Acumen Pharmaceuticals (ABOS) Teleconferência de Resultados do 3º Trimestre de 2026: Divulgação de Resultados do ALTITUDE-AD Prevista para Novembro

Principais Destaques

• A Acumen Pharmaceuticals espera divulgar os resultados preliminares do ensaio clínico de Fase II ALTITUDE-AD com sabirnetug em novembro de 2026.
• O ensaio de 18 meses foi projetado para detectar uma diferença estatisticamente significativa em relação ao placebo no desfecho primário iADRS. A administração identificou uma desaceleração de aproximadamente 30% na iADRS como um limiar claro de sucesso clínico para dar continuidade ao programa.
• Espera-se que o conjunto de dados preliminares inclua a escala CDR Sum of Boxes, eventos adversos, taxas de ARIA, exames de imagem PET de amiloide e biomarcadores fluidos, incluindo p-tau217.
• A Acumen encerrou o 3º trimestre de 2026 com aproximadamente US$ 79 milhões em caixa e títulos negociáveis, o que a administração espera ser suficiente para financiar as atividades clínicas e operacionais atuais até o início de 2027.
• As despesas com P&D no 3º trimestre foram de US$ 21,1 milhões, enquanto o prejuízo operacional e o prejuízo líquido foram de US$ 25,8 milhões e US$ 25,4 milhões, respectivamente.
• A empresa também está avançando com os candidatos ACU-301 e ACU-401 em seu programa aprimorado de entrega cerebral, com a submissão de um pedido de IND esperada para meados de 2027.

Principais Dados Financeiros

Desempenho Operacional e dos Negócios

O sabirnetug continua sendo o principal candidato clínico da Acumen. O anticorpo monoclonal IgG2 seletivo contra oligômeros de beta-amiloide está sendo avaliado no ensaio ALTITUDE-AD nas doses de 35 mg/kg e 50 mg/kg, administradas por via intravenosa a cada quatro semanas. A administração afirmou que ambas as doses foram selecionadas com base na exposição de Fase I, dados farmacodinâmicos e modelagem de dose, e que ambas podem estar dentro de uma faixa eficaz.

O ensaio de Fase II utiliza a iADRS como seu desfecho primário de eficácia após 18 meses de tratamento. A Acumen projetou o estudo como um componente potencial de um pacote de registro regulatório. Se os resultados forem positivos, a empresa prevê a realização de um ensaio confirmatório de Fase III.

A retenção de pacientes superou as expectativas da administração. Mais de 95% dos participantes elegíveis optaram e consentiram em entrar na extensão aberta de 12 meses. Os dados dessa extensão devem surgir ao longo de 2027 e é improvável que sejam incluídos na divulgação inicial de resultados preliminares.

A Acumen também está desenvolvendo o ACU-301 e o ACU-401 por meio de seu programa aprimorado de entrega cerebral. O ACU-301 incorpora o sabirnetug em um anticorpo biespecífico, enquanto o ACU-401 utiliza o anticorpo ACU-234. Em primatas não humanos, o ACU-401 alcançou uma exposição no córtex frontal até 40 vezes maior do que o ACU-234 não modificado, além de aumentar a exposição em regiões profundas do cérebro.

Perspectivas da Administração

A administração espera anunciar os dados preliminares do ALTITUDE-AD em novembro de 2026. A divulgação deve abranger os desfechos de eficácia primários e secundários, achados de segurança, taxas de ARIA e biomarcadores de imagem e fluidos.

A Acumen espera que sua posição de caixa de aproximadamente US$ 79 milhões suporte as atividades atuais até o início de 2027. A empresa projeta a submissão do pedido de IND para seu programa aprimorado de entrega cerebral em meados de 2027.

A empresa pode incorporar uma formulação subcutânea ao desenvolvimento futuro de Fase III, potencialmente por meio de uma extensão aberta. A abordagem final dependerá, em parte, dos resultados de Fase II e da seleção de dose.

