Q3 2023 Acumen Pharmaceuticals Inc Earnings Call
Okay.
Speaker 1: Good day, ladies and gentlemen. Thank you for standing by. Welcome to AcumenParma third quarter, 2023 conference call and webcast. At this time, all participants are on 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 automatic message advising your hand is raised. Please note that today's conference is being recorded.
Good day, ladies and gentlemen, thank you for standing by welcome to acumen pharma third quarter 2023 conference call and webcast. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session. Just a question. During this session you want.
The press Star one on your telephone you will then you an automatic message at this race.
Note that today's conference is being recorded.
Speaker 1: I will now hand the conference over to your speaker host, Alex Brock, head of invasibility.
I will now hand, the conference I'll, let you speak of host Alex Brown head of Investor Relations. Please go ahead.
Speaker 2: Thank you, Livia. Good morning and welcome to the Acumen Conference call to discuss our business update and financial results for the quarter ended September 30, 2023.
Thank you Olivia and good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended September 30th 'twenty to 'twenty three.
Speaker 2: 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.
With me today are Dan O'connell, our Chief Executive Officer Dr.
Dr. Eric <unk>, our Chief Medical officer, and that too, though our chief financial Officer, and Chief Business Officer.
Speaker 2: Before we begin, we encourage listeners to go to the investor section of the Acumen website to find our press release issued this morning and related slide presentations we'll discuss today.
Before we begin I encourage listeners to go to the investors section of the axon website to find our press release issued this morning and related slide presentation that we'll discuss 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.
Please note that during today's conference call.
Forward looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans.
Speaker 2: These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statement.
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, a 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 statement.
Please see slide two of the accompanying presentation.
Press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward looking statements. We undertake no.
Speaker 2: 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.
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.
Speaker 2: After our prepared remarks, we'll open the call for Q&A. So now I'll turn the call over to Dan.
After our prepared remarks, we'll open the call for Q&A.
Now I'll turn the call over to Dan.
Speaker 3: Thanks, Alex. Good morning and thanks everyone for joining us today. Throughout the third quarter and into November , our team is focused on advancing ACU-193, our monoclonal antibody, for the treatment of early Alzheimer's disease to the next phase of clinical development.
Thanks, Alex Good morning, and thanks, everyone for joining us today.
Throughout the third quarter and into November our team is focused on advancing <unk> 193, our monoclonal antibody for the treatment of a truly all service disease to the next phase of clinical development.
Speaker 3: We recognize the importance of additional treatment options for Alzheimer's patients and caregivers living with this disease, and we believe that ACU-193's high selectivity for toxic amyloid beta oligomers may lead to differentiation via increased clinical efficacy and improved safety and convenience as compared to approved and under reviewed antibodies.
We recognize the importance of additional treatment options for all service patients and caregivers living with this disease and we believe that issue 190 threes high selectivity for toxic amyloid beta oligomers may lead to differentiation via increased clinical efficacy and improved safety and convenience as compared to approved and under reviewed antibodies.
Speaker 3: We have made significant regulatory, operational, and strategic progress to this end, supported by the deep Alzheimer's development expertise of our team.
We have made significant regulatory operational and strategic progress to this AD supported by the deep Alzheimers development expertise of our team.
Speaker 3: Today we have positive updates to share regarding the CSF biomarkers from our phase one study, our recent FDA interaction, and the newly announced development partnership in financing to pursue a subcutaneous form of AC193.
Today, we have positive updates to share regarding the CSF biomarkers from our phase one study our recent FDA interaction and the newly announced development partnership and financing to pursue a subcutaneous form of HC 193.
Speaker 3: Starting with the biomarker data, when we disclosed our intercept AD phase one top line results this past July at the Alzheimer's Association International Conference or AAIC, our team had not yet had an opportunity to analyze the corresponding fluid biomarker data from the trial.
Starting with the biomarker data when we disclosed our intercept 80 phase one topline results. This past July at the Alzheimers Association International Conference or.
Our team had not yet had an opportunity to analyze the corresponding truth biomarker data from the trial.
Speaker 3: CSF biomarker data are now available, and plasma biomarker data will be received in the near future.
CSF biomarker data are now available and plasma biomarker data will be received in the near future.
Speaker 3: Today, I'm pleased to share positive results for AC193 on CSF biomarkers that further reinforce downstream pharmacology in addition to the previously presented target engagement and AMOLED PET data for AC193.
Today I'm pleased to share positive results Tracy 193 on CSF Biomarkers that further reinforce downstream pharmacology and in addition to the previously presented target engagement in amyloid pet data for AC 193.
Speaker 3: Consistent drug effects were observed in the multiple ascending dose cohorts in the intercept AD trial for phospho tau 181, tolba tau, neurogranin, and the 8 beta 42 to 40 ratio.
Consistent drug effects were observed in the multiple ascending dose cohorts in the intercept trial for phosphates out 181, total Tau neuro granted and a beta of 42 to 40 ratio.
Speaker 3: Statistically significant improvement was seen with reductions of neurogranin at 60 milligrams per kilogram MAD dose level, as well as significant correlation between target engagement and the change in neurogranin concentration.
Statistically significant improvement was seen with reductions of neuro granted at 60 milligrams per kilogram dose level as well as significant correlation between target engagement and a change in neuro, great Neurocrine and concentrations.
Speaker 3: These effects are particularly notable since with only three administrations of ACU-193, any multiple sending dose cohorts, any movement in CSF biomarker effects was not entirely expected.
These effects are particularly notable since with only three administrations of ACD 193, multiple ascending dose cohorts any movement in CSF Biomarkers FX was not entirely expected.
