Q4 2022 Acumen Pharmaceuticals Inc Earnings Call

Speaker 1: Thank you for standing by. Welcome to Acumen Pharmaceuticals full year 2022 conference call in 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.

Speaker 1: To ask a question during the session, you will need to press star 1 1 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.

Speaker 1: Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Braun, head of investor relations. Please go ahead. DR.

Speaker 2: Thank you, Michelle. Good morning and welcome to the Acumen Conference call to discuss our business update and financial results for the year ended December 31, 2022. With me today are Dan O'Connell, our Chief Executive Officer, Dr. Eric Simers, our Chief Medical Officer.

Speaker 2: Matt Duga, our Chief Financial Officer and Chief Business Officer.

Speaker 2: Before we begin, we encourage listeners to go to the investors section of the Acumen website to find a press release issue this morning and related slide presentation that we'll discuss today. Thank you for joining us today.

Speaker 2: Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.

Speaker 2: Please see slide two of the accompanying 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.

Speaker 2: We undertake no obligation to update or revise the information provided on this call or in any accompanying presentation as a result of new information or future results or developments.

Speaker 2: After our prepared remarks, we will open the call for Q&A. Now I'll turn the call over to Dan.

Speaker 3: Thank you, Alex. Good morning and thank you everyone for joining us today. 2022 was a pivotal year for Acumen marked by significant progress in advancing the critical development of ACU-193, the first monoclonal antibody tested in Alzheimer's patients that was discovered in the first year.

Speaker 3: and developed to selectively target soluble in-wood beta oligomers.

Speaker 3: Over the course of the year, we received fast-track designation from the FDA, added experience and talented members to our team to guide our development plan, and completed important CMC work to scale production in anticipation of upcoming Phase II study.

Speaker 3: In February of this year, we announced the completion of enrollment in our Phase 1 intercept AD trial, which sets us up to report top line results in the third quarter.

Speaker 3: The intercept AD results are anticipated to provide important proof of mechanism information for AC193, including safety, pharmacokinetic, and target engagement data that ERIC will speak to in greater detail shortly.

Speaker 3: Thus far, we are encouraged by preliminary PK and blinded safety data observed to date, which supports our thesis that at appropriate dose levels, an antibody selected for A beta oligomers, such as AC193, may provide a differentiated product profile in the fight against Alzheimer's disease. I want to briefly comment on the protocol amendment we disclosed in early February .

Speaker 3: We opted to amend the trials protocol to reduce dose level and cohort 7 are last cohort to 25 makes milligrams per kilogram every two weeks. We believe the 25 milligram per kilogram dose every two weeks and cohort 7 will provide us with more meaningful dose ranging safety and target engagement information in support of establishing clinical.

Speaker 3: to discuss the design of our phase 2 tree study, a design that incorporates an interim decision to expand the study.

Speaker 3: from a phase two size to a phase three study.

Speaker 3: On the CMC fund, we remain low position to scale manufacturing to have sufficient road supply to meet requirements of our current development plan.

Speaker 3: In addition, we have made meaningful progress in assessing various options for potential development of a subcutaneous formulation as part of our AC193 product development plans. We intend to continue to explore such options based on data generated in our Phase 1 study.

Speaker 3: On a final note, I would like to acknowledge the significant change in the overall treatment landscape for Alzheimer's disease over the past year. The positive clarity AD results from the Canemab in the fall of 2022, meaningfully advance the field. Because it is a protophiable targeting antibody, the Canemab has proven renewed interest in the role that's soluble, aggregated, A-beta species.

Speaker 3: such as EBITDA ligaments and EBITDA protocols may play in the pathology of all summers.

Speaker 3: and how targeting these species can contribute to safe and beneficial treatment options for patients.

Speaker 3: Furthermore, the negative graduate study results for Canton, Aramab, a plaque targeting antibody.

Speaker 3: support the hypothesis that for plaque targeting antibodies, clinical efficacy can only be achieved with a near complete removal of amyloid plaque.

Speaker 3: Most recently, the negative A4 results for civil and asymptomatic and AB8, a modern or targeting antibody. Reinforce the evidence that targeting moderners may not be a viable means to produce clinical benefit, even when intervening at the earliest stages of disease.

Speaker 3: Aside from these clinical datasets, the field is also seeing advancement with both fluid and imaging biomarkers, which continues to develop rapidly and could offer a diverse set of future alternatives that are predictive of effects in AD beyond amyloic pet imaging. Given the size of the disease burden, we are encouraged by these additional clarity and

Speaker 3: provided to the field.

Speaker 3: and look forward to additional upcoming data from many companies with differing approaches.

