's efficacy, safety, and dosing, and aware of how to expedite patient access to OJEMDA by leveraging our specialty pharmacy network and patient support programs. With the majority of physicians aware of OJEMDA prior to approval, it was easy for them to understand the benefits that OJEMDA delivers for patients. It was important for our sales team to update their knowledge with the latest data, safety, and dosing from our label. These messages were well-received, with many physicians expressing gratitude for a new option for children with PLGG.

Speaker Change: 200 target accounts.

Speaker Change: On these calls we ensured that prescribers were aware of our approval for.

Speaker Change: <unk> familiar with the agenda as efficacy safety and dosing.

Speaker Change: And aware of how to expedite patient access to agenda by leveraging our specialty pharmacy network and patient support programs.

Speaker Change: With the majority of physicians aware of agenda prior to approval. It was easy for them to understand the benefits that agenda delivered for patients.

Speaker Change: It was important for our sales team to update their knowledge the delay the data safety and dosing from our label.

Speaker Change: These messages were well received with many physicians expressing gratitude for a new option for children with <unk>.

Speaker Change: In addition to our work with HCP.

Speaker Change: The efforts of our payer team, both pre and post launch.

Lauren Merendino: In addition to our work with HCPs, the efforts of our payer team, both pre- and post-launch, to educate payers on the unmet needs of PLGG patients and the science behind OJEMDA were an important part of enabling early access, which I'll talk more about in a moment. First, let's talk about the most important measure of our impact, patients. We ended the quarter with 157 patients initiated on OJEMDA, including both those on paid drug or on one of our commercial free drug programs. This demand was driven almost equally by patients transitioning from our early access program or EAP and patients newly starting on OJEMDA. There were 84 patients who converted to commercial drugs from our EAP, which was opened after the enrollment in FIREFLY-1 was completed.

Speaker Change: Keep payors on the unmet needs of <unk> patients and the science behind the agenda. We are an important part of enabling early access, which I'll talk more about in a moment.

Speaker Change: First let's talk about the most important measure of our impact.

Speaker Change: <unk>.

Speaker Change: We ended the quarter with 157 patients initiated on agenda, including both those on paid drug or on one of our commercial free drug programs.

Speaker Change: This demand was driven almost equally by patients transitioning from our early access program for EAP.

Speaker Change: And patients newly starting an agenda.

There were 84 patients who converted to commercial drug from our EAP, which was opened after the enrollment and Firefly was completed.

Speaker Change: The efficiency of our process and the speed of payer approvals enabled us to transition most EAP patients in may.

Lauren Merendino: The efficiency of our process and the speed of payer approvals enabled us to transition most EAP patients in May, faster than initially expected. It's important to note that the large majority of EAP patients were transitioned this quarter, with only a handful of patients remaining to transition in Q3. Moving forward, new patient starts will be the primary driver of incremental demand. We had 73 new patients start OJEMDA in Q2, representing strong underlying demand. Two-thirds of the physicians starting these new patients had no prior experience with OJEMDA through clinical trials or early access, demonstrating the broad HCP awareness of the product and the unmet need for PLGG patients. This quarter, over 100 HCPs prescribed OJEMDA. This is an excellent start, but there remains tremendous potential to expand our prescriber base.

Speaker Change: After than initially expected.

Speaker Change: It's important to note that the large majority of EAP patients were transitioned this quarter with only a handful of patients remaining to transition in Q3.

Speaker Change: So moving forward new patient starts will be the primary driver of incremental demand.

Speaker Change: We had 73 new patients start on gender in Q2, representing strong underlying demand.

Speaker Change: Two thirds of the physicians starting these new patients had no prior experience with agenda through clinical trials or early access.

Speaker Change: Demonstrating the broad HCP awareness of the product and the unmet need for <unk> patients.

Speaker Change: Yes.

Speaker Change: This quarter over 100, Hcp's prescribed agenda.

Speaker Change: This is an excellent start.

Speaker Change: But there remains tremendous potential to expand our prescriber base.

Speaker Change: In the 200 accounts that treat 90% of the <unk> patients there are.

Lauren Merendino: In the 200 accounts that treat 90% of the PLGG patients, there are approximately 1,500 target prescribers. By expanding our pool of prescribers, more patients will be able to experience the benefits of OJEMDA in the future. Payers have been quick to respond to the needs of PLGG patients. As we expected, our payer mix is approximately 60% commercial and 40% Medicaid. Since it is still very early in launch, most commercial payers have not yet published policies for OJEMDA, which you can see here in the pie chart on the left. Medicaid coverage, however, has grown quickly, with 50% of covered lives now having OJEMDA covered to label. Across both payer types, we're seeing approval rates significantly higher than reported coverage, with over 80% of commercial patients and over 70% of Medicaid patients receiving approval for coverage.

Speaker Change: Approximately 1500 target prescribers.

Speaker Change: By expanding our pool of prescribers more patients will be able to experience the benefits of agenda in the future.

Speaker Change: Payers have been quick to respond to the needs of <unk> patients.

Speaker Change: As we expected our payer mix is approximately 60% commercial 40% Medicaid.

Speaker Change: Since it is still very early in launch most commercial payers have not yet published policies for our agenda, which you can see here in the Pie chart on the left.

Speaker Change: Medicaid coverage, however has grown quickly with 50% of covered lives now having agenda covered to label.

Speaker Change: Across both payer types, we're seeing approval rates significantly higher than reported coverage with over 80% of commercial patients and over 70% of Medicaid patients receiving approval for coverage.

Speaker Change: Overall, the response to agenda launch has been very positive with physicians expressing excitement about our product profile at our patient support programs and an openness to triangle agenda in the relapsed refractory <unk> patients.

Lauren Merendino: Overall, the response to OJEMDA launch has been very positive, with physicians expressing excitement about our product profile, and our patient support programs, and an openness to trying OJEMDA in their relapsed refractory PLGG patients. To continue our strong launch trajectory, we have three areas of focus. First, we must increase the breadth and depth of our prescriber base. Recent market research shows that over 80% of physicians surveyed intend to use OJEMDA in the future. For those physicians who have not written yet, increasing their confidence to get their first patient started on OJEMDA is critical. For those HCPs who have tried OJEMDA, expanding their use to multiple patients will be an important next step. Secondly, we want to establish OJEMDA as the first choice in second-line treatment of BRAF-altered PLGG patients.

Speaker Change: To continue our strong launch trajectory, we have three areas of focus.

Speaker Change: First we must increase the breadth and depth of our prescriber base.

Speaker Change: Recent market research shows that over 80% of physicians surveyed intend to use agenda in the future.

Speaker Change: So for those physicians, who have not written yet increasing their confidence to get their first patients started on our agenda is critical.

Speaker Change: For those <unk>, who have tried agenda expanding their use multiple patients will be an important next step.

Speaker Change: Secondly, we want to establish a agenda as the first choice in second line treatment of BRAF altered <unk> patients.

Speaker Change: Not surprisingly in the early weeks of launch we've seen a number of late line patients receiving agenda.

Lauren Merendino: Not surprisingly, in the early weeks of launch, we've seen a number of late-line patients receiving OJEMDA. As you can imagine, there are many existing patients who may have run through other options and are now in need of new treatment, and OJEMDA is a great choice for them. Over time, however, we want to increase the use of OJEMDA in patients in the second-line. With our compelling efficacy and safety profile and once-weekly dosing, we believe that OJEMDA can offer unique benefits to many of these patients. Finally, we're continuing to actively engage with payers to establish broad coverage for patients consistent with our label. While we are pleased with the current approval rates, we want to continue to move payers towards formalizing their coverage with a published coverage decision. This will help streamline the process for patient access in the future.

Speaker Change: As you can imagine there are many existing patients who may have run through other options and are now in need of new treatment and agenda is a great choice for them.

