Q4 2021 Acumen Pharmaceuticals Inc Earnings Call

Today's call is being recorded, and I would like to turn the call over to John Wilford from Westbrook, please go ahead.

Is being recorded and I would now like to turn the call over to John Woolford from Westwood. Please go ahead.

Thank you operator good afternoon. Thank you for joining us today to review arguments fourth quarter and full year 2021 operational progress and financial results before we start we incur.

John: Thank you, operator. Good afternoon. Thank you for joining us today to review Acumen's fourth quarter and full year 2021 operational progress and financial results. Before we start, we encourage you to view the slides for this webcast, as well as the operational and financial results press release issued this afternoon, both of which are accessible on our website in the investors section.

You can view the slides for this webcast as well as the operational and financial results Press release issued this afternoon, both of which are accessible on our website in the investors section.

John: As shown on slide two, 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.

As shown on slide two 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. All of these statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward looking statements.

John: All these statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forelooking statement.

John: Our actual results could differ materially due to a number of factors, including the extent and duration of the effects of the COVID-19 pandemic and the timing and extent of recovery from it.

Our actual results could differ materially due to a number of factors, including the extent and duration of the effects of the COVID-19, pandemic and the timing and extent of recovery from it.

John: Please refer to our recent findings with the SEC for a full review of the risks and uncertainties associated with our business.

Please refer to our recent filings with the SEC for a full review of the risks and uncertainties associated with our business forward looking statements speak only as of the date on which they are made and acumen undertakes no obligation to update or revise any forward looking statement.

John: Forward-looking statements speak only as of the date on which they are made, and Acumen undertakes no obligation to update or revise any forward-looking statement.

John: Dan O'Connell, President and Chief Executive Officer, will begin today's call with a high level overview document and review Select 2021 Business Highlight.

Dan O'connell, President and Chief Executive Officer will begin today's call with a high level overview of acumen and review select 2021 business highlights.

John: Dr. Eric Seamers, Chief Medical Officer, will then provide a quick primer on Amaloid Beta Oligomers and discuss the ongoing Intercept AD trial. Next, Madzuga Chief Financial Officer who will provide a brief financial update, we will then open the call for Q&A.

Dr. Eric Siemers, Chief Medical Officer will then provide a quick primer on amyloid beta oligomerous and discuss the ongoing intercept a D trial next magic Chief Financial Officer, who will provide a brief financial update we will then open the call for Q&A.

John: I'll now hand the call over to Dan O'Connell, President and Chief Executive Officer.

I'll now hand, the call over to Dan O'connell, President and Chief Executive Officer.

Dano O'Connell: Thank you, John . Good afternoon and thank you to everyone joining the call today. I'm delighted to be here on our first conference call as a public company.

Thank you John Good afternoon, and thank you to everyone joining the call today I'm delighted to be here on our first conference call as a public company.

Moving to slide three two.

Dano O'Connell: 2021 was a transformational year for acumen highlighted by the achievement of several major accomplishments, including our successful IPO. As this is our first public call, I want to take a moment to provide a brief introduction to acumen for those that may be new to the company.

2021 was a transformational year for acumen highlighted by the achievement of several major accomplishments, including our successful IPO. As this is our first public call I want to take a moment to provide a brief introduction to acumen for those that may be new to the company.

Dano O'Connell: Acumen is focused on the development of novel targeted therapeutics for Alzheimer's disease, which has received significant attention over the last year given the approval and launch of Biogen's Adderhelm. While controversial, the Adderhelm approval has brought substantial and needed attention to the enormous need to help people living with Alzheimer's disease. While many companies have pursued treatments targeted to amyloid plaques, fibrils, or monomers, Acumen is focused on targeting amyloid beta-oligomers.

Acumen is focused on the development of novel targeted therapeutics for all summers disease, which has received significant attention over the last year, given the approval and launch of biogen's out at home.

While controversial Datacom approval has brought substantial that needed attention to the enormous need to help people living with all summers disease, while many companies have pursued treatments targeting amyloid plaques fibrils for monomers.

<unk> is focused on targeting amyloid beta oligomers.

Dano O'Connell: We believe there is an emerging scientific consensus that oligomers are the most toxic form of amyloid data, and that the development of a product that reduces toxicity of oligomers is one of the most promising approaches for the potential treatment and prevention of the progression of Alzheimer's.

We believe there is an emerging scientific consensus that oligomers are the most toxic form of amyloid beta and the development of a product that reduces toxicity of oligomers as one of the most promising approaches for the potential treatment and prevention of progression of Alzheimers.

