Q1 2026 Acumen Pharmaceuticals Inc Earnings Call

May 12, 2026

Operator: Good day. Thank you for standing by. Welcome to the Acumen Pharma Q1 2026 Conference Call and Webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Alex Braun, Head of Investor Relations. Please go ahead.

Operator: Good day. Thank you for standing by. Welcome to the Acumen Pharma Q1 2026 Conference Call and Webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Alex Braun, Head of Investor Relations. Please go ahead.

Speaker #1: 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 your hand is raised.

Speaker #1: To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Alex Braun, Head of Investor Relations.

Speaker #1: Please go ahead. Thanks, DeeDee. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended March 31, 2026.

Alex Braun: Thanks, Didi. Good morning and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended 31 March 2026. With me today are Daniel O'Connell, our Chief Executive Officer, and Matthew Zuga, our CFO and Chief Business Officer. They will have brief prepared remarks, and then we'll open the call for questions. Joining for the Q&A session, we also have Dr. James Doherty, our President and Chief Development Officer, and Dr. Eric Siemers, our Chief Medical Officer.

Alex Braun: Thanks, Didi. Good morning and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended 31 March 2026. With me today are Dan O'Connell, our Chief Executive Officer, and Matt Zuga, our CFO and Chief Business Officer. They will have brief prepared remarks, and then we'll open the call for questions. Joining for the Q&A session, we also have Dr. Jim Doherty, our President and Chief Development Officer, and Dr. Eric Siemers, our Chief Medical Officer.

Speaker #1: With me today are Dan O'Connell, our Chief Executive Officer, and Matt Zuga, our CFO and Chief Business Officer. They will have brief prepared remarks, and then we'll open the call for questions.

Speaker #1: Joining for the Q&A session, we also have Dr. Jim Doherty, our President and Chief Development Officer, and Dr. Eric Seymours, our Chief Medical Officer.

Speaker #1: Before we begin, we encourage listeners to go to the investor section of the Acumen website to find our press release issued this morning that we'll discuss today.

Alex Braun: \Before we begin, we encourage listeners to go to the Investors section of the Acumen website to find our press release issued this morning 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.

Alex Braun: Before we begin, we encourage listeners to go to the Investors section of the Acumen website to find our press release issued this morning 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.

Speaker #1: 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.

Speaker #1: Please see slide two of our corporate 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.

Alex Braun: Please see slide 2 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 on this call or in the accompanying presentation as a result of new information or future results. With that, I'll turn the call over to Dan.

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 on this call or in the accompanying presentation as a result of new information or future results. With that, I'll turn the call over to Dan.

Speaker #1: We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results.

Speaker #1: With that, I'll turn the call over to Dan. Great, thanks, Alex. Good morning, everyone, and thanks for joining us today. I ended last quarter's call by emphasizing the progress we've achieved with Cybernetug and our next-generation blood-brain barrier EBD candidates, and highlighted the important work and upcoming milestones that lie ahead.

Daniel O'Connell: Great. Thanks, Alex Braun. Good morning, everyone, and thanks for joining us today. I ended last quarter's call by emphasizing the progress we've achieved with sabirnetug and our next-generation blood-brain barrier EBD candidates and highlighted the important work and upcoming milestones that lay ahead. That message has not changed. In Q1, we continued to advance sabirnetug through our phase II ALTITUDE-AD trial, building on the clinical momentum established over the past year. The study remains a critical proving ground for our central scientific thesis that selectively targeting synaptotoxic Aβ oligomers rather than amyloid plaques may constitute a more effective and/or safer path forward in Alzheimer's. Execution has stayed on track. Participants have been transitioning smoothly into the 12-month open label extension study and the conversion rate remains high.

Dan O'Connell: Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. I ended last quarter's call by emphasizing the progress we've achieved with sabirnetug and our next-generation blood-brain barrier EBD candidates and highlighted the important work and upcoming milestones that lay ahead. That message has not changed. In Q1, we continued to advance sabirnetug through our phase II ALTITUDE-AD trial, building on the clinical momentum established over the past year.

Speaker #1: That message has not changed in the first quarter. We continue to advance Cybernetug through our phase two altitude AD trial, building on the clinical momentum established over the past year.

Speaker #1: The study remains a critical proving ground for our central scientific thesis. That selectively targeting synaptotoxic A-beta oligomers rather than amyloid plaques may constitute a more effective and/or safer path forward in Alzheimer's.

Dan O'Connell: The study remains a critical proving ground for our central scientific thesis that selectively targeting synaptotoxic Aβ oligomers rather than amyloid plaques may constitute a more effective and/or safer path forward in Alzheimer's. Execution has stayed on track. Participants have been transitioning smoothly into the 12-month open label extension study and the conversion rate remains high.

Speaker #1: Execution has stayed on track, participants have been transitioning smoothly into the 12-month open-label extension study, and the conversion rate remains high. We see this discipline progress as bringing us closer to a potentially differentiated treatment option for people living with Alzheimer's.

Daniel O'Connell: We see this disciplined progress as bringing us closer to a potentially differentiated treatment option for people living with Alzheimer's. We expect our top line results for ALTITUDE-AD late this year. As we've described, ALTITUDE-AD is designed as a well-powered study to detect statistically significant difference after 18 months on our primary clinical efficacy endpoint, the amount of slowing as measured by the iADRS. We expect to also report on key secondary endpoints in the top line results, such as the Clinical Dementia Rating score, sum of boxes, certain safety measures such as adverse event rates, including ARIA rates, and key fluid and imaging biomarkers. The study is designed to evaluate safety and efficacy of two dose levels, 35 and 50 mg/kg, compared to placebo.

Dan O'Connell: We see this disciplined progress as bringing us closer to a potentially differentiated treatment option for people living with Alzheimer's. We expect our top line results for ALTITUDE-AD late this year. As we've described, ALTITUDE-AD is designed as a well-powered study to detect statistically significant difference after 18 months on our primary clinical efficacy endpoint, the amount of slowing as measured by the iADRS.

Speaker #1: We expect our top-line results for altitude AD late this year. As we've described, altitude is designed as a well-powered study to detect statistically significant difference after 18 months on our primary clinical efficacy endpoint.

Speaker #1: The amount of slowing as measured by the IDRAS. We expect to also report on key secondary endpoints in the top-line results, such as the clinical dementia rating score, some of boxes, certain safety measures, such as adverse event rates, including ARIA rates, and key fluid and imaging biomarkers.

Dan O'Connell: We expect to also report on key secondary endpoints in the top line results, such as the Clinical Dementia Rating score, sum of boxes, certain safety measures such as adverse event rates, including ARIA rates, and key fluid and imaging biomarkers. The study is designed to evaluate safety and efficacy of two dose levels, 35 and 50 mg/kg, compared to placebo.

Speaker #1: The study is designed to evaluate safety and efficacy of two dose levels, 35 and 50 milligrams per kilogram, compared to placebo. Both of the active doses are within the range of exposures shown to have exhibited pharmacodynamic target engagement in our INTERCEPT-AD Phase 1 trial.

