Q2 2024 Cytokinetics Inc Earnings Call

August 8, 2024

Good afternoon and welcome, ladies and gentlemen, to Cytokinetics' second quarter 2024 conference call.

Unknown Executive: This is the second quarter of 2024 conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call to questions after the presentation. We will allow only one question per participant. I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Affairs. Please go ahead.

Speaker Change: At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call to questions after the presentation. We will allow for only one question per participant.

Diane Weiser: I will now turn the call over to Diane Weiser, Cytokinetics Senior Vice President of Corporate Affairs. Please go ahead.

Diane Weiser: Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Fady Malik, EVP of R&D, will provide updates related to Sequoia's HCM and the ongoing clinical trials program for Aficamptin. Chris Murray, SVP, Regulatory Affairs and Quality, will provide an update on our recent interactions with FDA and EMA and the progress of our planned regulatory filings. Andrew Callos, EVP and Chief Commercial Officer, will address commercial readiness activities for Aficamptin. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates regarding Omicamptin-McCarbyl, CK586, and our earlier stage development pipeline.

Diane Weiser: Good afternoon and thanks for joining us on the call today.

Diane Weiser: Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments.

Fady Malik: Fady Malik, EVP of R&D, will provide updates related to sequoias HCM and the ongoing clinical trials program for apicampin.

Chris Murray: Chris Murray, SVP, Regulatory Affairs and Quality will provide an update from our recent interactions with FDA and EMA and the progress of our plan regulatory filings.

Andrew Callos: Andrew Callos, EVP and Chief Commercial Officer, will address commercial readiness activities for AFI-CAMPTN.

Stuart Kupfer: Stuart Kupfer, SVP and Chief Medical Officer, will provide updates regarding Omecampton-McCarble CK586 and our earlier stage development pipeline.

Robert Blum: Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the second quarter and review our updated financial guidance for 2024. And finally, Robert will review our corporate development strategies and review expected upcoming milestones. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements.

Speaker Change: Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the second quarter and review our updated financial guidance for 2024. And finally, Robert will review our corporate development strategies and review expected upcoming milestones.

Speaker Change: Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements.

Speaker Change: Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our second quarter 2024 financial results filed on Form 8K that was furnished to the SEC today.

Robert Blum: Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our second quarter 2024 financial results filed on Form 8K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call.

Speaker Change: We undertake no obligation to update any forward-looking statements after this call, and now I will turn the call over to Robert.

Robert Blum: Thank you, Diane, and thanks for joining us on the call today. The second quarter was marked by significant progress and notable achievements across our later stage clinical development programs built on the foundation of cardiac myosin modulation, as well as a significant strengthening of our balance sheet and capital structure, enabling continued execution of the potential commercial launch of afecampin, as well as further advancement of our pipeline. In May, we were pleased to present the primary results from Sequoia HCM in a late-breaking clinical trial session at the European Society of Cardiology's Heart Failure 2024 Congress in Lisbon. As Fady will elaborate, these results met our already high expectations.

Speaker Change: As well as a significant strengthening of our balance sheet and capital structure, enabling continued execution of the potential commercial launch of Aficampan, as well as further advancement of our pipeline.

Speaker Change: In May, we were pleased to present the primary results from Sequoia HCM in a late-breaking clinical trial session at the European Society of Cardiology's Heart Failure 2024 Congress in Lisbon.

Speaker Change: As Fady will elaborate, these results met our already high expectations.

Robert Blum: The safety and efficacy profile of afecamtin that has emerged from sequoia HCM points to a potentially category-expanding opportunity as a next-in-class cardiac myosin inhibitor for patients with HCM. During the quarter, we continued our dialogue with FDA, ahead of our planned submission of an NDA. We participated in a productive type B meeting with FDA to discuss potential strategies related to safety monitoring and risk mitigation for AFICAM-T. We are pleased with how these discussions went, and we're moving forward as planned. Chris Murray, SVP of Regulatory Affairs and Quality, joined us today to provide an update on our regulatory interactions globally.

Fady Malik: The safety and efficacy profile of afecamtin that has emerged from sequoia HCM points to a potentially category expanding opportunity as a next-in-class cardiac myosin inhibitor for patients with HCM.

Fady Malik: During the quarter, we continued our dialogue with FDA ahead of our planned submission of an NDA.

Fady Malik: We participated in a productive type B meeting with FDA to discuss potential strategies related to safety monitoring and risk mitigation for aficampin.

Chris Murray: We are pleased at how these discussions went and we're moving forward as planned. Chris Murray, SVP of Regulatory Affairs and Quality, has joined us today to provide an update on our regulatory interactions globally.

Robert Blum: With respect to Omicamptive-McCarble, over the past year, we conducted numerous analyses of the results from Galactic HF, spoke with regulators on several occasions, and conferred with heart failure experts on the unmet need and the potentially unique role that Omicamptive may play in treating patients with heart failure, all together while we evaluated our potential next steps. What we found was a compelling opportunity for Omicamptomacarbal to address a large and growing population of people with severe heart failure who have limited treatment options and are at increased risk of hospitalization.

Speaker Change: With respect to Omicampt of McCarble, over the past year we conducted numerous analyses of the results from Galactic HF

Fady Malik: We spoke with regulators on several occasions, and we conferred with heart failure experts on the unmet need and the potentially unique role that Omicamptive may play in treating patients with heart failure, all together while we evaluated our potential next steps.

Fady Malik: What we found was a compelling opportunity for Omicampta Macarbo to address a large and growing population of people with severe heart failure who have limited treatment options and are at increased risk of hospitalization.

Robert Blum: With high adjacency to HCM in terms of treating physicians, we believe we can deliver a high return on investment by advancing Omicamptomacarbal with minimal increased commercial costs. Following the launch of AFI-CAMPTAN, and again, should the confirmatory Phase 3 clinical trial of Omicamptive read out positively? Furthermore, alongside CK586, we see a synergistic opportunity from both an R&D and commercial standpoint to build a sustainable specialty cardiovascular franchise for patients and to further unlock and potentially maximize value for shareholders.

Fady Malik: With high adjacency to HCM in terms of treating physicians, we believe we can deliver a high return on investment by advancing Omicamptomacarbal with minimal increased commercial costs.

Fady Malik: Following the launch of AFI-CAMPTEN, and again, should the confirmatory Phase 3 clinical trial of Omicamptive read out positively?

Fady Malik: Furthermore alongside C.K. 586.

Fady Malik: we see a synergistic opportunity from both an R&D and commercial standpoint to build a sustainable specialty cardiovascular franchise for patients and to further unlock and to potentially maximize value for shareholders.

Robert Blum: Overall, we're proud to highlight an extensive development program for AFI-CAMTAN with multiple potential label-expanding clinical trials ongoing, plus later-stage development programs in adjacent specialty cardiology indications, with more still to come arising from our pioneering muscle biology research. We're carving out a specialty cardiology niche anchored in the foundation of our myosin platform and with our sights set on improving the lives of patients while also enhancing shareholder value And with that, I'll turn the call over to Fady, please.

Fady Malik: Overall, we're proud to highlight an extensive development program for AFI-CAMPTN, with multiple potential label-expanding clinical trials ongoing.

Fady Malik: Plus, later stage development programs in adjacent specialty cardiology indications, with more still to come arising from our pioneering muscle biology research.

Fady Malik: We're carving out a specialty cardiology niche anchored in the foundation of our myosin platform, and with our sights set on improving the lives of patients while also enhancing shareholder value. And with that, I'll turn the call over to Fady, please.

Fady Malik: Thanks, Robert. In the second quarter, we were very pleased to present three late-breaking clinical trial presentations in Lisbon, including the primary results of Sequoia HCM and two additional analyses from the trial. The primary results, which were also published simultaneously in the New England Journal of Medicine, are consistent with our target product profile that may enable apicampin to become the cardiac myosin inhibitor of choice among physicians and patients. The results show that treatment with apicamptin for 24 weeks significantly improved exercise capacity, increasing peak VO2 by 1.7 mL per kilo per minute compared to placebo with a p-value of 0.000002. This treatment effect was consistent across all pre-specified subgroups, including patients receiving beta blockers.

Fady Malik: The primary results, which were also published simultaneously in the New England Journal of Medicine, are consistent with our target product profile that may enable apicampin to become the cardiac myosin inhibitor of choice among physicians and patients.

Fady Malik: The results showed that treatment with apicamptin for 24 weeks significantly improved exercise capacity, increasing peak VO2 by 1.7 mL per kilo per minute compared to placebo with a p-value of 0.000002.

Fady Malik: This treatment effect was consistent across all pre-specified subgroups, including patients receiving beta blockers.

Fady Malik: Subsequent improvements, all P less than.001, were observed in each of the 10 secondary endpoints, and patients treated with apicamptin had substantial reductions in symptom burden, including a 7-point improvement in the KCCQ, and 34% of the patients improved by at least one NYHA functional class compared with placebo. Another way to evaluate the treatment benefit of apicamptin is by looking at its effect on the underlying In sequoia HCM, treatment with apicamptin resulted in a significant and substantial reduction in the post-Valsalva LVOT gradient of 50 millimeters of mercury, or 60% of the baseline post-Valsalva LVOT gradient.

Fady Malik: Subsequent improvements all P less than 0.001

Fady Malik: were observed in each of the 10 secondary endpoints, and patients treated with apicamptin had substantial reductions in symptom burden, including a 7-point improvement in the KCCQ, and 34% of the patients improving by at least one NYHA functional class compared with placebo.

Fady Malik: Another way to evaluate the treatment benefit of afecamptin is by looking at its effect on the underlying hypercontractility that's characteristic of HCM.

Fady Malik: In Sequoia HCM, treatment with apicamptin resulted in a significant and substantial reduction in the post-balsalva LVOT gradients of 50 mmHg, or 60% of the baseline post-balsalva LVOT gradient.

Fady Malik: Importantly, this reduction in LVOT gradient was paired with less than 5% of a reduction in LVEF on average. Overall, we observed rapid and substantial reductions in LVOT gradients without a negative impact on left ventricular ejection fraction, consistent with an improvement in the hypercontractility that occurs in HCM. A recent manuscript published by Dr. Caroline Coats and colleagues in the Journal of the American Heart Association detailed the safety and dosing results from CHOI-HCM and expanded and reinforced these initial observations.

Fady Malik: Importantly, this reduction in LVOT gradient was paired with less than 5% of a reduction in LVEF on average.

Fady Malik: Overall, we observed rapid and substantial reductions in LVOT gradients without a negative impact on left ventricular ejection fraction, consistent with an improvement in the hypercontractility that occurs in HCM.

Speaker Change: A recent manuscript published by Dr. Caroline Coats and colleagues in the Journal of the American Heart Association detailed the safety and dosing results from COI-ATM and expanded and reinforced these initial observations.

Speaker Change: The paper comprehensively describes the key results of Sequoia HCM that were tied to its aspirational pharmaceutical profile and engineered into Aficamptin.

Fady Malik: The paper comprehensively describes the key results of Sequoia HCM that were tied to its aspirational pharmaceutical profile and engineered into AFI-CAMP. Specifically, these analyses showed that affecamtin rapidly reduced LVOT gradients within two weeks of treatment initiation without the need for either treatment discontinuation or interruption during the dose escalation phase. Additionally, the pharmacokinetics were generally linear with low variability once the target dose was attained, and that led to very little change in LVEF during the maintenance phase of treatment, essentially indistinguishable from placebo in that regard. The effectiveness of down titration for LVEF less than 50% and the reversibility of its pharmacodynamics were convincingly demonstrated.

Speaker Change: Specifically, these analyses showed that afecamptin rapidly reduced LVOT gradients within two weeks of treatment initiation without the need for either treatment discontinuation or interruption during the dose escalation phase.

Speaker Change: Additionally, the pharmacokinetics were generally linear with low variability once the target dose was attained, and that led to very little change in LVEF during the maintenance phase of treatment, essentially indistinguishable from placebo in that regard.

Fady Malik: Importantly, there were no associated heart failure events. The goal of treatment in HCM is not only to reduce the LVOT gradient, but it's also to normalize left ventricular ejection fractures. As the paper outlines, patients treated with apicamptin with the largest excursions in LVEF from baseline, 20% or higher, all had baseline LVEFs greater than 75%. None of these individuals had an LVF below 50% at any visit

Speaker Change: Effectiveness of down titration for LVEF less than 50% and the reversibility of its pharmacodynamics were convincingly demonstrated. Importantly, there were no associated heart failure events.

Speaker Change: The goal of treatment in HCM is not only to reduce the LVOT gradient, but it's also to normalize left ventricular ejection fraction.

Speaker Change: As the paper outlines, patients treated with apicamptin with the largest excursions in LVEF from baseline, 20% or higher, all had baseline LVEFs greater than 75%.

Speaker Change: None of these individuals had an LVF below 50% at any visit.

Fady Malik: The largest reductions in LVEF occurred in the participants with the most severe hypercontractility, consistent with the objective of treatment. At the upcoming European Society of Cardiology meeting in London, we will have six presentations relating to apicamptin, including four late breakers and two oral presentations. Results from Sequoia HCM related to KCCQ, cardiac structure, function, and biomarkers will be presented. Alongside that, we'll be presenting an integrated safety analysis from Forest HCM and data related to the withdrawal of standard of care medication.

Speaker Change: Mr. Largest Reductions in LVF, occurred in the participants with the most severe hypercontractility and system with the objective of treatment.

Speaker Change: The upcoming European Society of Cardiology meeting in London will have six presentations relating to apicamptin, including four late breakers and two oral presentations.

Speaker Change: Results from Sequoia HCM related to KCCQ, cardiac structure, function, and biomarkers will be presented.

Speaker Change: Alongside that, we'll be presenting an integrated safety analysis from Forest HCM and data related to the withdrawal of standard of care medications. We believe the totality of these presentations will importantly elaborate on how Aficamten is achieving our target product profile.

Fady Malik: We believe the totality of these presentations will importantly elaborate on how Affy Kempton is achieving our target product profile. Moving on to the ongoing clinical trials program for Aficamptin, we're pleased to report that we're on track to complete enrollment in Maple HCM during this quarter. In fact, we're no longer seeking new patients to enter screening.

Speaker Change: Moving on to the ongoing clinical trials program for Affie Kampton, we're pleased to report that we're on track to complete enrollment in Maple HCM during this quarter.

Fady Malik: As a reminder, this clinical trial is evaluating the potential superiority of Afekampton as monotherapy compared to Metoprolol as monotherapy in obstructive HCM. We expect that completing enrollment this quarter should enable results to read out in the first half of 2025, ahead of when we hope to be launching AFI-CAMPTN commercially, and if positive, will represent a potential label enhancement opportunity and provide evidence of how AFI-CAMPTN could be positioned as first-line therapy relative to beta blockers and practice guidelines.

Speaker Change: In fact, we're no longer seeking new patient's to enter screening. As a reminder, this clinical trials evaluating the potential superiority of happy canptonism onotherapy compared to metoperallism onotherapy and obstructive ATM.

Speaker Change: We expect a completing enrollment this quarter should enable results to read out in the first half of 2025.

Speaker Change: Ahead of when we hope to be launching AFI-CAMPTN commercially, and if positive, will represent a potential label enhancement opportunity and provide evidence on how AFI-CAMPTN could be positioned as first-line therapy relative to beta blockers and practice guidelines.

Fady Malik: Enrollment in ACACI HCM, the pivotal Phase III clinical trial of apicamptin in patients with symptomatic non-obstructive HCM, has progressed substantially, and we continue to activate clinical sites during the quarter. Enrollment is brisk and remains consistent with our current projections.

Speaker Change: Enrollment in a K-Shade CM, the pivotal phase 3 clinical trial of africampton and patients with symptomatic non-obstructivate CM has progressed substantially and we continue to activate clinical sites during the quarter. Enrollment is brisk and remains consistent with our current projections.

Chris Murray: We look forward to continuing to enroll patients in the KCM through this year with the goal of completing patient enrollment in 2025. Recently, the European Journal of Heart Failure published a short report with data from 34 patients with NHCM through 36 weeks of treatment in Forest HCM, the Open Label Extension clinical trial. This is the first data we have on extended treatment with apicamps in patients with NHDM. Aficamptin appeared generally well-tolerated, with patients experiencing substantial improvements in symptom burden, NYJ functional class, and antiprobian P. There were no drug discontinuations due to adverse events.

Speaker Change: We look forward to continuing to enroll patients in the KTM through this year with the goal of completing patient enrollment in 2025.

Speaker Change: Recently, the European Journal of Heart Failure published a short report with data from 34 patients with NHCM through 36 weeks of treatment in Forest HCM, the Open Label Extension clinical trial.

Speaker Change: This is the first data we have on extended treatment with apicampin in patients with NHCM.

Speaker Change: Aficamptin appeared generally well-tolerated, with patients experiencing substantial improvements in symptom burden, NYCHA functional class, and antiprobian P. There were no drug discontinuations due to adverse events.

