resomelagon (AP1189) / SynAct Pharma - LARVOL DELTA

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

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

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

"SynAct Pharma completes clinical pharmacokinetic test of AP1189 tablet https://t.co/WNUoJTJfdy" (@CisionNews)

Clinical • PK/PD data

SynAct-CS002: A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease (clinicaltrials.gov) - P2; N=105; Completed; Sponsor: SynAct Pharma Aps; Active, not recruiting ➔ Completed

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

"SynAct Pharma reports positive PK data on AP1189 tablets https://t.co/iLwUCAaeer" (@CisionNews)

PK/PD data

SynAct Pharma strengthens its patent portfolio for AP1189 following an Intention to Grant from the European Patent Office (Market Screener) - "SynAct Pharma AB ('SynAct') today announced that the European Patent Office (EPO) has issued an Intention to Grant for the company's European patent application covering AP1189 in methods of treating arthritic diseases....The European patent, when granted, will provide protection until 2040 for the use of SynAct's lead compound AP1189 in combination with methotrexate in methods of treating arthritic disease...Importantly, the patent application among other also covers the use of combination treatment in other arthritic diseases, such as Psoriatic Arthritis and Ankylosing Spondylitis."

Patent • Ankylosing Spondylitis • Psoriatic Arthritis