Daniel O'Connell: Both of the active doses are within the range of exposures shown to have exhibited pharmacodynamic target engagement in our INTERCEPT-AD phase I trial. Our Enhanced Brain Delivery EBD program is also advancing nicely. We are conducting additional preclinical work to fully establish candidate profiles and are very pleased with the output. We intend to submit a notice to exercise our option to license two compounds developed as part of our collaboration with JCR Pharma in Q2 2026. This development is imminent. We expect to discuss those candidate profiles in greater detail at a future medical meeting and continue to anticipate an IND filing in mid 2027. We view EBD as a way to enhance our antibodies, enabling the potential to develop treatments with increased penetration and distribution in the brain while maintaining a favorable safety profile and allowing for patient-friendly subcutaneous dosing.

Dan O'Connell: Both of the active doses are within the range of exposures shown to have exhibited pharmacodynamic target engagement in our INTERCEPT-AD phase I trial. Our Enhanced Brain Delivery EBD program is also advancing nicely. We are conducting additional preclinical work to fully establish candidate profiles and are very pleased with the output. We intend to submit a notice to exercise our option to license two compounds developed as part of our collaboration with JCR Pharma in Q2 2026.

Speaker #1: Our enhanced brain delivery (EBD) program is also advancing nicely. We are conducting additional preclinical work to fully establish candidate profiles and are very pleased with the output.

Speaker #1: We intend to submit a notice to exercise our option to license two compounds developed as part of our collaboration with JCR Pharma in the second quarter of 2026.

Speaker #1: So this development is imminent. We expect to discuss those candidate profiles in greater detail at a future medical meeting and continue to anticipate an IND filing in mid-2027.

Dan O'Connell: This development is imminent. We expect to discuss those candidate profiles in greater detail at a future medical meeting and continue to anticipate an IND filing in mid 2027. We view EBD as a way to enhance our antibodies, enabling the potential to develop treatments with increased penetration and distribution in the brain while maintaining a favorable safety profile and allowing for patient-friendly subcutaneous dosing.

Speaker #1: We view EBD as a way to enhance our antibodies enabling the potential to develop treatments with increased penetration and distribution in the brain while maintaining a favorable safety profile and allowing for patient-friendly subcutaneous dosing.

Speaker #1: We recognize there is competition in this space. However, none with an A-beta oligomer targeted therapeutic cargo. This is where we see the potential to push the therapeutic index even further, attaining efficacy by engaging the soluble toxic species of A-beta throughout the brain.

Daniel O'Connell: We recognize there is competition in this space. However, none with an Aβ oligomer-targeted therapeutic cargo. This is where we see the potential to push the therapeutic index even further, attaining efficacy by engaging the soluble toxic species of Aβ throughout the brain. JCR, our collaborator on our EBD program, has clinically validated transferrin targeting blood-brain barrier receptor mediated transcytosis technology. JCR has an approved therapy in Japan which incorporates their technology and has exhibited little to no anemia. This anemia safety profile offers us further potential for differentiation with our carrier plus cargo EBD product strategy. Taken all together, our EBD program adds optionality to our pipeline as an additional oligomer-targeted therapeutic strategy.

Dan O'Connell: We recognize there is competition in this space. However, none with an Aβ oligomer-targeted therapeutic cargo. This is where we see the potential to push the therapeutic index even further, attaining efficacy by engaging the soluble toxic species of Aβ throughout the brain. JCR, our collaborator on our EBD program, has clinically validated transferrin targeting blood-brain barrier receptor mediated transcytosis technology. JCR has an approved therapy in Japan which incorporates their technology and has exhibited little to no anemia. This anemia safety profile offers us further potential for differentiation with our carrier plus cargo EBD product strategy. Taken all together, our EBD program adds optionality to our pipeline as an additional oligomer-targeted therapeutic strategy.

Speaker #1: Also, JCR, our collaborator on our ABD program, has clinically validated transferrin-targeting blood-brain barrier receptor-mediated transcytosis technology. JCR has an approved therapy in Japan which incorporates their technology and has exhibited little to no anemia.

Speaker #1: This anemia safety profile offers us further potential for differentiation with our carrier plus cargo EBD product strategy. Taken all together, our EBD program adds optionality to our pipeline as an additional oligomer-targeted therapeutic strategy.

Speaker #1: While not currently contemplated in our immediate clinical development plans, an anti-A-beta oligomer EBD therapeutic could also potentially be studied in preclinical Alzheimer's, a population earlier in the disease course that could benefit greatly from a next-generation oligomer-directed approach.

Daniel O'Connell: While not currently contemplated in our immediate clinical development plans, an anti-Aβ oligomer EBD therapeutic could also potentially be studied in preclinical Alzheimer's, a population earlier in disease course that could benefit greatly from a next generation oligomer-directed approach. The progress we've made with sabirnetug and our next generation EBD candidates reflect the strength of our science and ability to execute and sets a solid foundation for an exciting remainder of the year. I look forward to updating you on imminent candidate selections in our EBD program and on our ALTITUDE-AD phase II results in late 2026. With that, I'll turn the call over to Matt.

Dan O'Connell: While not currently contemplated in our immediate clinical development plans, an anti-Aβ oligomer EBD therapeutic could also potentially be studied in preclinical Alzheimer's, a population earlier in disease course that could benefit greatly from a next generation oligomer-directed approach. The progress we've made with sabirnetug and our next generation EBD candidates reflect the strength of our science and ability to execute and sets a solid foundation for an exciting remainder of the year. I look forward to updating you on imminent candidate selections in our EBD program and on our ALTITUDE-AD phase II results in late 2026. With that, I'll turn the call over to Matt.

Speaker #1: The progress we've made with CYBernetug and our next-generation EBD candidates reflects the strength of our science and ability to execute, and sets a solid foundation for an exciting remainder of the year.

Speaker #1: I look forward to updating you on the imminent candidate selections in our EBD program and on our ALTITUDE-AD phase two results in late 2026.

Speaker #1: And with that, I'll turn the call over to Matt. Thank you, Dan. As a reminder, our first quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today.

Matthew Zuga: Thank you, Dan. As a reminder, our Q1 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended 2025 with, excuse me, we ended 31 March with $128.4 million in cash and marketable securities on the balance sheet, which is expected to support our current clinical and operational activities into early 2027. This increase over the prior quarter is due to the private placement we completed in support of our EBD program that grossed $35.75 million, in which we announced in March of this year. R&D expenses were $16.5 million in Q1.

Matt Zuga: Thank you, Dan. As a reminder, our Q1 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended 2025 with, excuse me, we ended 31 March with $128.4 million in cash and marketable securities on the balance sheet, which is expected to support our current clinical and operational activities into early 2027. This increase over the prior quarter is due to the private placement we completed in support of our EBD program that grossed $35.75 million, in which we announced in March of this year. R&D expenses were $16.5 million in Q1.

Speaker #1: We ended 2025 with—excuse me—we ended March 31st with 128.4 million dollars in cash and marketable securities on the balance sheet. Which is expected to support our current clinical and operational activities into early 2027.

Speaker #1: This increase over the prior quarter is due to the private placement we completed in support of our EBD program that grossed 35.75 million dollars in which we announced in March of this year.

Speaker #1: R&D expenses were 16.5 million dollars in the first quarter. The decrease over the prior year was primarily due to a reduction in manufacturing and material costs, as well as a reduction in CRO costs associated with our altitude AD clinical trial, which completed enrollment in March 2025.

