What changed, and when

PAQ Therapeutics announced on 22 Jan 2026 a Series B extension bringing total Series B financing to 77 million dollars and first-patient dosing in a Phase 1 study of PT0511, a pan-KRAS degrader. (Company press release)

Independent listings and coverage note the PT0511 first-in-human trial and financing, though detailed third-party reporting is limited. (ClinicalTrials.gov NCT07300150, ApexOnco note, TipRanks brief)

60-second thesis frame

Signal strength is moderate but directionally important. PAQ now has two clinical KRAS degraders, mutation-selective PT0253 for G12D and pan-variant PT0511, moving beyond inhibitor classes into targeted degradation, which could address resistance and breadth limits of mutation-specific inhibitors. (May 2025 Series B PR with investor list, Company press release, Jan 2026)

Class precedents set expectations, degraders are already in clinic for KRAS G12D with ASP3082, while broad RAS-on inhibition with RMC-6236 shows manageable rash and GI toxicity, a potential on-target class watch-out for pan approaches. (Nature Communications on ASP3082, 2025, Revolution RMC-6236 WCLC poster PDF, ASCO abstract update on RMC-6236)

Trial specifics for PT0511 are sparse but the NCT record indicates first-in-human dose escalation in KRAS-altered solid tumors, with expansion and an EGFR-antibody combo arm noted by trial aggregators. (ClinicalTrials.gov NCT07300150, Power trial listing)

The seven diligence questions

Clinical

• What KRAS variants does PT0511 degrade in humans, and what depth and durability of target knockdown are achieved at tolerable doses in tumor tissue and ctDNA PD readouts, compared with inhibitor classes such as RMC-6236 and ERAS-4001? (ClinicalTrials.gov NCT07300150, Revolution Medicines update, Erasca program background)
• Does the Phase 1 design include mutation-stratified expansions and EGFR-antibody combination cohorts in mCRC, and how will response be parsed by KRAS mutation status and prior anti-EGFR exposure? (Power trial listing, ClinicalTrials.gov NCT07300150)

Payer or Access

• Is broad tumor genomic profiling required for screening and will US Medicare NCD 90.2 coverage for NGS mitigate site-of-care testing friction in advanced cancer populations targeted by the trial. (CMS NCD 90.2 summary PDF)
• For potential mCRC combinations, how will KRAS testing pathways used for anti-EGFR selection in the UK and EU translate into site readiness for identifying KRAS-mutant or amplified disease. (NICE quality statement on RAS testing in mCRC)

Ops or Adoption

• Can PAQ scale GMP supply and assay infrastructure to support parallel PT0253 and PT0511 Phase 1 programs across multiple tumor-specific expansions in 2026. (Company press release, Jan 2026)

Competitive

• How will a pan-KRAS degrader differentiate clinically versus pan-RAS or pan-KRAS inhibitors that already show activity and tolerability, and versus mutation-selective degraders like ASP3082. (Revolution RMC-6236 clinical materials, Nature Communications on ASP3082, BioCentury KRAS degrader landscape at AACR 2025)

Team or Cap table

• Does the investor mix and clinical leadership have the depth for rapid expansion, given Series B investors MRL Ventures Fund and Bayland co-led the initial 39 million dollar raise, with JJDC, LAV Fund, BioTrack Capital and Sherpa Health Partners participating, and the CMO and advisors named in 2025. (May 2025 Series B PR, CMO and SAB additions)

Red flags

• Class-effect toxicity risk if wild-type KRAS is degraded or suppressed in normal tissues, given rash and GI events seen with pan-RAS inhibitors, so safety margins for pan-KRAS degradation must be demonstrated. (Revolution RMC-6236 materials, ASCO abstract)
• Limited independent verification, most signals come from company PRs and trial registries, so early claims require cautious weighting until third-party data appear. (Company press release, ClinicalTrials.gov NCT07300150)
• Competitive speed, several pan-KRAS or RAS-on programs and the first clinical KRAS degrader ASP3082 set a high bar for differentiation on efficacy, safety, and combinability. (Nature Communications on ASP3082, Erasca and Revolution program pages, Revolution pipeline)

