Q4 2023 Acumen Pharmaceuticals Inc Earnings Call
Operator: Ladies and gentlemen, thank you for standing by. Welcome to Acumen Pharmaceuticals' full year 2023 conference call and webcast. At this time, all participants are in a listen-only mode.
Ladies and gentlemen, thank you for standing by welcome to acumen Pharmaceuticals full year 2023 conference call and webcast. At this time all participants are in a listen only mode.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised.
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Operator: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Alex Braun, Head of Investor Relations. Please go ahead.
To withdraw your question. Please press star one again, please be advised that today's conference is being recorded I would like now to turn the conference over to Alex Brown head of Investor Relations. Please go ahead.
Alex Braun: Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the year ended December 31, 2023. With me today are Dan O'Connell, our Chief Executive Officer; Dr. Jim Doherty, our President and Chief Development Officer; Dr. Eric Siemers, our Chief Medical Officer; and Matt Zuga, our Chief Financial Officer and Chief Business Officer. Before we begin, we encourage listeners to go to the investor section of the Acumen website to find our press release issued this morning and related slide presentation that we'll discuss today. Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statement.
Alex Braun: Thanks Michelle.
Alex Braun: Good morning, and welcome to the afternoon conference call to discuss our business update and financial results for the year ended December 31st 2023.
Alex Braun: Me today are Dan O'connell, our Chief Executive Officer, Dr. Jim Doherty, our President and Chief Development Officer, Dr. Eric Siemers, our Chief Medical Officer, and not do that our Chief Financial Officer, and Chief Business Officer.
Alex Braun: Donna will encourage listeners to go to the investors section of the Ackman website to find our press release issued this morning and related slide presentation that we'll discuss today.
Alex Braun: Yeah.
Alex Braun: Please note that during today's conference call. We may make forward looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward looking statements.
Alex Braun: Please see slide two of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided in this call or in the accompanying presentation as a result of new information or future results or developments. After our prepared remarks, we'll turn, and we'll open the call for Q&A. Now, we'll turn the call over to Dan. Thanks, Alex. Good morning.
Alex Braun: Please see slide two of our corporate presentation in our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward looking statements. We undertake no obligation to update or revise the information.
Alex Braun: <unk> provided on this call or in the accompanying presentation as a result of new information or future results or developments.
Alex Braun: After our prepared remarks, well open the call for Q&A.
Alex Braun: Now I'll turn the call over to Dan.
Unknown Executive: Thanks, Alex and good morning, and thanks to everyone, who is joining US today 2023 was a landmark year for academic.
Unknown Executive: And thanks to everyone who's joining us today. 2023 was a landmark year for AAC. Our Monoclonal Antibody for the Treatment of Early Alzheimer's Disease, AC193, which recently received its non-proprietary name, SobernatUG, delivered positive and exciting Phase I results first presented at AAIC last July. You'll hear more about these results and how they serve as the cornerstone for establishing SobernatUG's differentiated therapeutic profile later on this call. More recently, we welcomed Dr. Jim Doherty to Acumen as President and Chief Development Officer. Jim brings many years of experience in CNS drug development, and we're delighted to have him join our leadership team. We believe Acumen entered 2024 from a position of strength.
Unknown Executive: Monoclonal antibody for the treatment of early Alzheimers disease is 193, which recently received its.
Unknown Executive: Proprietary name subordinates delivered positive and exciting phase one results first presented.
Unknown Executive: I see last July.
Unknown Executive: You'll hear more about these results and how they serve as the cornerstone for establishing <unk> differentiated therapeutic profile later on this call.
Speaker Change: More recently, we welcomed Dr. Jim Doherty to acumen, as President and Chief Development Officer, Jim brings many years of experience in CNS drug development and we're delighted to have him join our leadership team.
Speaker Change: We believe acumen entered 2024 from a position of strength, we remain highly focused on the execution of key program and strategic initiatives to further establish the therapeutic potential of <unk> as a best in class treatment option for the substantial early alzheimers patient population.
Unknown Executive: We remain highly focused on the execution of key program and strategic initiatives to further establish the therapeutic potential of Sobernitug as a best-in-class treatment option for the substantial early Alzheimer's patient population. This month, we presented additional CSF biomarker data and details about our ABETA oligomer target engagement assay from our Phase 1 Intercept AD study at the International Conference on Alzheimer's and Parkinson's Disease, or ADPD, in We will also present analyses at the American Academy of Neurology meeting in Denver this April, which will introduce the development plan for Sobernitug and the results from Intercept AD to this broad group of practicing and academic neurologists. If you haven't already taken a look at our Phase I results in their entirety, I encourage you to go to our website, where you can find archived presentations, webcasts, and releases detailing the Suburna Tug data For us, it's difficult to overstate the significance of these results and how they position Sobernatyte in the broader anti-A-Beta field. We knew going into our phase one study that subernatantia possessed high selectivity for A-beta oligomers. Why does this matter?
Speaker Change: This month, we presented additional CSF biomarker data and details about our a beta ligament target engagement assay from our phase one intercept study at the International conference on all Ciber to Parkinson's disease, or ADP D in Lisbon, Portugal.
Speaker Change: We will also present analyses at the American Academy of Neurology meeting in Denver, This April which will introduce the development plan for savanna tug and the results from intercept a D to this broad group of practicing and academic neurologists.
Speaker Change: If you haven't already taken a look at our phase one results in their entirety I encourage you to go to our website, where you can find archived presentations webcasts and releases detailing the Sabrina Tech data.
Speaker Change: For us it's difficult to overstate the significance of these results and how they position subordinate side and the.
The broader anti a beta field.
Speaker Change: We knew going into our phase one study that's berta tug possess high selectivity for ebay to oligomers.