Speaker 3: At Acumen, we recognize the importance of these advances and strive to use the learnings to inform our approach to developing AC193 as a potential disease-modifying therapy in early Alzheimer's patient population. To this end, we look forward to sharing our intercept AD top-line data with you in the third quarter, a dataset we believe will be informative from a safety target engagement and dose ranging perspective.

Speaker 3: With that, I'll hand the call over to Dr. Seymour's. Eric.

Speaker 4: Thanks, Dad. Dan and good morning everyone from Gutenberg, Sweden, where I arrived today to attend the ADP meeting that's happening this week.

Speaker 4: We are delighted to have completed enrollment of our phase one intercepted AD trial as we announced in February . This is a true testament to the hard work and dedication shown by our team and by the investigators, the site personnel, our CRO, and most importantly, the patients, families, and their study partners. I would like to thank them for their ongoing support in advancing our...

Speaker 4: sad mad study with 65 patients enrolled with early Alzheimer's disease.

Speaker 4: The objectives of the trial are to evaluate safety and tolerability, evaluate PK, and establish target engagement for ACU-193 administered intravenously.

Speaker 4: The primary trial endpoints are focused on safety and PK. As far as safety and in support of our protocol amendment disclosure in February , we announced that we had seen two cases of asymptomatic REAE as of January 31st in this blinded trial.

Speaker 4: Based on the preclinical data, we had expected less RIA than that seen with some other monoclonal antibodies at their highest doses. And the preliminary blinded cases we observed in the first quarter were aligned with that expectation. We remain encouraged that the safety profile of ACU-193 today.

Speaker 4: will support targeting soluble Emily data allegomers.

Speaker 4: We also note that REAE cases do provide evidence of central pharmacology.

Speaker 4: that AC-193 crosses the blood brain barrier in sufficient cold heavilyieve ??? worst fact,

Speaker 4: Keep in mind as well that cohort 6 is ongoing at a dose of 60 milligrams per kilogram every four hours, which is considerably higher than doses pursued by several other antibodies, including adicantamab, lachantamab, and dynanamab. The preliminary PK data we disclose support this line of things.

Speaker 4: Oligomer concentrations in CSF are generally reported to be less than 2 picomolar, which is a very low concentration compared to other soluble species such as A-beta monomers.

Speaker 4: If this is the case, a dose of 25 milligrams per kilogram every four weeks could be a viable dose to test in the next phase of our program for ACU193.

Speaker 4: Turning to target engagement, as many of you know, the assay for our target engagement is designed to measure the complex of A-beta-Olligamers bound to AC-193 in CSF.

Speaker 4: Simply detecting that complex after administration will satisfy the target engagement threshold.

Speaker 4: In non-clinical studies, Merck was able to measure these complexes in brains from transgenic mice after AC193 administration using an immunosamol. Acumen is developing a conceptually similar methodology for the intercept AD trial to look at CSF using proprietary materials that increase the assays.

Speaker 4: specificity for both AC193 and A-Bata Oligomers, and thus specificity for the AC193 Oligomer complex.

Speaker 4: Importantly, we will be performing test runs of this assay prior to our database block to ensure the sensitivity is optimized.

Speaker 4: Exploratory measures that are built into our Phase I study include computerized cognitive testing for signs of early effects and arterial spin labeling with MRI scans to understand if cerebral blood flow is increased.

Speaker 4: While these analyses are exploratory and are unlikely to result in a statistically significant signal in this small study with a short treatment duration, the detection of a potential signal would suggest important central pharmacodynamic effects.

Speaker 4: Depending on our phase one results, these measures may be employed in subsequent clinical trials using ACU-193.

Speaker 4: Turning toward our upcoming Phase 2-3 clinical study, the team has been working diligently to develop an algorithm that would include evaluations by the data monitoring committee of clinical measures, computerized cognitive testing, and biomarkers to enable a go-no-go decision to scale a Phase 2 study to a Phase 3 study.

Speaker 4: We are confident that the algorithm we finalize will provide a rigorous method to allow a go-no-go decision to expand from phase 2 to phase 3.

Speaker 4: And with that, I'll turn the call over to Matt.

Speaker 4: Thank you, Eric. Good morning, everyone. Our complete year end 2022 financial results are available in the press release. We issued this morning and in our 10K, that will be filed later this afternoon.

Speaker 5: We ended 2022 with approximately $193 million in cash and marketable securities on the balance sheet, and we continue to expect that cash runway to last through 2025.

Speaker 5: R&D expenses were approximately $32.4 million in 2022. The increase over the prior year was primarily due to the increased activity in the ongoing intercept AD trial.

