resomelagon (AP1189) / SynAct Pharma - LARVOL DELTA

Resomelagon Phase-2B ADVANCE Study Update: 190 Patients Randomized Tracking for Year-End Recruitment Completion (SynAct Pharma Press Release) - "The Phase 2b ADVANCE is a 12-week randomized placebo-controlled study including newly diagnosed patients with Rheumatoid Arthritis, with elevated inflammation levels (CRP levels above 3mg/l), severe disease symptoms, and ready to initiate 1st line methotrexate therapy."

Trial status • Rheumatoid Arthritis

Baicalin ameliorates high-fat diet induced MAFLD by inhibiting ERK/PPARγ/CD36 pathway. (PubMed, Phytomedicine) - "This study by using integrates computational prediction demonstrated that PPARγ was the main target of BA, then with multi-level experimental validation, elucidated that BA could ameliorate MAFLD by modulating core ERK/PPARγ/CD36 signaling pathway, highlighting a novel therapeutic target for MAFLD."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD36 • IL1B • IL6 • PPARG • SCARB1 • TNFA

Clinical Trial Evaluating Safety and Efficacy of Resomelagon on Dengue Infection (RESOVIR-2) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Federal University of Minas Gerais | Initiation date: Apr 2025 ➔ Feb 2026

Trial initiation date • Dengue Fever • Infectious Disease

SynAct Pharma Refines Development Strategy for Lead Compound Resomelagon (AP1189) (TradingView) - "SynAct Pharma AB...updates on the development strategy for the lead compound resomelagon (AP1189). The compound offers an opportunity to promote inflammatory resolution and a novel treatment approach in inflammatory diseases....In brief SynAct will execute the strategy as follows: Continue recruitment in the ADVANCE Ph2b study with the aim to have all patients dosed in 2025; Initiate a Phase 2a Proof concept study in Polymyalgia Rheumatica."

Pipeline update • Trial status • Immunology • Inflammation • Rheumatoid Arthritis

SynAct receives Issue Notification and Patent Term Adjustment for US patent covering resomelagon (AP1189) combination therapy (SynAct Pharma Press Release) - "SynAct Pharma AB...announced today that the Unites States Patent and Trademark Office (USPTO) has provided the issue notification of US patent 12,303,489 with issue date 20 May 2025 and more than 2 years of Patent Term Adjustment added to the patent’s expiry date....SynAct’s recently announced that US patent application 17/609,849 with claims covering a method of treating rheumatoid arthritis (RA) with resomelagon (AP1189) in combination with methotrexate (MTX) had been allowed for grant of a US patent. The USPTO has now provided the Issue Notification with an issue date for US patent 12,303,489 of 20 May 2025. Importantly, the Issue Notification also determines that that the US patent is awarded a Patent Term Adjustment (PTA) of 769 days, which period is added to the ordinary expiration date of 7 May 2040 to extend the duration of the US patent until 15 June 2042."

Patent • Rheumatoid Arthritis

SynAct Pharma secures patent for resomelagon in combination with MTX (BioStock) - "The United States Patent and Trademark Office has issued a Notice of Allowance for SynAct Pharma’s patent application covering the use of resomelagon in combination with methotrexate (MTX) for the treatment of rheumatoid arthritis. This indicates that the patent office intends to grant the patent, further strengthening the company’s patent portfolio....The company’s phase IIb clinical trial in RA is underway in both the US and EU, with patient enrolment expected to be completed in Q4 2025....The patent will ensure protection at least until 2040."

Enrollment status • Patent • Rheumatoid Arthritis

SynAct Pharma Announces Initiation of Phase II Study with resomelagon (AP1189) for the Treatment of Patients with Dengue (SynAct Pharma Press Release) - "SynAct Pharma AB...announced that the RESOVIR-2 study, an exploratory Phase 2 trial to evaluate the safety and efficacy of the company’s lead candidate drug resomelagon (AP1189) in patients with Dengue has been initiated at clinical sites in Brazil....RESOVIR-2 is a randomized placebo-controlled, phase II study testing once daily oral dosing of Resomelagon (AP1189) vs placebo (1:1 randomization, n=120) as add on to standard treatment in patients with symptomatic Dengue. The potential treatment effect of resomelagon will be evaluated by time to disease resolution though a composite clinical end point. Secondary clinical end points include the ability to reduce the incidence of warning signs of and/or the development of severe dengue."

Trial status • Infectious Disease

Clinical Trial Evaluating Safety and Efficacy of Resomelagon on Dengue Infection (RESOVIR-2) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Federal University of Minas Gerais

New P2 trial • Dengue Fever • Infectious Disease

The European Patent Office issues an Intention to Grant a European Patent Covering the Clinical Formulation of Resomelagon (AP1189) (SynAct Pharma Press Release) - "SynAct Pharma AB...announced that the European Patent Office (EPO) on 14 March 2025 has issued an intention to grant of a European Patent with claims covering the formulation of resomelagon (AP1189) currently undergoing development in clinical phase 2b....In addition to the US patent recently issued covering the specific salt form under clinical development, the present European patent will issue in a complementary patent family covering the formulation of these salt forms and as such will fortify the protection of resomelagon and the drug product in development. The formulation patent will provide exclusivity in Europe for SynAct’s lead asset until 2042 in all uses."