Chris Murray: These results suggest that longer-term treatment with apicampin can be both safe and effective in patients with NHCM. We look forward to hopefully building on these findings with more data from Forest HCM and, of course, seeing the results from Acacia HCM when available. Our fourth ongoing clinical trial at Vaffey-Campden is CEDAR-HCM, evaluating a pediatric population of patients with symptomatic OHCM, which we will open to enrollment in the second quarter. CEDAR HCM provides an opportunity to further extend the potential utility of apicampin, an additional segment of the broader HCM population, as may further elaborate a next-in-class profile. Finally, during the quarter, we started a Phase 1 study evaluating the pharmacokinetics, safety, and tolerability of affecamtin in healthy Japanese and Caucasian participants to gather evidence that we believe will be required for potential approval of Now, I'd like to invite Chris Murray to provide an update on the regulatory front for AFI CAMP.

Speaker Change: These results suggest that longer term treatment with apicampin can be both safe and effective in patients with NHCM. We look forward to hopefully building on these findings with more data from Forest HCM and of course seeing the results from Acacia HCM when available.

Speaker Change: Our fourth ongoing clinical trial of AFI Campton is Cedar ATM, evaluating a pediatric population of patients with symptomatic OACM, which we open to enrollment in the second quarter.

Speaker Change: Cedar, HCM provides an opportunity to further extend the potential utility of Afie Campson, an additional segment of the broader HCM population, has made further elaborate a next-and-class profile.

Speaker Change: Finally, during the quarter we started a phase one study evaluating the pharmacokinetics, safety, and tolerability of African-Campson and healthy Japanese and Caucasian participants.

Speaker Change: to gather evidence that we believe will be required for potential approval of affecamton in Japan. Again, expanding where affecamton may be able to have a meaningful, positive, and differentiated impact on patient lives.

Speaker Change: Now I'd like to invite Chris Murray to provide an update on the regulatory front for AFI CAMFED.

Chris Murray: Thanks, Fady. I'm pleased to join today's call to share updates on our regulatory progress during the past quarter. As Robert mentioned, ahead of our planned NDA submission for Aficampton, during the quarter, we participated in a type B meeting with FDA, during which we discussed strategies related to safety monitoring and risk mitigation in support of our NDA submission. As a reminder, two earlier meetings with FDA were completed in February, including a first meeting to review the results of Sikora HCM, and a second pre-NDA meeting to cover specific topics related to our submission

Chris Murray: Thanks Fady. I'm pleased to join today's call to share updates on our regulatory progress during the past quarter.

Chris Murray: As Robert mentioned, ahead of our planned NDA submission for AFI Campton, during the quarter we participated in a Type B meeting with FDA, during which we discussed strategies related to safety monitoring and risk mitigation in support of our NDA submission.

Unknown Executive: 26th quarter, 2024 conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen only mode. At the company's request, we will open the call to questions after the presentation.

Unknown Executive: We will allow for only one question per participant.

Chris Murray: As a reminder, two earlier meetings with the FDA were completed in February , including a first meeting to review the results of Sequoia HCM, and a second, pre-NDA meeting to cover specific topics related to our submission.

Chris Murray: This more recent third meeting provided an important opportunity to elaborate on the safety and pharmaceutic properties of Aficampton and discuss how they may inform approaches to manage risk and gain insight into FDA's perspective on this matter. We are very pleased with the progress we have made with FDA in this series of meetings, and FDA is continuing to gain engagement ahead of the submission of the NDA for AfriKampton. While we understand that risk mitigation will ultimately be a review topic with FDA, following our recent Type B meeting, we plan to propose a distinct risk mitigation approach specific to AfriCampden in the NDA.

Diane Weiser: I will now turn the call over to Diane Weiser, Cytokinetics Senior Vice President of Corporate Affairs. Please go ahead. Good afternoon and thanks for joining us on the call today.

Speaker Change: This more recent third meeting provided the important opportunity to elaborate on the safety and pharmaceutic properties of aficampin and discuss how they may inform approaches to manage risk and gain insight into FDA's perspective on this matter.

Robert Blum: Robert Blom, President and Chief Executive Officer will begin with an overview of the quarter and recent developments.

Speaker Change: We are very pleased with the progress we have made with FDA in this series of meetings and FDA's continued to gain engagement ahead of this submission of the NDA for AfiCountton.

Fady Malik: That email, EVP of R&D, will provide updates related to Sequoias HCM and the ongoing clinical trials program for Ophi Campton.

Christine Murray: Chris Murray, SVP regulatory affairs and quality will provide an update from our recent interactions with FDA and EMA and the progress of our plan regulatory filings.

Speaker Change: While we understand that risk mitigation will ultimately be a review topic with FDA, following our recent Type B meeting, we plan to propose a distinct risk mitigation approach, specific traffic competence with the FDA.

Andrew Callos: Andrew Callos, EVP and Chief Commercial Officer will address commercial readiness activities for Ophi Campton.

Chris Murray: Another important outcome of our recent Type B meeting was that the agency agreed to a protocol amendment for the ongoing Open Label Extension Trial, FOREST-HCM, reducing the frequency of echo monitoring required during the treatment maintenance phase. The amendment allows patients with OHCM to now undergo echo monitoring every six months instead of every three months during maintenance treatment if their LVEF is above 55% and there's an absence of other conditions that may impair systolic function.

Speaker Change: Another important outcome of our recent Type B meeting was that the agency agreed to a protocol amendment for the ongoing Open Label Extension Trial, FOREST-HCM, reducing the frequency of echo monitoring required during the treatment maintenance phase.

Stuart Kupfer: Steward Kutzer, SVP and Chief Medical Officer, will provide updates regarding Oma Campton McCarble, CK586 and our earlier state development pipeline.

Sung Lee: Somely, EVP and Chief Financial Officer will provide a financial overview of the second quarter and review our updated financial guidance for 2024.

Chris Murray: The amendment allows patients with OHCM to now undergo echo monitoring every 6 months instead of every 3 months during maintenance treatment if their LVEF is above 55% and there is an absence of other conditions that may impair systolic function.

Robert Blum: And finally, Robert will review our corporate development strategies and review expected upcoming milestones.

Unknown Executive: Please note that portions of the following discussion, including our responses to questions, contains statements that relate to future events and performance rather than historical facts and constitute for looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our second quarter 2024 financial results filed on Form 8K that was furnished to the SEC today.

Chris Murray: The protocol amendment was based on the overall safety and tolerability profile observed in the development program thus far. As we've reported, there have been no treatment interruptions attributed to affectant observed in Forest HCM to date. The approach to echo monitoring now implemented in Forest HCM reflects the potential real world risk-based approach for how clinicians could manage patients who are taking affectant.

Speaker Change: The protocol amendment was based on the overall safety and tolerability profile observed in the development program thus far. As we've reported, there have been no treatment interruptions attributed to affectant observed in forest HCM to date.

Chris Murray: The approach to echo monitoring now implemented in Forest HCM reflects the potential real-world, risk-based approach for how clinicians could manage patients who are taking affectant.

Andrew Callos: As previously communicated, FDA has agreed to us submitting the NDA on a rolling basis, which will provide FDA the opportunity to potentially begin their review of completed modules sooner. I am happy to share today that we initiated the first part of the rolling submission in July and that we are on track to complete the rolling submission during this third quarter. Alongside our work enabling us to submit the NDA to FDA this quarter, we're also continuing to prepare our MAA for submission to the European Medicines Agency.

Chris Murray: As previously communicated, FDA has agreed to us submitting the NDA on a rolling basis, which will provide FDA the opportunity to potentially begin their review of completed modules sooner.

Robert Blum: We undertake no obligation to update any forward-looking statements after this call, and now I will turn the call over to Robert. Thank you, Diane, and thanks for joining us on the call today. The second quarter was marked by significant progress and notable achievements across our later stage clinical development programs built on the foundation of cardiac mice and modulation. As well as a significant strengthening of our balance sheet and capital structure, enabling continued execution of the potential commercial launch of aphy campan as well as further advancement of our pipeline.

Speaker Change: I am happy to share today that we initiated the first part of the Rolling submission in July and that we are on track to complete the Rolling submission join this third quarter.

Speaker Change: Alongside our work enabling us to submit the NDA to FDA this quarter, we're also continuing to prepare our MAA for submission to the European Medicines Agency.

Speaker Change: During the quarter we participated in pre-semission meetings with the EMA and National Agency in the EU during which we confirmed our plan to submit an MAA in the fourth quarter of this year and we aligned on the content of this submission.

Robert Blum: In May, we were pleased to present the primary results from Sequoia HCM in a late-breaking clinical trial session at the European Society of Cardiology as heart failure 2024 Congress and Lisbon. As Fadi will elaborate, these results met our already high expectations, the safety and efficacy profile of aphy campan that has emerged from Sequoia HCM points to a potentially category-expanding opportunity as a next-in-class cardiac mice and inhibitor for patients with HCM. During the quarter, we continued our dialogue with FDA ahead of our planned submission of an NDA. We participated in a productive type B meeting with FDA to discuss potential strategies related to safety monitoring and risk mitigation for aphy campan.

Andrew Callos: During the quarter, we participated in pre-submission meetings with the EMA and national agencies in the EU, during which we confirmed our plan to submit an MAA in the fourth quarter of this year, and we agreed on the content of this submission. In parallel, we have participated in recent pre-submission meetings with the Chinese Center for Drug Evaluation and are coordinating with our partner, Zixing, to support plans to submit an NDA in China later this year. Altogether, Cytokinetics is taking big steps forward to ensure submissions for AFI Campton across major geographies globally. Now I will turn it over to Andrew.

Speaker Change: In parallel, we have participated in recent pre-submission meetings with the Chinese Center for Drug Evaluation and are coordinating with our partner, Zixing, to support plans to submit an NDA in China later this year.

Andrew Callos: Altogether, Cytokinetics is taking big steps forward to ensure submissions for Affie Kampton across major geographies globally. Now I will turn over to Andrew.

Andrew Callos: Thanks, Chris. In the second quarter, we finalized our market development campaign for AFI Campton, which we plan to launch next month at HSSA, and continue to design the overall patient treatment experience, inclusive of our specialty pharmacy distribution strategy and patient support program. With the result from Sequoia HCM in hand, we also advanced several market research studies to better understand the impact of the results of the trial on our potential product positioning, value propositioning, and market opportunity. I'm encouraged by the results I'm seeing from recent preference share research, which will ultimately be informed by our label and distinct risk mitigation approach.

Andrew Callos: Thanks, Chris. In the second quarter, we finalized our market development campaign for Aficantin, which we plan to launch next month at HSSA, and continue to design the overall patient treatment experience inclusive of our specialty pharmacy distribution strategy and patient support programs.

Robert Blum: We are pleased at how these discussions went and we're moving forward as planned, Chris Murray, SVP of Regulatory Affairs and Quality, has joined us today to provide an update on our regulatory interactions globally. With respect to only Campt of McCarble, over the past year we conducted numerous analyses of the results from Galactic HF. We spoke with regulators on several occasions, and we conferred with heart failure experts, on the unmet need and the potentially unique role that OME Campt of May play in treating patients with heart failure, all together while we evaluated our potential next steps.

Andrew Callos: With the results from Sequoia HCM in hand, we also advanced several market research studies to better understand the impact of the results of the trial on our potential product positioning, value propositioning, and market opportunity.

Speaker Change: I'm encouraged by the results I'm seeing from recent preference share research, which will ultimately be informed by our label and distinct risk mitigation approach.

Stuart Kupfer: During the quarter, we also continued our engagement with U.S. payers. Recently, our payer account management team began pre-approval information exchange with key payers to review the results of Sequoia HEM and the economic burden of Obstructive HEM. And we expect to continue these interactions with our PDUFA data. We have also initiated the development of a payer value dossier for both the U.S. and Europe, which will define the overall value proposition in support of our planned reimbursement.

Andrew Callos: During the quarter, we also continued our engagement with U.S. Pirates. Recently, our Payera account management team began pre-approval information exchange with key payers to review the results of Sequoia ATM and the economic burden of obstructive ATM. And we expect to continue these interactions to our pedophodate.

Robert Blum: What we found was a compelling opportunity for OME Campt of McCarble to address a large and growing population of people with severe heart failure, who have limited treatment options, and are at increased risk of hospitalization. With high adjacency to HCM in terms of treating physicians, we believe we can deliver a high return on investment by advancing OME Campt of McCarble with minimal increased commercial costs, following the launch of AFI Campton, and again should the confirmatory phase 3 clinical trial of OME Campt read out positively.

Speaker Change: We also initiated development of payer value dossier for both the U.S. and Europe , which will define the overall value proposition in support of our planned reimbursement.

Stuart Kupfer: At the same time, we work to finalize plans for size, structure, and alignment of the field-based health teams leveraging HCM diagnosis and treatment claims. I'll remind you that we are taking a disciplined and gated approach to spending as we expect to build our commercial infrastructure. We currently have on board a nearly completed field sales leadership team, but that only represents a small percentage of our overall sales infrastructure, and we did and we plan to hire a full sales team in 2025 in close proximity to the potential regulatory approval that becant, We also continued progress in our European commercial planning activities related to positioning, branding, distribution, launch strategy, and reimbursement, focused on Germany as the first country in which we would expect to launch Aficampton with other key countries in Europe to follow.

Speaker Change: At the same time, we work to finalize plans for size, structure, and alignment of the field-based health teams leveraging HCM diagnosis and treatment claims. I'll remind you that we are taking a disciplined and gated approach to spending as we expect to build our commercial infrastructure.

Speaker Change: We currently have on board a nearly completed field sales leadership team, but that only represents a small percentage of our overall sales infrastructure, and we plan to hire a full sales team in 2025 in close proximity to the potential regulatory approval of Aficanton.

Robert Blum: Furthermore, alongside CK586, we see a synergistic opportunity from both an R&D and commercial standpoint to build a sustainable specialty cardiovascular franchise for patients and to further unlock and to potentially maximize value for shareholders. Overall, we're proud to highlight an extensive development program for AFI Campton with multiple potential label expanding clinical trials ongoing, plus later stage development programs in adjacent specialty cardiology indications, with more still to come arising from our pioneering muscle biology research. We're carving out a specialty cardiology niche anchored in the foundation of our myosin platform, and with our site set on improving the lives of patients, while also enhancing shareholder value.

Speaker Change: We also continued progress in our European commercial planning activities related to positioning, branding, distribution, launch strategy, and reimbursement, focused on Germany as the first country in which we would expect to launch Aficampton with other key countries in Europe to follow.

Stuart Kupfer: We're eager to continue to ramp up our commercial readiness activities through this year and into 2025. To remind you, our plan is to continue to build a specialty cardiology franchise where we believe there is great potential to compete and succeed. Unlike a broader cardiology approach, the special cardiology interactions are focused on concentrated prescriber bases across a subset of cardiologists, a limited distribution model, high-tech patient support services, and a large opportunity to address unmet patient needs, all pointing to the potential for high return on investment. We're well on our way to building toward that future, which will be led by Afi Kanton. With that, I'll turn the call over to Stuart.

Speaker Change: We're eager to continue to ramp up our commercial readiness activities through this year and into 2025.

Speaker Change: To remind you, our plan is to continue to build a specialty cardiology franchise where we believe there is great potential to compete and succeed.

Speaker Change: Unlike a broader cardiology approach.

Speaker Change: The special cardiology interactions are focused on concentrated prescriber base across a subset of cardiologists, a limited distribution model, high-touch patient support services, and a large opportunity to address unmet patient need, all pointing to the potential for high return on investment.

Fady Malik: And with that, I'll turn the call over to Fatty, please. Thanks, Robert. In the second quarter, we were very pleased to present three late breaking clinical trial presentations in Elizabeth, including the primary results of Sequoia HCM and two additional analyses from the trial. The primary results, which were also published simultaneously in the New England Journal of Medicine, are consistent with our target product profile that may enable AFI Campton to become the cardiac myosin inhibitor of choice among physicians and patients.

Stuart Kupfer: We're well on our way to building toward that future as we'll be led by Afi Kanton. With that, I'll turn the call over to Stuart.

Stuart Kupfer: I'll start with Omicamptin-McCarbyl. In our interactions with FDA, while the agency concluded that the results from Galactic HF were not alone sufficient for approval, they were supportive of the conduct of an additional clinical trial of Omicamptin-McCarbyl. As you recall, in Galactic HF, the Cardiovascular Outcomes Trial in more than 8,000 patients, we observed significant risk reduction of heart failure outcomes with omecamps and McCarvel on top of standard of care, the magnitude of which was doubled in the large pre-specified subgroup of higher risk patients with lower ejection practice.

Stuart Kupfer: Thanks, Andrew

Speaker Change: As you recall, in Galactic HF, the Cardiovascular Outcomes Trial in more than 8,000 patients, we observed significant risk reduction of heart failure outcomes with Omicampton-McCarville on top of standard of care.

Fady Malik: The results showed that treatment with AFI Campton for 24 weeks significantly improved exercise capacity, increasing peak VO2 by 1.7 millimeter per kilo per minute compared to placebo, with a p value of 0.00002. This treatment effect was consistent across all pre-specified subgroups, including patients receiving beta blockers. Subsequent improvements, all p-less 1.001, were observed in each of the ten secondary endpoints, and patients treated with AFI Campton had substantial reductions in symptom burden, including a seven point improvement in the KCCQ, and 34% of the patients improving by at least one NYJ function.