Matthew Zuga: The decrease over the prior year was primarily due to a reduction in manufacturing and material costs, as well as a reduction in CRO costs associated with our ALTITUDE-AD clinical trial, which completed enrollment in March 2025. G&A expenses were $4.7 million in the first quarter, the decrease primarily due to reductions in legal fees as well as reductions in accounting, consulting, and insurance expenses. This led to a loss from operations of $21.1 million and a net loss of $20.7 million in the first quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our phase II ALTITUDE-AD readout later this year and advance our EBD program. We remain dedicated to building value with our portfolio of Aβ oligomer-targeted antibodies for Alzheimer's patients, caregivers, and stakeholders.

Matt Zuga: The decrease over the prior year was primarily due to a reduction in manufacturing and material costs, as well as a reduction in CRO costs associated with our ALTITUDE-AD clinical trial, which completed enrollment in March 2025. G&A expenses were $4.7 million in the first quarter, the decrease primarily due to reductions in legal fees as well as reductions in accounting, consulting, and insurance expenses. This led to a loss from operations of $21.1 million and a net loss of $20.7 million in the first quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our phase II ALTITUDE-AD readout later this year and advance our EBD program. We remain dedicated to building value with our portfolio of Aβ oligomer-targeted antibodies for Alzheimer's patients, caregivers, and stakeholders.

Speaker #1: G&A expenses were $4.7 million in the first quarter. The decrease was primarily due to reductions in legal fees, as well as reductions in accounting, consulting, and insurance expenses.

Speaker #1: This led to a loss from operations of 21.1 million dollars and a net loss of 20.7 million dollars in the first quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our phase two altitude AD readout later this year and advance our EBD program.

Speaker #1: We remain dedicated to building value with our portfolio of A-beta oligomer targeted antibodies for Alzheimer's patients' caregivers and stakeholders. And with that, we can open the call for Q&A.

Matthew Zuga: With that, we can open the call for Q&A. Operator?

Matt Zuga: With that, we can open the call for Q&A. Operator?

Speaker #1: Operator?

Speaker #2: 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.

Didi: Thank you. 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 one again. Please stand by while we compile the Q&A roster. Our first question comes from Pete Stavropoulos of Cantor Fitzgerald. Your line is open.

Operator: Thank you. 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 one again. Please stand by while we compile the Q&A roster. Our first question comes from Pete Stavropoulos of Cantor Fitzgerald. Your line is open.

Speaker #2: Please stand by while we compile the Q&A roster. And our first question comes from Pete Stravopoulos of Cantor Fitzgerald. Your line is open.

Speaker #3: Good morning, Dan and team. Congratulations on continued execution of altitude. A question sort of about altitude and altitude is looking at Alzheimer's disease. Similar to the approved amyloid beta antibodies, however, there are ongoing studies for preclinical Alzheimer's.

Pete Stavropoulos: Good morning, Dan and team. Congratulations on continued execution of Altitude. A question sort of about Altitude and, you know, Altitude is looking at Alzheimer's disease, you know, similar to the approved amyloid-beta antibodies. However, there are ongoing studies for preclinical Alzheimer's with a phase III readout starting in 2027. You know, assuming that Altitude is positive and you move forward with sabirnetug, can you just give us your current thoughts on which populations or patient types you would target in phase III studies? You know, what would trigger you to expand to preclinical Alzheimer's?

Speaker #3: With a phase three readout starting in 2027, assuming that ALtitude is positive and you move forward with Cybernetug, could you just give us your current thoughts on which populations or patient types you would target in phase three studies?

Speaker #3: What would trigger you to expand to preclinical Alzheimer's?

Speaker #4: Thanks, Pete. And I can address that real quickly. In terms of our focus, we remain focused on the early AD population, such as we've enrolled in altitude AD and see that as the path forward for Cybernetug in a future registration study.

Daniel O'Connell: Thanks, Pete. I can address that real quickly. In terms of our focus, we remain focused on the early AD population, such as we've enrolled in ALTITUDE-AD and see that as the path forward for sabirnetug in a future registration study. I think our interest in the preclinical population remains quite high. As I mentioned, you know, potentially part of the future opportunities ahead for principally for an EBD candidate. That's not an immediate part of our plans, but certainly I think the science and mechanism in neutralizing toxic oligomers in the early course of the pathogenesis of disease is something that is promising on the horizon.

Dan O'Connell: Thanks, Pete. I can address that real quickly. In terms of our focus, we remain focused on the early AD population, such as we've enrolled in ALTITUDE-AD and see that as the path forward for sabirnetug in a future registration study. I think our interest in the preclinical population remains quite high. As I mentioned, you know, potentially part of the future opportunities ahead for principally for an EBD candidate. That's not an immediate part of our plans, but certainly I think the science and mechanism in neutralizing toxic oligomers in the early course of the pathogenesis of disease is something that is promising on the horizon.

Speaker #4: I think our interest in the preclinical population remains quite high, and as I mentioned, potentially part of the future opportunities ahead for principally for an EBD candidate.

Speaker #4: So that's not an immediate part of our plans, but certainly, I think the science and mechanism—and neutralizing toxic oligomers in the early course of the pathogenesis of disease—is something that is promising on the horizon.

Speaker #3: All right. Thank you. And another question, please, on the EBD program. You do have different versions of 193 and 234. They have different PK profiles.

Pete Stavropoulos: All right. Thank you. Another question, please, on the EBD program. You know, you do have different versions of ACU193 and ACU234. They have different PK profiles, at least what you've shown to date. What are sort of the key properties and preclinical data that will drive you or drive the decision on candidate selection? You know, with an IND targeted, I believe mid-2027, you know, if you could just walk us through how you're thinking about development plans and trial designs.

Speaker #3: At least what you've shown to date. What is sort of the key properties in preclinical data that will drive you or drive the decision on candidate selection?

Speaker #3: And with an IND targeted, I believe mid-2027, could you just walk us through how you're thinking about development plans and trial designs?

Speaker #4: Sure. That's a lot, Pete. So I think, as you know, we've explored a lot of diversity in the EBD program, both from a carrier and cargo perspective.

Daniel O'Connell: Sure. That's a lot, Pete. I think, as you know, we've explored a lot of diversity in the EBD program, both from a carrier and cargo perspective, and we like sort of having the ability to evaluate a series of candidates. We are down to the short list, as I mentioned, we anticipate exercising our option for two candidates in Q2 and remain confident that we will be filing an IND mid-2027. I don't know that we can go into the details of specific PK properties, but as we have characterized, I mean, the advantages of EBD really have to do with broad brain distribution, potentially a wider safety margin, and the subcutaneous dosing convenience.

Dan O'Connell: Sure. That's a lot, Pete. I think, as you know, we've explored a lot of diversity in the EBD program, both from a carrier and cargo perspective, and we like sort of having the ability to evaluate a series of candidates. We are down to the short list, as I mentioned, we anticipate exercising our option for two candidates in Q2 and remain confident that we will be filing an IND mid-2027. I don't know that we can go into the details of specific PK properties, but as we have characterized, I mean, the advantages of EBD really have to do with broad brain distribution, potentially a wider safety margin, and the subcutaneous dosing convenience.

Speaker #4: And we like, sort of, having the ability to evaluate a series of candidates. We were down to a short list, and as I mentioned, we anticipate exercising our option for two candidates in the second quarter.

Speaker #4: And remain confident that we will be filing an IND mid-2027. I don't know that we can go into the details of specific PK properties, but as we have characterized, I mean, the advantages of EBD really have to do with broad brain distribution, potentially a wider safety margin, and the subcutaneous dosing convenience.