Dano O'Connell: Our lead product is ACU-193, the first monoclonal antibody developed to selectively target amyloid beta oligomers to enter clinical testing. ACU-193's potential is supported by extensive pre-clinical data supporting its differentiation from other anti-amyloid programs.

Our lead product is <unk> hundred 93, the first monoclonal antibody developed to selectively target amyloid beta oligomers to enter clinical testing Acu 190, Three's potential is supported by extensive preclinical data supporting its differentiation from other anti amyloid programs.

Dano O'Connell: To guide AC-193's development, we've assembled an experienced leadership team with significant industry expertise in Alzheimer's drug discovery and development. Many of our employees were formally part of Eli Lilly's Alzheimer's

The guide issue on any trees development, we've assembled an experienced leadership team with significant industry expertise and all summers drug discovery and development. Many of our employees were formerly part of Eli Lilly's Alzheimers team.

Dano O'Connell: As I mentioned earlier, we successfully completed an IPO in 2021. We raised approximately $184 million in gross proceeds in the offering that included multiple well-respected biotech investors and provides us the financial resources to advance AC193 through multiple clinical milestones and extending our cash runway through 2025.

As I mentioned earlier, we successfully completed an IPO in 2021, we raised approximately $184 million in gross proceeds in the offering that included multiple well respected biotech investors and provides us the financial resources to advance issue one ninety-three through multiple clinical milestones.

And extending our cash runway through 2025.

Dano O'Connell: The next key milestone for AC-193 is proof of mechanism data from our ongoing phase 1 trial in early Alzheimer's disease, which is now expected in the first half of 2023. Eric will discuss the trial shortly.

The next key milestone for issue 193 is proof of mechanism data from our ongoing phase one trial and early Alzheimers disease, which is now expected in the first half of 2023.

Eric will discuss the trial shortly.

Eric Seer: I'll now move to some key business highlights in 2021 as shown on slide 4.

I'll now move to some key business highlights in 2021 as shown on slide four.

Eric Seer: Following the funding of a $30 million cross from a Series B financing in June , we rapidly strengthen our balance sheet further with the completion of our IPO raising gross proceeds of $184 million, as I mentioned.

Following the funding of a $30 million tranche from a series B financing in June we rapidly strengthened our balance sheet further with the completion of our IPO raising gross proceeds of $184 million as I mentioned.

Eric Seer: We then initiated the intercept AD trial, dosing the first patient in October .

We then initiated the intercept trial dosing the first patient in October .

Eric Seer: We were then pleased to be accepted to present at the 2021 clinical trials on Alzheimer's disease or CTAD conference in November in Boston.

We were then pleased to be accepted to present at the 2021 clinical trials on Alzheimer's disease, where she Tad conference in November in Boston.

Eric Seer: At the conference, we discussed the scientific rationale for targeting amyloid beta ligamers, the clinical trial design of Intercept AD and how the study is designed to establish safety and proof of mechanism and assess any potential improvements in cognition and blood flow in the brain.

At the conference we discussed the scientific rationale for targeting amyloid beta oligomers, the clinical trial design or intercept a D and how the study is designed to establish safety and proof of mechanism and assess any potential improvements in cognition and blood flow in the brain.

To support our expected growth over the coming years, we recently made several senior level appointments to the company's leadership team. The new leaders include Julie Bakken study head of human relations switching Gan head of clinical operations, and Steven Reynolds corporate controller and treasurer.

Eric Seer: To support our expected growth over the coming years, we recently made several senior level appointments for the company's leadership team. The new leaders include Julie Bakkensteady, Head of Human Relations, Soutine Gan, Head of Clinical Operations, and Stephen Reynolds, Corporate Controller and Treasurer.

Eric Seer: All three bring deep experience and collective passion for improving the lives of patients with all summer's disease.

All three bring deep experience and collect a passion for improving the lives of patients with Alzheimer's disease.

Eric Seer: I'd also like to use this opportunity to welcome Kim Drapkin to our Board of Directors, effective April 1st. Ms. Drapkin brings to Jounce more than 20 years of experience working with private and publicly traded biotechnology and pharmaceutical companies, including building and leading finance functions, raising capital and leading strategic financial planning.

I'd also like to use this opportunity to welcome Kim Drapkin to our board of directors effective April 1st Mr. Aitken brings to <unk> more than.

