Q1 2025 Cytokinetics Inc Earnings Call
Good afternoon and welcome to Cytokinetics, First Quarter, 2025 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 for 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: 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 repeat developments. Andrew Callos, EDT and Chief Commercial Officer will address commercial readiness activities for Happy Camping. Thank you for joining us on the call today.
Speaker Change: Stuart Kupfer, SVP, and Chief Medical Officer, both the right updates on the clinical development of only camps in Macarvel and the CK side-based sex. [inaudible]
Speaker Change: Isaac Sihann, EVP Corporate Development and Chief Business Officer will provide an update on business development in the context of our corporate development.
EBT: Sung Lee, EVP, and Chief Financial Officer will provide a financial overview of the past quarter. And finally, Robert will review our expected key milestone for the remainder of 2025.
Speaker Change: 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 constitutes solo-looking statements.
Speaker Change: To differ materially from those in these forward-looking statements, it's contained in our SEC filing, including our current report regarding our first quarter, 2025, financial results filed
Speaker Change: Now it's furnace to the SEC today. 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 to all for joining us on the call today. The first quarter provided a strong start to the year, laying a solid foundation for the increased momentum we're building as we approach a pivotal step towards potential commercialization.
Robert Blum: Of course, our principal focus is on our new drug application for Apikanton.
Robert Blum: As we disclosed last week, the FDA extended the pedophadate for the NDA for AFI Camping for the treatment of patients with OHCM to December 26, 2025 to provide
Robert Blum: and to be cleared. We had a series of three meetings with FDA ahead of our NDA submission for Alfie Campton, during which we discussed a range of topics related to the content of our submission, including safety monitoring and risk mitigation strategies.
Robert Blum: These included a top-line meeting to review the results of Sequoia HCM, a pre-MDA meeting to cover specific topics related to our submission.
Robert Blum: and the type B meeting during which we discuss strategies related to safety monitoring and risk mitigation in support of our NDA submission.
Robert Blum: Attending all three of these meetings where representatives from the division of cardiology and nephrology as well as representatives from the division of risk management within the office of surveillance and epidemiology of FDA. Thank you.
as we've previously shared.
Robert Blum: These interactions provided the opportunity to discuss in detail the data supporting the safety and intrinsic pharmaceutical properties of ATH, and how they may inform approaches to manage risk and gain insight into FDA's perspectives on this matter.
Robert Blum: Given these interactions, we considered it reasonable to propose a distinct risk mitigation approach specific to Afi-Campton and based on labeling and other tools such as voluntary education materials.
Robert Blum: However, we understood from FDA that the potential need for a REMS would be a focus of the agency's review. We made the determination to take this approach because under the circumstances we thought it was reasonable given the profile of Afi-Canton.
Robert Blum: However, as a contingency we developed our distinct REMS proposal and we were well prepared to submit it if necessary.
Robert Blum: During the NDA review, given the mechanism of Alfie Campton, the FDA requested that we submit a round specific to its intrinsic properties which we promptly provided.
Robert Blum: As we communicated last week, we recently learned from FDA that our subsequent submission of the REMS constitutes a major amendment to the NDA, and will now require a standard three-month extension to the original Kadoopa Action Date.
Robert Blum: To remind you, please, we discovered and developed Kathy Campton with objective to advance it as a potential next-in-class cardiac myosin inhibitor.
Robert Blum: Based on its inherent characteristics, we evaluated it in pre-clinical and clinical studies to understand how it's half-life [inaudible]
Robert Blum: It's rapid onset, it's reversibility, as well as an optimized relationship between PT and PD could enable a unique convenient dosing regimen.
Robert Blum: We extensively steady its DDI profile to similarly ensure that it was a enabling of a distinct clinical profile to support potential differentiation.
Robert Blum: We believe the results of our clinical studies, including Sequoia HCM and Forest HCM, support a potential label and risk mitigation profile, that if approved by FDA, will differentiate outfitampton.
Robert Blum: Nothing has changed in that regard. And again, to confirm, no additional clinical data or studies were requested by FDA.
Robert Blum: As we disclosed in an AK filing in March, during the first quarter, we completed a mid-cycle review with FDA.
Robert Blum: During the meeting, FDA confirmed that the agency does not plan to convene an advisory committee meeting which is consistent with prior communications to us and that our late cycle meeting is expected to occur in June .
Robert Blum: While the producer extension does delay the potential approval of Afi Campton, it does not change our confidence in its distinct benefit risk and pharmaceutical profile.
Robert Blum: Norton had changed our expectation for a potentially differentiated label and risk mitigation profile upon potential approval.
Robert Blum: Given the FDA review of the NDA is ongoing, we do not intend to provide further color or detailed updates on our communications with FDA.
Moving on.
during the first quarter and recently.
Robert Blum: We also advance regulatory activities outside of the U.S. In April , we received 120-day questions from the EMA regarding the MAA for Alfie Canton in Europe and we're now working to develop responses.
Robert Blum: I'm pleased to share that we believe we are on track for potential approval by the EMA in the first half of 2026.
Robert Blum: During the quarter, we also worked with Sanity, our partner in China, to support the NDA review of Alfie Campton with the NMPA. And overall, we're encouraged by the steady progress of our regulatory
Robert Blum: Moving to other activities, in the first quarter, we continue to dial up our commercial readiness, not only in the U.S. but also in Europe . As Andrew will elaborate, during the quarter, we may teach dries on all commercial planning work streams. [inaudible]
Andrew Callos: Yes, the producer date extension will shift out certain elements of our commercial readiness but we are moving forward with launch planning.
Andrew Callos: In the first quarter, we also achieved meaningful milestones in our ongoing clinical trials program for Kathy Campton. We're pleased to share today that we plan to report top-line results from Maple HCM this month.
Andrew Callos: If the results are positive, we believe these data may represent a potential label expansion opportunity for Fady Campton following an initial potential FDA approval in OHCM.
Andrew Callos: In addition to OHCM, we're also focused on MHCM in which there is a significant unmet need for effective treatments.
Andrew Callos: and with increasing recognition and diagnosis of the condition, the market opportunity continues to grow.
Andrew Callos: will please to share today that Akasha H.C.M., while pivotal phase three clinical trial of South-Ecampain in N.H.C.M., has completed enrollment in the first quarter.
Andrew Callos: Mons ahead of schedule, enabling us to read out the top-line results in the first half of 2026.
Andrew Callos: Fady will elaborate on this achievement, as well as on some additional updates that we made to the trial, as guided by global regulatory feedback.
Andrew Callos: As the prevalence rate of NHCM rises, we remain optimistic regarding the promise of alpha camp and in this population of underserved patients.
Andrew Callos: As you know, Apicampton for the treatment of both O and NHEM represents the first potential new medicine arising from our specialty cardiology franchise .
Andrew Callos: which also includes only tamper McCarble and CT-586, each advancing in respective later stage clinical trials in two different forms of heart failure.
Andrew Callos: The progress we made in the first quarter reflects thoughtful planning, disciplined resource management and a steadfast commitment to rigorous clinical research, all of which propel us towards our ambitious vision 2030.
Andrew Callos: Certain works will be adjusted, we are not losing our sense of urgency or monitoring this momentum. This year has been focused on building, implementing and executing our go-to-market plans, as we intend to keep building this momentum towards our revised December-pidupidae.
Andrew Callos: During the first quarter we initiated our South Force recruiting. Given the December Pduphidate will be revising our South Force on boarding plan while maintaining current recruiting schedule.
Andrew Callos: which is off to a great start. Today, we received several thousand applications, many from Hollywood qualified shelves for professionals, with the majority possessing abundant cardiology experience.
Andrew Callos: and existing relationships, giving us a strong talent base from which to identify top candidates for these positions.
Andrew Callos: In late April , we held a virtual recruiting webinar for Salesforce official candidates that crew nearly a thousand and ten bees.
Andrew Callos: These figures show high level of interest in how well-positioned we are to attract top talent and build the stand-out sales organization. In parallel, a work around sales operational planning continued, including analytics targeting, incentive crop, as well as finalizing the sales training curriculum.