Speaker #4: So those are elements of what we are using as part of the filter for prioritizing candidates in that program. Jim, Dory, who's on the call—I don't know, Jim, if you want to add some additional color to comment on Pete's question.

Daniel O'Connell: Those are elements of what we are using as part of the filter for prioritizing candidates in that program. James Doherty, who's on the call, I don't know, Jim, if you wanna add some additional color to comment on Pete's question.

Dan O'Connell: Those are elements of what we are using as part of the filter for prioritizing candidates in that program. James Doherty, who's on the call, I don't know, Jim, if you wanna add some additional color to comment on Pete's question.

Speaker #1: Yeah. No, I think that sounded great, Dan. I guess, Pete, the only other thing I would add, you asked about clinical programming. It's early days, so we're still thinking about what the early phase clinical program is going to look like.

James Doherty: Yeah, no, I think that sounded great, Dan. I guess, Pete, the only other thing I would add, you asked about clinical programming. I mean, it's early days, so we're still thinking about what the early phase clinical program's gonna look like. I think we have a huge benefit in having conducted the Intercept study with sabirnetug, and it really gave us quite a lot of data. Not only the safety and tolerability and PK data you typically get in a phase I study, but since we were looking at Alzheimer's patients in the MAD phase, we were able to collect data on PET imaging for A-beta, for biochemical biomarkers for a number of different things. That's really helped us with the sabirnetug program.

Jim Doherty: Yeah, no, I think that sounded great, Dan. I guess, Pete, the only other thing I would add, you asked about clinical programming. I mean, it's early days, so we're still thinking about what the early phase clinical program's gonna look like. I think we have a huge benefit in having conducted the Intercept study with sabirnetug, and it really gave us quite a lot of data. Not only the safety and tolerability and PK data you typically get in a phase I study, but since we were looking at Alzheimer's patients in the MAD phase, we were able to collect data on PET imaging for A-beta, for biochemical biomarkers for a number of different things. That's really helped us with the sabirnetug program.

Speaker #1: But I think we have a huge benefit in having conducted the Intercept study with Cybernetug, and it really gave us quite a lot of data not only the safety and tolerability and PK data that you typically get in the phase one study, but since we were looking at Alzheimer's patients in the MAD phase, we were able to collect data on PET imaging for a beta for biochemical biomarkers for a number of different things.

Speaker #1: And that's really helped us with the Cybernetug program. And so we're actively discussing how to incorporate that kind of thinking into the early clinical studies for the EBD program.

James Doherty: We're actively discussing how to incorporate that kind of thinking into the early clinical studies for the EVD program. More to come, but we're modeling what we've done on the sabirnetug program as a way to go forward.

Jim Doherty: We're actively discussing how to incorporate that kind of thinking into the early clinical studies for the EVD program. More to come, but we're modeling what we've done on the sabirnetug program as a way to go forward.

Speaker #1: So more to come, but we're modeling what we've done on the Cybernetug program as a way to go forward.

Speaker #3: All right. Thank you very much for taking my questions.

Eric Siemers: All right. Thank you very much for taking my questions.

Speaker #2: Thank you. And our next question comes from Jeff Meacham of Citi. Your line is open.

Operator: Thank you. Our next question comes from Geoff Meacham of Citi. Your line is open.

Speaker #5: Good morning. This is Mary Keith Davis on for Jeff. Thanks for taking our questions. Just was wondering, could you please walk us through the early physician interest and feedback of Cybernetug, especially given the unmet need in early Alzheimer's and mechanism of the treatment?

Mary Kate Davis: Good morning. This is Mary Kate Davis. I'm for Geoff. Thanks for taking our questions. Just was wondering, could you please walk us through the early physician interest and feedback of sabirnetug, especially given the unmet need in early Alzheimer's and mechanism of the treatment? As a follow-up, could you just walk us through the ongoing regulatory interactions and anticipated discussions for the late-stage development of the program? Thank you.

Speaker #5: And then as a follow-up, could you just walk us through the ongoing regulatory interactions and anticipated discussions for the late-stage development of the program?

Speaker #5: Thank you.

Speaker #4: Thanks, Mary Kate. And actually, Jim, why don't you take that? Jim and Eric, I think, are on the feedback we've received. We've done a lot of work at meetings and visited with a number of KOLs and other clinicians that have provided a broad set of feedback on the Cybernetug program in particular.

Daniel O'Connell: Thanks, Mary Kate. Actually, Jim, why don't you take that? As Jim and Eric, I think on the feedback we've received, we've done a lot of work at meetings and visited with a number of KOLs and other clinicians that have provided a broad set of feedback on the sabirnetug program in particular.

Dan O'Connell: Thanks, Mary Kate. Actually, Jim, why don't you take that? As Jim and Eric, I think on the feedback we've received, we've done a lot of work at meetings and visited with a number of KOLs and other clinicians that have provided a broad set of feedback on the sabirnetug program in particular.

Speaker #1: Yeah. Happy to do that, Mary Kate. And as Dan says, we've spoken to quite a number of KOLs about the Cybernetug program. And I think there's a lot of interest, obviously.

James Doherty: Yeah, happy to do that, Mary Kate. As Dan says, we've spoken to quite a number of KOLs about the sabirnetug program. You know, I think there's a lot of interest, obviously. I mean, we're testing a hypothesis that is slightly different than what's been tested so far with the approved therapeutics. I think, you know, we can talk about both what those therapies have been able to do in treating patients, and where there's opportunity. We do think that the sabirnetug approach offers a differentiated opportunity from what's been done to date. I think that's generally understood by KOLs.

Jim Doherty: Yeah, happy to do that, Mary Kate. As Dan says, we've spoken to quite a number of KOLs about the sabirnetug program. You know, I think there's a lot of interest, obviously. I mean, we're testing a hypothesis that is slightly different than what's been tested so far with the approved therapeutics. I think, you know, we can talk about both what those therapies have been able to do in treating patients, and where there's opportunity. We do think that the sabirnetug approach offers a differentiated opportunity from what's been done to date. I think that's generally understood by KOLs.

Speaker #1: I mean, we're testing a hypothesis that is slightly different than what's been tested so far with the approved therapeutics. And I think we can talk about both what those therapies have been able to do in treating patients and where there's opportunity.

Speaker #1: And we do think that the Cybernetug approach offers a differentiated opportunity from what's been done to date. And I think that's generally understood by KOLs.

Speaker #1: So I think everyone's very much looking forward to seeing the data as we release the results for the altitude trial in late 2026. But I think at this point, there's a level of anticipation to see that potential for a differentiated response.

James Doherty: I think, you know, everyone's very much looking forward to seeing the data as we release the results for the ALTITUDE-AD trial in late 2026. I think at this point, there's a level of anticipation to see that potential for a differentiated response.

Jim Doherty: I think, you know, everyone's very much looking forward to seeing the data as we release the results for the ALTITUDE-AD trial in late 2026. I think at this point, there's a level of anticipation to see that potential for a differentiated response.

Speaker #3: Yeah. And I might just add, we have spent a lot of time thinking about the differentiation of Cybernetug. And I think to some well, obviously, we don't have the data right now.