Speaker Change: Over time, however, we want to increase the use of agenda in patients in the second line.

Speaker Change: With our compelling efficacy and safety profile and once weekly dosing, we believe that agenda can offer unique benefits to many of these patients.

Speaker Change: And finally, we are continuing to actively engage with payers to establish broad coverage for patients consistent with our label.

Speaker Change: While we are pleased with the current approval rates, we want to continue to move payors towards formalizing their coverage with a published coverage decision. This.

Speaker Change: This will help streamline the process for patient access in the future.

Speaker Change: We're excited about the speed of our progress this quarter and the results confirm that there is a substantial and sustainable market and serving children with P. O T G.

Lauren Merendino: We're excited about the speed of our progress this quarter, and the results confirm that there is a substantial and sustainable market in serving children with PLGG. This is just the beginning, and we've been encouraged by the positive response from HCPs, patients, and payers. Our team continues to be energized by the promise of OJEMDA to make a difference in the lives of more patients challenged by PLGG. We're also excited about building the future of our company and potentially expanding our impact to other patients. For more on that, I'll turn it over to Sam for a pipeline update. Sam?

Speaker Change: This is just the beginning and we've been encouraged by the positive response from Hcp's patients and Payors.

Speaker Change: Our team continues to be energized by the promise of our agenda to make a difference in the lives of more patients challenge by P. L. G.

Speaker Change: We're also excited about building the future of our company and potentially expanding our impact to other patients.

Speaker Change: For more on that I will turn it over to Sam for a pipeline update.

Speaker Change: Sam.

Sam: Thanks, Laura and good morning, everyone I'm very excited to be able to provide some updates on our pipeline and programs.

Samuel Blackman: Thanks, Lauren, and good morning, everyone. I'm very excited to be able to provide some updates on our pipeline and programs. I'll start with our newest program, DAY301. As we announced last month, we in-licensed a potentially first-in-class antibody drug conjugate program from MabCare Therapeutics, which we've named DAY301. This molecule targets PTK7 or protein tyrosine kinase 7, which has been shown by multiple groups to be consistently and highly expressed on the cell surface of multiple adult and pediatric cancers. PTK7 is a pseudokinase, meaning it lacks catalytic activity. Because of its high degree of cell surface expression and internalization upon antibody binding, it makes for an important ADC target. There are multiple reasons why we're excited to add DAY301 to our pipeline.

Sam: I'll start with our newest program <unk> hundred one.

Sam: As we announced last month, we in license to potentially first in class antibody drug conjugate program from that pure therapeutics, which we've named <unk> hundred one.

Sam: This molecule targets PTK, seven or protein tyrosine kinase setting.

Sam: Which has been shown by multiple groups to be consistently in highly expressed on the cell surface of multiple adult and pediatric cancers.

Speaker Change: <unk> seven is a pseudo tyrosine kinase, mainly get lax catalytic activity.

Speaker Change: But because of its high degree of cell surface expression and internalization column antibody binding it makes for an important ADC target.

Speaker Change: There are multiple reasons why we are excited to add phase III of <unk> pipeline first and importantly, PTK seven has been clinically validated as an ADC target with first generation <unk> based ADC programs, showing antitumor activity in a variety of tumor types, including platinum resistant ovarian cancer triple.

Samuel Blackman: First, and importantly, PTK7 has been clinically validated as an ADC target, with first-generation auristatin-based ADC programs showing antitumor activity in a variety of tumor types, including platinum-resistant ovarian cancer, triple-negative breast cancer, and non-small cell lung cancer. We believe that a better-engineered next-generation ADC program has the potential to take full advantage of PTK7 as a target. Second, PTK7 has been shown to be highly expressed in various pediatric cancers that have seen little to no new drug development activity in the past 30 years, including neuroblastoma, rhabdomyosarcoma, and osteosarcoma. In keeping with the mission of Day One, we intend to develop DAY301 with equal intensity in adult and pediatric patients. Finally, we're excited about the properties that have been carefully engineered into this particular ADC.

Speaker Change: Negative breast cancer, and non small cell lung cancer.

Speaker Change: We believe that a better engineered next generation ADC program has the potential to take full advantage of <unk> seven as a target.

Second <unk>.

Speaker Change: <unk> seven has been shown to be highly expressed in various pediatric cancers.

Speaker Change: Seen little to no new drug development activity in the past 30 years, including Neuroblastoma Rhabdomyosarcoma osteosarcoma.

Speaker Change: In keeping with emission of day, one we intend to develop phase III, a one with equal intensity in adult and pediatric patients.

And finally, we're excited about the properties that have been carefully engineered into this particular ADC.

Speaker Change: <unk> hundred one is built around our proprietary monoclonal antibody.

Samuel Blackman: DAY301 is built around a proprietary monoclonal antibody coupled to a novel hydrophilic linker and exatecan payload. Preclinical studies have demonstrated the potential of this linker payload to overcome resistance to other topoisomerase inhibitors. Other features of DAY301 that made this program exciting include a comprehensive preclinical evaluation showing tumor regressions at tolerable doses in multiple patient-derived xenograft models, favorable stability for the ADC construct, and a large exposure-based therapeutic index based on data from cyno tox studies. With an IND cleared by the FDA, we're working hard towards operationalizing the Phase 1 study and plan to have the first patient dosed by the end of the year or shortly thereafter. Our initial clinical development plan outlined here leverages the tolerability seen in the GLP tox studies.

Speaker Change: Two a novel hydrophilic linker and exit you can payload.

Speaker Change: Preclinical studies have demonstrated the potential of this linker payload to overcome resistance to other topoisomerase inhibitors.

Speaker Change: Other features of <unk> hundred one that made this program exciting include a comprehensive preclinical evaluation showing tumor regressions at tolerable doses and multiple patient derived xenograft models.

Speaker Change: Favorable stability for the ADC construct and a large exposure base therapeutic index based on data from snow Tox studies.

Speaker Change: With an IND cleared by the FDA, we are working hard towards operational I think the phase one study and plan to have the first patient dosed by the end of the year or shortly thereafter.

Speaker Change: Our initial clinical development plan outlined here.

Speaker Change: Leverage is the tolerability as seen in the GOP Tox studies.

Speaker Change: We believe that the FDA approves starting dose puts us within one to three dose escalation steps of a dose level expected to be therapeutically relevant.

Samuel Blackman: We believe that the FDA-approved starting dose puts us within 1 to 3 dose escalation steps of a dose level expected to be therapeutically relevant. Following conversations with some of the premier Phase 1 clinical trial sites and investigators in the United States, we'll be focusing enrollment in dose escalation on tumor types known to have high PTK7 expression. In the Phase 2a dose expansion and optimization, we will likely select patients based on PTK7 expression and focus on indications where patients continue to have limited therapeutic options, including platinum-resistant ovarian cancers, squamous non-small cell lung cancer, esophageal squamous cell carcinoma, endometrial cancers, and others. The exact choice of indications for expansion cohorts will be determined based on data from the Phase 1 portion of the study, as well as an expanded analysis of PTK7 expression in tumor samples.

Speaker Change: Following conversations with some of the Premier Phase one clinical trial sites and investigators in the United States, we'll be focusing enrollment and dose escalation on tumor types are known to have high PTK seven expression.

Speaker Change: In the phase Iia dose expansion and optimization we.

Speaker Change: We will likely select patients based on PTK, seven expression and focus on indications where patients continue to have limited therapeutic options, including platinum resistant ovarian cancers witness non small cell lung cancer, esophageal squamous cell carcinoma, endometrial cancer and others.

The exact choice of indications for expansion cohorts will be determined.

Speaker Change: On data from the phase one portion of the study.

Speaker Change: As well as an expanded analysis of PTK seven expression in tumor samples.