Riscos e Pontos-Chave de Atenção

A próxima divulgação de dados do ALTITUDE-AD é o primeiro grande teste clínico da hipótese central da Acumen de que focar seletivamente nos oligômeros solúveis de beta-amiloide pode desacelerar a progressão da doença de Alzheimer. O foco principal será verificar se alguma das doses produz um benefício estatisticamente significativo na iADRS após 18 meses.

A segurança também será central para o perfil de risco-benefício do programa. A administração prevê taxas de ARIA-E na faixa inferior de dois dígitos no geral e resultados potencialmente consistentes entre os genótipos, mas o estudo permanece em duplo-cego e os resultados reais ainda não estavam disponíveis.

O horizonte de caixa (runway) estende-se apenas até o início de 2027 nos planos clínicos e operacionais atuais. Enquanto isso, o cronograma e o desenho do desenvolvimento de Fase III, a dosagem subcutânea e os estudos clínicos iniciais para ACU-301 ou ACU-401 permanecem dependentes do conjunto de dados do ALTITUDE-AD.

Destaques das Perguntas e Respostas dos Analistas

• Limiar de sucesso clínico: A administração afirmou que uma desaceleração de aproximadamente 30% na iADRS após 18 meses forneceria a base para dar continuidade ao sabirnetug.
• Diferenciação de dose: Ambas as doses de 35 mg/kg e 50 mg/kg podem ser eficazes. A administração observou que a dose de 50 mg/kg poderia potencialmente produzir um efeito maior na PET de amiloide.
• Manutenção pós-placa: A Acumen vê uma justificativa científica para usar um anticorpo seletivo para oligômeros após a eliminação da placa, porque agregados solúveis podem continuar a impulsionar a patologia da doença. O ALTITUDE-AD, no entanto, está focado no sabirnetug como tratamento primário.
• Efeitos mais precoces do tratamento: O ensaio inclui avaliações destinadas a capturar se a neutralização de oligômeros tóxicos poderia produzir efeitos em pontos temporais mais precoces. Os resultados podem orientar se estudos futuros poderão estabelecer a atividade do fármaco mais cedo.
• Desenvolvimento de próxima geração: As descobertas do ALTITUDE-AD ajudarão a moldar a seleção de dose, a estratégia de biomarcadores e os planos clínicos iniciais para os candidatos com entrega cerebral aprimorada.
• Dados ausentes e retenção: A administração disse que a retenção superou as expectativas e que os dados ausentes serão tratados usando métodos convencionais definidos pelo protocolo.

Transcrição Completa da Teleconferência de Resultados

Transcrição completa da teleconferência de resultados

Comentários da administração

Operator

Good day, and welcome to the Acumen Pharmaceuticals Third Quarter 2026 Conference Call and Webcast. [Operator Instructions] Please note, this call may be recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

Alex Braun

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended September 30, 2026. With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer. They'll have a brief prepared remarks, and then we'll open the call for questions. And before we begin, we encourage listeners to go to the Investors section of the Acumen website to find our press release issued this morning 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. Please see Slide 2 of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. 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. So, with that, I'll turn the call over to Dan.

Daniel O'Connell

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. In the third quarter, our team has been very busy readying for the top line readout from our Phase II ALTITUDE-AD trial investigating our lead product candidate, sabirnetug. If you've been following our company for some time, you're likely well aware that these results are highly anticipated. We are testing our central scientific thesis that arresting the harm done by synaptotoxic amyloid beta oligomers in the brain may offer a differentiated approach to treating Alzheimer's disease. So, today, I'm pleased to confirm that we expect to announce these Phase II results this November.

We are confident that we are fully evaluating the A-beta oligomer hypothesis with this study. ALTITUDE-AD is a large, well-powered Phase II trial with clinically meaningful endpoints. We are testing 2 doses of sabirnetug against placebo, carefully considered based on our Phase I study in Alzheimer's patients, such that either dose may prove efficacious in the Phase II. We have executed the study to a very high operational standard with rapid enrollment, close engagement with study sites and investigators, and high rollover into the open-label extension of the study. As previously mentioned, we envision this study as part of a potential registration package and have conducted the study as such with a single confirmatory Phase III anticipated following positive Phase II results.

As previously outlined, ALTITUDE-AD was designed to detect a statistically significant difference between sabirnetug and placebo on the primary efficacy endpoint, iADRS, following 18 months of treatment. We expect the top line data set to encompass primary endpoint results, key secondary outcomes, including the CDR Sum of Boxes, safety evaluations covering adverse events and ARIA rates, and a range of informative fluid and imaging biomarkers. We believe that sabirnetug has the potential to demonstrate a differentiated benefit-to-risk profile given its unique product attributes as a selective anti-A-beta oligomer IgG2 monoclonal. We look forward to sharing the data in November.

We also continue to advance our enhanced brain delivery program, or EBD, for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier penetrating technology with an A-beta oligomer selective therapeutic antibody. As a reminder, we are working on 2 candidates in the lead up to an IND filing expected in mid-2027. One candidate, ACU-301, is based on a bispecific antibody incorporating sabirnetug. And ACU-401 incorporates a novel A-beta selective antibody with differentiated properties known as ACU-234. We presented encouraging data at the AAIC meeting in July, showing that after intravenous dosing, all tested EBD bispecific antibodies achieved multifold greater brain exposure than unmodified ACU-234 alone.

ACU-401, in particular, achieved up to a 40-fold greater frontal cortex exposure in nonhuman primates and significant increase in exposures in deep brain regions. The degree of brain penetration we observed in the cynomolgus monkeys combined with the preserved soluble A-beta oligomer selectivity and a clean hematological profile exceeded our expectations and give us confidence in the differentiated potential of our EBD program. The imminent data readout for sabirnetug and the development of our next-generation EBD candidates demonstrate both the robustness of our pipeline and our ability to deliver on key priorities, positioning us for an important period of value-creating milestones ahead, both near and longer term. Again, we look forward to updating you in November. And, with that, I'll turn the call over to Matt.

Matt Zuga

Thanks, Dan. As a reminder, our third quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended the third quarter with approximately $79 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027. R&D expenses were $21.1 million in the third quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs as well as CRO costs, which are both associated with our ALTITUDE-AD clinical trial.

G&A expenses were $4.7 million in the third quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $25.8 million and a net loss of $25.4 million in the third quarter. We look forward to reporting on our Phase II ALTITUDE-AD study next month and remain committed to maximizing the potential of our portfolio of A-beta oligomer targeted antibodies to generate value for patients living with Alzheimer's disease, their caregivers, and our stakeholders. And, with that, we can open the call for Q&A. Operator?

Operator

[Operator Instructions] Our first question comes from Jason Zemansky with Bank of America.

Perguntas e respostas

Jason Zemansky

Congratulations on the progress. Looking forward to the results. This may seem like a random question now. But as we think about the evolving treatment paradigm, it looks like Biogen is now positioning LEQEMBI as a follow-on after donanemab clears plaque. And the argument is that soluble species, sort of, keep driving disease after the plaque has gone. So, it seems like a natural place for an oligomer selective antibody. How do you think about sabirnetug in addition to, sort of, a primary role, but as a maintenance after plaque clearance or in combination with a plaque clearer? And could anything in the ALTITUDE-AD data set inform that?

Daniel O'Connell

Thanks, Jason. Great question. So, we've always been advocates for chronic dosing, essentially while patients are stable within an early AD stage of disease as we believe these soluble aggregates are present and persistent in driving disease pathology. So, it would be a logical extension to consider sabirnetug or an oligomer selective antibody as a post-plaque clearance follow-on. But we -- so, in the primary mode, we're focused on the primary outcome for sabirnetug in ALTITUDE-AD with an 18-month primary using the iADRS. So, I think we'll have the first case evidence is really out of that Phase II moving towards Phase III, but the therapeutic rationale for sabirnetug as a follow-on would make sense to us as we sit here today.

Operator

Our next question comes from Paul Matteis with Stifel.

Jo Yi Chudy

This is Emily on for Paul. We were just wondering if you could talk a little bit about your dose selection and what might you expect to see in this upcoming readout that would look different on efficacy and safety between those 2 doses?