20 years of experience working with private and publicly traded biotechnology and pharmaceutical companies, including building and leading finance functions, raising capital and leading strategic financial planning.

Turning to slide five.

Eric Seer: We've continued to make significant progress in advancing the intercept AD trial. As I mentioned previously, we now expect to report top line results in the first half of 2023, a slight revision from our previous timing of year-end 22.

We've continued to make significant progress in advancing the intercept a D trial as I mentioned previously we now expect to report topline results from the first half of 2023, a slight revision from our previous timing of year end 'twenty two.

Eric Seer: We believe the COVID-19 pandemic impacted our site activation timeline and enrollment somewhat. However, given our strong financial position, we also now plan to incorporate a larger data set expanded to the end of study and database law.

We believe the COVID-19 pandemic impacted our site activation timeline enrollment somewhat.

However, given our strong financial position. We also now plan to incorporate a larger dataset expand it to the end of study and database lock regarding enrollment we have experienced continued success in activating clinical trial sites.

Eric Seer: Regarding enrollment, we have experienced continued success in activating clinical trial sites.

Eric Seer: And enrollment is now ongoing at eight active sites with six additional sites selected for potential activation.

And enrollment is now ongoing at eight active sites with six additional sites selected for potential activation.

Eric Seer: time to activation of these sites has accelerated dramatically starting in 2022.

Time to activation of these sites has accelerated dramatically starting in 2022.

Eric Seer: In parallel to conducting the Intercept AD trial, we have also made significant progress in preparing for a future Phase 2-3 trial of AC193. Chronic GLP toxicity testing has been initiated, and our new drug substance production process and drug product formulation are being finalized. We have begun designing the Phase 2-3 study and planning for an end of Phase 2 meeting with the FDA.

In parallel to conducting the intercept trial. We have also made significant progress in preparing for a future phase three trial of issue on 93 crore.

Chronic G O P toxicity testing has been initiated and our new drug substance production process and drug product formulation or being finalized.

We've begun designing the phase two three study and planning for an end of phase II meeting with the FDA.

Eric Seer: Given this headway, we anticipate being able to initiate the next trial rapidly after demonstrating proof of mechanism in the intercept AD trial.

Given this headway, we anticipate being able to initiate the next trial rapidly after demonstrating proof of mechanism in the intercept trial.

Speaker Change: I'll now turn the call over to Dr. Eric Seeners or Chief Medical Officer.

I'll now turn the call over to Dr. Eric Siemers, our Chief Medical Officer.

Eric Stemers: Thanks, Dan. Good afternoon, everyone. I'll start today with Quick Primer on AC-193 and AMOLED beta,

Thanks, Dan and good afternoon, everyone I'll start today with a quick primer on Acu 193 in amyloid beta all like immerse.

Eric Stemers: Turning to slide 6, as Dan mentioned, our monoclonal antibody ACU-193 is designed to address a major component of Alzheimer's disease pathology by binding to amyloid beta-algamers, also known as a beta-algamers, which are a toxic form of the a-beta protein.

Turning to slide six as Dan mentioned, our monoclonal antibody AC 193.

Designed to address a major component of bulk clamorous disease pathology by binding to amyloid beta olive <unk> also known as a beta all comers, which are toxic form of the a beta protein.

Eric Stemers: A growing body of evidence indicates that these oligomers are a primary trigger and persistent driver of Alzheimer's topology and neurodegeneration.

A growing body of evidence indicates that these oligomer or a primary trigger and persistent driver of all time or pathology in neuro degeneration.

Eric Stemers: The accumulation of a-beta oligomers is associated with loss of the connections between nerves as well as inflammation.

Cumulation of Bay Beta all comers associated with loss of the connections between nerves as well as information.

Eric Stemers: there is substantial evidence that a beta oligmer's lead to the memory impairment, cognitive decline, and progressive neurodegeneration that are seen in Alzheimer's disease.

There is substantial evidence that a beta olive mers lead to the memory impairment cognitive decline and progressive neuro degeneration that are seen in alzheimers disease.

Eric Stemers: By binding to A beta oligmers, ACU-193 prevents them from binding to specialized parts of nerves called dendritic spines, which we believe may help to preserve nerve function and protect cells from neurodegeneration.

By binding to a beta all comers acu wasn't ninety-three prevents them from binding to a specialized parts observes called been critics borrowings, which we believe may help to preserve nerve function and protect cells from neuro degeneration.