Unknown Executive: Unlike Abeta monomers and insoluble amyloid plaque, Abeta oligomers are toxic in distinct and important ways, in particular to neurons and synapses. Our approach with CERBERTUG is to selectively target toxic Abeta oligomers. And as a consequence, protect synapses in a way that may provide additional therapeutic benefit to patients, especially from an efficacy perspective. The Intercept AD results exceeded our expectations and provided a substantial amount of data indicating subarachnoid drug effects. Overall, we see multiple paths towards Subaru Tug's next-generation differentiation in efficacy, safety, or both, any of which would be beneficial to patients as compared to existing options. I'm pleased to note that we are making great progress with the launch of our Phase 2 study, Altitude AD, which remains on track to initiate in the first half of this year. Simultaneously, we are also on track to initiate our subcutaneous Phase 1 study, expected in mid-2024. And with that, I'd like to hand the call over to Eric.
Speaker Change: Why does this matter unlike ebay to monomers and insoluble amyloid plaque EBITDA oligomers are toxic and distinct and important ways in particular to neurons and synapses.
Speaker Change: Our approach with <unk> is to selectively target toxic EBIT oligomers.
Speaker Change: And as a consequence to protect synapses in a way that may provide additional therapeutic benefit to patients, especially from an efficacy perspective.
The intercept <unk> results exceeded our expectations and provide a substantial amount of data, indicating some type of drug effect.
Speaker Change: Overall, we see multiple paths towards <unk> next generation differentiation on efficacy safety or both.
Speaker Change: Any of which would be beneficial to patients as compared to existing options.
Speaker Change: I am pleased to note that we are making great progress with the launch of our phase III study altitude, a D, which remains on track to initiate in the first half of this year.
Speaker Change: Simultaneously. We are also on track to initiate our subcutaneous phase one study expected for mid 2024.
Speaker Change: And with that I'd like to hand, the call over to Eric.
Eric Siemers: Thanks, Dan and thanks to those listening into the call today I'm very pleased with the progress with the clinical development of <unk> last year, and thus far in 2024 with our achievements last year, we are well positioned to potentially deliver a differentiated treatment to the Alzheimer's community.
Eric Siemers: Thanks, Dan. And thanks to those listening in on the call today. I'm very pleased with the progress with the clinical development of SabernaTUG last year and thus far in 2024. With our achievements last year, we are well positioned to potentially deliver a differentiated treatment to the Alzheimer's community. I'll provide a brief update on feedback we have received from the scientific community on our Phase 1 Intercept AD results and then review our study design for our next trial, Altitude AD. Recall that our Phase I top-line results were announced in July of last year at AIC, and we had subsequent updates throughout the second half of the year on the fluid biomarker results as those were analyzed. The totality of the Phase I data has only recently become available and can now be evaluated by the broader external community. We believe the fluid biomarker results have helped to relate the mechanism of Sobernitug to its downstream pharmacologic activity.
Eric Siemers: I'll provide a brief update on feedback we have received from the scientific community on our phase one intercept a D results and then review our study design for our next trial altitude a D.
Eric Siemers: Recall that our phase <unk> top line results were announced in July of last year at AIC and we had subsequent updates throughout the second half of the year on a fluid biomarker results as those were analyzed.
Eric Siemers: Totality of the phase one data has only recently become available and can now be evaluated by the broader external community. We believe the fluid biomarker results have helped to relate the mechanism of subordinates hug to its downstream pharmacologic activity as first reported in July.
Eric Siemers: A dose dependent increase in target engagement approaching an EMACS was found in CSF and a reduction in plaque measured by amyloid pet was seen at the highest doses of subordinate Todd in the multiple ascending dose cohorts.
Importantly, after just three administrations of <unk> and the multiple ascending dose portion of the study patients demonstrated downstream improvements across town and amyloid biomarkers in CSF, which are the two main pathologic hallmarks of Alzheimer's disease.
Eric Siemers: As first reported in July, a dose-dependent increase in target engagement approaching an Emax was found in CSF, and a reduction in plaque measured by amyloid PET was seen at the highest doses of Sobernitug in the multiple ascending dose cohort. Importantly, after just three administrations of Cibernetug in the multiple ascending dose portion of the study, patients demonstrated downstream improvements across tau and amyloid biomarkers in CSF, which are the two main pathologic hallmarks of Alzheimer's disease. Remarkably, there were additional clear effects on synaptic biomarkers, suggesting Sobernitug's target engagement of neurotoxic oligomers may protect synapses after only three administrations of the drug.
Eric Siemers: Marketplace, there were additional clear effects on synaptic biomarkers, suggesting <unk> target engagement.
Eric Siemers: Zero toxic olive <unk> may protect synapses after only three administrations of drug.
Eric Siemers: As Dan mentioned, our team recently returned from ADP D. In Lisbon, the feedback to our data package at medical conferences has been very positive.
Eric Siemers: The excitement around our intercept <unk> results caused us to be even more enthusiastic about beginning our next study altitude.
Eric Siemers: Altitude is planned as a randomized double blind placebo controlled three arm study designed to evaluate the clinical efficacy safety and Tolerability of <unk> with approximately 180 participants per arm for a total of 540 participants with <unk>.
Eric Siemers: As Dan mentioned, our team recently returned from ADPD in Lisbon, and the feedback on our data package at medical conferences has been very positive. The excitement around our Intercept AD results causes us to be even more enthusiastic about beginning our next study, Altitude AD. Altitude AD is planned as a randomized, double-blind, placebo-controlled, three-arm study designed to evaluate the clinical efficacy, safety, and tolerability of subornitype in approximately 180 participants per arm for a total of 540 participants with MCI or mild dementia due to Alzheimer's disease. We intend to use IDRIS at 18 months as the primary outcome measure. The study is planned to include a one-year open-label extension. Based on the results from Intercept-AD, the doses for Altitude-AD will be 35 mg per kg and 50 mg per kg, both dosed every four weeks.