Speaker Change: In keeping with the day, one approach to clinical development in parallel with a monotherapy dose expansion in adults, we will initiate the phase <unk> pediatric monotherapy dose confirmation study in tumor types with high PTK seven expression.

Samuel Blackman: In keeping with the Day One approach to clinical development, in parallel with the monotherapy dose expansion in adults. We will initiate a Phase 1b pediatric monotherapy dose confirmation study in tumor types with high PTK7 expression, leveraging the adult Phase 1 dose escalation data to allow us to start a pediatric study at a dose level that has been shown to have the potential for antitumor activity. We are very excited for the DAY301 program and look forward to providing additional updates in the quarters to come as the Phase 1 study progresses. Now turning to PLGG. Evaluation of data emerging from the FIREFLY-1 trial continues as patients move into long-term follow-up.

Speaker Change: Leveraging the adult phase one dose escalation data to allow us to start a pediatric study at a dose level that has been shown to have the potential for anti tumor activity.

Speaker Change: We are very excited for the day for your own program and look forward, providing additional updates in the quarters to come as the phase one study progresses.

Speaker Change: Yes.

Speaker Change: Now turning to PSEG.

Speaker Change: Evaluation of data emerging from the Firefly, one trial continues as patients move into long term follow up.

Speaker Change: We performed a data cut on May 10 of this year in order to gain an updated understanding of safety duration of response and durability of response.

Samuel Blackman: We performed a data cut on 10 May of this year in order to gain an updated understanding of safety, duration of response, and durability of response, and to support our post-marketing commitments around long-term safety. While we continue to clean and analyze the data to prepare for future presentations and publications, I can share with you that we're seeing, as expected, a long duration of treatment. For the 77 patients enrolled in arm one, which was a data set used to assess the efficacy of OJEMDA in our NDA, the median duration of treatment is now 23.7 months, with some patients being on treatment up to 32 months. Additional analyses will be presented at future medical conferences. We also had the opportunity to present data on the recovery and the rate of growth velocity at both ASCO and the International Symposium on Pediatric Neuro-Oncology meetings.

Speaker Change: And to support our post marketing commitments are on long term safety.

Speaker Change: While we continue to clean and analyze the data to prepare for future presentations and publications I can share with you that we're seeing as expected a long duration of treatment.

Speaker Change: For the 77 patients enrolled in arm, one which was the data set used to assess the efficacy of agenda in our NDA.

The median duration of treatment is now 23 seven months.

Speaker Change: With some patients being on treatment after 32 months.

Speaker Change: Additional analysis will be presented at future medical conferences.

Speaker Change: We also had the opportunity to present data on the recovery and the rate of growth velocity at both <unk> and the international Society for pediatric neuro oncology meetings.

Over the course of the past nine months, we've discussed the decrease in gross velocity observed in some patients treated with the agenda.

Samuel Blackman: Over the course of the past nine months, we've discussed the decrease in growth velocity observed in some patients treated with OJEMDA with experts within the pediatric neuro-oncology community, and their feedback has been both reassuring and valuable. There is a broad awareness that children with brain tumors, and children receiving anti-cancer therapy can have alterations in the rate of growth, and they've indicated that an understanding of the potential mechanism of growth velocity decrease and demonstration of recovery of growth velocity after holding the drug or after completion of treatment would be helpful for them in discussions with patients and families. The two presentations included a proposed reversible mechanism of action for the observed decrease in growth velocity, as well as data showing for the 15 patients where we had post-treatment height measurements, a 100% rate of recovery of growth velocity.

Speaker Change: With experts within the pediatric neuro oncology community and their feedback has been both reassuring and valuable.

Speaker Change: There's a broad awareness that children with brain tumors in children, receiving anti cancer therapy can have alterations in the rate of growth and they've indicated that an understanding of the potential mechanism of growth velocity decrease and demonstration of recovery of growth velocity after holding the drug or after completion of treatment would be helpful for them in <unk>.

Speaker Change: Discussions with patients in pounds.

Speaker Change: The two presentations included a proposed reversible mechanism of action for the observe decrease in growth velocity as.

Speaker Change: As well as data showing for the 15 patients where we had post treatment height measurements, a 100% rate of recovery of growth philosophy.

Speaker Change: Moreover, these presentations included data showing that 87% of patients had evidence of ketchup group and that no patient has deficiencies and bone integrity for fusion of growth. Please.

Samuel Blackman: Moreover, these presentations included data showing that 87% of patients had evidence of catch-up growth and that no patients had deficiencies in bone integrity or fusion of growth plates. The feedback from physicians was that these data were extremely helpful and reassuring. We will continue to monitor growth and development of patients on FIREFLY-1, and we have included routine bone age monitoring on and off treatment as part of the FIREFLY-2 trial. The FIREFLY-2 trial continues to make excellent progress in its accrual. We are now open at 100 sites worldwide and plan to add a few more sites. We held a successful investigator meeting last month in parallel with the ISPNO meeting in Philadelphia that was extremely well attended, and it was clear that enthusiasm for enrollment to the study is high.

Speaker Change: Feedback from physicians was that these data were extremely helpful and reassuring.

Speaker Change: We will continue to monitor growth and development of patients on Firefly, one and we have included routine bonita monitoring on and off treatment as part of the Firefly can trial.

Speaker Change: The Firefly two trial continues to make excellent progress and its accrual.

Speaker Change: We are now open at 100 sites worldwide and plan to add a few more sites.

Speaker Change: We held a successful investigator meeting last month in parallel with the ISP in one meeting in Philadelphia that was extremely well attended and it was clear that enthusiasm for enrollment to the study is high.

Speaker Change: In addition, we recently gained alignment with the FDA on some updates to Firefly tools that are being incorporated into a protocol amendment.

Samuel Blackman: In addition, we recently gained alignment with the FDA on some updates to FIREFLY-2 that are being incorporated into a protocol amendment. First, we'll be harmonizing the starting dose of tovorafenib in FIREFLY-2 to the FDA-approved starting dose for OJEMDA of 380 mg/m². Second, consistent with the accelerated approval of OJEMDA, which is based on overall response rate based on RAPNO-LGG criteria, we will be changing the response assessment criteria in FIREFLY-2 from RANO-LGG, which are the adult low-grade glioma criteria, to RAPNO-LGG, which is the appropriate criteria for pediatric low-grade glioma. Finally, we'll be adding monthly carboplatin to the list of acceptable standard of care regimens in the control arm in response to investigator feedback. This option may reduce the travel burden for patients and families enrolled on this trial.

Speaker Change: First we'll be harmonizing, the starting dose of October estimate and Firefly too to the FDA approved starting to us for agenda of 380 milligrams per meter square.

Speaker Change: Second consistent with the accelerated approval of agenda, which was based on overall response rate based on rational low grade glioma criteria.

Speaker Change: We will be changing the response assessment criteria and Firefly tool for Marino LPG, which are the adult lucrative we own the criteria to Raphael <unk>, which is the appropriate criteria for pediatric with great deal.

Speaker Change: And finally, we will be adding monthly carboplatin to the list of acceptable standard of care regimens and the control arm in response to investigator feedback.

Speaker Change: This option may reduce the travel burden for patients and families enrolled on this trial.

Speaker Change: Finally, I would like to mentioned both our work on our mechanism or Kim asserted as well as our work on developing a small molecule <unk> specific inhibitor in collaboration with sprint Biosciences.

Samuel Blackman: Finally, I'd like to mention both our work on our MEK inhibitor, pimasertib, as well as our work on developing a small molecule VRK1-specific inhibitor in collaboration with Sprint Biosciences. First, with regard to pimasertib, we've been evaluating the combination of tovorafenib and pimasertib in adolescent and adult patients with MAP kinase-driven solid tumors as part of a Phase 1b dose-ranging combination study that we call FIRELIGHT-1. Preclinical data from our group, as well as other companies, and academic groups, have shown the potential for therapeutic synergy when a type II RAF inhibitor is combined with a MEK inhibitor. This is a concept known as vertical MAP kinase pathway inhibition.

