Peer-reviewed results from Phase 1b/2a Trial of Anti-pTau Active Immunotherapy from AC Immune Published in eBioMedicine
AC Immune (NASDAQ: ACIU) announced the peer-reviewed publication of Phase 1b/2a trial results for its anti-pTau active immunotherapy in eBioMedicine. The study compared two formulations: ACI-35.030 and JACI-35.054 in early Alzheimer's disease patients.
Key findings showed that ACI-35.030, developed using AC Immune's SupraAntigen® technology, demonstrated superior performance by generating rapid and potent polyclonal response against pathological Tau forms after a single dose. The treatment maintained 94-100% response rates through week 74 in high-dose cohorts, with no clinically relevant safety concerns.
Based on these positive results, ACI-35.030 has advanced to a potentially registration-enabling Phase 2b ReTain clinical trial in preclinical Alzheimer's disease, becoming the first active immunotherapy targeting Tau to be investigated in approximately 500 participants.
AC Immune (NASDAQ: ACIU) ha annunciato la pubblicazione sottoposta a revisione paritetica (peer-reviewed) dei risultati dello studio di fase 1b/2a della sua immunoterapia attiva anti-pTau su eBioMedicine. Lo studio ha confrontato due formulazioni: ACI-35.030 e JACI-35.054 in pazienti con Alzheimer precoce.
I principali risultati hanno mostrato che ACI-35.030, sviluppata con la tecnologia SupraAntigen® di AC Immune, ha dimostrato performance superiori generando una risposta policlonale rapida e potente contro le forme patologiche di Tau dopo una singola dose. Il trattamento ha mantenuto tassi di risposta dal 94% al 100% fino alla settimana 74 nei gruppi ad alta dose, senza preoccupazioni di sicurezza clinicamente rilevanti.
Sulla base di questi esiti positivi, ACI-35.030 è passata a una potenziale trial di fase 2b ReTain abilitante per la registrazione in malattia di Alzheimer preclinica, diventando la prima immunoterapia attiva mirata al Tau ad essere studiata in circa 500 partecipanti.
AC Immune (NASDAQ: ACIU) anunció la publicación revisada por pares de los resultados del ensayo de fase 1b/2a de su inmunoterapia activa anti-pTau en eBioMedicine. El estudio comparó dos formulaciones: ACI-35.030 y JACI-35.054 en pacientes con Alzheimer en etapas tempranas.
Los hallazgos clave mostraron que ACI-35.030, desarrollada con la tecnología SupraAntigen® de AC Immune, demostró un rendimiento superior al generar una respuesta policlonal rápida y potente contra las formas patológicas de Tau tras una única dosis. El tratamiento mantuvo tasas de respuesta del 94-100% hasta la semana 74 en cohortes de dosis alta, sin preocupaciones de seguridad clínicamente relevantes.
Con base en estos resultados positivos, ACI-35.030 ha avanzado a un ensayo clínico de fase 2b ReTain potencialmente habilitante para la registro en la enfermedad de Alzheimer preclínica, convirtiéndose en la primera inmunoterapia activa dirigida al Tau en ser investigada en aproximadamente 500 participantes.
AC Immune (NASDAQ: ACIU)은 eBioMedicine에서 1b/2a상 결과의 동료 평가(peer-reviewed) 출판을 발표했습니다. 연구는 두 제형 ACI-35.030와 JACI-35.054를 초기 알츠하이머 병 환자에서 비교했습니다.
핵심 결과는 ACI-35.030가 AC Immune의 SupraAntigen® 기술로 개발되어 단 1회 투여 후 병리적 Tau 형태에 대한 빠르고 강력한 다클론 반응을 생성함으로써 우수한 성능을 보였다는 점을 시사했습니다. 고용량 코호트에서 주 74까지 94-100%의 반응률이 유지되었고 임상적으로 관련 있는 안전 문제는 없었습니다.