Eric Stemers: What makes ACU193 so unique and differentiated from other monoclonal antibodies studied in Alzheimer's disease is ACU193's high selectivity for A-beta oligomers relative to other anti-amyloid monoclonal antibodies that are less selective or target different amyloid species such as A-beta monomers or deposited A-beta amyloid plaques.

Well it makes acu wasn't ninety-three, so unique and differentiated from other monoclonal antibodies studied in Alzheimers disease.

As they see you won 90 threes high selectivity for a beta alcohol relative to other anti amyloid monoclonal antibodies that are less selective or target different amyloid species, such as a beta monomers were deposited a beta amyloid plaques.

Eric Stemers: We believe this can lead to improved clinical efficacy compared to other monoclonal antibodies studied in Alzheimer's disease, and importantly, with an expected lack of aria-related safety concerns, which are seen with other monoclonal antibodies.

We believe this can lead to improved clinical efficacy compared to other monoclonal antibodies studied in Alzheimers disease, and importantly, with an expected lack of Oreo related safety concerns, which are seen with other monoclonal antibodies.

Eric Stemers: We also believe there is some potential for possible cognitive improvement in addition to disease-slowing.

We also believe there is some potential for possible cognitive improvement in addition to disease or what.

Eric Stemers: With that introduction, I'll now provide a brief overview of the ongoing Intercept AD Phase 1 trial. As shown on slide.

With that introduction I'll now provide a brief overview of the ongoing intercept a D phase one trial.

As shown on slide seven.

Eric Stemers: The study is a randomized placebo-controlled phase 1A slash B trial. As a standard, there are two portions, including a single ascending dose portion, part A, and a multiple ascending dose portion, part B.

The study is a randomized placebo controlled phase one a slash b trial.

As is standard there are two portions, including a single ascending dose portion part a and a.

The goal of ascending dose portion part b.

Eric Stemers: The trial is being conducted in patients with early Alzheimer's disease, those with mild cognitive impairment, and mild dementia.

The trial is being conducted in patients with early Alzheimer's disease.

As with mild cognitive impairment and mild dementia.

Eric Stemers: To participate in the trial, patients must be amyloid positive, as determined by PET-C.

<unk> in the trial patients must be amyloid positive as determined by pet scans.

Eric Stemers: As Dan mentioned, a key objective of the trial is to demonstrate targeting engagement and proof of mechanism that's determined by demonstrating that ACU-193 is bound to oligomers in cerebrospinal fluid.

As Dan mentioned the key objective of the trial is to demonstrate targeting great engagement and proof of mechanism. That's determined by demonstrating that Acu 193 is bound to olive emerged in cerebrospinal fluid.

Eric Stemers: Other important outcomes include the evaluation of safety and tolerability, pharmacokinetics, and measures of cognition.

Other important outcomes include the evaluation of safety and Tolerability pharmacokinetics and measures of cognition.

Slide eight illustrates the trial design of intercept a D.

Eric Stemers: Slide eight illustrates the trial design of Intercept AD.

Eric Stemers: Part A, the single ascending dose portion, includes four cohorts with eight patients per cohort at doses of two, 10, 25, and 60 milligrams per kilogram or placebo.

A the single ascending dose portion includes four cohorts with eight patients per cohort at doses up to 10, 25, and 60 milligrams per kilogram or placebo.

Eric Stemers: Part B, the multiple ascending dose portion, includes three cohorts with 10 patients per cohort at doses of 10 and 60 milligrams per kilogram dosed every four weeks and 60 milligrams per kilogram dosed every two weeks for placebo.

Part b the multiple ascending dose portion.

<unk> three cohorts with 10 patients per cohort at doses of 10, and 60 milligrams per kilogram dosed every four weeks and 60 milligrams per kilogram dose every two weeks.

Or placebo.

Speaker Change: I want to highlight that included in the trial design is the ability to initiate the first cohort of the multiple ascending dose portions after safety and tolerability is demonstrated in the second cohort of the single ascending dose portion.

I want to highlight that included in the trial design is the ability to initiate the first cohort of the multiple ascending dose portion after safety and Tolerability as demonstrated in the second cohort.

The single ascending dose portion.

Speaker Change: Slide nine shows the objectives of the trial in detail. In the interest of time, I'm not going to read them all out, but we wanted to give everyone an indication of the data that we plan to ultimately report from the study. If you can see, we expect the trial to provide a significant amount of data that will be crucial in the design of the planned phase two slash three trial, as well as our regulatory strategy.

Slide nine shows the objectives of the trial in detail.