Speaker 5: GNA expenses work $12.9 million in 2022 and the increase over the prior year, primarily the result of increased headcount.

Speaker 5: This led to a loss from operations of $45.2 million in 2022.

Speaker 5: Regarding our exposure to Silicon Valley Bank, we had approximately $1.7 million in cash in our operating accounts there as of March 10, 2023, all of which has been moved to another institution.

Speaker 5: In conclusion, we remain well resourced to execute against our strategic priorities over the next few years. We look forward to reporting top-line data for intercept AD in the third quarter of 2023 and will remain financially disciplined as we use our capital to advance our clinical program for ACES.

Speaker 1: your name to be announced.

Speaker 1: To withdraw your question, please press Store 1-1 again.

Speaker 1: Please stand by while we compile the Q&A roster.

Speaker 1: First question comes from Paul Matisse with Feeful. Your line is now open. Hey, thanks so much. On the interim analysis that you're planning, how is this similar difference to just your typical interim? Yes.

Speaker 3: where a blinded group looks at the data, recommend sample size adjustments or to stop the study.

Speaker 6: No, I have one for you. Thank you.

Speaker 4: Hey, thanks, Paul. I was going to invite Eric to comment on that. There's a simple explanation, I think. Right, yeah. Well, of course, you're right. A lot of times, interim analyses are done to adjust sample sizes. Usually, that's based on purely a statistical look at the data.

Speaker 4: One thing I should just emphasize is that it's not a futility analysis, and so everyone should be clear about that. But the interim analysis itself is actually quite a bit more complex than the sort of thing that's done just to adjust sample size. In other words, we, as I discussed, we're developing the algorithm.

Speaker 4: But we'll look at the clinical measures. I mean, we have things like the CDR cell boxes in the trial. And so in a little study like this, it would be surprising to see a drug effect there, but we'll look at those things. We'll look at the ADAS-CoG. And again, we'll look at our computerized cognitive testing and some of the MRI results.

Speaker 4: and also some biomarkers.

Speaker 4: And we will develop this algorithm to give to the DMB. And the DMB, if the algorithm is successful, so to speak, then the study will be scaled up to the side of the phase three study. If it doesn't fulfill the algorithm. The algorithm.

Speaker 4: then it will be completed as a Phase II study. So at a minimum, we'll complete the next study as a Phase II study.

Speaker 6: Okay, thanks. And then you've talked a little bit more about enthusiasm. Oh, sorry, Dan. Go ahead.

Speaker 3: Well, I was just going to say, and Paul, of course, the 2-3 design is really intended to be the fastest path to a potential registration for the product, hypothetically. So if that's not obvious, I just want to make that comment. No, that's clear. Thank you. And then you talked more about confidence in this 25 Maycartig dose. Is that based on anything you're seeing? I guess, what if?

Speaker 3: What if you don't see a clear dose response?

Speaker 3: on the target engagement assay. Does that mean you might take forward a lower dose? Like how are you guys thinking about these scenarios in the second half of this year? Thank you.

Speaker 3: Yeah, thank you. So, I mean, I'll just come and I think we really made the amendment to the protocol amendment in February based on some observations in the study, including the and the case.

Speaker 3: So I don't think we're not in a position to continue to roll out information until the third quarter. I do think that when we made the decision to modify the cohort 7 dose level, it became sort of obvious to us at the time given that might be a viable dose in terms of just the overall drug required to dose at 25 megs versus 60 every couple of weeks, which was the original concept.

Speaker 3: and the 60 makes per cake that's ongoing in cohort 6.

Speaker 1: Thank you. Please stand by.

Speaker 1: Please stand by for our next question.

Speaker 1: The next question comes from Tom Schrader with BTIG. Your line is now open.

Speaker 4: Thanks. If you had more to say, it's almost the same question anyway. So I have a little bit of a question about the world of plaque removal. There's still some controversy about how important it is. I think we might call it confusion. But what's your sense about where the FDA is on that issue and how important that would be in an interim look? Are they going to be okay with the trial?

Speaker 4: that is ignoring plaque removal or is that kind of all your own business. But given that it's kind of unknown how important it is, how much do you have to think about it going into a trial with an interim look? So maybe I can...

Speaker 4: Try that so that from an FDA standpoint in the plaque reduction that was for an accelerated approval. In other words, FDA considered plaque reduction to be reasonably likely to predict a clinical effect. And that led then to the accelerated approval. Now one of the things that I think has become even more clear, I think it was clear before, but

Speaker 4: of an accelerated approval or any sort of a regulatory approval. It's for our internal decision making in terms of the phase two study and then scaling it up to a phase three study. So there really isn't a regulatory piece to the interim analysis as we're doing it.