Speaker 3: The fact that we've seen such movement is highly supportive of our antibodies downstream pharmacological effects in the brain, and it's also tied to a beta oligomer target engage.
The fact that we have seen such movement is highly supportive of our antibodies downstream pharmacological effects in the brain and it's also tied to a beta of legwork target engagement.
Speaker 3: Eric, we'll walk you through the CSF biomarker data in more detail shortly.
Eric will walk you through the CSF biomarker data in more detail shortly.
Speaker 3: This October , we presented a deeper dive into our phase one results at the clinical trials for Alzheimer's disease meeting or CTAD, which was very well received by the medical community.
This October we presented a deeper dive into our phase one results at the clinical trials for all service disease meeting or <unk>, which was very well received by the medical community.
Speaker 3: Overall, we continue to be very pleased with the quality of the data generated in our intercept AD phase 1 trial and the corresponding insights that have helped to guide the design of our phase 2 study, such as our compelling target engagement, amyloid plaque reduction, and now CSF biomarker effects.
Overall, we continue to be very pleased with the quality of the data generated in our intercept 80 phase one trial and a corresponding insights that have helped to guide the design of our phase III study such as our compelling target engagement amyloid plaque reduction and now CSF biomarker effects.
Speaker 3: Importantly, as part of our presentation at CTAD, we announced the doses we are taking forward in phase two. The two treatment arms versus placebo are 50 milligrams per kilogram and 35 milligrams per kilogram. Both administered IV every four weeks.
Importantly, as part of our presentation at <unk>, we announced the doses, we're taking forward in phase III. The two treatment arms versus placebo or 50 milligrams per kilogram and 35 milligrams per kilogram administered IV every four weeks.
Speaker 3: These doses were selected based on extensive PKPD modeling of our phase 1 data that showed direct target engagement of A beta ligamers at near maximal effect.
These doses were selected based on extensive PK PD modeling of our phase one data that showed direct target engagement.
Speaker 3: In other words, on the basis of the phase one data and subsequent PKPD modeling, we have confidence that at both these doses of AC193, we'll adequately saturate our intended target, toxic A-beta oligomers in the brain.
<unk> effect.
In other words on the basis of the phase one data and subsequent PK PD modeling, we have confidence that at both these doses of <unk> hundred 93 adequately saturate, our intended target toxic a beta Omega person there Brian.
Speaker 3: As we think about the phase two study and the dosing strategy, we anticipate the 50 milligram per kilogram dose level will replicate and presumably extend the plaque reduction observed in phase one, and the 35 milligrams per kilogram dose may achieve sufficient oligomer target engagement, but possibly with a lower rate of RAE than the 50 milligram per kilogram dose cohort.
As we think about the phase III study and the dosing strategy, we anticipate that 50 milligram per kilogram dose level will replicate and presumably extending the plaque reduction observed in phase one and a 35 milligrams per kilogram dose achieved sufficient oligomer target engagement, but possibly with a lower rate of ARIA E and the 50 milligram per kilogram dose.
Speaker 3: To be clear, both of these dose levels may produce clinical efficacy, and we are keen to see whether they will differentiate in terms of therapeutic index or overall benefit-risk ratio.
Cohort.
To be clear both of these dose levels may produce clinical efficacy and we're keen to see whether they will differentiate in terms of therapeutic index or overall benefit risk ratio.
Speaker 3: Turning to our regulatory update, recently we met with the FDA in an end of phase 2 meeting to discuss our next clinical study, ACU-193-201, which we are calling Altitude AD. The agency indicated that it is aligned in principle with the study design.
Turning to our regulatory update recently, we met with the FDA in an end of phase II meeting to discuss our next clinical study.
93, <unk> hundred one, which we are calling altitude.
The agency indicated that it is alive in principle with the study design.
Speaker 3: We were planning the study as a randomized, double-blind, placebo-controlled, three-arm study designed to evaluate the clinical efficacy, safety, and tolerability of ACU193 with up to 180 participants per arm for a total of 540 participants with mild cognitive impairment or mild dementia due to AD.
We are planning the study is a randomized double blind placebo controlled three arm study designed to evaluate the clinical efficacy safety and Tolerability of <unk> hundred 93.
With up to 180 participants per arm for a total of 540 participants with mild cognitive impairment or mild dementia due to <unk>.
Speaker 3: We will initiate Altitude AD as a standalone phase 2 study with an 18-month treatment duration commencing in the first half of 2024.
We will initiate altitude <unk> as a stand alone phase II study with an 18 month treatment duration commencing in the first half of 2024.
Speaker 3: The study plan incorporates an adaptive design with interim analyses to inform the possibility of expanding the size of the study from a Phase II to a Phase III study, which we believe is the most expeditious route to a BLA filing and potential approval.
The study plan incorporates an adaptive design with interim analyses to inform the possibility of expanding the size of the study from our phase two to a phase III study, which we believe is the most expeditious route to a BLA filing and potential approval.
Speaker 3: As a reminder, these interims are not futility analyses, and in alignment with guidance from the FDA and to avoid bias and to protect the study's integrity as a potential registration study, the timing of and data from interims will not be disclosed publicly.
As a reminder, these interims or not futility analyses.
In alignment with guidance from the FDA and to avoid bias and to protect the study's integrity as a potential registrational study the timing of data from Aaron's will not be disclosed publicly.
Speaker 3: Now, I'd like to provide an update on our efforts to assess the viability of subcutaneous dosing of ACY1.
Now I'd like to provide an update on our efforts to assess the viability of subcutaneous dosing of <unk> with.
Speaker 3: We recognize the attractiveness of this mode of administration to offer additional flexibility and convenience for patients and caregivers.
