BWC0977 / Bugworks - LARVOL DELTA

Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity. (PubMed, Commun Biol) - "It targets both DNA gyrase and topoisomerase IV with balanced low-nanomolar potencies, showing remarkable superiority over ciprofloxacin and gepotidacin. The compound also demonstrates more than 5000-fold selectivity for bacterial over human topoisomerases and retains efficacy against fluoroquinolone and carbapenem-resistant clinical isolates. Together, these structural, biochemical, and microbiological insights elucidate BWC0977's broad-spectrum antibacterial activity and reduced vulnerability to resistance, establishing it as a promising next-generation antibiotic to address the global threat of antimicrobial resistance."

Journal • Infectious Disease • Pneumonia

A Phase 1 Study of the Safety and Tolerability of Single and Multiple Ascending Doses of BWC0977 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Bugworks Research Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Phase 1 Study of the Safety and Tolerability of Single and Multiple Ascending Doses of BWC0977 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Bugworks Research Inc.

New P1 trial

BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections. (PubMed, Nat Commun) - P1 | "BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias."

Clinical • Journal • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases

Evaluating the In Vivo Efficacy of BWC0977 in an Inhalational Mouse Model of Melioidosis (ASM Microbe 2024) - "At 24 hours (h) post-challenge, mice were treated with saline, ceftazidime (150 mg/kg), trimethoprim-sulfamethoxazole (TMP-SMX, 78 mg/kg), or BWC0977 (150 mg/kg). It is important to note that the challenge dose in the study was exceedingly high (350 x LD50) and that recrudescence is common in acute mouse models with much lower challenge doses. Overall, BWC0977 was statistically noninferior to comparator antimicrobials and this proof-of-concept study supports continued investigation of BWC0977 as a PEP for melioidosis."

Preclinical • Infectious Disease

The Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Bugworks Research Inc. | N=56 ➔ 4 | Trial completion date: Jul 2024 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2024 ➔ Jan 2024; CMC challenges

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease

The Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Bugworks Research Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2024 ➔ Jul 2024 | Trial primary completion date: Aug 2024 ➔ Apr 2024

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease

The Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Bugworks Research Inc.

New P1 trial • Infectious Disease

A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of BWC0977 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: Bugworks Research Inc. | Recruiting ➔ Completed | N=64 ➔ 44

Enrollment change • Trial completion • Infectious Disease

Efficacy of BWC0977 Treatment in an Inhalational Mouse Model of Tularemia (ASM Microbe 2023) - "Treatment with the comparator control antibiotics ciprofloxacin (30 mg/kg, BID, IP) or gentamicin (24 mg/kg, BID, SC), saline or test article vehicles (BID, PO), or with BWC0977 (150 mg/kg, BID, PO) were initiated 24 h or 48 h post-pathogen challenge to mimic post-exposure prophylaxis (PEP) or treatment after onset of clinical symptoms (TX), respectively. These data indicate that BWC0977 was similar to treatment controls in clearing bacteria. By meeting or exceeding the efficacy observed with two strong standard-of-care antibiotics, BWC0977 demonstrates exceptional promise for future development in the treatment of inhalational tularemia."

Preclinical • Infectious Disease

Preclinical intravenous pharmacokinetics of BWC0977, a novel bacterial topoisomerase inhibitor in preclinical species (ECCMID 2023) - No abstract available

PK/PD data • Preclinical

Pharmacokinetics of BWC0977 in pulmonary epithelial lining fluid and efficacy in a neutropaenic lung infection model in rats (ECCMID 2023) - No abstract available

PK/PD data • Preclinical • Infectious Disease • Respiratory Diseases

PK-PD of new broad-spectrum agent BWC0977 (ECCMID 2023) - No abstract available

PK/PD data

Efficacy of oral BWC0977 against drug resistant Escherichia coli ST131-H30 in normal and diabetic murine model of ascending UTI infection (ECCMID 2023) - No abstract available

Preclinical • Infectious Disease

Resistance frequency in Escherichia coli , Pseudomonas aeruginosa , and Acinetobacter baumannii exposed to BWC0977, a novel bacterial topoisomerase inhibitor (ECCMID 2023) - No abstract available

Minimum inhibitory concentration evaluation of BWC0977, a novel bacterial topoisomerase inhibitor, against recent drug resistant clinical isolates (ECCMID 2023) - No abstract available

Clinical

Molecular interactions of BWC0977: a dual inhibitor of bacterial DNA gyrase and topoisomerase IV (ECCMID 2023) - No abstract available

Preclinical evaluation of a novel antibiotic drug candidate, BWC0977, for activity against multidrug-resistant bacteria implicated in U.S. military combat wound infections (ECCMID 2023) - No abstract available

Preclinical • Infectious Disease

A First in Human Study of the Safety and Tolerability of Single and Multiple Doses of BWC0977 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Bugworks Research Inc. | Trial completion date: Jun 2022 ➔ Feb 2023 | Trial primary completion date: May 2022 ➔ Oct 2022

Trial completion date • Trial primary completion date • Infectious Disease

Bugworks Research Inc. secures US$18M Series B1 Funding from Reputed Global Investor Syndicate (The EU, UK, Japan, South Africa & India), led by Lightrock India (Canada Newswire) - "Bugworks Research...announced the financing of US$18M Series B1. This round will support the clinical development of BWC0977, a novel broad spectrum anti-bacterial agent available in both IV and Oral forms, and the pre-clinical development of its best-in-class Adenosine immuno-oncology asset."

Financing • Oncology