RSLV-132 / Resolve - LARVOL DELTA

Targeted therapies against type I interferon and TNF-alpha in cutaneous lupus erythematosus: A systematic review of randomized trials. (PubMed, Dermatol Online J) - "Anifrolumab showed significant benefit in TULIP-2 (CLASI-50: 49% vs 25%; P = .001) and MUSE (63% vs 30.8%). Sifalimumab achieved CLASI-50 responses up to 73%. Deucravacitinib (TYK2 inhibitor) and BIIB059 (anti-BDCA2) also showed clinical improvements. RSLV-132 and epratuzumab did not demonstrate efficacy...Evidence for anti-TNF therapies remains insufficient. Further trials stratified by CLE subtype and patient-reported outcomes are warranted to inform clinical guidelines."

Journal • Review • Cutaneous Lupus Erythematosus • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Oncology • Systemic Lupus Erythematosus • Varicella Zoster • TNFA • TYK2

Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting. (PubMed, Mol Biomed) - "Diagnostically, nuclease-specific cleavage signatures have matured into cell-free DNA fragmentomics validated across 13 cancer types in a 3,021-patient cohort; therapeutically, the field now spans engineered actin-resistant DNASE1/DNASE1L3 biologics, selective TREX1 and ADAR1 inhibitors entering first-in-human evaluation, STING-activating nanomedicines, RNase Fc-fusions such as RSLV-132 in phase 2a lupus, and JAK1/2 inhibition as standard of care in Aicardi-Goutières syndrome. We synthesize this evidence as a two-fate problem: whether an endogenous nucleic acid accumulates at these sensors to drive autoinflammation or is cleared by nucleases before detection is set by the balance between sensor engagement and clearance capacity. The therapeutic corollary acts on the ligand rather than the enzyme, restoring ligand availability where disease is malignant and restoring clearance where disease is self-directed."

First-in-human • Journal • Review • Aicardi Goutieres Syndrome • Colorectal Cancer • Genetic Disorders • Immunology • Inflammatory Arthritis • Interferonopathies • Lung Adenocarcinoma • Lung Cancer • Lupus • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Systemic Lupus Erythematosus • ADAR • DNASE1L3 • IFIH1 • JAK1 • STING • TLR3 • TREX1

Efficacy and safety of emerging immunomodulatory agents versus standard therapies in refractory cutaneous lupus: A systematic review. (PubMed, Dermatol Online J) - "Emerging immunomodulatory agents, including thalidomide, lenalidomide, anifrolumab, belimumab, and intravenous immunoglobulin, may offer improved outcomes...RSLV-132 and tofacitinib demonstrated partial efficacy. Herpes zoster was more frequent with anifrolumab. Anifrolumab and belimumab provide superior efficacy with acceptable safety in RCL, supporting their inclusion in personalized treatment algorithms."

Journal • Review • Cutaneous Lupus Erythematosus • Herpes Zoster • Immunology • Inflammatory Arthritis • Lupus • Varicella Zoster

A Study of RSLV-132 in Females With Sjögren's Disease (clinicaltrials.gov) - P2 | N=106 | Recruiting | Sponsor: Resolve Therapeutics | Trial completion date: Jul 2026 ➔ Mar 2027 | Trial primary completion date: May 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Immunology • Sjogren's Syndrome

A Study of RSLV-132 in Females with Primary Sjögren's Syndrome (clinicaltrials.gov) - P2 | N=106 | Recruiting | Sponsor: Resolve Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Sjogren's Syndrome

A Phase 2 Study of RSLV-132 in Females With Primary Sjögren's Syndrome (clinicaltrials.gov) - P2 | N=106 | Not yet recruiting | Sponsor: Resolve Therapeutics

New P2 trial • Immunology • Sjogren's Syndrome

Phase 2 Study of RSLV-132 in Subjects With Long COVID (clinicaltrials.gov) - P2 | N=112 | Completed | Sponsor: Resolve Therapeutics | Active, not recruiting ➔ Completed | N=70 ➔ 112 | Trial completion date: Mar 2023 ➔ Nov 2023 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132. (PubMed, Clin Infect Dis) - "While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings."

Clinical • Journal • P2 data • Fatigue • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • RNASE1

Resolve Therapeutics Announces Publication of Lupus Clinical Trial Results (PRNewswire) - "Resolve Therapeutics....today announced the publication of results from its phase 2a clinical trial of RSLV-132 in patients with Systemic Lupus Erythematosus (SLE) in Lupus Science & Medicine...The publication entitled 'Evaluation of RNase therapy in systemic lupus erythematosus: a randomized phase 2a clinical trial of RSLV-132' describes a proof-of-concept study in SLE patients with moderate-severe cutaneous disease activity."

P2a data • Systemic Lupus Erythematosus

Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132. (PubMed, Lupus Sci Med) - "Six months of RSLV-132 therapy consisting of a weekly loading dose of RSLV-132 for 1 month, followed by 5 months of biweekly administrations did not significantly improve the mean CLASI score relative to placebo in this cohort of patients with SLE. The study entry criteria selected patients with moderate-severe cutaneous disease activity and no minimum SLEDAI score, which resulted in a wide range of systemic disease activity from inactive to severe as measured by SLEDAI. When the participants with higher SLEDAI and CLASI scores were analysed, a trend towards clinical improvement favouring RSLV-132 was observed. The results warrant further evaluation of RSLV-132 in SLE and suggest that patients with more active systemic disease are most likely to benefit from RNase therapy."