Speaker Change: First with regard to Tim assertive.

Speaker Change: <unk> been evaluating the combination of <unk> and Tim asserted in adolescent and adult patients with map kinase driven solid tumors as part of a phase <unk> dose ranging combination study that we call fire late one.

Speaker Change: Preclinical data from our group as well as other companies and academic groups have shown the potential for therapeutic synergy when a type two RAF inhibitor is combined with <unk> inhibitor. This is a concept known as vertical map kinase pathway inhibition.

Speaker Change: This is a different type of combination compared to typhon RAF inhibitor with a mechanism where the mechanisms that are in that combination as activity and offset some of the specific type one rep toxicities.

Samuel Blackman: This is a different type of combination compared to a type one RAF inhibitor with a MEK inhibitor, where the MEK inhibitor in that combination adds activity and offsets some of the specific type one RAF toxicities. Our trial was open to patients with a variety of RAS and RAF alterations. After evaluating a variety of dose combinations and schedules, we've concluded that the therapeutic synergy predicted by preclinical models was not evident at dose combinations that we believe would be tolerated over a sufficient period of time to lead to true clinical benefit for patients. While we did see responses in patients with multiple relapsed solid tumors with MAP kinase alterations, the frequency and duration of responses was not sufficient to give us confidence that the benefit risk profile of this combination would have a sufficiently high probability of success in subsequent clinical trials.

Speaker Change: Our trial was open to patients with a variety of bras and Iraq operations.

Speaker Change: After evaluating a variety of dose combinations and schedules.

Speaker Change: We've concluded that the therapeutic synergy predicted by preclinical models was not evident at dose combination that we believe will be tolerated over a sufficient period of time.

Speaker Change: So we need to shrink clinical benefit for patients.

Speaker Change: While we did see responses in patients with multiply relapsed solid tumors with no currently salt durations.

Speaker Change: <unk> and duration of responses was not sufficient to give us confidence that the benefit risk profile of this combination would have a sufficiently high probability of success in subsequent clinical trials.

Speaker Change: In addition, it was more challenging to identify relapsed and restaurant in patients than was predicted by the published molecular epidemiology data.

Samuel Blackman: In addition, it was more challenging to identify relapsed NRAS mutant patients than was predicted by the published molecular epidemiology data. We view this as a more limited opportunity than was necessary to support further investment. As a result, we've made the decision to close the pimasertib program and focus our development resources on DAY301. We look forward to sharing results from the study and our experience at a future medical meeting or in a future presentation or publication. We will also have updated data on tovorafenib as monotherapy in adolescent and adult RAF altered solid tumors at a medical meeting later this year. Finally, with regard to VRK1, we continue to make progress in our effort to identify a drug development candidate. To remind everyone, VRKs are a family of kinases that are critical for cell cycle entry, nuclear envelope formation, and regulation of various transcription factors.

Speaker Change: We view this as a more limited opportunities than was necessary to support further investment.

Speaker Change: As a result, we have made the decision to close the <unk> program and focus our development resources on dates for year one.

Speaker Change: We look forward to sharing the results from the study and our experience at a future medical meeting or in a future presentation or publication.

Speaker Change: We will also have updated data October <unk> as monotherapy in adolescent and adult rec altered solid tumors at a medical meeting later this year.

Speaker Change: And finally with regard to the RK one we continue to make progress in our effort to identify a trunk development candidate.

Speaker Change: To remind everyone VR case or a family of companies that are critical for cell cycle entry nuclear envelope formation in regulation at various transcription factors.

Speaker Change: <unk> and BLK to our peril logs recent data from multiple groups that reveals that <unk>. Two is epigenetic lease signings in two thirds of high grade Gliomas.

Samuel Blackman: VRK1 and VRK2 are paralogs. Recent data from multiple groups has revealed that VRK2 is epigenetically silenced in two-thirds of high-grade gliomas, as well as a significant proportion of low-grade gliomas and in a large percent of aggressive neuroblastomas, one of the more common solid tumors of childhood. A synthetic lethal interaction between VRK1 and VRK2 results in the sensitization of VRK2-silenced tumors to inhibition of VRK1 kinase activity, supporting VRK1 as a novel drug discovery target. We anticipate providing updates on our research program for VRK1 in 2025. To wrap up, the past 12 months in their totality have been both remarkable and transformative for Day One from a research and development perspective. We've added two new programs in VRK1 and DAY301, have seen tovorafenib advance to approval, and have reached an important decision point for our efforts to combine tovorafenib and pimasertib.

Speaker Change: As well as a significant proportion of <unk> and in a large percent of aggressive neuroblastoma is one of the more common solid tumors a childhood.

Speaker Change: Our synthetic lethal interaction between <unk> and <unk> results in the sensitization of the RK to silence tumors, the inhibition of <unk> kinase activity.

Speaker Change: <unk> is a novel drug discovery targets.

Speaker Change: We anticipate providing updates on our research program for <unk> one in 2025.

Speaker Change: To wrap up the past 12 months in their totality had been both remarkable and transformative for day, one from a research and development perspective.

Speaker Change: We've added two new programs in <unk>, one and <unk> hundred one I've.

Speaker Change: Ive seen <unk> advanced to approval and have reached an important decision point for our efforts to combine to overestimate the Missouri.

Speaker Change: We continue to recognize the potential value of October <unk> and PLT Chi is data from the Firefly One program has matured further.

Samuel Blackman: We continue to recognize the potential value of tovorafenib in PLGG as data from the FIREFLY-1 program has matured further, and we have made considerable progress in accruing our FIREFLY-2 trial. Our pipeline has evolved and will continue to grow and evolve to develop value for patients. I am personally very proud, and even a little verklempt, about the addition of DAY301 to the pipeline, and I look forward to seeing this molecule enter clinical development. Beyond this, our research and development and business development teams will continue our work of identifying, in-licensing, and developing additional novel therapeutics in order to build a long-term sustainable company. Now Charles will share our Q2 financial results.

Speaker Change: And have made considerable progress in accruing our Firefly two trial.

Speaker Change: Our pipeline has evolved and we will continue to grow and evolve.

Speaker Change: To develop value for patients.

Speaker Change: Personally very proud.

Speaker Change: And even a little for clinics about the addition of <unk> hundred one to the pipeline and I look forward to seeing this molecule enter clinical development.

Speaker Change: Beyond this our research and development and business development teams will continue our work of identifying in licensing and developing additional novel Therapeutics in order to build a long term sustainable company and.

Speaker Change: And now Charles will share our second quarter financial results.

Charles Horn: Detailed second quarter financial results can be found in the press release, we issued earlier. This morning for this call I'd like to touch on a few key highlights where a strong quarter of execution throughout the company has built a solid foundation for the remainder of 2024.

Charles York: Detailed Q2 financial results can be found in the press release we issued earlier this morning. For this call, I'd like to touch on a few key highlights where a strong Q2 of execution throughout the company has built a solid foundation for the remainder of 2024. The relapsed PLGG opportunity for OJEMDA represents a substantial market. Strong commercial execution paired with clear patient demand generated $8.2 million in net revenue for the first 8 weeks of OJEMDA's launch. Included in net revenue is inventory in the channel, which totaled $2.1 million at the end of Q2. As is expected and customary in the early months of launch, we shipped OJEMDA to our specialty pharmacies in order to meet the needs of our growing customer base.

Charles Horn: The <unk> opportunity for Jim Jim that represents a substantial market strong commercial execution paired with clear patient demand generated $8 $2 million from net revenue for the first eight weeks of <unk> launch.

Charles Horn: Included in that revenue is inventory in the channel, which totaled $2 1 million at the end of the second quarter.

