fluticasone propionate controlled release (EP-104) / Eupraxia Pharma - LARVOL DELTA

Eupraxia Pharmaceuticals Reports Additional 52-week Follow-up Data from the RESOLVE Trial in Eosinophilic Esophagitis (EoE) Demonstrating Consistent Results after Dosing with EP-104GI (GlobeNewswire) - "In Cohort 6, a durable clinical symptom response was observed 52 weeks after a single administration of EP-104GI. All 3 patients in Cohort 6 maintained a clinical benefit and 2 out of 3 patients remain in clinical remission 52 weeks after treatment of EoE with EP-104GI. In combination with patients from Cohort 5, at 52 weeks, 4 out of 6 patients remain in clinical remission. At week 36, 67% of all patients in the trial that were measured at 36 weeks, were in clinical remission (Cohorts 5-7, n=9)....The top-line data from the Phase 2b part of the RESOLVE trial is expected in Q3 2026."

P1/2 data • Eosinophilic Esophagitis

Persistent Improvement in Dysphagia Symptoms for 52 Weeks Following a Single Administration of EP-104GI in RESOLVE, an Ongoing Phase 1b/2 Trial in Eosinophilic Esophagitis (Late-Breaking Abstract) (ACG 2025) - P1/2 | "Prior, completed cohorts, with single administrations of up to 12x2.5mg of EP-104GI resulted in sustained mean improvements in eosinophil counts, histological scores and SDI score over 24 weeks. After 12, 24, 36 and 52 weeks respectively, following a single administration of 12x4mg EP-104GI, participants reported mean relative changes from baseline in SDI total score of -41%, -65%, -65% and -35% (mean absolute changes: -2.3, -3.7, -3.7 and -2). Changes from baseline in individual SDI subscales showed improvements in both frequency (-43%, -71%, -43%, -29%) and intensity (-40%, -60%, -80%, -40%) of dysphagia at week 12, 24, 36 and 52, respectively."

Late-breaking abstract • P1/2 data • Candidiasis • Endocrine Disorders • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Nephrology • Renal Disease • Solid Tumor

Results From Dose Escalation Cohorts 1-6 of RESOLVE, an Ongoing Phase 1b/2a Study of EP-104GI (Long-Acting Fluticasone Propionate Injectable Suspension) for Eosinophilic Esophagitis (ACG 2025) - P1/2 | "Previously reported data from cohorts 1-2 (total doses 4-8 mg) showed decreases in SDI for all patients, which were maintained to Week 24 where follow-up data are available. A decrease in mean PEC was observed for all patients in Cohort 2.Cohorts 3-6 (total doses 20-64 mg) showed symptom (SDI) reductions at Week 12 for 11/12 patients; the majority maintained to Week 24. Mean PEC declined for 10/12 participants at Week 12, including one patient in Cohort 5 who achieved PEC ≤6 at all biopsy sites, representing complete histological remission."

P1/2 data • Candidiasis • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Solid Tumor

RESULTS FROM RESOLVE, AN ONGOING PHASE 1B/2A STUDY OF EP-104GI (LONG-ACTING FLUTICASONE PROPIONATE INJECTABLE SUSPENSION) FOR EOSINOPHILIC ESOPHAGITIS: DOSE ESCALATION COHORTS 3 THROUGH 6 (UEGW 2025) - P1/2 | "Therapy for EoE includes proton-pump inhibitors, swallowed topical corticosteroids, dupilumab, and dietary elimination, but these are not always effective and have potential side effects.EP-104GI is a long-acting fluticasone propionate (FP) injectable suspension being developed as a first-in-class treatment for EoE. These data support that local delivery of FP via EP-104GI has been feasible and safe in the ongoing study. Higher doses yield improved patient responses such as histological remission, enhanced patient-reported symptom scores, and favorable histology results, without the occurrence of corticosteroids-related side effects."