For some time I'm not going to read them all out, but we wanted to give everyone an indication of the data that we plan to ultimately report from this study.

You can see we expect the trial to provide a significant amount of data that will be crucial in the design of the planned phase two slash three trials as well as our regulatory strategy.

Speaker Change: Ultimately, what's most important is that we expect that the data will justify advancement into a Phase 2-3 trial.

Ultimately, what's most important is that we expect that the data will justify advancement into a phase two slashed three trial.

Speaker Change: Assuming Intercept AD demonstrates acceptable safety and tolerability shows ACU-193 gets into the central compartment and confirms target engagement. We plan to advance the program to the Phase 2-3 study.

Sumit intercept a D demonstrates acceptable safety and Tolerability shows Acu 193 gets into the central compartment and confirmed target engagement, we plan to advance the program to the phase two slash three study.

Speaker Change: With that, I will turn the call over to Matt Zuga, our Chief Financial Officer and Chief Business Officer. Thank you, Eric.

With that I will turn the call over to Matt <unk>, Our Chief Financial Officer, and Chief Business Officer.

Thank you, Eric and thanks to everyone for joining.

Matt Zga: To start, I want to reiterate what Dan said earlier. As a result of planning and executing on our private and public financing strategy in 2020 and 2021.

To start I want to reiterate what Dan said earlier as a result of planning and executing on our private and public financing strategy in 2020 in 2021.

Matt Zga: we are well capitalized and have the resources to achieve multiple clinical development milestones.

We are well capitalized and have the resources to achieve multiple clinical development milestones.

Matt Zga: As of December 31st, 2021, we had approximately $225 million in cash and marketable securities. Looking ahead, based on our current operating plan, we expect our cash runway to last through 2025.

As of December 31, 2021, we had approximately $225 million in cash and marketable securities looking ahead based on our current operating plan, we expect our cash runway to last through 2025.

Matt Zga: Our strong balance sheet is the result of the proceeds from Series B and IPO financing completed in 2020.

Our strong balance sheet is the result of the proceeds from series B and IPO financings completed in 2020 in 2021.

Matt Zga: Our complete financial results for 2021 are available in the press release we issued this afternoon and in our 10-K , which will be filed shortly.

Our complete financial results for 2021 are available in the press release, we issued this afternoon and in our 10-K, which will be filed shortly I'm.

Matt Zga: I'm not going to review our results in detail, but I do want to highlight a few items.

I'm not going to review our results in detail, but I do want to highlight a few items.

Matt Zga: R&D expenses were $12.3 million in 2021. The increase over 2020 was primarily the result of the initiation of the Intercept AD trial during the year.

R&D expenses were $12 $3 million in 2021, the increase over 2020 was primarily the result of the initiation of the intercept trial during the year.

Matt Zga: E&A expenses were $7.3 million in 2021, with the increase primarily the result of increased headcount and the cost of going public and being a public company following our IPO.

G&A expenses were $7 $3 million in 2021 with the increase primarily the result of increased head count and the cost of going public and being a public company following our IPO.

Matt Zga: This led to a loss from operations of $19.6 million for the full year.

This led to a loss from operations of $19 $6 million for the full year.

Matt Zga: Note that our net loss for the full year was $100.6 million. This was primarily driven by a non-cash expense of $81.2 million that represents the changes in fair value of our Series B tranche liability and our Series A1 warrant liability. The tranche liability and the warrant liability were initially recorded at fair value as a liability on Acumen's balance sheet and are subsequently remeasured at fair value at the end of each reporting period.

Note that our net loss for the full year was $106 million. This was primarily driven by a noncash expense of $81 $2 million that represents the changes in fair value of our series B tranche liability and our series a one warrant liability the tranche liability in the warrant liability we're in.

Initially recorded at fair value as a liability on acumen as balance sheet and our subsequently re measured at fair value at the end of each reporting period.

Matt Zga: Both liabilities were extinguished by the conversion of our preferred shares and warrants to common shares at the IPO.

Both liabilities were extinguished by the conversion of our preferred shares and warrants to common shares at the IPO.

Matt Zga: We will continue to work hard over the coming quarters to enroll Intercept AD and look forward to reporting top line data in the first half of 2020.

We will continue to work hard over the coming quarters to enroll intercept a D and look forward to reporting topline data in the first half of 2023.

Matt Zga: Importantly, we will continue to operate Acumen efficiently and cost effectively to ensure our cash runway is maintained through 2025. We thank our shareholders and partners for their ongoing trust and support and will now open up the floor for questions.

