Acumen Pharmaceuticals Inc. Q1 2023 Earnings Call
Okay.
Good day, and thank you for standing by and welcome to the acumen Pharma Q1, 2023 conference call and webcast.
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I would now like to hand, the conference over to Alex Brown head of Investor Relations.
Thanks, Joe.
And welcome to the acumen conference call to discuss our business update and financial results for the quarter ended March 31st 2023.
To me today are Dan O'connell, our Chief Executive Officer, Dr. Eric Schwartz, our Chief Medical Officer, and that do Bell, our Chief Financial Officer, and Chief Business Officer.
Before we begin I'd encourage listeners to go to the investors section of the acumen website to find our press release issued this morning and related slide presentation that we'll discuss today.
Please note that during today's conference call. We may make forward looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans.
Statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward looking statements. Please see slide two of the accompanying presentation. Our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ much.
You really can 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&A I'll turn the call over to Dan.
Thanks, Alex Good morning, and thank you to everyone for joining us today. The first quarter of 2023 marked the completion of enrollment in our phase one intercept 80 trial.
Are you waiting issue 193 in early Alzheimers patients.
The study is near completion with top line results expected in the third quarter.
For those of you who may be new to acumen of our product candidates. If you want any tree is differentiated from other monoclonal antibodies studied in Alzheimer's disease based on its high selectivity for any beta oligomers.
Scientific consensus a search that lingers Rd, most toxic format the data and once they bind to neurons inhibits synaptic function and reduce neuro degeneration.
We're pleased that our top line results are positioned to provide important clinical proof of mechanism data to a monoclonal antibody developed to selectively target toxic abid oligomers any effort to develop a next generation therapeutic for Alzheimers patients.
Intercept Eddie will provide valuable information required to finalize the design of our next phase of the program, including dose selection at present, we have.
Growing confidence that every four week dosing is a viable scenario for HC 193.
In addition, as previously disclosed preliminary CSF PK data from cohort three are 25 milligram per kilogram single ascending dose cohort showed acu was 93 concentrations substantially above reported levels of EBITDA oligomers, indicating this may be a dosing option to include in our next study.
We continue to prepare for phase III three activities in anticipation of successful results from our phase one study.
An end of phase two meeting with the FDA to discuss the design of the next trial is anticipated to be held in the fourth quarter.
Previously disclosed the study design incorporates an interim decision to expand the size of the study from our phase II to phase III study, which is the most expeditious route to a BLA registration.
We along with the rest of the field are encouraged by the positive momentum in the evolving Alzheimers landscape. We are keen to see upcoming outcomes for Makena maps Advisory Committee meeting date, and any shift in CMS coverage decision, which would increase access and uptake for this therapeutic option for patients. We're also highly interested in digesting.
The full dataset from container maps Trailblazer, two phase III study announced last week, we recognize that robust quite clear it to show clinical benefit, albeit modest and with safety caveats. We believe there is potential better options for patients that involve selective targeting of toxic species more closely related to disease pathology and that <unk> 93.
Bodies that product profile.
We look forward to sharing our intercept Eddie topline data with you in the third quarter of this year, a dataset that will be informative from a safety target engagement and dose ranging perspective.
With that I'll hand, the call over to Dr. Siemers Eric.
Thanks, Dan and good morning, everyone. We continue to work diligently as we near the finish line of our phase one trial as Dan highlighted the totality of the data from intercept will be important for choosing doses for subsequent studies of <unk> hundred 93.
This includes data on safety CSF PK amcs's target engagement.
As I mentioned on our last call at the end of March the assay for our target engagement is designed to measure the complex of a beta oligomerous bound to AC <unk> hundred 93, and CSF, we have since run preliminary assay tests using CSF from patients, which have increased our confidence that the assay is.
As intended.
Recall that all of our concentrations in CSF are generally reported to be less the two peak or more which means that our target engagement assay must be very sensitive.