Next catalyst

Potential first data sliver for PT0511 at a 2026 oncology congress if accepted, for example ASCO Annual Meeting 29 May–2 Jun 2026, or ESMO Congress 23–27 Oct 2026, with no company commitment disclosed. (ASCO 2026 program guide, ESMO Congress 2026 page)

FAQ

• What exactly changed by PAQ’s Series B extension to 77 million dollars and first patient dosing for PT0511, and why does it matter for KRAS-driven cancers?
  PAQ added capital to 77 million dollars total for Series B and dosed the first patient in a Phase 1 study of PT0511, a pan-KRAS degrader for KRAS-altered solid tumors, expanding its KRAS degradation clinical footprint. This matters because degraders may address resistance and coverage gaps of mutation-specific inhibitors. (Company press release, BioCentury context on KRAS degraders)
• What is the regulatory path after PAQ’s Therapeutics’ 22 Jan 2026 announcement, and what are the next formal steps in the US, UK, and EU?
  PT0511 remains in first-in-human dose escalation with site activation and safety monitoring, then expansion cohorts before any registrational planning, which would require successful Phase 2 signals and later randomized data. Public registries and standard oncology pathways apply across regions. (ClinicalTrials.gov NCT07300150)
• Which endpoints in the PT0511 program are assessed, and how meaningful might the effect size be?
  Primary endpoints are safety and tolerability, including MTD or RP2D, with pharmacokinetics and preliminary anti-tumor activity as secondary, typical for oncology Phase 1. Clinical meaning will hinge on objective responses and durability across multiple KRAS variants versus historical controls. (ClinicalTrials.gov NCT07300150)
• What safety issues matter post–PAQ Therapeutics’ announcement  regarding first patient dosed with PT0511, and do class effects change real-world use expectations?
  On-target toxicities like rash and GI AEs seen with pan-RAS inhibitors suggest careful dose-optimization and supportive care planning for broad KRAS approaches. Early degraders for KRAS G12D and RAS-on inhibitors have shown manageable profiles, but pan-KRAS degradation needs its own human safety evidence. (Revolution RMC-6236 WCLC poster PDF, Nature Communications on ASP3082)
• Who are the key investors backing the $77M Series B extension announced on 22 Jan 2026?
  The financing included participation from new and existing investors such as Casdin Capital, Johnson & Johnson Innovation (JJDC), MRL Ventures Fund, and Bayland Capital (MedPath, Company press release). This syndicate suggests strong validation from both corporate venture arms (Merck, J&J) and specialist biotech investors.

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 25 Jan 2026, 14:00 London. Purpose: general and impersonal information. Not investment research or advice, no offer or solicitation, no suitability assessment. UK: directed at investment professionals under Article 19(5) and certain high-net-worth entities under Article 49(2)(a)–(d) of the Financial Promotion Order 2005. Others should not act on this. Sources and accuracy: public sources believed reliable, provided “as is,” may change without notice. No duty to update. Past performance is not reliable. Forward-looking statements carry risks. Methodology: questions-first framework using public sources. No conflicts. Authors do not hold positions unless stated. © 2026 LucidQuest Ventures Ltd.

Entities / Keywords

PAQ Therapeutics; PT0511; PT0253; KRAS; KRAS G12D; pan-KRAS; targeted protein degradation; degrader; NCT07300150; MRL Ventures Fund; Bayland Capital; Johnson & Johnson Innovation JJDC; LAV Fund; BioTrack Capital; Sherpa Health Partners; cetuximab; EGFR; metastatic colorectal cancer; NSCLC; pancreatic ductal adenocarcinoma; Revolution Medicines; RMC-6236; daraxonrasib; Erasca; ERAS-4001; Astellas; ASP3082; FDA; EMA; MHRA; CMS NCD 90.2; ASCO 2026; ESMO 2026; dose escalation; RP2D; pharmacokinetics; pharmacodynamics.

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