Q2 2023 Acumen Pharmaceuticals Inc Earnings Call

Thank you for standing by and welcome to the argument that Pharmaceuticals second quarter 2023 update call. At this time all participants are in a listen only mode. There will be a brief overview followed by a question answer session.

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I'd now like to turn the call over to Alex Brown head of Investor Relations. Please go ahead.

Thank you Lisa.

Morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 30th 2023.

With me today are Dan O'connell, our Chief Executive Officer, Dr. Eric <unk>, our Chief Medical Officer, and not to do that our Chief Financial Officer, and Chief business Officer before we begin I will 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.

Please note that during today's conference call. The forward looking statements for 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.

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 that 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&A now I'll turn the call over to Dan.

Okay.

Thanks, Alex Good morning, and thanks to everyone, who has joined US today, a few weeks ago acumen presented compelling clinical data in support of <unk> 93, our asset for the treatment of early Alzheimers disease.

Our positive phase one topline results solidify <unk> hundred 90, <unk> potential as a future option.

All summers treatment paradigm.

The success of our novel target engagement assay robust study design.

Created execution enabled us to demonstrate convincing proof of mechanism inclusive of significant.

Black reduction.

<unk> hundred 93 was shown to be safe with a broad therapeutic index.

And with attractive dosing options for our next phase of development.

We believe these results substantially derisked, our asset beyond our expectations at this stage in its clinical development.

I'm extremely proud of our team's achievement and we'd like to thank our employees investigators and staff and patients and caregivers for their dedication to advance Ace you want 93, as a potential best in class treatment in this important field.

If you have not already done so I encourage you to go to the investors section of our website and view the webcast from July 17th.

With our full presentation of the intercept phase one topline results.

Moving forward, we are firmly committed to harnessing the optionality provided by the phase one data set we have a knowledgeable and adept clinical regulatory and CMC team that actually met with significant large pharma experience in all summers drug development given.

Given the positive intercept trial data, including the observed.

Plaque reduction by EUR 93, our team is working urgently to integrate the findings into both our future clinical plans and our broader strategic priorities.

We continue to analyze the data from this study and expect further biomarker data to be available in the fourth quarter.

We are also finalizing our doses for our next clinical trial, which Eric will discuss.

Made modest changes to our planned phase III design, given <unk> ability to rapidly reduce plaque such as incorporating amyloid pet into interim analyses.

As previously disclosed our phase three design incorporates interim analyses to inform the potential of expanding the size of the study from our phase II to phase III study, which we believe is the most expeditious route to a BLA filing and potential approval.

We continue to anticipate an end of phase II meeting with the FDA to discuss this phase three design in the fourth quarter.

As mentioned on our July 17th call. We are investigating the viability of subcutaneous dosing of <unk> hundred 93, as we recognize the potential attractiveness of this mode of administration to expand patient dosing options.

We have made meaningful progress on this front and aim to have more details to share later this year.

I should also comment that we are continuously evaluating strategic partnerships and are committed to exploring value enhancing opportunities could advance <unk> hundred 93, as development and align with acumen shareholders' interests.

Before I turn the call over to Eric I would like to emphasize the degree to which our phase one results had elevated <unk> hundred 90, <unk> profile in the field.

We believe <unk> hundred 90, threes high selectivity to Baidu to toxic soluble a beta oligomers and the brain.

<unk> CSF target engagement assay.

Or is it the potential to differentiate in terms of clinical efficacy.

<unk> hundred 90, <unk> ability to significantly reduce plaque in only three months in.

With currently approved and under review anti a beta antibodies, we believe further de risks the assets potential to deliver efficacy.

Monthly dosing provides another important point of differentiation.

We intend we intend to drive significant momentum from these timely results and look forward to sharing our progress with you as we execute against our operational and strategic priorities in the weeks and months ahead.

With that I'll hand, the call over to Dr. Siemers.

Eric.