Stuart Kupfer: The magnitude of which was doubled in a large, pre-specified subgroup of higher risk patients with lower ejection fraction.

Stuart Kupfer: Heart Failure Risk and Treatment Benefit Increase. Even further, in those patients with more recent heart failure hospitalizations, higher antiprobian P and lower blood pressure, Given that the subgroup of lower ejection fraction was over 4,000 patients, we're very confident in the potential benefit of treatment with Omecamtid mecarbil as an add-on therapy to standard of care in patients with severe heart failure. The planned confirmatory Phase III clinical trial will enroll approximately 2,000 HF-REF patients with severe heart failure and will include pragmatic design elements that enable it to be both smaller and more efficient than galactic HF, including less stringent safety monitoring requirements, a run-in period to enrich for more adherent patients, and simplified entry criteria.

Stuart Kupfer: Heart Failure Risk and Treatment Benefit Increased

Stuart Kupfer: Even further in those patients with more recent heart failure hospitalizations, high-ranking Caribbean P and lower blood pressure.

Stuart Kupfer: Given that the subgroup of lower ejection fraction was over 4,000 patients, we're very confident in the potential benefit of treatment with omacamphetamocarbal as an add-on therapy to standard of care in patients with severe heart failure.

Stuart Kupfer: The land confirmatory phase three clinical trial will enroll approximately 2,000 HEPRF patients.

Stuart Kupfer: The Severe Heart Failure and will include pragmatic design elements that enable it to be both smaller and more efficient than galactic HS.

Fady Malik: The original class compared with placebo. Another way to evaluate the treatment benefit of apicampton is by looking at its effect on the underlying hypercontractility that's characteristic of HCM. In Sequoia HCM, treatment with apicampton resulted in a significant and substantial reduction in the post-balsalva LVOT gradients of 50 millimeters of mercury or 60% of the baseline post-balsalva LVOT gradient. Importantly, this reduction in LVOT gradient was paired with less than 5% of a reduction in LVEF on average. Overall, we observed rapid and substantial reductions in LVOT gradients without a negative impact on left ventricular ejection fraction consistent with an improvement in the hypercontractility that occurs in HCM.

Stuart Kupfer: Including less stringent safety monitoring requirements, a running period to enrich for more adherent patients, and simplified entry criteria.

Stuart Kupfer: We're preparing to begin this trial in the fourth quarter of this year. Now, shifting now to our additional cardiac myosin inhibitor, CK586. I'll remind you that we described this mechanism in some detail at the 2023 biophysical meeting.

Stuart Kupfer: We're preparing to begin this trial in the fourth quarter of this year.

Stuart Kupfer: Shifting now to our additional cardiac myosin inhibitor, CK586, I'll remind you that we described this mechanism in some detail at the 2023 biophysical meeting.

Stuart Kupfer: We pursued optimization of the LEAP series that produced CK586 because it had a different mechanism of action than AFI-K. CK586 does not bind to the motor domain of myosin like apicamp but instead binds to the regulatory light chain of myosin and is a partial inhibitor of the myofibril ATPase. We still consider CK586 to be a cardiac myosin inhibitor with its own distinct mechanism of action, and we're advancing it into further clinical development for HFPEP.

Stuart Kupfer: We pursued optimization of a lead theory that produced CK586 because it had a different mechanism of action than aftercampons.

Stuart Kupfer: CK586 does not bind to the motor domain of myosin like apicampin, but instead binds to the regulatory light chain of myosin and is a partial inhibitor of the myofibril ATPase.

Stuart Kupfer: We still consider CK586 to be a cardiac myosin inhibitor with its own distinct mechanism of action, and we're advancing it into further clinical development for HFPEP.

Fady Malik: A recent manuscript published by Dr. Carolyn Coats and colleagues in the Journal of the American Heart Association detailed the safety and dosing results from CoATM and expanded and reinforced these initial observations. The paper comprehensively describes the key results of the CoATM that were tied to its aspirational pharmaceutical profile and engineered into apicampton. Specifically, these analyses showed that apicampton rapidly reduced LVOT gradients within two weeks of treatment initiation without the need for either treatment discontinuation or interruption during the dose escalation phase.

Stuart Kupfer: During the second quarter, we announced top-line data from the Phase 1 study showing that CK586 was safe and well-tolerated in healthy participants with generally linear pharmacokinetics at single dose. At the highest single dose of 600 mg, the mean decrease in LVA ejection fraction compared to placebo was less than 5%. The PK-PD relationship for CK586 appears to be even shallower than for epi, and it has a shorter half. We plan to present these data in full at a medical meeting this quarter.

Stuart Kupfer: At the highest single dose of 600 mg, the mean decrease in LVA ejection fraction compared to placebo was less than 5%.

Stuart Kupfer: The PK-PD relationship for CK586 appears to be even shallower than apicampin.

Stuart Kupfer: and it has a shorter half-life.

Stuart Kupfer: We plan to present these data in full at a medical meeting this quarter, and because the top-line findings are supportive of advancing the program, we're preparing to start a Phase IIa clinical trial in the fourth quarter of this year in patients with Hep-PET.

Fady Malik: Additionally, the pharmacokinetics were generally linear with low variability once the target dose was attained and that led to a very little change in LVEF during the maintenance phase of treatment, essentially indistinguishable from placebo in that regard. Effectiveness of down titration for LVEF less than 50%, and the reversibility of its pharmacokinetics were convincingly demonstrated, importantly, there were no associated heart failure events. The goal of treatment in HCM is not only to reduce the LVOT gradient, but also to normalize left ventricular ejection fraction.

Stuart Kupfer: And because the top-line findings are supportive of advancing the program, we're preparing to start a Phase IIa clinical trial in the fourth quarter of this year in patients with Hep PEP. We're pleased with the profile of CK586 and believe it may further solidify our leadership in cardiac myosin modulation and our specialty cardiology franchise. Finally, I want to provide an update on TK1. During the second quarter, we completed analyses of data from the Phase 1 study, which met its primary objective to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of CK136 in healthy participants.

Stuart Kupfer: We're pleased with the profile of CK586 and believe it may further solidify our leadership in cardiac myosin modulation and our specialty cardiology franchise.

Stuart Kupfer: Finally, I want to provide an update on TK136.

Stuart Kupfer: During the second quarter, we completed analyses of data from the Phase I study, which met its primary objective to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of CK136 in healthy participants.

Fady Malik: As the paper outlines, patients treated with apicampton with the largest excursions in LVEF from baseline, 20% or higher, all had baseline LVF greater than 75%. None of these individuals had an LVF below 50% at any visit. As the largest reductions in LVEF occurred in the participants with the most severe hypercontractility, consistent with the objective of treatment.

Stuart Kupfer: There were no safety signals or negative effects observed in the Phase 1 study. However, in light of our recent decision to advance omicantin-micarbol, which is also a sarcomere activator, and after a review of the Phase I data and other strategic priorities by our Portfolio Review Committee, we did not identify a compelling opportunity for CK136 relative to omicantin-micarbol. As a result, we've decided to discontinue further development of CK136. And with that, I'll pass it to Sean.

Stuart Kupfer: There were no safety signals or negative effects observed in the Phase 1 study. However, in light of our recent decision to advance Omicantin-McCarbol, which is also the sarcomere activator.

Stuart Kupfer: And after a review of the Phase I data and other strategic priorities by our Portfolio Review Committee, we did not identify a compelling opportunity for CK136 relative to Omicam's McCarvel. As a result, we decided to discontinue further development of CK136.

Fady Malik: The upcoming European Society of Cardiology meeting in London will have six presentations relating to apicampton, including four-lay breakers and two-oral presentations. Results from SCOIA HCM related to KCCQ, cardiac structure, function, and biomarkers will be presented. Alongside that, we'll be presenting an integrated safety analysis from four-stage HCM and data related to the withdrawal of standard of care medications. We believe that totalities presentations will importantly elaborate on how apicampton is achieving our target product profile.

Sung Lee: Thanks, Stuart. We're pleased to report our second quarter of 2024 financial results. Starting with the balance sheet, we finished the second quarter of 2024 with approximately $1.4 billion in cash, cash equivalents, and investments, compared to $634.3 million at the end of the first quarter of 2024. The quarter-over-quarter increase was primarily driven by the execution of a public offering of common stock in the second quarter that resulted in net proceeds of $563.2 million after deducting underwriting discounts and commissions.

Stuart Kupfer: And with that, I'll pass it to someone.

Speaker Change: Thanks, Stuart. We're pleased to report our second quarter of 2024 financial results.

Speaker Change: Starting with the balance sheet, we finished the second quarter of 2024 with approximately $1.4 billion in cash, cash equivalents, and investments, compared to $634.3 million at the end of the first quarter of 2024.

Speaker Change: The quarter-over-quarter increase was primarily driven by the execution of a public offering of common stock in the second quarter that resulted in net proceeds of $563.2 million after deducting underwriting discounts and commissions.

Fady Malik: Moving on to the ongoing clinical trials program for apicampton, we're pleased to report that we're on track to complete enrollment in Maple HCM during this quarter.

Sung Lee: In addition, we entered into a $575 million strategic financing agreement with Royalty Pharma in May that delivered $250 million upon signing. The upfront amount is comprised of $100 million funding for a confirmatory Phase III clinical trial of Omicamptomacarbal, $50 million investment in a Phase IIa clinical trial of CK586 and HFPAF, $50 million term loan to support the potential commercial launch of Aficaptan and Obstructive HCM, and $50 million for shares of common stock in a private placement.

Stuart Kupfer: In addition, we entered into a $575 million strategic financing agreement with Royal Teaparma in May that delivered $250 million upon signing.

Fady Malik: In fact, we are no longer seeking new patients to enter screening. As a reminder, this clinical trials evaluating the potential superiority of apicampton as monotherapy compared to Metoprolol as monotherapy in obstructive HCM. We expect that completing enrollment this quarter should enable results to read out in the first half of 2025 ahead of when we hope to be launching apicampton commercially. And if positive, we'll represent a potential label enhancement opportunity and provide evidence on how apicampton could be positioned as first-line therapy relative to beta blockers and practice guidelines.

Stuart Kupfer: The upfront amount is comprised of $100 million funding for a confirmatory Phase III clinical trial of Omacamptin-McCarbyl, $50 million investment in a Phase IIa clinical trial of CK586 and HFPEF,

Stuart Kupfer: $50 million term loan to support the potential commercial launch of Afi Campton in an obstructive HCM, and $50 million for shares of common stock in a private placement.

Sung Lee: The remaining $325 million is comprised of a term loan of up to $175 million that we have the option to draw upon the satisfaction of certain conditions and an investment by Royalty Pharma of up to $150 million in a Phase III clinical trial of CK586 should Royalty Pharma choose to opt in to fund the trial in exchange for an increase in their revenue interest in CK586. We believe the overall financing package comes with an attractive and market-competitive cost of capital and, combined with the net proceeds from the equity financing, positions us well to support the commercial launch of AppyCampden, expand its development program, and advance our pipeline.

Stuart Kupfer: The remaining $325 million is comprised of a term loan of up to $175 million that we have the option to draw upon the satisfaction of certain conditions.

Fady Malik: Enrollment in Acacia HCM, the pivotal phase three clinical trial of api-campton and patients with symptomatic non- obstructive HCM has progressed substantially, and we continue to activate clinical sites during the quarter. Enrollment is brisk and remains consistent with our current projections. We look forward to continuing to enroll patients in Acacia HCM through this year with the goal of completing patient enrollment in 2025.

Stuart Kupfer: and an investment by royalty-parma of up to $150 million in a phase three clinical trial of CK586 should royalty-parma choose to opt in to fund a trial in exchange for an increase in their revenue interest in CK586.

Stuart Kupfer: We believe the overall financing package comes with an attractive and market competitive cost of capital and combined with the net proceeds from the equity financing positions us well to support the commercial launch of ATHCAPTAN, the expanded development program and advance our pipeline.

Fady Malik: Recently, the European Journal of Heart Failure published a short report with data from 34 patients with NACM through 36 weeks of treatment in forest HCM, the Open Label Extension Clinical Trial.

Speaker Change: Moving on to the income statement, total revenues in the second quarter of 2024 were $0.2 million compared to $0.9 million for the same period in 2023.

Fady Malik: This is the first data we have on extended treatment with api-campton and patients with NACM. Api-campton appeared generally well-tolerated with patients experiencing substantial improvements in symptom burden, NYJ Functional Class and NT-ProBNP. There were no drug discontinuations due to adverse events. These results suggest that longer-term treatment with api-campton can be both safe and effective in patients with NACM.

Stuart Kupfer: R&D expenses in the second quarter of 2024 were $79.6 million compared to $83.2 million for the same period in 2023.

Stuart Kupfer: The decrease was primarily driven by the timing of clinical trial activities and wind-down activities for COURAGE-ALS, which ended in the first quarter of 2023.

Fady Malik: We look forward to hopefully building on these findings with more data from forest HCM and, of course, seeing the results from Acacia HCM one available.

Sung Lee: GNA expenses in the second quarter of 2024 were $50.8 million, compared to $39.7 million for the same period in 2023. The increase was primarily driven by investments toward commercial readiness and personnel expenses. The net loss for the second quarter of 2024 was $143.3 million, or $1.31 per share, basic and diluted, compared to a net loss of $128.6 million, or $1.34 per share, basic and diluted, for the same period in 2023. Now I'd like to turn to our updated financial guidance for 2024.

Stuart Kupfer: GNA expenses in the second quarter of 2024 were $50.8 million, compared to $39.7 million for the same period in 2023. The increase was primarily driven by investments toward commercial readiness and personnel expenses.

Fady Malik: Our fourth ongoing clinical trial of api-campton is Cedar HCM, evaluating a pediatric population of patients with symptomatic OACM, which we open to enrollment in the second quarter.

Stuart Kupfer: Net loss for the second quarter of 2024 was $143.3 million, or $1.31 per share, basic and diluted, compared to a net loss of $128.6 million, or $1.34 per share, basic and diluted, for the same period in 2023.

Fady Malik: Cedar HCM provides an opportunity to further extend the potential utility of api-campton, an additional segment of the broader HCM population, as may further elaborate a NACM class profile.

Sung Lee: We expect GAAP operating expenses to be between $555 million and $575 million, compared to the previous range of $535 million to $555 million. Non-cash operating expense comprised of stock-based compensation and depreciation, which is included in GAAP operating expense, is now expected to be between $105 million and $110 million, compared to the previous range of $105 million to $115 million. Non-GAAP operating expenses, which exclude stock-based compensation and depreciation, are expected to be between $445 million and $470 million, compared to the previous range of $420 million to $450 million.

Fady Malik: Finally, during the quarter, we started to phase one study, evaluating the pharmacokinetic safety and tolerability of api-campton and healthy Japanese and Caucasian participants to gather evidence that we believe will be required for potential approval of api-campton in Japan. Again, expanding where api-campton may be able to have a meaningful, positive and differentiated impact on patient lives.

Speaker Change: Now, I'd like to turn into our updated financial guidance for 2024.

Stuart Kupfer: We expect GAAP operating expenses to be between $555 million to $575 million compared to the previous range of $535 million to $555 million.

Stuart Kupfer: Non-cash operating expense comprised of stock-based compensation and depreciation, which is included in GAAP operating expense, is now expected to be between $105 million to $110 million,

Christine Murray: I'd like to invite Chris Murray to provide an update on the regulatory front for api-campton. Thanks, Fabi, and pleased to join today's call to share updates on our regulatory progress during the past quarter. As Robert mentioned, ahead of our planned NDA submission for api-campton, during the quarter, we participated in a type B meeting with FDA, during which we discussed strategies related to safety monitoring and risk mitigation in support of our NDA submission.

Stuart Kupfer: Compared to the previous range of $105 million to $115 million.

Stuart Kupfer: non-GAAP operating expenses, which exclude stock-based compensation and depreciation, is expected to be between $445 million to $470 million, compared to the previous range of $420 million to $450 million.

Christine Murray: As a reminder, two earlier meetings where the FDA were completed in February, including a first meeting to review the results of the Ciccoria HCM, and a second pre-NDA meeting to cover specific topics related to our submission. This more recent third meeting provided the important opportunity to elaborate on the safety and pharmaceutical properties of api-campton and discuss how they may inform approaches to manage risk and gain insight into FDA's perspective on this matter.

Sung Lee: Net cash utilization is expected to be between $400 million and $420 million compared to the previous range of $390 million to $420 million. The increase in GAAP and non-GAAP operating expenses is primarily being driven by the initiations of the Phase 2a trial of CK586 and the Phase 3 trial of Omicampta-McCarville.

Stuart Kupfer: Net cash utilization is expected to be between $400 million to $420 million compared to the previous range of $390 million to $420 million.

Robert Blum: The increase in gap and non-gap operating expenses is primarily being driven by the initiations of the Phase 2A trial of CK586 and the Phase 3 trial of OmaCaptain McCarble. With that, I'll hand it back over to Robert. Thank you, son.

Robert Blum: With that, I'll hand it back over to Robert. Thank you, Scott.