P1/2 data • Candidiasis • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation

RESOLVE: A Trial to Evaluate EP-104GI in Adults With Eosinophilic Esophagitis (EoE). (clinicaltrials.gov) - P1/2 | N=117 | Recruiting | Sponsor: Eupraxia Pharmaceuticals Inc. | N=57 ➔ 117 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

RESULTS FROM DOSE ESCALATION COHORTS 1 THROUGH 5 FROM RESOLVE, AN ONGOING PHASE 1B/2A DOSE-ESCALATION STUDY OF EP-104GI (LONG-ACTING FLUTICASONE PROPIONATE INJECTABLE SUSPENSION) FOR EOSINOPHILIC ESOPHAGITIS (DDW 2025) - P1/2 | "Therapy for EoE includes swallowed topical corticosteroids, dupilumab, and dietary elimination, but these are not always effective and have potential side-effects. These data support that the ongoing study of local delivery of FP via EP-104IAR is feasible and safe. Higher doses yield improved patient responses such as histological remission, enhanced patient-reported symptom scores, and favorable histology results, without occurrence of corticosteroids-related side-effects."

P1/2 data • Candidiasis • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation

Eupraxia Pharmaceuticals to Present at Investor and Scientific Conferences in April and May (GlobeNewswire) - "Eupraxia Pharmaceuticals...will be presenting a poster on the Company’s behalf at the Osteoarthritis Research Society International ('OARSI') World Congress 2025, being held April 24-27, 2025 in Incheon (Seoul), South Korea."

P1/2 data • P2 data • Eosinophilic Esophagitis • Osteoarthritis

Eupraxia Pharmaceuticals Announces Positive Data from RESOLVE Phase 1b/2a Trial of EP-104GI for Treatment of Eosinophilic Esophagitis (PRNewswire) - P1b/2a | N=57 | NCT05608681 | Sponsor: Eupraxia Pharmaceuticals Inc | "Histological scores and symptom scores continue to improve as EP-104GI dose, and area of esophageal coverage, increase; Cohort 6 showed the greatest symptom relief scores ('SDI') of all cohorts to date at 12 weeks; Cohort 6 had the greatest magnitude and percentage change in tissue health scores ('EoEHSS') of any cohort to date at 12 weeks; Cohort 6 saw the greatest reduction in Peak Eosinophil Count ('PEC') of any cohort to date; Cohort 5 demonstrated the greatest symptom score reduction (SDI) seen to date at 24 weeks, showing continuously improving symptom relief over that time; For tissue health (EoEHSS) and PEC there is a clear dose-response from Cohorts 3 to 6, with Cohort 6 showing the greatest response; No serious adverse events nor any events of oral or gastrointestinal candidiasis were reported in any of the six cohorts; Cohort 7 is fully enrolled, with 12-week data expected in Q2 2025"

P1/2 data • Eosinophilic Esophagitis

EP-104IAR (Long-Acting Intra-Articular Injection of Fluticasone Propionate) Shows Sustained Improvement in Pain for Subjects with Moderate Baseline Pain and BMI Less Than 30 in SPRINGBOARD, a Phase 2, Randomized, 24-Week Study of Osteoarthritis of the Knee (ACR Convergence 2024) - P2 | "In this subgroup analysis of patients with moderate baseline pain and/or BMI < 30, a single dose of EP-104IAR provided statistically significant improvement in WOMAC scores for up to 22 weeks. This analysis reinforces that EP-104IAR has potential for sustained clinically meaningful benefit in KOA, which is of particular relevance in patients with moderate pain and/or reduced risk of progression to severe pain who may require treatment for a longer period of time before progressing to surgical intervention. Phase 3 trials of EP-104IAR are now planned."

