On May 11, 2026 Pheast Therapeutics, a clinical-stage biotechnology company advancing macrophage-directed immunotherapies for cancer, reported the identification of CDH1 (E-cadherin) as a novel immune-activating target for antibody-drug conjugates (ADCs), and the first presentation of preclinical data on PHST677, the company’s CDH1-targeting bispecific ADC, at the PEGS Boston Summit 2026.
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"Today’s presentation marks an important milestone for Pheast, representing the first public disclosure of CDH1 as a novel immune-regulatory ADC target," said Roy Maute, Ph.D., Co-founder and Chief Executive Officer of Pheast Therapeutics. "PHST677, designed to combine immune activation with targeted cytotoxicity, demonstrates how our discovery platform and deep engineering capabilities can unlock targets previously inaccessible to traditional ADC approaches. The data presented also reflects our continued expansion into ADCs and the broadening of our pipeline beyond monoclonal antibodies, highlighting the versality of our platform to generate differentiated therapies across multiple modalities."
CDH1, a cell surface protein previously known for its role in cell-cell adhesion was identified by Pheast’s proprietary functional genomic screening platform as a negative regulator of macrophage phagocytosis. This newly defined role positions CDH1 as a novel immuno-oncology target and reveals significant upregulation across multiple solid tumor types.
An anti-CDH1 monoclonal antibody demonstrated robust single-agent efficacy in preclinical tumor models, providing initial validation of CDH1 as a therapeutic target. Pheast developed PHST677, a bispecific ADC designed to combine CDH1-mediated macrophage-driven tumor clearance with tumor-selective targeting via Nectin-4. Importantly, the cytotoxic payload enables direct killing of tumor cells, complementing immune-mediated clearance.
"What differentiates PHST677 is that the CDH1 arm actively engages the immune system at the tumor site, rather than acting solely as a targeting mechanism," said John S. Burg, Ph.D., Senior Director of Protein Sciences at Pheast Therapeutics. "By combining the CDH1 blockade with Nectin-4-directed payload delivery, we’re pairing direct tumor-killing activity with macrophage activation. Together, these orthogonal mechanisms represent a truly differentiated approach to ADC design."
CDH1 and Nectin-4 are co-expressed across multiple solid tumors, including breast, bladder, colorectal, lung, and gastric cancers. The bispecific design restricts payload delivery to cells expressing both targets, improving selectivity and reducing on-target, off-tumor toxicity. Preclinical studies demonstrated selective internalization and efficacy in breast and bladder cancer xenograft models, supporting the therapeutic potential of PHST677.
Pheast’s pipeline now spans two distinct macrophage checkpoint targets across two modalities. The company’s lead program, PHST001, an anti-CD24 monoclonal antibody, is currently in Phase 1 clinical trials for advanced solid tumors and has received FDA Fast Track Designation for ovarian cancer. The advancement of PHST677 expands Pheast’s footprint into ADCs and reinforces the continued productivity of its discovery platform.
PEGS Boston Summit Presentation Details:
Presentation Title: "Coupling Tumor-Specific Payload Delivery with a Novel Target for Immune Engagement"
Presenter: John Burg, Ph.D., Senior Director of Protein Sciences, Pheast Therapeutics
Session Date & Time: Monday, May 11, 2026 at 11:30 AM ET
About CDH1
CDH1 (E-cadherin) is a cell surface protein that mediates cell-cell adhesion in epithelial tissues and is significantly upregulated in multiple human cancers. Through functional genomic screening, Pheast identified CDH1 as a novel negative regulator of macrophage phagocytosis. CDH1 acts as a "don’t eat me" signal that enables tumor cells to evade innate immune clearance. With no previously published role in immune regulation, CDH1 offers a potentially first-in-class macrophage checkpoint mechanism distinct from known macrophage checkpoints such as the CD47–SIRPα and CD24–Siglec-10 axes. Blocking CDH1 increases tumor cell susceptibility to macrophage-mediated phagocytosis and weakens the cell-cell interactions that would otherwise limit access by immune cells and therapeutic agents. CDH1 is co-expressed with Nectin-4 across multiple solid tumor types, making it a compelling target for combination therapeutic strategies.
(Press release, Pheast Therapeutics, MAY 11, 2026, View Source [SID1234665473])