Christine Murray: We are very pleased with the progress we have made with FDA in this series of meetings, and FDA's continued engagement ahead of the submission of the NDA for api-campton. While we understand that risk mitigation will ultimately be a review topic with FDA following our recent type B meeting, we plan to propose a distinct risk mitigation approach specific to api-campton with the NDA.

Robert Blum: As Sung summarized, we're in an advantaged financial position, with a fortified capital structure that we believe will carry us through the potential commercial launch of AFI Campton and also allow us to continue to conduct potential label and category expanding global clinical trials of AFI Campton, all while also advancing our later stage development pipeline, including Omicampt of McCarvel and CK586 focused on one area of biology in adjacent cardiology specialty segments. To that end, we recently reaffirmed our intentions to advance our commercial strategies and build our specialty cardiology franchise.

Robert Blum: As Sung summarized, we're in an advantaged financial position.

Speaker Change: with a fortified capital structure that we believe will carry us through the potential commercial launch of Affy Campton.

Speaker Change: And also allow us to continue to conduct potential label and category expanding global clinical trials of afecamtin, all while also advancing our later stage development pipeline, including Omicamptiv-McCarbyl and CK586,

Christine Murray: Another important outcome of our recent type B meeting was that the agency agreed to approach a column amendment for the ongoing open-label extension trial for the HCM, reducing the frequency of echo monitoring required during the treatment maintenance phase. The amendment allows patients with OHCM to now undergo echo monitoring every six months instead of every three months during maintenance treatment. If their LVEF is above 55%, and there's an absence of other conditions that may impair systolic function.

Speaker Change: focus to one area of biology in adjacent cardiology specialty segments.

Speaker Change: To that end, we recently reaffirmed our intentions to advance our commercial strategies and build our specialty cardiology franchise.

Robert Blum: However, as we stated in an 8K issued during the second quarter, we also recognize our fiduciary responsibilities to consider all potential opportunities to maximize shareholder value. This may take the form of building our business in the ways we've outlined today, or it may involve M&A. We fully understand our obligation to shareholders, and we will consider alternatives, but the way we can ourselves plan to maximize shareholder value today is by building enduring value in our pipeline and becoming a category leader anchored by AFI Campton. We also envision leveraging our R&D and financial strengths to augment our pipeline with potential external opportunities.

Speaker Change: However, as we stated in an 8K issued during the second quarter, we also recognize our fiduciary responsibilities to consider all potential opportunities to maximize shareholder value.

Christine Murray: The approach column amendment was based on the overall safety and polar royalty profile observed in the development programme thus far. As we've reported, there have been no treatment interruptions attributed to Afi-Campton observed in Forest HCM to date. The approach to echo monitoring now implemented in Forest HCM reflects the potential real-world risk-based approach for how clinicians could manage patients who are taking Afi-Campton.

Speaker Change: This may take the form of building our business in the ways we've outlined today, or it may involve M&A.

Speaker Change: We fully understand our obligation to shareholders, and we will consider alternatives. But the way we can ourselves plan to maximize shareholder value today is by building and during value in our pipeline and becoming a category leader anchored by Afi Campton.

Christine Murray: As previously communicated, FDA has agreed to our submitting the NDA on a rolling basis, which will provide FDA the opportunity to potentially begin their review of completed modules sooner. I am happy to share today that we initiated the first part of the rolling submission during this third quarter. Alongside our work enabling us to submit the NDA to FDA this quarter, we're also continuing to prepare our MAA for submission to the European Medicine Agency.

Speaker Change: We also envision leveraging our R&D and financial strengths to augment our pipeline with potential external opportunities.

Robert Blum: To that end, during the quarter, we were pleased to welcome a new member to our Corporate Steering Committee, Isaac Chekanova, who joins us as Executive Vice President, Corporate Development, and Chief Business Officer. Isaac previously served as CEO of Attara Biotherapeutics. He led business development at Celgene and held partner positions at leading venture capital firms. Isaac will be responsible for expanding the company's presence into new geographies, catalyzing external R&D activities, and mapping out potential new business objectives, which may include potential divestitures and spin-out companies, as well as potentially M&A, both buy side and sell side, and other business combinations.

Speaker Change: To that end, during the quarter, we were pleased to welcome a new member to our Corporate Steering Committee, Isaac Chekanova, who joins us as Executive Vice President, Corporate Development, and Chief Business Officer.

Speaker Change: Isaac previously served as CEO of Atara Biotherapeutics. He led business development at Celgene and held partner positions at leading venture capital firms.

Speaker Change: Isaac will be responsible for expanding the company's presence into new geographies.

Christine Murray: During the quarter, we participated in pre-submission meetings with the EMA and national agencies in the EU during which we confirmed our plan to submit an MAA in the content of the submission. In parallel, we have participated in recent pre-submission meetings with the China-Chinese Centre for Drug Evaluation and are coordinating with our partners, Xi Jinping, to support plans to submit an NDA in China later this year. All together, scientific and ethics is taking big steps forward to ensure submissions for Afi-Campton across major geographies globally.

Speaker Change: Tatolizing External R&D activities and mapping out potential new business objectives, which may include potential investors and spin-out companies, as well as potentially M&A, both by side and sell side and other business combinations.

Robert Blum: Isaac brings with him a wealth of knowledge and expertise for which we're grateful as we continue to build cytokinetics. I'm proud of our accomplishments this past quarter, and as you've heard, we're especially pleased with the progress we made with FDA relating to the NDA submission for afecamton and its potential for a distinct risk mitigation profile if approved for commercialization. Before we move to questions, however, I want to emphasize that due to the proprietary and confidential nature of our discussions with FDA, we do not intend to provide further details about our meetings with FDA, and we do not plan to present further updates on these matters, knowing that answers to any remaining questions will depend on FDA review. Now, I'd like to recap our upcoming milestones.

Speaker Change: Isaac brings with him a wealth of knowledge and expertise for which we're grateful as we continue to build cytokinetics.

Speaker Change: I'm proud of our accomplishments this past quarter, and as you've heard, we're especially pleased with the progress we've made with FDA, relating to the NDA submission for affecamtin,

Andrew Callos: Now, I will turn over to 100. Thanks, Chris. In the second quarter, we finalized our market development campaign for Afi-Campton, which we plan to launch next month at HSSA, and continue to design the overall patient treatment experience inclusive of our specialty pharmacy distribution strategy and patient support programs. With the result from Sequoia HCM in hand, we also advanced several market research studies to better understand the impact of the results on the trial of the trial on our potential product positioning, value propositioning, and market opportunity.

Speaker Change: and its potential for a distinct risk mitigation profile.

Speaker Change: If approved for commercialization.

Speaker Change: Before we move to questions, however I want to emphasize that due to the proprietary and confidential nature of our discussions with FDA, we do not intend to provide further details about our meetings with FDA.

Speaker Change: And we do not plan to present further updates on these matters, knowing that answers to any remaining questions will depend on FDA review.

Speaker Change: Now I'd like to recap our upcoming milestones.

Robert Blum: For AFI Campton, we expect to present additional results from Sequoia HCM at the European Society of Cardiology Congress later this month. We expect to submit an NDA to the FDA in Q3 2024, an MAA to the EMA in Q4 2024, and to coordinate with Zhejiang to support the planned NDA submission to the MMPA in China in the second half of this year. We expect to complete enrollment in Maple HCM in this third quarter of 2024.

Speaker Change: For AFI-CAMPTON, we expect to present additional results from Sequoia HCM at the European Society of Cardiology Congress later this month.

Andrew Callos: I'm encouraged by the results I'm seeing from recent preference year research, which will ultimately be informed by our label and distinct risk mitigation approach. During the quarter, we also continued our engagement with U.S, payers. Recently, our payer account management team began pre-approval information exchange with key payers to review the results of Sequoia HCM and the economic burden of obstructive HCM. And we expect to continue these interactions through our producer. We also initiate a development of pay-re-value dossier for both the US and Europe, which will define the overall value proposition and support of our plan reimbursement.

Speaker Change: We expect to submit an NDA to the FDA in Q3 2024, an MAA to the EMA in Q4 2024, and to coordinate with Zhejiang to support the planned NDA submission to the MPA in China in the second half of this year.

Speaker Change: We expect a complete enrollment in Maple HCM in this third quarter, 2024.

Speaker Change: We expect to continue enrollment in ACACIA HCM throughout 2024 with objective to complete enrollment in 2025.

Andrew Callos: At the same time, we work to finalize plans for size, structure, and alignment of the field-based sales teams leveraging HEM, diagnosis, and treatment claims. I'll remind you that we are taking a disciplined and gated approach to spending as we expect to build our commercial infrastructure. We currently have on board a nearly-compliant field sales leadership team, but that only represents a small percentage of our overall sales infrastructure.

Robert Blum: We expect to continue enrollment in Acacia HCM throughout 2024 with the objective to complete enrollment in 2025. We expect to continue enrollment in Cedar HCM this year, and we expect to continue the Phase 1 study of AfiKamton in Japanese and Caucasian participants this year, and we expect to continue advancing our go-to-market strategies for AfiKamton through the year. For Omicampt of McCarble, we expect to start a confirmatory Phase III clinical trial in the fourth quarter of 2024.

Speaker Change: We expect to continue enrollment in Cedar H.C.M. this year to continue the phase one study of Afie Campton in Japanese and Caucasian participants this year. And we expect to continue advancing our go to market strategies for Afie Campton through the year.

Speaker Change: For Omicampt of McCarble, we expect to start a confirmatory Phase III clinical trial in the fourth quarter, 2024.

Andrew Callos: And we plan to hire our full sales team in 2025 in close proximity to the potential regulatory approval of Attecansons. We also continued progress in our European commercial planning activities related to positioning, branding, distribution, launch strategy, and reimbursement, focused on Germany as the first country in which we would expect to launch Attecansons with other key countries in Europe. We're eager to continue to ramp up our commercial readiness activities through this year and into 2025.

Robert Blum: For CK586, we expect to present primary data from the Phase I study at a medical meeting in the third quarter of 2024 and to start a Phase IIa clinical trial in the fourth quarter of 2024. And for preclinical development and ongoing research, we expect to initiate clinical development with a fast skeletal muscle troponin activator later this year and continue ongoing preclinical development and research activities directed to additional muscle biology-focused programs through the remainder of the year. And Operator, with that, we can now open up the call to questions, please. Thank you.

Speaker Change: For CK586, we expect to present primary data from the Phase I study at a medical meeting in this third quarter, 2024, and to start a Phase IIa clinical trial in the fourth quarter, 2024.

Speaker Change: and for preclinical development and ongoing research.

Speaker Change: We expect to initiate clinical development with a fast skeletal muscle troponin activator later this year and continue ongoing preclinical development and research activities directed to additional muscle biology focused programs through the remainder of the year.

Andrew Callos: To remind you, our plan is to continue to build a specialty cardiology franchise where we believe there is great potential to compete and succeed. Unlike a broader cardiology approach, the special cardiology interactions are focused on concentrated prescriber base across a subset of cardiologists, a limited distribution model, high-touch patient support services, and a large opportunity to address unmet patient need, all pointing to the potential for a high return on investment. We're wrong on our way to building toward that future, as we'll be led by Affy Campon.

Speaker Change: Operator, with that, we can now open up the call to questions, please.

Unknown Executive: Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. As a reminder, the company has requested that each participant please adhere to the allowance of one question per person. Please stand by while we compile the Q&A roster. And our first question comes from Salim Syed of Mizzou. Your line is open.

Speaker Change: Thank you to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again.

Speaker Change: As a reminder, the company has requested that each participant please adhere to the allowance of one question per person. Please stand by while we compile the Q&A roster.

Stuart Kupfer: With that, I'll turn the call over to Stuart. Thanks, Andrew. I'll start with Oman Campon McCarvel. In our interactions with FDA, while the agency concluded that the result from Galactic HF were not alone sufficient for approval, they were supportive of the conduct of an additional clinical trial of Oman Campon McCarvel. As you recall, in Galactic HF, the Cardiovascular Outcomes trial in more than 8,000 patients, we observed significant risk reduction of heart failure outcomes with Oman Campon McCarvel on top of standard of care.

Speaker Change: Hello and welcome to the next episode of The End of The End of The End of The End

Speaker Change: And our first question comes from the line of Salim Syed of Mizzou. Your line is open.

Salim Syed: Good afternoon, Salim. Good afternoon, Robert. Thanks for taking the question and congratulations on the progress.

Salim Syed: Good afternoon, Salim. Good afternoon, Robert. Thanks for taking the question and congrats on the progress. I guess I want to welcome Isaac to the company. I had a question on just that related matter with Isaac joining.

Robert Blum: I guess I want to welcome Isaac to the company. I had a question on just that related matter with Isaac joining. Is it possible to just give us sort of like your framework for thinking here? I know there was no 8K or press release that I came across. But it seems like something that's important to the business, so just maybe the cadence of the business development activities we should be expecting, and primarily updated thoughts around Athacampton Europe, if that's in the cards, or was this more gated to potentially doing business development around Omakampton Macarple? Thank you.

Stuart Kupfer: The magnitude of which was doubled in the large pre-specified subgroup of higher risk patients with lower ejection fractions. Heart failure risk and treatment benefit increased even further in those patients with more recent heart failure hospitalizations, higher anti-probe and P and lower blood pressure. Given that the subgroup of lower ejection fraction was over 4,000 patients, we're very confident in the potential benefit of treatment with Oman Campon McCarvel as an add-on therapy to standard of care and patients with severe heart failure.

Speaker Change: Is it possible to just give us sort of like how you're frameworking to think in here? I know there was no 8K or press release that I came across.

Salim Syed: but it seems like it seems like something that's important to the business so

Speaker Change: This may be the cadence of the business development activities we should be expecting and primarily updated thoughts around Athacampton Europe , if that's in the cards, or was this more gated to potentially doing business development around Omakampton Macarple? Thank you.

Stuart Kupfer: The planned confirmatory phase to reclinital trial will enroll approximately 2,000 HF rep patients with severe heart failure, and will include pragmatic design elements that enable it to be both smaller and more efficient than Galactic HF. Including less stringent safety monitoring requirements, a run-in period to enrich for more adherent patients, and simplified entry criteria. We're preparing to begin this trial in the fourth quarter of this year.

Robert Blum: Yeah, certainly, this doesn't change the way we're thinking about AFI Campton, either in Europe or in North America. And I do believe that our ongoing business development activities with respect to AFI Campton in Japan are already well on track. The bringing on board of Isaac really speaks less to those matters and more to what I would fall under corporate development as opposed to business development. And I foresee where Isaac is going to take the lead, as we think about what geographies we might want to increase our footprint in as an ongoing R&D and commercial enterprise, and even more so to augment how we think about muscle biology, both by side and potential cell side activities.

Speaker Change: Yes, so certainly this doesn't change the way we're thinking about Affey-Campton.

Speaker Change: by there in Europe.

Speaker Change: or in North America.

Speaker Change: and I do believe that our ongoing business development activities with respect to Afi Campton in Japan are already well on track.

Speaker Change: The bringing on board of Isaac really speaks less to those matters and more to what I would fall under corporate development as opposed to business development.

Stuart Kupfer: Shifting now to our additional cardiac mice and inhibitors, CK586, I'll remind you that we described this mechanism in some detail at the 2023 Biophysics. Medical Meeting. We pursued optimization of a lead series that produced K586 because it had a different mechanism of action than Afi-Campons. K586 does not bind to the motor domain of Mayas and like Afi-Campons, but instead binds to the regulatory light chain of Mayas and is a partial inhibitor of the myfibral ATPase.

Speaker Change: and I foresee where Isaac is going to take the lead as we think about what geographies we might want to increase our footprint in as a ongoing R&D and commercial enterprise.

Speaker Change: and even more so to augment how we think about muscle biology, both by side and potential cell-side activities, meaning the following. We think that as a pioneer and a leader in this space, we're in a good position.

Robert Blum: Meaning the following, we think that as a pioneer and a leader in this space, we're in a good position to imagine new possibilities and opportunities both to monetize the things we're currently doing and to combine with potential others. As we've discussed, and many investors have asked in the past, how do we think about spinning out companies? How do we think about potentially being an aggregator of technologies? I wouldn't expect anything meaningfully large.

Stuart Kupfer: We still consider CK586 to be a cardiac Mayas and inhibitor with its own distinct mechanism of action and we're advancing it into further clinical development for HEPP. During the second quarter, we announced top-line data from the phase one study showing that CK586 was safe and well-tolerated and healthy participants, which generally linear pharmacokinetics at single doses from 10 to 600 milligrams. At the highest single dose of 600 milligrams, the mean decrease and that will be a jetting for action compared to placebo was less than 5%. The PK-PD relationship for CK586 appears to be even shallower than Afi-Campons and it has a shorter half-blood.

Speaker Change: To imagine new possibilities and opportunities both to monetize the things we're currently doing and combine with potential others.

Speaker Change: As we've discussed...

Speaker Change: and many investors have asked in the past.

Speaker Change: How do we think about spinning out companies? How do we think about potentially being an aggregator of technologies? I wouldn't expect anything meaningfully large.