Andrew Callos: We are also building our bespoke patient support program by integrating our strategic partners into a seamless patient-focused implementation. We also finalize the selection of our channel's distribution partner and specialty pharmacy partners.
Andrew Callos: Adorning the quarter, we continue to refine our promotional launch campaign for HEPs and patients.
Andrew Callos: Accounting for the most recent market dynamics, AQP advisory boards as well as primary market research testing.
Andrew Callos: At the same time, our ungranted disease, the awareness campaign, H.M. Beyond the Heart, continued. The H.M.P. focused awareness campaign direct H.A.P. to consider the broader H.M. burden and practice full-perfect care.
Andrew Callos: And likewise, the patient campaign helps educate people living with HCM, not just about the condition, but about the holistic burden of HCM.
Andrew Callos: We also maintained our engagement with Piers and plan to continue educating their moment data from the clinical development program of Frappi Campon, as well as the clinical and economic burden of the HGM.
Andrew Callos: On top of the burden of disease, we expect to have several H.O.R. presentations at upcoming meetings to further characterize both O and N.H.C.N. and deep and understanding of the disease.
Andrew Callos: To that point, an exciting milestone during the first quarter with our launch of EarthHM, an online, open access, interactive public health education tool developing collaboration with leading academic institutions.
Andrew Callos: Outside of our U.S. commercial planning, we advanced through a keen commercial readiness and activities in engaged manner, including higher in key leadership positions for marketing, finance, legal, compliance and human resources. And we set up new regional entities in France and the UK within country leaders. Thank you very much.
Andrew Callos: During the quarter, we also validated our reimbursement strategy in country-long sequence, which as we previously stated begins with Germany in 2026, pending EMA approval. Finally, we began dossier preparation for HTA submission across multiple geographies. [inaudible]
Andrew Callos: To summarize, we've made progress in our commercial readiness activities over the past quarter and will continue to finalize the robust commercial framework to support the potential U.S. and U.S. and U.K. and mortgages of ASI campus. With that, I'll turn the call over to find out if it's your updates on our ongoing clinical trial program for ASI campus.
Fady: Thanks, Andrew. As Robert mentioned, we plan to report top-line results from Maple HCM this month with a presentation of the primary results at a medical meeting later this year.
Fady: We want to set expectations now for the top line relief to be qualitative as we don't want to jeopardize this presentation of the major medical meeting by disclosing details of the results.
Fady: Elfate of Blockers, or Standard of Care at NCM. Their impact on exercise performance symptoms, and LVFT-gradient
Fady: The same time, the impact of treatment without the cancer as the model therapy, the number of same measures, is important to understand to inform the implementation of cardiac mice and inhibitors into the standard of care.
Fady: We look forward to the results of the 10 billion comparison made by TM. That may help differentiate the effects of African-Canton, non-exercise capacity, symptoms, and credit structure and function, as well as take intolerability from the long-established standard of care, mature through all.
Fady: We also have two important updates to share regarding the K-Trade VM.
Fady: Purti, Professor of police report, and in the first quarter of 2025, here with six months ahead of schedule, we completed patient enrollment for the primary cohort of this trial, which encompasses all sites in North and South America, Australia, Europe , China, and Israel.
Fady: We randomized 516 patients in only 18 months, which was driven by high interest in participation in accelerated screening and enrollment through the end of 2024 and into early 2025.
Fady: The primary co-work of Acacia 18M includes the region's originally designated for enrollment when we initiated the trial in 2023. [inaudible]
Fady: However, on the collaboration and licensing agreement, we entered into the fire.
Fady: Cracket Camp in Japan late last year, we also agreed to expand the K-8 CM to Japan, Targeting in March of 2002-2025, the support of potential marketing authorization for NHGM.
Fady: Given the primary cohort, completed enrollments, months ahead of schedule, the divided vacation it seemed in the two parts, the primary cohort and the Japan cohort, the approach supported by regulators in Japan.
Fady: With the proffman enrollment now completed in the primary cohort, we expect the share of top line results from that cohort in the first half of 2026.
Fady: To a dual primary endpoint, a change in KTQ's clinical summer score, and a measure of exercise capacity, PCO2, each measures the change from baseline in week 36.
Fady: This change is made to align the end points of the trial to feed back what you received from regulators outside the US and harmonize some interpretation globally.
Fady: Prior to this change, CPET measurements were already being obtained for all patients. So this change did not alter the conduct of the clinical trial. It only elevates a measured exercise performance from the first secondary endpoint to an additional primary endpoint. [inaudible]
Fady: Given the brisk enrollment of AK-8CM, we enacted this change knowing that we could also power the trial adequately
Fady: by increasing the sample size from 420 to at least 500 patients.
Fady: to ensure each of the primary endpoints at 90% power at an alpha of 0.025 to detect a conservative clinically
Fady: Comparative placebo for KTQQ, that's five points. And for PQQ, that's 1.0 nolier per kilogram per minute.
Fady: To be clear, however, it's either clinical endpoint that comprises of dual primary endpoint is statistically significant, in case the HCM will be considered positive.
Fady: In some, we believe these changes maximize the chances of a success on this trial and will also satisfy regulatory requirements globally.
Fady: And demonstrated improvements in case, EQ and NOI <unk> functional class and an average reduction expenses brought BNP a 66%. The majority of patients achieved the highest dose offers 15 milligram and there were no drug discontinuation due to low ejection fractions and few instances of LTE.
Fady: Less than 50%.
Fady: These findings were replicated when patients transitioning the open label extension trial for safety.
Speaker Change: And importantly in case ACM built on this phase II experience by using the same dosing approach with rapid attainment of target dose within eight weeks refinements in the entry criteria and careful patient selection based on Echocardiographic review.
Fady: Specialists.
Fady: Although ATM currently accounts for about one third of the ATM population, it's now being diagnosed at a much faster rate than OEM and as a result, we anticipate that any CMO comprised eventually nearly half of all HCM diagnose it.
Fady: The results from our casing.
Fady: This would represent a significant opportunity to help this underserved patient population, who currently have limited treatment options.
Fady: To close out the update on our ongoing clinical trials program enrollment in <unk> and is progressing and we remain on track to complete enrollment in the adolescent cohorts in the second half of this year.
Fady: As you've heard in the first quarter has been strong progress advancing the ongoing clinical trial program for <unk> in Canada.
Fady: We believe will pave the way for multiple opportunities to reach more patients living with HCM worldwide.
Stuart Kupfer: Now I'll turn it over to Stuart.
Fady: Yes.
Fady: Thanks Patty.
Speaker Change: I am pleased to provide updates on our later stage development programs.
Speaker Change: During the quarter. We continued conduct of ampere have passed the phase II clinical trial of CK 586 in patients with symptomatic heart failure with preserved ejection fraction of at least 60%.
Speaker Change: We continue to progress towards our goal of completing enrollment in the first two cohorts in the second half of this year.
Speaker Change: Approximately 2 million people with heart failure in the U S have an ejection fraction greater than or equal to 60%.
Speaker Change: Despite advances in care and broad use of standard of care treatments. These patients often have a poor prognosis following heart failure hospitalization and.
In our high re hospitalization rate that also drives up health care costs.
Speaker Change: The unmet need to deliver better options for patients is clear.
Speaker Change: And we believe and perhaps path will help elucidate whether a cardiac myosin inhibitor may benefit the subset of patients with heart failure and builds on our experience in non obstructive HCM.
Speaker Change: We also continue enrolling comment HFF, the confirmatory phase III clinical trial of <unk> in patients with symptomatic heart failure, which severely reduced ejection fraction of less than 30%.
We maintain progress in activating sites in the U S and convenient well attended U S investigator meeting at the end of April.
Speaker Change: During the meeting we were pleased to see a high level of investigator engagement, reflecting their recognition of the urgency of developing safe and effective treatments for this high risk population.
Speaker Change: And their motivation to enroll patients in the trial.
Speaker Change: Many of these investigators participated in galactic HFF the firm.
Speaker Change: First phase III trial in Camden the Carnival.
Speaker Change: We expect to continue enrolling common Hs this year and complete enrollment in 2026.
