Acumen Pharmaceuticals Q3 2023 Earnings Call Transcript

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November 13, 2023

There are 8 speakers on the call.

Operator

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 speakers' presentation, there will be a question and answer Please note that today's conference is being recorded.

Operator

I will now hand the conference over to your speaker host, Alex Sprague, Head of Investor Relations. Please go ahead.

Speaker 1

Thank you, Olivia. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended September 30, 2023. With me today are Dan O'Connell, our Chief Executive Officer Doctor. Eric Siems, 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 our press release issued this morning and related slide presentation we'll discuss today.

Speaker 1

Please note that during today's conference call, we may make forward looking statements within the meaning of the federal securities laws, including statements concerning our financial to 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 2 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 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'll open the call for Q and A.

Speaker 1

So now I'll turn the call over to Dan.

Speaker 2

Thanks, Alex. Good morning and thanks everyone for joining us today. Throughout the Q3 and into November, our team is focused on advancing ACU-one hundred and ninety three, our monoclonal antibody for the treatment of early Alzheimer's disease to the next phase of clinical development. We recognize the importance of additional treatment options for Alzheimer's patients and caregivers living with this disease. And we believe that AC-one hundred and ninety three'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.

Speaker 2

We have made significant regulatory, operational and strategic progress to this end, supported by the deep Alzheimer's development expertise of our team. Today, we have positive updates to share regarding the CSF biomarkers from our Phase 1 study, our recent FDA interaction and the newly announced development partnership and financing to pursue a subcutaneous form of AC-one hundred and ninety three. Starting with the biomarker data, when we disclosed our INTERCEPT AD Phase 1 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. CSF biomarker data are now available and plasma biomarker data will be received in the near future.

Speaker 2

Today, I'm pleased to share positive results for AC-one hundred and ninety three on CSF biomarkers that further reinforce downstream in addition to the previously presented target engagement and amyloid PET data for AC193. Consistent drug effects were observed in the multiple ascending dose cohorts in the INTERCEPT AD trial for phospho tau-one hundred and eighty one, total tau, Neurogranin and A beta 42 to 40 ratio. 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 neurogranate concentrations. These effects are particularly notable since with only 3 administrations of ACU-one hundred and ninety three in the multiple ascending dose cohorts, any movement in CSF biomarker effects was not entirely expected. The fact that we have seen such movement is highly supportive of our antibodies down stream pharmacological effects in the brain and is also tied to abetaoligmore target engagement.

Speaker 2

Eric will walk you through the CSF biomarker data in more detail shortly. This October, we presented a deeper dive into our Phase 1 results at the clinical trials for Alzheimer's disease meeting or CTAD, which was very well received by the medical community. 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. Importantly, as part of our presentation at CTAD, we announced the doses we are taking forward In Phase 2, the 2 treatment arms versus placebo are 50 milligrams per kilogram and 35 milligrams per kilogram, both administered IV every 4 weeks. These doses were selected based on extensive PKPD modeling of our Phase 1 data that showed direct target engagement of A beta lumars at near maximal effect.

Speaker 2

In other words, on the basis of the Phase 1 data We have confidence that at both these doses of AC-one hundred and ninety three will adequately saturate our intended target, of Toxic A Beta Oligomers in the Brain. As we think about the Phase 2 study and the dosing strategy, we anticipate 50 milligram per kilogram dose level will replicate and presumably extend the plaque reduction observed in Phase 1 and the 35 milligrams 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. 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-one hundred and ninety three-two zero one, which we are calling ALTITUDE AD. The agency indicated that it is aligned in principle with the study design.

Speaker 2

We are planning the study as a randomized double blind placebo controlled 3 arm study designed to evaluate the clinical efficacy, Safety and Tolerability of AC193 with up to 180 participants per arm for a total of 540 participants with mild cognitive impairment or mild dementia due to AD. We will initiate ALTITUDE AD as a standalone Phase 2 study with an 18 month treatment duration commencing in the first half of twenty twenty four. The study plan incorporates an adaptive design with interim analyses to inform the possibility of expanding the size of the study from a Phase 2 to a Phase 3 study, which we believe is the most expeditious route to a BLA filing and potential approval. 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.

Speaker 2

Now, I'd like to provide an update on our efforts to assess the viability of subcutaneous dosing of AC-one hundred and ninety three. We recognize the attractiveness of this mode of administration to offer additional flexibility and convenience for patients and caregivers. Over the last 9 to 12 months, we have evaluated several delivery technologies to support the doses we are exploring in our clinical studies. We are very excited about our recently signed global collaboration and licensing agreement with Palazyme. Using Palazyme's commercially validated enhanced Drug Delivery Technology, we plan to initiate a Phase 1 study to compare the PK of subcutaneous form of HD-one hundred and ninety three to the IV form in mid-twenty 24.