Clinical • P2 data • Cardiovascular • Diabetes • Hypertension • Immunology • Metabolic Disorders • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Eupraxia Pharmaceuticals Announces Positive Data from Fifth Cohort of RESOLVE Phase 1b/2a Trial of EP-104GI for Treatment of Eosinophilic Esophagitis (PRNewswire) - P1b/2 | N=24 | RESOLVE (NCT05608681) | Sponsor: Eupraxia Pharmaceuticals Inc. | "The results announced today from the fifth cohort of the RESOLVE trial, for treatment of EoE, are derived from 12, 4 mg injections of EP-104GI (total dose of 48 mg) administered to the lower two-thirds of each patient's esophagus. The data show: Straumann Dysphagia Index ('SDI'), a patient-reported outcome measure designed to assess symptom severity, was lower for all three patients post-administration with peak reductions up to 3 points (50% from baseline). At 12 weeks post-administration, mean SDI reduction was 41% or 2.3 points. Eosinophilic Esophagitis Histology Scoring System ('EoEHSS') scores, which evaluate the severity and extent of EoE, showed the largest percent reduction of any cohort to date at 12 weeks, with peak reduction of 100% in Stage and Grade scores, and a mean 54% reduction in Composite Stage and Grade scores."

P1/2 data • Eosinophilic Esophagitis

Efficacy and Pharmacokinetic Results From Ongoing Dose Escalation in RESOLVE, a Phase 1b/2a Study of EP-104GI (Extended-Release Fluticasone Propionate Intra-Esophageal Injection) for Eosinophilic Esophagitis (ACG 2024) - P1/2 | "Cohorts 1-4 (Fig 1) have shown mean decreases in SDI maintained to Week 24 (Cohorts 1 and 2). PK data show increasing FP exposure with dose with the anticipated low initial peak followed by stable concentrations throughout follow-up. Mean PEC at injected sites has declined for Cohorts 2-4 at the latest timepoint currently assessed (Week 12 for Cohorts 2 and 3; Week 4 for Cohort 4)."

Clinical • P1/2 data • PK/PD data • Eosinophilia • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation

Pharmacokinetics and Local Tolerability of EP-104GI, an Extended-Release Formulation of Fluticasone Propionate for Treatment of Eosinophilic Esophagitis, After Intra-Esophageal Injection in Mini-Pigs (ACG 2024) - "A plasma C max of 25 pg/mL was observed 1 day after sub-mucosal injection of EP-104GI in the esophagus. After that, plasma FP was stable from 9-15 pg/mL for the next 6 weeks, showing EP-104GI achieved extended FP release. For an FP solution given by oral gavage, C max of 454 pg/mL was at 4 hours and thereafter decreased rapidly with concentrations below 4 pg/mL by Day 10."

PK/PD data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Eupraxia Pharmaceuticals to Present at American College of Gastroenterology Annual Scientific Meeting 2024 (Eupraxia Pharmaceuticals Press Release) - "Poster Details: [1] Pharmacokinetics and Local Tolerability of EP-104GI, an Extended-Release Formulation of Fluticasone for Treatment of Eosinophilic Esophagitis, after Intra-Esophageal Injection in Mini-Pigs; [2] Efficacy and Pharmacokinetic Results From Ongoing Dose Escalation in RESOLVE, a Phase 1b/2a Study of EP-104GI (Extended-Release Fluticasone Propionate Intra-Esophageal Injection) for Eosinophilic Esophagitis"

P1/2 data • Preclinical • Eosinophilic Esophagitis

RESULTS FROM DOSE ESCALATION IN RESOLVE, AN ONGOING PHASE 1B/2A DOSE-ESCALATION STUDY OF EP-104GI (EXTENDED-RELEASE FLUTICASONE PROPIONATE INTRA-ESOPHAGEAL INJECTION) FOR EOSINOPHILIC ESOPHAGITIS (UEGW 2024) - P1/2 | "Therapy for EoE includes swallowed/topical corticosteroids, dupilumab, proton pump inhibitors, and dietary elimination; but these are not always effective.EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection being developed as a novel treatment for EoE. A novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE in this initial escalating dose cohort study. Initial efficacy data show improvement in symptom outcomes and histological findings which may increase with dose. These findings support the potential for extended intervals of at least 6 months between injections."

P1/2 data • Endocrine Disorders • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Nephrology • Pain • Renal Disease

Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial. (PubMed, Lancet Rheumatol) - P2 | "These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR."

