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A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055

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  • June 20, 2025
  • Caroline Owen, et al., Astra Zeneca
Topic/Product:
Inflammation, Inflammation Panel 250
Disease Area:
PK PD Safety
Sample Type:
Serum

Highlights

  • Oral dosing with AZD5055 for 14 days was well tolerated by healthy volunteers
  • The pharmacokinetic properties of AZD5055 support once daily oral dosing
  • AZD5055 treatment reduced AXIN2 mRNA levels in skin and hair follicle biopsies
  • AZD5055 treatment reduced serum levels of Wnt7a and Wnt16

Summary

Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.

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Authors & Affiliations

Xiao-Hong Zhou,1,14Susanne Prothon,2,14Engin Liathdale,3,14Nicola Ferrari,4Kebria Hezaveh,5Zhi Liu,5Szilard Nemes,6 Joachim Almquist,2Michael L. Williams,2Olami Sobande,7Christer Gottfridsson,8Bernadette R. Gochuico,9Adam Platt,4 Zach Brohawn,5Maria G. Belvisi,10,11Ronald Goldwater,12Ellinor Hornberg,13and Caroline A. Owen9,15,*

  1. Patient Safety Biopharma, Chief Medical Office, Oncology R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo ¨lndal, Sweden
  2. Clinical Pharmacology & Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo¨lndal, Sweden
  3. Early Clinical Development, Research and Early Development, Respiratory and Immunology (RI), BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo ¨lndal, Sweden
  4. Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0AA, UK
  5. Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA
  6. BioPharma Early Biometrics and Statistical Innovation, Data Science & AI, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo ¨lndal, Sweden
  7. Late-stage Development, Respiratory and Immunology (RI), Inhaled Clinical Development, Respiratory, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA
  8. Cardiovascular Safety Centre of Excellence, Global Patient Safety, Chief Medical Office, Oncology R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo¨lndal, Sweden
  9. Early Clinical Development, Research and Early Development, Respiratory and Immunology (RI), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA
  10. SVP and Head of Research and Early Development, Respiratory and Immunology (RI), BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo ¨lndal, Sweden
  11. Respiratory Pharmacology, National heart and Lung Institute, Imperial College, London SW7 2AZ, UK
  12. Parexel Early Phase Clinical Unit (Baltimore), Harbor Hospital, Baltimore, MD 21225, USA
  13. Projects, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 51 Mo¨lndal, Sweden
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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.