Speaker Change: Our later stage pipeline represents our next highest opportunity following out the campaign with.
Speaker Change: With multiple opportunities to positively impact patients with adjacent cardiovascular diseases of high unmet need.
Speaker Change: With that I'll pass it to either.
Speaker Change: Thanks Stuart.
Speaker Change: In the first quarter, we participated in a series B financing Embraer pharmaceuticals to support the advancement of <unk> for the treatment of MHC.
Speaker Change: This deal represents our first equity investment in which we can participate in and advise on the development of a novel therapy in the cardio metabolic space that may be of interest to us in the future without committing significant financial or operational resources.
Speaker Change: As we stated in our vision 2030 external innovation and business development is a key pillar of our growth strategy.
Speaker Change: Our current R&D pipeline has arisen entirely from internal discovery, and we see a significant opportunity to complement and enhance this foundation through investments partnering and licensing opportunities.
Speaker Change: By engaging selectively and prudently and opportunities to balance our own R&D activities by also externalizing innovation, we aim to gain access to additional novel science expand into adjacent therapeutic areas and ultimately accelerate the development of new therapies for patients importantly, we continue.
Speaker Change: To be open to all strategic levers to remain the partner of choice and continue to be both pioneer and leader in muscle biology.
Sam: Now I'll hand, it over to Sam.
Sam: Thanks, Isaac we're pleased to report our first quarter of 2025 financial results starting with the balance sheet. We finished the first quarter with approximately $1 $1 billion in cash cash equivalents and investments compared to $1 2 billion at the end of the fourth quarter of 2024.
Sam: Cash cash equivalents and investments declined by approximately $132 2 million during the first quarter of 2025.
Sam: R&D expenses for the first quarter were $99 8 million.
Sam: Compared to $81 6 million for the same period in 2024.
Sam: The increase was primarily due to advancing our clinical trials and higher personnel related costs.
Sam: G&A expenses for the first quarter of 2025 were $57 4 million compared.
Sam: Compared to $45 5 million for.
Sam: For the same period in 2024.
Sam: The increase was primarily due to investments in commercial readiness activities and higher personnel related costs.
Sam: Net loss for the first quarter of 2025 was $161 4 million.
Sam: Or $1 36 per share compared to a net loss of $135 6 million.
Sam: Or $1 33 per share for the same period in 2024.
Sam: Turning to our financial guidance, we are maintaining our full year 2025 financial guidance with GAAP operating expense is expected to be between $670 million and $710 million.
Sam: Stock based compensation that is included in GAAP operating expense is <unk>.
Sam: Expected to be between $110 million and $120 million.
Sam: Excluding stock based compensation from our GAAP operating expense results in a range of $550 million to $600 million.
Sam: While the guidance range remains unchanged and there are two dynamics that move expenses within the range meaningfully.
The range incorporates the U S. <unk> date extension for Ft, Camden, which we anticipate will drive a decrease in G&A expense, mainly due to the adjusted timing of launch expenses.
Sam: Second the range accounts for the acceleration and increased enrollment of Acacia our phase III trial without the Camden, and HCM, which will increase R&D expense.
Sam: Given the U S. Producer date extension, we will continue to monitor the pace of prelaunch investments and update you accordingly.
Sam: Our balance sheet continues to be a source of strength and we are well positioned to fund the potential launch of <unk> in the U S. Later, this year and advance our pipeline.
Speaker Change: With that I'll hand, this off to lever.
Speaker Change: Thank you Shawn the first quarter was marked by meaningful progress across our business given the uncertainties of the macro market. We are operating within we're pleased to be an advantage position with a strong balance sheet and cash position, reflecting thoughtful planning and preparation.
Speaker Change: <unk> in 2024 that will allow us to execute on all of our key priorities in 2025.
Speaker Change: Looking ahead at the next several months Theres a lot in store for our company. Most importantly, the potential FDA approval of <unk> at the end of this year and our full transition them to becoming an integrated commercial biopharmaceutical company.
Speaker Change: But also the near term topline readout of Maple HCM.
Speaker Change: With all of this moving forward alongside continued conduct of multiple additional later stage clinical trials as well as our ongoing research our prospects remain bright as we advance our vision 2030 based on our pioneering foundation in muscle biology, we're closer than ever.
Speaker Change: To realizing the benefit of our science as may potentially impact the lives of patients living with diseases of muscle dysfunction.
Speaker Change: And now I'll recap our upcoming milestones for <unk>, we expect to advance NDA review activities with FDA to support the potential U S approval of RP Kimpton in the second half of this year, we expect.
Speaker Change: Back to advanced go to market strategies and prepare to commercially launch <unk> in the United States in the second half of this year subject to approval by the FDA.
Speaker Change: We expect to continue to go to market plans in Germany, and expand commercial readiness activities in Europe in 2025 and preparation for potential approval by the EMA in the first half of 2026.
Speaker Change: We expect to coordinate with paying a fee to support the potential approval of <unk> in China pending approval by the MTA and we expect topline results from Maple HCM. This month. We also expect to report topline results from the primary cohort of Acacia HCM in the first half of <unk>.
Speaker Change: <unk> 2026, and begin enrollment of patients in the Japan cohort of Acacia HCM in this quarter and.
Speaker Change: And we expect to complete enrollment of the adolescent cohort in Cedar HCM in the second half of this year.
Speaker Change: For <unk>, we expect to continue patient enrollment in Carmel HCF through 2025 to enable completion of enrollment in 2026 for CK 586, we expect to complete enrollment of the first two patient cohorts and Amber H R. Rather amber.
Speaker Change: In the second half of this year and finally for preclinical development and ongoing research. We expect to continue ongoing preclinical development as well as research activities directed to additional muscle biology focused programs.
Speaker Change: Operator with that said, we can now open the call up to questions. Please.
Speaker Change: Thank you.
Speaker Change: As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.
Speaker Change: The interest of time, we do ask that you kindly limit yourself to one question at this time.
Speaker Change: Please standby, we compile our Q&A roster.
Speaker Change: And our first question will come from Sean Mccutcheon from Raymond James Your line is now open.
Sean McCutcheon: Good afternoon, guys. Thanks, so much.
Speaker Change: Hi, Robert Thanks for the question based on the failure of Odyssey.
And the BMS verbiage around.
Speaker Change: <unk> HCM being different from non instructive.
Getting a lot of questions on what that means for Acacia can you speak to how you designed.
Speaker Change: Keisha around the properties of epic campaign to drive higher probability of success and how you view the importance of pushing.
Speaker Change: The CMI dose higher in non obstructive disease, given youre able to get the majority of patients on that 20 milligram dose in the forest.
Speaker Change: Non obstructive cohort thanks.
Speaker Change: Sure I'll speak generally and then our study to answer your specific questions. Firstly as it relates to our case HCM. We're very excited about the fact that it completed enrollment as it did ahead of schedule and with such enthusiastic participation around the globe.
Speaker Change: And at the same time. Please also understand that for taking the same dosing regimen forward into phase III and going to centers, where we believe there's already ample experience.
Speaker Change: At the Kimpton. This gives us optimism for what may be ultimately the results from that study you heard us referring to end HCM, both with regard to Redwood cohort four and how it leads we believe.
Speaker Change: In an encouraging way on what we should expect testing the same hypothesis in phase three so we maintain our very optimistic views towards Acacia with that I will turn it over to <unk> to answer the specific questions.
Speaker Change: Yes, I think.
Speaker Change: Points of Robert <unk> made are the important ones when we designed acacia when youre able to base. It very closely on what we had experienced in the phase II study.
Speaker Change: Cohort four of Redwood HCM. So the devastating is essentially the same although we did implement a higher dose.
Speaker Change: And Acacia lease.
Speaker Change: We've seen that dose be very successfully deployed and for us.
Speaker Change: And patients have.
Speaker Change: Have the availability to 20 milligram dose.
Speaker Change: And some of them are currently taking it we've.
Speaker Change: We've seen.
Speaker Change: And our Redwood very few treatment interruption.
Discontinuation.
Speaker Change: And tolerance and other things I think are very important dosing and getting the right dosing regimen. So often one of the most critical things in determining the success of a phase III trial.