Charles Horn: As we've been expecting and customary in the early months of launch we shipped a gym diverse specialty pharmacies in order to meet the needs of our growing customer base as we move into the back half of 2024, we expect limited revenue from channel inventory stocking as we target two to four weeks of inventory on hand to ensure we are able to meet demand.

Charles York: As we move into the back half of 2024, we expect limited revenue from channel inventory stocking as we target 2 to 4 weeks of inventory on hand to ensure we are able to meet demand. Cost of sales for the current quarter include intangible amortization and sales-based royalties. Cost of sales did not include any product costs as inventory produced prior to FDA approval was fully expensed at the time of production. We expect cost of sales to be in the range of 9% to 12% of revenue for H2 of the year. Our operating expenses were $122.3 million for the current quarter, compared to $439.3 million for the prior year quarter.

Charles Horn: Cost of sales for the current quarter includes intangible amortization and sales based royalties.

Charles Horn: Cost of sales did not include any project cost is inventory produced prior to FDA approval was fully expense at the time of production.

Charles Horn: We expect cost of sales to be in the range of 9% to 12% of revenue for the second half of the year.

Charles Horn: Okay.

Charles Horn: Our operating expenses were $122 $3 million for the current quarter compared to $489 3 million for the prior year quarter of note. The second quarter of 2024 includes a onetime charge of $55 million in R&D expense associated with the in license a day 301.

Charles York: Of note, Q2 2024 includes a one-time charge of $55 million in R&D expense associated with the in-license of DAY301. In addition to the OJEMDA launch, we're maintaining a disciplined fiscal approach. We've discontinued the FIRELIGHT-1 program and reallocated our resources to DAY301. We sold the priority review voucher for $108 million in May 2024, and we licensed ex-US rights of OJEMDA to Ipsen for approximately $111 million up front. This agreement includes cash, an equity investment, and a premium, and up to $350 million in additional sales milestone payments. We will also receive a tier royalty percentage of net sales between the mid-teens and high twenties. Finally, we continue to form and allocate capital in a manner that focuses on generating durable growth for Day One.

Charles Horn: In addition to the agenda launch, we're maintaining a disciplined fiscal approach.

Charles Horn: We've discontinued the firelight, one program and reallocate our resources today 301.

Charles Horn: We sold the priority review voucher for $108 million in May 2024.

Charles Horn: And we licensed ex U S rights of agenda to ipsen for approximately $111 million upfront.

Charles Horn: This agreement includes cash and equity investment under premium and up to $350 million in additional sales milestone payments. We will also receive a tiered royalty percentages of net sales between the mid teens and high twenties.

Charles Horn: And finally, we continue to form and allocate capital in a manner that focuses on generating durable growth for day one.

Charles Horn: It's also important to note that we continuously review of BD opportunities that align with our mission and fit in our pipeline of targeted oncology focused on adult and pediatric patients are future growth requires pipeline expansion clinical development and commercial execution.

Charles York: It's also important to note that we continuously review BD opportunities that will align with our mission and fit in our pipeline of targeted oncology focused on adult and pediatric patients. Our future growth requires pipeline expansion, clinical development, and commercial execution. These attributes are optimized with a strong balance sheet, and we ended June 2024 with $361.9 million in cash equivalents, and short-term investments. The 30 June 2024 cash balance does not include proceeds from the recent ex-US licensing agreement or our announcement this morning of an oversubscribed private placement of approximately $175 million. In closing, and before we turn to Q&A, we would like to thank the investigators, patients, and caregivers who participated in our clinical trials.

Charles Horn: These attributes are optimized with a strong balance sheet and we ended June of 2024 with $361 9 million in cash cash equivalents and short term investments.

Charles Horn: The June 32024 cash balance does not include proceeds from the recent ex U S licensing agreement, where our announcement. This morning of an over scribed private placement of approximately $175 million.

Speaker Change: In closing and before we turn to Q&A, we would like to thank the investigators patients and caregivers who participated in our clinical trials as well as our team for advanced planning continued effort and patient focus that allows us to go.

Jeremy Bender: As well as our team for their advanced planning, continued effort, and patient focus that allows for a great start to the OJEMDA launch and the work in the clinical portfolio. We recognize that we have much to do and work ahead of us together, and we will continue to execute on our goals to bring OJEMDA to the patient community and build durable growth over time.

Speaker Change: It allows for a great start to the agenda launch and the work in the clinical portfolio. We recognize that we have much to do and work ahead of US together and we will continue to execute on our goals to bring agenda to the patient community and build durable growth over time.

Speaker Change: Thank you were ready for the question and answer session for the Q&A session, we ask that all participants limit.

Operator: Thank you. We are ready for the question-and-answer session. For the Q&A session, we ask that all participants limit their questions to one, with an opportunity to have one follow-up question. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. Our first question is from Anupam Rama with JP Morgan. Please proceed.

Speaker Change: Questions to one with an unfortunate.

Speaker Change: One follow up question.

Speaker Change: Yeah.

Speaker Change: As you would like to ask a question. Please press star one on your telephone keypad.

Speaker Change: Your line is in the question queue, you May press star two if he would like to remove your question from the queue.

<unk> Rama: Our first question is from <unk> Rama with Jpmorgan. Please proceed.

Rama: Hey, guys. Thanks for taking my question and congrats on the early metrics here.

Anupam Rama: Hey, guys. Thanks for taking the question and, congrats on the early launch metrics here. I think you guys just briefly commented on this, but wanted to get a little bit more color on what you're seeing in the early innings of the launch for OJEMDA from a gross to net perspective and how you expect this to evolve over time. Thanks so much.

Speaker Change: Just briefly commented on this but wanted to get a little bit more color on what youre seeing in the early innings of the launch for <unk> from a gross to net perspective, and how you expect this to evolve over time. Thanks, so much.

Speaker Change: Thanks, so much for joining in the question I may ask Charles to comment on gross to nets.

Jeremy Bender: Anupam, thanks much for joining and the question. I'm gonna ask Charles to comment on gross to nets.

Charles Horn: Good morning, <unk>, so from our perspective, we won't provide guidance over the long term, but I think it's important here in the early days of launch to recognize some level of understanding thats as you heard from Lauren.

Charles York: Good morning, Anupam. From our perspective, we won't provide guidance over the long term, but I think it's important here in the early days of launch to recognize some level of understanding this. As you heard from Lauren in earlier notes during the call, we're seeing a payer mix, at least at this point, that is consistent with what we believe to be prior to launch, about a 60/40 commercial to Medicaid. Our standard discounts here put us in a situation where we believe over time we'll be in that 15% to 18% range of gross to nets. We think that, absent any change in that mix, that's where the long-term status lands, around 15% to 18%.

Charles Horn: Earlier notes during the call.

Charles Horn: Being a payer mix at least at this point that is consistent with what we believe to be prior to launch about a 60 40 commercial to Medicaid or standard discounts here put us in a situation, where we believe over time will be in that 15% to 18% range of gross nets.

Charles Horn: We think that absent any change in that mix, that's where the long term space labs around 15, 18%.

Speaker Change: Great. Thanks, so much for taking our question.

Anupam Rama: Great. Thanks so much for taking our question.

Jonathan: Thanks, Jonathan.

Joe <unk>: Our next question is from Joe <unk> with Piper Sandler. Please proceed.

Jeremy Bender: Thanks, Anupam.

Operator: Our next question is from Joe Catanzaro with Piper Sandler. Please proceed.

Joe <unk>: Hey, guys. Thanks for taking my questions and congrats on all the execution here I guess my first question is maybe on the new patient starts.

Joe Catanzaro: Hey, guys. Thanks for taking my questions. Congrats on all the execution here. I guess my first question is maybe on the new patient starts and what you're seeing there. I know you said that they are tending to maybe be later line patients. Is there anything else, sort of a common shared feature that you're seeing in these new patient starts? Then I guess maybe going back to the new patient starts being later line patients, any potential impact there on your expected duration of treatment? Anything that FIREFLY-1 tells you about what you might expect in those later line patients? Thanks. I have maybe a follow-up.