Eric Siemers: Mci or mild dementia due to alzheimers disease.
Eric Siemers: We intend to use the idea is it 18 months is the primary outcome measure.
Eric Siemers: The study is planned to include a one year open label extension.
Eric Siemers: Based on the results from intercept a D. The doses for altitude.
Eric Siemers: Will be 35 milligrams per kilogram and 50 milligrams per kilogram, both dosed every four weeks.
Eric Siemers: Extensive PK PD modeling Humira phase, one data, especially with regard to target engagement and consideration of safety data led to the selection of these doses.
Eric Siemers: Both of these dose levels may produce clinical efficacy and we are.
Eric Siemers: Keen to see whether they will differentiate in terms of the overall benefit risk ratio.
Eric Siemers: Importantly, this study is designed as a registration eligible study for <unk> and we look forward to providing further updates as the study initiate and progresses.
Eric Siemers: In short our phase one results have allowed us to move to our next study that we're more definitively investigate how uniquely targeting a beta olive <unk> may lead to a best in class treatment for patients with Alzheimers disease.
Eric Siemers: Extensive PK-PD modeling of our Phase I data, especially with regard to target engagement and consideration of safety data, led to the selection of these doses. Both of these dose levels may produce clinical efficacy, and we are keen to see whether they will differ in terms of the overall benefit-risk ratio. Importantly, this study is designed as a registration-eligible study for Sobernatyte, and we look forward to providing further updates as the study initiates and progresses. In short, our Phase I results have allowed us to move to our next study that will more definitively investigate how uniquely targeting A-beta oligomers may lead to a best-in-class treatment for patients with Alzheimer's disease. And with that, I'll turn the call over to Jim. Thanks, Eric. And good morning, everyone.
Eric Siemers: And with that I'll turn the call over to Jim.
Unknown Executive: Thanks, Eric and good morning, everyone.
Unknown Executive: Firstly, thank Dan and the entire team at acumen for the warm welcome I've been on board for nearly two months now and then that time I've grown even more excited about the potential for a bit more selectivity to offer our next generation Alzheimer's treatment.
Unknown Executive: And it's hard I see this the Barnett tug program is testing a very clear hypothesis.
Unknown Executive: <unk> are neurotoxic amyloid species in the brain by.
By targeting these oligomers <unk> may offer a differentiated profile compared to other therapies, including the potential for greater efficacy or reduced side effects like ARIA.
Unknown Executive: The phase one intercept <unk> results show that <unk> can indeed bind to its intended target and improved downstream Alzheimers biomarkers.
Unknown Executive: We believe there is great potential for this approach to be beneficial to patients and it is incumbent on us to progress our clinical program efficiently and strategically to maximize the Brennan tugs value for patients and shareholders.
Unknown Executive: I'd first like to thank Dan and the entire team at Acumen for their warm welcome. I've been on board for nearly two months now. And in that time, I've grown even more excited about the potential for A-beta oligomer selectivity to offer a next-generation Alzheimer's treatment. At its heart, I see the Suburna Tug Program as testing a very clear hypothesis. A-beta oligomers are neurotoxic amyloid species in the brain.
Unknown Executive: To support the altitude <unk> trial, we have contracted with a highly experienced sciarra with a strong track record in.
Unknown Executive: That should provide advantageous from trial recruitment and site readiness.
Unknown Executive: As Dan mentioned earlier, we are also planning to initiate a phase one bioavailability study in healthy volunteers for a subcutaneous formulation of <unk> in mid 2024.
Unknown Executive: By targeting these oligomers, Sobernitug may offer a differentiated profile compared to other AD therapies, including the potential for greater efficacy or reduced side effects like ARIA. The Phase I Intercept AD results show that Subernata can indeed bind to its intended target and improve downstream Alzheimer's biomarkers. We believe there is great potential for this approach to be beneficial to patients, and it's incumbent on us to progress our clinical program efficiently and strategically to maximize Subernata Tug's value for patients and shareholders. To support the Altitude AD trial, we have contracted with a highly experienced CRO with a strong track record in AD that should provide advantages for trial recruitment and site readiness. As Dan mentioned earlier, we are also planning to initiate a phase one bioavailability study in Healthy Volunteers for a subcutaneous formulation of Sobernitug in mid-2024.
Unknown Executive: We believe our competitive product profile for some Barnett hub includes a subcutaneous option to offer additional flexibility and convenience for patients and caregivers and we have a productive collaboration with <unk> for that work stream.
Speaker Change: Before I turn the call over to Matt I'd like to take a moment to highlight the excitement we observed at the $2024 PD conference. A few weeks ago. We are clearly entering a new era for the diagnosis and treatment of Alzheimer's disease with novel Therapeutics increasingly more precise biomarkers and diagnostics that will in turn help the field develop.
Matt: Even better treatment.
Matt: <unk> just recently joined acumen I can clearly census, the team's pride in how the intercept a biomarker data have contributed to the perception that <unk> is a treatable disease.
Matt: In particular, the effects observed on downstream fluid biomarkers after only three administrations of drug underscore the potential of stubbornness and targeting a beta oligomers for the treatment of early <unk>.
Matt: We believe suburban type of clinical development will continue to move the field forward from his perspective.
Unknown Executive: We believe a competitive product profile for Subarna Tug includes a subcutaneous option to offer additional flexibility and convenience for patients and caregivers, and we have a productive collaboration with Halozyme for that workflow. Before I turn the call over to Matt, I'd like to take a moment to highlight the excitement we observed at the 2024 ADPD conference a few weeks ago. We're clearly entering a new era for the diagnosis and treatment of Alzheimer's disease with novel therapeutics, increasingly more precise biomarkers, and diagnostics that will, in turn, help the field develop even better treatments. Having just recently joined Acumen, I can clearly sense the team's pride in how the Intercept AD biomarker data have contributed to the perception that AD is a treatable disease. In particular, the effects observed on downstream fluid biomarkers after only three administrations of the drug underscore the potential of Sobernitug in targeting Abeta oligomers for the treatment of early AD.
