Purple Biotech Highlights Significant Advantages of the Novel CAPTN-3 Tri-Specific Antibody Platform at the EACR 2025 Annual Congress

Rhea-AI Summary

Purple Biotech (NASDAQ/TASE: PPBT) presented new preclinical data on its CAPTN-3 tri-specific antibody platform at EACR 2025. The platform creates antibodies that safely activate both innate and adaptive immune systems to fight cancer. The lead product, IM1240, features a conditional anti-CD3 arm that activates only in tumor environments, an anti-NKG2A arm that engages NK cells and blocks immune checkpoints, and a tumor-targeting arm. Key data showed sustained tumor regression in triple negative breast cancer models, selective activation in tumor microenvironment, and synergistic effects between NK and T cell engagement. The platform demonstrated superior efficacy compared to individual antibodies and showed flexibility with other candidates like IM1060 and IM1065 also achieving significant tumor regression.

Insights

Immunology Scientist

Purple Biotech's novel CAPTN-3 platform shows promising preclinical data with tri-specific antibodies that uniquely engage both T cells and NK cells against tumors.

Purple Biotech has presented compelling preclinical data for their innovative CAPTN-3 platform at the EACR 2025 congress. This platform represents a significant advancement in cancer immunotherapy by creating tri-specific antibodies with three distinct functional arms that work synergistically. The most notable innovation is the conditional activation mechanism - the anti-CD3 arm remains "capped" until cleaved by proteases in the tumor microenvironment (TME), providing tumor-specific targeting while minimizing systemic toxicity.

What makes this platform particularly valuable is the incorporation of an anti-NKG2A arm, which serves dual functions: it engages natural killer cells and blocks an immune checkpoint present on both T and NK cells. This is scientifically significant because NKG2A interacts with HLA-E (often upregulated in tumors as an immune evasion mechanism) and its blockade can reinvigorate exhausted T cells within the tumor microenvironment.

The data demonstrated that their lead candidate IM1240 induced sustained tumor regression in triple-negative breast cancer xenograft models. The platform also showed modularity with other candidates (IM1060 and IM1065) targeting different tumor antigens while maintaining the core mechanism. This flexibility allows for potential application across multiple cancer types.

The simultaneous engagement of both innate and adaptive immunity represents a sophisticated approach to overcome tumor immune evasion, addressing a major challenge in immunotherapy. The conditional activation mechanism also addresses the critical safety concerns of cytokine release syndrome that have limited many T-cell engagers. While these results are preclinical, they demonstrate rational design principles addressing known limitations of current immunotherapies.

REHOVOT, Israel, June 23, 2025 (GLOBE NEWSWIRE) -- Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance, today announced the presentation of new preclinical data on its novel CAPTN-3 tri-specific antibody platform in a poster presentation at the 2025 Annual Congress of the European Association for Cancer Research (EACR 2025), that was held in Lisbon, Portugal from June 16-19, 2025.

“Purple’s proprietary CAPTN-3 platform of T-cell engagers enables the creation of a large number of antibodies to different targets, and by capping the anti-CD3 arm for conditional activation and adding an NK cell antibody arm, we are creating tri-specific antibodies that safely activate both the innate and adaptive immune systems,” said Gil Efron, Purple Biotech CEO. “Our poster at EACR 2025 highlights the flexibility and efficiency of the platform.”

The design of the CAPTN-3 lead product and other candidates in this platform includes an anti-NKG2A arm, which acts both as an NK cell antigen and as an immune checkpoint on both T cells and NK cells through its interaction with HLA-E, which is often upregulated in tumors to evade immune detection.

NKG2A expression identifies a subset of human gamma delta 2 T cells exerting the highest antitumor effector functions. Anti-NKG2A function is required to unleash the NKG2A+ gamma delta 2 T cell anti-cancer activity. Our data demonstrate that the NKG2A arm in CAPTN-3 TCE synergizes with the anti-CD3 arm to induce significant cytotoxic effects against solid tumor cells.

NKG2A is an immune checkpoint that plays an important role in the exhaustion of cytotoxic T cells in the tumor microenvironment (TME). The preclinical data demonstrate the potential of CAPTN-3 to re-invigorate exhausted T cells and efficiently kill solid tumor cells, largely attributed to the significant contribution of the unique anti-NKG2A arm.

These activities are further supported by the in-vivo data demonstrating that both the NKG2A and CD3 arms contribute to the sustained tumor regression observed in mice models. These results underscore the innovative design of CAPTN-3, highlighting the impact of the novel anti-NKG2A arm and its synergistic effect with the anti-CD3 arm.

The CAPTN-3 platform creates a tri-specific scaffold with three binding arms. In the variable region, one arm conditionally binds to CD3, only after the cap has been cleaved by proteases in the TME. The other variable region engages natural killer (NK) cells, activating the innate immune system to join activated T cells in the killing of tumor cells. The constant region of the tri-specific antibody targets tumor associated antigens (TAA) to recruit both NK and T cells to the tumor. Through activation of both the innate and adaptive immune systems, the CAPTN-3 platform can generate synergistic responses within the TME, without the risk of off-target cytokine release.

