ADS024 / Adiso Therap, Artugen Therap - LARVOL DELTA

Mining Microorganisms for GPCR Ligands: Identification of LPA3 Agonism as a Key Modulator of Neuroinflammation by ADS024 (DOT 2024) - No abstract available

Inflammation • LPAR3

LPA3 agonist-producing Bacillus velezensis ADS024 is efficacious in multiple neuroinflammatory disease models. (PubMed, Brain Behav Immun) - "ADS024 efficacy was partially inhibited by Ki16425 in vivo suggesting LPA3 may be part of its mechanism. Altogether, these data suggest that ADS024 and its LPA3 agonism activity should be investigated further as a possible treatment for diseases with a neuroinflammatory component."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Inflammation • Movement Disorders • Multiple Sclerosis • Pain • Parkinson's Disease • LPAR3

ADS024, a single-strain live biotherapeutic product of Bacillus velezensis alleviates dextran sulfate-mediated colitis in mice, protects human colonic epithelial cells against apoptosis, and maintains epithelial barrier function. (PubMed, Front Microbiol) - "Oral live ADS024 treatment reduced weight loss, disease activity, colonic mucosal injury, and colonic expression of interleukin 6 (IL-6) and TNFα in dextran sodium sulfate (DSS)-treated mice with colitis. Thus, ADS024 may protect the colonic epithelial barrier in UC via anti-inflammatory, anti-apoptotic, and tight-junction protection mechanisms."

IO biomarker • Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CASP3 • IFNG • IL6 • TJP1 • TNFA

ADS024, a Bacillus velezensis Strain, for Prevention of Recurrence of Clostridioides difficile Infection: Results From a Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study (ACG 2023) - P1 | "Of 36 enrolled patients, 17 had prior episodes (rCDI); 31 completed the study; 69% were female, median age was 58 years, and median (range) duration of exposure was 28 days (2-28). Adverse event data show ADS024 was well-tolerated (Table). Recurrence was observed in 4/27 patients (15%, 3/4 rCDI) treated with ADS024 (median TTR, 10 days [range, 2-14]) and 1 (11%) with placebo (TTR, 108 days)."

Clinical • P1 data • Infectious Disease

ADS024, a single strain live biotherapeutic product, attenuates MOG-EAE induced clinical symptoms in mice and zebrafish (MSMilan 2023) - "Mice were treated orally D0-23 with saline (BID; n=4), ADS024 (5x108 colony forming units (CFU) BID; n=12), positive control FTY720 (3 mg/kg QD; n=8)...Larvae (6 dpf) were treated by addition of ADS024 (4x106 CFU/ml), or positive control Tecfidera (2 ug/g); n=24/group... Oral treatment of MOG-EAE murine and zebrafish models with SS-LBP ADS024 improved clinical symptoms and motor movement suggesting potential for treatment of MS."

Preclinical • CNS Disorders • Gastrointestinal Disorder • Immunology • Infectious Disease • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis

Novel, non-colonizing, single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo. (PubMed, World J Gastrointest Pathophysiol) - "Our findings, demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models, support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Ulcerative Colitis

ADS024, A SINGLE STRAIN LIVE BIOTHERAPEUTIC PRODUCT OF BACILLUS VELEZENSIS, PROTECTS HUMAN COLONIC EPITHELIAL CELLS AGAINST APOPTOSIS AND MAINTAINS EPITHELIAL BARRIER FUNCTION (DDW 2023) - "Conclusion : ADS024 filtrate exhibits direct anti-inflammatory and anti-apoptotic effects on intestinal explants from IBD patients. ADS024 filtrate specifically prevents caspase 3-dependent apoptosis and maintains the barrier functions of human intestinal epithelial cells."

IO biomarker • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • ANXA5 • BAX • CASP3 • IFNG • TNFA

ADS024 in patients recently cured of a Clostridioides difficile infection: results from a randomised, placebo-controlled, double-blind, phase 1b study (ECCMID 2023) - No abstract available

Clinical • Late-breaking abstract • P1 data • Infectious Disease

The Urgent Threat of Clostridioides difficile Infection: A Glimpse of the Drugs of the Future, with Related Patents and Prospects. (PubMed, Biomedicines) - "Many possible drugs of the future for CDI, with diverse mechanisms of action, are in development in the form of microbiota-modulating agents (e.g., ADS024, CP101, RBX2660, RBX7455, SYN-004, SER-109, VE303, DAV132, MET-2, and BB128), small molecules (e.g., ridinilazole, ibezapolstat, CRS3123, DNV3837, MGB-BP-3, alanyl-L-glutamine, and TNP-2198), antibodies (e.g., IM-01 and LMN-201), and non-toxic strains of CD (e.g., NTCD-M3). The development of some therapeutic agents (e.g., DS-2969b, OPS-2071, cadazolid, misoprostol, ramoplanin, KB109, LFF571, and Ramizol) stopped due to failed clinical trials or unknown reasons...The current pipeline of anti-CDI medications appears promising. However, it will be fascinating to see how many of the cited are successful in gaining approval from drug regulators such as the US FDA and becoming medicines for CDI and r-CDI."

Journal • Review • Developmental Disorders • Infectious Disease

ADS024, a Bacillus velezensis strain, protects human colonic epithelial cells against C. difficile toxin-mediated apoptosis. (PubMed, Front Microbiol) - "The anti-apoptotic effects of ADS024 filtrate and ethyl acetate extract were dependent on the inhibition of caspase 3 cleavage. The sterile filtrate, but not ethyl acetate extract, of ADS024 partially degraded toxin B. ADS024 inhibits toxin B-mediated apoptosis in human colonic epithelial cells and colonic explants."