Robert Blum: For instance, I don't think this factors into how we're thinking about spending in a meaningfully large way, but I do think it ties to how we capitalize on our leadership in the space and maintain that ongoing leadership. And I believe that Isaac will be a great architect working with R&D colleagues for how that strategy can ultimately be implemented, less so this year and more in years to come. I hope that answers your question.

Speaker Change: For instance, I don't think this...

Speaker Change: factors into how we're thinking about

Speaker Change: Spending in a meaningfully large way, but I do think it ties to

Speaker Change: Now we capitalize on our leadership in this space.

Isaac: And I believe that Isaac will be a great architect working with R&D colleagues for how that strategy can ultimately be implemented, less so this year and more in years to follow. I hope that answers your question.

Stuart Kupfer: We plan to present these data in full at a medical meeting this quarter and because the top-line findings are supportive of advancing the program, we're preparing to start a phase two A clinical trial and fourth quarter of this year in patients with HEPP.

Salim Syed: Yes, I did. Thank you so much.

Stuart Kupfer: We're pleased with the profile CK586 and believe it may further solidify our leadership in cardiac Mayas and modulation and our specialty cardiology franchise.

Akash Tewari: Our next question comes from the line of Akash Tewari of Jeffries. Your line is open.

Speaker Change: Yes it did. Thanks so much.

Speaker Change: Our next question comes from a line of Akash Tewari of Jeffries. Your line is open.

Unknown Executive: Good afternoon. Hey, good afternoon.

Akash Tewari: I realize you can't talk about your meeting with the FDA, but how much should we read into this protocol amendment on Forrest, which now allows a six-month echo for patients with an LAVF above 55? Shouldn't it strongly predict what a REM should ultimately be? And is there a possibility that the FDA won't require REMs at all, pending more follow-up data from Forrest?

Stuart Kupfer: Finally, I want to provide an update on CK136. During the second quarter, we completed analyses of data from the phase one study, which met its primary objective to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of CK136 and healthy participants. There were no safety signals or negative effects observed in the phase one study.

Akash Tewari: Good afternoon, I think.

Akash Tewari: Hey, good afternoon. I really can't talk about your meeting with the FDA, but how much should we read into this protocol amendment on for us, which now allows the six month echo for patients with an LVF above 55, shouldn't this strongly predict what a rum should ultimately be, and is there a possibility of the FDA won't require a rum that all pending more follow-up data from for us? And maybe Robert, if I could speak in one more, you talk about it.

Stuart Kupfer: However, in line of our recent decision to advance on the cancer macarabal, which is also the sarcomere activator, and after review of the phase one data and other strategic priorities by our portfolio review committee, we did not identify a compelling opportunity for CK136 relative to on the cancer macarabal. As a result, we've decided to discontinue for the development of CK136.

Robert Blum: And maybe, Robert, if I can sneak in one more, you talk about why you might spin off some assets. Can you talk about why it might be preferable to spin off certain assets ahead of, let's say, pending M&A if, let's say, there is an overlap in a company that has a HECTF portfolio? You know, I'm thinking specifically about CK586 and spinning that asset off. Thank you.

Speaker Change: Why you might spin off some assets?

Speaker Change: Can you talk about why it might be preferable to spin off certain assets?

Robert Blum: ahead of let's say pending M&A if let's say there is an overlap in a company that has a HECTF portfolio. You know, I'm thinking specifically about CK586 and spinning that asset off. Thank you.

Robert Blum: Yes, but I wouldn't interpret my earlier comments to suggest that we're thinking about spinning off any later stage clinical programs, as we believe our specialty cardiology franchise is the way that we maximize shareholder value, whether that's on our own or through, as you asked, potential M&A. But I do think there's a lot of value in what we're doing preclinically and otherwise, as we're expanding beyond specialty cardiology that could ultimately be monetized in other ways, and which could benefit from funding in other ways.

Sung Lee: And with that, I'll pass it to Sun. Thanks, Stuart.

Speaker Change: Yes, I wouldn't interpret my earlier comments to suggest that we're thinking about spinning off any later stage clinical programs.

Sung Lee: We're pleased to report our second quarter of 2024 financial results. Starting with the balance sheet, we finished the second quarter of 2024 with approximately $1.4 billion in cash, cash equivalence, and investments compared to $634.3 million at the end of the first quarter of 2024. The quarter of a quarter increase was primarily driven by the execution of a public offering of common stock in the second quarter that resulted in that proceeds of $563.2 million after deducting underwriting discounts and commissions.

Speaker Change: As we believe our specialty cardiology franchise

Speaker Change: is the way that we do maximize shareholder value, whether that's on our own or through, as you asked, potential M&A.

Speaker Change: But I do think there's a lot of value in what we're doing preclinically and otherwise as we're expanding beyond specialty cardiology that could ultimately be monetized in other ways and as could benefit from funding in other ways.

Robert Blum: As it relates to your question pertaining to FDA, again, I'll underscore, I'm not really in a position to elaborate on the meeting, but, however, we do believe FOREST represents a real-world evaluation of affecamtin, and we're pleased that FDA foresees, much like we do, how, for having been monitoring echoes on a more frequent basis in FOREST for a long time and having accumulated quite a lot of data, data that isn't contributing from a clinical standpoint to any meaningful changes in the way these patients are managed, FDA seemed amenable to our recommendation that we change the frequency by which echo monitoring needed to occur. So that's encouraging, but ultimately, I don't think I'll go so far as to make a direct correlation, as you're asking, between that change and what FDA may choose to do with respect to a potential risk mitigation profile. That's perhaps connecting of the dots that I'm unwilling to do on this call. Fatih, is there anything more that you might want to add on that matter? I mean, I think

Speaker Change: As it relates to your question pertaining to FDA, again I'll underscore I'm not really in a position to elaborate on the meeting

Sung Lee: In addition, we entered into a $575 million strategic financing agreement with royalty parma in May that delivered $250 million upon signing. The upfront amount is comprised of $100 million funding for a confirmatory phase III clinical trial of Omicaptive Macarabal, $50 million investment in a phase IIA clinical trial of CK586 and half past $50 million investment in a phase IIA clinical trial of CK586 and half past $50 million. $50 million term loan to support the potential commercial launch of Affi Campton and obstructive HCM, and $50 million for shares of common stock in a private placement.

Speaker Change: But however, we do believe forest represents a real world evaluation of Afi Campton and we're pleased that FDA foresees much like we do, how for having been monitoring echoes on a more frequent basis.

Speaker Change: in forest for a long time and having accumulated quite a lot of data.

Speaker Change: Data that isn't...

Speaker Change: Contributing from a clinical

Speaker Change: Stand Point, any meaningful changes in the way these patients are managed, FDA seemed amenable to our recommendation that we change the frequency by which echo monitoring needed to occur.

Sung Lee: The remaining $325 million is comprised of a term loan of up to $175 million that we have the option to draw upon the satisfaction of certain conditions, and an investment by Roate Farma of up to $150 million in a phase of the month. The number three clinical trial of CK-586 should Roate Farma choose to opt in to fund the trial in exchange for an increase in their revenue interest in CK-586. We believe the overall financing package comes with an attractive and market competitive cost of capital. And combined with the net proceeds from the equity financing, positions us well to support the commercial launch of Affi Campton, expanded development program, and advance our pipeline.

Speaker Change: So that's encouraging, but ultimately I don't think I'll go so far as to make a direct correlation as you're asking between that change and what FDA may choose to do with respect to a potential risk mitigation profile.

Speaker Change: That's perhaps connecting of the dots that I'm unwilling to do on this call. Fady, is there anything more that you might want to add on that matter?

Fady Malik: I mean, I think the FDA's acceptance of our protocol amendment for forest and the consequent every six months of echo are reflective of the data that we've generated to date. So I would expect those data also to be important in their review of our NDA. As a reminder, we ask that you please limit yourself to one question and one question only. Our next question comes from a line with Jeffrey Hung of Morgan Stanley. Your line is open.

Speaker Change: Weiser, Ching Jaw, Fady Malik,

Sung Lee: Moving on to the income statement, total revenues in the second quarter of 2024 were $0.2 million compared to $0.9 million for the same period in 2023. R&D expenses in the second quarter of 2024 were $79.6 million compared to $83.2 million for the same period in 2023. The decrease was primarily driven by the timing of clinical trial activities and wind down activities for Courage ALS which ended in the first quarter of 2023. GNA expenses in the second quarter of 2024 were $50.8 million compared to $39.7 million for the same period in 2023. The increase was primarily driven by investments toward commercial readiness and personal expenses.

Unknown Executive: As a reminder, we ask that you please limit yourself to one question and one question only. Our next question comes from the line of Jeffrey Hung of Morgan Stanley. Your line is open.

Speaker Change: As a reminder, we ask that you please limit yourself to one question and one question only.

Speaker Change: Our next question comes from a line of Jeffrey Hung of Morgan Stanley . Your line is open.

Michael Ons: Hi, this is Michael, we are at Ons for Jeff. Hey, this is Mike Ons for Jeff Hong. Thanks for taking our question. Clicking at HCM and just thinking more generally, physicians are likely aware of the benefits of CMI at this point, but uptake remains more gradual, and a lot of these patients are still coming in on a prior beta blocker.

Michael Ons: So like thinking about that, how do you think about the results from Maple and is that what's needed to like position CMI's as frontline and really see that broad rapid uptake? Thanks.

Unknown Executive: I'll ask Fady to respond to that, please. Well, you see, I think quite a lot.

Sung Lee: Net loss for the second quarter of 2024 was $143.3 million or $1.31 per share basic and diluted compared to a net loss of $128.6 million or $1.34 per share basic and diluted for the same period in 2023.

Fady Malik: Well, you see, that's a good question. I think the reason we designed and executed MAPLE was primarily to provide evidence for the use of apicampinus as first-line therapy, and not only just with regard to symptom improvement and improvement in function, as we hope to demonstrate straight up against beta blockers, but also looking at the differences in how the heart remodels, how does it affect the wall thickness. You know, some of the things we've seen with chronic dosing of cardiac myosin inhibitors, but no one's ever really characterized whether those things occur with beta blockers.

Speaker Change: I'll ask Fady to respond to that, please.

Fady Malik: Well, you see, after your question, I think the reason we designed and executed MAPLE was primarily to provide evidence for

Fady Malik: The use of apicampin is first-line therapy and not only just with regards to symptom improvement and improvement in function as we as we hope to demonstrate straight up against beta blockers but

Sung Lee: Now I'd like to turn to our updated financial guidance for 2024. We expect gap operating expenses to be between $555 million to $575 million compared to the previous range of $535 million to $555 million. Non-cash operating expense comprised of stock-based compensation and depreciation which is included in gap operating expense is now expected to be between $105 million to $110 million compared to the previous range of $105 million to $115 million. Non-gap operating expenses which excludes stock-based compensation and depreciation is expected to be between $445 million to $470 million compared to the previous range of $420 million to $450 million.

Fady Malik: You know, also looking at the differences in how the heart remodels, how does it affect the wall thickness? You know, some of the things we've seen with chronic dosing of cardiac mice and inhibitors, don't ever really characterize whether those things occur with beta blockers.

Fady Malik: You know, we think the data in aggregate would suggest not only a...

Fady Malik: a functional and symptomatic improvement, but we hope will also show some evidence of disease modification. So all of those things, I think, should contribute eventually changing the standard of care from from a beta blocker first to to a CMI.

Fady Malik: And, you know, we think the data in aggregate would suggest not only a functional and symptomatic improvement, but we hope we'll also show some evidence of disease modification. So, all of those things should contribute, eventually, to changing the standard of care. From a beta blocker first to a CMI.

Roanna Ruiz: Thanks so much. Thanks. Our next question comes from the line of Roanna Ruiz with Lerink. Partners, your line is open.

Speaker Change: Thanks so much.

Fady Malik: Thanks.

Fady Malik: Our next question comes from the line of Roanna Ruiz with Lerink. Partners, your line is open.

Sung Lee: Net cash utilization is expected to be between $400 million to $420 million compared to the previous range of $390 million to $420 million. The increase in gap and non-gap operating expenses is primarily being driven by the initiations of the Phase 2A trial of CK-586 and the Phase 3 trial of Omicampd, McCarble.

Roanna Ruiz: Hi. Afternoon, everyone.

Roanna Ruiz: Hi, I have to do everyone.

Roanna Ruiz: So maybe tagging on to the discussion about MAPLE, I was curious if you could elaborate a bit more. It sounded like you mentioned that you could leverage some of the MAPLE data or initial results to help provide that to the FDA while they're reviewing AFI-CAMPTEN's filing. And is there any impact there that could happen with AFI-CAMPTEN's possible labeling as well?

Unknown Executive: I think what I said in my section was that the data would be available, you know, prior to approval of AFI-CAMPTN, not that we would necessarily include them in our application, because the application would already have been in and underway, but so that we hope a publication of the data would be available around the time of AFI-CAMPTN's potential approval. And, you know, I think the data are exciting, and they will just provide another point of reference for physicians and our commercial colleagues to show the benefits of this mechanism of action. And physicians would be able to reference this as well, right? Well, if it gets published, they certainly will, as I expect it will.

Robert Blum: With that, I'll hand it back over to Robert. Thank you, Sung. As Sung summarized, we're in an advantaged financial position with a fortified capital structure that we believe will carry us through the potential commercial launch of Athei Campton and also allow us to continue to conduct potential label and category expanding global clinical trials of Athei Campton. All while also advancing our later stage development pipeline, including Omicampd of McCarble and CK-586, focused to one area of biology in adjacent cardiology specialty segments. To that end, we recently reaffirmed our intentions to advance our commercial strategies and build our specialty cardiology franchise.

Speaker Change: I think what I did say in my section was that the data would be available.

Speaker Change: You know, prior to approval of Evaphy Campton, not that we would include them necessarily in our application, because the application will already have been in an under way, but so that we hope a publication of the data would be available around the time of Evaphy Campton's potential approval.

Speaker Change: and I think the data are exciting and they just will provide another point of reference for physicians and our commercial colleagues to show benefits of this mechanism of action.

Speaker Change: Got it. And physicians would be able to reference this as well, right?

Robert Blum: However, as we stated in Athei issued during the second quarter, we also recognize our fiduciary responsibilities to consider all potential opportunities to maximize shareholder value. This may take the form of building our business in the ways we've outlined today or it may involve M&A. Be fully understand our obligation to shareholders and we will consider alternatives. But the way we can ourselves plan to maximize shareholder value today is by building enduring value in our pipeline and becoming a category leader anchored by Athei Campton. We also envision leveraging our R&D and financial strengths to augment our pipeline with potential external opportunities.

Speaker Change: Well, if it gets published, they certainly will, as I expect it will. Fair enough, thanks.

Paul Choi: Our next question comes from the line of. Paul Choi of Goldman Sachs, your line is open.

Unknown Executive: Fair enough. Thanks. Our next question comes from the line of Paul Choi of Goldman Sachs. Paul Choi, your line is open. Hey, can you hear me? Yes. Hi. Good afternoon. And thank you for taking our question.

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

Speaker Change: Paul Choi of Goldman Sachs, your line is open.

Paul: Hey, Paul.

Paul Choi: Hey, can you hear me?

Speaker Change: Yes.

Speaker Change: Hi!

Paul Choi: Good afternoon and thank you for taking our question. Robert and Fady, I want to ask your view just on sort of next stages and planning of development for both HFPEF and HFREF.

Speaker Change: and the context of recently positive GLP1 data and just your thoughts there as to how that might be potential treatment target in the algorithm or modality for heart failure and just your thoughts on planning trials for 586 and OmaCampive Macarble down the road here. Thank you very much for taking our question.

Robert Blum: To that end, during the quarter, we were pleased to welcome a new member to our Corporate Steering Committee. Isaac Chukinova who joins us as Executive Vice President Corporate Development and Chief Business Officer. Isaac previously served as CEO of Atari Biothera Putex.

Robert Blum: He led business development at Selgin and held partner positions at Leading Venture Capital Firms. Isaac will be responsible for expanding the company's presence into new geographies, catalyzing external R&D activities, and mapping out potential new business objectives, which may include potential divestitures and spin-out companies as well as potentially M&A, both by side and cell side, and other business combinations. Isaac brings with him a wealth of knowledge and expertise for which we're grateful as we continue to build cytokinetics.

Robert Blum: Yeah, thanks for that question. I think it's a very important one in light of what we believe to be complementary mechanistic work that we're doing that is rooted in myosin modulation and can provide an opportunity that would be sitting alongside other therapies, but also for patients who may not benefit in the same way from those other therapies. For that, I'll turn to Fady to elaborate.

Speaker Change: Thanks for that question, I think it's a very important one in light of

Speaker Change: What we believe to be complementary mechanistic work that we're doing that is rooted in myosin modulation and as can provide an opportunity that would be sitting alongside of other therapies, but also for patients who may not benefit in the same way from those other therapies. For that, I'll turn to Fady to elaborate.

Fady Malik: Well, I think like many background therapies, they begin to treat a certain population, a segment of the population that is responsive to them. Obviously, they're focused on patients that have significant obesity. There are lots of HF and HCM patients that are not obese and for whom, you know, you're not expected really to see uptake of HF and HCM of the GLP and GIP agonists. So I think it's mostly just refining the patient population so that there's not, you know, sort of, a moving target.