We recognize the attractiveness of this mode of administration to offer additional flexibility and convenience for patients and caregivers.
Speaker 3: Over the last nine to 12 months, we've evaluated several delivery technologies to support the doses we are exploring in our clinical studies.
Over the last nine to 12 months, we are evaluating several delivery technologies to support the doses we are exploring in our clinical studies.
Speaker 3: We are very excited about our recently signed global collaboration and licensing agreement with Talazin.
We are very excited about our recently signed global collaboration and licensing agreement with Palestine.
Speaker 3: Using Halozyme's commercially validated enhanced drug delivery technology, we plan to initiate a phase one study to compare the PK of subcutaneous form of HC193 to the IV form in mid-2024.
Using <unk> commercially validated enhanced drug delivery technology, we plan to initiate a phase one study to compare the PK of subcutaneous form of <unk> 93 to the IV form in mid 2024.
Speaker 3: Based on our dose model, we believe there's a potential for competitive commercial product profile of a subcutaneous dosage form of AC193, which may ultimately be commercialized alongside every four-week IV AC193 to potentially broaden treatment options for patients.
Based on our dose modeling, we believe there is a potential for competitive commercial product profile of a subcutaneous dosage form of <unk> hundred 93, which may ultimately be commercialized alongside every four week IV <unk> to potentially broaden the treatment options for patients.
Speaker 3: Today, we also announced that we've secured a credit facility for up to 50 million dollars with K2 Health Ventures, a health care focused specialty finance company. I'll let Matt tell you more on how this funding provides us with additional operational flexibility.
Today, we also announced that we secured a credit facility for up to $50 million with K, two health ventures health care focused specialty finance company.
Let me tell you more on how this funding provides us with additional operational flexibility.
Speaker 3: Taking a look back at 2023, the year thus far has been a transformational one for Acumen. Our positive phase one top line results enabled us to demonstrate convincing proof of mechanism for AC193 further supported by the CSF biomarker data shared today. We received encouraging feedback from the FDA on the design of our next phase of clinical development, which we are operationalizing as we speak.
Taking a look back at 2023 year, thus far has been a transformational about tracking them our positive phase one topline results enabled us to demonstrate convincing proof of mechanism for <unk> III further supported by the CSF biomarker data share today.
We received encouraging feedback from the FDA on the design of our next phase of clinical development, which were operationalized as we speak.
Speaker 3: Our partnership with Halozyme for the development of a subcutaneous option of AC193 extends its product profile in pursuit of greater patient choice and convenience.
Our partnership with <unk> for the development of a subcutaneous option of <unk> 93 extends its product profile and pursuit of greater patient choice and convenience.
Speaker 3: And the additional financing to support subcutaneous development provides the capital to support the focus of our talented team, working to solidify AC-193's potential as a future differentiated and potential best-in-class option for early Alzheimer's treatment. And with that, I'll turn the call over to Eric.
And the additional financing to support subcutaneous development provides the capital to support the focus of our talented team working to solidify <unk> hundred 93, its potential as a future differentiated and potential best in class option for early Alzheimer's treatment.
And with that I'll turn the call over to Eric.
Thanks, Dan and good morning, everyone. We have been very productive since our last quarterly update update I'm pleased to have data to share with you today regarding the CSF biomarker changes we are measured in our phase one intercept study.
Speaker 4: We have been very productive since our last quarterly update, and I'm pleased to have data to share with you today regarding the CSF biomarker changes we have measured in our Phase 1 Intercept AD study.
Speaker 4: If you turn to slides five to eight in the earnings presentation posted today on our website and on the webcast, in the first slide, you can see and observe dose-dependent trend in the multiple ascending dose cohorts indicating a drug effect of ACU193 in CSF levels of P-tau 181, total tau, neurogramin, and the A-beta 42 over 40 ratio.
If you turn to slides five to eight and the earnings presentation posted today on our website and on the webcast.
First slide you can see and observed dose dependent.
Trend in the multiple ascending dose cohorts, indicating a drug effect of Acu and <unk> 93, and CSF levels of <unk> 181, total Tau neuro Graham and <unk>.
And the a beta 42 over 40 ratio. This is after only three administrations of drug. So the fact that we are observing changes is highly supportive of AC 190, <unk> target engagement and downstream pharmacology as determined in our phase one study.
Speaker 4: This is after only three administrations of drug. So, the fact that we are observing changes is highly supportive of ACU-193's target engagement and downstream pharmacology as determined in our phase one study.
Speaker 4: Neurogranin is a synaptic protein that has been shown to modulate glutamatergic neuronal activity and may be linked to enhancement in synaptic plasticity and cognitive function. And the 60 milligrams per kilogram every four weeks dose of ACU-193 showed a nominally statistically significant improvement in neurogranin as compared to the placebo group with a p-value of 0.037.
Neuro granting us the synaptic protein that has been shown to modulate glutamatergic neuro activity and maybe linked to enhancement in synaptic plasticity in cognitive function and the 60 milligrams per kilogram every four weeks dose of Acu and 93 showed a nominally statistically.
Significant improvement in Europe granted as compared to the placebo group with a P value of 0.037.
Speaker 4: There was also significant correlation between A-beta oligomer target engagement and change in neurogranin across all those.
There was also a significant correlation between a beta aligarh target engagement and change in euro granted across all doses.
Speaker 4: These data are consistent with the mechanism of action and target engagement of ACU-193 and also provide evidence beyond target engagement of downstream pharmacological effects of ACU-193 on neuro-granted.
These data are consistent with the mechanism of action and target engagement of Acu and <unk> 93.