이러한 긍정적 결과를 바탕으로 ACI-35.030은 미등록 알츠하이머 병 전임상에서의 가능성 있는 등록 가능 2b상 ReTain 임상시험으로 진행되었으며, Tau를 표적으로 하는 최초의 활성 면역요법으로 약 500명의 참가자를 대상으로 연구될 예정입니다.
AC Immune (NASDAQ: ACIU) a annoncé la publication par examen par les pairs des résultats de l’essai de phase 1b/2a de son immunothérapie active anti-pTau dans eBioMedicine. L’étude a comparé deux formulations : ACI-35.030 et JACI-35.054 chez des patients atteints d’un Alzheimer à un stade précoce.
Les résultats clés ont montré que ACI-35.030, développée grâce à la technologie SupraAntigen® d’AC Immune, a démontré une performance supérieure en générant une réponse polyclonale rapide et puissante contre les formes pathologiques de Tau après une seule dose. Le traitement a maintenu des taux de réponse de 94-100% jusqu’à la semaine 74 dans les cohorte à haute dose, sans préoccupations de sécurité cliniquement pertinentes.
Sur la base de ces résultats positifs, ACI-35.030 est passée à un essai de phase 2b ReTain potentiellement enable pour l’enregistrement dans la maladie d’Alzheimer préclinique, devenant la première immunothérapie active ciblant Tau à être étudiée chez environ 500 participants.
AC Immune (NASDAQ: ACIU) gab bekannt, dass eine begutachtete Veröffentlichung der Ergebnisse der Phase-1b/2a-Studie zu ihrer anti-pTau-aktiven Immuntherapie in eBioMedicine erschienen ist. Die Studie verglich zwei Formulierungen: ACI-35.030 und JACI-35.054 bei Patienten mit frühem Alzheimer.
Wichtige Ergebnisse zeigten, dass ACI-35.030, entwickelt mit der SupraAntigen®-Technologie von AC Immune, eine überlegene Leistung zeigte, indem sie nach einer einzigen Dosis eine schnelle und starke polyklonale Reaktion gegen pathologische Tau-Formen erzeugte. Die Behandlung hielt die Reaktionsraten von 94-100% bis Woche 74 in Hochdosis-Kohorten aufrecht, ohne klinisch relevante Sicherheitsbedenken.
Aufgrund dieser positiven Ergebnisse hat ACI-35.030 den Weg in eine potenziell registrierungsfähige Phase-2b-ReTain-Studie in präklinischem Alzheimer fortgesetzt, und wird zur ersten aktiven Immuntherapie gegen Tau, die mit ca. 500 Teilnehmern untersucht wird.
AC Immune (بورصة ناسداك: ACIU) أعلنت عن نشر مراجَع من قبل زملاء حول نتائج تجربة المرحلة 1ب/2أ لـ immunotherapy النشطة المضادة لـ p-Tau في مجلة eBioMedicine. درست الدراسة شكلين دوائيين: ACI-35.030 و JACI-35.054 عند مرضى الزهايمر في مراحله المبكرة.
أظهرت النتائج الأساسية أن ACI-35.030، المطورة باستخدام تقنية SupraAntigen® من AC Immune، أظهرت أداءً تفوقياً من خلال توليد استجابة بوليكلاونية سريعة وقوية ضد أشكال Tau المرضية بعد جرعة واحدة. حافظ العلاج على معدلات استجابة من 94-100% حتى الأسبوع 74 في دفعات الجرعات العالية، دون مخاوف أمان ذات بال.
استناداً إلى هذه النتائج الإيجابية، تقدمت ACI-35.030 إلى تجربة Phase 2b ReTain محتملة تمكّن التسجيل في مرض الزهايمر قبل السريرية، لتصبح أول immunotherapy نشطة تستهدف Tau يتم فحصها في نحو 500 مشارك.