Joe <unk>: What youre seeing there I know you said that they are tending to maybe it'd be later line patients is there anything else sort of common shared feature that you are seeing in these new patient starts.

Speaker Change: Then I guess, maybe going back to the new patient starts being later line patients any potential impact there on your expected duration of treatment anything that Firefly. One tells you about what you might expect in those later.

Speaker Change: Later line patients, thanks, and maybe a follow up.

Speaker Change: Okay. Thanks, Joe I appreciate you joining the call. This morning, let me ask more on the comment on both of those elements.

Jeremy Bender: Okay, thanks, Joe. Appreciate you joining the call this morning. Let me ask Lauren to comment on both of those elements, and then I'll add.

Yeah. Thank you Joe.

Speaker Change: So from a new patient starts perspective, we're actually seeing a pretty broad populations. So when we look at the location of tumor fusion.

Lauren Merendino: Yeah. Thank you, Joe. From a new patient starts perspective, we're actually seeing a pretty broad population. When we look at the location of tumor, fusion or mutation, we're seeing a broad mix. From a line perspective, we see about half of those new patient starts are in the second to third line, and about half are in later lines. That's something we'll want to change over time because the second line patients are a larger population, and we do believe that OJEMDA is best used in the second line. That will be the focus for the commercial team in order to move that up in consideration.

Speaker Change: Fusion or mutation, we're seeing a broad mix.

Speaker Change: From a line perspective, we see about half.

Of those new patients that are in the second to third line.

Speaker Change: And about half are in later lines.

And so that's something we'll want to change over time, because the second line patients or a larger population and we do believe that agenda is best used in the second line. So that will be the focus for the commercial team.

Speaker Change: In order to move that up.

Speaker Change: Iteration.

Speaker Change: Okay. Thanks, that's helpful and maybe I had one follow up I guess as I try to think about maybe early days of patient turnover I'm wondering if you could tell us what the average duration of treatment.

Joe Catanzaro: Okay, thanks. That's helpful. I maybe had one follow-up, I guess, as I try to think about maybe early days of patient turnover. Wondering if you could tell us what the average duration of treatment was on OJEMDA for patients who are on the EAP and transition before they transition. You know, how long were they on the EAP for and on drug before they transitioned to commercial product?

<unk> was on our agenda for patients who are on the EAP and transition before they transition. So how long were they on the EAP for an on drug before they.

Speaker Change: Transition to commercial product.

Speaker Change: Yes important question go ahead, yes. Thank you.

Jeremy Bender: Yeah, important question. Lauren, go ahead.

Speaker Change: So on average.

Lauren Merendino: Yeah. Thank you. On average, patients were on OJEMDA approximately six months prior to transitioning to commercial. That's an average for all of those who transition. There were about 15% that were on drug for over a year.

Speaker Change: Patients were on agenda, approximately six months prior to transitioning to commercial that's an average for all of those who transition there were about 15% that were on drug for over a year.

Speaker Change: Thanks, Lauren and Joe one other comment regarding what we're seeing in the early days of the launch that I think is important to emphasize is.

Jeremy Bender: Thanks, Lauren. Joe, one other comment regarding what we're seeing in the early days of the launch that I think is important to emphasize is, in particular, with respect to the new patient starts, so these patients who have not been on tovorafenib through the EAP, but are new to OJEMDA post-approval. The pace of new patient starts has been consistent since launch, and we're expecting that consistency will continue.

Speaker Change: In particular with respect to the new patient starts. So these patients who have not been on tomo raffinate through the EAP, but our new two new two agenda.

Speaker Change: <unk> approval.

Speaker Change: The pace of new patient starts has been consistent since launch and we're expecting that that consistency will continue.

Speaker Change: Not specifically guiding to what we'll see in the rest of the year, but I think it's important to note that that incremental growth is going to be driven by.

Jeremy Bender: Not specifically guiding to what we'll see in the rest of the year, but I think it's important to note that that incremental growth is gonna be driven by the process that we've discussed in the past, by which those patients who are relapsed PLGG patients may come on to a new therapy, either because they have a progression event, either on a treatment or off a treatment, or because they're intolerant to a current treatment. That pattern means that we are going to see that steady incremental growth, and that's consistent with what we've observed so far post-approval.

Speaker Change: The process that we've discussed in the past by which.

Speaker Change: Those patients who are relapsed <unk> patients may come onto a new therapy, either because they have a progression event.

Speaker Change: They're on a treatment or off of treatment or because theyre intolerable to current treatment that pattern means that we are going to see that steady incremental growth and thats consistent with what we've observed so far post approval.

Okay, Great. That's all really helpful. I appreciate you taking my questions. Thank you guys.

Joe Catanzaro: Great. That's all, really helpful. Appreciate you taking my questions. Thanks again.

Joe <unk>: Thank you Joe.

Speaker Change: Our next question is from Andrea <unk> with Goldman Sachs. Please proceed.

Jeremy Bender: Thank you, Joe.

Operator: Our next question is from Andrea Tan with Goldman Sachs. Please proceed.

Andrea: Good morning, Thanks for taking my question and congratulations on the quarter, Jeremy maybe a follow up visit to some comments that you just made there just curious if you could speak a little bit more as to how youre schemes position to utilize our agenda are you seeing patients being switched off of active therapy because of intolerance, whether it's chemotherapy or another.

Andrea Tan: Good morning. Thanks for taking my question, and congratulations on the quarter. Jeremy, maybe a follow-up to some comments that you just made there. Just curious if you could speak a little bit more as to how you're seeing physicians utilize OJEMDA. Are you seeing patients being switched off of active therapy, because of intolerance, whether it's chemotherapy or another MEK inhibitor? Or is it more so that these are patients who are progressing, and eligible for treatment? And then I have a follow-up. Thank you.

Speaker Change: <unk> inhibitor or is it is it more so that's these are patients who are progressing.

Speaker Change: And eligible for treatment and then I have a follow up thank you.

Speaker Change: Thanks, Andrew for the question, let me ask more and to comment on that what we're seeing in the field at this stage.

Jeremy Bender: Thanks, Andrea, for the question. Let me ask Lauren to comment on that, what we're seeing in the field at this stage.

Andrea: Yes, thanks, Andrea so.

Andrea: There are limits to our data at this point.

Lauren Merendino: Yeah. Thanks, Andrea. There are limits to our data at this point. What we're able to see is if a patient was on a prior treatment, what we aren't able to see is why they changed treatment. Did their disease progress? Did they have an intolerable AE, or was it more of a preference switch? We don't have the ability to see that information. At this point, there's, you know, there's just limits to what we know about switching and the reasons for that switch.

Speaker Change: So what we're able to see if a patient was on a prior treatment what we arent able to see is why they changed treatment.

Speaker Change: Did their disease progressed did they have an uncountable.

Speaker Change: Or was it a more of a preference.

Speaker Change: Switch, we don't have the ability to see that information.

Speaker Change: So at this point there.

Speaker Change: Limits to what we know.

Speaker Change: About switching and the reasons for that switch.

Speaker Change: Okay, and then maybe one more question here.

Andrea Tan: Okay. Lauren, maybe one more question here. If you could speak to the dynamics that you have been seeing with prescribers to date and maybe specifically for those who have yet to prescribe, if you could provide some color on the reason for that and what you believe is needed to get them to write their first script.

Speaker Change: Could speak to the dynamics that you have been seeing with prescribers to date.

Speaker Change: And maybe specifically for those who have yet to prescribe. If you can provide some color on the reason for that and what you believe is needed to get them to write their first script.

Speaker Change: Okay.