Eric Siemers: Yeah. I might just add, we have spent a lot of time thinking about the differentiation of sabirnetug. Well, obviously, we don't have the data right now. We're in a blinded trial. When we get the data, one of the things that we'll look at, number 1, would be efficacy because, again, we target oligomers, which is different than the 2 approved drugs. The second thing is we'll look to see if we can differentiate on safety because our antibody is an IgG2. The 2 approved antibodies are IgG1s. IgG1s have more effector function, the potential for more ARIA. We're gonna look at the safety data very carefully when those become available.

Speaker #3: We're in a blinded trial. But when we get the data, one of the things that we'll look at, number one, would be efficacy because, again, we target oligomers, which is different than the two approved drugs.

Speaker #3: And then the second thing is we'll look to see if we can differentiate on safety because our antibody is an IgG2. The two approved antibodies are IgG1s.

Speaker #3: IgG1s have more effector function. The potential for more ARIA. And so we're going to look at the safety data very carefully when those become available.

Speaker #4: Yeah. And to your question, yeah, so go ahead.

James Doherty: Yeah.

Jim Doherty: Yeah.

Daniel O'Connell: Eric, I have another question. Go ahead.

Jim Doherty: Eric, I have another question.

Eric Siemers: Go ahead.

Speaker #1: Yeah. And to your question around regulatory interactions, the altitude study, of course, is running in multiple countries across multiple jurisdictions. So we're obviously speaking to regulatory agencies in the US and Canada and in Europe as part of all that.

James Doherty: Yeah. To your question around regulatory interactions, the ALTITUDE-AD study, of course, is running in multiple countries across multiple jurisdictions. We're obviously speaking to regulatory agencies in the US and Canada and in Europe as part of all that. Then, thinking strategically about the program, we're of course engaging with regulators about the overall progress of both of our programs, both the sabirnetug program as well as our EVD programs. That's something we'll continue to do. Obviously, it's quite important to stay in contact and to keep them apprised of progress. That's just a fundamental thing that we're always doing.

Jim Doherty: Yeah. To your question around regulatory interactions, the ALTITUDE-AD study, of course, is running in multiple countries across multiple jurisdictions. We're obviously speaking to regulatory agencies in the US and Canada and in Europe as part of all that. Then, thinking strategically about the program, we're of course engaging with regulators about the overall progress of both of our programs, both the sabirnetug program as well as our EVD programs. That's something we'll continue to do. Obviously, it's quite important to stay in contact and to keep them apprised of progress. That's just a fundamental thing that we're always doing.

Speaker #1: And then thinking strategically about the program, we're, of course, engaging with regulators about the overall progress of both of our programs, both the Cybernetug program as well as our EBD programs.

Speaker #1: And so that's something we'll continue to do. Obviously, it's quite important to stay in contact and to keep them apprised of progress. And so that's just a fundamental thing that we're always doing.

Speaker #2: Thank you. And our next question comes from Paul Matthijs of Stifel. Your line is open.

Operator: Thank you. Our next question comes from Paul Matteis of Stifel. Your line is open.

Speaker #5: Hi. This is Emily on for Paul. I wanted to say congrats on the quarter. And just two quick questions from us. As it relates to the upcoming phase two readout, what do you think would be a clear win that would prove out Cybernetug to be a unique alternative to denimab and lecanemab and do you see kind of different scenarios with the different doses?

[Analyst] (Stifel): Hi, this is Emily on for Paul. Wanted to say congrats on the quarter and just 2 quick questions from us. You know, as it relates to the upcoming phase II readout, you know, what do you think, you know, would be a clear win that would, you know, prove out sabirnetug to be a unique alternative to donanemab and lecanemab? You know, do you see kinda different scenarios with the different doses? As a follow-up to that, you know, assuming success in phase II, would you be able to incorporate a subcutaneous arm in a phase III program? Maybe any color on the subcutaneous timelines would be helpful too. Thanks so much.

Speaker #5: And then, as a follow-up to that, assuming success in Phase 2, would you be able to incorporate a subcutaneous arm in a Phase 3 program? And maybe any color on the subcutaneous timelines would be helpful too.

Speaker #5: Thanks so much.

Daniel O'Connell: Thanks, Emily. I think in terms of a clear win in ALTITUDE-AD would be an efficacy signal, yeah, at least at 30% of slowing, which is sort of the maximal or the upper end of the boundary, I think, for the current approved agent. We, you know, we are hopeful and anticipating that by targeting toxic species in a directed fashion, selective fashion, that it will unlock greater efficacy. I think the safety profile, I think, you know, there's now real-world evidence to sort of suggest what the overall rates of ARIA and of course, those rates of ARIA differ by genotype. Those are some of the other elements of what we'll be looking to establish in terms of ARIA.

Dan O'Connell: Thanks, Emily. I think in terms of a clear win in ALTITUDE-AD would be an efficacy signal, yeah, at least at 30% of slowing, which is sort of the maximal or the upper end of the boundary, I think, for the current approved agent. We, you know, we are hopeful and anticipating that by targeting toxic species in a directed fashion, selective fashion, that it will unlock greater efficacy. I think the safety profile, I think, you know, there's now real-world evidence to sort of suggest what the overall rates of ARIA and of course, those rates of ARIA differ by genotype. Those are some of the other elements of what we'll be looking to establish in terms of ARIA.

Speaker #4: Thanks, Emily. So I think in terms of a clear win in altitude AD would be an efficacy signal at least at 30% of flowing, which is sort of the maximal or the upper end of the boundary, I think, for the current approved agent.

Speaker #4: So we are hopeful and anticipating that by targeting toxic species in a directed fashion, selective fashion, that it will unlock greater efficacy. I think the safety profile, I think there's now real-world evidence to sort of suggest what the overall rates of ARIA.

Speaker #4: And of course, those rates of ARIA differ by genotype and so those are some of the other elements of what we'll be looking to establish in terms of ARIA.

Speaker #4: So I think it will be the totality of the altitude data and really this sort of the risk-benefit profile of Cybernetug with a combination of efficacy and/or safety is positioned as the primary means of differentiation relative to the current approved agents.

Daniel O'Connell: I think it will be the totality of the ALTITUDE-AD data and really the sort of the risk-benefit profile of sabirnetug with a combination of efficacy and/or safety is positioned as the primary means of differentiation relative to the current approved agents. In terms of subQ, I think we've previously guided that we will be looking at the phase II data, particularly in respect of the 2 active doses that are being investigated in ALTITUDE-AD to inform precisely where and how we would advance the ongoing work in subQ as part of the phase III program.

Dan O'Connell: I think it will be the totality of the ALTITUDE-AD data and really the sort of the risk-benefit profile of sabirnetug with a combination of efficacy and/or safety is positioned as the primary means of differentiation relative to the current approved agents. In terms of subQ, I think we've previously guided that we will be looking at the phase II data, particularly in respect of the 2 active doses that are being investigated in ALTITUDE-AD to inform precisely where and how we would advance the ongoing work in subQ as part of the phase III program.

Speaker #4: And in terms of sub-Q, I think we've previously guided that we will be looking at the phase two data, particularly in respect of the two active doses that are being investigated in altitude.

Speaker #4: To inform precisely where and how we would advance the ongoing work in sub-Q as part of the phase three program.

Speaker #1: And I might add, Emily, I think you asked an interesting question as well around doses. As you know, there are two different doses included in the ALTITUDE study.