AC Immune（纳斯达克股票代码：ACIU）宣布在eBioMedicine上发表其抗p-Tau活性免疫治疗的1b/2a期同行评审结果。研究比较了两种制剂：ACI-35.030和JACI-35.054，针对早期阿尔茨海默病患者。
关键发现显示，ACI-35.030采用AC Immune的SupraAntigen®技术开发，在单次给药后就能产生快速且强大的多克隆反应，对病理性Tau形式具有更高的活性。该治疗在高剂量组中在74周时仍维持94-100%的反应率，且没有临床相关的安全性问题。
基于这些积极结果，ACI-35.030已推进至潜在可注册的2b期ReTain临床试验，用于前临床 Alzheimer 病，成为首个靶向Tau的活性免疫疗法，预计约有500名参与者参与研究。
- Rapid antibody response achieved with single ACI-35.030 dose, showing 100% responder rate at 2 weeks
- High response rates (94-100%) maintained through week 74 in high-dose cohorts
- Demonstrated specific targeting of pathological Tau species while sparing normal Tau
- Significant changes in plasma pTau and brain-derived Tau levels compared to placebo
- No clinically relevant safety or tolerability issues reported
- Multiple administrations required for JACI-35.054 to reach consistent titers
- JACI-35.054 showed more heterogeneous antibody response compared to ACI-35.030
Insights
AC Immune's anti-tau vaccine shows promising safety and immune response in early Alzheimer's, advancing to Phase 2b with differentiated technology.
The peer-reviewed publication in eBioMedicine validates AC Immune's anti-tau active immunotherapy approach, demonstrating several critical advantages in the Alzheimer's treatment landscape. The key finding is that ACI-35.030 generated a rapid, robust, and specific immune response against pathological tau proteins after just a single dose, with response rates of 94-100% maintained through week 74 in high-dose cohorts.
The immunological profile shows remarkable specificity for disease-causing tau forms while sparing normal tau, which is crucial for preventing off-target effects. This selectivity differentiates it from competitor approaches and potentially improves the safety profile. The clean safety data reported supports this hypothesis, with no clinically relevant safety or tolerability issues observed.
What's particularly valuable is the sustained antibody response requiring less frequent dosing compared to monoclonal antibodies. This addresses a major limitation of passive immunotherapies like donanemab, which require regular infusions. For chronic conditions like Alzheimer's, this represents a significant practical advantage and potentially better compliance and lower healthcare burden.
The advancement to a Phase 2b "ReTain" trial with approximately 500 participants focuses on preclinical Alzheimer's - targeting the disease before significant symptoms appear. This prevention-focused approach aligns with evolving understanding that intervention must occur earlier in the disease process.
The demonstration that AC Immune's SupraAntigen platform produces differentiated responses even with identical immunogens showcases their technological advantage. This platform validation extends beyond this specific candidate to their anti-Abeta program (ACI-24.060), strengthening the company's broader pipeline prospects.
The publication in eBioMedicine represents a significant validation for AC Immune's anti-tau active immunotherapy platform. What stands out here is the differentiated mechanism compared to most competitors pursuing passive immunotherapy approaches (monoclonal antibodies).
AC Immune's active immunotherapy has three compelling advantages: 1) It requires less frequent dosing while maintaining antibody titers, addressing a key limitation of monoclonals which require regular infusions; 2) It demonstrates remarkable specificity for pathological tau forms while sparing normal tau, potentially improving safety; and 3) It shows initial signals of target engagement with significant changes in plasma biomarkers.
The advancement to a Phase 2b trial in preclinical Alzheimer's is particularly noteworthy as it's the first active tau immunotherapy to reach this stage. This positions AC Immune well in the evolving Alzheimer's treatment landscape, which is increasingly focused on earlier intervention.
The partnership with Johnson & Johnson provides significant validation and resources for development. The fact that J&J selected ACI-35.030 over the alternative formulation (JACI-35.054) after seeing comparative data demonstrates confidence in the SupraAntigen platform's superiority.