Okay.

Thanks, Dan and good morning, everyone.

As I'm sure you can tell we are very pleased that our intercept <unk> topline results for <unk> hundred 93 provided important clinical proof of mechanism data for a monoclonal antibody developed to selectively target toxic a beta olive emerge. We believe these results support our efforts efforts to develop a best in.

In class therapeutic for Alzheimers disease.

In addition to the demonstration of AC you were 93, Bounder oligomer and CSF our measure of target engagement. We are also very encouraged by the rapid dose related amyloid plaque reduction at our higher doses 60 milligrams per kilogram every four weeks and 25 milligrams per kilogram.

Every two weeks.

Black appeared to be reduced at a rate comparable to approved or soon to be approved monoclonal antibodies at a similar time point after starting treatment in this case around three months.

The finding of plaque reduction further demonstrates the evidence of 193 as activity in the brain and is a positive development given the established relationship between robust plaque reduction and slowing of cognitive decline.

You will see in the data we presented that 193 also demonstrated robust dose related target engagement 193 bound to <unk> as measured by a novel assay developed by acumen that exceeded expectations.

We observed that our higher doses approach maximal target engagement. This is a finding that we are particularly excited about given that this is the first time.

All of them are targeted antibody has demonstrated target engagement.

Taken together the decrease in <unk> seen at higher doses and clear demonstration of target engagement with all other tumors provide substantial evidence of the intended central pharmacology of <unk> hundred 93 and proof of mechanism.

With regard to safety 193 was well tolerated with no drug related aes in overall low rates of ARIA E <unk>.

Interestingly, we did not observe ARIA E and six study participants who were dosed with 193, and who were eight Boe E for homozygous and we will continue to monitor this finding in our next study as a potential point of differentiation compared to other monoclonal antibodies for AAD.

And based on the pharmacokinetic profile observed monthly dosing is supported.

Importantly, intercept a D provided valuable information required to design. The next phase of the program, including dose selection decisions.

We are currently in the process of modeling doses for our phase two study.

Harms.

Have provisionally identified a high dose of approximately 50 to 60 milligrams per kilo Gram and are considering a mid dose in the range of 25 to 35 milligrams per kilogram. These would be every four week doses. We are confident in our modeling algorithm and are targeting a mid dose that lies in our.

Target engagement, EMACS curve, and an area where substantial target engagement occurs.

This is because of that location, we can potentially observed robust target engagement with regard to olive boomers.

Based on our phase one plaque reduction data, we believe it is likely that the higher dose in our phase three study will result in plaque reduction and at the lower dose plaque reduction could be demonstrated in a longer term study.

Finally, as far as broader sediment in the Alzheimers space. We attended the Alzheimer's Association International Conference in Amsterdam. This July and the general tone of the meeting was very positive.

With one monoclonal antibody now having traditional FDA approval and a secondhand nobody likely to achieve traditional approval after decades of attempting to develop disease modifying therapies for Alzheimer's disease. The field is now seeing early successes.

While these new treatments are not a cure for alzheimers disease, they represent a substantial step forward for patients and families.

We had acumen and hope to further advance disease modifying treatment for Alzheimer's disease by developing <unk> 193, as a best in class treatment option.

And with that I'll turn the call over to Matt.

Thank you Eric good morning, everyone.

As a reminder, our second quarter 2023 financial results are available in the press release, we issued this morning and in our 10-Q that will be filed later today.

As of June 30, we had approximately $172 million in cash and marketable securities on our balance sheet. Following the announcement of our positive phase one results in mid July we closed an upsized follow on offering which brought in net proceeds of approximately $122 2 million.

Our cash on hand is expected to support our clinical our current clinical and operational activities into the second half of 2026.

Accordingly, we believe that we have enough runway to complete our phase two standalone study.

Highlighted in our risk factors this timeline could be affected by clinical trial enrollment rates and other variables as is typical in the course of clinical development.