Journal • P2 data • Immunology • Osteoarthritis • Pain • Rheumatology

Eupraxia Pharmaceuticals Announces Data from RESOLVE Phase 1b/2a Trial of EP-104GI for Treatment of Eosinophilic Esophagitis (PRNewswire) - P1b/2 | N=24 | RESOLVE (NCT05608681) | Sponsor: Eupraxia Pharmaceuticals Inc. | "Eupraxia Pharmaceuticals...today announced additional positive clinical data from its RESOLVE Phase 1b/2a trial, which is evaluating the safety and efficacy of EP-104GI as a treatment for eosinophilic esophagitis ('EoE')....New Clinical Data from the Fourth Cohort of the RESOLVE Trial: Straumann Dysphagia Index ('SDI')1, a patient-reported outcome measure designed to assess symptom severity, was lower for all three patients post-administration with peak reductions up to four points (67% from baseline). At 12 weeks post-administration, SDI was reduced by a mean of 45% or 3.3 points – a level comparable with currently approved therapies....New Clinical Data from the Third Cohort in the RESOLVE Trial: SDI was 50% lower in one of two evaluable patients at 24 weeks. A third patient in this cohort discontinued evaluation for reasons unrelated to the study."

P1/2 data • Eosinophilic Esophagitis • Immunology

A Trial to Evaluate EP-104IAR in Adults With Eosinophilic Esophagitis (EoE). (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Eupraxia Pharmaceuticals Inc. | N=24 ➔ 57 | Trial completion date: Nov 2024 ➔ Dec 2025 | Trial primary completion date: Nov 2024 ➔ Dec 2025

Enrollment change • Trial completion date • Trial primary completion date • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

EFFICACY OF A NOVEL LONG-ACTING FLUTICASONE PROPIONATE INTRA ARTICULAR INJECTION (EP-104IAR) IN KNEE OSTEOARTHRITIS: PER-PROTOCOL ANALYSIS OF A RANDOMISED, DOUBLE-BLIND, PHASE 2 TRIAL OF EP-104IAR VS VEHICLE PLACEBO (SPRINGBOARD) (EULAR 2024) - P2 | "In this PP analysis, a single dose of EP-104IAR provided statistically and clinically meaningful improvement in WOMAC scores for up to 20 weeks compared to vehicle, with greater separation between treatment arms than in preliminary intent-to-treat analyses 1 . The PP analysis demonstrated duration of effect is longer than the currently approved immediate- and extended-release corticosteroids. This analysis and previously reported safety data reinforces that EP-104IAR has potential for sustained clinically meaningful benefit in KOA, addressing a significant unmet need."

Clinical • P2 data • Immunology • Osteoarthritis • Pain • Rheumatology

INITIAL RESULTS FROM RESOLVE, AN ONGOING PHASE 1B DOSE-ESCALATION STUDY OF EP-104GI (LONG-ACTING FLUTICASONE PROPIONATE INJECTABLE SUSPENSION) FOR EOSINOPHILIC ESOPHAGITIS (DDW 2024) - P1/2 | "Therapy for EoE includes swallowed/topical corticosteroids dupilumab and dietary elimination; but these are not always effective. ConclusionsInitial data support that the ongoing study of local delivery of FP via EP-104IAR is feasible and suggest it is safe. This novel therapy has a potential interval of 6-1 months between inter-esophageal injections without side-effects typically associated with corticosteroids."

P1 data • Back Pain • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Musculoskeletal Pain • Pain

Eupraxia Pharmaceuticals Announces Expansion of RESOLVE Phase 1b/2a Trial of EP-104GI for Treatment of Eosinophilic Esophagitis (PRNewswire) - "Eupraxia Pharmaceuticals...today announced that regulators in Australia and Canada have cleared the Company's request to expand its Phase 1b/2a RESOLVE trial, which is evaluating the safety and efficacy of EP-104GI as a treatment for eosinophilic esophagitis ('EoE')...as well as encouraging safety and duration of impact from EP-104GI, support the significant expansion of the RESOLVE trial as a pathway to a potential registration trial commencing in 2025....The protocol amendment for trial expansion includes: The addition of 4 mg/injection site and 6 mg/injection site doses and an option of up to 20 injections for dose escalation....To evaluate the potentially longer duration of effect of EP-104GI at higher doses, the study follow-up was extended from 24 weeks to 52 weeks for participants who receive doses of >40 mg (total dose) of EP-104GI."