Speaker 3: Great, thank you. And I think in time just to come here, we are doing a look at in the current study and would anticipate doing it. Again, not that we would expect to see it move dramatically, but just as a kind of the convention standard practice.

Speaker 4: Okay, great. Thanks for the answer.

Speaker 1: Please stand by for our next question. Our next question comes from Colin Bristow with UBS. Your line is now open.

Speaker 7: Morning everyone, this is for Colin. Thanks for taking our questions. So we have 2 questions and a full up if we may do the 1st question is for patients in the cohort 6 in our last correspondence. You noted they have not yet received MRI scans.

Speaker 7: Just wondering if they have received by now and if so could you provide any 50 updates? And then, second question, more general. Do you think there's a general correlation to dose a oligmo-tugged antibody more frequently than those core plug-tugged ones, given the faster turnover kinetics here? Thank you.

Speaker 3: I think, thanks for your question. I think on the first one, as I mentioned, and as Eric mentioned, we've disclosed the RA cases back in February in conjunction with protocol amendment. We, and Eric just noted the cohort 6 continues to proceed for protocol. So we haven't provided any other information in terms of RA cases and so forth.

Speaker 3: I think maybe I would turn it to Eric in terms of the dosing frequency question, which respect to an illegal antibody. I mean, Eric, you would care to comment on that aspect of things question.

Speaker 4: Yeah, so it's a really interesting question. And I think what you're really asking is that for an antibody that targets plaque, that antibody binds to the plaque, it actually starts in a inflammatory response with microglia. Yeah.

Speaker 4: And so it's not necessarily so dependent on the PK that you would see even in spinal fluid at any given time since once it's found a plaque, it's obviously not going to show up in spinal fluid. In our case, it may be a little bit more straightforward in that we do want to show that we're in antibody excess. In other words, that you have more antibody there than you have...

Speaker 4: But I think in our case, again, I think the important thing is to show that we're in antibody access.

Speaker 8: Thank you much.

Speaker 7: Sorry, yeah, sorry, thank you for providing all the colors really helpful. We have a full up question, which kind of like, echoing Tom's earlier question. Also, what Dan has mentioned, you know, prepare remark on a for so we understood solo news map is primarily.

Speaker 7: sorry, primarily a monomer targeting, but it had some capacity to oligmas, although it does not touch any plugs. So there were some concerns following solar needs maps completely failure. That maybe some love of plug clearance are still needed for the best treatment advocacy. We curious to hear your thoughts.

Speaker 4: And if you could provide any colors to us, we'll be greatly appreciated. Thank you so much. Well, then, you want me to go ahead and take that since I have a bit of familiarity with Solonazamab.

Speaker 4: First of all, for the A4 resolve, of course, there's really just been press releases and we'll need to see all the data. What for me was a bit surprising and interesting is that actually even though there were no statistical differences, the trends actually favored placebo over drug.

Speaker 4: And that was at a dose of 1600 milligrams every four weeks.

Speaker 4: Well, when Tom A. Zimab was given to people with mild Alzheimer's disease at 400 milligrams every four weeks, the trends were very consistent in terms of favoring drug.

Speaker 4: So why you didn't see that with the higher dose of solanazemab is a bit of a mystery, and I think we'll have to see all the data to understand that. But again, our thesis has always been that if you want to target plaque, you really...

Speaker 4: you could approach this as saying, well, let's target monomers and then we need a little bit of plaque reduction. I think that probably would not end up being successful.

Speaker 4: And Eric, to your knowledge, just to clarify, are you aware of any oligomer binding properties for solanoids? It's almost a pure monomer targeting antibiotic, is my understanding. Well, and that's always been my... Now, you can always find publications where somebody shows a little binding to this or that, and typically those are in vitro.

Speaker 3: really 193 has been developed to principally target oligomers and not have much

Speaker 3: interactions with moderate.

Speaker 7: Thank you so much.

Speaker 1: Please stand by for our next question. Next question comes from Judah, Burmer with Credit Sleece. Your line is now open. Yeah, hi. Good morning, guys. Thanks for taking the question.

Speaker 9: Just getting back to the protocol amendment and probably the key question we got around that, you know, how are you thinking about potential impact to a commercial profile? And I guess a reimbursement profile for 193, does this change the story in some way in that, you know, you might need.

Speaker 9: MRI monitoring when you thought you might not have needed that prior and have you had any preliminary discussions with payers on sort of acceptable levels of REI or how that might compare to the Can-A-Map or anything else that comes between now and then.

Speaker 3: Yeah, thanks, Julie. Good question. So I think, you know, in terms of.