It also provide evidence beyond target engagement of downstream pharmacological effects of Acu was 93 under our granted.
Speaker 4: Turning to P Tau 181, we saw changes directionally similar to Neurogranin. A nominally significant decrease of P Tau 181 was seen with the 60 milligrams per kilogram dose in the Intercept AD multiple ascending dose cohort. And a trend was seen for correlation of change in CSF P Tau 181 versus target engagement.
Turning to <unk> 181, we saw changes directionally similar to neuro greater than nominally significant decrease of <unk> 181 was seen with the 60 milligrams per kilogram dose in the intercept a multiple ascending dose cohort and a trend we've seen for a correlation of change.
In CSF pizza, our 91 versus target engagement.
Speaker 4: This is encouraging because it further supports that ACU193's mechanism may lead to clinical efficacy given PTAL's established relationship with cognitive decline.
This is encouraging because it further supports that Acu were 90 Three's mechanism may lead to clinical efficacy given <unk> established relationship with cognitive decline.
Speaker 4: Remarkably, as shown in slide 6, we observed that the change in neurogranin was significantly correlated with the change in p-tau 181.
Okay.
Remarkably as shown in slide six we observed that the change in her granted was significantly correlated with the change in <unk> 181.
Speaker 4: Researchers in the field have found correlations between CSF, Neurogranin, and P-tau which suggests a biological link between these two biomarkers and provides further confidence in our biomarker observations with ACU193.
Researchers in the field have found correlations between CSF neuro granted in pizza.
Which suggests a biological link between these two biomarkers and provides further confidence in our biomarker observations with Acu 193.
Speaker 4: As shown in slide 7, correlations between changes in neurogran and PTAL181 were more closely related to target engagement, that is binding of CC193 to A-beta oligomers, than to decreases in amyloid plaque load as determined by PET.
As shown in slide seven correlations between changes in neuro Grant and Pete tell 181 or more closely related to target engagement that is binding of DC were 93 to a beta augurs decreases in amyloid plaque load is determined by Pat.
Speaker 4: While not conclusive, these analyses support the concept that ACU193 binding to A-beta oligomers rather than plaque reduction mediates its downstream pharmacology and potential clinical benefits.
Not conclusive these analyses support the concept that <unk> 93 binding to a beta olive dimmers, rather than plaque reduction mediates downstream pharmacology and potential clinical benefits.
Speaker 4: We would not expect every biomarker to change with ACU193 treatment, and as shown in slide 8, we did not see an effect on neuropentraxin 2. Additional study will be required to understand more about this relatively new biomarker.
We would not expect every biomarker to change with <unk> 93 treatment as shown in slide eight we did not see an effect on Europe and tracks into additional study will be required to understand more about this relatively new biomarker.
Speaker 4: Please note that plasma biomarkers are in the process of being analyzed, and we expect to be able to share some of that data in the near future.
Please note that plasma biomarkers are in the process of being analyzed and we expect to be able to share some of that data in the near future.
Speaker 4: I'd also like to highlight that our symposium presentation at CTAB was well-received by the medical community, as Dan mentioned. A couple of important points from our presentation in particular supported the conclusion from our phase one study that ACU193 is pharmacologically active and engages its intended target in the brain.
I'd also like to highlight that our symposium presentation at <unk> was well received by the medical community as Dan mentioned.
Couple of important points from our presentation in particular supported the conclusion from our phase one study that Acu and <unk> 93 is pharmacologically active and engages its intended target in the brain.
Speaker 4: The main takeaway I would highlight from our presentation is the confidence we have in the dose selection for our phase two trial based on the observed maximal target engagement derived from our novel target engagement assay.
The main takeaway I would highlight from our presentation is the confidence we have in the dose selection for our phase III trial based on the observed maximal target engagement derived from our novel target engagement assay at.
Speaker 4: At the 35 milligram per kilogram dose, we would expect to nearly saturate our primary target, A beta oligomers, and fully interrogate the oligomer hypothesis that points to A beta oligomers as being the most toxic species of A beta.
That's a 35 milligram per kilogram dose, we would expect to nearly saturate our primary target a beta olive mers and fully interrogate the oligomer hypothesis that points to a beta olive mers as being the most toxic species of a beta.
Speaker 4: At the 50 milligram per kilogram dose, we would expect to reach even greater engagement of A-beta oligomers. But in addition, we would also expect to lower plaque load based on our phase one data.
At the 50 milligram per kilogram dose, we would expect to reach even greater engagement of ABB to Alzheimers, but in addition, we would also expect to lower plaque load based on our phase one data we.
Speaker 4: We would expect a lower level of ARIAe using 35 milligrams per kilogram as compared to the 50 milligrams per kilogram dose.
We would expect a lower level of ARIA E. Using 35 milligrams per kilo gram as compared to the 50 milligrams per kilogram dose.
Speaker 4: The bottom line is that because of our robust Phase I results, we have been able to choose two Phase II study active dose arms that could both be potentially efficacious and reduce cognitive decline.
The bottomline is that because of our robust phase one results, we have been able to choose two phase two study active dose arms that could both be potentially efficacious and reduce cognitive decline.
Speaker 4: Another important takeaway from our CTAB presentation is the consistency of plaque reduction in the multiple ascending dose cohorts of Intercept AD. For the 10 milligram per kilogram MAD cohort, five of six patients on treatment had a decline in amyloid PET scintilloids, and the single patient without a decline had a small increase of 3.4 scintilloids, which is essentially test-retest noise.
Another important takeaway from our <unk> presentation is the consistency of plaque reduction and the multiple ascending dose cohorts of intercept.