Fady Malik: Well, I think like many background therapies, they begin to treat a certain population, a segment of the population that is

Timmy: Response to Timmy, obviously they're focused on the patients that have significant obesity.

Robert Blum: I'm proud of our accomplishments this past quarter, and as you've heard, we're especially pleased with the progress we made with FDA relating to the NDA submission for Athei Campton and its potential for a distinct risk mitigation profile, if approved for commercialization. Before we move to questions, however, I want to emphasize that due to the proprietary and confidential nature of our discussions with FDA, we do not intend to provide further details about our meetings with FDA, and we do not plan to present further updates on these matters, knowing that answers to any remaining questions will depend on FDA review.

Fady Malik: There are lots of Hep-Pef and HCM, or rather Hep-Pef and Hep-Ref patients that are not obese and for whom you're not expected really to see uptake of

Fady Malik: You'd rather not have, just as we do with other background therapy, we require them to be stable on their background therapy before entering the trial. And similarly, you know, a patient that was interested in beginning at GLP-1 probably wouldn't be eligible to continue or to be enrolled in our trial, at least until they had reached some stable weight and still continued to meet the eligibility criteria. So, you know, there's sort of a standard way to deal with that that I think will certainly apply. And, you know, maybe just add one comment.

Fady Malik: of the GLP and GIP agonists.

Fady Malik: So I think it's mostly just refining the patient population so that there's not a, you know, sort of a moving target. You'd rather not have...

Fady Malik: Just as we do with other background therapy, we require them to be stable.

Fady Malik: On their background therapy, before entering the trial, and similarly, you know, patient that wasn't entertaining, beginning a GLP-1 probably wouldn't be eligible to.

Robert Blum: Now, I'd like to recap our upcoming milestones. For Affie Campton, we expect to present additional results from Sequoia HCM at the European Society of Cardiology Congress later this month. We expect to submit an NDA to the FDA in Q3, 2024, and MAA to the EMA in Q4, 2024, and to coordinate with Xi Jinping to support the planned NDA submission to the M P.A, in China in the second half of this year.

Fady Malik: continue or to be enrolled in our trial, at least until they had reached some stable weight and still continue to make continue to meet the eligibility criteria. So, you know, there's sort of standard ways to deal with that, that I think will certainly imply.

Stuart Kupfer: And, you know, maybe just to add one comment, and while we are pleased to see some of these innovations in HFREF and HFPEF, I think it's sometimes lost on analysts and investors how unacceptably high the residual morbidity and mortality remains in these patients, and especially how many patients still can't tolerate the standard of care. And this is where we do believe opportunities exist for myosin modulation alongside those therapies. So we're looking forward to evaluating Omicamptive and also CK586 in places and in patients where they may not benefit from these other modalities and mechanisms.

Speaker Change: And you know, maybe just add one comment and while we are pleased to see some of these innovations in F-RF and have tough, I think it's sometimes lost.

Speaker Change: On Analyst Investors, How Unacceptably High.

Robert Blum: We expect to complete enrollment in Maple HCM in this third quarter, 2024. We expect to continue enrollment in Acacia HCM throughout 2024 with objective to complete enrollment in 2025. We expect to continue enrollment in Cedar HCM this year to continue the phase one study of Affie Campton in Japanese and Caucasian participants. This year, and we expect to continue advancing our go-to-market strategies for Affie Campton through the year.

Speaker Change: The residual morbidity and mortality remains in these patients, and especially how many patients still can't tolerate standard of care. And this is where we do believe opportunities exist for myosin modulation alongside of those therapies.

Speaker Change: So we're looking forward to evaluating Omicamptive and also CK586 in places and in patients where they may not benefit from these other modalities and mechanisms.

Kripa Devaranda: Our next question comes from the line of Kripa Devaranda, Truist Securities. Your line is open.

Kripa Devaranda: Our next question comes from the line of Kripa Devaranda, Truist Securities. Your line is open. Good afternoon. Good afternoon, Robert. Thank you so much for taking my questions.

Fady Malik: i

Stuart Kupfer: For Ome Campton, McCarble, we expect to start a confirmatory phase three clinical trial in the fourth quarter, 2024.

Fady Malik: Our next question comes from the line of Kripa Devaranda, Truist Securities. Your line is open.

Stuart Kupfer: For CK 586, we expect to present primary data from the phase one study at a medical meeting in this third quarter, 2024.

Kripa Devaranda: Good afternoon.

Kripa Devaranda: Good afternoon, Robert. Thank you so much for taking my question. You know, your slides seem to indicate...

Stuart Kupfer: And to start a phase two A clinical trial in the fourth quarter, 2024.

Speaker Change: He and my preference share for Happy Camton, an eligible patient population is about 60%.

Speaker Change: I was wondering about the potential of patients to switch from Leverkampton to Africampton if, especially if they're concerned about safety or not satisfied with the efficacy. That may not be your base case, but was just wondering whether based on your market survey or, you know, survey of care wells, you see this as a possibility. Thank you.

Stuart Kupfer: And for pre-clinical development and ongoing research, we expect to initiate clinical development with a fast skeletal muscle turpone and activator later this year and continue ongoing pre-clinical development and research activities directed to additional muscle biology focused programs through the remainder of the year.

Robert Blum: Yeah, you and other analysts have done work in that regard that we find compelling as relates to potential switches, but which Andrew can now elaborate on. And as you pointed out, that's not core to our strategy.

Andrew Callos: Yeah, you and other analysts have done work in that regard that we find compelling as relates to potential switches, but for which, as Andrew can now elaborate, and as you pointed out, that's not core to our strategy, but maybe, Andrew, you want to speak to that?

Unknown Executive: And operator with that, we can now open up the call to questions, please. Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. As a reminder, the company has requested that each participant please adhere to the allowance of one question per person. Please stand by while we compile the Q&A roster.

Andrew Callos: Yes, certainly. So I guess a couple of things.

Andrew Callos: But maybe Andrew, you want to speak to that? Yeah, certainly. So I guess a couple.

Andrew Callos: Yes, certainly. So I guess a couple things. One is we expect the vast majority of patients, probably over 80% of the market, to be available and not on a CMI treatment when affected, you know, if it were to be approved.

Andrew Callos: One is we expect the vast majority of patients, probably over 80% of the market, to be available and not on a CMI treatment when Aficamptin, you know, if it were to be approved, is available. Second, we will focus on new patients, educating physicians on Aficamptin and its differentiation. Our research tells us that it'll probably expand the market. So more patients, more physicians, and more patients on a CMI, and it'll expand its share. We're not going to talk about switches now.

Salim Syed: And our first question comes from the line of Salim Sayed of MISIO. Your line is open. Good afternoon, Robert. Thanks for taking the question and congrats on the progress. I guess one and one and one to welcome Isaac to the company.

Andrew Callos: Second, we will focus on new patients educating physicians on africanthin and the differentiation of africanthin.

Andrew Callos: Our research tells us that I'll probably expand the market, so more physicians and more patients.

Andrew Callos: We're not going to go for switches. If patients are stable and Aficamptin or any other product works for them, then that'll be up to the physician and the patient and that dialogue if they want to make a switch.

Robert Blum: I had a question on just that related matter with Isaac joining just is it possible to just give us sort of like how you're frameworking the thinking here. I know there was no there was no 8k or press lease that I came across. But it seems like it seems like something that's important to the business. So just maybe the cadence of the business development activities we should be expecting and primarily updated thoughts around AFICAMPT in Europe.

Speaker Change: Honestly, and my and expand share, we're not going to talk about switches, we're not going to go for switches if patients are stable and MAVIC Hampton or any other product work for them, then that'll be up to the physician and the patient and that dialogue if they want to make a switch.

Andrew Callos: Thank you so much.

Yasmeen Rahimi: Our next question comes from the line of Yasmeen Rahimi on Piper Sandler. Your line is open. Good afternoon, Yasmeen. Hey, good afternoon, Robert. It's Jungu on for Yas. Thanks for taking our question.

Andrew Callos: Thank you.

Andrew Callos: Our next question comes from the line of Yasmeen Rahimi of Piper Sandler. Your line is open.

Yasmeen Rahimi: Good afternoon, Yasmeen. Hey, good afternoon, Robert. It's Jungu Andriaz.

Yasmeen Rahimi: Thanks for taking our questions. For omicantin in the carpool, could you provide a little bit of additional color on what are the rate-limiting steps or gating steps left to kick off the study? Sure, and there are not many. Fady and the team have been working very diligently to get ready to start this study, and I'll ask him to speak to those in some detail.

Speaker Change: Good afternoon, Yasmeen.

Robert Blum: If that's in the cards or was this more gated to potentially doing business development around OMICAMPT in Macarple. Thank you. Yes, so certainly this doesn't change the way we're thinking about Affy Campton either in Europe or in North America. And I do believe that are ongoing business development activities with respect to Affy Campton in Japan are already well on track.

Jung Kwon: Hey, good afternoon, Robert. It's Jung Kwon for YAS. Thanks for taking our question. For Omicantin-McCarpal, could you provide a little bit of additional color on what are the rate-limiting steps or gating steps left to kick off the study?

Speaker Change: Sure, and there are not many. Fady and the team have been working very diligently to get ready to start this study and I'll ask him to speak to those in some detail.

Robert Blum: I'll start on that, Stuart, to elaborate. But, you know, the trial essentially, as we've indicated before, we had regulatory interactions. We've generally agreed on the protocol, so it's a matter of putting the operational aspects of the trial in place. If you'll remember, we also use a plasma concentration assay that we have to also stand up against. So it's mostly operational at this point. I'll ask Stuart if he's got anything to add to that.

Fady Malik: I'll start on that, Stuart, to elaborate, but, you know, the...

Fady Malik: The trial essentially, as we've indicated before, we've had regulatory interactions, we've generally agreed on the protocol, so it's a matter of putting up the operational aspects of the trial.

Akash Tewari: The bringing on board of Isaac really speaks less to those matters and more to what I would fall under corporate development. As opposed to business development and I foresee where Isaac is going to take the lead as we think about what geographies we might want to increase our footprint in as a ongoing R&D and commercial enterprise and even more so to augment how we think about muscle biology, both by side and potential cell side activities, meaning the following we think that as a pioneer and a leader in this space.

Speaker Change: If you'll remember, we also use a plasma concentration assay that we have to also stand up again, so it's mostly operational at this point. I'll ask Stuart if he's got anything to add to that.

Stuart Kupfer: Just to, you know, add to that, we're really in a position where we've learned a lot, of course, from GalacticHF. We have this huge database. That informs the appropriate target population, optimizes the study design for this new trial even further, and helps us to essentially run a study that's even more efficient and focusing on a higher risk population. It also needs a more lenient trial design. So I think we're in a good position to start the fourth quarter.

Stuart Kupfer: Just to, you know, add to that. We're really in a position where we've learned a lot of course from galactic HF, we have this huge database.

Akash Tewari: We're in a good position to imagine new possibilities and opportunities both to monetize the things we're currently doing and combine with potential others. As we've discussed and many investors have asked in the past, how do we think about spinning out companies? How do we think about potentially being an aggregator of technologies? I wouldn't expect anything meaningfully large. For instance, I don't think this factors into how we're thinking about spending in a meaningfully large way, but I do think it ties to how we capitalize on our leadership in the space and maintain that ongoing leadership.

Stuart Kupfer: that informs the perfect target population, optimizes the study design for this new trial even further and helps us to essentially run a study that's even more efficient.

Stuart Kupfer: And focusing on a higher risk population also means a more lean trial. So I think we're in a good position to start in the fourth quarter.

Speaker Change: Thank you very much.

Charles Duncan: Our next question comes from the line of Charles Duncan of Kantor. Your line is open.

Speaker Change: Our next question comes from the line of Charles Duncan of Kantor. Your line is open.

Charles Duncan: Robert and team, congrats on the good progress and recent meeting with the agency. I had a quick question about Maple enrollment.

Akash Tewari: And I believe that Isaac will be a great architect working with R&D colleagues for how that strategy can ultimately be implemented less so this year and more in years to follow. I hope that answers your question. Thanks so much.

Robert Blum: Hey Charles. Robert.

Robert Blum: Robert and team, congrats on the good progress and recent meeting with the agency. I had a quick question on Maple enrollment. Yeah, looks like it's going to be done soon. Comments from Fady, though, suggested absolutely anticipate that to be post

Akash Tewari: Our next question comes from a line of Akash Tawari of Jeffries. Your line is open.

Speaker Change: Approval. And so I guess I'm wondering if you could provide a little bit of color on what you anticipate to be

Robert Blum: Good afternoon. Hey, good afternoon. I realize you can't talk about your meeting with the FDA, but how much should we read into this protocol amendment on forest, which now allows a six month echo for patients with an LVF about 55. Students that strongly predict what a REM should ultimately be, and is there a possibility of the FDA won't require a REMD at all pending more follow up data from forest.

Charles Duncan: Yeah, looks like it's going to be done soon. Comments from Fady, though, suggested absolutely that it would be post approval. And so I guess I'm wondering if you could provide a little bit of color on what you anticipate to be the timeline for review for AFI. Are you assuming a rapid review and approval? Or is it possible that the Maple results could be requested or included upon the initial NDA?

Speaker Change: The timeline to review for AFI, are you assuming a rapid review and approval or is it possible that the MAPLE results could be requested or included upon the initial NDA?

Robert Blum: I think you might have misheard what Fady said about timing, and his point was that we expect MAPLE results to come in prior to when we might anticipate approval of AFI-CAMPTN. But Fady, is there anything else you want to add?

Robert Blum: And maybe Robert, if I can seek in one more, you talk about why you might spin off some assets. Can you talk about why it might be preferable to spin off certain assets ahead of let's say pending MNA, if let's say there is an overlap in a company that has a heft task portfolio. You know, I'm thinking specifically about CK 586 and spinning that asset off.

Speaker Change: I think you might have misheard what Fady said about timing and his point was that we expect maple results to come in prior to when we might anticipate approval of Fee Campton, but Fady is or anything else you want to add.

Fady Malik: Yeah, I think I said in my prepared remarks that we would expect it in the first half of 2025. You can kind of do the math and guess where in the first half it may land, but whether we get priority review or standard review, that still lies ahead of when we might have a potential approval. And so I would expect those data to be in the public domain but not necessarily contribute to the filing. Now, I should add, you know, there will be a safety update during our review, and we'll include blinded safety data, but that's the extent to which the MAPLE data would contribute to an NDA.

Fady Malik: Yeah, I think I said in my...

Speaker Change: prepared remarks that we would expect it in the first half of 2025.

Robert Blum: Thank you. Yes, I wouldn't interpret my earlier comments to suggest that we're thinking about spinning off any later stage clinical programs as we believe our specialty cardiology franchise is the way that we do maximize shareholder value, whether that's on our own or through as you asked potential MNA. But I do think there's a lot of value in what we're doing pre clinically and otherwise as we're expanding beyond specialty cardiology that could ultimately be monetized in other ways and as could benefit from funding in other ways.

Speaker Change: You know, you can kind of do the math and guess to where in the first half it may land, but whether we get priority review or standard review, that

Speaker Change: Still lies ahead of when we might have a potential approval, and so I would expect those data be in the public domain, but not necessarily contribute.

Speaker Change: There will be a safety update during our review and we'll include blinded safety data, but that's the extent of which the MAPLE data would contribute to an NDA.

Charles Duncan: Got it. It's clear to me now.

Robert Blum: As it relates to your question pertaining to FDA, again, I'll underscore I'm not really in a position to elaborate on the meeting. But however, we do believe forest represents a real world evaluation of afficampton and we're pleased that FDA foresee is much like we do how for having been monitoring echoes on a more frequent basis in forest for a long time and having accumulated quite a lot of data. Data that isn't contributing from a clinical standpoint to any meaningful changes in the way these patients are managed FDA seemed amenable to our recommendation that we change the frequency by which echo monitoring needed to occur.

Speaker Change: Got it, and it's clear to me now. Thanks for taking the question.

Mayank Mamtani: Thanks for taking the question. Thank you. Thanks, Charles. Our next question comes from the line of Mayank Mamtani with Riley Securities.

Mayank Mamtani: Our next question comes from the line of Mayank Mamtani with Riley Securities. Your line is open.

Speaker Change: Thank you. Thanks, Charles.

Speaker Change: Our next question comes from the line of Mayank Mamtani with the Riley Securities. Your line is open.

Mayank Mamtani: Your line is open. Good afternoon. Good afternoon, and thanks for taking our questions. This is actually William Owen from Mayank.

Mayank Mamtani: Good afternoon.

Speaker Change: Good afternoon, and thanks for taking our questions. This is actually a William on from my own.

William: When thinking about, say, a non-CMI cardiac sarcomere modulator, how should we expect treatment effects across an obstructive HCM patient or no, you know,

Speaker Change: If hypercontractability is the main ideology, should we expect these to be the same or vastly different? Just to look at your thoughts on that.

