CDH17 becomes flavour of the month

A recent proliferation of industry projects targeting CDH17 has thrust this cell adhesion molecule to the forefront of early-stage scientific work. The promise of hitting this protein, most commonly with an antibody-drug conjugate modality, has also seen three licensing deals struck recently; interestingly, all three kept secret their targets, which have only recently been revealed to be CDH17.Two of the three licensed ADCs, Lepu/Arrivent's MRG007 and Sotio/Biocytogen's SOT109, were the subject of posters at the recent AACR conference, which also featured preclinical presentations on 14 other CDH17-targeting molecules. That's a large chunk of the 31 projects hitting CDH17 that OncologyPipeline lists as being in development at present.According to OncologyPipeline eight of these are in clinical trials, comprising four ADCs, three Car-T therapies and one T-cell engager. On show at AACR was only one of the above, namely MediLink's YL217, but the meeting posters revealed clinical plans for at least two others.US and China IND filings for Huadong Medicine's HDM2017 are due in the third quarter of this year, the poster for that molecule disclosed, while global INDs for VelaVigo's VBC108, a bispecific ADC against CDH17 and Claudin18.2, are to be filed in mid-2026. Already disclosed earlier were 2025 and 2026 IND filing plans for MRG007 and SOT109 respectively.Licensing dealsArrivent licensed ex-China rights to MRG007 in January for $47m in up-front fees and near-term milestones, shortly after GSK paid $30m for DualityBio's DB-1324; at around the same time Sotio doubled down on a discovery alliance with Biocytogen by picking up specific rights to the MAb that will be developed as an ADC as SOT109.At the time all three deals were known to gave a gastrointestinal cancer focus, but it was only later that CDH17 was confirmed as the target of each of the ADC molecules involved. Targeting CDH17 is said to have utility in GI cancers, especially colorectal, pancreatic and gastric, though some groups also claim CDH17 overexpression in NSCLC.Among the AACR presentations two companies, Nanjing Leads and Tavotek, were notable for presenting two separate modalities against CDH17: an ADC and T-cell engager, and an ADC and gamma-delta T-cell engager, respectively. Also notable were a handful of bispecifics, including Innovent's NK cell engager IBI3019.It's possible that one factor accounting for the recent popularity of CDH17 is the claim that this protein is often overexpressed in GI cancers, but that in normal tissues it remains inaccessible because of being hidden within tight junctions of intestinal epithelial cells. However, no human data are available yet to back up such a claim clinically. Anti-CDH17 projects featured in preclinical AACR postersProjectMechanismCompanyNoteYL217CDH17 ADCMediLinkTopo1i (YL0010014) payload (DAR=8), in vivo & in vitro dataMRG007CDH17 ADCLepu/ ArriventTopo1i payload (DAR=4), China IND planned for H1 2025HDM2017CDH17 ADCHuadong MedicineTopo1i payload, US & China IND filings in Q3 2025SOT109CDH17 ADCSotio/ BiocytogenTopo1i (Syntecan E) payload (DAR=4), preclinical models of colorectal cancer, US IND planned for H2 2026LM-350CDH17 ADCLaNova MedicinesTopo1i (LDX2) payload (DAR=8), preclinical models of GI malignanciesBR116CDH17 ADCBioRayTopo1i payload, preclinical models of GI malignanciesLBL-054CDH17 ADCNanjing LeadsTopo1i payload, outperformed Dxd-based ADC in CDH17+ve cancer cellsSCR-A008CDH17 ADCJiangsu SimcereTopo1i (CPT116) payload (DAR=8), preclinical models of GI malignancies7MW4911CDH17 ADCMabwellTopo1i (MF-6) payload (DAR=4), outperformed MMAE-based ADCs in GI cancer modelsBSI-721CDH17 ADCBiosionMMAE payload (DAR=4), preclinical models of GI malignanciesTAVO307ACDH17 ADCTavotekMMAE/F payload (DAR=4), preclinical models of GI malignanciesVBC108CDH17 x Claudin18.2 ADCVelaVigoTopo1i payload, global IND filing scheduled mid-2026LBL-054-CD3CDH17 T-cell engagerNanjing LeadsActivity in mouse models across various CDH17 expression levelsTAVO307BCDH17 gamma-delta T-cell engagerTavotekUses pan-γδTCR, said to be less prone to cytokine storm than CD3-based T-cell engagersHXN-2004CDH17 x CEACAM5 T-cell engagerHelixonPreclinical work in colorectal cancer models suggests better efficacy than monospecific TCEs against the same targetsIBI3019CDH17 x EGFR NK-cell engagerInnoventPreclinical work in colorectal cancer models suggests better efficacy than Erbitux or RybrevantSource: AACR.