For the 10 milligram per kilogram cohort five of six patients on treatment had a decline in amyloid pet.
And the single patient without a decline had a small increase of three four set of Lloyds, which is essentially test retest noise.
Speaker 4: For the 60 milligrams per kilogram cohort, seven of eight patients had a decline in centelloids. For the 25 milligrams per kilogram every two weeks cohort, all eight people on treatment had a decline in centelloid values. The consistency of these results aligns with the conclusion that reduction in plaque load is due to treatment with ACU 193.
For the 60 milligrams per kilo Gram cohort seven of eight patients had a decline in several ways.
For the 25 milligrams per kilo Gram every two weeks cohort all eight people on treatment had a decline in satellite values. The consistency of these results aligns with the conclusion that reduction in plaque load is due to treatment with <unk> hundred 93.
Speaker 4: In summary, our clinical team has been working diligently to prepare for the initiation of our phase two study, altitude AD, in the first half of 2024.
In summary, our clinical team has been working diligently to prepare for the initiation of our phase II study altitude.
In the first half of 2024.
Speaker 4: I won't reiterate Dan's summary of our encouraging FDA interaction this quarter, though I will emphasize that we are committed to executing on the promise of the A-beta oligomer theory hypothesis and the potential for ACU193 to be a best in class therapeutic option for Alzheimer's patients and their families. And with that, I'll turn the call over to Matt.
I won't reiterate Dan summary of our encouraging FDA interaction this quarter.
I'll emphasize that we are committed to executing on the promise of the a beta oligomer or theory hypothesis and the potential for IC 193 to be a best in class therapeutic option for alzheimers patients and their families.
And with that I'll turn the call over to Matt.
Thank you Eric good morning, everyone.
Speaker 3: As a reminder, our third quarter 2023 financial results are available in the press release we issued this morning and in our 10-Q that we will file after the close today.
As a reminder, our third quarter 2023 financial results are available in the press release, we issued this morning and in our 10-Q that we will file after the close today.
Speaker 3: As of September 30th, we had approximately $282.7 million in cash and marketable securities on the balance sheet. Our cash on hand is expected to support our current clinical and operational activities into the second half of.
As of September 30, we had approximately $282 $7 million in cash and marketable securities on the balance sheet. Our cash on hand is expected to support our current clinical and operational activities in.
In the second half of 2026.
Speaker 5: R&D expenses were approximately $11.2 million in the third quarter. The increase over the prior year was primarily due to increased costs related to drug manufacturing costs, consulting,
R&D expenses were approximately $11 $2 million in the third quarter the increase over the prior year was primarily due to increased costs related to drug manufacturing costs.
Salting and personnel.
Speaker 5: GNA expenses were $4.9 million in the quarter, with the increase over the prior year primarily the result of costs related to personnel and consulting. This led to a loss from operations of $6.2 million.
G&A expenses were $4 $9 million in the quarter with the increase over the prior year, primarily the result of costs related to personnel and consulting.
This led to a loss from operations of $16 million in the quarter.
Speaker 5: Today, I'm pleased to announce an agreement with K2 Health Ventures for a senior secured credit facility of up to $50 million. Upon closing, $30 million of the $50 million loan facility was funded. An additional tranche of up to $20 million is also available, which may be funded in installments upon Acumen's request.
Today I am pleased to announce an agreement with K two health ventures for a senior secured credit facility of up to $50 million upon closing $30 million of the $50 million loan facility was funded an.
An additional tranche of up to $20 million is also available which may be funded installments upon documents request.
Speaker 5: subject to review and discretionary approval from K2.
Subject to review and discretionary approval from K too.
Speaker 5: This financing provides additional capital to pursue the development of the subcutaneous dosage form of ACU-193, which we view as value enhancing for both patients and shareholders, as well as for general consumers.
This financing provides additional capital to pursue the development of a subcutaneous dosage form of Acu 193.
Which we view is value enhancing for both patients and shareholders as well as for general corporate purposes.
Speaker 5: And with that, we can open the call for Q&A. Operator?
And with that we can open the call for Q&A operator.
Speaker 1: Thank you. Ladies and gentlemen, if you'd like to ask a question at this time, you will need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, you may press star 1 1 again. Please stand by while we compile the Q&A box.
Thank you, ladies and gentlemen, if you'd like to ask a question at this time, you will need to press star one on your telephone and wait for your name to be announced so withdraw. Your question you May Press Star one again, please standby, while we compile the Q&A roster.
Speaker 1: And our first question coming from the line of Tom Schrader with BTIG, your line is open.
Okay.
And our first question coming from the line of Thomas Shrader with BG AIG. Your line is now open.
Speaker 3: Good morning. Congratulations on the biomarker data wasn't good. It changed. Eric, I was wondering if you can for us slow thinkers walk through your logic for a data 42 to 40 going up. I think we talked about we weren't really sure which way it would go. I guess it's good. It changes.
Hi, good morning, congratulations on the biomarker data.
It changed right Eric I was wondering if you can for us slow thinkers walk through your logic for a beta 42 to 40 going up I think we talked about we weren't really sure which way. It would go I guess its good it changes and then.
Speaker 3: And then with the robust cow readout, are you thinking about a third lower dose for at least a while where you could get a sense of maybe if you have some PD at much lower doses, it would almost certainly be very safe? So those are my questions. Thanks.
With the robust how readout are you thinking about a third lower dose for at least a while where you could get a sense of.
Maybe if you have some PD.
At much lower doses.
Almost certainly be very safe.
All my questions. Thanks.
Speaker 4: Yeah, thanks. Great questions. Um, as far as the, uh, a beta 42 over 40 ratio, um, yeah, it's a little, uh.
