Dekavil (F8-IL10) / Pfizer, Philogen - LARVOL DELTA

EFFICACY AND SAFETY OF THE INTERLEUKIN-10-FRAGMENT F8 FUSION PROTEIN, PF06687234, AS ADD-ON THERAPY TO INFLIXIMAB IN PATIENTS WITH ACTIVE ULCERATIVE COLITIS: A RANDOMIZED, PHASE 2A CLINICAL TRIAL (DDW 2025) - P2a | "PF06687234 was well tolerated, but when combined with background infliximab treatment, did not meet the efficacy endpoints in this small cohort of participants with active UC. The inability to detect high levels of PF06687234 in mucosal biopsies, suggests that efficacious tissue concentrations may not have been achieved at the dose tested. This therapeutic hypothesis should be investigated in larger studies and with higher doses than studied here."

Clinical • P2a data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL10

A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX (clinicaltrials.gov) - P2 | N=27 | Terminated | Sponsor: Philogen S.p.A. | Active, not recruiting ➔ Terminated; Approvals of new agents for the same indication have significantly slowed down the recruitment in this trial making the prosecution of the present investigation extremely difficult.

Trial termination • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL17A • IL18 • IL2 • IL22 • IL6 • MMP3

A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Philogen S.p.A. | Trial completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL17A • IL18 • IL2 • IL22 • IL6 • MMP3

DekaJoint: Safety and Preliminary Signs of Efficacy of F8IL10 for Intra-articular Treatment (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Philogen S.p.A.

New P1 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Philogen S.p.A. | Recruiting ➔ Active, not recruiting | N=87 ➔ 27 | Trial completion date: Apr 2018 ➔ Dec 2022

Enrollment change • Enrollment closed • Trial completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL17A • IL18 • IL1B • IL2 • IL22 • IL6 • MMP3 • TNFA

Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission. (clinicaltrials.gov) - P2a; N=20; Terminated; Sponsor: Pfizer; Trial completion date: Jul 2021 ➔ Jan 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Jul 2021 ➔ Jan 2021; The Sponsor changed R&D strategy and priority.

Clinical • Trial completion date • Trial primary completion date • Trial termination • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL10

Distribution of a Single IV Dose Of [124I]-Pf 06687234 and Pf 06687234 Assessed With PET-CT Imaging In Moderate To Severe Ulcerative Colitis and Crohn's Disease (clinicaltrials.gov) - P1b; N=0; Withdrawn; Sponsor: Pfizer; Suspended ➔ Withdrawn

Clinical • Trial withdrawal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission. (clinicaltrials.gov) - P2a; N=20; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting; N=76 ➔ 20

Clinical • Enrollment change • Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Distribution of a Single IV Dose Of [124I]-Pf 06687234 and Pf 06687234 Assessed With PET-CT Imaging In Moderate To Severe Ulcerative Colitis and Crohn's Disease (clinicaltrials.gov) - P1b; N=5; Suspended; Sponsor: Pfizer; Trial completion date: Mar 2021 ➔ Feb 2022; Trial primary completion date: Mar 2021 ➔ Feb 2022

Clinical • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission. (clinicaltrials.gov) - P2a; N=98; Recruiting; Sponsor: Pfizer; N=68 ➔ 98

Enrollment change • Biosimilar • Immunology • Inflammation • Inflammatory Bowel Disease

A phase Ib clinical trial with dekavil (F8-IL10), an anti-inflammatory immunocytokine for the treatment of rheumatoid arthritis, used in combination with methotrexate (EULAR 2012) - Presentation time: 08.06.2012; 11:45; Anticipated presentation at EULAR 2012

Anticipated P1 data presentation • Rheumatoid Arthritis

A phase Ib clinical trial with Dekavil (F8-IL10), an anti-inflammatory immunocytokine for the treatment of rheumatoid arthritis, used in combination with methotrexate (EULAR 2012) - P1b, N= NA; The clinical trial is still on-going and has so far confirmed the excellent tolerability of DEKAVIL at the doses used; These safety data are in line with the ones which had previously been established for IL10 in patients with rheumatoid arthritis

Trial update • Rheumatoid Arthritis

A phase Ib clinical trial in rheumatoid arthritis of dekavil (F8-IL10), a novel anti-inflammatory immunocytokine (EULAR 2014) - Presentation time: 14.06.2014, 10:15; Abstract #SAT0232; P1, N=20; NCT02076659; Sponsor: Philogen S.p.A; "Considering the maximum ACR response achieved: three patients achieved an ACR 70 response, three patients achieved an ACR 50 response and six patients achieved an ACR20 response at various time points during regular or extended follow-up...Of note stand out two patients in the 30 µg/kg cohort and in the 60 µg/kg cohort who achieved long-lasting remission: ACR70s at week 60 (Patient 8) and week 44 (Patient 11), still on-going."

P1 data • Rheumatoid Arthritis

Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis. (PubMed, BMC Rheumatol) - "Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil)...The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA."

Journal • IL6

Distribution of a Single IV Dose Of [124I]-Pf 06687234 and Pf 06687234 Assessed With PET-CT Imaging In Moderate To Severe Ulcerative Colitis (clinicaltrials.gov) - P1b; N=5; Suspended; Sponsor: Pfizer; Trial completion date: Dec 2020 ➔ Mar 2021; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date

F8-IL10: a new potential anti-rheumatic drug evaluated by a PET-guided translational approach. (PubMed, Mol Pharm) - "Patient observations and subsequently arthritic animal studies pointed to awareness of increased [124I]I-F8-IL10 uptake in liver and spleen associated with moderate systemic inflammation. This translational study demonstrated the value of in vivo biodistribution and PET-CT guided imaging in development of new and potential anti-rheumatic drugs'."

Journal

Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission. (clinicaltrials.gov) - P2a; N=76; Recruiting; Sponsor: Pfizer; Trial completion date: Feb 2020 ➔ Jul 2021; Trial primary completion date: Feb 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date

Distribution of a Single IV Dose Of [124I]-Pf 06687234 and Pf 06687234 Assessed With PET-CT Imaging In Moderate To Severe Ulcerative Colitis (clinicaltrials.gov) - P1b; N=5; Suspended; Sponsor: Pfizer; Trial completion date: May 2020 ➔ Oct 2020; Initiation date: Mar 2019 ➔ Sep 2019; Trial primary completion date: May 2020 ➔ Oct 2020

Clinical • Trial completion date • Trial initiation date • Trial primary completion date