Beyond this specific candidate, the publication demonstrates the versatility of AC Immune's SupraAntigen platform technology, which has implications for their broader pipeline. The mention of upcoming results for their anti-Abeta active immunotherapy (ACI-24.060) in H1 next year suggests multiple potential catalysts on the horizon.
Peer-reviewed results from Phase 1b/2a Trial of Anti-pTau Active Immunotherapy from AC Immune Published in eBioMedicine
- Detailed results from completed Phase 1b/2a trial of ACI-35.030 and JACI-35.054 demonstrated that two different active immunotherapy formulations against the same target can induce a differential antibody response in individuals with early Alzheimer’s disease
- ACI-35.030, developed using AC Immune’s SupraAntigen® technology, generated rapid, potent polyclonal response against pathological forms of Tau after first dose
- No clinically relevant safety and tolerability observations were reported
- ACI-35.030 (JNJ-64042056) selected to advance and now in ongoing potentially registration-enabling Phase 2b ReTain clinical trial in preclinical Alzheimer’s disease
Lausanne, Switzerland, 25, 2025 -- AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision therapeutics for neurodegenerative diseases, today announced the peer-reviewed publication in eBioMedicine of results from the completed Phase 1b/2a trial of active immunotherapy ACI-35.030’s (JNJ-2056) partnered with Janssen Pharmaceuticals, Inc., a Johnson & Johnson company. ACI-35.030 generated a rapid, robust and durable polyclonal response against pathological forms of Tau including phosphorylated Tau (pTau) and brain-derived Tau (enriched paired helical filament, ePHF). There were no clinically relevant safety or tolerability observations for either ACI-35.030 or JACI-35.054.
Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “These data show that ACI-35.030 (JNJ-2056) was well tolerated at all tested doses and induced a rapid and sustained response against pathological Tau, while requiring less frequent dosing to maintain titers as compared to monoclonal antibodies. Safety and rapid, durable responses are key advantages of active immunotherapies, which make them particularly well suited to the long-term treatment needed to achieve precision prevention. ACI-35.030 is continuing to progress according to plan in the Phase 2b ReTain trial, being conducted by our development partner Johnson & Johnson.”
Dr. Pfeifer added: “This study also demonstrated the ability of AC Immune’s SupraAntigen® platform to generate active immunotherapies that are highly differentiated from other approaches even when the immunogen is identical. We are encouraged by the excellent performance of the SupraAntigen® technology as this also powers our ACI-24.060 anti-Abeta active immunotherapy program in Phase 2 development where further results are expected in H1 next year.”
The publication is entitled "Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer’s disease: a Phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study" and reports the following key findings from the completed trial (NCT04445831):
- ACI-35.030 is based on AC Immune’s proprietary SupraAntigen® technology which anchors the pTau peptide in a liposome and also incorporates non-Tau T-cell epitopes and adjuvants. JACI-35.054 covalently linked the immunogen to the carrier protein CRM197 and was mixed with adjuvants. Both active immunotherapies used the same target pTau peptide sequence.
- ACI-35.030 required only one injection to induce anti-pTau Immunoglobulin G (IgG) antibody titers in all participants and consistently boosted levels with subsequent immunizations. JACI-35.054 raised a more heterogenous anti-pTau IgG antibody response and required multiple administrations to reach consistent titers.
- All participants across all dose-levels were considered anti-pTau IgG responders at 2 weeks post treatment with ACI-35.030. In the two high-dose cohorts, response rates remained between
94% and100% until week 74. Most participants generated an anti-ePHF antibody response after the first administration and antibody levels further increased with additional immunizations. - Antibody titers against unphosphorylated (normal) Tau declined and were not boosted with subsequent administrations of ACI-35.030, demonstrating specific targeting of the pathological Tau species. In contrast, JACI-35.054 induced antibody titers against normal Tau after the second treatment and these increased with subsequent administrations.
- An exploratory post-hoc analysis showed that at multiple time points for the two highest doses ACI-35.030, treatment resulted in a significant (p<0.05) change from baseline of plasma pTau and brain-derived Tau plasma levels compared to the pooled placebo group.