Speaker Change: Barely I think we have again.
Speaker Change: Confidence in the.
Speaker Change: The data that we saw in phase II with regards to <unk> in any way J class improvement we didn't look at the two in phase III, just as we didn't do that for Sequoia as well for the OE.
Speaker Change: Sam patients but.
Speaker Change: But we expect again with the improvement in symptoms and functional class to see some improvement.
Speaker Change: He cared sale and we're very well powered to see even a modest change in peak <unk>.
Speaker Change: I think the last thing I'll point out is that lease.
Speaker Change: We stayed with centers, where we had a lot of experience.
Speaker Change: When we add that had very clear carefully.
Speaker Change: Basically.
Speaker Change: <unk> that reviews every patient.
Speaker Change: Enrollment in trials I'm sure that.
Speaker Change: Patients not only meet the entry criteria, but that their imaging.
Speaker Change: System with what you would expect in an ATM.
Speaker Change: All of the pieces, we're still very optimistic about the chances of success for Acacia.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question will come from Salim Sayed from Mizuho. Your line is open.
Robert Blum: Great. Good luck, Hey, Hey, Robert Good afternoon. Thanks for the question.
Speaker Change: The color today.
Speaker Change: So I guess all the SaaS.
Speaker Change: The obvious.
Speaker Change: Just a question here on asset Camden.
Speaker Change: Just wanted to be clear so did the FDA initially guide you to not submit.
Speaker Change: The Rams and then what happened was it something internal at the FDA or was there something in the package that that caused them to change there.
Speaker Change: Stance, if do you want to call it that and ask you to actually submit the ramp if you could provide some color around that thank you.
Speaker Change: Sure I understand you want to get more detail I'll share with you what I can but please understand that may be very selective in my language.
Speaker Change: As you probably know well when you have these interactions with FDA ahead of an NDA submission. They give you feedback and response to questions and as you've probably read the summary basis of approval for <unk> and you know that FDA.
Speaker Change: Guided for the submission of our Rems prior to its occurring.
Speaker Change: In our case that did not happen in our case, we did not receive such guidance in fact, we discussed.
Speaker Change: Safety risk mitigation and based on that discussion we believed it reasonable to submit as we did without our rents. It was not an omission we understood very well the feedback that we were receiving and we elected to proceed submission with <unk>.
Speaker Change: <unk>.
Speaker Change: It was accepted by FDA.
Speaker Change: Without a rems and.
Speaker Change: And it was doing the review itself that FDA notified us that they would like to see us submit a rooms, we can't know all that was going on within the FDA that prompted there want to see a rems.
Speaker Change: As you know there is a lot going on around.
Speaker Change: In FDA, but we do know that we were well prepared for that scenario, where FDA to then consider during the review that a rems would be appropriate and they did so it was then that we submitted the rems and as is <unk>.
Speaker Change: Linked.
Speaker Change: We believe consistent with feedback we received with FDA relating to inherent characteristics or intrinsic properties of kimpton.
Speaker Change: So I think thats going to have to suffice for what.
Speaker Change: We can share.
Speaker Change: We don't want to communicate things.
Speaker Change: Things that would be deemed speculation because frankly, we don't know all of that contributed to fda's ask us, but I've shared with you what we know and the determination we made based on the feedback we have received.
Speaker Change: Okay helpful. Thank you very much.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question will come from <unk> <unk> from Barclays. Your line is open.
Speaker Change: Good afternoon.
Gena Wang: Gena Wang actually this is gena Wang from Barclays.
Speaker Change: Maybe Rob just follow your comments.
Speaker Change: Don't know if you can comment there.
Speaker Change: Can you tell us whether the Rems program you submit to the FDA was that consistent with the value share with the investors.
Speaker Change: That the apps.
Speaker Change: Uh huh.
Speaker Change: Political was that consistent when you ship when you submit that to the FTE and also given this unfortunate event, but can you take advantage of it.
Speaker Change: There is only one time extension for the producer and if you cannot extend twice.
Speaker Change: Can you use the maple data in the trial.
Speaker Change: To submit the <unk> data and you're trying to be included in the label.
Speaker Change: For the December 26th approval.
Speaker Change: So I'll answer the second question first we do not intend to submit the maple data as part of this review cycle of apathy Camden in HCM.
Speaker Change: That would constitute a different.
Speaker Change: Submission that would.
Speaker Change: Likely not.
Speaker Change: Be well received by FDA, given how far along they are in this review.
Speaker Change: We do intend.
Speaker Change: Positive.
April results are obtained later this quarter, we do intend to move swiftly to be enabling.
Speaker Change: Subsequent submission, but that would follow a potential approval of <unk> in OE HCM.
Speaker Change: As it relates to your first question I just would like some clarification. Please.
Speaker Change: You asked whether the Rems, we submitted is consistent with something we shared with investors.
Speaker Change: Alright.
Speaker Change: The previous communication that will be like see the frequency will be week to week.
Speaker Change: Week, eight I'm trying to pull out the actual information that you've shared in the past with investors. So just wondering have you and then also minimal.
Speaker Change: The second.
Speaker Change: <unk> monitoring protocol was that consistent with what you propose that you would think it will be differentiating from.
Speaker Change: Ken Xyrem Rems program.
Speaker Change: Yes. Please also understand in the interest of maintaining.
Speaker Change: Competitive advantage, we're not going to provide specific information regarding the rems, we did submit but I will ask study to elaborate in a general way about how we're approaching safety and risk mitigation.
Gena Wang: Yes, Hi, Gena I think.
Gena Wang: What we submitted as being as consistent with what we've said all along or is it differentiated properties of Apple camp and so.
Gena Wang: As we did in Florence, we amended the protocol to enable every six months monitoring to widening the dosing window from from.
Gena Wang: Every two weeks every two to six or eight weeks.
Gena Wang: To enable physicians to.
Gena Wang: Guide dosing directly.
Gena Wang: And we.
Gena Wang: We've as we've been I think straightforward and presented those data recently to Marin American College of Cardiology.
Gena Wang: We don't really have any comments clinically common drug drug interactions and so.
Gena Wang: And expect all of those features.
Gena Wang: We have gone into the design of our Rems program that we think will be.
Gena Wang: Gains and well received by physicians that treat these patients.
Gena Wang: Thank you.
Speaker Change: Thank you. Thank you.
Speaker Change: Thank you. Our next question comes from Paul Choi from Goldman Sachs. Your line is open.
Speaker Change: Hey, Paul.
Paul Choi: Good afternoon, everyone. Thanks for taking the question.
Speaker Change: Yes.
Speaker Change: However earlier you said.
Speaker Change: Camden will it be differentiated but maybe just to continue on what Bobby was saying.
Speaker Change: With the recent changes to the campus iOS label, removing the Senate that drug drug interaction warnings as well as extended monitoring.
Speaker Change: Increasing the monitoring periods up to six months.
Speaker Change: I guess a lot of investors are just wondering what sort of left on the table for <unk>. If you could differentiate here maybe slight.
Speaker Change: <unk> points here to help clarify that that would be helpful. Thanks for taking our question.
Speaker Change: Sure again in a general way without specifics please.
Speaker Change: I will.
Speaker Change: Correct. The statement you made as it relates to <unk>.
Speaker Change: And as it relates to echo monitoring there were.
Speaker Change: Modifications made to the existing Xyrem rems, but still there are limitations as it relates to Didi is still there are limitations as it relates to echo monitoring certainly during the up titration phase, but also during the maintenance.
Speaker Change: Since space.
Speaker Change: It pertains to certain patients.
Speaker Change: So I would answer your question as follows.
Speaker Change: It remains we believe ample opportunity for differentiation based on the revenues that we have submitted.
Speaker Change: Okay.
Speaker Change: Thank you.
Speaker Change: And our next question will come from Cory <unk> from Evercore. Your line is open.
Cory: Hey, Carter.
Speaker Change: Hey, Robert Hey, guys. Thanks for taking the question.
Speaker Change: My question is did you submit a rems as part of your EMA filing and if not was that brought up as part of your de 120 list of questions. Thank you.
Speaker Change: So there is no rems per se as part of a.