James Doherty: I might add, Emily, I think you ask an interesting question as well around doses. As you know, there are two different doses included in the ALTITUDE-AD study, and those doses were chosen to sort of bracket the range of oligomer clearance as measured by our target engagement assay in phase I. We think we've got an interesting range of doses chosen, and I'll be very curious to see how that impacts the results, both from a point of view of efficacy and safety, as Dan says. That's an interesting feature of the ALTITUDE-AD study, is that we've got both of those doses to investigate.

Jim Doherty: I might add, Emily, I think you ask an interesting question as well around doses. As you know, there are two different doses included in the ALTITUDE-AD study, and those doses were chosen to sort of bracket the range of oligomer clearance as measured by our target engagement assay in phase I. We think we've got an interesting range of doses chosen, and I'll be very curious to see how that impacts the results, both from a point of view of efficacy and safety, as Dan says. That's an interesting feature of the ALTITUDE-AD study, is that we've got both of those doses to investigate.

Speaker #1: And those doses were chosen to sort of bracket the range of oligomer clearance as measured by our target engagement assay in phase one. So we think we've got an interesting range of doses chosen and it'll be I'll be very curious to see how that impacts the results both from a point of view of efficacy and safety as Dan says and so that's an interesting feature on the altitude study is that we've got both of those doses to investigate.

Speaker #3: Yeah. And just one other point about the ARIA. I think one of the concepts that's across the field now that's being better appreciated is that it's really symptomatic ARIA that you're really concerned about.

Eric Siemers: Yeah. Just one other point about ARIA. I think one of the concepts that's across the field now that's being better appreciated is that it's really symptomatic ARIA that you're really concerned about. Even of the symptomatic ARIAs, it's serious adverse events that you really worry about. Those aren't nearly as common, but obviously they have a bigger impact. That's one of the things that we'll be benchmarking pretty carefully when we do get our data.

Speaker #3: And even if the symptomatic ARIA is—it’s serious adverse events that you’re really worried about. So those aren’t nearly as common, but obviously, they have a bigger impact.

Speaker #3: And so that's one of the things that we'll be benchmarking pretty carefully when we do get our data.

Speaker #5: Great. Thanks, guys, so much.

[Analyst] (Stifel): Great. Thanks, guys, so much.

Speaker #2: Thank you. And our next question comes from Jason Zemansky of Bank of America. Your line is open.

Didi: Thank you. Our next question comes from Jason Zemansky of Bank of America. Your line is open.

Operator: Thank you. Our next question comes from Jason Zemansky of Bank of America. Your line is open.

Speaker #6: Good morning. Congrats on the great progress, and thanks so much for taking our question. I wanted to ask a question, maybe from a different perspective here, but over the last several weeks, we've seen both the Cochrane report questioning the value of the anti-amyloid class.

Jason Zemansky: Good morning. Congrats on the great progress, and thanks so much for taking our question. I wanted to ask a question maybe from a different perspective here, but over the last several weeks, we've seen both the Cochrane report questioning the value of the anti-amyloid class. I guess a few days ago, there was an article that detailed that use of the current commercially available anti-amyloid antibodies has been slower than expected.

Speaker #6: And I guess a few days ago, there was an article that detailed that use of the current commercially available anti-amyloid antibodies has been slower than expected.

Speaker #6: So, as we kind of take a step back and think about both the overall unmet need and sort of the overall view of the class itself, what do you think is necessary from ALTITUDE and any sort of Phase 3 you do to really demonstrate that there's a level of differentiation here, as well as overall efficacy to the point that it sort of turns back some of the skepticism?

Jason Zemansky: You know, as we kinda take a step back and think about both the overall unmet need and sort of the overall sort of view of the class itself, what do you think is necessary from ALTITUDE-AD and any sort of phase III you do to really demonstrate that there's a level of differentiation here as well as, you know, overall, you know, efficacy to the point that it sort of turns back some of the skepticism? Thanks.

Speaker #6: Thanks.

Speaker #4: Thanks, Jason. So I think in terms of the Cochrane report, I think it's been a good bit of follow-up in terms of the methodology there and I think there's a real question about kind of the merits of the approach from a methodology standpoint.

Daniel O'Connell: Thanks, Jason. I think in terms of the Cochrane report, I think there's been, you know, a good bit of follow-up in terms of the methodology there. I think there's a real question about kind of the merits of the approach from a methodology standpoint. I do think that I'm familiar with the stat article as well. I think it speaks to sort of two things, the unmet need and the demand for better options, and the fact that there is the clinical infrastructure is now it has been established and continues to adopt and progress the make available these first couple agents and build out essentially the marketplace.

Dan O'Connell: Thanks, Jason. I think in terms of the Cochrane report, I think there's been, you know, a good bit of follow-up in terms of the methodology there. I think there's a real question about kind of the merits of the approach from a methodology standpoint. I do think that I'm familiar with the stat article as well. I think it speaks to sort of two things, the unmet need and the demand for better options, and the fact that there is the clinical infrastructure is now it has been established and continues to adopt and progress the make available these first couple agents and build out essentially the marketplace.

Speaker #4: I do think that and I'm familiar with the stat article as well. And I think it speaks to sort of two things. The unmet need and the demand for better options and the fact that there is the clinical infrastructure is now has been established and continues to adopt and progress the make available these first couple of agents and build out essentially the marketplace.

Speaker #4: I think what the market is looking for is a more clear value proposition in terms of the risk-benefit profile. And that's really where reading altitude and validating the oligomer hypothesis, I think Acumen and Cybernetug stand at a really attractive position from a timing perspective.

Daniel O'Connell: I think what the market is looking for is a more clear value proposition in terms of their risk-benefit profile. That's really where, you know, meeting at ALTITUDE-AD and validating the oligomer hypothesis, I think Acumen and sabirnetug stand at a really attractive position from a timing perspective to sort of re-energize the space and position next-generation treatment options. I think, you know, the field has progressed over a number of years to develop better insights into clinical trial design, you know, which patients to treat, you know, underlying aspects of the pathophysiology of the disease. You know, we view sabirnetug as sort of that next position, you know, advancing the field forward on the basis of positive data.

Dan O'Connell: I think what the market is looking for is a more clear value proposition in terms of their risk-benefit profile. That's really where, you know, meeting at ALTITUDE-AD and validating the oligomer hypothesis, I think Acumen and sabirnetug stand at a really attractive position from a timing perspective to sort of re-energize the space and position next-generation treatment options. I think, you know, the field has progressed over a number of years to develop better insights into clinical trial design, you know, which patients to treat, you know, underlying aspects of the pathophysiology of the disease. You know, we view sabirnetug as sort of that next position, you know, advancing the field forward on the basis of positive data.

Speaker #4: To sort of re-energize the space and position next-generation treatment options. I think the field has progressed over a number of years to develop better insights into clinical trial design, which patients to treat, and underlying aspects of the pathophysiology of the disease.

Speaker #4: And so, we view Cybernetug as sort of that next position, advancing the field forward on the basis of positive data.

Speaker #6: Got it. Thanks for the color.

Jason Zemansky: Got it. Thanks for the color.

Speaker #2: Thank you.