Matt: And now I'll hand, the call over to Matt to discuss the financials.
Matt: Thanks, Jim.
Matt: As a reminder, our full year 2023 financial results are available in the press release, we issued this morning and in our 10-K, we will file later today.
Matt: We ended 2023 with approximately $306 million in cash and marketable securities on the balance sheet.
Matt: Which provides us with the financial resources to deliver against our strategic objectives. The increase from the prior years due to the net proceeds from our public offering last July of approximately $122 million.
Matt: As well as approximately $30 million from K to help ventures as part of the debt financing, we announced in November of up to $50 million.
Matt: Our cash on hand is expected to support our current clinical and operational activities into the first half of 2027.
Matt: R&D expenses were approximately $42 $3 million in 2023.
Matt: Increase over the prior year was primarily due to increased costs related to materials drug manufacturing costs consulting and personnel.
Matt: G&A expenses were $18 8 million.
Unknown Executive: We believe Sobernitug's clinical development will continue to move the field forward from this perspective. And now, I'll hand the call over to Matt to discuss the financials. Thanks, Jim. As a reminder, our full year 2023 financial results are available in the press release we issued this morning and in our 10k we will file later today. We ended 2023 with approximately $306 million in cash and marketable securities on the balance sheet, which provides us with financial resources to deliver on our strategic objectives.
Matt: <unk> three with the increase over the prior year, primarily the result of costs related to personnel and consulting.
Matt: This led to a loss from operations of $61 $1 million in 2023.
Matt: Our positive phase one results in 2023 are a clear reflection of our strong drug development capabilities, which.
Matt: Which we have further elevated with Jim's experience and insight.
Matt: We are well capitalized to execute on our upcoming phase III altitude, <unk> study and to develop a subcutaneous formulation.
Matt: We are committed to delivering on the opportunity ahead of us and look forward to providing additional updates this year as we advanced suburban tug for the benefit of patients caregivers and shareholders and with.
Matt Zuga: The increase from the prior year is due to the net proceeds from our public offering last July of approximately $122 million, as well as approximately $30 million from K2 Health Ventures as part of the debt financing we announced in November of up to $50 million. Our cash on hand is expected to support our current clinical and operational activities into the first half of 2027. R&D expenses were approximately $42.3 million in 2023. The increase over the prior year was primarily due to increased costs related to materials, drug manufacturing costs, consulting, and personnel. G&A expenses were $18.8 million in 2023, with the increase over the prior year primarily the result of costs related to personnel and consultants.
Matt: That we.
Speaker Change: We can open the call for Q&A operator.
Speaker Change: As a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced.
Speaker Change: To withdraw your question. Please press star one again, please standby, while we compile the Q&A roster.
Speaker Change: The first question comes from Neena <unk> Garg with DB. Your line is open.
Neena Garg: Hey, guys. Thanks for taking my question I was just wondering about I know you mentioned recently that you may consider doing an interim analysis and the altitude.
Neena Garg: In order to determine whether or not you can start a phase three study can you just walk us through.
Neena Garg: I guess the rationale for doing that interim analysis that protocol adjustments that youre expected to make an answer today be based off of recent regulatory feedback and then anything you can share in terms of how you're thinking about the criteria for that interim analysis will be great. Thank you.
Matt Zuga: This led to a loss from operations of $61.1 million in 2023. Our positive phase one results in 2023 are a clear reflection of our strong drug development capabilities, which we have further elevated with Jim's experience and insight. We are well capitalized to execute on our upcoming Phase 2 Altitude AD study and to develop a subcutaneous formulation. We are committed to delivering on the opportunity ahead of us and look forward to providing additional updates this year as we advance Sobernitug for the benefit of patients, caregivers, and shareholders. And with that, we can open the call for Q&A. Operator?
Thanks Nina.
Neena Garg: Dan maybe I'll quickly take that so a great question in terms of the interim analysis. These will these will not be analysis that change in any way. The altitude 80 protocol. They are really intended to provide some early visibility on data to allow us to make a decision as to whether it progress.
A phase III study. So these are not they're not futility analysis theyre not theyre no longer expansion analysis, but they will be employed just for the purposes of getting some early visibility too.
Neena Garg: In effort to potentially minimize the white space between the phase II and phase III.
Operator: Thank you. As a reminder, 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. Please stand by while we compile the Q&A. The first question comes from Neena Bitritto Garg with DB. Your line is open.
Unknown Executive: Okay got it that's super helpful. And then I guess any changes that you may consider making to the altitude design based on feedbacks from the planned 10 nanometer outcomes.
Speaker Change: Thanks, David So I don't think we have any a priori expectations to make changes based on the I would call me outcome.
Speaker Change: Distinct development for the field certainly should serve as a good venue for exploring some of the considerations associated with Trailblazer two design in the overall dynamic dataset.
Neena Marie Bitritto: Hey guys, thanks for taking my question. So I was just wondering, I know you mentioned recently that you might consider doing an interim analysis in the Altitude AD study in order to determine whether or not you should start a Phase 3 study. Can you just walk us through, I guess, the rationale for doing that interim analysis, some of the protocol adjustments that you're expected to make in Altitude AD based on recent regulatory feedback, and then anything you can share in terms of how you're thinking about the criteria for that interim analysis would be great. Thank you. Thanks, Neena. This is Dan.