Speaker Change: Yeah. So we're talking about a broad population here. So as I mentioned, we are targeting 1500 physicians and so each.

Lauren Merendino: Yeah. We're talking about a broad population here. As I mentioned, we are targeting 1,500 physicians, and so each, you know, conversation is different. But if I were to draw a trend, I would say that many of the physicians who haven't utilized OJEMDA yet, who have expressed a desire to use it, are simply expressing they're waiting for the right patient, right? To Jeremy's point, they need a patient to either in watch and wait progress or on a product progress or have intolerable AE in order for them to consider a new treatment. That doesn't always happen every day, right? They're waiting for the opportunity.

Speaker Change: Conversation is is is different but if I were to draw a trend I would say that in many of the physicians, who havent utilized the agenda, yet who have expressed the desire to use it.

Simply expressing there waiting for the right patient right and so to Jeremy's point, they need a patient to either in watch and wait progressed or on a product progressed or have a intolerable AE in order for them to consider a new treatment and that doesn't always happen every day.

Jeremy Bender: And so they are waiting for the opportunity.

Speaker Change: And then of course, it's our sales team's job to help paint the picture of appropriate patients.

Lauren Merendino: Of course, it's our sales team's job to help paint the picture of appropriate patients and help physicians see the broad application we see for OJEMDA over time.

Speaker Change: And helps physicians see the broad application, we see four agenda overtime.

Speaker Change: Great. Thanks, so much.

Andrea: Thanks Andrea.

Andrea Tan: Great. Thanks so much.

Speaker Change: Yes.

Speaker Change: Our next question is from Marc Frahm with TD Cowen. Please proceed.

Jeremy Bender: Thanks, Andrea.

Operator: Our next question is from Marc Frahm with TD Cowen. Please proceed.

Marc Frahm: Thanks for taking my questions and congrats on all the progress so far on the launch.

Marc Frahm: Thanks for taking my questions, and congrats on all the progress so far on the launch. Maybe on that-

Marc Frahm: Thanks for taking my questions, and congrats on all the progress so far on the launch. Maybe on that.

Marc Frahm: Maybe on the next 23 months median duration of therapy. So far it does speak to the maturity of then and how much.

Jeremy Bender: Thanks.

Marc Frahm: 23 months median duration of therapy so far, can you guys speak to the maturity of that and how much that may change as follow-up continues? Then maybe this is kind of a follow-on to one of Joe's questions. Just can you speak to what you're seeing for duration, kind of impact of the line of therapy there, of how that changes duration and maybe looking forward to the first line trial, kind of how much longer could it get by moving to those patients? In first line, is it really just going to be driven by the decision to start a drug holiday maybe at 24 months or a bit after that?

Speaker Change: That may change as follow up continues.

Speaker Change: Then maybe this is a kind of a follow on to Joe's questions. Just can you speak to the <unk>.

Speaker Change: What youre seeing for duration kind of impact of the line of therapy, there how that changes duration and maybe looking forward to the first line trial.

Speaker Change: Much longer could it get by moving to those patients or in first liens are really just going to be driven by the decision to start a drug holiday, maybe at 24 months or or good after that.

Speaker Change: Mark Thanks for the question, let me start with your second question and just.

Jeremy Bender: Marc, thanks for the question. Let me start with your second question and just let you know that with respect to the commercial effort, it's too early to say anything definitive about what we may observe in terms of duration of treatment for commercial use. Similarly, in the frontline setting, I think in the absence of, you know, real data from the real world trial FIREFLY-2 here, it's gonna be difficult to state, you know, what the potential change in possible duration of treatment may be in the frontline relative to the relapse setting. With respect to the FIREFLY-1 result and the new cutoff from May that has resulted in the updated duration of treatment, let me ask Sam to comment on maturity.

Speaker Change: You know that with respect to the commercial effort.

Speaker Change: Too early to say anything definitive about what we may observe in terms of duration of treatment.

Speaker Change: For commercial use.

Speaker Change: Similarly in the frontline setting I think in the absence of.

Speaker Change: A real data from the real World trial trial Firefly to here, it's going to be difficult to state what the potential change in possible duration of treatment maybe in the frontline relative to the relapsed setting.

Speaker Change: With respect to the <unk>.

Speaker Change: Firefly, one result, and a new cutoff from May.

Sam: That has resulted in the updated duration of treatment, let me ask Sam to comment on cognate surety.

Sam: Yes.

Sam: We will probably look at the data ones last time as part of our long term follow up but.

Samuel Blackman: Yeah. You know, we'll probably look at the data one last time as part of our long-term follow-up. But you know, I think at the end of the day, you know, as more patients come off trial or reach a treatment or go into a drug holiday, I don't expect that number to shift significantly more. One other point that I think is important to make is that the duration of treatment data from FIREFLY-1, the 20 to 23.7 months that I mentioned, represents data from a population where the median line of therapy prior to the initiation of treatment was 3. This is a median fourth line patient population.

Sam: I think at the end of the day.

Sam: More patients come off trial of <unk>.

Speaker Change: We're going to light truck holiday and expect that number to shift.

Significantly more one other point that I'd be I think it's important to make is that the duration of treatment data from Firefly, one 'twenty two 'twenty three seven months I mentioned represents data from a population where the median line of therapy prior to the initiation of treatment with <unk>. Three. So this is a median fourth line patient population.

Speaker Change: So when I think about it.

Speaker Change: The impact of line of therapy duration of treatment.

Samuel Blackman: When I think about the impact of line of therapy on duration of treatment, I think the data from FIREFLY-1 makes it clear that duration of treatment does not seem to be significantly impacted by what line of therapy they're in.

Speaker Change: The data from Firefly, one makes it clear that.

Speaker Change: Duration of treatment does not seem to be significantly impacted by.

Speaker Change: What line of therapy that you're right.

Speaker Change: Alright, thanks very helpful.

Marc Frahm: Great. Thanks. Very helpful.

Mark: Thanks Mark.

Speaker Change: Our next question is from Amy <unk>.

Jeremy Bender: Thanks, Marc.

Operator: Our next question is from Ami Fadia with Needham & Company. Please proceed.

Amy: Thank you.

Speaker Change: Please proceed.

Amy: Yeah.

Amy: Hi, Good morning, Thanks for taking my question and congrats on the strong initial launch.

Ami Fadia: Hi, good morning. Thanks for taking my question, and congrats on the strong initial launch. Firstly, just following up on the comment regarding duration of treatment, could you clarify what drives the decision for a patient to take a drug holiday? Is it just duration of treatment or is it some other aspect?

Amy: Firstly, just following up on.

Speaker Change: The comments regarding duration of treatment.

Speaker Change: Satisfy what can drive that decision for a patient to take a drug holiday is it just duration of treatment or is it some other aspects.

Speaker Change: And with regard to the.

Ami Fadia: With regards to the mix of patients, you mentioned that going forward, or at least over time, you expect the mix of second-line patients to increase. I guess what I'd like to understand is sort of given the high pool of prevalent population and some of the reasons that you mentioned, such as, you know, lack of tolerability of other treatments, is it not possible that there would still be a meaningful percentage of patients that are in later lines of treatment? Thank you.

Speaker Change: The mix of patients you mentioned that going forward or at least till the time you expect the mix of second line patients to increase.

Speaker Change:

Speaker Change: But.

Speaker Change: I guess.

Speaker Change: What I'd like to understand is sort of given the.

Paul: Hi, Paul prevalent population.

Paul: And some of the reasons that you mentioned a question.

Paul: Lack of Tolerability of the treatment.

Paul: Is it not possible that there would still be a meaningful percentage of patients that are in later lines of treatment. Thank you.

Amit Thanks for the question, let me start with that second question first I do think and we've discussed in the past.