Eric Siemers: Yeah. I'd like to add, I was recently at the American Academy of Neurology meeting in Chicago, and these are practicing neurologists for the most part. There was a great deal of interest and enthusiasm for information concerning the two approved drugs, so lecanemab and donanemab. Even though there have been these relatively negative analyses, and again, as Dan mentioned, the Cochrane report was pretty flawed in a lot of people's opinions in terms of how they did the analysis. I think if you actually talk to neurologists, they understand that the infrastructure has been rate-limiting, but that infrastructure is going to continue to improve. There is a lot of interest from neurologists at the AAN meeting.

Speaker #3: Dan, I'd like to say that I was recently at the American Academy of Neurology meeting in Chicago. And these are practicing neurologists, for the most part.

Speaker #3: There was a great deal of interest and enthusiasm for information concerning the two approved drugs, lecanemab and donanemab. So even though there have been these relatively negative analyses and again, as Dan mentioned, the Cochrane report was pretty flawed and a lot of people's opinions in terms of how they did the analysis, I think if you actually talk to neurologists, they understand that the infrastructure has been rate limiting but that infrastructure is going to continue to improve.

Speaker #3: And so there was a lot of interest from neurologists at the AAN meeting.

Speaker #2: Thank you. And our next question comes from Tom Schrader of BTIG. Your line is open.

Didi: Thank you. Our next question comes from Thomas Shrader of BTIG. Your line is open.

Operator: Thank you. Our next question comes from Thomas Shrader of BTIG. Your line is open.

Speaker #5: Good morning. This is Ginny Kim on for Tom Schrader. Thank you for taking our question. At altitude A, the approach at the slate 2026 top line readout, could you give us some additional color on the blinded operational metrics or tracking, things like protocol deviation rates, site level dropout patterns, or any shifts in enrolled patient population profile relative to your original assumptions?

Jenny Kim: Good morning. This is Jenny Kim on for Thomas Shrader. Thank you for taking our question. As ALTITUDE-AD approaches its late 2026 top line readout, could you give us some additional color on the blinded operational metrics you're tracking, things like protocol deviation rates, site-level dropout patterns, or any shifts in enrolled patient population profile relative to your original assumptions? More broadly, what distinguishes the quality of this data set relative to prior and the avoide trial? Thank you.

Speaker #5: More broadly, what distinguishes the quality of this data set relative to prior anti-amyloid trials? Thank you.

Daniel O'Connell: Thanks, Jenny. Jim, do you wanna lead out on that and Eric provide some color?

Dan O'Connell: Thanks, Jenny. Jim, do you wanna lead out on that and Eric provide some color?

Speaker #4: Thanks, Ginny. Jim, do you want to lead out on that and Eric provide some color?

Speaker #3: Yeah, Ginny, I'll give you a first pass and then ask Eric to weigh in. I think probably the best thing to say is that we, at this point, have been very pleased with the progress of the ALTITUDE study.

James Doherty: Yeah, Jenny, I'll give you a first pass then ask Eric to weigh in. I think probably the best thing to say is that we, at this point, have been very pleased with the progress of the ALTITUDE-AD study. Any of these studies is a 542 subject study. There's a lot of data and a lot of information flowing in the study. We've been relatively pleased with the conduct of the study. It's a great team that is working extremely hard across multiple geographies to deliver the data. I think, you know, to date, we have been tracking to the assumptions that we built into our study design. We have confidence in our study design as well.

Jim Doherty: Yeah, Jenny, I'll give you a first pass then ask Eric to weigh in. I think probably the best thing to say is that we, at this point, have been very pleased with the progress of the ALTITUDE-AD study. Any of these studies is a 542 subject study. There's a lot of data and a lot of information flowing in the study. We've been relatively pleased with the conduct of the study. It's a great team that is working extremely hard across multiple geographies to deliver the data. I think, you know, to date, we have been tracking to the assumptions that we built into our study design. We have confidence in our study design as well.

Speaker #3: And any of these studies is a 542 subject study. There's a lot of data and a lot of information flowing in the study. But we've been relatively pleased with the conduct of the study.

Speaker #3: It's a great team that is working extremely hard across multiple geographies to deliver the data. And I think, to date, we have been tracking to the assumptions that we built into our study design.

Speaker #3: So we have confidence in our study design as well. And I'll turn it over to Eric to give you any specific commentary.

James Doherty: I'll turn it over to Eric to give you any specific commentary.

Jim Doherty: I'll turn it over to Eric to give you any specific commentary.

Speaker #7: Yeah. So thanks for the question. The study is progressing quite well. I think as you know, we completed enrollment in a very short period of time in 10 months.

Eric Siemers: Yeah. Thanks for the question. The study is progressing quite well. I think, as you know, we completed enrollment in a very short period of time, in 10 months. One of the things that we did in our study, which it's being done in other studies, but is quite innovative, I think, was to use this plasma p-tau217 test as part of a screening procedure. In other words, when we did our phase I study, to get into the study, you had to have a positive PET scan, and it turned out that about 60% of the time, the PET scans were negative.

Speaker #7: One of the things that we did in our study, which is being done in other studies, but it is quite innovative, I think, was to use this plasma pTau217 test as part of a screening procedure.

Speaker #7: So, in other words, when we did our Phase One study, to get into the study you had to have a positive PET scan. And it turned out that about 60% of the time, the PET scans were negative.

Speaker #7: When we added this blood test, simple blood test, as a screening step before you got to PET scans, the rate of negative PET scans dropped from, again, around 60% to under 20%.

Eric Siemers: When we added this blood test, simple blood test as a screening step before you got to PET scans, the rate of negative PET scans dropped from, again, around 60% to under 20%. It made the screening process much better. We heard feedback from the sites that they really liked that approach. I think that's something that could be used in clinical practice. Actually, at the American Academy of Neurology meeting, there was a lot of discussion about how you would use these plasma biomarkers as part of your screening process for patients. We were really very pleased at how that worked out in our trial, and we're looking forward to seeing that utilized in clinical practice.

Speaker #7: So it made the screening process much better. We heard feedback from the sites that they really liked that approach. I think that's something that could be used in clinical practice.

Speaker #7: And actually, at the American Academy of Neurology meeting, there was a lot of discussion about how you would use these plasma biomarkers as part of your screening process for patients.

Speaker #7: So we were really very pleased how that worked out in our trial. And we're looking forward to seeing that utilized in clinical practice.

Speaker #5: Thank you for the color.

Jenny Kim: Thank you for the color.

Speaker #2: Thank you. And our next question comes from Dev Prasad of Lucid Capital Markets. Your line is open.

Didi: Thank you. Our next question comes from Dev Prasad of Lucid Capital Markets. Your line is open.

Operator: Thank you. Our next question comes from Dev Prasad of Lucid Capital Markets. Your line is open.

Speaker #8: Hi. Congrats on the process and progress. And thank you for taking our question. Just following up on the previous question, regarding phase two doses.

Dev Prasad: Hi. Congrats on the process and progress, and thank you for taking our question. Just following up on the previous question regarding phase II doses, how much separation between 35 mg and 50 mg do you expect, and what would you need to see to select a phase III dose? Also, on EBD program, can you provide more detail on 14 to 40x higher brain exposure that you observed in the primates? What differentiated those exposures such as dose, route, brain distribution, et cetera? Thank you.

Speaker #8: How much separation between 35 meg and 50 meg do you expect? And what would you need to see to select a phase three dose?

Speaker #8: Also, on EBD program, can you provide more detail on 14 to 40x higher brain exposure that you observed in the primates? What differentiated those exposures, such as dose, root, brain distribution, etc.?