Speaker Change: MAA filing with EMA.
Speaker Change: But obviously there are ways that one wants to ensure safe use and mitigate risk I'll turn it over to Paddy maybe to elaborate.
Paddy: Yes, EMEA approaches it differently.
Speaker Change: They don't have a rems program or say you asked even submit a risk mitigation program RMP.
Paddy: As a standard part of any submission, which.
Speaker Change: Which we did.
Speaker Change: Yes.
Speaker Change: <unk>.
Speaker Change: Again, we don't expect.
Speaker Change: Any changes if you will no additional submissions in Europe relating to that so.
Speaker Change: Very different than the way, it's priced in the United States.
Speaker Change: But to the point of your question.
Speaker Change: For now receipt of the day 120 questions and are proceeding to respond.
Speaker Change: We believe we are well served by what we submitted.
Speaker Change: Thank you.
Speaker Change: And our next question will come from over a lot of relief from Leerink partners. Your line is open.
Speaker Change: Hey, everyone afternoon.
Speaker Change: So a question on the Acacia trial can you talk a bit more about the pros and cons of changing the primary endpoint to a dual primary of peak <unk> and KC Kew and I was also curious if you could share more details of the current statistical plan for Acacia and if you're able to share with the dual primary end point that would be real.
Helpful.
Speaker Change: Yes, so before I ask Todd to answer I will just say I think as.
Speaker Change: I look at this this gives us two opportunities to win with Acacia.
Speaker Change: And building off of what we've seen with.
Speaker Change: Ft Kimpton, both in <unk> as well as in Redwood cohort for.
Speaker Change: This is encouraging in light of.
Speaker Change: How we proceeded in the design of conduct of Acacia and maybe fatty can go into more detail with you.
Speaker Change: Yes.
Speaker Change: And in case, one of the important characteristics to make it as efficient a trial as possible.
Speaker Change: We didn't know at the time, nobody really knew at the time now and HCM trial would enroll.
Speaker Change: How quickly it would enroll.
Speaker Change: And consequently.
Speaker Change: The most efficient thing to do is to declare a single primary endpoint and assign all the outlook to it.
Speaker Change: And your secondary endpoint can be your next most important endpoint in the first one is positive in all the alpha <unk> flows through the second endpoint.
Speaker Change: That was an approach that was endorsed by FDA and.
Speaker Change: Of course, they even if the trials are positive on the first primary endpoint they wanted to see consistency across multiple endpoints, including exercise performance and so.
Speaker Change: The the design in Acacia.
Speaker Change: And we originally put.
Speaker Change: Sure, it's really the most efficient in doing that well powered with at 420 patients.
Speaker Change: Now other regulators just didn't have the same.
Speaker Change: Depreciation of that.
Speaker Change: As we got advice in Europe.
Speaker Change: In Japan, they are much more consistent on that.
Speaker Change: Imposition of a.
Speaker Change: Dual primary endpoint with two components, one being the <unk> and the other being <unk>.
Speaker Change: And rather than leaving it to be a review issue.
Speaker Change: What we also are benefiting up is that.
Speaker Change: Towards the end of last year.
Speaker Change: Moment in our trial really began to accelerate.
Speaker Change: And it became quite feasible for us to enroll more patients.
Speaker Change: To satisfy regulators around the world by designating a dual primary end point.
Speaker Change: Losing any power they are both powered at 90%.
Speaker Change: And essentially allow us to SaaS, Casey CQ and PPL two in parallel and so if we went on both endpoints then the next secondary endpoint is evaluated at <unk>.
Speaker Change: We've been on one of the two endpoints and the secondary endpoint. The next secondary endpoint, which Susan White shade class will be evaluated at point <unk> five.
Speaker Change: But again just to be clear, both both endpoints and the secondary endpoints for that matter, even appointed whats implied at more than 90% power.
Speaker Change: Just on the increase in enrollment.
Speaker Change: So we think it puts us in the best possible position to.
Speaker Change: Really satisfying regulators around the world and I'm, all set and done.
Speaker Change: And ultimately it doesn't change.
Speaker Change: The interpretation of the strong outlets required I think by regulators, which requires both I think they want to see both symptoms and exercise performance.
Consistent.
Speaker Change: Hopefully that's got it.
Speaker Change: Yeah helpful. Thank you.
Speaker Change: Thank you.
Speaker Change: Okay.
Thank you. Our next question comes from Zaki movie from Jefferies. Your line is open.
Speaker Change: Hey, this is actually cost so couple of things what would you have to show with the FDA and real world data to potentially get at yearly Echo requirement over time is that a discussion you've already had with the agency and then just to be clear is cytogenetics confident that a differentiated brand.
Speaker Change: <unk> Camden means an educational Rams and not in the top two one.
Speaker Change: Thanks, so much.
Speaker Change: Sure again.
Speaker Change: Youll. Please understand if we won't answer all of the specific questions relating to elements of differentiation within.
Speaker Change: The Rems itself. So your question about frequency of Echo monitoring is.
Speaker Change: Same as how we approach other matters.
Robley: Robley best for us not to address specifically.
What I will say is I think it's reasonable for us to be assuming over the Tulsa Rems. That's the approach we're taking.
Robley: Okay.
Robley: Okay.
Robley: Thank you.
Speaker Change: And as a reminder, in the interest of time, we do ask that you. Please limit yourself to one question.
Speaker Change: And our next question will come from Charles Duncan from Cantor. Your line is open.
Charles Duncan: Hello, Charles Anthony.
Robert Blum: Robert Good afternoon. Thanks for taking the question and congrats on the progress I do have what I'll call a multi part question and that is the same subject and that is <unk>.
Robert Blum: Regarding maple HCM absolutely respect.
Robert Blum: With regards to the FDA, but how are you thinking about the same type of strategy with regard to submitting maple after the fact for the EMEA as well as in China to the NFPA and if so why.
Speaker Change: Good question and I'll turn that to fatty please.
Speaker Change: Yes, I think Charles the answer really is the same in all jurisdictions.
Speaker Change: Adding maple HCM to an application and the applications are already well into review would be quite disruptive and so.
Speaker Change: <unk> plans to do that we will plan to submit that.
Speaker Change: Following approvals in those.
Speaker Change: Sure tradition.
Speaker Change: Okay.
Speaker Change: To that data.
Speaker Change: Thanks, John.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Ken <unk> from Merrill from Jpmorgan. Your line is open.
Speaker Change: Hello, Thank you.
Speaker Change: Thank you good afternoon.
Speaker Change: Did that.
Speaker Change: Indicate at any point during these three meetings that you outlined before your NDA was filed that they did not think that <unk> would be necessary.
Speaker Change: And why didn't you disclosed that there was no ran submitted back when you submitted the NDA and when exactly did the FDA request <unk>. Thanks.
Speaker Change: So I'll do my best to answer the questions.
Speaker Change: I prefer not to.
Speaker Change: You indicate what the FDA told us.
Speaker Change: As I think.
Speaker Change: That's for FDA to communicate what I can communicate is how we.
Speaker Change: Determined based on FDA feedback, what we should do.
Speaker Change: That's what we're communicating today.
Speaker Change: Therapy campaign results immediately approved that I expect in a summary basis of approval. This will all be laid out for you then to understand.
Speaker Change: But I hope you can appreciate that for the fact that we continue to have ongoing interactions with FDA.
Speaker Change: I don't think it would make sense for us to let this play out in a public way and any such way that FDA.
Speaker Change: Ultimately be concerned.
Speaker Change: That's number one.
Speaker Change: Currently U S. When did we received this information.
Speaker Change: We received it very promptly.
Speaker Change: Around the time that.
Speaker Change: We communicated.
Speaker Change: As we did.
Speaker Change: We made this decision and work.
Speaker Change: Getting feedback from FDA regarding the amendment.
Speaker Change: So it was recently.
Speaker Change: We submitted the Rems and recently.
Speaker Change: The FDA came back to us and said upon.
Speaker Change: A review of the Rems. They believe this constitutes a major amendment.
Speaker Change: Did I answer your questions.