Clinical protocol • Eosinophilic Esophagitis

PHARMACOKINETICS OF EP-104IAR LONG-ACTING FLUTICASONE PROPIONATE FOR INTRA ARTICULAR INJECTION IN 163 SUBJECTS FROM SPRINGBOARD, A PHASE 2 STUDY IN KNEE OSTEOARTHRITIS (OARSI 2024) - "Purpose (the aim of the study): Eupraxia Pharmaceuticals is developing EP-104IAR (long-acting fluticasone propionate (FP) for intra articular (IA) injection) to treat knee osteoarthritis (KOA) symptoms. EP-104IAR employs a novel controlled-release technology to optimize the pharmacokinetics (PK) of FP, maximizing IA residence time while limiting systemic exposure, providing a greater duration of efficacy with fewer systemic side effects."

Clinical • P2 data • PK/PD data • Immunology • Osteoarthritis • Pain • Rheumatology

EFFICACY OUTCOMES IN PATIENTS WITH KNEE OSTEOARTHRITIS: PER-PROTOCOL ANALYSES FROM SPRINGBOARD, A PHASE 2, RANDOMIZED, 24-WEEK STUDY OF EP-104IAR (LONG-ACTING INTRA-ARTICULAR INJECTION OF FLUTICASONE PROPIONATE) (OARSI 2024) - "EP-104IAR is a long-acting fluticasone propionate (FP) IA injection being developed for OA symptoms. EP-104IAR employs a novel controlled-release technology to optimize the pharmacokinetics of FP, maximizing IA residence time while limiting systemic exposure, providing a greater duration of efficacy with fewer systemic and local side effects."

Clinical • P2 data • Immunology • Osteoarthritis • Pain • Rheumatology

Eupraxia Pharmaceuticals Announces Upcoming Presentations at the Osteoarthritis Research Society International World Congress 2024 (Canada Newswire) - P2 | N=318 | SPRINGBOARD (NCT04120402) | Sponsor: Eupraxia Pharmaceuticals Inc. | "Eupraxia Pharmaceuticals Inc...today announced that the Company will present two abstracts at the upcoming Osteoarthritis Research Society International ('OARSI') World Congress 2024. The meeting is being held in Vienna, Austria from April 18-21, 2024....The Phase 2b SPRINGBOARD study met its primary and key secondary endpoints, showing a clinically and statistically meaningful impact on pain, while also demonstrating that EP-104IAR has an encouraging safety profile. In combination with our pre-clinical and MRI results, these data suggest a potential best-in-class candidate in terms of managing cartilage health."

P2b data • CNS Disorders • Osteoarthritis • Pain

A Trial to Evaluate EP-104IAR in Adults With Eosinophilic Esophagitis (EoE). (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Eupraxia Pharmaceuticals Inc. | Phase classification: P1b ➔ P1/2

Phase classification • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Eupraxia Pharmaceuticals Announces Updated Positive Clinical Data in EP-104GI RESOLVE Trial for the Treatment of Eosinophilic Esophagitis (Canada Newswire) - P1b/2 | N=24 | RESOLVE (NCT05608681) | Sponsor: Eupraxia Pharmaceuticals Inc. | "The results announced today from the second cohort of the RESOLVE trial, using Eupraxia's Diffusphere™ technology for EoE, are derived from a low dose of eight 1 mg injections of EP-104GI administered to a portion of each patient's lower esophagus...There were no serious adverse events or treatment-related adverse events in either cohort; All three of the patients in the second dose cohort showed reductions in their patient-reported outcomes with an average 60% reduction in their Dysphasia Likert score (difficulty swallowing) and an 80% reduction in their Odynophagia Likert score...The third cohort of the RESOLVE trial has been fully recruited and the dosing is five times that of the first cohort...further results are expected in the second quarter of 2024."

P1/2 data • Trial status • Eosinophilic Esophagitis