Patent • Renal Disease • Rheumatoid Arthritis

Pivotal US Patent Protecting Resomelagon (AP1189) Granted to SynAct Pharma (SynAct Pharma Press Release) - "SynAct Pharma AB...announced that today, March 4, 2025, the United States Patent and Trademark Office (USPTO) has issued US patent 12,239,631 with claims covering the crystal form of resomelagon (AP1189) currently undergoing development in clinical phase 2b....The US patent is a major cornerstone in the strategy to further protect SynAct’s intellectual property rights with respect to resomelagon and will add to the layers of protection ensuring exclusivity in the US of its lead asset as composition of matter until 2042.....The patent that has now issued by the USPTO is the first in its extended family of patent applications in all major markets around the globe. SynAct continues to pursue additional patent families to further enhance its existing patent estate protecting aspects of resomelagon."

Patent • Rheumatoid Arthritis

A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: SynAct Pharma Aps | Trial completion date: Dec 2024 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Glomerulonephritis • Nephrology • Renal Disease

Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation. (PubMed, Pharmacol Ther) - "In addition to SPMs, we highlight the discovery, biosynthesis, biofunctions, and latest research updates on innovative therapeutics (including annexin-A1 peptide-mimetic RTP-026, small molecule FPR2 agonist BM-986235/LAR-1219, biased agonist for FPR1/FPR2 Cmpd17b, lipoxin mimetics AT-01-KG and AT-02-CT, melanocortin receptor agonist AP1189, gold nanoparticles, angiotensin-(1-7), and CD300a) that can promote resolution of inflammation directly or through modulation of SPMs production. Drug development strategies based on the biology of the resolution of inflammation can offer novel therapeutic means and/or add-on therapies for the treatment of chronic diseases."

Journal • Review • Allergy • Cardiovascular • Immunology • Infectious Disease • Inflammation • Rheumatology • ANXA1

Efficacy and Safety of the Biased Melanocortin Receptor Agonist AP1189/resomelagon in Combination with Methotrexate in DMARD-naïve Rheumatoid Arthritis Patients: The EXPAND Trial (ACR Convergence 2024) - "While there was no observed difference between AP1189 in combination with MTX and placebo+MTX in the study cohort as a whole, post hoc analyses in newly diagnosed RA patients with high disease activity including elevated hsCRP, together with safety data, suggest that AP1189 could be a promising treatment option in this patient group."

Clinical • Combination therapy • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

RESOLVE: A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (clinicaltrials.gov) - P2 | N=125 | Completed | Sponsor: SynAct Pharma Aps | Recruiting ➔ Completed | N=420 ➔ 125

Enrollment change • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Dose Response Study to Evaluate the Efficacy and Safety of Oral AP1189 Administered in Disease-Modifying Anti-Rheumatic Drug (DMARD) Naïve Participants Participants with Early Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: SynAct Pharma Aps

Combination therapy • New P2 trial • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Effects of a pro-resolving drug in COVID-19: preclinical studies to a randomized, placebo-controlled, phase Ib/IIa trial in hospitalized patients. (PubMed, Br J Pharmacol) - "Treatment with AP1189 was associated with less disease caused by beta-coronavirus infection both in mice and in humans. This is the first demonstration of the effects of a pro-resolving molecule in the context of severe infection in humans."

Journal • P1/2 data • Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CXCL10 • IL1B • TNFA

SynAct Pharma announces outcomes of the independent audit of the 4-week RESOLVE P2a clinical trial in Rheumatoid Arthritis - "In November 2023 SynAct Pharma reported that during the evaluation of the data from part A of the RESOLVE study, a four-week dose range study of resomelagon (AP1189) in rheumatoid arthritis patients with an inadequate response to methotrexate treatment, issues were identified that needed further evaluation and initiated an audit of the study by an independent third-party auditor....The independent audit has identified that safety data from all sites should be included in the product safety base and that drug exposure and efficacy data could be utilized for further assessment except for the data from one site where drug exposure and efficacy data should be excluded."

Clinical protocol • Rheumatoid Arthritis

A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: SynAct Pharma Aps | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Glomerulonephritis • Nephrology • Renal Disease

EXPAND: A Safety & Efficacy Study of Treatment With AP1189 in Rheumatoid Arthritis Patients naïve to DMARD Treatment (clinicaltrials.gov) - P2 | N=127 | Completed | Sponsor: SynAct Pharma Aps | Recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

RESOLVE: A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (clinicaltrials.gov) - P2 | N=420 | Recruiting | Sponsor: SynAct Pharma Aps | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: SynAct Pharma Aps | Trial primary completion date: Nov 2022 ➔ Dec 2023

Trial primary completion date • Glomerulonephritis • Nephrology • Renal Disease

The BEGIN Study: A Double-blind, Multi-center, Two-part, Randomized, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of 4 Weeks of Treatment with AP1189 in Early Rheumatoid Arthritis (RA) Patients with Active Joint Disease (ACR Convergence 2022) - "AP1189 is novel oral available compound with anti-inflammatory and pro-resolving effects with the potential to treat active RA. Data from the BEGIN study support the further development of AP1189 as a potential safe and efficacious oral therapy for RA and other inflammatory diseases"

Clinical • Fatigue • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

RESOLVE: A Dose-range Study of the Safety and Efficacy of Treatment in Adult Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (clinicaltrials.gov) - P2 | N=420 | Not yet recruiting | Sponsor: SynAct Pharma Aps

New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: SynAct Pharma Aps | Trial completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Glomerulonephritis • Nephrology • Renal Disease

EXPAND: A Safety & Efficacy Study of Treatment With AP1189 in Rheumatoid Arthritis Patients naïve to DMARD Treatment (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: SynAct Pharma Aps | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology