AZD5055 / Redx, AstraZeneca - LARVOL DELTA

Human iPSC-based Alveolosphere Model to Investigate Fibrotic Disease Signalling in IPF (ATS 2025) - "These experiments provided a novel characterization of fibroblast-epithelial interactions and a deeper understanding of disease-specific molecular mechanisms and stimuli affected in IPF lung, leading to impaired alveolar repair in these patients."

Fibrosis • Idiopathic Pulmonary Fibrosis • Inflammation • VIM

Novel oral PORCN inhibitor does not alter the PK of nintedanib, an approved therapy for idiopathic pulmonary fibrosis (ERS 2024) - P1 | "Both treatments were well tolerated. These data indicate there is no relevant pharmacokinetic DDI between AZD5055 and nintedanib, when co-administered in healthy volunteers."

Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A First-in-human Study in Healthy Volunteers Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5055, A Novel Oral Porcupine Inhibitor Under Development as a Treatment for Pulmonary Fibrosis (ATS 2024) - P1 | "Once daily oral dosing of AZD5055 was safe and well tolerated with favorable PK characteristics in healthy volunteers. Target engagement was demonstrated by reduced AXIN2 gene expression in dermal tissue. These results support progression of AZD5055 to a Phase II study in patients with IPF."

Clinical • P1 data • PK/PD data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • AXIN2

Preclinical Data Supports Assessment of Target Engagement in Skin as a Surrogate for Lung in Clinical Trials of the Porcupine Inhibitor AZD5055 (ATS 2024) - P1 | "The ability of AZD5055 to inhibit Wnt signalling in skin and hair follicles has now been confirmed in a phase I clinical trial (NCT05134727) and our preclinical data provide confidence that this effect translates to the lung tissue. Altogether these data provide evidence that AZD5055 treatment inhibits Wnt signalling in both lung and skin and support the progression to evaluate efficacy of AZD5055 in IPF patients."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • AXIN2

Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 in Japanese and Chinese Healthy Volunteers.. (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

A Study to Assess the Effect of AZD5055 on the Pharmacokinetics (PK) of Nintedanib in Healthy Participants. (clinicaltrials.gov) - P1 | N=18 | Terminated | Sponsor: AstraZeneca | Recruiting ➔ Terminated; The study was terminated as no drug-drug interactions were observed in Part-A of the study and therefore Part-B of the study was not required as per protocol.

Trial termination

Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 in Japanese and Chinese Healthy Volunteers.. (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 in Japanese and Chinese Healthy Volunteers.. (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A Study to Assess the Effect of AZD5055 on the Pharmacokinetics (PK) of Nintedanib in Healthy Subjects. (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

The Porcupine Inhibitor AZD5055 Inhibits Wnt Palmitoylation and Release, and Has Potential to Repair Damaged Alveoli Through Increasing Type 1 Alveolar Epithelial Cell Numbers (ATS 2023) - P1 | "Finally, when iPSC-derived type 2 alveolar cells co-cultured with IPF fibroblasts are treated with AZD5055, we demonstrate that inhibition of Wnt signalling promoted differentiation to the type 1 alveolar epithelial cells (AT1), responsible for gas exchange in the lung, and decreased expression of α-smooth muscle actin, a marker of fibrosis-driving myofibroblast activity.CONCLUSIONS We have shown that AZD5055 is a potent inhibitor of palmitoylation and release of Wnts in vitro. Furthermore, using complex multicellular models we demonstrated that AZD5055 facilitates a key disease modifying process in driving differentiation of alveolar progenitor cells to gas exchange epithelial cells."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • WNT3

Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 Following Single and Multiple Ascending Doses in Healthy Participants (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | N=90 ➔ 63

Enrollment change • Trial completion • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Effect of AZD5055 on the Pharmacokinetics (PK) of Nintedanib in Healthy Subjects. (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2023 ➔ Sep 2023 | Trial primary completion date: Apr 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date