Speaker Change: You did I just curious why a disclosure wasn't made back when you submitted the NDA that there was no rinse that was submitted.
Speaker Change: Oh because.
Speaker Change: That would be.
Speaker Change: Unconventional irregular and certainly.
Speaker Change: That would be.
Speaker Change: Potentially subtracting from downstream competitive advantage.
Speaker Change: We didn't think that was information that required disclosure in fact, instead, because we did not submit a rems. We were very disciplined about what we were saying that we believed upon approval.
Speaker Change: Ft, Kimpton would carry a differentiated safety and risk mitigation profile.
Speaker Change: You'll note that we did not say with rems or we did not say without realms.
Speaker Change: But only upon asking.
Speaker Change: For us to submit our revenues.
Speaker Change: Did we then submit the Rems and we began communicating now differently that we expect the differentiation would be within the realms.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Maxwell score from Morgan Stanley. Your line is open.
Maxwell Score: Great. Thank you for taking my question so.
Speaker Change: We approach this a little bit differently or try to but given that <unk>. Just updated recently submitted a 100 day 120 day safety update from the <unk> trial.
Just wondering whether the Rins you recently submitted to the FDA potentially differs from what you would have submitted with the initial filings or discussed during your pre NDA meetings. Thank you.
Speaker Change: Yes. This is a very fluid situation, what we might have submitted how do we submitted a rems in 2024.
Speaker Change: One reflection speculation.
Speaker Change: That I prefer not to go there what I will say is that.
Speaker Change: We have been monitoring quite closely not only our conversations with FDA, but also how the FDA approached.
Speaker Change: The modification of the Rems program for <unk> and.
Speaker Change: And we believe we've submitted a rems that would be enabling of a differentiated distinct profile.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Liana <unk>, Tim Michelle from RBC. Your line is open.
Speaker Change: Hey, Thanks for taking my question I figured I'd give you guys a break from the Rems discussion.
Speaker Change: I was just curious on an H C M.
Speaker Change: With only one drug potentially going to be approved in the near term yours I guess, how are you thinking about what that means for potential uptake of kimpton in HCM. If it's approved I mean would you expect or patient warehousing and therefore more rapid launch or would you have preferred someone building out that market and then I guess on EU <unk>.
Speaker Change: Versus U S and you've talked about 50% of patients ultimately coming from HCM as that dynamic just for the U S for both internationally as well thanks.
Speaker Change: Good questions I'm going to turn to Andrew Carlos to answer those please.
Speaker Change: From an M&A standpoint of view.
Speaker Change: Diagnosis rate is increasing pretty dramatically I think when when you do market development for HCM.
Speaker Change: Restricted to obstructive HCM, it's really broader for the disease. So when we look at uptake for an HCM I would expect that HCM uptake would be faster than <unk> because of all the market development work because of physician utilization of <unk>.
Speaker Change: As well as expansion beyond the current prescribing base so.
Speaker Change: We're already thinking with maple with the properties.
Speaker Change: <unk>.
Speaker Change: At the campaign that we have the ability to expand beyond the centers of excellence I think that would get accelerated with maple and further accelerate greeted with acacia.
Speaker Change: And they're likely to be a halo effect, if you will in terms of utilization across both obstructive and non obstructive.
Speaker Change: Both maple advocates are positive as well.
Speaker Change: Thank you.
Speaker Change: And our next question will come from David Leibowitz from Citi. Your line is open.
Speaker Change: Hello, Thank you very much for taking <unk>.
Speaker Change: Thank you very much for taking my question.
Speaker Change: Could you characterize the nature of the.
Speaker Change: The market opportunity presented by Maple.
Speaker Change: Given.
Speaker Change: Well in beta blockers might not necessarily be the most effective they are cheap.
Speaker Change: Chris cried by a wider array of doctors.
Speaker Change: Yes, we've been consistent that we do believe that if maple were positive in.
And ultimately.
Speaker Change: That's reflected in guidelines that this would be incremental but not transformative to what we believe.
Speaker Change: Ultimately could be the adoption curve for <unk>, kimpton and could be enabling of more category penetration, especially amongst cardiologists, who may be very comfortable with beta blockers, but youre absolutely right.
Speaker Change: They are inexpensive.
Speaker Change: And as payers.
Speaker Change: Go they may likely want to see the guidelines be modified reflecting of the use of a CMI.
Speaker Change: For patients first.
Speaker Change: First line therapy, Andrew has done some market research here and he may have more to add.
Robert Blum: Only to say that in this and Robert said that when you have a second dataset that assuming it's positive level of positive the second dataset that confirm efficacy that confirm safety.
Speaker Change: Safety.
Speaker Change: That adds to guidelines.
Speaker Change: Generally we will increase penetration within use of CMI. So simply said that more physicians with more patients will use a CMI.
Speaker Change: Yeah.
Speaker Change: Then without Maple and then Theres, an increased share potential for epic campaign as well so you really get.
Speaker Change: All of those things collectively when you add a second dataset around the same disease area and I do think.
Speaker Change: From our research is going to enable broader penetration into community cardiology.
Speaker Change: Got it thank you for taking my question.
Speaker Change: If the results are positive and we hope they are.
Speaker Change: Then we can do further market research around that particular profile.
Speaker Change: And that May inform how we may communicate down the road, but I think at this point in time that's.
Thats the way, we see things.
Speaker Change: Thank you.
Speaker Change: Thank you our.
Speaker Change: Our next question will come from my Mom Tony from B Riley Securities. Your line is now open.
Mom Tony: Good afternoon.
Speaker Change: Thanks for taking the questions. Two quick process question really could you could you touch on your confidence level in this newly submitted James to.
Mom Tony: To be accepted as is.
Mom Tony: Blood startup communication, we can receive from you on this.
Mom Tony: A follow up to the June our late cycle meeting that is coming up in this high level like do you sense independent physician feedback, saying follow up and add comments something that could be valuable headed.
Mom Tony: So the agency in the community, particularly since you'd have the Maple HCM data.
Mom Tony: By then to go out.
Mom Tony: To that tier differentiation.
Mom Tony: So I believe that was three questions and I'm going to try to remember now the first one.
Mom Tony: I think you asked me if I thought that the Rems as submitted would be accepted as submitted.
Mom Tony: These things are never exactly as they are submitted theres always a back and forth.
Mom Tony: We do believe it's for that reason that FDA chose to.
Make the submission a major amendment, but we believe there is ample time to address those matters.
Mom Tony: Within the.
Mom Tony: The extended time.
Speaker Change: I know your third question related to the AD com.
Mom Tony: Yes.
Mom Tony: Because the FDA communicated they don't expect an outcome, we're not expecting an outcome.
Mom Tony: <unk> believes that.
Mom Tony: That.
Mom Tony: Could change based on anything that we're having conversation about today. So you are suggesting that maybe the outcome could be to our advantage. If I heard you correctly I don't think that's practical at this point.
Mom Tony: Yes.
Mom Tony: Has the more data to be shared in a public forum about the drug's profile, especially the treatment initiation fees.
Mom Tony: Monitoring so.
Mom Tony: I don't know again, the agency benefit from having that independent physician feedback.
Mom Tony: Florida was the time.
Mom Tony: As we've stated before with.
Mom Tony: The choice to have an AD com or not.
Mom Tony: Rarely if ever I believe pivots around things that are included in our revenues.
Mom Tony: They don't typically have expertise amongst advisers, who.
Mom Tony: Populate an outcome pertaining to revenues.
Mom Tony: They look at risk mitigation at FDA.
Mom Tony: So that would be I think a quite a regular type of outcome.
Mom Tony: I don't foresee that something that investors or analysts.
Mom Tony: Should we be thinking about.
Mom Tony: I believe your second question.
Mom Tony: Pertained.
Mom Tony: Two.
Mom Tony: What was it Andrew.
Speaker Change: Late cycle meeting and based on communications, we've received from FDA.
Mom Tony: We're expecting that to occur.
Mom Tony: This second quarter in June.
Robert Blum: Thank you Robert.
Mom Tony: Thank you.
Mom Tony: Thank you.
Speaker Change: And as a reminder, we do ask that you. Please limit yourself to one question.