Fady Malik: Well, I think a non-CMI, I don't really know whether one exists, so I can't really speculate on how it might address the hypercontractility in HCM. You know, all of the current drugs being evaluated in clinical trials bind to myosin, and they, you know, modulate myosin's function in ways that reduce the number of active crossbridges and subsequently reduce the contractility in the sar So, they may have differences in the way in their exposure response relationship or other differences.

Speaker Change: [inaudible]

Robert Blum: So that's encouraging, but ultimately I don't think I'll go so far as to make a direct correlation as you're asking between that change and what FDA may choose to do with respect to a potential risk mitigation profile. That's perhaps connecting of the dots that I'm unwilling to do on this call. I think the FDA's acceptance of our protocol amendment for forest and the consequent every six months of echo are reflective of the data that we've generated to date, so I would expect those data also to be important in the review of our NDA.

Speaker Change: Well, I think a non-CMI, I don't really know whether one exists, so I can't really speculate on how they might, how it might address the hypercontractility and

Speaker Change: In HCM, you know, we think all of the current drugs being evaluated in clinical trials bind to myosin and they, you know, modulate myosin's function in ways that reduce the number of active crossbridges and subsequently reduce the contractility in the sarcomere. So,

Speaker Change: They may have differences in the way in their exposure response relationship or other differences, obviously that leads to different clinical profiles. But I can't really speculate on something that doesn't maybe exist.

Fady Malik: Obviously, that leads to different clinical profiles, but I can't really speculate on something that doesn't maybe exist. I guess the other mechanism that's being explored are SGLT2 inhibitors in HCM, and I think there certainly is some context to believe that there is a potential for them to show effectiveness. I mean, we've seen SGLT2 inhibitors have promise and have PEP, preserved ejection fraction heart failure, but they, you know, in HCM, in obstructive HCM, certainly the issue is really that gradient and reducing it, and it's not clear to me how effective an SGLT2 will be in that population as opposed to maybe an HCM that's more of a mimic, a closer approximation to the HFPEP population.

Speaker Change: Fady Malik, Diane Weiser, Fady Malik,

Speaker Change: I guess the other mechanism that's being explored are SGLT2 inhibitors.

Unknown Executive: Our next question comes from a line of Jeffrey Hung, of Morgan Stanley, your line is open. Hi, this is my free add on for Jeff. Hey, this is Mike on for Jeff. Thanks for taking our question. Looking at HCM and just thinking more generally, physicians are likely aware of the benefits of CMI at this point, but uptake remains more gradual and a lot of these patients are still coming in on the prior beta blocker. It's like thinking about that, how do you think about the results from Maple? And is that what's needed to like position CMI's at front line and release that broad rapid uptake? Thanks.

Speaker Change: and A.C.M., and I think there certainly is some context to believe that there is a potential for them to show effectiveness. I mean, we've seen STL-T2 inhibitors have promised and have preserved ejection fraction heart failure.

Speaker Change: But they, you know, in ACM.

Speaker Change: Wee!

Speaker Change: In obstructive HCM, certainly the issue is really that gradient and reducing it, and it's not clear to me how effective an SGLT2 will be in that population, as opposed to maybe an HCM that's more of a mimic, a closer approximation to the HFPEF population.

Fady Malik: Well, that's fatty to respond to that, please. Well, you see after a question, I think the reason we designed an executed Maple was primarily to provide evidence for the use of api-campinist first line therapy. And not only just with regards to symptom improvement and improvement in function as we hope to demonstrate straight up against beta blockers, but also looking at the differences in how the heart remodels, how does it affect wall thickness?

Speaker Change: Got it. Thanks so much.

Jason Butler: Our next question comes from the line of Jason Butler of Citizens J&P. Your line is open.

Jason Butler: Got it. Thanks so much. Thank you. Our next question comes from the line of Jason Butler of Citizens J&P.

Speaker Change: Sir, thank you!

Speaker Change: Our next question comes from a line of Jason Butler of Citizens J and P. Your line is open.

Jason Butler: Good day, thanks.

Jason Butler: Hi Robert, thanks for taking the question.

Jason Butler: She's just another one on the other campus study. Just when you think about the target of patient population, and the positive data you've already generated, how should we think about enrollment timelines, and is there any comparison to the prior study here in terms of potential enrollment timelines?

Fady Malik: You know, some of the things we've seen with chronic dosing of cardiac mice and inhibitors, those ever really characterized whether those things occur with beta blockers. And, you know, we think the data and aggregate would suggest not only a functional and symptomatic improvement, but we hope we'll also show some evidence of disease modification. So all of those things I think should contribute eventually changing the standard of care from up from a beta blocker first to to a CMI. Thanks a lot. Thanks.

Robert Blum: Yeah, so I'll ask Fady and Stuart to speak to that. But we're talking about a subset of the market for which the event rate is especially high, and for which the unmet need is not being addressed by drugs currently being studied in other clinical trials. So we foresee that this will be a study that will be embraced by investigators who are already telling us they have lots of patients that meet the criteria that we're outlining. And I'll remind you that the advanced heart failure patients in Galactic were the subject of a publication. Mike Felker was the lead author.

Speaker Change: Yes, so I'll ask Fady and Stuart to speak to this, but we're talking about...

Speaker Change: A subset of the market, but for which the event rate is especially high and for which the unmet need is not being addressed by drugs currently being studied in other clinical trials.

Speaker Change: So we foresee that this will be a study that will be embraced by investigators for which they already are telling us they have lots of patients that meet the criteria that we're outlining. And I'll remind you that the advanced heart failure patients...

Fady Malik: Our next question comes from the line of Rona Ruiz with LeeRink partners. Your line is open. Hi, afternoon, everyone. So maybe talking on to the discussion about Maple, I was curious if you could elaborate a bit more. It sounded like you mentioned that you could leverage some of the maple data or initial results to help provide that to the FDA while they're reviewing api-campins filing. And is there any impact that could happen with api-campins possible labeling as well?

Jason Butler: in Galactic.

Stuart Kupfer: And there you can see high morbidity, high mortality, for which the economic value there could be especially important. So, Fady and Stuart, do you want to talk about enrolling that population in a study? Stuart, why don't you go ahead?

Speaker Change: were the subject of a publication. Mike Felker was the lead author. And there you can see high morbidity, high mortality, and for which the economic value there could be especially important. So, Fady and Stuart, do you want to talk about enrolling that population in a study?

Stuart Kupfer: Why don't you go ahead? Thanks, Robert. You know, as you pointed out, and Robert pointed out, we are targeting a high-risk population and those patients with higher unmet needs. And it's also the subgroup of patients we observed in Galactic HF that had, you know, a larger magnitude of treatment benefit. So the advantage, of course, is that we can run a smaller trial. You've already mentioned that the target population will be about one-fourth.

Unknown Executive: I'll take that. Rona, I think what I did say in my section was that the data would be available, you know, prior to approval of api-campin. Not that we would include them necessarily in our application because the application will already been in an underway, but so that we hope a publication of the data would be available around the time of api-campins potential approval. And I think the data are exciting and they just will provide another point of reference for physicians and our commercial colleagues to show the benefits of this mechanism of action. [inaudible] Cytokinetics Inc. Cytokinetics Inc. Inc. Cytokinetics Inc. [inaudible] Cytokinetics Inc. Cytokinetics Inc.

Speaker Change: Stewart want to go ahead. Thanks Robert. You know as Robert pointed out, we are targeting a high risk population.

Fady Malik: and those patients under hire, unmet need and it's also the subgroup patients we observed.

Speaker Change: and Galactic HF that had, you know, a larger magnitude of treatment benefit. So the advantage, of course, is that we can run a smaller trial,

Speaker Change: You've already mentioned that the target population will be about one-fourth the size of galactic HF and that's again because of the higher event rate

Stuart Kupfer: And that's again because of the higher event rate that we expect and so we can run a smaller, more lean study. I think that's a good analog. That trial was run for just a little over three years from first patient in to study closure, and so, I think that's kind of the way we're thinking about how the study will proceed.

Fady Malik: that we expect. And so we can run a smaller, more lean, hopefully faster trial. And you know, if you sort of consider a contemporary trial, such as Victoria.

Speaker Change: The Victoria trial, then I think that's a good analog. That trial was ran just a little over three years from.

Speaker Change: First Patient N to the study closure and so on.

Speaker Change: I think that's kind of the way we're thinking about how the study will proceed.

Sean McCutcheon: Thank you. And our next question comes from the line of Sean McCutcheon of Raymond James. Your line is open. Hi guys, thanks for the question. Can you speak to the importance

Sean McCutcheon: And our next question comes from the line of Sean McCutcheon of Raymond James. Your line is open.

Speaker Change: Thank you.

Speaker Change: And our next question comes from the line of Sean McCutcheon of Raymond James. Your line is open.

Sean McCutcheon: Hi guys, thanks for the question. Can you speak to the importance of dosing optimization, specifically in the context of the 36-week non-obstructive cohort from Forrest?

Sean McCutcheon: You know, thinking about the necessity of getting patients to those higher doses, maybe as an advantage you have over your competitor. You know, what's your interpretation of how this

Speaker Change: has and potentially will impact the KCCQ results. Maybe speak to the prior KCCQ data and how it's informed your powering assumptions for Acacia. Thanks.

Robert Blum: Right, so firstly, I'll start by referring you back to the Coats manuscript that Fady spoke about in his prepared remarks and what we think Sequoia underscored, which was that following a principle of targeting the lowest effective dose and stepwise progression. And for that reason, we're especially pleased to see that we're not seeing dose discontinuations on any dose relating to low EF, nor dose down titrations on the lower doses.

Speaker Change: So, firstly, I'll start by referring you back to the coach manuscript that Fady spoke to in his prepared remarks.

Speaker Change: and what we think Sequoia underscored, which was that following a principle of targeting the lowest effective dose and step-wise progression.

Speaker Change: Each dose level can be associated with

Sean McCutcheon: Incrementally Higher Plasma Drug Concentration and Incremental Efficacy.

Speaker Change: And for that reason, we're especially pleased to see that, you know, we're not seeing dose discontinuations on any dose relating to low EF.

Robert Blum: Only when you get to higher doses are we seeing an occasional dose down titration associated with an excursion in EF, but for which that's accompanied by larger-magnitude effects on gradient. So that's the underlying therapeutic hypothesis that we think Sequoia answered that question very well. As relates to translation to NHCM, maybe I'll ask Fady and Stuart to speak to that, please.

Speaker Change: Nor dose down titrations on the lower doses.

Speaker Change: Only when you get to higher doses are we seeing an occasional dose down titration associated with an excursion in EF, but for which that's accompanied by larger magnitude effects on gradient.

Speaker Change: So that's the underlying therapeutic hypothesis that we think Sequoia answered that question very well. As relates to translation to NHCM, maybe I'll ask Fady and Stuart to speak to that please.

Fady Malik: Well, so I think in NHCM, you know, the hypothesis really is improving on the hyper contractility of the NHCM state. And, you know, it's a very, quite a variable population; some patients will need more; some patients will need less. So having a drug that can be titrated quite easily, and we can use, you know, a full range, if you will, of doses. In order to maximize potential treatment effect in patients but also not have, you know, concern potentially of overdoing it, having to back off or stop the drug, and so forth, it is very useful.

Fady Malik: Also, I think in any CM, you know, the hypothesis really is improving on the hypercontractility of the NHCM state and, you know, it's a very, quite a variable population, some patients will need more, some patients will need less.

Speaker Change: So having a drug that can be titrated quite easily, and we can use a full range, if you will, of doses in order to maximize potential treatment effect in the patients.

Speaker Change: but also not have, you know, concern potentially, of overdoing it having to back off or stop the drug and so forth. Is very useful and the data that we saw in

Fady Malik: And the data that we saw in Both the open-label extension and forest that I referred to that's been published, as well as the published data from Redwood, show a pretty remarkable effect on symptoms, KCCQ, and biomarkers. So, in designing ACACIA, you know, we took into account what we thought would be the effect size that we observed in the Phase 2 study, Redwood, Cohort 4 of Redwood. You know, when Sequoia came out, that helped us, if you will, solidify the fact that the placebo effect in that study was in the range that we expected, because Cohort 4 in Redwood was not placebo-controlled. And so, we took that all into account, and we think we powered it adequately with about 400 patients.

Speaker Change: both the open label extension and forest that I referred to that's been published

Speaker Change: as well as the public data from Redwood.

Kripa Devarakonda: Our next question comes from the line of Kripa Devarakonda, true of security, if your line is open. Good afternoon. Good afternoon, Robert. Thank you so much for taking my question. You know, your slides seem to indicate the M.I, preference chair for African-Tan and eligible patient population is about 60%. I was wondering about the potential of patients to switch from the accountant to African-Tan, especially if they're concerned about safety or not satisfied with the efficacy.

Speaker Change: So pretty, remarkable effect on symptoms.

Speaker Change: KCCQ and biomarkers. In designing a case, we took into account what we thought would be the fact size that we observed in the phase 2 study Redwood, co-work 4 of Redwood. You know, when Sequoia came out that helped us.

Speaker Change: If you will solidify the fact that the placebo effect in that study was in the range that we expected because the cohort

Kripa Devarakonda: That may not be your base case, but was just wondering whether based on your market survey or, you know, survey of Kowals, you see this as a possibility. Thank you. Yeah, you and other analysts have done work in that regard that we find compelling as relates to potential switches, but for which as Andrew can now elaborate, and as you pointed out, that's not core to our strategy. But maybe Andrew, you want to speak to that?

Speaker Change: Foreign Redwood was not placebo controlled. And so, you know, we took that all into account and we think we powered it adequately with about 400 patients.

John Gianco: Maybe I'll stop there for now. Thank you. And our next question comes from the line of John Gianco of Needham & Co. Your line is open.

Speaker Change: So maybe I'll stop there and now.

Speaker Change: Thank you. And our next question comes from the line of John Gianco of Needham & Co. Your line is open.

Kripa Devarakonda: Yes, certainly. So I guess a couple of things. One is we expect the vast majority of patients, probably over 80% of the market to be available and not on a CMI treatment. When African-Tan, you know, if it were to be approved, second, we will focus on new patients educating physicians on African-Tan and the differentiation of African-Tan. Our research tells us that I'll probably expand the market. So more patients, more, more physicians and more patients on a CMI and expand share.

John Gianco: Hi, this is John . Hi, Robert. This is John for Surge Today. Thanks for taking our question. We just wanted to touch on whether you guys had any updated thoughts or learnings from the Mavicanton launch regarding the HCM market opportunity and how you may be able to improve on their launch trajectory when the time comes for you guys. Thanks.

John Gianco: Thank you for the question. First of all, we should emphasize that we think that the Q2 sales for Mavicampton addressed a lot of the lingering questions relating to the Q1 numbers, and we think that they're demonstrating exactly what one should expect from a launch of a drug that is meeting the needs of certain patients in certain centers. We think that it's an impressive quarter-to-quarter growth. With that said, as Andrew highlighted, there are still, we believe, over 90% of eligible patients who aren't receiving a cardiac myosin inhibitor, and that number will be perhaps still over 80% when we, hopefully, come to market.

Speaker Change: Thank you for the questions. So firstly...

Speaker Change: We should emphasize that we think that the Q2 sales for Mavicampton addressed a lot of the lingering questions relating to the Q1 numbers, and we think that they're demonstrating exactly what one should expect from a launch of a drug that is meeting the needs of

Andrew Callos: We're not going to talk about switches. We're not going to go for switches if patients are stable. And Mavicantin or any other product works for them, then that'll be up to the physician and the patient and that dialogue if they want to make a switch. Thank you so much. Thank you.

Speaker Change: Certain patients in certain centers, we think that it's an impressive quarter to quarter growth.

Yasmeen Rahimi: Our next question comes from a line of Yasmin Rahimi, a Piper Sandler. Your line is open. Good afternoon, Yasmin. Hey, good afternoon, Robert. I'll go on for Yas. Thanks for taking our question. For Mavicantin, the carpool.

Speaker Change: With that said, as Andrew highlighted,

Andrew Callos: There's still, we believe, over 90% of eligible patients who aren't receiving

Andrew Callos: A cardiac mice and inhibitor in that number will be perhaps still over 80% when we hopefully will come to market.

Unknown Executive: Could you provide a little bit of additional color on what are the rate limiting steps or dating steps left to kick off the study? Sure. And there are not many. Fadi and the team have been working very diligently to get ready to start this study and I'll ask him to speak to those in some detail. I'll start on my Stuart to elaborate, but the trial essentially, as we've indicated before, we've had regulatory interactions.

John Gianco: And we do believe that the next-in-class profile of Afecampton should be expected, hopefully, to be expanding the category for the benefit of more patients to be receiving the benefit of cardiac myosin inhibition and from more physicians prescribing it. Perhaps I could ask Andrew to comment on what he's hearing in the marketplace and how our next-in-class profile for Afecampton may hopefully deliver on market need.

Speaker Change: And we do believe that the next-in-class profile of Affy Campton should be expected, hopefully, to be expanding the category for the benefit of more patients to be receiving benefit of cardiac myosin inhibition and from more physicians prescribing.