A Study to Compare Bioavailability of AZD5055 Film-coated Tablet With AZD5055 Oral Suspension and to Assess the Effect of Food and an Acid Reducing Agent on Pharmacokinetics (PK) of AZD5055 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

AZD5055: Data from P1 trial (NCT05134727) for healthy volunteers in H1 2023 (AstraZeneca) - Q4 & FY2022 Results: Data from P1 trial (NCT05630677) for healthy volunteers in H1 2023

P1 data • Idiopathic Pulmonary Fibrosis

A Study to Assess the Effect of AZD5055 on the Pharmacokinetics (PK) of Nintedanib in Healthy Subjects. (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A Study to Compare Bioavailability of AZD5055 Film-coated Tablet With AZD5055 Oral Suspension and to Assess the Effect of Food and an Acid Reducing Agent on Pharmacokinetics (PK) of AZD5055 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: AstraZeneca

New P1 trial

"$19m in milestones triggered in December by progress with @AstraZeneca #porcupineinhibitor & @JazzPharma #oncology collaborations. AZD5055 (formerly RXC007) is the 4th clinical asset discovered by @RedxPharma's medicinal chemistry #drugdiscovery platform. #REDX" (@trinity_delta)

Clinical • Oncology

Redx to Receive Milestone Payment of $9 Million Following Initiation of Phase 1 Trial of AZD5055 (RXC006) (Market Screener) - "Redx...announces that a milestone payment from AstraZeneca has been triggered as a result of the initiation of a Phase 1 clinical trial of AZD5055 (RXC006), a Porcupine inhibitor targeting fibrotic diseases including idiopathic pulmonary fibrosis (IPF)...'We are delighted that AstraZeneca is progressing AZD5055 (RXC006) into a Phase 1 study in healthy volunteers to support the further development in IPF.'"

Commercial • New P1 trial • Idiopathic Pulmonary Fibrosis

Redx Pharma to pocket US$4mln milestone payment from AstraZeneca (Proactiveinvestors) - "Redx Pharma...said it will receive the first ‘milestone payment’ under its early payments agreement with AstraZeneca (LON:AZN) following the pair’s licensing deal last summer....It will receive US$4mln of the US$17mln before the start of clinical trials of Redx-developed RXC006, which is targeting fibrotic diseases including idiopathic pulmonary fibrosis...first-in-human studies on RXC007, its oral ROCK2 inhibitor, which also targets fibrosis started earlier this month."

Commercial • New trial • Idiopathic Pulmonary Fibrosis

Redx Pharma surges on AstraZeneca licensing agreement (Sharecast) - "Redx Pharma shares soared on Tuesday after it signed a licensing agreement with AstraZeneca for its porcupine inhibitor for fibrotic diseases, RXC006....At 0917 BST, Redx shares were up 220% to 80p."

Licensing / partnership • Stock price • Idiopathic Pulmonary Fibrosis

Redx shares soar after IPF drug licence deal with AstraZeneca (pharmaphorum) - "Shares in Redx Pharma were soaring this morning after it licensed its preclinical fibrotic disease drug RXC006 to AstraZeneca....AstraZeneca has bought an exclusive global licence to develop and market RXC006, a porcupine inhibitor for fibrotic diseases including idiopathic pulmonary fibrosis (IPF). Redx will receive up to $17m in early payments between signing the deal and the successful start of the first clinical trial....Redx is also eligible for tiered royalties of mid-single digit percentages, based on any future net sales."

Licensing / partnership • Idiopathic Pulmonary Fibrosis

"Redx outlicenses its porcupine inhibitor RXC-006 for almost $380 million to AstraZeneca for development in fibrotic diseases" (@Cortellis)

Redx Pharma focused on cancer and fibrosis treatment (Proactiveinvestors) - "RXC006 is designed to tackle a condition called idiopathic pulmonary fibrosis (IPF), a type of chronic lung disease....Second fibrosis drug candidate RXC007 to start trials in 2021....Phase 1-ready idiopathic pulmonary fibrosis candidate ready to enter the clinic in 2020."

New P1 trial • New trial • Idiopathic Pulmonary Fibrosis