Importantly, we will continue to operate acumen efficiently and cost effectively to ensure our cash runway is maintained through 2025.

Thank our shareholders and partners for their ongoing trust and support and we'll now open up the floor for questions.

Speaker Change: Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the one key on your touch tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key.

Ladies and gentlemen, if you have a question or a comment at this time. Please press Star then the one key on your Touchtone telephone.

It has been answered or you wish to move yourself from the queue. Please press the pound key.

Yeah.

Our first question comes from Paul Matteis with Stifel.

Speaker Change: Hi there, thanks for taking our questions. This is Alexander for Paul. I was wondering, I think in the prepared remarks, Dan, you mentioned that the slight delay for intercepts would allow you to have an expanded data set for the top line. I wonder if you could elaborate a little bit more on kind of what that looks like and how that would impact the top line data. And I have a couple other follow-ups.

Hi, there thanks for taking our questions. This is Alex on for Paul I was wondering I think in the prepared remarks, Dan you mentioned that the slight delay for intercept would allow you to have an expanded dataset for the top line I Wonder if you could elaborate a little bit more on kind of what that looks like and how that would impact the topline data that a couple of other follow ups. Thanks.

Speaker Change: Hey, Alex. Thanks for your question. Yeah, just real quickly. I think in terms of

Hey, Alex Thanks for your question, Yeah, just real quickly I think in terms of.

Speaker Change: The follow up period what we've what we've looked at is COVID is definitely impacted the front end of the study I think we're really encouraged by the rate of progression, both at the site level and with enrollment. Right now we've got more work to do, but certainly.

The follow up period, what we've what we've looked at as Covid has definitely impacted the front end of the study I think we're really encouraged by the rate of progression both at the site level and with enrollment right now we've got more work to do but certainly the.

Speaker Change: The momentum is building in terms of the follow up period, we are looking at following patients out there with day 168 follow up. There had been some discussion around putting a preliminary top line results a little bit earlier, but I think the prudence would be to carry out the study to that day 168 follow up and allow us to basically have the data set.

The momentum is building in terms of the follow up period, we are looking at following patients out there day 168 follow up.

There had been some discussion around putting a preliminary top line results a little bit earlier, but I think the prudence would be to carry out. The study two that day 168 follow up and allow us to basically have the dataset that would be the basis for the end of phase two meeting and any subsequent.

Speaker Change: that would be the basis for the end of phase two meeting and any subsequent presentation at a major meeting as the data set that's reported on.

<unk> at a major meeting as the as the dataset that's reported on.

Speaker Change: So that's really our goal with the call today was to set expectations both on the timeframe and clarity on what top line results might be and when they would be announced.

So that's really our goal with the with the call today was to set expectations. Both on the timeframe and clarity on what topline results might be and when they would be announced alright.

Speaker Change: But yeah, that makes sense. And I guess, you know, I don't know if you've commented on, you know, how far you are in terms of dosing, but I wonder if you could confirm that you started dosing patients and whether or not you've had a chance to look at blinded safety data and can confirm any.

All right, Yeah that makes sense and I guess, you know I don't know if you've commented on how far you are in terms of dosing, but I wonder if you could confirm that you started dosing patients and whether or not you've had a chance to look at blinded safety data and can confirm any.

Speaker Change: instances of ARIA, and if you can't answer that, that's fine. And then my final question on runway, I wonder if you could talk a little about what's embedded in your expectations for 2025 runway and how that, or if that includes expectations for a phase 2-3 study and how you're thinking about that. Thanks. Yeah, thanks Alex. So in terms of where we are in the study, I think we announced at the end of the third quarter that we dose the first patient. We continue to dose patients at multiple sites.

Instances of ARIA and if you can't answer that that's fine.

And then my final question on runway I Wonder if you could talk a little about what's embedded in your expectations for 2025 runway and how that or if that includes expectations for phase two three study and how youre thinking about that thanks.

Yeah. Thanks, Alex So in terms of where we are in the study I think we announced in the at the end of the third quarter that we dose. The first patient we continue to dose patients at multiple sites, we're not providing patient level or cohort level information at this point I can I can say that there is nothing that we have seen and we have looked at blinded safety data.

Speaker Change: We're not providing patient level or cohort level information at this point. I can say that there is nothing that we have seen and we have looked at blinded safety data that has suggested us to modify or shift our expectations both in terms of the study design and duration. So we're, it's really just more of an operational element.