Speaker Change: We do as perhaps youre referencing we anticipate using the address at 18 months as a primary outcome measure in altitude J D.
Speaker Change: Barring some unforeseen change in development with the outcome.
Speaker Change: Continue to use it.
Speaker Change: So that's our primary.
Speaker Change: Awesome. Thank you.
Speaker Change: One moment for our next question.
Speaker Change: The next question comes from Tom Shrader with <unk>. Your line is open.
Hey, Good morning. This is Tom on for Tom Thanks for taking my questions.
Thomas Eugene Shrader: For sub Q as maintenance therapy in immediate application for sub Q dosing and what are your thoughts on integrating a sub Q dose option in the open label extension part of the opportunity study.
Unknown Executive: Maybe I'll quickly take that. So, great question. In terms of the interim analyses, you know, these will not be analyses that change in any way the Altitude AD protocol. They're really intended to provide some early visibility on data to allow us to make a decision as to whether to progress towards a Phase III study. So, these are not, they're not futility analyses. They're not, they're no longer expansion analyses, but they will be employed just for the purposes of getting some early visibility in an effort to potentially minimize the white space between the Phase II and the, Okay, got it. That's super helpful.
Tom Shrader: Okay.
Speaker Change: So thanks.
Speaker Change: Thanks for your question and I think the quick answer on that.
Speaker Change: The next phase of development for <unk> beyond the phase one is yet to be determined and decided so our immediate focus is on getting the phase one healthy volunteer.
Speaker Change: With our ability PK study done.
Speaker Change: It means to really inform what the next dosing strategy in study might be for phase III.
Speaker Change: As you mentioned there are a couple of different options that might be available to us in the future, but I think for the near term we're focused on executing the phase one as to the primary gate prior to <unk>.
Speaker Change: Prescribing in greater detail the phase II plans.
Speaker Change: Thank you.
Neena Marie Bitritto: And then I guess any changes that you may consider making to the Altitude AD design based on feedback from the plan for Nanomab Adcom? Thanks, Neena. But I don't think we have any a priori expectations to make changes based on the outcome.
Speaker Change: One moment for the next question.
Speaker Change: The next question comes from Paul Mcneice with Stifel. Your line is open.
Hi, This is James on for Paul Thanks for taking our question.
James: Maybe just a quick one on the phase two I guess can you talk about how you powered the study.
Unknown Executive: The outcome, you know, is an interesting development for the field and certainly should serve as a good venue for exploring some of the considerations associated with the Trailblazer 2 design and the view of all the Nanomab data set. We do, as perhaps you're referencing, we anticipate using the IDRIS at 18 months as our primary outcome measure in Altitude AD. And, you know, barring some unforeseen change in development with the outcome, we'll continue to use the IDRIS as our primary outcome measure. It was awesome.
James: You are looking to see in terms of being a clear win there and then maybe just quickly on again following up on this and term.
James: At a high level curious if youre thinking about biomarkers are clinical scales or just kind of a collection of both of those datasets just curious.
James: What you can share in terms of what that May actually consist of thanks. So much.
Speaker Change: Thanks, James and Eric do you want to take that one.
Eric Siemers: Yes sure Thanks, Dan.
Eric Siemers: For our phase II <unk> study.
Eric Siemers: Okay as I mentioned, its 504 participants with 180 per arm.
Operator: Thank you. One moment for our next question. The next question comes from Thomas Shrader with BTIG. Your line is open. Hey, good morning. This is Tom.
Eric Siemers: For the IRS gives you.
Eric Siemers: Pretty typical power for a phase II study.
Thomas Eugene Shrader: Thanks for taking our question. So, for sub-q, is maintenance therapy an immediate application for sub-q dosing? And what are your thoughts on integrating a sub-q dose option in the open-label extension part of the altitude agency? So, Tom, thanks for your question. And I think the quick answer on that is the next phase of development for SubQ beyond Phase I is yet to be determined or decided. So, our immediate focus is on getting this Phase I Healthy Volunteer Bioavailability PK study done as a means to really inform what the next dosing strategy and study might be for Phase II. As you mentioned, there are a couple of different options that might be available to us in the future, but I think for the near term, we're focused on executing Phase I as the primary gate prior to describing in greater detail the Phase II plan.
So we feel like that should really answered the question in terms of.
Eric Siemers: How the program develops we will also look at a variety of Biomarkers most of which we looked at interface. One study two and so we really interesting to see after 18 months of treatment pillows Biomarkers of response since we actually already saw response after just three doses and essentially three months.
Eric Siemers: So we're looking forward to that in terms of.
Eric Siemers: What goes into the interim analyses were not going to get into details about that.
Eric Siemers: I guess I can say that it's an algorithm that doesn't include just one thing.
Eric Siemers: And again as Dan mentioned, the utility of that is to reduce the white space between phase II and the phase III trial, because if the algorithms look positive.
Unknown Executive: One moment for the next question. The next question comes from Paul Matteis with CFO. Your line is open. Hi, this is James on behalf of Paul.
Eric Siemers: One of the things that tells us that the study's design of the phase two study is good.
Eric Siemers: And a lot of times, what creates white space in drug development programs is redesigning studies and if we don't have to do that that will cut down on our white space. So that's how we plan to use those algorithms.
Paul Andrew Matteis: Thanks for taking our question. Maybe just a quick one on phase two, I guess. Can you talk about how you powered the study and, you know, what you're looking to see in terms of, you know, being a clear win there? And then maybe, just quickly, following up on this interim, just, you know, at a high level, curious if you're thinking about biomarkers or clinical scales, or just kind of a collection of both of those data sets. Just curious, you know, what you can share in terms of what that may actually consist of. Thanks so much.
Speaker Change: Thanks, that's super helpful.
Speaker Change: One moment for the next question.
Speaker Change: The next question comes from Colin Bristow with UBS. Your line is open.