Daniel O'Connell

Thanks, Emily. Yes. So, for the Phase II, we chose doses of 35 mg/kg and 50 mg/kg, and this is IV dosing every 4 weeks. So, we arrived at those doses as a consequence of the dose exposure and some of the pharmacodynamic effects we observed in the Phase I. So, a combination of the Phase I results with some dose modeling allowed us to select these 2 doses. And importantly, we think both 35 and 50 each are within the zone that could be efficacious.

It may be that the higher dose of 50 mg/kg may have perhaps more observed effects on the amyloid PET signal, but we will see how that reads out in the weeks ahead. We're getting close to that data set. So, very excited to see it. But important to establish that both of these doses, we think, are within that zone of efficacy in conjunction with the safety profile that we think could offer a benefit-to-risk profile that's attractive to patients.

Operator

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

Pete Stavropoulos

Congrats on the execution, looking forward to the data next month. A couple for me. I'm wondering what your current thinking is in terms of the bar or what is the minimum we'd like to, sort of, see out of ALTITUDE-AD to move forward, especially since this is the first time that the oligomer hypothesis is being tested. So, the bar for both clinical scales and biomarker data. And what would we expect any OLE data in the readout?

Daniel O'Connell

Thanks, Pete. So, as you may recall, we've been guiding towards a clear clinical success of 30% slowing on the iADRS after 18 months of placebo-controlled period. We think that's a zone in which that would give us the basis for moving forward. And in terms of the safety profile, I mean, the overall adverse event profile, inclusive of ARIA rates and infusion site reactions and other elements of the safety profile that's going to be part of this top line readout. We would anticipate low double-digit ARIA-E in totality and maybe consistent across the genotypes as part of the support of the oligomer hypothesis and the grounds in which sabirnetug would be moving forward to Phase III. So, that's, kind of, how we're thinking about that.

Sorry, your second question, Pete? OLE data. So, yes, as you are good to point out, our open-label extension is a 12-month open-label extension. We've had high rollover. Essentially greater than 95% of people eligible to participate in the open-label extension have elected and consented to do so. That portion of the study will be reading out over an extended period of time. We do think that, that will generate evidence into 2027 and likely won't be part of the top line results. I think important to establish, however, the top line results, as I just mentioned on the scripted call, will be inclusive of the primary and secondary, both efficacy and safety and include biomarker effects, both imaging and fluid.

In terms of the -- we'll be looking at the amyloid PET as a conventional imaging measure. We'll also be looking at fluid biomarkers, CSF and plasma. I think we'll principally be looking at things such as the p-tau217 as a measure of disease status, potentially progression. And I think that's going to be a complete data set to inform stakeholders on the merits of sabirnetug and provide evidence in support of the oligomer hypothesis.

Pete Stavropoulos

All right. And just a question on EBD. How are you thinking about the other path forward for ACU-301 or 401, the MAD/SAD studies? Are you going to go straight into patients or healthy volunteers first and the length of time you, sort of, aim to have patients on the -- in the MAD study? And what optionality do these candidates offer?

Daniel O'Connell

Yes. Thanks, Pete. Well, yes, so, we think there's a lot of optionality in our EBD program. And I think having both 301 and 401 in the mix is really helpful because it affords us a bit of diversity in terms of the profiles and ways to move the program forward. I think we've learned so much in the development of sabirnetug, both initially with INTERCEPT, which was our Phase I study exclusively in Alzheimer's patients that gave us really solid Phase I proof of mechanism data in support of sabirnetug and that, of course, as I just mentioned, informed dosing strategy and the plan for Phase II.

I think the team is still working on refining precisely what we want to do with EBD in the early phase and translational studies. And we'll be looking at the ALTITUDE results, in particular, to assess dosing strategy as well as biomarker strategy for the EBD program. So, we think one of the advantages we at Acumen have is all of the experience we've undertaken with sabirnetug not only through Phase I, but through a robust Phase II, that really serves as a foundation for our strategy for developing the EBD candidates.