We also anticipate announcing exploratory data with our top line results from our phase one study, including current state computerized cognitive testing as well as arterial spin labeling pulse sequences on MRI, which will determine if cerebral blood flow is increased after treatment with <unk>.
193.
While these analyses are exploratory and may not result in a clearer signal in this small study with a short duration of treatment. These techniques may be employed in the subsequent larger clinical trial using <unk> 193.
As a reminder, we have included typical clinical measures like the CVR sum of boxes and the Adas cog in our phase one study. However, because this is a small short study it is unlikely that those measures will show a drug effect.
During the first quarter our team also.
So presented a poster at ADP in Sweden that demonstrated the utility of a human in vitro model of induced pluripotent stem cell derived excited Tory neurons for a better understanding of which forms of a beta olive <unk> contribute to the pathogenesis of <unk> in the human brain.
This study found that soluble a beta size may influence synaptic binding.
Low molecular weight soluble a beta species, such as monomers dimers and primers demonstrated at the lowest levels of detectable synaptic binding compared to those of mid and high molecular weight defined as greater than 150 kilo Daltons. We believe that these research efforts can contribute.
Two the development of next generation therapies with higher selectivity for toxic soluble amyloid species that are the most relevant to alzheimers Genesis such as Acu and <unk> 93.
Finally, the success of dynamic map in the Trailblazer Alts to study announced last week provides further scientific support for the amyloid beta hypothesis broadly.
These results build on the success of what here May have reported in the phase III clarity trial.
Broadly speaking these antibodies are both related to the amyloid hypothesis there are important differences between them.
The nanometer targets deposited amyloid plaques and reduces plaque load substantially with dosing every four weeks, but kitimat targets a beta prototype roles, but also reduces plaque with every two week dosing.
The rate of ARIA E with Banana may have been Trailblazer <unk> two was reported to be 24% for <unk> the rate of ARIA E was reported to be 12, 6%.
For both antibodies about 20% to 25% of ARIA E cases, where symptomatic.
We believe that <unk> hundred 93 targeting solid tumors has the potential to have lower rates of ARIA E with equal or better efficacy compared to <unk> <unk>.
We applaud the well run study results from Trailblazer alts to clarity that solidify forward momentum in the field. While these treatments are a good first generation start.
You were 93 may further improve the benefit risk profile profile of a disease modifying treatment for patients and families navigating alzheimers disease.
And with that I'll turn the call over to Matt.
Thank you Eric good morning, everyone.
As a reminder, our first quarter 2023, <unk> 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 March 31, we had approximately $184 million in cash and marketable securities on the balance sheet and continue to expect that cash to last through 2025.
R&D expenses were approximately $8 7 million in the first quarter <unk>.
The increase over the prior year was primarily due to the increased activity in the ongoing intercept trial.
G&A expenses were $4 $4 million in the quarter with the increase over the prior year, primarily the result of increased head count as we built the company to support intercept.
This led to a loss from operations of $13 $1 million in the quarter.
We are encouraged to report topline data for intercept a day in the third quarter and we will remain financially disciplined as we use our capital to advance our clinical program, Tracey 193, and deliver value to patients and shareholders.
And with that we can open the call for Q&A operator.
Great. Thank you.
This time, we will conduct a question and answer session as a reminder.
If you want to ask a question. Please press star one on your telephone and then wait for your name to be announced.
Your question. Please press star one again, please standby, while we compile the Q&A roster.
Our first question.
I believe this is James on the phone for Stefan.
Hi, This is Jason.
Thanks for taking our question on for Paul Matteis.
We're just wondering how are you thinking about the different scenarios for what Youre phase Tim could look like and what exactly you will be able to test.
For example, let's say.
190, <unk> you were to have a similar effect size as the a beta antibodies.
With this study would be powered for stats on these clinical sales scales or would you be looking at something else.
At the end term and basing your decision to expand the trial.