Jeremy Bender: Bomi, thanks for the questions. Let me start with that second question first. I do think, and we've discussed in the past this property of the prevalent pool of PLGG patients, that there will be an appreciable number of patients who are later line, so to speak, you know, third, fourth, fifth line and beyond, just given the, you know, relative sort of survival dynamics of this population, fortunately. That being said, I think what we're expecting based on just prior experience in commercializing oncology therapies, and even in clinical trials we observed this, is that as physicians have additional experience with a new medicine, they tend to use it in earlier lines of therapy.

Paul:

Judy: Property of the prevalent pool appeal, Judy patients that there will be an appreciable number of patients who are later line. So to speak third fourth fifth line and beyond just given the.

Judy: Relative.

Judy: Survival dynamics of this population.

Judy: Fortunately.

Speaker Change: That being said I think what we're expecting based on prior experience in commercializing oncology therapies and even in clinical trials. We observed is that as physicians have additional experience with.

Speaker Change: New medicine.

Speaker Change: <unk> two.

Speaker Change: Use it in earlier lines of therapy.

Speaker Change: And that's the reason that we're expecting that over time, we will see agenda use in patients in the second line setting and at a higher rate than perhaps we're observing earlier in our launch.

Jeremy Bender: That's the reason that we're expecting that over time, we will see OJEMDA use in patients in the second line setting and at a higher rate than perhaps we're observing earlier in our launch. So I think that's the overall dynamic that I would anticipate with respect to the element. Now I've forgotten the second element of your question, Bomi. Apologies.

Speaker Change: So I think that the overall dynamic that I would anticipate with respect to the.

Speaker Change: Element and now I've forgotten the second element of your question Amit policies.

The drive decision for drug holiday, yes, yes on that front I think it's a.

Ami Fadia: The drive to the decision for drug holiday.

Speaker Change: A little bit early but I'll ask.

Jeremy Bender: Oh, yeah. On that front, I think it's a little bit early, but I'll ask Sam to comment on, from a clinical standpoint, you know, what he would expect based on knowledge of the space.

Sam: Sam to comment on from a clinical standpoint.

Sam: What you.

Speaker Change: You would expect based on knowledge of the space.

Sam: Yes, it's a great question.

Speaker Change: I wanted to just sort of preface my remarks by saying that it's hard to speak for all families in all pediatric neuro oncologist because this really is.

Samuel Blackman: Yeah. It's a great question. You know, I wanna just sort of preface my remarks by saying that, you know, it's hard to speak for all families and all pediatric neuro-oncologists because this really is, you know, such a different disease going from patient to patient, owing to the location of the tumor, the risks to the patient of progression of that tumor, and also the age of the patient. Recall that low-grade gliomas tend to spontaneously, and that's when patients get to their third decade of life, that is their early to mid-twenties. The decision to take a drug holiday integrates all of that in addition to the prior velocity of growth of the tumor, as well as, you know, how the patient is tolerating that drug. You can imagine many different permutations for different patients.

Speaker Change: Such a different disease going from patient to patient.

Speaker Change: Owing to the location of the tumor the risks to the patient of progression of that tumor and also the age of the patient recall correctly illness tend to spontaneously soon that's when patients get to their third decade life that is their early to mid twenties.

Speaker Change: And so the decision to take a drug quality integrates all of that in addition to.

Speaker Change: Prior velocity of growth of the tumor.

Speaker Change: As well as how the patient is tolerating byproduct. So you can imagine many many different permutations for different patients.

Speaker Change: Patient in their late teens, who may be a second or third relapsed patient may be close to the point of having their tumor undergo senescence.

Samuel Blackman: A patient in their late teens who may be a second or third relapsed patient, who may be close to the point of having their tumor undergo senescence, where the growth of the tumor may not necessarily have significant impact on vision or on motor function. There may be a greater willingness to take a drug holiday because it's possible that the tumor may have undergone senescence or may be close to undergoing senescence. On the other hand, a much younger patient who may have had many relapses and has an optic pathway tumor, where the risk of growth of that tumor may mean complete loss of vision, there may be a greater hesitation to take a drug holiday, if the patient, for example, is tolerating the drug well.

Speaker Change: The growth of the tumor may not necessarily have significant impact on fishing or a motor function there may be.

Speaker Change: More a greater willingness to take a drug holiday because it's possible that the tumor may have.

Speaker Change: Undergone senescence or maybe close to undergoing some assets on the other hand, a much younger patient who may have had many relapses in Hudson pathway tumor.

Speaker Change: The risks of growth of that tumor remaining complete loss of vision there.

Speaker Change: There may be greater hesitation to take a drug holiday.

Speaker Change: The patient for example, as tolerating the drug well.

Speaker Change: So it's hard to come up with a single.

Samuel Blackman: It's hard to come up with a single heuristic for how long to treat a patient because it really takes into account so many different variables.

Speaker Change: Terrific.

Speaker Change #100: How long to treat a patient because it really takes into account so many different variables.

Speaker Change #100: Yeah.

Speaker Change #101: That's very helpful. Thank you.

Ami Fadia: That's very helpful. Thank you.

Speaker Change #101: Our next question is from Sumit Roy with Jones Research. Please proceed.

Operator: Our next question is from Soumit Roy with Jones Trading. Please proceed.

Sumit Roy: Good morning, everyone and congrats again on the second quarter of <unk>.

Soumit Roy: Morning, everyone, and congrats again on the second quarter. A question about the safety profile. Has it improved, 420 milligram versus 380 milligram or still staying in line with the FIREFLY-1, when you look at FIREFLY-2 trial or the commercial product?

Speaker Change #101: About.

Sumit Roy: The safety profile has it improved a full 20 milligram versus 380 milligram all things staying in line with our Firefly one when you look at sort of like two trial R&D, how much of a problem.

Speaker Change #101: Yeah.

Speaker Change #101: Sure and thanks for the question I'll ask Tim to comment on the safety question as it relates to dose.

Jeremy Bender: Soumit, thanks for the question. Let me ask Sam to comment on the safety question as it relates to dose.

Tim: Yes, it's a great question, we have not conducted a formal analysis of 420 versus three recall that 380.

Samuel Blackman: Yeah. It's a great question. You know, we've not conducted a formal analysis of 420 versus 380. Recall that 380 was the approved commercial dose, and obviously for commercial patients, we don't collect, day-to-day or garden variety adverse events. There's certainly been nothing that we've detected thus far in our pharmacovigilance database to indicate any change in pattern of adverse events.

Tim: Commercial dose and obviously for commercial patients we don't collect.

Tim: Day to day of garden variety adverse events.

Tim: There's certainly been nothing that we've detected thus far in our pharmacovigilance database to indicate any change in pattern of adverse events.

Speaker Change #104: Okay, and you are seeing any dose for the dose reduction.

Soumit Roy: Okay. You are seeing any further dose reduction on top of 380 for any reason, or if patients are fairly staying on that dose? I know it's still early in the launch process.

Tim: Top of 380 for any reason.

Speaker Change #108: Patients are.

Tim: Early staying on that dose.

Tim: Early in the launch button.

Speaker Change #105: I can't comment whether or not we have visibility into that data.

Samuel Blackman: I can't comment as to whether or not we have visibility into that data.

Yes, I don't I don't think were anecdotally hearing or seeing anything that's inconsistent with what we've observed in the clinical trial.

Jeremy Bender: Yeah. I don't think we're anecdotally hearing or seeing anything that's inconsistent with what we've observed in the clinical trial.

Speaker Change #109: Thank you and congratulations again.

Kevin: Thanks, Kevin.

Soumit Roy: Thank you. Congratulations again.

Speaker Change #107: With no further questions and that clearly will conclude today's conference you may disconnect. Your lines at this time and thank you for your participation.

Jeremy Bender: Thanks, Soumit. Yeah.

Operator: With no further questions in the queue, we will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.

Speaker Change #110: Thank you operator.

Jeremy Bender: Thank you, operator.

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