Living dossier · Competitive landscape

WRN helicase in MSI-H colorectal cancer

Primary identifiers: 6
Sponsors tracked: 6
Evidence types: 2 of 3
Last refreshed: 2026-07-28 · monthly

MightyRayn panel synthesis

OmniRayn’s reading of this landscape — our interpretation, not a registry fact

Three of the largest oncology developers are in the clinic against the same synthetic-lethal vulnerability, which makes single-agent WRN inhibition a crowded position rather than an opening. The field is competing on chemistry rather than biology: covalent and non-covalent allosteric approaches appear side by side, and the literature already anticipates on-target resistance to the first generation. Note what is absent as much as what is present — several MSI-H programmes now in the clinic do not disclose a target, so the real density of this field is probably higher than the citable record shows.

Programs and primary evidence

Sponsor	Asset	Phase	Mechanism	Primary source
Novartis Pharmaceuticals	HRO761	1	allosteric WRN helicase inhibitor	NCT05838768 — Phase I/Ib single agent and in combination with pembrolizumab or irinotecan in MSI-H/dMMR advanced solid tumours
GlaxoSmithKline	GSK4418959	1/2	oral DNA helicase Werner inhibitor	NCT06710847 — SYLVER first-time-in-human study alone or with a PD-1 inhibitor in dMMR/MSI-H solid tumours
Vividion Therapeutics	VVD-214 / RO7589831	—	covalent allosteric inhibitor engaging C727	10.1021/acs.jmedchem.5c01805 — Identification of a clinical-stage covalent allosteric WRN inhibitor; tumour regression in MSI-H colorectal models
Hebei University of Science & Technology	review	—	covalent, non-covalent and degrader approaches	10.1016/j.bioorg.2025.108771 — Review of the WRN inhibitor landscape including proof-of-concept WRN-targeting degraders
Southern Medical University	review	—	WRN inhibition combined with immunotherapy	10.1016/j.bcp.2025.117022 — WRN as a synthetic-lethal vulnerability in MSI cancers and a route to address immunotherapy resistance
Korea Research Institute of Bioscience and Biotechnology	KWR095	—	bioisosteric replacement on a non-covalent scaffold	10.1016/j.bmcl.2025.130141 — Novel WRN inhibitors with in vivo anti-proliferative effect in MSI-H colorectal models

Method and limits

Programs are enumerated from primary registries (ClinicalTrials.gov, PubMed). A program appears here only if a primary record links this target to this indication as a therapeutic hypothesis — associations and risk markers are excluded by design.
Every claim above carries the identifier it rests on. We report what the record states; we do not assert efficacy, and computational findings are pending wet-lab confirmation.
Absence is not evidence of absence: unregistered, non-US and stealth-stage programs are not visible to these sources.
This page refreshes monthly (no net-new primary entity in 313 days). Mechanism classifications are our reading of the public record and may be revised.

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The public page is the map. The full dossier adds differentiation analysis, kill-tests and the whitespace read for this target — the parts we do not publish.

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