Key Highlights from the Poster Presentation:

• Robust In Vivo Anti-Tumor Activity: The lead CAPTN-3 tribody, IM1240 (capped-CD3×5T4×NKG2A), induced sustained tumor regression in a triple negative breast cancer (TNBC) xenograft model.
• Conditional, Tumor-Restricted Activation: The ‘capped’ CD3 arm remained inactive in serum samples of advanced cancer patients and healthy donors and is selectively unmasked by TME proteases, expanding the therapeutic window and reducing potential systemic NKG2A⁺NK cell depletion.
• Dual Innate and Adaptive Engagement: IM1240’s NKG2A checkpoint blockade arm synergizes with the CD3 engager to activate both innate and adaptive immune subsets, translating to potent cytotoxicity in vitro and in vivo. The poster demonstrates:
  • Activation of the extremely high antitumor NKG2A⁺ gamma delta 2 T effector cells
  • Reinvigoration of exhausted T cells against solid tumor cells
  • The added value of IM1240 NKG2A arm to the in-vivo tumor suppression
• Plug & Play Flexibility: Additional CAPTN‑3 tribodies, such as IM1060 (CD3×5T4×NKG2D) and IM1065 (CD3×EGFR×NKG2A), demonstrated significant tumor regression, underscoring the platform’s modularity and customizable capabilities.
• Superior efficacy versus combination of individual antibodies was demonstrated.

EACR 2025 poster details are as follows:

Abstract #: EACR25-1964
Title: “CAPTN-3: A novel platform of conditionally activated T cell and NK cell engagers”
Session Title: Immunotherapy
The poster is available in the Publications section on Purple Biotech’s website.

Abstracts related to the EACR meeting will be published online following the presentation. For more information, please visit the EACR 2025 website.

About Purple Biotech

Purple Biotech Ltd. (NASDAQ/TASE: PPBT) is a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance. The Company's oncology pipeline includes CM24, NT219, and CAPTN-3. CM24 is a humanized monoclonal antibody that blocks CEACAM1, which supports tumor immune evasion and survival through multiple pathways. CEACAM1 on tumor cells, immune cells and neutrophil extracellular traps is a novel target for the treatment of multiple cancer indications. As proof of concept of these novel pathways, the Company completed a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC) with CM24 as a combination therapy with the anti-PD-1 checkpoint inhibitor nivolumab and chemotherapy, demonstrating clear and consistent improvement across all efficacy endpoints and the identification of two potential serum biomarkers. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A Phase 1 dose escalation study was concluded as a monotherapy and in combination with cetuximab, in which NT219 demonstrated anti-tumor activity in combination with cetuximab in second-line patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). A Phase 2 study, in collaboration with the University of Colorado, to treat R/M SCCHN patients with NT219 in combination with cetuximab or pembrolizumab. was initiated. The Company is also advancing CAPTN-3, a preclinical platform of conditionally activated tri-specific antibodies, which engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound's therapeutic activity to the local tumor microenvironment, thereby potentially increasing the anticipated therapeutic window in patients. The third arm specifically targets the Tumor Associated Antigen (TAA). The technology presents a novel mechanism of action by unleashing both innate and adaptive immune systems to induce an optimal anti-tumoral immune response. IM1240 is the first tri-specific antibody in development that targets the 5T4 antigen, which is expressed in a variety of solid tumors and is associated with advanced disease, increased invasiveness, and poor clinical outcomes. The Company's corporate headquarters are located in Rehovot, Israel. For more information, please visit https://purple-biotech.com/.

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CONTACTS:

Company Contact:
IR@purple-biotech.com

FAQ

What is Purple Biotech's CAPTN-3 platform and how does it work?

CAPTN-3 is a tri-specific antibody platform that creates antibodies with three binding arms: a conditional CD3-binding arm that activates only in tumors, an NK cell-engaging arm, and a tumor-targeting arm. This design enables both innate and adaptive immune responses against cancer cells.

What were the key findings from Purple Biotech's (PPBT) EACR 2025 presentation?

The presentation showed that CAPTN-3's lead product IM1240 achieved sustained tumor regression in TNBC models, demonstrated selective activation in tumor environments, and showed synergistic effects between NK and T cell engagement, with superior efficacy versus individual antibodies.

How does Purple Biotech's IM1240 antibody target cancer cells?

IM1240 uses three mechanisms: it conditionally activates T cells through a capped CD3 arm, engages NK cells through an anti-NKG2A arm that also blocks immune checkpoints, and targets tumor-associated antigens to recruit both NK and T cells to the tumor site.

What makes Purple Biotech's CAPTN-3 platform unique in cancer treatment?

The platform's uniqueness lies in its tri-specific design, conditional activation only in tumor environments to reduce side effects, and ability to simultaneously engage both innate and adaptive immune responses while blocking immune checkpoints.

What other drug candidates is Purple Biotech developing with the CAPTN-3 platform?

Purple Biotech has developed additional CAPTN-3 tribodies including IM1060 (CD3×5T4×NKG2D) and IM1065 (CD3×EGFR×NKG2A), which have also demonstrated significant tumor regression in preclinical studies.