Data that has suggested us to modify or shift our expectations. Both in terms of the study design and duration. So we're.

It's really just more of an operational element.

Speaker Change: I think from the runway, the cash runway perspective, we've always envisioned, you know, part of the capital strategy, you know, from the B and as well as the IPO was to ensure that we have the resources on hand to hit multiple clinical milestones. So we do think, you know, the Intercept AD.

I think from the runway the cash runway perspective, we've always envisioned to be a part of the capital strategy from the B and as well as the IPO was to ensure that we had the resources on hand to hit multiple clinical milestones. So we do think the intercept a D day.

Speaker Change: data set, essentially that safety target engagement in general observations to support moving forward into a phase two, three study.

Dataset essentially that safety target engagement in general observations to support moving forward into a phase three study.

Speaker Change: um you know it is intact and in fact that the resources on hand would allow us to fund

It is intact and in fact that the resources on hand would allow us to fund a phase two study to its completion into demonstration of proof of concept.

Speaker Change: phase two study to its completion and to demonstration of proof of concept.

So I think the.

The markets have been a bit volatile in this recent period, but we're feeling at a minimum that we have the runway provided the product performs as we will hope in the intercept study to at least carried into the two to a phase II study.

Great. That's helpful. Thank you.

Our next question comes from Geoff Meacham with Bank of America.

Good afternoon. This is Jason on for Jeff. Thanks, So much for taking our questions.

Speaker Change: uh... wanted to get your broader level comments on

Wanted to get your broader level comments on.

Speaker Change: the regulatory environment. Certainly there's, on one hand, FDA has signaled a more permissive attitude, potentially towards the approval of Alzheimer's treatments, while at the same time, CMS has kind of.

Obviously, the regulatory environment, certainly there's on one hand, FDA signaled more permissive attitude potentially towards the approval of Alzheimers treatments. While at the same time CMS is kind of done the opposite and suggested a much more.

Great.

Environment in terms of reimbursement, but has has this dynamic influenced your thinking at all as far as moving forward.

Speaker Change: Has this dynamic influenced your thinking at all, as far as moving forward with the results of the phase two and a willingness?

With the results of the phase II and a willingness to move forward with a phase two three and then what dynamics are you specifically looking for as you think about putting these trials together, obviously, it's a little early but would love to get your thinking on this.

Speaker Change: forward with a phase two, three, and then, you know, what dynamics are you specifically looking for as you think about, you know, putting these trials together. Obviously it's a little early, but we'd love to.

Speaker Change: Jason, thanks for the question, and it's a good one. And I will say, you know, we'll all learn a little bit more on the basis of the CMS determination on the 11th of April . So that is, I think, an important development for the Alzheimer's drug development field. We're tuned into that. I think we will also be observant of, you know, other study readouts and regulatory actions over the course of the next 12 months.

Hey, Jason Thanks for the question and it is a good one and I will say.

We will all learn a little bit more on the basis of the CMS determination on the 11th of April . So that is I think an important development for the.

The Alzheimers drug development field.

Tuned into that I think we will also be observing of other study readouts and regulatory actions over the course of the next 12 months.

Speaker Change: To be clear, our plan is to take the Intercept AD dataset into an end of phase two type interaction with the FDA with those results and really establish the basis for the next study to be either a phase two or if certain criteria are met on an interim basis, move to a phase three study. The possibility of submitting on the phase two data exists, but I think we'll have, it's probably too early for me to speculate as to how and when that would come about.

To be clear our plan is to take the intercept <unk> dataset into an end of phase II type of interaction with the FDA with those results and really establish the basis for the next study to be either a phase two or if certain criteria are met on an interim basis move to a phase III study the possibility of submitting on the.

These two data exists, but I think we will have it's probably too early for me to speculate as to how and when that would come about in and again, we're going to learn much from the additional regulatory interactions that some of our peers will undertake in in the next 12 18 months.

Speaker Change: And again, we're going to learn much from the additional regulatory interactions that some of our peers will undertake in the next 12, 18 months. Perfect. Really, thank you for the...

Perfect really thank you for the color.

Our next question comes from Judah Frommer with credit Suisse.

Speaker Change: Yeah. Hi guys. Thanks for taking the questions. Maybe just a quick follow up on that one. Maybe just your thoughts on pricing for a beta antibodies, right? Obviously.

Yeah, Hi, guys. Thanks for taking the questions maybe just a quick follow up on that one maybe just your thoughts on pricing for a beta antibodies right. Obviously, Andrew Helms started at a higher price than where it is now and kind of how that might factor or maybe not affect your internal pricing assumptions in there.