Speaker 2

Based on our dose model, we believe there is a potential for competitive commercial product profile of a subcutaneous dosage form of AC-one hundred and ninety three, which may ultimately be commercialized alongside every 4 week IV AC-one hundred and eighty three to potentially broaden treatment options for patients. Today, we also announced that we've secured a credit facility for up to $50,000,000 with K2 Health Ventures, a healthcare focused specialty finance company. And I'll let Matt tell you more on how this funding provides us with additional operational flexibility. Taking a look back at 2023, the year thus far has been a transformational one for Acumen. Our positive Phase 1 top line results enabled us to demonstrate convincing proof of mechanism for AC-one hundred and eighty three further supported by the CSF biomarker data shared today.

Speaker 2

We received encouraging feedback from the FDA on the design of our next phase of clinical development, which we are operationalizing as we speak. Our partnership with Halozyme for the development of a subcutaneous option of AC-one hundred and ninety three extends its product profile in pursuit of greater patient choice and convenience. Any additional financing to support subcutaneous development provides the capital to support the focus of our talented team working to solidify AC-one hundred and ninety three'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.

Speaker 3

Thanks, Dan, and good morning, everyone. 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. If you turn to Slides 5 to 8 in the earnings presentation posted today on our website and on the webcast. In the first slide, you can see an observed dose dependent Trend in the multiple ascending dose cohorts indicating a drug effect of ACU-one hundred and ninety three in CSF levels of p Tau-one hundred and eighty one, total tau, neurogranin and the abeta42 over 40 ratio. This is after only 3 administrations of drug.

Speaker 3

So the fact that we are observing changes is highly supportive of ACU-one hundred and ninety three's target engagement and downstream pharmacology as determined in our Phase 1 study. 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 4 weeks dose of ACU-one hundred and ninety three showed a nominally statistically significant improvement in neurogranate as compared to the placebo group with a p value of 0.037. There was also significant correlation between abetaligomer target engagement and change in neurogranin across all doses. These data are consistent with the mechanism of action and target engagement of ACU-one hundred and ninety three and also provide evidence beyond Turning to PTAL-one hundred and eighty one, we saw changes directionally similar to neurogranate. An nominally significant decrease of PTAL-one hundred and eighty one was And a trend was seen for correlation of change in CSF PTAU-one hundred and eighty one versus target engagement.

Speaker 3

This is encouraging because it further supports that ACU-one hundred and ninety three's mechanism may lead to clinical efficacy given PTAU's established relationship with cognitive decline. Remarkably, as shown in Slide 6, We observed that the change in neurogranin was significantly correlated with the change in PTAL-one hundred and eighty one. Researchers in the field have found correlations between CSF, neurogranate and p Tau, which suggests a biological link between these two biomarkers and provides further confidence in our biomarker observations with ACU-one hundred and ninety three. As shown in Slide 7, correlations between changes in neurogranin and p tau-one hundred and eighty one were more closely related to target engagement, that is binding of PC193 to abeta oligomers than to decreases in amyloid plaque load as determined by PET. While not conclusive, these analyses support the concept that ACU-one hundred and ninety three binding to abeta oligomers rather than plaque reduction mediates its downstream pharmacology and potential clinical benefits.

Speaker 3

We would not expect every biomarker to change with ACU-one hundred and ninety three treatment. And as shown in Slide 8, We did not see an effect on neuropintraxin II. Additional study will be required to understand more about this relatively new biomarker. 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. I'd also like to highlight that our symposium presentation at CTAB was well received by the medical community as Dan mentioned.

Speaker 3

A couple of important points from our presentation in particular, supported the conclusion from our Phase 1 study that ACU-one hundred and ninety three is pharmacologically active and engages its intended target in the brain. The main takeaway I would highlight from our presentation is the confidence we have in the dose selection for our Phase 2 trial based on the observed maximal target engagement derived from our novel target engagement assay. 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 abeta oligomers as being the most toxic species of abeta. At the 50 milligram per kilogram dose, we would expect to reach even greater engagement of abeta oligomers. But in addition, we would also expect to lower plaque load based on our Phase 1 data.

Speaker 3

We would The bottom line is that because of our robust Phase 1 results, we have been able to choose 2 Phase 2 study active dose arms that could both be potentially efficacious and reduce cognitive decline. Another important takeaway from our CTAD presentation is the consistency of plaque reduction in the multiple ascending dose cohorts of INTERCEPT AT. For the 10 milligram per kilogram MAD cohort, 5 of 6 patients on treatment had a decline in amyloid PET celluloids And the single patient without a decline had a small increase of 3.4 centiloids, which is essentially test retest noise. For the 60 milligrams per kilogram cohort, 7 of 8 patients had a decline in celluloids. For the 25 milligrams per kilogram every 2 weeks cohort, all 8 people on treatment had a decline in celluloid values.