Any color there would be great. Thanks, so much.
Yeah. Thanks, James So I'm going to invite Eric to comment on that question. Good question, Yes, sure. So yes. Thanks, great question.
So the team has been working hard on finalizing the design of that study, it's not completely finalized yet but.
Yes. So the question that you've raised we'll look at a number of different things in order to make the decision whether to continue the study is a phase two or to increase the size of the study and make it a phase III registration trial, so that interim analysis.
This involves an algorithm that we'll look at a number of different things. So of course, they'll look at things like the.
The Iris, which will be actually our primary outcome, but also the CVR sum of boxes, Ddos cog that sort of thing.
Obviously, if you would have statistical significance on one of those clinical measures at an interim analysis I think that would be a fairly clear signal.
Up to a phase III.
But we will look at a variety of other things.
And those things may include things like the computer archive computerized cognitive testing that we're using in our phase one study.
And also a variety of Biomarkers.
And just to give you. One example of that phosphorylated Tau.
Both in blood and spinal fluid seems to be quite good.
Biomarker for effects of drugs.
<unk> pathology in Alzheimer's disease. So in other words, if youre drug effects amyloid plaques or in our case.
To all our numbers if you see a change in <unk> that really gives you a sign that you are having an effect on the underlying disease process.
So we have an algorithm put together.
We will look at several different things like that and then that will trigger the decision of do you increase the size of the study to a phase III or do you just continue it out.
As a phase two study.
So hopefully that addresses the question that you brought up.
Yeah very helpful. Thank you.
Great.
The next question into Q. Please.
Okay. Our next question comes from Tom Shrader with Bts. Please go ahead with your question.
Good morning, Thanks for taking the question.
You're doing all this elegant work with I think one of the biggest questions in the field, which is which all the <unk> really matter is it changing your thoughts on target engagement.
I assume you'd like to have antibody levels that only hit the relevant particles. So is it are you learning to.
<unk> is an overestimate or do you think you need to get most of the particles in order to be safe or is that something you need to read out from clinical data. Thanks.
So maybe al.
I'll take that one too so again I always have to provinces. So thanks that.
Another good question, but I always have to preface this by saying I'm a clinical trial is by nature and so I think the real answers ultimately have to come from the clinic, but as.
Our poster illustrated at ADP.
There is a lot that we're still learning about what are the most toxic species.
We.
Thus far it would appear that the species that AC 493 targets are the ones that are relatively more toxic I mean, the most toxic.
<unk> been able to find where to put it the other way around we don't see any evidence that <unk> hundred 93 binds to species that are not toxic.
But again the proof is always in the clinic the one other point that some.
Some interest and this is a little bit more hypothetical but.
The concentrations of volatile mers and spinal fluid as mentioned youre very well less than two picomolar, but no one knows really the concentration of olive <unk> in interstitial space and so on.
Our antibody <unk> hundred 93 has to exit.
The arterial system and then enter the interstitial space and they are the actual concentrations Gaelic orders may be more.
Maybe higher.
So again, we've had some some.
Positive results regarding our target engagement assay.
We think that assay appears to be working well and we're really looking forward to seeing those results along with all the others.
Update.
Great. Thank you.
Okay, Great I'll bring our next call up to the stage hold on please.
And now we have Judah frommer with credit Suisse go ahead with your card.
Yes, hi, good morning, Thanks for taking the questions first.
First just as we think about potentially having to a beta antibodies on the market in any evolve thinking.
Including a comparator a combination arm.
With another ABN antibody and in any subsequent trials, whether it's for a potential phase III or beyond that and how could that effect.
One nine three's clinical profile and then separately can you just remind us or give us some direction on cash runway and potential to get you through phase two or how you would deal with with moving into the phase III given the cash position. Thank you.
Yes, let me maybe take your first question and then turn it over to Matt for your second question, but in terms of comparator that question has come up a lot, especially since last week with the.