Kim: Hi, This is Kim.
Kim: And thank you for taking our questions.
Kim: Just a quick one following the.
Kim: Earlier question on the sub Q from the other.
Kim: Since the earlier question was more centered around foreman tinnitus study.
Eric Siemers: Thanks, James. And Eric, do you want to do do you want to take that one? Yeah, sure. Thanks, Dan. So for our Phase 2 Altitude AD study, As I mentioned, it's 540 participants with 180 per arm. That, for the IDRSS, gives you pretty typical power for a Phase II study. So we feel like that should really answer the question in terms of how the program develops. We'll also look at a variety of biomarkers, most of which we looked at in our Phase I study too. And so it will be really interesting to see, after 18 months of treatment, how those biomarkers respond since we actually already saw a response after just three doses in essentially three months. So we're looking forward to that. In terms of what goes into the interim analyses, we're not going to get into details about that, but I guess I can say that it's an algorithm that doesn't include just one thing.
Kim: For sub Q as the initial therapy.
Kim: As in the upcoming <unk> study, what dosing trials and dosing schedules are you currently thinking.
Kim: Especially with regards to Esi's recent pushback.
Kim: Kudos as initial therapy.
Kim: Do you think it's reasonable to start with some lower doses.
Kim: And test out for the safety first.
Kim: Q.
Okay. Thanks, Doug go ahead please.
No I think those are all great questions and all the questions that we really don't have any answer to this early point I mean, we don't have even our healthy volunteer data yet. So those are all things to be considered I think it's interesting that broadly in the field people are talking about maybe starting with <unk>.
Kim: Off with IV administration.
Kim: Australia, and then switching to sub Q as more of a maintenance dose. So that's not just something that we're thinking about it is something that a lot of people are thinking about but we'll just need to get actual data before we start to narrow things down on those questions.
Eric Siemers: And again, as Dan mentioned, the utility of that is to reduce the white space between a Phase II and a Phase III trial because if the algorithms look positive, one of the things that tells you is that the study design of the phase two study is good, and a lot of times, what creates white space in drug development programs is redesigning studies, and if we don't have to do that, that will cut down on our white space. So that's how we plan to use those algorithms. Thanks, that's super helpful.
Speaker Change: Okay. Thank you and maybe a quick follow up question.
Speaker Change: Hey.
So how do you see yourself evolving data in the field.
Speaker Change: The most recent update from rushed county map. Thank you.
Operator: One moment for the next question. The next question comes from Colin Bristow with UBS. Your line is open.
Speaker Change: Sure sure I can take that I think we.
Speaker Change: We noted the ADP data, which is early but encouraging.
Colin Nigel Bristow: Oh, hi, this is Ting-Pu Colin, and thank you for taking our questions. Just a quick one following the earlier question on the sub-cure formula since the earlier question was more centered around the maintenance study. So, for sub-cure as the initial therapy, like as in the upcoming sub-cure bioavailable study, what dosing choice and dosing schedules are you currently thinking, especially with regard to ECI's recent pushbacks for sub-cure doses as the initial therapy? Do you think it's reasonable to start with some lower doses and test out for safety first? Thank you. Yeah, no. I think those are all great questions and all questions that we really don't have any answers to at this early point.
Speaker Change: We take the view that targeting oligomers as a differentiated mechanism from Infinera Mab shuttle construct which is.
Speaker Change: And so we're very much committed to exploiting the oligomer targeting mechanism of <unk> generating evidence and supportive of it as a treatment option and feel that the field in general as <unk>.
Speaker Change: <unk> enough to accommodate a variety of different product formats and options. So.
Speaker Change: It's interesting and something we're looking at but.
Speaker Change: Staying very focused on execution for Subaru.
Speaker Change: One moment for our next question.
Unknown Executive: I mean, we don't even have our healthy volunteer data yet. So those are all things to be considered. I think it's interesting that, broadly in the field, people are talking about maybe starting off with IV administration and then switching to sub-q as more of a maintenance dose. So that's not just something that we're thinking about. It's something that a lot of people are thinking about, but we'll just need to get some actual data before we start to narrow things down on those questions. Okay, thank you. And maybe a quick follow-up question, if we may. So how do you view some of the evolving data in the field, including the most recent update from Rush's Chanting the Map?
Speaker Change: The next question comes from Geoff Meacham with Bank of America. Your line is open.
Speaker Change: Good morning. This is Jason on for Jeff. Thank you so much for taking our questions and congratulations on the progress.
Jason: I wanted to ask maybe a little bit more broadly we've seen the publication of a number of recent studies that have found that a number of the signals or biomarkers for amyloid beta.
Jason: Here quite some time before the symptoms.
Jason: Specifically regarding the ratio of a beta 42 to a beta 40 Pops up 14 years.
Unknown Executive: Thank you. Sure, sure, I can take that. I think, you know, we noted the ADPD, and tritinumab data, which is early but encouraging. We take the view that targeting oligomers is a differentiated mechanism from a gantanarumab shuttle construct, which is tritinumab. And so we're very much committed to exploiting the oligomer targeting mechanism of Sobernatug and generating evidence in support of it as a treatment option, and feel that the field, in general, is large enough to accommodate a variety of different product formats and options. So it's interesting and something we're looking at, but we stay very focused on execution for Sobernaty. One moment for our next question. The next question comes from Geoff Meacham with Bank of America. Your line is open.
Jason: Prior to the onset of symptoms and Im curious has that influenced.
Jason: The design of some of your clinical studies do you think you may need to go a little bit earlier or.
Jason: Do you do you feel that kind of early.
Jason: Sufficient enough for four kind of a.
Jason: Either a reversal of the symptoms are or delaying them.
Speaker Change: Yes, So Dan you want me to take that one Greg Greg Church.