R&D expenses were approximately $9 $1 million in the second quarter of 2023, the increase over the prior year was primarily due to increased costs related to personnel consulting and other items related to the phase one clinical trial, which we completed during the quarter G&A expenses were $4 $3 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 $13 $5 million in the quarter.

We are encouraged by the strong support.

For the development of Acu 193, following our positive phase one results.

And we will remain financially disciplined as we use our capital to advance our clinical program for the asset and deliver value to patients and shareholders.

And with that we can open the call for Q&A operator.

Thank you.

If you would like to ask a question. Please press star one on your telephone.

One moment, while both compile the Q&A roster.

Okay.

And our first question today will be coming from Colin Bristow of UBS. Your line is open.

Hey can you guys hear me okay.

We can yes.

Hey, good morning, guys and thanks for taking my question. So I was just wondering.

What additional analyses.

Any sort of referring to the CSF and plasma Biomarkers have you done since your topline.

And anything you could perhaps share with us and if not what sort of additional updates on the CS can we expect over the next six to 12 months and then just maybe.

193 has a mechanistic profile, which is now closer approximates to the Academy.

Can you maybe just again just take us through how you see or what you expect to be the key points of differentiation into Canada. Thank you.

Well, Greg Yes. So this is Eric and as far as the biomarker question.

It's a really turned in question as you well know CSF and plasma Biomarkers is a rapidly developing field and we've all along said that we are.

Im going to follow the field carefully and send off the biomarkers that appear to be the most promising and so we didn't have all of that pre arranged at the time, we did the study, but what we've now done and we're in the process of finalizing.

Establishing contra.

Contracts to look at Biomarkers to ship the samples to get the results and those results will come in.

Later in the year so.

We'll look at the kinds of things that appear to be promising in the field right now so as you probably know.

Beta of 42 to 40 ratio, especially in CSF, but also in plasma.

Is receiving a lot of attention.

P Tau, especially P. Till 2017 is receiving a lot of attention we think that <unk>.

Because it represents astrocyte function could be very interesting along with neuro Brandon because it reflects synaptic function.

So we'll be sending the CSF and plasma samples out for those assays.

In terms of what results we might anticipate this was a short study people got it most doses of drug.

And so it's possible that we would see a drug effect, but not necessarily likely.

So the biggest reason for doing these assays in this study is to provide experience for the next studies when those biomarkers will actually be very crucial in the development program. So.

We may see a drug effect in this study we may not but the important thing is we all have them the experience with these assays to apply our next study.

With regard to differentiation.

I think I'll, just turn that one back to them.

Sure. Thanks, Eric and Thanks, Scott for the question I think in terms of differentiation from our Cana map.

At both dimensions of safety and efficacy.

Got it.

With some basis for.

That supported in the intercept study, but also most importantly in the next study being the one to really provide clinical proof of concept and maybe a path towards registration and those would be the ability to push dose and have better therapeutic coverage over toxic ABL <unk> is an important aspect of this that I think the general selectivity for.

193, as we've reported it is 500 fold selective for oligomers over monomer and roughly 90 fold selective for <unk> over fibrils. So we think that the.

Roche that we're taking is to demonstrate.

Comparable or better safety profile, but ultimately, we're really looking to drive clinical benefit in terms of efficacy.

And that would obviously be a key point of differentiation within the field.

Alright, Thank you very much.

Thank you and my Mom is Brian next question.

And our next question is coming from Paul Matteis of Stifel. Your line is open.

Hey, there. Thanks for taking my question I wanted to clarify some of the comments you made around that 25% to 35 Meg per kg once monthly dose that youre planning.

What exactly would you expect as it relates to plaque reduction from that dose level. You. Obviously soft plaque reduction at 25 every other week in this study and I think in your prior comments you had talked about CSF exposure data from earlier in this trial supporting that sufficient drug levels.