Pete Stavropoulos

Congrats on the progress once again.

Operator

Our next question comes from Tom Shrader with BTIG.

Thomas Shrader

I guess we'll all hold our breath for 30 days. But I think one of the interesting things about sabirnetug is that it might act faster given the monomer binding, things like that. And the question is, how set up are you to capture that? When are you looking at patients? When are you scanning? When are you taking soluble biomarkers? I think a fantastic readout from this might be that your next Phase III could be shorter because the drug works faster. And the question is, how set up are you to catch some sort of readout like that?

Daniel O'Connell

Thanks, Tom. So, with sabirnetug's high selectivity for toxic A-beta oligomers, we do hear the thesis holds that neutralizing those toxic species early in the early course of disease could have not only a slowing of disease, but some other potentially, sort of, symptomatic benefit. I think that's an interesting possibility. I do know that our plans have incorporated elements of observing or essentially capturing that possibility.

So, I think we will know a lot in the coming weeks as the ALTITUDE reads out as to whether, given the mechanism, there is a potential to look at earlier time points for establishing a drug effect going forward. So, yes, it's a really -- as you mentioned, we think ALTITUDE is a robust test of this central scientific hypothesis and are eagerly awaiting the unblinding and the interpretation of those results.

Operator

Our next question comes from Geoff Meacham with Citi.

Mary McKeown

This is Mary Keown on for Geoff. Could you speak to some of the KOL feedback you're receiving on sabirnetug and the ALTITUDE-AD program? Maybe what are physicians looking for in a treatment? And how could sabirnetug address these needs? And then just as another one, maybe what feedback do they have on the mechanism here as well?

Daniel O'Connell

Great. So, in our travels and interactions with KOLs, I mean, they're mostly principally focused on better treatment options for patients. And I think as such, sabirnetug, with a different mechanism, not a plaque-busting agent, but rather something that targets these soluble toxic species, is something of high interest and given that potential.

So, they are keenly -- as is everybody in the field, I think, kind of, looking at ALTITUDE as a differentiated study where sabirnetug could shift some people's thinking on what the primary mode of treatment should be, whether it be oligomers versus plaque and so forth. So, we think there's a lot of anticipation going into next month's readout. And we do think that the study has a mix of data outcomes and readouts that will be very informative as to the merits of sabirnetug and underpin the attractiveness of targeting toxic oligomers in a primary, selective and direct fashion.

Operator

Our next question comes from Dev Prasad with Lucid Capital Markets.

Dev Prasad

Congrats on the progress. A couple of questions. One is, as we approach the readout, can you comment on patient retention? And maybe how should we think about the impact of missing data or discontinuation on primary efficacy analysis? And another one is on subcutaneous. I believe the subcu work was on hold until the dosage chosen. So, wondering, do you plan to initiate that work after the Phase II trial?

Daniel O'Connell

Thanks, Dev. So, in terms of retention in the primary ALTITUDE-AD study, as we mentioned, we've conducted the study to a very high standard. We have -- our retention within the primary portion of the study has exceeded, sort of, our expectations, which is great, and we've had high rollover into the open-label extension. So, just objectively, we think people that are participating in the study like the study and have been inclined to stay in and/or extend their involvement in the study. So, that's encouraging. And yet it's obviously still blinded data.

In respect to your question on missing data, I think we will be addressing those issues in a, kind of, conventional and per protocol basis. So, I don't know that there's more I can offer -- more specifics I can offer on that question.

And thirdly, in terms of the subcu, yes, we completed a healthy volunteer, essentially a bioavailability study back that read out in early '25. We think we have what we need in terms of the contrast between IV dosing, subcutaneous dosing of the sabirnetug formulation. We anticipate using the Phase III in one direction or another to incorporate a subcutaneous advancement. And I think you can look at some predicates out there, if you look at what Eisai and Biogen did with LEQEMBI, incorporating the subcu as part of the open-label extension in Phase III, that could be analogous to how we would be moving forward in the future with a subcutaneous option.

Operator

This concludes the question-and-answer session. Thank you for your participation. You may now disconnect. Good day.