Speaker 3: A lot wrapped into that. I think in terms of the safety profile, you know, we continue to believe that oligomer targeting antibodies such as 193 may offer an attractive safety profile relative to plaque targeting antibodies. And you know, the LikenB does have a rate of RAE in 12.5%. So that's sort of...

a safety benchmark that we use internally. In terms of dropping the 25 mgs per kg, that becomes a dose level that may be more amenable to a subcutaneous formulation. So that was actually part of the consideration in early February as we contemplated what to do really with cohort set and what made the most sense.

from a programmatic standpoint. So that was, you know, and we'll see. As I mentioned earlier on the call, we've looked at a couple of different options as to moving 193 at some point into a subcutaneous.

format and that modified dose of the Procord 7 does provide important PK information that will help inform the prospects of that. We haven't had any payer interactions per se. I do think that as we've

In vision, the next study, we've always anticipated routine MRI scans for safety and other, you know, for general development purposes. I think that study is much more likely to be instructed as to what would be required commercially. So we just won't have enough product exposure in this, in the intercept A.D.

Study to definitively say what's required from a safety and really what's required from the overall. This is a phase 1 study in terms of the overall RIA rates. Thank you.

As a reminder, to ask a question, please press star 11 on your telephone.

Standby for our next question. I show no further questions at this time. I would now like to turn the conference back to Alex for closing remarks.

Thanks, Michelle. Thanks everyone for joining us today. As always, we're available for follow-ups. If you have any additional questions, so please reach out to us at the company and have a great Monday.

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

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Thank you for standing by. Welcome to Acumen Pharmaceuticals' 4-year 2022 conference call in WebKF.

At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session.

To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised.

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 speaker today, Alex Braun, head of investor relations. Please go ahead. Please stand by.

Thank you, Michelle. Good morning and welcome to the Ackerman conference call to discuss our business update and financial results for the year-end of December 31, 2022.

With me today are Dan O'Connell, our Chief Executive Officer, Dr. Eric Simers, our Chief Medical Officer, and Matt Zuga, our Chief Financial Officer and Chief Business Officer.

Before we begin, we encourage listeners to go to the investors section of the Acumen website to find a press release issue this morning and related slide presentation that we'll discuss today. Thank you for joining us today.

Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans.

These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.

Please see slide two of the accompanying presentation. Our press release issued this morning in our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to different materialism of expressed our implies 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 or developments.

After our prepared remarks, we will open the call for Q&A. Now I'll turn the call over to Dan.

Thank you, Alex. Good morning and thank you everyone for joining us today. 2022 was a pivotal year for Acumen marked by significant progress in advancing the critical development of ACU-193, the first monoclonal antibody tested in Alzheimer's patients that was discovered and developed to selectively target soluble in the beta oligomers. Over the course of the year, we received fast-track designation from the FDA.

added experienced and talented members to our team to guide our development plan, and completed important CMC work to scale production in anticipation of upcoming Phase II study. In February of this year, we announced the completion of enrollment in our Phase I intercept AD trial, which sets us up to report top-line results in the third quarter. The intercept AD results are anticipated to provide important proof of mechanism information

profile in the fightinga after all of his disease.

I want to briefly comment on the protocol amendment we disclosed in early February just prior to completion of enrollment. Based on the preliminary CSF PK data observed that indicated that AC193 antibody concentrations were in excess of reported ABA to oligomer concentrations. And considering the blinded case of REE observed in the cohort four at the time.

We opted to amend the trials protocol to reduce dose level and cohort 7, our last cohort to 25 makes milligrams per kilogram every two weeks. We believe the 25 milligrams per kilogram dose every two weeks and cohort 7 will provide us with more meaningful dose ranging safety and target engagement information in support of establishing.

in the fourth quarter to discuss the design of our phase 2 tree study, a design that incorporates an interim decision to expand the study.

from a phase 2 size to a phase 3 study. On the CMC front, we remain well positioned to scale manufacturing to have sufficient drug supply to meet requirements of our current development plan.

In addition, we have made meaningful progress in assessing various options for potential development of a subcutaneous formulation as part of our AC193 product development plans. We intend to continue to explore such options based on data generated in our Phase 1 study.

On a final note, I would like to acknowledge the significant change in the overall treatment landscape for Alzheimer's disease over the past year. The positive clarity AD results for lakanumab in the fall of 2022 meaningfully advanced the field. Because it is a protofiable targeting antibody, lakanumab has driven renewed interest in the role of a soluble aggregated A-beta species.

such as A beta ligamers and A beta protofibilis may play in the pathology of Alzheimer's, and how targeting these species can contribute to safe and beneficial treatment options for patients.