<unk> announcement, I think there's a pretty broad agreement that well first of all a head to head trial with drugs like that is very difficult to do you have to do what's called a non inferiority study, which require really huge studies.
And at least of all of the people I've talked to.
I don't think anyone really we would expect certainly regulatory agencies to require that kind of head to head comparison at this point.
The other thing Thats really of interest is how.
Quickly these things will be taken up.
In clinical medicine, there was actually a.
At the American Academy of Neurology meeting couple of weeks ago. They have what they call a fireside chat and someone who has a I think a lead investigator in the clarity style for leukemia was talking about all the things that you would have to do to use that in your clinical practice. So these are practicing neurologists.
And there was a lot of.
A bit of angst I might say among the clinical neurologists that this is really complicated because the infrastructure for pet scans and mris and all of that just isn't there yet I think <unk> actually will be even more complicated because they have this this tower requirements. So now you have to get maybe an amyloid pet scan.
And then a tau pet scan so uptake in the marketplace I think is not going to be overnight the infrastructure needs to be built that actually to some degree works to our favor because by the time, we would launch with they see 193 that infrastructure should be much more better developed.
So.
Stay tuned but for right now we do not expect.
There'd be any requirement for a head to head trial.
So Matt I'll turn it over to you.
Thanks, Eric Judah with regard to the cash.
Until we.
Meet with the FDA and know exactly which clinical trial, we're going to run next it's hard for me to tell you exactly when the cash might run out.
However, all the forecasting that we've done.
It gives us confidence that our current cash will last through 2025, we've got said.
As we've disclosed in our filings any next trial that we do is likely to take us out past 2025.
And how far out past 2025, we have to go just simply depends on our interactions with FDA. So we.
We can get very far down the road.
But if we're running a phase two three clinical trial then at some point, we're going to have to finance and even if we run a very large phase II clinical trial to be determined we would have to finance at some point after 2025.
Okay.
Thank you.
Okay, Great I'll bring that next question.
Next we have Colin Bristow with UBS Cowen go ahead with your question.
Hi, Good morning, this is Kim Collins.
Thanks for detail question.
At ADP does cross sell cool.
He presented interesting finding target lab that the previously called out.
Soluble oligomer traveling supernatant.
90 980 brain.
<unk> actually be repetitive and led to the discovery of new spaces.
Which they call short fiber.
So that somehow raises a question if the.
<unk> toxicity on bio activity.
It's the opposite of the way those carnival, great extracts are solely a triple could almost I think some of that work well from the famous workshop another HMS not.
Just thought over this finding and we are just wondering like auto.
Curiosity, besides tolerability of how differentiated are.
So all of those fiber rich fiber real stated from total fiber is our oligos a ligament.
Thank you.
Yes, so thanks.
Dr. <unk> of course does some really cutting edge research and I think your question is a good example of just where the cutting edge is in the field right now so.
One of the things we've talked about before is that.
<unk> hundred 93 of course targets Olive <unk> <unk> was designed to target <unk>.
Fibrils.
Partly this gets into definitions and Dr.
<unk> in the past.
And I think currently actually would sort of define anything that soluble as an oligomer. So a proto fibril is actually one type of volume or if you want to use that definition, but he recently presented and I think this was part of the ADP presentation that how you define soluble can vary so in other words you.
What happens is the centrifuge things and whatever ends up in the in the pellet is not soluble and whatever ends up in the supernatant insoluble, but if you centrifuges faster and harder you can change what is in the power and what in the.
Supernatant.
All of these things are kind of evolving including the terminology just to get back to the Proto fibril differentiation with <unk> 193 targets Proto fibrils are linear structures the structures that acu were 93 targets.
Our globular so.
<unk> is different and atomic force microscopy.
So they're not exactly the same thing there we think of those as cousins. So theyre both soluble by usual definition definitions they are both toxic.
They don't have exactly the same structure.
And so one.
One of the things that's really unique about.