Journal • Infectious Disease • CASP3

ADS024, a Single Strain Live Biotherapeutic Product, Reduces Colonic Inflammation in DSS-Induced Colitis When Dosed Twice Daily (ACG 2022) - "DSS-exposed animals treated with ADS024 twice daily at high dose (5x10 8 CFU/dose) demonstrated significant attenuation of weight loss (p< 0.05) and decreased composite Disease Activity Index (DAI) (p< 0.01) compared to control (DSS only) animals. This ADS024 dosing regimen also decreased mean colon weight:length ratio, a measure of inflammation, as compared to controls (p< 0.005 respectively). The anti-p40 mAb, with a mechanism of action similar to ustekinumab, an approved treatment for UC, reduced DAI but did not significantly reduce colon weight:length ratio."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL1B • IL6 • MPO

A Study of ART24 in Subjects Recently Cured of a Clostridioides Difficile Infection (CDI) (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Adiso Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Feb 2023 ➔ Oct 2022 | Trial primary completion date: Nov 2022 ➔ Jul 2022

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease

Adiso Therapeutics Provides Development Update Reflecting Strong Progress Across Its Pipeline (PRNewswire) - "Adiso also presented data at a third medical meeting from a preclinical study of ADS024, an oral single strain live biotherapeutic product, exploring the gut-brain axis. This highly encouraging data demonstrated the potential of ADS024 to prevent dopamine loss, demonstrating improved motor movement in animal models....The International Congress of Parkinson's Disease and Movement Disorders (September 17, 2022)....In the study, treatment with ADS024 improved dopamine and DOPAC striatal levels in an MPTP mouse model of Parkinson's and led to improved motor movement in an MPTP zebrafish model. Together, these results suggest that ADS024 could potentially have a positive impact on patients with Parkinson's disease by preventing dopamine loss and improving motor movement."

Preclinical • CNS Disorders • Parkinson's Disease

Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities. (PubMed, Sci Rep) - "Here, we describe the identification and initial characterization of ADS024 (formerly ART24), a novel therapeutic bacterium that can kill C. difficile in vitro with limited impact on other commensal bacteria. In addition to directly killing C. difficile, ADS024 also produces proteases capable of degrading C. difficile toxins, the drivers of symptoms associated with most cases of CDI. ADS024 is in clinical development for the prevention of CDI recurrence as a single-strain live biotherapeutic product, and this initial data set supports further studies aimed at evaluating ADS024 in future human clinical trials."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease

Adiso Therapeutics (BIO 2022) - "Adiso has three distinct candidates that may change the treatment paradigm for inflammatory diseases: ADS051, an oral gut-restricted modulator of neutrophil trafficking and activation; ADS024, an oral single strain live biotherapeutic product (SSLBP); and ADS032 a dual NLRP1/NLRP3 inflammasome inhibitor. Adiso has built these programs upon a rich history of institutional and academic collaboration, including the University College Cork, Ireland, the APC Microbiome Institute, the University of Massachusetts Chan Medical School, the Hudson Institute of Medical Sciences Centre for Innate Immunity and Infectious Diseases in Australia and the University of Edinburgh Centre for Inflammation Research. Adiso was founded in 2022 and is based in Concord, MA,"

Immunology • Infectious Disease • Inflammation • NLRP1 • NLRP3

ART24, A BACILLUS VELEZENSIS STRAIN, PROTECTS HUMAN COLONIC EPITHELIAL CELLS AGAINST CLOSTRIDIOIDES DIFFICILE TOXIN-MEDIATED APOPTOSIS (DDW 2022) - "Both ART24 filtrate and ART24 culture media extract inhibited cleaved caspase 3 protein expression in toxin B-treated fresh human colonic tissues. Conclusion : ART24 produces proteases and metabolites with anti-apoptotic properties that are protective against toxin B in human colonic epithelial cells."

Infectious Disease • Oncology • CASP3

Adiso Therapeutics to Present at BioNJ's 12th Annual BioPartnering Conference (PRNewswire) - "Adiso Therapeutics, Inc...will present virtually at BioNJ's 12th Annual BioPartnering Conference....Mr. Megaffin will present the Adiso pipeline of products...The Adiso pipeline includes two small molecules with novel mechanisms of action and single strain live biotherapeutic products (SS-LBP), rapidly advancing in clinical-stage development programs for ulcerative colitis and c. difficile."

Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study of ART24 in Subjects Recently Cured of a Clostridioides Difficile Infection (CDI) (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Adiso Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease

Morningside Ventures Launches Adiso Therapeutics to Advance Novel Therapies for Inflammatory Diseases (PRNewswire) - "Morningside Ventures today announced the launch of Adiso Therapeutics, a clinical-stage biotechnology company advancing a pipeline of novel therapeutics targeting inflammatory diseases. Morningside has financed the Adiso development plans to date, with plans to further support the company's rapid growth moving forward. Adiso is advancing an innovative pipeline of small molecules with novel mechanisms of action and single strain live biotherapeutic products (SS-LBP), pursuing lead indications in ulcerative colitis (UC), and C. difficile infection (CDI)."

Financing • Inflammatory Bowel Disease • Ulcerative Colitis