Furthermore, the negative graduate study results for Canton Air Map, a plaque targeting antibody support the hypothesis that through plaque targeting antibodies, clinical efficacy can only be achieved with the near complete removal of ANOA plaque.

Most recently, the negative A4 results for cilinazomab and A-beta monomer targeting antibody reinforced the evidence that targeting monomers may not be a viable means to produce clinical benefit even when intervening at the earliest stages of disease.

Aside from these clinical data sets, the field is also seeing advancement with both fluid and imaging biomarkers, which continue to develop rapidly and could offer a diverse set of future alternatives that are predictive of effects in AD beyond amyloid PET imaging.

Given the size of the disease burden, we are encouraged by the additional clarity these data have provided to the field and look forward to additional upcoming data from many companies with differing approaches.

At Acumen, we recognize the importance of these advances and strive to use the learnings to inform our approach to developing AC193 as a potential disease-modifying therapy in general health centers patient population.

To this end, we look forward to sharing our intercept AD top-line data with you in the third quarter, a dataset we believe will be informative from a safety target engagement and dose ranging perspective.

With that, I'll hand the call over to Dr. Simers. Eric? Thanks, Dan, and good morning, everyone, from Gutenberg, Sweden, where I arrived today to attend the ADP meeting that's happening this week. We are delighted to have completed enrollment of our Phase 1 intercept AD trial, as we announced in February . When we call the name for the file of the

This is a true testament to the hard work and dedication shown by our team and by the investigators, the site personnel, our CRO, and most importantly, the patients, families, and their study partners. I would like to thank them for their ongoing support in advancing our understanding of the potential of ACU-193.

With top-line results now expected in the third quarter, I'd like to take a few minutes to provide some context around our expectations for those results.

Our phase one study is a randomized placebo controlled first in humans SAD-MAD study with 65 patients enrolled with early Alzheimer's disease. The objectives of the trial are to evaluate safety and tolerability, evaluate PK, and establish target engagement for ACU 193 administered in the United States.

of January 31st in this blinded trial.

Based on the preclinical data, we had expected less ARIA than that seen with some other monoclonal antibodies at their highest doses. And the preliminary blinded cases we observed in the first quarter were aligned with that expectation. We remain encouraged that the safety profile of ACU-193 today is achieved by developing i Randlelestine syndrome and batches of ARIASam levels as Thunder renters have reported previous Deep Surators in all four of the C see and were determined to visit on 2 November 2017 13Bar pillow and he explained that the label is not definite and his own

will support targeting soluble amyloid beta oligomers.

We also note that REE cases do provide evidence of central pharmacology.

that ACU-193 crosses the blood-brain barrier in sufficient quality for the central effect. Keep in mind as well that CoV-6 is ongoing at a dose of 60 milligrams per kilogram every four hours, which is considerably higher than doses pursued by several other antibodies, including adacamab, and american aben

that were substantially above the levels reported for oligomers.

Oligomer concentrations in CSF are generally reported to be less than 2 picomolar, which is a very low concentration compared to other soluble species such as A-beta monomers.

If this is the case, a dose of 25 milligrams per kilogram every four weeks could be a viable dose to test in the next phase of our program for ACU-193.

Turning to target engagement, as many of you know, the assay for our target engagement is designed to measure the complex of A-beta oligomers bound to AC193 in CSF.

Simply detecting the complex after administration will satisfy the target engagement threshold. In nonclinical studies, Merck was able to measure these complexes in brains from transgenic mice after AC193 administration using an immunoassay.

Acumen is developing a conceptually similar methodology for the intercept AD trial to look at CSS using proprietary materials that increase the assay's specificity for both ACU193 and A beta oligomers and thus specificity for the ACU193 oligomer complex.

Importantly, we will be performing test runs of this assay prior to our database block to ensure the sensitivity is optimized.

Exploratory measures that are built into our Phase I study include computerized cognitive testing for signs of early effects and arterial spin labeling with MRI scans to understand if cerebral blood flow is increased.

While these analyses are exploratory and are unlikely to result in a statistically significant signal in this small study with a short treatment duration, the detection of a potential signal would suggest important central pharmacodynamic effects. Depending on our phase 1 results, these measures may be employed in subsequent clinical trials.

computerized cognitive testing and biomarkers to enable a go no-go decision to scale a phase two study to a phase three study. We are confident that the algorithm we finalize will provide a rigorous method to allow a go no-go decision to expand from phase two to phase three. And with that, I'll turn the call over to Matt.