Speaker Change: started at a higher price than where it is now and kind of how that might affect or maybe not affect your internal pricing assumptions. And then beyond that, is it right to think about now potentially having longer follow-up for those earlier cohorts when we do get the phase 1 data? And if so, how might that affect the Cogstate battery? Would that be given, you know, I guess beyond those 168 days for the earlier cohorts?

Beyond that is is it right to think about now potentially having longer follow up for those earlier cohorts. When we do get the phase one data and if so how might that affect.

The Cogs state battery.

Would that be giving I guess beyond those 168 days for the earlier cohorts.

Speaker Change: Yeah, hey, thanks, Judah. In terms of pricing, and like I think we have, you know, we really

Yeah, Hey, thanks, Judy in terms of pricing.

I think we have we really.

Speaker Change: haven't adopted or changed any of our particular models. I mean, I think that the Biogen history suggested they came out high relative to maybe expectations. They made a modification. We'll see where CMS goes. I think that we have.

Haven't adopted or changed any of our particular models I mean, I think that the Biogen history suggests that they came out.

Hi relative to maybe expectations. They made a modification we will see where CMS CMS goes I think that we have.

Speaker Change: You know, we're cognizant of looking at cost of materials and dosing and ensuring that we have, you know, pharmaceutical margins at a particular price point that may be in a marketplace that has, you know, several other products approved.

We're cognizant of looking at.

Cost of materials, and dosing and ensuring that we have pharmaceutical margins at a particular price point that.

Maybe in a marketplace that has several other products.

Speaker Change: So we, I guess the simple answer is it's probably a little bit too early for us to go into a pricing discussion, but again, we're in a position to look at what, how the market develops, you know, what reimbursement rates are available. And ultimately, you know, our goal is to generate differentiated data, both in terms of ARIA safety and ultimately with clinical efficacy. And I think those are factors that certainly would contribute to a pricing strategy that we would pursue in the future.

Peru.

I guess the simple answer is it's probably a little bit too early for us to go into a pricing discussion, but again, we're in a in a position to look at how the market develops.

Reimbursement rates are available and ultimately our goal is to.

Generate differentiated data both in terms of are you safety and ultimately with clinical efficacy and I think those are factors that certainly would fact would contribute to a pricing strategy that we would pursue in the future.

Speaker Change: I think on the second question, in terms of the follow-up duration, essentially this gives us additional imaging and other clinical assessments, primarily for safety. You referenced the Cogstate battery, and yes, we are employing a computer battery. Really in the interest that if there is an acute pharmacodynamic effect based on neutralizing the toxicity of A beta-ligamers, that that highly repeated and highly sensitive.

I think on the on the second question in terms of the follow up duration.

Essentially this gives us additional additional imaging and other clinical assessments, primarily for safety you referenced the Cogs state battery and yes, we are employing.

Our computer battery really any interest.

If there is an acute pharmacodynamic effect based on neutralizing the toxicity of EBIT of oligomers that that.

Highly repeated in highly sensitive.

Speaker Change: measure administered on a computer, would be able to detect those types of signals. We really, again, just a word of caution, we're not powered or, you know, calling that out as a criteria for the, for this phase one study. And I think it's unlikely that

Measure administered on a computer would be able to detect those types of signals. We really again, just a word of caution we're not powered or.

Calling that out as a criteria for the phase one study and I think it's unlikely that.

Speaker Change: those measurements would impact the day 168 follow up, which is really just a full determination of the safety profile.

Those measurements would impact day 168 follow up which is really just a full determination of the safety profile.

Got it thank you.

Speaker Change: And I'm not showing any further questions at this time, I'd like to turn the call back over to Dan for.

And I'm not showing any further questions at this time I'd like to turn the call back over to Dan for any closing remarks.

Speaker Change: Well, thank you, Kevin, and thank you, everybody, for joining our first public company earnings and business highlights call. We look forward to reengaging with you in the near future and updating you on our progress, both in the clinic and with the company, so thank you, everyone.

Well, thank you Kevin and thank you everybody for joining our first public company earnings and business highlights call. We look forward to engaging with you in the near future and updating you on our progress.

Both in the clinic and with the company. So thank you everyone.

Speaker Change: Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect and have a wonderful day.

Okay.

Speaker Change: ?? ?? ??

Okay.

Okay.

[music].

Yeah.