Speaker Change: And our next question will come from Crypto Denver Khanda from Cheerless. Your line is open.
Speaker Change: Hey, guys. Thank you so much for taking my question.
Speaker Change: Sorry to belabor the point, but just wanted to make sure I understood. It correctly. You said you did not receive any guidance from FDA to submit <unk>, whereas NEVA Kempton David Ritchie.
Speaker Change: The guidance, but you also said that during these meetings. The three meetings that you talked about the good feedback in response to your questions. So based on what you're saying is it fair to assume that you asked the FDA. If you should submit the rents and then based on the feedback you concluded that it was not it was not just a.
Speaker Change: Midland program.
Speaker Change: I think thats correct.
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: Thank you I'll stick to one question.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question will come from James Conduit from Stifel. Your line is open.
Speaker Change: Thanks for sneaking me in and sorry for one more question on the <unk> here. So it sounds like the ask from the FDA kind of came after the mid cycle review I guess is that right and just wondering if theres any color on sort of that mid cycle review that you can give in terms of.
Speaker Change: Discussion around the need for the rins or lack of that and just kind of curious if theres any color you can provide.
Speaker Change: Yes, I think we've provided the color that we can provide.
Speaker Change: And as you know we do.
Speaker Change: Did issue an 8-K after the mid cycle review meeting.
Speaker Change: We did indicate that we submitted.
<unk>.
Speaker Change: We got the feedback <unk> received that it constitutes a major amendment I'm thinking that.
Speaker Change: All that we can communicate at this time.
Speaker Change: I hope that's good enough it seems.
Speaker Change: May be over indexing, a little bit about this matter now but.
Speaker Change: I do think that.
Speaker Change: We're going to try to stay within.
Speaker Change: Consistent language.
Speaker Change: Around which we have now made these disclosures.
Speaker Change: All makes sense. Thank you.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Jason Domanski from Bank of America. Your line is open.
Speaker Change: Good afternoon.
Speaker Change: Congrats on the quarter and I appreciate you squeezing and I.
Speaker Change: Apologize I do want to return to the Rems.
Speaker Change: Just given everything Thats happened I know you.
Speaker Change: We are reluctant to discuss what FDA has said, but focusing in on the side of kinetic side of things.
Speaker Change: Given that the <unk> has been such a focal point and it was a big matter and May have a captain's review why not just include the Rems initially and then work around it seems like this was a risk hindsight being 2020 that that was sort of always out there.
Speaker Change: I would agree with you that it was a risk that was out there. It was a calculated one and we've made a determination based on multiple meetings with FDA.
Speaker Change: Please understand that.
Speaker Change: We not only have within cytogenetics.
Speaker Change: Substantial expertise as it relates to such matters, but also we convened with consultants, including ex FDA officials.
Speaker Change: On this matter.
Speaker Change: And <unk>.
Speaker Change: Collectively we all together concluded that.
Speaker Change: The way we approached.
The submission without the loans was reasonable.
Speaker Change: And.
Speaker Change: We address feedback we received as pertains to labor.
Speaker Change: Labeling.
Speaker Change: And risk mitigation absent, including a rems in that submission.
Speaker Change: The NDA was accepted for filing with the other wells.
Speaker Change: And as we knew was a possibility during Fda's review.
Speaker Change: Does it come back and ask for our revenues.
Speaker Change: So we believed.
Speaker Change: Then that we were doing the right thing to be enabling of RP kimpton as could be differentiated and distinct and its positioning but for addressing safety and risk mitigation within labeling.
Speaker Change: FDA has come back and now is asking for a rems.
Speaker Change: Thats reasonable.
Speaker Change: Opponents review has determined the rems is appropriate given the mechanism but for.
Speaker Change: We believe FDA has also communicated that.
Speaker Change: <unk> distinct.
Speaker Change: Intrinsic pharmaceutics and inherent characteristics of that the khamsin is appropriate.
Speaker Change: So we've submitted such a rems.
Speaker Change: Don't know that there is much more that we can say.
Speaker Change: I hope that answers your question.
Speaker Change: It does I appreciate the color.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question comes from Leland <unk> from Oppenheimer. Your line is open.
Thanks very much.
Actually I'm going to ask a non rems question.
Speaker Change: Robert just wanted to ask in terms of any real world studies that you might be performing.
Speaker Change: After a presumptive.
Speaker Change: Captain approval of the 24 weeks equate data will you be looking to collect real world data that may.
Speaker Change: Further flesh out or delineate.
Speaker Change: Benefit to support action surgery for patients who are accretive.
Speaker Change: Yeah.
Speaker Change: Yes, so the forest study continues to enroll.
Speaker Change: And.
Speaker Change: The conduct of that study continues to support what we believe to be.
Speaker Change: A distinct profile for RP, Camden, Youll see more of that data this year.
Speaker Change: And.
Speaker Change: While this wasn't a specific question of yours are.
Speaker Change: We believe this data is supportive.
How we foresee <unk>.
Speaker Change: Hampton.
Speaker Change: As could be.
Speaker Change: Enabling us to continue to maintain a distinct profile.
Speaker Change: Maybe all.
Speaker Change: Turning to Friday, I think you asked a specific question about septal reduction.
Speaker Change: Yes, that's right.
Speaker Change: Yes.
Speaker Change: In.
Speaker Change: And Sequoia, we conducted an analysis of patients qualified for septal reduction therapy and showed essentially treatment.
Speaker Change: After the campaign.
Speaker Change: Does that need by 90% or 90% of patients are no longer eligible for it.
Speaker Change: That we've seen again as those patients go in the fourth at the same.
Speaker Change: Sort of dynamics.
Speaker Change: And what we anticipate.
Speaker Change: As we look at now much longer term experience in Florida.
Speaker Change: Ah patients that didn't qualify to start.
Speaker Change: As to get a sense of the natural history of that you would expect some of those patients would have gone on to begin to qualify their conditions worsen.
Speaker Change: And we can begin to compare those ORF data to real World registry and look at the progression of event rates and for us versus the progression of event rates, perhaps elsewhere I think what we'll see is that after the <unk>.
Speaker Change: Actually slowing those rates in the long run.
Speaker Change: Add to the.
Speaker Change: Jason.
Speaker Change: Then at the captain of the cardiac myosin inhibitors of disease modifying mechanism.
Speaker Change: Great. Thank you very much.
Speaker Change: Thanks.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Jason Butler from citizens JMP. Your line is open.
Speaker Change: Hi, Thanks for taking the question just wanted to switch gears here.
Speaker Change: Ask the question about CK 586 in the <unk> study.
Speaker Change: I guess two parts one can you give us color on how you plan to disclose data from the first two cohorts, but I guess more importantly, how should we think about these first two doses in terms of being effective doses or when we would expect to see something that's optimally affective out of the study.
Speaker Change: Okay.
Speaker Change: Thank you, Jason and I will turn to <unk> and also to Stewart to answer that question. Please.
Speaker Change: Yes, I think that.
Speaker Change: I'll, let Stewart answer most of this but just remember this is a phase II study objectives are really defined dose.
Speaker Change: And to begin to get some sense.
Stuart Kupfer: Of effectiveness and Stuart maybe you can take it from there.
Stuart Kupfer: Hi, Jason Thanks for the questions.
Speaker Change: First of all.
Speaker Change: You wouldn't expect that we will disclose the results of the first two cohorts.
Speaker Change: Independently of having that.
Speaker Change: For the final study so yes.
Speaker Change: Yes, we will look at the totality of data and then.
Speaker Change: The results.
To answer your second question.
Speaker Change: It's Patty alluded to this is a dose finding study.
Speaker Change: <unk> a dose titration strategy study.
Speaker Change: And when a population with a lot of Comorbidities.
Speaker Change: This is an older population than the non obstructive HCM patients we're studying in Acacia and so we're taking a very careful systematic approach as you would with.
Speaker Change: How many dose finding study starting with lower doses and Ty trading up.
Speaker Change: Based on what we observe in terms of the Pharmacodynamic effect attacked on injection fraction safety and Tolerability.
Speaker Change: And with this sort of systematic and safe approach than we will.