Thank you, Eric. Good morning, everyone. Our complete year-end 2022 financial results are available in the press release we issued this morning and in our 10K that will be filed later this afternoon. We ended 2022 with approximately $193 million.

year was primarily due to the increased activity in the ongoing intercept AD trial.

G&A expenses were $12.9 million in 2022, and the increase over the prior year primarily the result of increased headcount. This led to a loss from operations of $45.2 million in 2022.

Regarding our exposure to Silicon Valley Bank, we had approximately $1.7 million in cash and are operating accounts there as of March 10, 2023, all of which has been moved to another institution.

In conclusion, we remain well resourced to execute against our strategic priorities over the next few years. We look forward to reporting top-line data for intercept AD in the third quarter of 2023 and will remain financially disciplined as we use our capital to advance our clinical program for ACU193.

your question, please press star 11 again. Please stand by while we compile the Q&A roster. This question comes from Paul Matisse with FIFL. Your line is now open.

Hey, thanks so much. On the interim analysis that you're planning, how is this similar difference to just your typical interim where a blinded group looks at the data, recommend sample size adjustments or stop the study.

I'm going to have one follow up. Thank you. Thanks, Paul. I was going to invite Eric to comment on that. There's a simple explanation, I think.

Right, yeah. So, well, of course you're right. A lot of times interim analyses are done to adjust sample sizes and usually that's based on, you know, purely a statistical look at the data. One thing I should just emphasize is that it's not a futility analysis and so...

But we'll look at the clinical measures. I mean, we have things like the CDR cell boxes in the trial. And so in a little study like this, it would be surprising to see a drug effect there, but we'll look at those things. We'll look at the ADAS-CoG. And again, we'll look at our computerized cognitive testing, some of the MRI results.

and also some biomarkers. And we will develop this algorithm to give to the DMB and the DMB if the algorithm is successful, so to speak, then the study will be scaled up to the size of phase three study.

If it doesn't fulfill the algorithm, then it will be completed as a phase two study. So at a minimum, we'll complete the next study as a phase two study. Okay, thanks. And then you've talked a little bit more about enthusiasm. I'm sorry, Dan, go ahead. Well, I was just going to say, and Paul, of course, the two-three design is really intended to be the fastest path to a potential.

your dose response.

on the target engagement assay, does that mean you might take forward a lower dose? Like, how are you guys thinking about these scenarios in the second half of this year? Thank you. Yeah, thank you, Paul. So, I mean, I'll just comment. I think we really made the amendment, the protocol amendment in February based on some observations in the study, including the PK and the RA case. So I don't think we're not in a position to continue to roll out information until the third quarter.

I do think that when we made the decision to modify the cohort 7 dose level, it became sort of obvious to us at the time, given that might be a viable dose in terms of just the overall drug required to dose at that 25 Mages versus 60 every couple of weeks, which was the original concept for cohorts 7. So

I think we're really encouraged that, you know, sort of the overall thesis for the issue 193 is very much intact and are confident that the modification for cohort 7 in particular gives us more information kind of with a mid-dose level between the 10 mg per kg and the 60 mg per kg that's ongoing in cohort 6.

Thank you. Please stand by. Please stand by for our next question. Next question comes from Tom Schrader with BTIG. Your line is now open.

that would be in an interim look? Are they gonna be okay with a trial that is ignoring plaque removal, or is that kind of all your own business? But given that it's kind of unknown how important it is, how much do you have to think about it going into a trial with an interim look? Thanks.

So maybe I can try that. So from an FDA standpoint in the plaque reduction, that was for an accelerated approval. In other words, FDA considered plaque reduction to be quote, reasonably likely to predict a clinical effect. And that led then to the accelerated approval.

Now, one of the things that I think has become even more clear, I think it was clear before, but as Dan mentioned, if you're going to target plaque, you have to essentially get rid of all of it to have any clinical efficacy. And I think that again, neuromap graduate studies demonstrated that

very well. And in our case, this interim analysis that we're doing is not really in anticipation of an accelerated approval or any sort of a regulatory approval. It's for our internal decision-making in terms of this phase 2 study and then scaling it up to a phase 3 study.

There really isn't a regulatory piece to the interim analysis as we're doing it. All right, great. Thank you. And I think, and Tom, just to copy, we are doing it in the current study and would anticipate doing it, again, not that we would expect to see it move dramatically, but just as a kind of the convention standard practice.

Okay, great. Thanks for the answer. Please stand by for our next question.

Our next question comes from Colin Bristow with UBS. Your line is now open.

Morning everyone, this is for Colin. Thanks for taking our question. So we have 2 questions and a follow up. If we may do the 1st question is for patients in the cohort 6 in our last correspondence. You noted they have not yet received MRI scans. Just wondering if they have received by now and if so.