Greg Church: So yes.
Greg Church: One of the ways that the field has made some real progress.
Greg Church: The last 10 years and maybe even the last 20 years is the understanding of this fact that as you pointed out that you develop the plaques.
Greg Church: 20 years before you develop any symptoms.
Operator: Good morning, this is Jason Ahn for Geoff. Thank you so much for taking our questions and congratulations on the progress. I wanted to ask maybe a little bit more broadly, we've seen the publication of a number of recent studies that have found that a number of the signals or biomarkers for amyloid beta appear quite some time before symptoms. I think specifically regarding the ratio of A-beta 42 to A-beta 40 pops up 14 years prior to the onset of symptoms. I'm curious, has that influenced the design of some of your clinical studies? Do you think you may need to go a little bit earlier, or do you feel that early A-D is sufficient enough for either a reversal of the symptoms or delaying the onset? Yeah, so Daniel, let me take that one. Great question.
Greg Church: And there has been.
Greg Church: <unk> in the field that if you were going to.
Greg Church: Target Android or a beta in one way or another because of that time period, you actually had to do it before people had any symptoms at all and there are ongoing studies and there have been ongoing there have been studies of what's called preclinical Alzheimer's disease. So in other words, you have the plaques, but you don't have any symptoms yet.
Greg Church:
Greg Church: Thus far none of those studies have been successful I think there is a lot of reasons for that partly its the study design is much more complicated the studies need to be longer.
Greg Church: Technical reasons why.
Greg Church: That's a challenge, but what's really important is that for drugs like <unk> and <unk> and.
Greg Church: It'll even out of Cana Mab, Youre seeing a signal and people who have either.
Greg Church: Mci or mild dementia with Alzheimer's pathology and the reason why that's so important is that means you don't have to go all the way back to that preclinical stage, where the study designs are much more challenging does not as well worked out so we feel really good about the fact that we.
Geoffrey Christopher Meacham: So, yeah, one of the ways that the field has made some real progress in the last 10 years and maybe the last 20 years is the understanding of this fact that, as you point out, you develop Plaks, 15 to 20 years before you develop any symptoms. And there has been a thought in the field that if you were going to target amyloid or Abeta in one way or another, because of that time period, you actually had to do it before people had any symptoms at all. And there are ongoing studies, and there have been ongoing, there have been studies of what's called preclinical Alzheimer's disease. So in other words, you have the plaques, but you don't have any symptoms. Um...
Greg Church: We're in this population of Mci plus mile debenture other drugs are starting to see a signal there apparently what that means is that is not too late in the process and Thats I think a really good insight for the field broadly.
Speaker Change: Interesting. Thanks for the color and then maybe a quick follow up if I may.
Speaker Change: The FDA.
Speaker Change: Released draft guidance for Alzheimers earlier this month.
Speaker Change: I think one of the big takeaways here is that really codify the.
Eric Siemers: Thus far, none of those studies have been successful. I think there are a lot of reasons for that. Partly it's the study design is much more complicated. The studies need to be longer. There are some, you know, technical reasons why that's a challenge.
Speaker Change: Driver push too.
Speaker Change: Maybe shorten the length of clinical studies potentially using again kind of biomarkers and other.
Speaker Change: Indicators, rather than waiting for several years that it might take to detect a meaningful change in him again kind of curious has has that translated to your discussions with the regulators.
Eric Siemers: But what's really important, I think, is that for drugs like Hanumab and Denanumab and potentially even Atacanumab, you're seeing a signal in people who have either MCI or mild dementia with Alzheimer's pathology. And the reason why that's so important is that it means you don't have to go all the way back to that preclinical stage where the study designs are much more challenging and not as So, we feel really good about the fact that we're in this population of MCI plus mild dementia. Other drugs are starting to see a signal there, and apparently, that means it's not too late in the process. And that's, I think, a really good insight for the field broadly. Interesting. Thanks for the color.
Speaker Change: Again are we thinking ahead to maybe a shorter phase III if need be.
Speaker Change: Having read.
Speaker Change: The draft guidance.
Speaker Change: A lot of times for these draft guidance.
It's a little hard to read between lines and they certainly did have some language in there about shortening.
Speaker Change: Timelines.
Speaker Change: Based on using Biomarkers, but then they talk about a validated biomarker, but that's what it is validated to really mean.
So there is still a number of things there.
Need to be worked out.
Speaker Change: It may be that they were directing some of those covenants to just taking an antibody that is IV and then converting it to sub Q I think thats, probably the most straightforward case.
Speaker Change: We're more of a reliance on the biomarkers, but at this early stage.
Eric Siemers: And then maybe a quick follow-up, if I may. The FDA released draft guidance for Alzheimer's earlier this month. I think one of the big takeaways here is that it really codified the, maybe shorten the length of clinical studies, potentially using again, kind of biomarkers and other indicators rather than waiting for several years that it might take to detect a meaningful change. And I'm, again, kind of curious, has that translated to your discussions with the regulators?
Speaker Change: We have not really considered using a biomarker.
Speaker Change: Alone to try to get accelerated approval.
Speaker Change: For <unk> because of course, the payers at least to this point, we haven't really.
Speaker Change: Offered to reimburse for accelerated approval. So we will continue to watch that very closely but at this point I don't think we have enough information to make any real changes.
Speaker Change: What we would anticipate would be our phase III design.
Eric Siemers: And again, are we thinking ahead to maybe a shorter phase three, if need be? Having read the draft guidance, like a lot of times for these draft guidance, it's a little hard to read between the lines, and they certainly did have some language in there about shortening timelines based on using biomarkers, but then, you know, they talk about a validated biomarker, but then what does validated really mean? So there's still a number of things that need to be worked out. So we'll continue to watch that very closely, but at this point, I don't think we have enough information to make any real changes to what we would anticipate would be our Phase III design. Got it. Thank you again for the color.