Speaker Change: Essentially characterize what is the appropriate dose to.
Speaker Change: To take forward in terms of the benefit risk profile.
Speaker Change: Okay.
Thank you.
Speaker Change: And our next question will come from Serge Belanger from Needham <unk> Co. Your line is open.
Speaker Change: Hi, This is John on for Serge Thanks for taking my question.
Speaker Change: Just want to underscore that the expectations now.
Speaker Change: Between both the U S and EU with the amendment to the cashier.
Speaker Change: Our regulators aligned on what would be considered approvable based on which shifts at both endpoints.
Speaker Change: The trial need to satisfy or is there any disparity on whether KCP fewer TBA or two on what that.
Speaker Change: In a different light between the two agencies.
Speaker Change: Yes, I believe that as Patti can elaborate we've harmonized feed.
Speaker Change: Feedback we received.
Speaker Change: Regulatory agencies, but I'll ask him to comment.
Speaker Change: I think again.
Speaker Change: When you don't have a hard endpoints like mortality or hospitalization.
Speaker Change: Regulators on both sides of the Atlantic are looking for consistency cross feel and function.
Speaker Change: And.
Speaker Change: There is no good.
Speaker Change: Improved someone's exercise capacity in <unk> too.
Speaker Change: If they have no.
Speaker Change: Perceptive.
Speaker Change: They don't receive any benefit from it and vice versa.
Speaker Change: People are perceiving benefit you'd like to understand that because they are receiving some direct benefit from the drug and not something else.
Speaker Change: I might be off target or whatnot.
Speaker Change: So the FY <unk> to be consistent.
Speaker Change: Both sides of the Atlantic any degree in that the way we approached it.
Speaker Change: Frankly, we will provide that information to both sets of regulators.
Speaker Change: I think each of them has a different concept of what.
Speaker Change: How to approach that by designating certain endpoints.
Speaker Change: And by Upsizing the trial harmonizing the primary endpoints include both components.
Speaker Change: We're able really to satisfy everybody.
Speaker Change: And.
Speaker Change: Ultimately I think.
Speaker Change: Very similar interpretations of the data at the end of the day.
Speaker Change: Great. Thank you.
Yeah.
Speaker Change: Thank you our.
Speaker Change: Our next question comes from Yasmin Rahimi from Piper Sandler Your line is open.
Speaker Change: Good afternoon, Tim Thanks for the update I guess.
Speaker Change: Well, we're trying to figure out is like with all these different variety of questions around the room.
Speaker Change: Is it just a procedural mishap that it wasn't.
Speaker Change: You should have asked you to submit it and they did it in any of that didn't submit that you wanted to follow up with their instruction.
Speaker Change: Is there more to read into it.
Speaker Change: I think that that's what it comes down to like is it just to preserve chilled mishap and now it's in play.
Speaker Change: Or is there more to make sense out of them.
Speaker Change: Them coming back and asking so really I'm struggling to figure that part out.
Speaker Change: I understand.
Speaker Change: The sequence of events that are coordinating all earmarked for that very helpful. But.
Speaker Change: Maybe help us understand which one which one it is because the stock is trading in a way that makes the thing it's not just procedural theres more to it. So it would be wonderful if you could comment to the extent you can.
Speaker Change: I hear you're struggling it I'll try to address this in a constructive way, but please understand there was no mishap.
Speaker Change: I read what.
Speaker Change: Is causing some consternation amongst certain investors and please understand we don't believe at all that there was anything to suggest that irregularity.
Speaker Change: As part of a process by which.
Speaker Change: Our sponsor communicate with the FDA you get feedback based on that feedback you've taken action.
Speaker Change: FDA is.
Speaker Change: Within reason to be able to make a certain additional request. There is nothing here that would suggest anything new we believe in terms of risk and safety, but instead of having this addressed through label.
Speaker Change: Now it's being addressed.
Speaker Change: Through a more formal rems, but the distinction with differentiation those things that we believed coming into this submission when the submission was accepted for filing and even now through the review.
Speaker Change: Those things all speak to the same profile without the kimpton that has been emerging through its clinical study there.
There is nothing that FDA has communicated to us to suggest otherwise we do believe that the Rems program as a form of management of risk that now.
Speaker Change: It makes it more structured but it's.
Speaker Change: Still fundamentally as we have been communicating.
Speaker Change: I hope that.
Speaker Change: Address some of the questions and concerns.
Speaker Change: But you used the word mishap I would not at all suggest that thats what occurred here.
Speaker Change: Okay.
Speaker Change: That's helpful.
Speaker Change: Thank you.
Speaker Change: Thank you. Our next question will come from Ash Verma from UBS. Your line is open.
Speaker Change: This is Natalie for action. Thank you guys for your time and for the updates so I'm going to switch gears, a little bit and I actually have a question related to edge wise and in particular, we want to understand how you view the recent clinical data and to get even more specific.
Speaker Change: Really look at the numbers here and we were wondering if the ejection fraction measurements were done at peak like you've done in your program as opposed to doing them at trough.
You have a difference do you think that would have made to their measurements and just do you have any other broad comments on that data that they put out thank you.
Speaker Change: Yes. So we did note the data that was presented and it's not for us to make comparative statements about <unk> kimpton.
Speaker Change: Versus an investigational drug.
Speaker Change: In its early phase two.
Speaker Change: But.
Speaker Change: Specifically.
Speaker Change: You asked about measurement of effect on <unk>.
Speaker Change: And as you point out we have been measuring changes in our studies when we believe the drug is having its more maximal effect and that's C. Max exposures I'll ask Patty to address what could be a delta between peak and trough.
Speaker Change: I Trust you understand thats determined by each individual drug.
Speaker Change: Yes, I mean I think.
Speaker Change: Okay.
The the.
Speaker Change: Change in ejection fraction on average only about 4%.
What <unk>.
Speaker Change: Transpires between peak and trough.
Speaker Change: Maybe one or two points, it's hard to speculate we didn't make any measurements of those at.
Speaker Change: At those points in time is a lot of things that affect ejection fraction and including time of day and diurnal variation migration and so forth.
Speaker Change: So it's very difficult to say exactly.
Speaker Change: What the magnitude would be other than it would have been less.
Speaker Change: And.
Speaker Change: Similarly, I would expect if you measured.
Speaker Change: A drug that affect that.
Speaker Change: Any drug edgewise, this drug or otherwise.
Speaker Change: There is.
Speaker Change: Our relationship you would see a bit more of an effect.
Speaker Change: And that goes for other measurements.
Speaker Change: Efficacy as well so.
Speaker Change: I think thats about as far as I can really say.
Speaker Change: Comparisons there.
Speaker Change: Great. Thank you.
Robert Blum: Thank you and I am showing no further questions from our phone lines I'd now like to turn the conference back over to Robert <unk> for any concluding remarks.
Speaker Change: I want to thank everybody for your participation in this call I hope you've got clarification to.
Robert Blum: To the questions that you were.
Robert Blum: Pondering coming into this call, obviously, we addressed a lot of topics, including our conversation about rems.
Robert Blum: And I hope that.
Robert Blum: We can feel comfortable that we took.
Robert Blum: Appropriate steps.
Four things continue to evolve and Thats fair and reasonable and were prepared given that we had a contingency plan that we executed on with that said, we remain confident in the potential approval of <unk> Camden and upon its potential approval.
Robert Blum: With a label and a rems program that would provide.
Robert Blum: Stinker positioning for Camden, and as could be enabling of us to execute on the commercial readiness program, albeit three months delayed perhaps but one that we have been aiming forward towards for quite some time.
Robert Blum: We're optimistic about how that will be received and we're encouraged by the reception we're getting for candidates for our open commercial positions and at the same time, we point you to upcoming data from April and.
Robert Blum: We're excited also about Acacia only captive and CK 586, so lots of good things happening in and around sort of kinetics. We look forward to providing you further updates when appropriate we thank you for your interest in this call and operator with that we can now conclude.
Robert Blum: Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.
Robert Blum: Okay.
Robert Blum: [music].
Robert Blum: Okay.
Robert Blum: [music].
Robert Blum: Yes.
Robert Blum: [music].