ExpreS2ion avancerar ES2B-C001 efter positiv granskning av fas I-data

Kampen mot HER2-positiv bröstcancer kräver innovativa tillvägagångssätt som kan utlösa ett varaktigt immunförsvar. ExpreS2ion Biotech adresserar just detta kliniska behov med ES2B-C001. Den aktiva immunoterapikandidaten är utformad för att stimulera patientens eget immunsystem till att producera ett starkt immunsvar mot HER2-proteinet, som är en välkänd drivkraft bakom aggressiv tumörtillväxt.

Nyligen utvärderade en oberoende säkerhetskommitté (DSMB) de senaste kliniska uppgifterna från den pågående fas I-studien. Expertkommittén gav grönt ljus att fortsätta. Att klara den rigorösa säkerhetsutvärderingen bekräftar en gynnsam tolerabilitetsprofil, vilket innebär en riskreducerande milstolpe för hela utvecklingsprogrammet.

Bryter immuntoleransen

Utöver att påvisa säkerhet levererar den kliniska uppdateringen uppmuntrande effektsignaler. Patienter som behandlas med ES2B-C001 uppvisar konsekventa och mycket varaktiga anti-HER2-antikroppstitrar. Åtta av nio utvärderingsbara individer över dosnivåerna 50 µg och 150 µg uppvisade minst en fördubbling av de anti-HER2-specifika antikroppstitrarna jämfört med baslinjen.

De robusta siffrorna bekräftar en stark induktion av riktade immunsvar hos patienter med avancerad bröstcancer. Antikroppsnivåerna ökade dessutom vid påföljande besök, vilket visar på en tydlig förstärkande effekt efter upprepad dosering. Hos den första utvärderade patienten förblev titrarna förhöjda i cirka fem månader efter den sista dosen, vilket bevisar en genuint ihållande immunreaktion.

– These early results strengthen our confidence in ES2B-C001 as a first-in-class active immunotherapy targeting HER2, CEO Bent U. Frandsen comments in a press release. The consistent immune responses, indications of durability, and favourable safety profile seen to date support continued clinical evaluation. In addition, with the DSMB recommending progression of the study, we remain excited about potential further validation from the coming data readouts in 2026 from this on-going clinical trial.

Vd kommenterar

Det kliniska teamet kommer nu att höja dosen till 450 µg och samtidigt utöka 150 µg-kohorten. BioStock hörde av sig till Bent U. Frandsen för att få veta mer om vad detta innebär för projektet.

Clinical data show consistent and durable anti-HER2 responses. How does the magnitude of the immune reaction compare to early preclinical expectations?

– In preclinical non-human primate studies, we saw that animals developed immune responses across all dose levels tested, but without a clear increase in magnitude at higher doses. In other words, the response was present across doses rather than increasing stepwise with dose. Based on that, we considered it possible that a similar pattern could be seen in humans, while recognising that these findings do not directly translate to humans.

– It is also important to keep in mind that preclinical studies are more uniform, whereas patients in a clinical trial vary in terms of prior and ongoing treatments, including other HER2-targeted therapies like monoclonal antibodies and antibody-drug conjugates. This can influence baseline antibody levels, so baseline antibody levels can vary significantly across patients. Consequently, we focus on changes relative to each patient’s baseline and overall trends across the group.

– What we see so far, and find encouraging, is that nearly all patients show an increase from baseline, and that these responses remain elevated over time within the observation period. That consistency and persistence of the immune response is, in our view, the most relevant aspect of the data at this stage.

Breast cancer treatment is evolving rapidly. How does an immunotherapy like ES2B-C001 fit into the future treatment paradigm alongside existing targeted therapies?

– We see ES2B-C001 as complementary to existing HER2-targeted therapies, with a particular focus on combination use. Current treatments such as monoclonal antibodies and antibody-drug conjugates provide targeted activity, but disease progression remains a challenge for many patients.

– Our approach is designed to activate the patient’s own immune system to generate a polyclonal antibody response against HER2, potentially broadening target coverage beyond single-epitope therapies. In that context, ES2B-C001 may provide an additional layer of immune-mediated pressure when used alongside standard treatments.

– As development progresses, we will continue to explore how this approach can be integrated into existing treatment paradigms, including in combination with standard of care and potentially in earlier or maintenance settings.

Generating a sustained immune response remains a massive challenge in oncology. What specific features of the ES2B-C001 design enable this lasting effect?

– The key idea behind ES2B-C001 is that by exposing the immune system to the full HER2 target, it can recognise and respond to multiple parts of it rather than just a single site. This broader recognition is intended to make the immune response more robust.

– By contrast, existing HER2-targeted therapies typically focus on specific parts of the receptor and rely on continued dosing to maintain their effect. With ES2B-C001, the aim is to stimulate the patient’s own immune system to produce antibodies, which may allow the response to persist over time. What we see so far is that antibody levels increase from baseline and remain elevated during the observation period, which is consistent with this rationale.

Apart from recommending escalation to 450 µg, DSMB also recommended an expansion of the 150-µg cohort. Why is that?

– The recommendation reflects the need to build a more robust dataset at the 150-µg dose level. In a phase I study, patients are heterogeneous in terms of prior treatments, disease stage and other factors, which can influence how they respond. Expanding the cohort allows us to better understand the consistency of the immune response and safety profile at that dose.

– At the same time, the study is progressing to the next dose level, so we are effectively generating data in parallel. At this stage, we do not yet know what the recommended phase II dose will be, and additional data at 150 µg will be important in informing that decision.

How do these results impact ongoing partnering discussions?

– For potential partners, the key is always the quality and maturity of the clinical dataset. With this update, we have meaningfully expanded the data, both in terms of the number of patients evaluated and the pool of immunogenicity measurements, which strengthens the overall dataset.

– In our interactions to date, it is clear that partners are looking for a certain level of clinical maturity before engaging more deeply. As the dataset grows, with more patients and more follow-up, it allows for a more robust assessment of consistency, durability and safety.

– We believe this update represents a step in that direction, and we will continue to build the dataset as the study progresses to support future discussions.

Finally, you view these results as a validation of ES2B-C001 as a first-in-class immunotherapy. What are your expectations for the upcoming data readouts in 2026?

– For 2026, the focus is on continuing to build and mature the phase I dataset. In the near term, that means completing dose escalation and further strengthening the safety and immunogenicity profile.

– As the year progresses, we expect to generate additional data on the consistency and durability of the immune response, while also expanding at the selected dose levels to support definition of a recommended phase II dose and inform a combination strategy.

– While there, naturally, is interest in clinical efficacy, this phase I study is primarily designed to assess safety and immune activation, which are the key objectives at this stage. We are collecting standard exploratory clinical endpoints, such as disease stability and progression, but it is still early and the dataset is not yet mature enough to draw conclusions.

– Taken together, these readouts are intended to support a phase II decision and the next stage of development.