Yes, Thanks, Great question.
As far as the a beta of 42 over 40 ratio.
Yes, it's a little.
Speaker 4: complicated, maybe a little confusing. But for whatever reason, even though A-beta plaques are made up of A-beta 1 to 42, and they're obviously increased in the brain, in spinal fluid, the concentration of A-beta 42 is decreased in patients with Alzheimer's disease. And that's thought to be because of equilibrium shifts and the fact that it's sort of tied up in the brain.
A complicated maybe a little confusing but for whatever reason even though.
Beta plaques are made up of Bay beta one to 42 and Theyre, obviously increased in the brain and spinal fluid the concentration of a beta 42 has decreased in patients with alzheimers disease and that is thought to be because of equilibrium shifts and the fact that it's sort of tied up in the brain.
Speaker 4: So when you're abnormal in Alzheimer's, your A-beta 42 is low.
So when you are abnormal at all timers Youre a beta of 42 is low.
Speaker 4: So if you have your A beta 40, 42, and it works better to use the 42 over 40 ratio, but if you take the 42 over 40 ratio and it goes up, that means you're returning people towards a normal non-all-timers state.
So if you have your a beta of 40 42, and it works better to use the 42 over 40 ratio, but a few.
Take the 42 over 40 ratio and it goes up that means you're returning people towards a normal non all timers state.
Speaker 4: So, you know, we tend to think of A beta 42 being a bad thing, but really in spinal fluid, going up is a good thing. So, you know, we looked at it as a really positive result. With regard to the tau, you have to think about the
So we.
We tend to think of a beta 42, being a bad thing, but really in the spinal fluid.
Going up is a good thing so we looked at is.
A really positive result.
With regard to the Tao.
Yes those were.
Speaker 4: fairly impressive results after just three administrations have tried. And you could, you know, raise the possibility of do we need to explore even lower doses?
Fairly impressive results. After just three administration has drawn.
And you could raise the possibility of do we need to explore even lower doses.
Speaker 4: Now, from a regulatory standpoint, there's no requirement to find a minimally effective dose. We chose those doses as we outlined, you know, really carefully based on our target engagement assay. We do have, built into the protocol, a dose escalation for the 50 milligrams per kilogram dose group, which.
Now from a regulatory standpoint, there is no requirement to find a minimally effective dose.
We chose those doses.
Outlined really carefully based on our target engagement assay.
We do have built into the protocol a dose escalation for the 50 milligrams per kilogram.
Speaker 4: it should cut down on the ARIA rate. So the first two doses that people get will actually be 35 milligrams per kilogram, and then they go to 50.
Most group, which.
It should cut down on the ARIA right. So the first two doses that people get will actually be 35 milligrams per kilogram and then they go to <unk>.
Speaker 6: So yeah, it's, you know, eventually it would be scientifically certainly interesting to look at lower doses, but we wanted to pick two doses that we thought really could have clinical efficacy. Got it. Okay. Thanks.
Yes.
Eventually it will be scientifically certainly interesting to look at lower doses, but we were at two doses that we thought really could have clinical efficacy.
Got it okay. Thanks for that Bob.
Thank you Juan for next question.
Yes.
Speaker 1: And our next question coming from the lineup, Pete Strapopoulos with Cantor Fitzgerald, your line is open.
And our next question coming from the line of Keith Joseph <unk> with Cantor Fitzgerald. Your line is open.
Speaker 7: Hi, good morning, Dan, Matt, Eric, thank you for the update. So, you know, 1 question that I have is, you know, at the pad, you know, there was a great, you know, sub. A group analysis for the map, you know, with certain subgroups of patients have greater clinical benefit, you know, versus others. Uh, for example, baseline towel levels age, you know, things of that nature. So, you know, how are you thinking about these data? And, uh, will you incorporate any of these learnings for the inclusion exclusion criteria for altitude?
Hi, Good morning, Dan, Matt and Eric.
Thank you for the update so one question that I have at <unk>.
Great.
Group analysis for Donana Madam Academy.
Certain subgroups of patients had greater clinical benefit versus others for <unk>.
Example, baseline Tau levels age.
Things of that nature. So how are you thinking about these data.
Will you incorporate any of these learnings for.
For the inclusion exclusion criteria for our output.
Yes, thanks, another great question.
Speaker 4: So those were, you know, very interesting presentations. And I think, you know, from a standpoint, actually the Lilly program, you know, they focused on people who had moderate amounts of tau, but it turns out that actually the people with less tau did actually better with the drug. So it all gets back to this idea that people who were earlier in the disease can benefit more.
So those were.
Very interesting presentations and I think.
From a standpoint of actually the Lilly program.
We are focused on people, who had moderate amounts of tau, but it turns out that actually the people with less talented did actually better with the drug. So it all gets back to this idea that people who are earlier in the disease Kim can benefit more so.
Speaker 4: So we've thought quite a bit about that in terms of our upcoming study.
Quite a bit about that in terms of our upcoming.
Speaker 4: And one of the things in our presentation that you may have noticed is that we do have people who were included in this study based on a visual read of their amyloid PET scans with actually very low scintilloid level.
Study and one of the things in our presentation.
You may have noticed is that we do have people who were included in the study based on a visual read of their amyloid pet scans with actually very low sand Lloyd levels.
Speaker 4: And initially, there was some discussion of maybe we shouldn't include those people in our trial because, you know, their plaque load was so low. But after seeing those presentations, I think we decided we're going to keep those people in our study. So essentially, the way the study was set up, based on our phase one results, we know that we'll already be getting some of those really early people.
Initially.
Some discussion of maybe we shouldnt include those people in our trial because.