Journal • P2a data • Cutaneous Lupus Erythematosus • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

"Don't forget RSLV-132 https://t.co/URenPTxiM4" (,@tiredguineapig)

Phase 2 Study of RSLV-132 in Subjects With Long COVID (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Resolve Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Phase 2 Study of RSLV-132 in Subjects With Long COVID (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Resolve Therapeutics | Trial completion date: Mar 2022 ➔ Mar 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Phase 2 Study of RSLV-132 in Subjects With Long COVID (clinicaltrials.gov) - P2; N=90; Recruiting; Sponsor: Resolve Therapeutics

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • PCR

Resolve Therapeutics Receives FDA Approval to Initiate Phase 2 Clinical Trial of RSLV-132 in Long Covid Patients (PRNewswire) - "Resolve Therapeutics...announced that the US Food and Drug Administration has approved a New Investigational Drug application for RSLV-132 to initiate a phase 2 clinical trial in patients with long covid."

IND • Infectious Disease • Novel Coronavirus Disease

RSLV-132 Demonstrates Clinically Meaningful Improvement in Patients With Systemic Lupus Erythematosus in Phase 2a Clinical Trial (PRNewswire) - P2a, N=66; NCT02660944; Sponsor: Resolve Therapeutics; "Resolve Therapeutics....today announced results from its Phase 2a study of RSLV-132 in patients with Systemic lupus erythematosus (SLE)....On the primary endpoint, change in CLASI score between the two groups at day 169; 23% of patients in the placebo group had a 50% reduction in CLASI score, and 33% of RSLV-132 treated subjects had a CLASI 50 response. Secondary endpoints included the BICLA and SRI-4 composite endpoints....'The study identified the segment of SLE patients for whom RSLV-132 will have the most clinical benefit, Resolve will confirm this finding in a larger Phase 2 study planned for 2021.'"

New P2 trial • P2a data • Immunology • Lupus • Systemic Lupus Erythematosus

Resolve Therapeutics Publishes Positive Sjogren's Syndrome Clinical Trial Results (PRNewswire) - P2, N=28; NCT03247686; Sponsor: Resolve Therapeutics; "Resolve Therapeutics...today announced publication of results from its Phase 2 study of RSLV-132 for the treatment of primary Sjogren's syndrome (pSS). The work was published in the leading rheumatology journal, Arthritis and Rheumatology (doi.org/10.1002/art.41489). The Phase 2 study demonstrated a clinically meaningful improvement in four separate, independent, validated measures of fatigue in the RSLV-132 group...'Resolve will confirm the finding in a large Phase 3 study starting in early 2021.'

P2 data • P3 data • Immunology

Should we finally consider the biopsychosocial model in systemic autoimmune diseases? (PubMed, Arthritis Rheumatol) - "(1) evaluating the therapeutic effects of RSLV-132 (a new RNase compound) in patients with primary Sjogren syndrome (pSS)...However, therapeutic trials are also a unique opportunity to learn about the pathogenesis of such complex condition. Indeed, this study showed a significant improvement of fatigue (measured by various validated scales) in treated patients, surprisingly correlated with the increased expression of ISG."

Journal • Complement-mediated Rare Disorders • Fatigue • Immunology • Sjogren's Syndrome

A Phase 2a of RSLV-132 in Subjects With Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2a; N=64; Completed; Sponsor: Resolve Therapeutics; Active, not recruiting ➔ Completed; Trial completion date: Jan 2020 ➔ Aug 2020; Trial primary completion date: Jan 2020 ➔ May 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Nuclease Therapy Improves Severe Fatigue in Primary Sjögren's Syndrome: A Randomized Clinical Trial. (PubMed, Arthritis Rheumatol) - "Administration of RSLV-132 improved severe fatigue in pSS patients as determined by four independent measures of fatigue."

Clinical • Journal • Fatigue • Rheumatology • Sjogren's Syndrome

Resolve initiates RSLV-132 clinical studies (Resolvebio Press Release) - "Resolve Therapeutics...announced today the initiation of clinical studies with its lead compound RSLV-132. Resolve administered the first doses to humans of RSLV-132 its first-in-class targeted nuclease therapy designed to decrease the burden of circulating RNA-containing immune complexes in SLE patients...a multi-dose study in SLE patients planned to begin in the second quarter of 2014."

Anticipated new trial • Phase shift • Trial initiation date • Immunology • Lupus

A Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome (clinicaltrials.gov) - P2; N=28; Completed; Sponsor: Resolve Therapeutics; Active, not recruiting ➔ Completed; Trial completion date: Jan 2019 ➔ Aug 2018; Trial primary completion date: Oct 2018 ➔ Jul 2018

Trial completion • Trial completion date • Trial primary completion date • Biosimilar • Complement-mediated Rare Disorders • Dry Eye Disease • Ophthalmology • Sjogren's Syndrome

A Phase 2a of RSLV-132 in Subjects With Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2; N=50; Not yet recruiting; Sponsor: Resolve Therapeutics

New P2 trial • Biosimilar • Lupus

A Phase 2a of RSLV-132 in Subjects With Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2; N=50; Recruiting; Sponsor: Resolve Therapeutics; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Lupus

Resolve announces positive clinical data from RSLV-132 lupus study (PRNewswire) - P1, N=32; NCT02194400; "Resolve Therapeutics...today announced the successful completion of a multiple ascending dose study in patients with systemic lupus erythematosus (SLE) with its lead compound RSLV-132...Of the evaluable subjects with a SLEDAI >0 (N=22), a greater proportion of RSLV-132 treated subjects (44%) had an improvement in disease activity as compared to placebo treated subjects (33%)."

P1 data • Immunology • Lupus