We are still on board out to I think three weeks that you were hopeful in monthly and so certainly encouraging that you're pursuing monthly, but I guess, what what's the gap there for why you wouldn't expect this dose to match.

As well on plaque reduction of some of the other <unk> antibodies.

So, yes, I guess I can take that this is Eric.

We've spent a lot of work obviously looking at doses for the next study and we are narrowing down the range as you pointed out but we haven't finalized those so one of the things to be aware of and this is a little bit of an anecdote, but when we first designed the intercept study.

Our phase one study.

There was a.

Post dose pet scan in there and a few people acumen said well why do you need that we don't target plaque and my reply was.

That's the theory, let's find out what happens and so when we got the data.

We saw we did see this plaque reduction at the higher doses that I think it's just an important lesson for drug development generally is.

Don't expect that you know what the results are going to be but you have to look for those results.

So that's really exactly what we're going to do.

Actually even for both doses in our next study so I think at the higher dose based on our intercept data we have.

Pretty high likelihood that we will see plaque reduction at that higher dose at.

At the lower dose.

We really we will see what we get.

We got some plaque reduction at 25 mix per kg every two weeks. So a total of 50 megs per kg every month.

But that was only with three administrations of drug. So the next study will be 18 months. So it will be a longer study and we'll see what will happen to plaque.

That lower dose now again, our target is actually olive mers or original target the plaque reduction.

No it's.

It's not a bad thing, but it is not necessary for us to have efficacy or at least that's our view.

So I think it's.

This is why you should do the studies to get the results and so whether we will see plaque reduction at the lower dose. We're not I think is an open question at this point.

But either way once you get into a phase two three study, it's all about clinical efficacy and that's what you really need to be starting to focus on it. So it's a great science experiment, we're going to do it.

But we're also sort of shifting to where the emphasis is going to be on some of the clinical measures.

Okay. Thanks, Eric I appreciate it and then just one question on the sub Q I know, it's early but based on some of your preliminary modeling work. What do you think you might be looking at in terms of.

The range of different drug volumes, you might tasks and also that frequency of potential injections.

Yes, Thanks Paul.

It's a little.

Early for us to comment on it.

Those are all the details.

Sure.

Sorry, there's a little feedback.

So in the fourth quarter. This work is ongoing we've got some good insights into where we're headed I do think that the.

We do not anticipate a high dose of 50 or 60 mix per kg could be amenable to a sub Q4, Matt I think we could be.

Clear on that but I do but we will have more details I'll take out precisely the plan and how we expect to proceed with the sub Q in the fourth quarter.

Okay alright, thank you.

Thank you for your question one moment.

The next question.

Yes.

And our next question will be coming from Tom Shrader of <unk>.

<unk> Your line is open.

Good morning, Thanks for taking the call.

Given the robustness of Euro oligomer binding assay, how interested are you in the level of 193, you need to saturate oligomer. Once plaque is gone and do you think youll get those data from the next trial and then a second inclusion trial is how appealing is to do some screening for Tao I think Lilly has shown.

Our suggested you can really increase the separation between treated and untreated if you screen for Tau. Thank you.

So yes, thanks, Tom for the question in terms of.

Essentially being an antibody excess versus olive emerge. So I mean, that's something that we've spent a lot of time thinking about.

One sort of <unk>.

Detailed but I think it addresses the point is that if you take 193, the antibody and just spike it into spinal fluid from a personal a bold climbers you get a little bit of a signal on that target engagement assay, but not very much but when you give it to people intravenously and then it obviously is.

Goes through bringing interstitial space and whatnot, you get a much bigger signal so that tells us or at least.

I think that that means that it's going through a compartment, where the all of them are concentrations are substantially higher than in CSF, which I think intuitively. It makes a lot of sense. So in terms of.

When are you really in antibody excess so you are talking about an antibody excess and a compartment, bringing interstitial fluid that you can't directly sample so.