Theyre plaque load was so low but after seeing those presentations I think we've decided we're going to keep those people in our study so essentially the way. The study was set up based on our phase one results. We know that will already be getting some of those really early people. So it.
Speaker 4: So it was a, you know, the data were fascinating. We had to think about them quite a bit, but at the end of the day, we decided that we actually don't need to change the design of our study.
As of the date of our fascinating we have to think about them quite a bit but at the end of the day, we decided that we actually don't need to change the design of our study.
Speaker 7: All right, thank you. And, you know, and for the, the changes in biomarkers that you showed today, you know, was there any correlation between, let's say, plaque reduction and changes any, any of the biomarkers or levels of a beta plaque or levels with those changes?
Alright, Thank you and.
And for the changes in Biomarkers that you showed today.
Was there any correlation between let's say plaque reduction and changes in any of the biomarkers or levels of a beta plaque or sand fluid levels.
Speaker 4: Yeah, well, the correlations between.
Those changes.
Yeah, well the correlations.
Between.
Speaker 4: target engagement and the biomarker changes were greater than the correlations with plaque reduction and those biomarker changes. So again.
Target engagement in the biomarker changes were greater than the correlations with plaque reduction and.
Those biomarker changes so again, it's not absolutely conclusive directionally, that's the way the data turned out but we think that's very consistent with our hypothesis that the efficacy in this case the biomarker changes are related to binding to these eight beta unlike emerge.
Speaker 4: absolutely conclusive. Directionally, that's the way the data turned out. But we think that's very consistent with our hypothesis that the efficacy, in this case, the biomarker changes, are related to binding to these A-beta oligomers more than related to plaque reduction.
More than related to plaque reduction.
Okay. Thank you and thank you for taking my questions.
Speaker 1: Thank you. And our next question, coming from the lineup, Palmatics with Steve Foley, your line is open.
Thank you and our.
Next question coming from the line of Paul Matteis with Stifel. Your line is open.
Speaker 8: Hi, this is Catherine on for Paul. Thanks for taking our question on the phase two, three. What do you expect to look at in the interim and what would prompt a move into expanding the study? And you can say on when you might be interested in taking the interim. Thank you.
Hi, This is Katherine on for Paul Thanks for taking our question.
On the phase two three what do you expect to look at in the interim.
And what would prompt a move into expanding the study.
So you can say on when you might be.
And taking the interim thank you.
Speaker 3: Hi, Catherine, thanks for your question. So, as we mentioned, we had a favorable interaction recently with the FDA on the, on the phase 2, 3 design. I don't think we're going to go into details on the algorithms and elements. That will inform the decision to scale from phase 2 to phase 3, but as we get the meeting minutes and get the study up and running, I think we have an opportunity to maybe share some additional information, but not in a position to comment today. Thank you.
Hi, Katherine Thanks for your question. So as we mentioned we had a.
A favorable interaction recently with the FDA on the phase III design.
Don't think we're going to go into details on the algorithms and elements that will inform the decision to scale from phase II to phase III.
But as we get the meeting minutes you can get the study up and running I think we have.
The opportunity maybe share some additional information, but not in a position to comment today.
Thank you.
Thank you.
Our next question.
Speaker 1: And our next question coming from the lineup, Colin Bristow with UBS, your line is open.
And our next question coming from the line of Colin Bristow with UBS. Your line is open.
Speaker 9: Good morning and congrats on all the progress. Maybe first one for Eric. Eric, I'm curious, what did you, in terms of the Lakembi sub-Q data that you saw at CTAD, I'm curious, like what were the key sort of learnings that you had from that and any surprises there? And then how will this change your approach to sub-Q193? And then just secondly, more of a sort of administrative question, but how long do you think it's going to take to enroll phase two? Thank you.
Hey, good morning, and congrats slow progress.
Maybe first one for Eric Eric I'm curious.
What did you in terms of the <unk> data that you saw at <unk>.
I'm curious like what are the key learnings.
Learnings you had from that and any surprises there and then how this the chain how will this change your approach to sub Q1 93, and then just secondly, more of a sort of administered your question, but how long do you think it's going to take to enroll the phase two thank you.
Speaker 4: Okay, well, let me talk about the subcute first and then we'll take the other question afterwards with Dan.
Okay.
Let me talk about the sub Q first and then.
Let's take the other question afterwards.
Speaker 4: But anyway, in terms of the sub-Q, what was really interesting about that was there was this hypothesis that was pretty prevalent with a lot of researchers that ARIAe was driven by C-Max.
But anyway in terms of the sub Q, what was really interesting about that was.
There was this.
A hypothesis that was pretty prevalent with a lot of researchers that ARIA E was driven by C. Max.
Speaker 4: rather than AUC and so with the sub-q formulation, you would have a lower C-max and so you'd have less ARIA.
Other than AUC, and so with the sub Q formulation, you would have a lower C. Max and so you'd have less ARIA and that just turned out not to be the case.
Speaker 4: And that just turned out not to be the case. It's, you know, it's unusual in science that to have one experiment be so definitive, but I think in this case, it was pretty definitive that CMAX was not driving REAE, and it was more related to AUC. And so.
Unusual in science, the SAB, one experiment, so definitive but I think in this case it was pretty definitive that C. Max was not driving ARIA E and it was more related to AUC.
And so.
Speaker 4: You know, so we got an answer to that question. I think from our standpoint, having, well, and for other people in the field, actually, having a sub-Q formulation is more a matter of patient convenience, what people prefer, that sort of thing. There's probably not going to be a safety benefit.
So we've got an answer to that question I think from our standpoint.