Speaker Change: Got it thank you again for the color.
Speaker Change: One moment for our next question.
Speaker Change: The next question comes from Ananda Couche with H C. Wainwright Your line is open.
Ananda Couche: Hi, Thank you.
The first question is probably what are some of the advantages of <unk> over <unk>.
Ananda Couche: <unk> behind choosing ideally so let's figure out is b.
Ananda Couche: For the study and.
Ananda Couche: And the second thing is there has been lot of formulations.
Ananda Couche: He'd be strong how much of a flock reductions you're seeing and what's the probability of success in terms of some of these anti EBITDA immunotherapy trials.
Ananda Couche: Are there other.
Operator: One moment for our next question. The next question comes from Ananda Ghosh with H.C. Wainwright. Your line is open.
Ananda Couche: Associations, which has been done with other biomarkers such as <unk>.
Ananda Kumar Ghosh: Hi, thank you. The first question is probably, what are some of the advantages of IADRS over CDRS-B and, you know, the rationale behind choosing IADRS over CDRS-B for the Attitude Study? And the second thing is, you know, there have been a lot of correlations made based on how much plaque reduction you are seeing and what's the probability of success in terms of some of these anti-A-beta immunotherapy trials. But are there other associations which have been done with other biomarkers, such as tau 181 or 217, where, at least some modeling-based studies can tell you to what extent you might need to see a Yeah, maybe I can try to take that one too.
Ananda Couche: 100, <unk> hundred seven.
Ananda Couche: At least some modeling based studies continue to what extent you might see you might need to see a change in these two biomarkers.
Ananda Couche: As to kind of have an impact.
Ananda Couche: I did see the RSP our ideas.
Ananda Couche: Yes.
Speaker Change: Yes, I can.
Speaker Change: Try to take that one too as far as the.
Speaker Change: Use of the <unk> versus the CVR sum of boxes, one of the things that was interesting in that.
Speaker Change: Recent draft guidance was that they no longer called out the CVR sum of boxes and they are actually presented at public meetings. The idea that in the previous draft guidance, where they did mentioned the CVR sum of boxes. They didn't mean to endorse that as sort of that.
Speaker Change: We scale.
Speaker Change: What they did say in this most recent draft guidance is that a scale that is a composite of cognitive measures.
Speaker Change: <unk> measures.
Speaker Change: They have real utility and that's what the IRS since our combination of cognitive measures from need us cognitive function of measures from our scale called the Adcs ADL.
Eric Siemers: As far as the use of the IDRIS versus the CDR-SUMMIT boxes, one of the things that was interesting in the recent draft guidance was that they no longer called out the CDR-SUMMIT boxes, and they've actually presented at public meetings the idea that in the previous draft guidance where they did mention the CDR-SUMMIT boxes, they didn't mean to endorse that as sort of the only scale. But what they did say in this most recent draft guidance is that a scale that's a composite of cognitive measures and functional measures may have real utility. And that's what IDRIS is for. It's a combination of cognitive measures from the ADOS COG and then functional measures from a scale called ADC-SADL.
Speaker Change: So we think that is very positive actually.
Speaker Change: In terms of our use of the Iris.
Speaker Change: I would assume that Lilly since of the Trailblazer studies, that's their primary they were.
Speaker Change: Happy to see that.
Speaker Change: Yes, I think thats, a really good clarification from FDA.
Speaker Change: In terms of that those kind of scales.
Speaker Change: In terms of correlations between plaque reduction.
Speaker Change: And clinical benefit.
Speaker Change: I think what's really the company <unk>.
Speaker Change: Consensus opinion now is that you actually have to get plaque below a certain threshold and this is something that we.
Eric Siemers: So, we think that is very positive, actually, in terms of our use of the IDRIS. I would assume that Lilly, since in the trailblazer studies, that's their primary concern, they were happy to see that. So, yeah, I think that's a really good clarification from FDA in terms of that, those kind of scales. In terms of correlations between plaque reduction and clinical benefit, I think what's really becoming a consensus opinion now is that you actually have to get plaque below a certain threshold. And this is something that we at Acumen have been saying for a long time, is that if you're going to target plaque, you have to basically get rid of it. And so the goal seems to be, based on existing data, that you want to get below 25 centiloids or, at most, 30. So if you want to, if your target is plaque, that's what you need to do. But again, our target's not plaque; our target is oligomer. So it'll be interesting to see what effects we have on plaque, but with our differentiated mechanism, that's really not the construct of our development.
Speaker Change: We had actually we had been saying for a long time is that if youre going to target plaque you have to basically get rid of it and so the.
Speaker Change: Goal seems to be based on existing data that you want to get below 25 say central Lloyds.
Speaker Change: Most 30.
Speaker Change: So if you want to if your target is plaque that.
Speaker Change: What you need to do but again, our target is not class are targeted as alzheimers. So it'll be interesting to see what effect, we have on plaque but with our differentiated mechanism that's really not the construct of our development plan.
Speaker Change: Thanks, Jim.
Speaker Change: I show no further questions at this time I would now like to turn the call back over to Alex Brown for closing remarks, Thanks, Michelle and thanks for everyone for taking the time to tune and today. We are always available at the company for any follow up questions. Please be in touch and have a great day.
Speaker Change: Thanks.
Speaker Change: This concludes today's conference call. Thank you for your participation you may now disconnect.
Eric Siemers: Thanks. I have no further questions at this time. I would now like to turn the call back over to Alex Braun for closing remarks. Michelle, and thanks everyone for taking the time to tune in today. We are always available at the company for any follow-up questions. Please be in touch, and have a great day! Thanks. This concludes today's conference call. Thank you for your participation. You may now disconnect.
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