A tricky thing to figure out we do know that and we are constantly doing additional analysis on these data, but if you look at plaque load with regard to target engagement signal.

There is no relationship there there was some thought that maybe the augurs for sort of attached to the plaques and the more plaque you had a baseline the bigger target engagement signal you would get in there is no real clear evidence that that's the case. So these are all under mers or in a compartment.

That is it.

Here's to be independent really of plaque.

But it's different than spinal fluid. So the team is working on an assay now to look at free olive <unk> and spinal fluid with all the caveat spinal fluid is not really the compartment where.

Where the action is but the team is working on an assay to do that it's technically really difficult all of them are concentrations in spinal fluid, a really low or less than two picomolar to start with and then with the antibody.

They will become even lower so it's technically a difficult thing to do but the team is working on that.

And then the other thing just briefly in terms of Tau and.

Using that to select patients.

That again.

Which obviously is what Lilly did.

<unk>.

Really wonderful science experiment Im not sure how that will play out in terms of clinical medicine.

Because that means that people have to be amyloid positive based on a pet scan or spinal fluid and then on top of that you have to be <unk> positive, but right in the right range of tower positive and basically it means that one out of 10 people that you screen for the therapy.

<unk> will be essentially eligible for it.

So it's a really interesting from a scientific standpoint, I'm just not sure that practically.

That would be something you could do in the clinic. So we're.

Obviously look at Tau at baseline and see if that co varies with the efficacy and all of that but we have made the decision not to include Tao as an inclusion exclusion criteria.

We will of course make.

Amyloid positivity in an inclusion exclusion criteria, but we're not going to specify a certain level of tau.

Great. Thanks for the thoughtful answers.

Thank you one moment for the next question.

Yeah.

And our next question will be coming.

One moment please.

Our next question will be coming from Pete Stavropoulos of Cantor Fitzgerald. Your line is open.

Hi, Dan, Matt and Eric Thank you for taking our questions.

So now that you've had several weeks to socialize the data internally and externally just curious to hear your thoughts have evolved in terms of possible reasons from a mechanistic standpoint on the lack of ARIA in April .

<unk> and observe the owning females as if by chance or is there some plausible mechanistic reasoning.

Thank you.

Yes, Eric.

That's a great question too in terms of it just occurring in females.

Honestly don't have a good explanation for that.

It could be GM will see alzheimers disease is a bit more common in females, but.

So I don't have off the top answer on that in terms of the <unk> homozygous.

There was a preprinted paper that just came out this week that actually show that people.

Who were April four carriers had a different morphologies are there plaque than people who are non carriers, which.

Suggest that one possibility is that <unk> 193 targets, an epitope, that's maybe a little bit different than the plaque targeting <unk>.

<unk> antibodies that have this relationship between <unk> and <unk>.

So the first thing and the other thing even in terms of the homozygous.

Bob surveys <unk> I mean, this is a small sample size phase one study we need to see if it replicates.

But if it does replicate I think that is a clear point of differentiation.

For <unk> hundred 93.

And we will have to have a lot of further discussions about what the mechanism might be but clearly differentiate <unk> hundred 93.

Alright, Thank you for taking my questions.

Thank you one moment to the next question.

And the next question will be coming from.

Judah Frommer of credit Suisse. Your line is open.

Hey, guys. This is Nick on for Julian Thanks for.

Thanks for taking our question.

So with what can I, mab reimbursement and post infusion market monitoring seemingly getting any more traction recently.

We're just wondering what's what's the read through for 193, if the safety profile that we saw last month hold up.

I know we were just talking about differentiation from Mccann amount, but I just wanted to.

So just to confirm.

Is the are you occurrence that we see with a cameraman does that the right bar that you'd be looking to be with with 193.

Yes, thanks, Nick.

I think.

Clearly, we do think that the R&D rate for the <unk> as the benchmark for sort of a safety profile in this in this indication and we think well 93 it can be.