And for other people in the field actually having a sub Q formulation.
As more of a matter of patient convenience what people prefer that sort of thing, there's probably not going to be a safety benefit but it still means that it can be useful for people in terms of convenience and that sort of thing so.
Speaker 4: But it still means that it can be useful for people in terms of convenience and that sort of thing. So, you know, from that standpoint, we got a definitive answer to that question. And, uh, but sub Q is still something we want to look at. So, I'll turn over to.
From that standpoint, we got a definitive answer to that question and.
But sub Q is still something we would look at.
So ill turn it over to Dan to talk about timelines.
Speaker 3: Sure, thanks. Thanks Arkin. Thanks Colin for the question. In terms of the altitude AD study, as we mentioned, we are in the mode of operationalizing and focused on execution.
Thanks, Eric and thanks, Colin for the question in terms of the altitude <unk> study as we mentioned we are.
In the motive of operational housing and focused on execution.
Speaker 3: In terms of feedback that we had at CTAD, interacting with the site investigators and others in the field, there was a strong demand and interest in participating in the study. So, we're optimistic that the interest in participating in research and particularly.
In terms of feedback that we had at <unk>.
Interacting with site investigators and others in the field.
Strong demand and interest in participating in the study so we're optimistic that the.
The interest in participating in research.
Speaker 3: with respect to 193 is we're in a good moment of time for that.
Particularly.
With respect to 193 is.
Speaker 3: In terms of specific timelines, it's it's just too early to say. I mean, we've got to get sites up and running. You know, there are a series of.
Good moment of time for that in terms of specific timelines. It's just too early to say I mean, we've got to get sites up and running.
Speaker 3: developments over the over the next 12 months that will.
A series of.
Elements over the over the.
Speaker 3: inform more specifically what our timelines are for enrollment, but we'll be happy to provide additional details when we have some visibility on where we stand in terms of enrollment and outcomes.
The next 12 months that will inform more specifically what our timelines are for enrollment, but we'll be happy to provide additional detail. When we have some visibility on where we stand in terms of enrollment and outcomes.
Great. Thank you.
Thank you.
Speaker 7: And I see we have a follow-up question from Pete Trapopoulos from Cancer Fitzgerald. You'll let us open. Yeah, thank you for taking the follow-up. Again, Eric, you know, another, I guess, you know, very interesting presentation at CTAD had to do with an analysis of baseline characteristics and ARIA by Ford's Nanomap. Just wanted to hear your take on that data and sort of how...
And so we have a follow up question from.
Populus from Cantor Fitzgerald Your line is open.
Yes, thank you for taking the follow up.
Again, Eric.
Another I guess.
Very interesting presentation of Etsy that had to do with an analysis of baseline.
Characteristics and ARIA.
I just wanted to I just want to hear your take on that data and sort of.
Speaker 7: How are you going to implement that for your phase two, if you're going to implement any of those factors for your phase two?
How are you going to implement that for your phase II. If you can implement any of those factors.
This too.
Speaker 4: Well, yeah, we've, you know, thought a lot about risk factors for aria. And as you know, one of the big ones is a boe for status. And one of the interesting things that we've presented before is that in our 68, but we for homozygous.
Well, yes.
It's a lot about risk factors for ARIA and.
As you know one of the big ones is April four.
Status and one of the interesting things that we've presented before is that in our.
Six eight Bowie for homozygous.
Speaker 4: we didn't have any cases of ARIA. So from that standpoint, I think it's good.
We didn't have any cases of ARIA so from that standpoint.
I think it's good.
Speaker 4: It's interesting, but not surprising that, you know, some of these findings were found. And in our upcoming Phase 2-3 study, we'll more clearly determine whether ApoE4 carrier status is a risk factor for ARIA-E.
It's.
It's.
Interesting, but not surprising.
Some of these findings were found in in our upcoming phase two three study will more clearly determine whether a bowie for carrier status as a risk factor for ARIA E.
Eliminating that risk factor would obviously be really beneficial in the clinic because.
Now there is some recommendations that people be tested for their April carrier status before you begin treatment. Some clinicians if you were in April.
For homozygous would not.
Speaker 4: Would not initiate some of the drugs that are either approved or.
Would not initiate some of the drugs that.
Are either approved or.
Speaker 6: being looked at for approval. So not having that as a liability would be really clinically, I think, a really major benefit.
Being looked at for approval, so not having that as a liability would be really clinically I think a really major benefit.
Speaker 7: Okay, and, you know, some of the other factors, you know, like anti hypertensives, you know, the number of yeah. Yeah. Yeah.
Okay, and then some of the other factors like anti hypertensive.
No.
Yes, yes.
Speaker 6: You know, it's really difficult, at least for me, to interpret those data. They're kind of interesting. It's a little bit of a head scratcher. I don't think there's anything definitive enough in there that we would change the design of our study. That's the sort of thing that I would want to see those results replicated before we take those too seriously.
Sorry.
It's really difficult at least for me to interpret those data they're kind of interesting its a little bit of a head scratcher I don't think theres anything definitive enough in there that we would change the design of our study.
That's the sort of thing that I would want to see those results replicated before we.
Take those too seriously.
Thank you and I'm showing no further questions I will now turn the call back over to Alex Brown for any closing remarks.
Speaker 2: Great. Thanks, everyone, for joining us today. We did present a lot of information, so if you have any follow-up questions, we are available at the company for you. Have a great day.
Great. Thanks, everyone for joining us today.
We did present a lot of information. So if you have any follow up questions. We are available at the company have a great day.
Speaker 1: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.
Ladies and gentlemen that does conclude our conference for today. Thank you for your participation you may now disconnect.
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