Speaker #8: Thank you.

Speaker #4: Thanks, Jim. I'm going to direct those straight to you.

Daniel O'Connell: Thanks, Dev. Jim, I'm gonna direct those, put those straight to you.

Dan O'Connell: Thanks, Dev. Jim, I'm gonna direct those, put those straight to you.

Speaker #3: Yeah, Dev, so happy to take those questions. So, when we think about dosing for the ALTITUDE study, first, the doses are 35 mg per kg and 50 mg per kg.

James Doherty: Yeah, Dev, happy to take those questions. When we think about dosing for the ALTITUDE study, first, the doses are 35 mg per kg and 50 mg per kg. I was mentioning earlier, those doses were sort of chosen with the idea in mind that that is what looks to be a key part of the dynamic range and exposure of soluble oligomers, which of course is our key primary target. I think, you know, there's the opportunity to see differential effects of the 2 doses in a couple of different ways. I mean, we'll have to wait and see what the data actually show, one possibility is differences in efficacy. You might expect to see dose-related differences in efficacy.

Jim Doherty: Yeah, Dev, happy to take those questions. When we think about dosing for the ALTITUDE study, first, the doses are 35 mg per kg and 50 mg per kg. I was mentioning earlier, those doses were sort of chosen with the idea in mind that that is what looks to be a key part of the dynamic range and exposure of soluble oligomers, which of course is our key primary target. I think, you know, there's the opportunity to see differential effects of the 2 doses in a couple of different ways. I mean, we'll have to wait and see what the data actually show, one possibility is differences in efficacy. You might expect to see dose-related differences in efficacy.

Speaker #3: And I was mentioning earlier, those doses were sort of chosen with the idea in mind that that is what looks to be a key part of the dynamic range and exposure of cyboligamers, which of course is our key primary target.

Speaker #3: And I think the opportunity to see effects differential effects of the two doses in a couple of different ways. I mean, we'll have to wait and see what the data actually show.

Speaker #3: But one possibility is differences in efficacy. You might expect to see dose-related differences in efficacy. Although I think part of what we're testing there is what the role of the cyboligamers is and how that's different from what you've seen to date with more plaque targeting antibodies.

James Doherty: Although I think part of what we're testing there is what the role of the soluble oligomers is and how that's different from what you've seen to date with more plaque-targeting antibodies. In some ways, the lower dose may give more of an oligomer-specific signal, although we do expect some contribution from other species of Aβ even at that dose. Certainly as you go to a higher dose, you would expect some additional effects on larger species as we've seen in the INTERCEPT-AD study in phase I. I think also one might expect that there could be some differences in tolerability, right? I mean, that would be again, consistent with the phase I data.

Jim Doherty: Although I think part of what we're testing there is what the role of the soluble oligomers is and how that's different from what you've seen to date with more plaque-targeting antibodies. In some ways, the lower dose may give more of an oligomer-specific signal, although we do expect some contribution from other species of Aβ even at that dose. Certainly as you go to a higher dose, you would expect some additional effects on larger species as we've seen in the INTERCEPT-AD study in phase I. I think also one might expect that there could be some differences in tolerability, right? I mean, that would be again, consistent with the phase I data.

Speaker #3: So, in some ways, the lower dose may give more of an oligomer-specific signal. Although we do expect some contribution from other species of Aβ, even at that dose.

Speaker #3: And then certainly, as you go to a higher dose, you would expect some additional effects on larger species as we've seen in the Intercept study in phase one.

Speaker #3: And I think also one might expect there could be some differences in tolerability, right? I mean, that would be, again, consistent with the Phase 1 data.

Speaker #3: So we're very excited to see the study at the end of the year. And we'll be looking at all of these things for differential effects, at multiple doses.

James Doherty: We're very excited to see the study at the end of the year, we'll be looking at all these things for differential effects at multiple doses. I think your other question around the EBD programs. Of course, what we're trying to achieve is both an improvement in the brain penetration, but also the brain distribution of our oligomer targeting antibodies by coupling with the carrier technology from JCR. What we've done is we've investigated multiple candidates, is we've been able to vary both sides of that equation. Looking at the changes to the carrier choices from JCR as well as modifications on the cargo side.

Jim Doherty: We're very excited to see the study at the end of the year, we'll be looking at all these things for differential effects at multiple doses. I think your other question around the EBD programs. Of course, what we're trying to achieve is both an improvement in the brain penetration, but also the brain distribution of our oligomer targeting antibodies by coupling with the carrier technology from JCR. What we've done is we've investigated multiple candidates, is we've been able to vary both sides of that equation. Looking at the changes to the carrier choices from JCR as well as modifications on the cargo side.

Speaker #3: And then I think your other question around the EBD programs. So of course, what we're trying to achieve is both an improvement in brain penetration but also the brain distribution of our oligomer targeting antibodies by coupling with the carrier technology from JCR.

Speaker #3: And so what we've done is we've investigated multiple candidates is we've been able to vary both sides of that equation. So looking at the changes to the carrier, choices from JCR, as well as modifications on the cargo side.

Speaker #3: And really, the quick way to summarize it is what you're seeing is a range of substantial improvements in brain exposure. And that's in both rodent studies using humanized transfer receptor, and then also in primate studies.

James Doherty: Really, the quick way to summarize it is what you're seeing is a range of substantial improvements in brain exposure, and that's in both rodent studies using humanized transferrin receptor and then also in primate studies. We're looking at multiple brain regions, in the primate study, we're seeing really substantial improvements, and you quoted the range between 15-fold and 40-fold improvements in exposure. We're seeing both that improved brain penetration as well as distribution. We really think it's both properties that are part of what make this technology so exciting for the treatment of Alzheimer's and specifically for a soluble oligomer approach. That's what I can say to date.

Jim Doherty: Really, the quick way to summarize it is what you're seeing is a range of substantial improvements in brain exposure, and that's in both rodent studies using humanized transferrin receptor and then also in primate studies. We're looking at multiple brain regions, in the primate study, we're seeing really substantial improvements, and you quoted the range between 15-fold and 40-fold improvements in exposure. We're seeing both that improved brain penetration as well as distribution. We really think it's both properties that are part of what make this technology so exciting for the treatment of Alzheimer's and specifically for a soluble oligomer approach. That's what I can say to date.

Speaker #3: And so we're looking at multiple brain regions and so in the primate study. And so we're seeing really substantial improvements and you quoted the range between 15-fold and 40-fold improvements in exposure.

Speaker #3: And so we're seeing both that improved brain penetration as well as distribution. And we really think it's both properties that are part of what make this technology so exciting for the treatment of Alzheimer's and specifically for cyboligamer approach.

Speaker #3: So that's what I can say to date. We are keeping a close eye on which are the best candidates to give us the broadest distribution in multiple brain regions.

James Doherty: We are keeping a close eye on which are the best candidates to give us the broadest distribution in multiple brain regions.

Jim Doherty: We are keeping a close eye on which are the best candidates to give us the broadest distribution in multiple brain regions.

Speaker #8: Great. Thank you.

Dev Prasad: Great. Thank you.

James Doherty: Of course.

Jim Doherty: Of course.

Speaker #4: Of course.

Operator: Thank you. This concludes our question and answer session and also today's conference call. Thank you for participating, and you may now disconnect.