As good or better on that score so that as that is our intent to demonstrate that in a longer one.

The duration study.

Thank you and our next question.

Okay.

Our next question is coming from Charlie Yang of Bank of America. Your line is open.

Hello.

Okay.

Thanks, Charlie.

Alright, sorry, I think.

I missed that earlier.

Yes, Thanks for taking the question this is Charlie for Jeff.

Two questions. Please.

First could you clarify regarding the reason for it not specifying that the towel level I mean I understand that.

It's it's.

Oh scientifically interesting, but I think given the consistency in terms of what really has shown the.

The trial as well as I guess somewhat with vault <unk>.

Preliminarily, we will post hoc data with the Canada, Matt that also show some favorability in terms of the efficacy in the.

It's kind of a lower to intermediate Hao.

<unk> just one.

Wouldn't it make sense to have that as our inclusion exclusion criteria to improve the.

D a success.

<unk> one.

And number two can you just discuss.

The kind of the cash the way that you have I think just given how little bit travel for phase two.

It seems like by the end of the.

By the end of cash go away.

Around the timing.

You will.

And with your cash so.

What's the.

I guess, what's the.

In terms of how do we get another raise or perhaps having some sort of a partnership.

Prior to the actual read out.

Yes, Thanks Charlie.

If you were to hit the first one I can take the second yeah, yeah exactly.

So again in terms of using Tau as an inclusion exclusion criteria, which essentially and we'll see what the label ends up being for the nanometer, but more than likely youll have something in the label that will track with that.

Again, I think it's a great science experiment I don't think I think it will be a real challenge in terms of making that work in the world of clinical medicine.

Now what we are doing in our study and so our patient population is an early alzheimers disease right and so these are people with either mci or mild dementia, but not beyond that so the lowest mini mental score you can have is 'twenty two for instance.

We've also and this is some ongoing.

And now have crews that were doing is in our intercept study, we actually used a hybrid model of looking at amyloid positivity. So it wasn't just based on a pet scan SUV or it could also be based on a visual read which may actually.

Be able to allow you to pick up people, who are amyloid positive, but not so blatantly that they crossover SUV or threshold.

And so that I think will help us dial in with this milder population.

Without having to take the extra step of a tau pet scan.

Looking to the future.

And I don't think the field is there just yet but there may be some time in the future. When one of these plasma Tao phosphates, how assays could be useful and we'll obviously continue to track that but in terms of our next trial, which is a phase two slash three so if it becomes a phase III.

While that's a registration trial, we have to make that mirror clinical practice as it exists more or less today.

And.

So that's that was the overall thought process in terms of the design of the phase three trial.

So for the cash question, yes.

Thanks, Eric.

Charlie at the current time, we have runway through interim readouts anticipated for our phase III study.

Based on our current assessment today, we believe that we have enough runway to finish up phase III Standalone study shouldnt be not expand it to phase III. Following a positive interim analysis of course, the timeline could be affected by the peso.

Clinical site initiation enrollment rates et cetera, but generally based on our current tenant we do have a cash runway through a standalone phase III study.

Subject to the qualifiers that I mentioned.

In terms of partnering we think the optionality.

Using a phase II III design with the potential to expand the phase III as I mentioned earlier on the call is that.

Fast as potential path to a BLA filing and potential approval and we would anticipate and continue to have engagement from prospective partners as to.

Potentially.

Working with us, particularly in terms of the phase III portion.

The development of <unk> hundred 93, so those things are kind of part of our bread and butter.

Strategy will continue to evolve.

Over the course of the next.

Year itself.

Great. Thanks, so much.

Okay.

Thank you. This concludes the Q&A session I don't see any more questions in queue I would like to turn the call back over to management for closing remarks.

Great. Thanks, Lisa and thank you everyone today for listening in.

We here at the company are always available and have further questions.

This concludes today's conference call. Thank you all for joining you may now disconnect everyone have a great day.

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