Speaker 3

The consistency of these results aligns with the conclusion that reduction in plaque load is due to treatment with ACU-one hundred and ninety three. In summary, our clinical team has been working diligently to prepare for the initiation of our Phase 2 study, of Altitude AD in the first half of twenty twenty four. I won't reiterate Dan's summary of our encouraging FDA interaction this quarter, So I will emphasize that we are committed to executing on the promise of the abeta oligomer theory hypothesis and the potential for ACU-one hundred and ninety three 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.

Speaker 4

Thank you, Eric. Good morning, everyone. As a reminder, our Q3 2023 financial results are available in the press release we issued this morning and in our 10 Q that we will file after closed today. As of September 30, we had approximately $282,700,000 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 twenty twenty six.

Speaker 4

R and D expenses were approximately $11,200,000 in the 3rd quarter. The increase over the prior year was primarily due to increased costs related to drug manufacturing costs, consulting and personnel. G and A expenses were $4,900,000 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 $16,000,000 in the quarter. Today, I'm pleased to announce an agreement with K2 Health Ventures for a senior secured credit facility of up to $50,000,000 Upon closing, dollars 30,000,000 of the $50,000,000 loan facility was funded.

Speaker 4

An additional tranche of up to $20,000,000 is also available, which may be funded in installments upon Acumen's request, subject to review and discretionary approval from K2. This financing provides additional capital to pursue the development of the subcutaneous dosage form of ACU-one hundred and ninety three, which we view as value enhancing for both patients and shareholders, as well as for general corporate purposes. And with that, we can open the call for Q and A. Operator?

Operator

Thank you. And our first question coming from the line of Tom Schroeder with BTIG. Your line is open.

Speaker 3

Good morning. Congratulations on the biomarker data. It's pleasant because it changed. Eric, I was wondering if you can, for us slow thinkers, walk through your logic for abeta42 to 40 going up. I think we talked about we weren't really sure which way it would go.

Speaker 3

I guess it's good it changes. And then with the robust tau 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 that would almost certainly be very safe. So Those are my questions. Thanks. Yes.

Speaker 3

Thanks. Great questions. As far as the A beta forty two over 40 ratio, yes, it's a little complicated, maybe a little confusing. But for whatever reason, even though abeta plaques are made up of abetaoneforty two and they're obviously increased in the brain. In The concentration of abeta42 has 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.

Speaker 3

So when you're abnormal in Alzheimer's, your abeta42 is low. So if you have your A beta 4042 and it works better to use the 42 over 40 ratio, but if you Take the 40 two over 40 ratio and it goes up, that means you're returning people towards a normal non Alzheimer's state. So we tend to think of abeta42 being a bad thing, but really in spinal fluid, Going up is a good thing. So we looked at it as a really positive result. With regard to the tau, Yes, those were fairly impressive results after just 3 administrations of trial.

Speaker 3

And you could raise the possibility of do we need to explore even lower doses. Now from a regulatory standpoint, there is no requirement to find a minimally effective dose. We chose those doses as we 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 dose group, which 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.

Speaker 3

So, yes, it's 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 for the call.

Operator

Thank you. One moment for next question. And our next question coming from the line of Pete Strapolos with Cantor Fitzgerald. Your line is open.

Speaker 5

Hi, good morning, Dan, Matt and Eric. Thank you for the update. So one question that I have is, at CTAD, There was a great subgroup analysis for denanumab and lukanumab where certain subgroups of patients have greater clinical benefit versus others. For example, baseline tau levels, age, things of that nature. So how are you thinking about these data?

Speaker 5

And Will you incorporate any of these learnings for the inclusion exclusion criteria for Altitude?

Speaker 3

Yes. Thanks. Another great question. So those were very interesting presentations. And I think from a standpoint actually the Lilly program, 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.

Speaker 3

So it all gets back to this idea that people who are earlier in the disease can benefit more. So we've thought quite a bit about that in terms of our upcoming study. And one of the things in our presentation that you may have noticed is that we do have people who were included in the Based on a visual read of their amyloid PET scans with actually very low celluloid levels. And initially, there is some discussion of maybe we shouldn't include those people in our trial because 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.

Speaker 3

So essentially the way the study was set up based on our Phase 1 results, we know that we'll already be getting some of those really So it was a 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.

Speaker 5

All right. Thank you. 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 centaloid levels What are those changes?

Speaker 3

Yes. Well, the correlations between Target engagement and 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 In this case, the biomarker changes are related to binding to these abeta oligomers more than related to plaque reduction.

Speaker 5

Okay. Thank you. Thanks for taking my questions.

Operator

Thank you. And our next question coming from the line of Paul Matteis with Stifel. Your line is open.