Based on the results from this trial, ACI-35.030 was selected for further clinical testing and is now being investigated in the ongoing Phase 2b ReTain trial (NCT06544616). It is the first active immunotherapy targeting Tau to be investigated in approximately 500 participants with preclinical AD.
Reference
Sol O. et al, Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer’s disease: a Phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study, eBioMedicine, 2025; 120: 105940.
About ACI-35.030 (JNJ-64042056)
ACI-35.030 (JNJ-64042056) is an investigational active immunotherapy designed using AC Immune’s SupraAntigen® platform. Its liposomal formulation incorporates a conformationally-constrained, membrane bound target peptide antigen, phosphorylated Tau (pTau), in addition to adjuvants and non-Tau T-helper peptides. Immunization with ACI-35.030 has been shown in a recent Phase 1b/2a clinical trial to rapidly elicit antibodies after the first injection against extracellular pathological pTau in
About the Phase 2b ReTain Study (ClinicalTrials.gov Identifier: NCT06544616)
The Phase 2b ReTain trial is a potentially registration-enabling randomized, multicenter, double-blind, placebo-controlled clinical study in participants with preclinical AD to assess the clinical effect of active immunization with JNJ-64042056 (JNJ-2056). It is designed to test the hypothesis that JNJ-2056 has a disease-modifying effect that can delay or prevent the onset of cognitive impairment or other clinical symptoms in individuals with preclinical AD through inhibition of seeding and spreading of pathological Tau.
The study will include approximately 500 participants with preclinical AD (cognitively normal, Tau positive), who will be randomized in a 1:1 ratio to a single dose level of JNJ-2056 or placebo and administered as intramuscular injections for a maximum of 4 years. It is currently being conducted at more than 40 clinical trial sites in the U.S., Japan, UK and Australia, and more are expected to open shortly.
The primary endpoint will measure cognitive decline as assessed by the Preclinical AD Cognitive Composite 5 (PACC-5) score. The key secondary efficacy endpoint will assess the effect of JNJ-2056 on the propagation and/or accumulation of Tau pathology compared with placebo, as measured by Tau PET imaging.
The ReTain trial is fully funded and conducted by Janssen Pharmaceuticals, Inc., a Johnson & Johnson company, pursuant to a global license, development and commercialization agreement with AC Immune.
About AC Immune SA
AC Immune SA is a clinical-stage biopharmaceutical company and a global leader in precision prevention for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features a range of therapeutic and diagnostic programs, including candidates in Phase 2 and Phase 3 development. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies, resulting in substantial non-dilutive funding to advance its proprietary programs and >
SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CN, CH, EU, GB, JP, KR, NO, RU and SG.
The information on our website and any other websites referenced herein is expressly not incorporated by reference into, and does not constitute a part of, this press release.
For further information, please contact:
| SVP, Investor Relations & Corporate Communications Gary Waanders, Ph.D., MBA AC Immune Phone: +41 21 345 91 91 Email: gary.waanders@acimmune.com | |
| International Media Chris Maggos Cohesion Bureau Phone: +41 79 367 6254 Email: chris.maggos@cohesionbureau.com |
Forward looking statements
This press release contains statements that constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or AC Immune’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as “may,” “might,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “outlook” or “continue,” and other comparable terminology. Forward-looking statements are based on management’s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include those described under the captions “Item 3. Key Information – Risk Factors” and “Item 5. Operating and Financial Review and Prospects” in AC Immune’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and AC Immune does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement.
Attachment
FAQ
What were the key results of AC Immune's (ACIU) Phase 1b/2a trial for ACI-35.030?
How does AC Immune's ACI-35.030 differ from JACI-35.054 in treating Alzheimer's disease?
What is the current development status of AC Immune's (ACIU) ACI-35.030?
Is AC Immune's (ACIU) ACI-35.030 treatment safe for Alzheimer's patients?
What technology does AC Immune use for ACI-35.030 development?