Andrew Callos: Perhaps I could ask Andrew to comment on what he's hearing in the marketplace and how our next-in-class profile for Baffi Campton may hopefully deliver on market need.

Unknown Executive: We've generally agreed on the protocol. So it's a matter of putting up the operational aspects of the trial. I feel we remember we also use a plasma concentration assay that we have to also stand up again. So it's mostly operational.

Andrew Callos: So I think when I think about the launch trajectory, clearly, it's going to be making sure that we educate cardiologists. I started to engage with them and get broader utilization outside of centers of excellence and HCM experts. Making sure we can support patients from a patient and support service point of view, as well as affordability. So we're really focused on all those elements to make sure that our launch trajectory is what we're expecting. In terms of what we're hearing from the market, we certainly welcome a second option and alternative in the CMI arena. We certainly think it's going to expand the utilization of CMIs and continue to engage the community. Great, thank you for that. And now for our next question.

Andrew Callos: So I think when I think about launch trajectory, clearly it's going to be making sure that we educate cardiologists.

Andrew Callos: started to engage and get broader utilization outside of centers of excellence and HCM experts.

Stuart Kupfer: And at this point, I'll ask Stuart if he's got anything to add to that. Just to add to that, we were really in a position where we've learned a lot of course from Galactic HF. We have this huge database that informs the appropriate target population. Optimize the study design, for this new trial even further, and helps us to essentially run a study that's even more efficient, and focusing on a higher risk population, also leads to more lean trials. So I think we're in a good position to start in the fourth quarter.

Speaker Change: Making sure we can support patients from a patient and support service point of view, as well as affordability. So we're really focused on all those elements to make sure that our launch trajectory is what we're expecting.

Unknown Executive: All right. Thank you very much.

Unknown Executive: Thank you.

Speaker Change: In terms of what we're hearing from the market, we certainly welcome a second option, an alternative in the CMI arena. We certainly think it's going to expand utilization of CMIs and continue to engage the community.

Speaker Change: i

Speaker Change: Thank you for that.

Rohan Mathur: And our next question comes from the line of Rohan Mathur with Oppenheimer. Your line is open.

Speaker Change: In our next question comes from the line of Rohan Mather with op-on-hymer, your line is open.

Charles Duncan: Our next question comes from the line of Charles Duncan of Cantor. Your line is open. Hey, Robert. Yeah.

Speaker Change: Hi, this is Roland Onn for The Lehringer Show. Thanks for taking my question.

Roland Onn: Just on CK586, other learning learning from the African-American studies that might inform design of the Phase 2 trial for 586, with respect to health safety and efficacy findings might be evaluated, given that it's a greater spurty of disease and has that population. Thank you.

Robert Blum: Hey, Robert and Kim, congrats on the good progress and recent meeting with the agency. I had a quick question on maple enrollment. Yeah, it looks like it's going to be done soon. Comments from Fatty, those suggested absolutely anticipate that to be post approval. And so I guess I'm wondering if you could provide a little bit of color on what you anticipate to be the timeline to review for Afi. Are you assuming a rapid review and approval or is it possible that the maple results could be requested or included upon the initial NDA?

Rohan Mathur: Just so I'm clear, your question relates to Haffey-Campden in NHCM as in Forms 586 in HFPAF. Yes. Okay, Fady, do you or Stuart want to take this?

Speaker Change: Just so I'm clear, your question relates to Haffey-Campden in NHCM as in Forms 586 in Half Path. Is that right?

Stuart Kupfer: Yes, Stuart. Do you want to go ahead and answer? Well, the short answer is...

Speaker Change: OK, Fady, you are Stuart, want to take that?

Stuart Kupfer: Well, the short answer is there's a lot we can learn from the At the Camping program. Not only a non-obstructive HCN, but, of course, an obstructive HCN. But clearly, it's a non-destructive ACM population that is more relevant in terms of the patients with HEF that we're targeting. You know, the main focus here is on improving diastolic function and essentially calibrating what we think some of a decrease in cardiac contractility would improve: that diastolic function. And now we have some sense some understanding of the magnitude of the decrease, targeting the populations we think that could benefit the most.

Speaker Change: Yes, Stuart, do you want to go ahead and answer?

Stuart Kupfer: Well, the short answer is there's a lot to learn. We've learned a lot to learn from the At the Camping Program.

Speaker Change: Not only a non-obstructive HCM, but of course an obstructive HCM.

Robert Blum: I think you might have misheard what Fatty said about timing, and his point was that we expect maple results to come in prior to when we might anticipate approval of Afi Campton, but Fatty, is there anything else you want to add? Yeah, I think I said in my prepared remarks that we would expect it in the first half of 2025. You know, you can kind of do the math and guess to where in the first half it may land, but whether we get priority review or standard review that still lies ahead of when we might have a potential approval.

Speaker Change: But clearly, it's a non-destructive ACM population that is more relevant in terms of the patients with HETs that we're targeting. You know, the main focus here is on improving diastolic function.

Speaker Change: and essentially calibrating what we think some of a decrease in cardiac contractility would improve.

Speaker Change: And now we have some sense, some understanding of the magnitude of the decrease.

Speaker Change: An ejection fraction that might confer the potential benefit in terms of die stock function and how that would translate.

Robert Blum: And so I would expect those data being the public domain, but not necessarily contribute to the filing. Now it should add, you know, there will be a safety update during our review and will include blinded safety data, but that's the extent of which the maple data would contribute to an NDA. Got it. That's clear to me now. Thanks for taking the question. Thank you. Thanks, Charles.

Speaker Change: of course in the symptomatic and functional improvement and what goes along with that of course is

Speaker Change: What we have observed in the non-obstructive population is a very favorable safety profile that corresponds with the evidence of improved efficacy, so we'll certainly translate those observations into designing

Speaker Change: Optimizing study design and targeting the populations we think that could benefit the most.

William: Our next question comes from the line of my ink. With the Riley securities. Your line is open.

Unknown Executive: And I'm showing no further questions at this time. I would now like to turn the conference back to Robert Blum, President and CEO, for closing remarks.

Speaker Change: Thank you.

Speaker Change: And I'm showing no further questions at this time. I would like to turn the conference back to Robert Blum, President and CEO for closing remarks.

Robert Blum: Good afternoon. Thanks for taking our questions. This is actually William on from my own. When thinking about say a non-CMI cardiac circummier modulator, how should we expect treatment effects across an obstructive HCM patient or no, you know, if hypercontractility is the main ideology, you know, should we expect these to be the same or are vastly different just to look at your thoughts on that. Well, I think a non-CMI, I don't really know whether one exists.

Robert Blum: Thank you, operator. And thanks to everybody for joining us on this Q2 earnings call today. An especially important call in light of some of the things we've been talking about. Given the progress of Affy Campton, we're especially pleased that we've initiated the rolling submission of the NDA. And we're on track to complete that this quarter.

Robert Blum: Thank you, Operator, and thanks to everybody for joining us on this webinar.

Speaker Change: Q2 earnings call today.

Robert Blum: An especially important call in light of some of the things we've been talking about.

Speaker Change: Given the advancement of AFI-CAMPTN, we're especially pleased that we've initiated the rolling submission of the NDA, and we're on track to complete that this quarter, and especially coming away from the meetings we've had with FDA,

Robert Blum: And especially coming away from the meetings we've had with FDA, which we believe inform strategy as pertains to risk mitigation and other matters that will be considered in light of the review. We're also especially pleased that we've fortified the capital structure of the company and that we are putting it to good use in a capital efficient way as relates to both Omicamptive and CK586. And we look forward to updating shareholders as we advance our go-to-market strategies for Affy Campton and also as relates to the later stage pipeline. With that, we'll also point to presentations later this month at the European Society of Cardiology and look forward to speaking with you after those. Operator, we can now conclude the call, please.

Speaker Change: that we believe inform strategy as pertains to risk mitigation and other matters that will be considered in light of the review.

Robert Blum: So I can't really speculate on how they might, how it might address the hypercontractility and in HCM, you know, we think all of the current drugs being evaluated in clinical trials, bind to my sense. And they, you know, modulate my sense function in ways that reduce the number of active cross bridges and subsequently reduce the contractility and the sarcomy or so. They may have differences in the way in their exposure response relationship or other differences.

Speaker Change: We're also especially pleased that we've fortified the capital structure of the company and that we are putting it to good use in a capital efficient way as relates to both Omicamptive and CK586

Speaker Change: and we look forward to updating shareholders as we advance our go-to-market strategies for Affy Kemp and also as relates to later stage pipeline.

Speaker Change: With that, we'll also point to presentations later this month at the European Society of Cardiology, and look forward to speaking with you after those. Operator, we can now conclude the call, please.

Robert Blum: Obviously that leads to different clinical profiles, but I can't really speculate on something that doesn't maybe exist. I guess the other mechanism that's being explored are SGLT-2 inhibitors in NACM, and I think there certainly is some context to believe that there is a potential for them to show effectiveness. I mean, we've seen SGLT-2 inhibitors have promise and have PEP, preserved ejection fraction heart failure, but they, you know, in NACM, the, in obstructive ACM, certainly the issue is really that gradient in reducing it, and it's not clear to me how effective a SGLT-2 will be in that population as opposed to maybe NACM that's more of a mimic, the closer approximation. To the HFEP population.

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

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

Speaker Change: Fady Malik, Stuart Kupfer, Fady Malik, Diane

Robert Blum: Janet, thanks so much. Sir, thank you.

Stuart Kupfer: Our next question comes from a line of Jason Butler of Citizens JMP. Your line is open. Thank you. Hi, thanks. Hi, Robert. Thanks for taking the question. Just another one on the Omicamp to study, just want to think about the targeted patient population and the positive data you've already generated. How should we think about enrollment timelines? And is there any comparison to, you know, the prior study here in terms of potential enrollment timelines?

Stuart Kupfer: Yeah, so I'll ask Fatty and Stewart to speak to this, but we're talking about a subset of the market, but for which the event rate is especially high and for which the unmet need. Is not being addressed by drugs currently being studied in other clinical trials. So we foresee that this will be a study that will be embraced by investigators for which they already are telling us they have lots of patients that meet the criteria that we're outlining.

Stuart Kupfer: And I'll remind you that the Advanced Hard Failure Patients in Galactic were the subject of a publication Mike Felker was the lead author. And there you can see high morbidity, high mortality, and for which the economic value there could be especially important. So Fatty and Stewart, do you want to talk about enrolling that population in a study? Stewart went to go ahead. Thanks Robert. You know, as Robert pointed out, we are targeting a high risk population and those patients under higher unmet need.

Stuart Kupfer: And it's also the subject of patients we observed in Galactic HF that had, you know, larger magnitude of treatment benefits. So the advantage, of course, is that we can run a smaller trial. You already mentioned that the target population will be about one fourth the size of Galactic HF. And that's again because of the higher event rate that we expect. And so we can run a smaller, more lean, hopefully faster trial.

Stuart Kupfer: You know, if you sort of consider a contemporary trial, such as Victoria, the Victoria trial, then I think that's a good analog. That trial was ran just a little over three years from first patient end to study closure. And so I think that's kind of the way we're thinking about how the study will proceed. Thank you.

Fady Malik: And our next question comes from a line of Sean McCutcheon of Raymond James. Your line is open. Hi guys, thanks for the question. Can you speak to the importance of dosing optimization, specifically in the context of the 30s, which we've not obstructive cohort and forest. You know, thinking about the necessity of getting patients to those higher doses, maybe as a advantage you have over your competitor, you know, how what's your interpretation of how this has, and potentially will impact the cases.

Fady Malik: I may be speak to the the prior cases to Q data and how it's informed your powering assumptions for occasion. Thanks. Right. So, firstly, I'll start by referring you back to the coach manuscript that fatty spoke to in his prepared remarks. And what we think Sequoia underscored, which was that following a principle of targeting the lowest effective dose and stepwise progression. Each dose level can be associated with incrementally higher plasma drug concentration and incremental efficacy.

Fady Malik: And for that reason, we're especially pleased to see that, you know, we're not seeing dose discontinuations on any dose relating to low EF nor dose down titrations on the lower doses. Only when you get to higher doses, are we seeing an occasional dose down titration associated with an excursion in EF. But for which that's accompanied by larger magnitude effects on gradient. So that's the underlying therapeutic hypothesis that we think Sequoia answered that question very well as relates to translation to NHCM.

Fady Malik: Maybe I'll ask Fatty and Stewart to speak to that, please. Well, so I think in NHCM, you know, the hypothesis really is improving on the hypercontractility of the NHCM state. And, you know, it's a very quite a variable population. Some patients will need more. Some patients will need less. So having a, you know, a drug that can be titrated quite easily. And we can use, you know, a full range, if you will, of doses in order to maximize potential treatment effect in the patients, but also not have, you know, concerned potentially of overdoing it and having to back off or stop the drug and so forth.

Fady Malik: It's very useful. And the data that we saw in. Both the open label extension and forest that I referred to that's been published as well as the published data from Redwood show a pretty remarkable effect on symptoms, KCCQ and biomarkers. So in designing a case, you know, we took into account what we thought would be the effect size that we observed in the phase two study Redwood co-op for Redwood. You know, when Sequoia came out that helped us if you will solidify the fact that the placebo effect in that study was in the range that we expected because the cohort for Redwood was not placebo controlled. And so, you know, we took that all into account and we think we powered it adequately with about 400 patients.

Fady Malik: So maybe I'll stop there and for now. Thank you.

John Gianco: And our next question comes from the line of John Gianco of Needham and Co. Your line is open. Hi, John. Hi, Robert. This is John in the search today. Thanks for taking our question.

Robert Blum: We just wanted to touch on whether you guys had any updated thoughts or learnings from the Mavicanton launch regarding the HCM market opportunity and how you may be able to improve on their their launch trajectory when the time comes for you guys. Thanks. Thank you for the question. So firstly, we should emphasize that we think that the Q2 sales for Mavicanton addressed a lot of the lingering questions relating to the Q1 numbers and we think that they're demonstrating exactly what one should expect from a launch of a drug that is meeting the needs of certain patients in certain centers.

Robert Blum: We think that it's an impressive a quarter to quarter growth with that said is Andrew highlighted. There's still we believe over 90% of eligible patients who aren't receiving a cardiac mice and inhibitor and that number will be perhaps still over 80% when we hopefully will come to market. And we do believe that the next in class profile of apicampton should be expected hopefully to be expanding the category for the benefit of more patients to be receiving benefit of cardiac mice and inhibition and from more physicians prescribing.

Andrew Callos: Perhaps I could ask Andrew to comment on what he's hearing in the marketplace and how our next in class profile for apicampton may hopefully deliver on market need. So I think when I think about launch trajectory, clearly it's going to be making sure that we educate cardiologists started to engage and get broader utilization outside of centers of excellence and HTML experts, making sure we can support patients from a patient that support service point of view as well as affordability.

Andrew Callos: So we're really focused on all those elements to make sure that our launch trajectory is what we're expecting. In terms of what we're hearing from the market, we're suddenly welcome a second option and alternative in the CMI arena. We certainly think it's going to expand utilization of CMI's and continue to engage the community. Great. Thank you for that.

Stuart Kupfer: [inaudible] Just so I'm clear, your question relates to Happy Campton in NHCM as informs five eight six in half past. Yes. All right. Okay.

Stuart Kupfer: Fadi, you were Stuart. Want to take that? Yes, Stuart. You want to go ahead and answer. Well, the short answer is a lot to learn. We learned a lot from the at the camping program. Not only non-structive HCM, but of course, obstructive HCM. But clearly the non-structive HCM population that is more relevant in terms of the patients with tests that we're targeting. You know, the main focus here is on improving diastolic function.

Stuart Kupfer: And essentially, calibrating what we think some a decrease in cardiac contractility would improve that diastolic function. And now we have some sense, some understanding of the magnitude of a decrease in injection fraction that might confer the potential benefit in terms of diastolic function. And how that would translate, of course, into symptomatic and functional improvement. And what goes along with that, of course, is, well, we have observed an non-structive population as a very favorable safety profile that corresponds to the evidence of improved efficacy. So we'll certainly translate those observations into designing, you know, optimizing study design and targeting populations. We think the benefit the most. Thank you.

Unknown Executive: And I'm showing no further questions at this time.

Robert Blum: I would like to turn the conference back to Robert Blum, President and CEO for closing remarks. Thank you, operator. And thanks to everybody for joining us on this Q2 earnings call today. And especially important call in light of some of the things we've been talking about. Given the advancement of AFI Campton, we're especially pleased that we've initiated the, initiated the rolling submission of the NDA. And we're on track to complete that this quarter.

Robert Blum: And especially coming away from the meetings we've had with FDA that we believe inform strategy as pertains to risk mitigation and other matters that will be considered in light of the review. We're also especially pleased that we've fortified the capital structure of the company and that we are putting it to good use in a capital efficient way as relates to both only captive and CK586. And we look forward to updating shareholders as we advance our go to market strategies for AFI Campton and also as relates to later stage pipeline. With that, we'll also point to presentations later this month at the European Society of Cardiology and look forward to speaking with you after those operator.

Unknown Executive: We can now conclude the call please.

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

Q2 2024 Cytokinetics Inc Earnings Call

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