Could you provide any safety updates? And then second question is more general. Do you think there's a general correlation to Dose A oligomode-targeted antibody more frequently than those core plug-targeted ones, given the faster turnover kinetics here? Thank you. Hi, Teng. Thanks for your question. I think on the first one, as I mentioned, and as Eric mentioned, we disclosed the ARIA cases back in February in conjunction with the protocol amendment. And Eric just noted that cohort 6 continues to proceed per protocol.

So we haven't provided any other information in terms of ARIA cases and so forth. I think maybe I would turn it to Eric in terms of the dosing frequency question with respect to an oligomer antibody. I think Eric, maybe you would care to comment on that aspect of Ting's question.

Yeah, so it's a really interesting question. And I think what you're really asking is that for an antibody that targets plaque. The antibody binds to the plaque, it actually starts an inflammatory response with microglia.

And so it's not necessarily so dependent on the PK that you would see even in spinal fluid at any given time since once it's found a plaque, it's obviously not going to show up in spinal fluid. In our case, it may be a little bit more straightforward in that we do want to show that we're in an area.

was so exciting for us is that we were in antibody access.

And so the situation is a little bit different, you're right, but I think in our case, again, I think the important thing is to show that we're in antibody excess. Thank you much. Yeah, sorry. Yeah. Yeah. Sorry. Thank you for providing all the colors really helpful.

We have a follow-up question, which kind of like, echoing Tom's earlier question, also what Dan has mentioned in a prepared remark on A4. So, we understood Solonism map is primarily, sorry, primarily monomer targeting, but it has a high sound capacity to oligomers.

to hear yourselves. And if you could provide any colors to us, it would be greatly appreciated. Thank you so much.

Well, Dan, you want me to go ahead and take that since I have a bit of familiarity with Solanae Zumab.

First of all, for the A4 results, of course there's really just been press releases and we'll need to see all the data. What for me was a bit surprising and interesting is that actually even though there were no statistical differences, the trends actually favored placebo over drug.

and that was at a dose of 1600 milligrams every four weeks. Well, when solanazemab was given to people with mild Alzheimer's disease at 400 milligrams every four weeks, the trends were very consistent in terms of favoring drug. So why you didn't see that with the higher dose of solanazemab.

noise map has taught the field that a little bit of plaque reduction doesn't really get you anywhere. So I don't think that you could approach this as saying well let's target monomers and then we need a little bit of plaque reduction. I think that probably would not end up being successful. And Eric, you're not, just to clarify, do you have, are you aware of any oligomer binding?

that I'm aware of has really been quite consistent that actually solanazemab is remarkably specific for monomers.

Really, 193 has been developed to principally target oligomers and not have much

interactions with moderate. Thank you so much.

Please stand by for our next question. Next question comes from Judah Fermer with Credit Suisse. Your line is now open.

Yeah, hi, good morning guys. Thanks for taking the question. Just just getting back to the protocol amendment and probably the key question we got around that, you know, how are you thinking about potential impact to a commercial profile? And I guess the reimbursement profile for 193.

Acceptable levels of Aria are how that might compare to the kind of map or anything else that comes between now and then Yeah, thanks to the good question. So I think you know in terms of

A lot wrapped into that. I think in terms of the safety profile, you know, we continue to believe that oligomer targeting antibodies such as 193 may offer an attractive safety profile relative to plaque targeting antibodies. And you know, the LikenB does have a rate of RAE in 12.5%. So that's sort of a safety benchmark that we use internally.

In terms of dropping the 25 megs per kg, that becomes a dose level that may be more amenable to a subcutaneous formulation. So that was actually part of the consideration in early February as we contemplated what to do really with cohort SEP and like what made the most sense from a programmatic standpoint. So that was, and we'll see, as I mentioned earlier on the call, we've looked at a couple of different options as to moving 193 at some point into a subcontainment.

That study is much more likely to be instructive as to what would be required commercially. So we just won't have enough product exposure in this in the intercept study to definitively say what's required from a safety and really what's required from the overall. Again, this is a phase one study in terms of the overall RIA rates.

likely to be instructive as to what would be required commercially. So we just won't have enough product exposure in the intercept A.D. study to definitively say what's required from a safety and really what's required from the overall. You know, this is a phase one study in terms of the overall R.A.R.H. Thank you.

As a reminder, to ask a question, please press star 11 on your telephone. Standby for our next question. I show no further questions at this time. I would now like to turn the conference back to Alex for closing remarks. Thanks, Michelle. Thanks, everyone, for joining us today. As always, we're available for follow-ups. If you have any additional questions, please reach out to us at the company.