<unk> hundred 93 is that we are targeting a type of oligomer. That's unique I mean, there is no other antibody that targets what we target. That's currently in the clinic.
So I hope that helps but it's a complicated question.
Yes.
That's really helpful. Thank you Jeremy.
We have a follow up question.
You mentioned.
<unk> four does it too as a primary endpoint.
Demos.
<unk> two top line.
To be some disconnection IHS benefits with Hi, Tao group versus Cte RFP.
We see the RSP benefit with more consistent across the top.
Subgroups. So what's your thought on the demand got Diane Aswell as well, where it's sofie your primary reasons to use <unk>.
<unk> got off the RFP for the primary endpoint. Thank you much.
Yeah right so.
One of the things just to remind everybody is that we only have a press release from Lilly on the nano map data. So there is they included quite a bit in their press release, which was great. But they didn't include everything so questions like that how does the iris perform compared to whatever else the CVR sum of boxes and the high Tao group versus the.
Intermediate Tao group those are things I think we just have to wait.
For the presentation.
IC two to really better evaluate our decision and again.
Things can change depending on new data, but our decision to use the I address is really based on everything up until this point in time. It actually appears to be a very good scale and as you know that's what Lilly is used as their.
Primary outcome.
We will be looking forward to seeing more of those data from <unk>.
Trailblazer <unk>, two and we will always further refine our.
Choices, depending on the new data.
Okay. Thank you Eric if we May maybe one last September .
Two questions from our side.
Will there be additional PK PD or 50 updates ahead of that.
Can we queue opportunities.
Keith.
No we don't.
<unk>.
Yes, we don't anticipate any new disclosures prior to our top line results in the third quarter.
Yes.
And then study was going well.
There were some new safety information or something.
Obviously, we'd have to say something about that but at this point in any study even though we're all blinded.
We're feeling pretty comfortable about the safety profile and so I wouldn't anticipate any new disclosures before our topline results.
Thank you so much gentlemen, yeah. Thank you Kevin.
Okay, great and now looks to be our last question.
Yes.
And this is from Charlie Yang with Bofa go ahead with your question.
Hi, Thanks for taking the questions.
Geoff Meacham.
Can you talk about.
Given like Godaddy I missed data.
Potentially to include.
Well the API that drugs in your phase II phase III trial.
Yes, Im sorry, Im not sure I quite understood. The question, where do we include other a beta drugs in our phase II three right.
Alright.
But we just haven't combination therapy.
Given the recent.
Yeah.
Right Gotcha, no well so combination therapy is an important topic and it's something that we had acumen have certainly had some discussions about now our approach to that would probably be the combination would be a drug that different complementary mechanism.
Rather than.
Another one that's related to David or emulated in one way or another.
In terms of our phase two three study.
We don't have any safety data from animal studies based on combinations of <unk> with <unk> hundred 93, and so I don't think it would make a lot of sense for our phase two three study to allow that kind of combination obviously that would make it a lot more.
Complicated study too.
But as we've thought through this as I mentioned previously.
That's where our clinical uptake is going to be pretty slow actually for both <unk> and <unk> and so I think for us to run a placebo controlled trial for our phase III three is certainly going to be feasible.
But looking down the road in terms of combination therapies, which is the future I think we all agree for Alzheimers disease, I think it would make more sense to use some complementary mechanisms. So you would use something that's related to tower something he was related inflammation something like that to combine with <unk> 93 to see whether you get.
Additive or even synergistic effects.
Thank you.
Great I'd now like to turn the call back over to Dan O'connell.
Thanks, Joe and thank you everyone for joining this morning's call. We are very much looking forward to sharing the intercept <unk> topline data in the third quarter.
Data that will be informative.
93 <unk>.
Selective agent neutralizing toxic a beta of oligomers. So thanks again for joining we look forward to speaking with you again soon.
Thank you all for your participation in today's call. This does conclude the program and you may now disconnect.
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