Speaker 6

Hi, this is Catherine on for Paul. Thanks for taking our question. On the Phase twothree, what do

Operator

you expect to look at

Speaker 6

in the interim? And what would prompt a move into

Speaker 2

Hi, Catherine. Thanks for your question. So as we mentioned, we had a favorable interaction recently with the FDA on the Phase twothree 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, maybe share some additional information, but not in a position to comment today.

Speaker 6

Thank you.

Operator

Thank you. One moment for next question. And our next question coming from the line of Colin Bristol with UBS. Your line is open.

Speaker 7

Hey, good morning and congrats on all the progress. Maybe first one for Eric. Eric, I'm curious, what did you in terms of the Lechembe subcu 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 subcu193. And then just Stephanie, more of a sort of administrative question, but how long do you think it's going to take to enroll Phase 2?

Speaker 7

Thank you.

Speaker 3

Okay. Well, let me talk about the subcu first and then we'll take the other question afterwards with Dan. 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 ARIA E was driven by Cmax rather than AUC. And so with the subcu formulation, you would have a lower Cmax and so you'd have less ARIA. And that just turned out not to be the case.

Speaker 3

It's unusual in science 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 we got an answer to that question. I think from our standpoint, having well and for other people in the field actually, Having a subcu 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, but it still means that it can be useful for people in terms of convenience and that sort of thing.

Speaker 3

From that standpoint, we got a definitive answer to that question and but subcu is still something we want to look at. So I'll turn it over to Dan to talk about timelines.

Speaker 2

Sure. Thanks, Eric, and thanks, Colin, for the question. In terms of the ALTITUDE AD study, as We are in the mode of operationalizing and focused on execution. 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 with respect to 193 is we're in a good moment of time for that.

Speaker 2

In terms of specific timelines, it's just too early to say. I mean, we've got to get sites up and running. There are a series of developments over the next 12 months that will inform more specifically what our timelines are for enrollment, We'll be happy to provide additional detail when we have some visibility on where we stand in terms of enrollment and outcomes.

Speaker 7

Great. Thank you.

Operator

Thank you. And I see we have a follow-up question from Pete Strapolos from Cantor Fitzgerald. Your line is open.

Speaker 5

Yes. Thank you for taking the follow-up. Again, Eric, another, I guess, Very interesting presentation that ETSIT had to do with an analysis of baseline characteristics and ARIA by fordzinonumab. Just wanted to hear your take on that data and sort of how you're going to implement that for your Phase 2, if you can implement any of those factors for your Phase 2.

Speaker 3

Well, yes, we've You know, a lot about risk factors for ARIA. And as you know, one of the big ones is APOE4 status. And one of the interesting things that we've presented before is that in our 6 APOE4 homozygous, we didn't have any cases of ARIA. So from that standpoint, I think it's good. It's interesting, but not surprising that Some of these findings were found and in our upcoming Phase twothree study, we'll more clearly determine whether APOE4 Carrier status is a risk factor for RIAE.

Speaker 3

Eliminating that risk factor would obviously be Really beneficial in the clinic because now there's some recommendations that people We tested for their APOE carrier status before you begin treatment. Some clinicians, if you were in APOE for homozygous would not initiate some of the drugs that are either approved or being looked at for approval. So not having that as a liability would be really clinically, I think, a really major benefit.

Speaker 5

Okay. And some of the other factors like antihypertensives,

Speaker 3

The Northrop Yes, yes. I'm sorry. It's really difficult, at least for me to interpret those 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 That's the sort of thing that I would want to see those results replicated before we take those too seriously.

Operator

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 1

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.

Operator

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

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Key Takeaways

  • Acumen reported positive CSF biomarker results from its INTERCEPT AD Phase 1 trial, including significant reductions in neurogranin and directional improvements in p-tau181, total tau and Aβ42/40 ratio after only three doses of ACU-193.
  • The FDA has aligned in principle with the ALTITUDE AD Phase 2 study design—a randomized, double-blind, placebo-controlled three-arm trial (35 mg/kg and 50 mg/kg IV every 4 weeks) with an 18-month treatment period—and Acumen plans to initiate the study in H1 2024 with adaptive interim analyses enabling a potential Phase 3 expansion.
  • Acumen entered a global collaboration and licensing agreement with Palazyme to develop a subcutaneous formulation of ACU-193, targeting a Phase 1 PK comparison study against the IV form in mid-2024 to improve patient convenience.
  • The company secured a senior secured credit facility of up to $50 million from K2 Health Ventures (initial $30 million funded), supplementing its $283 million cash and marketable securities and supporting operations and subcutaneous development through H2 2026.
  • Robust Phase 1 top-line results were well-received at AAIC and CTAD, validating ACU-193’s mechanism of action against toxic Aβ oligomers and informing the dosing strategy for the upcoming Phase 2 trial.
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Earnings Conference Call
Acumen Pharmaceuticals Q3 2023
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