usnoflast (ZYIL1) / Zydus Lifesci - LARVOL DELTA

UNITE-ALS: Usnoflast Neuromuscular Investigation for Treatment Efficacy in Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Zydus Therapeutics Inc.

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL

A phase 2, proof-of-concept, placebo-controlled, randomized, multicenter, double-blind study to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of Usnoflast (ZYIL1) in patients with amyotrophic lateral sclerosis. (PubMed, Amyotroph Lateral Scler Frontotemporal Degener) - "Usnoflast was well-tolerated at tested doses, and there was no treatment-emergent serious adverse event or death during the study duration. Usnoflast 50 and 75 mg doses were well-tolerated in ALS patients, providing rationale for further studies of Usnoflast in ALS."

Journal • P2 data • PK/PD data • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL

Zydus receives USFDA Fast Track Designation for Usnoflast in the treatment of ALS (Business Upturn) - "Zydus, a discovery-driven global pharmaceutical company, has announced that the United States Food and Drug Administration (USFDA) has granted Fast Track Designation to its investigational drug, Usnoflast, for the treatment of amyotrophic lateral sclerosis (ALS)....In India, Zydus completed a Phase 2(a) randomized, double-blind, placebo-controlled trial of Usnoflast in 24 ALS patients across seven clinical trial sites. The study is registered under the ClinicalTrials.gov Identifier NCT05981040."

Fast track • Amyotrophic Lateral Sclerosis

Zydus announces USFDA Orphan Drug Designation to Usnoflast for the treatment of Amyotrophic Lateral Sclerosis (ALS) (Zydus Press Release) - "Zydus has previously completed a Phase 2(a) randomized, double-blind, placebo controlled clinical trial in 24 ALS patients across 7 clinical trial sites in India. [ClinicalTrials.gov Identifier: NCT05981040]. It is planned to present this Phase 2(a) trial data in upcoming medical conference and publish in medical journal."

Orphan drug • Amyotrophic Lateral Sclerosis

Zydus Lifesciences receives approval from USFDA to conduct Phase II(b) clinical trial for Usnoflast (Indian Pharma Post) - "Zydus...has received approval from USFDA to conduct Phase II(b) clinical trial for Usnoflast, a novel oral NLRP3 inflammasome inhibitor in patients with Amyotrophic Lateral Sclerosis (ALS)."

IND • Amyotrophic Lateral Sclerosis

A Study to Evaluate the Efficacy and Safety of ZYIL1 Oral Capsules for the Treatment of Patients With Mild to Moderately Active Ulcerative Colitis Resistant or Intolerant to Oral Aminosalicylates (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Zydus Lifesciences Limited | Recruiting ➔ Completed | Trial primary completion date: Aug 2024 ➔ Nov 2024

Trial completion • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Zydus Lifesciences Limited | Active, not recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Jun 2024

Trial completion • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Zydus Lifesciences completes phase IIa trial of Usnoflast in ALS patients (CNBC-TV18) - P2a | N=24 | NCT05981040 | Sponsor: Zydus Lifesciences Limited | "Zydus Lifesciences Ltd on Tuesday (September 10) announced the successful completion of a Phase II(a) clinical trial for its novel NLRP3 inflammasome inhibitor, Usnoflast (ZYIL1)...The trial lasted 12 weeks and showed that Usnoflast was safe for patients...Additionally, it helped lower Neurofilament Light chain (NfL) levels, a marker used to measure nerve damage in the body. This suggests that Usnoflast might benefit people with neurodegenerative conditions, where nerve cells gradually break down. The trial also showed improvements in the ALS Functional Rating Scale (ALSFRS-R) scores and Slow Vital Capacity (SVC). This suggests that Usnoflast might help slow down the progression of ALS, a disease that affects muscle control."

P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

A novel selective NLRP3 inhibitor shows disease-modifying potential in animal models of Parkinson's disease. (PubMed, Brain Res) - "There were positive changes in the genes related to walking, locomotor activity, neurogenesis, neuroblast proliferation and neuronal differentiation in the PD brain indicating improvement in neural health which translated into improved mobility. These findings clearly indicate that selective NLRP3 inhibitor ZYIL1, ameliorates neuroinflammation and appears to have the potential for disease modification and progression associated with PD."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • IL1B • NLRP3

Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Zydus Lifesciences Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

Zydus Lifesciences completes enrolment for clinical trial of Usnoflast (The Hindu Business Line) - "Zydus Lifesciences announced the completion of enrolment for its Phase II clinical trial of Usnoflast (ZYIL1), an oral NLRP3 inflammasome inhibitor, in patients with Amyotrophic Lateral Sclerosis (ALS)...The Phase II clinical trial has enrolled 24 ALS patients across seven sites in India. The trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Usnoflast...The company further informed they initiated a Phase II clinical study of Usnoflast in Ulcerative Colitis..."

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Efficacy and Safety of ZYIL1 Oral Capsules for the Treatment of Patients With Mild to Moderately Active Ulcerative Colitis Resistant or Intolerant to Oral Aminosalicylates (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Zydus Lifesciences Limited

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Zydus Lifesciences Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL

Zydus begins Phase II trial of ZYIL1, NLRP3 inhibitor in patients with ALS (ExpressPharma) - "Zydus Life Sciences has received permission from CDSCO, India, to initiate the Phase II clinical study of NLRP3 inhibitor ‘ZYIL1’ in patients with amyotrophic lateral sclerosis (ALS)."

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZY-IL1 in Three Patients with Cryopyrin-Associated Periodic Syndromes. (PubMed, Clin Pharmacol Drug Dev) - "Three adult subjects with a confirmed diagnosis of CAPS were enrolled and administered 50 mg of ZYIL1 twice daily for 7 days...At steady state, the average plasma concentration and trough concentration ranged from 2.5 to 4.2 and 1.4 to 2.5 μg/mL, respectively. Inflammatory markers and disease activity (physician and patient global assessment score) decreased notably 12 hours post-last dose."

Journal • PK/PD data • Inflammation • NLRP3

Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Zydus Lifesciences Limited

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral NLRP3 Inflammasome Inhibitor ZYIL1: First-in-Human Phase 1 Studies (Single Ascending Dose and Multiple Ascending Dose). (PubMed, Clin Pharmacol Drug Dev) - "Inhibition in IL-1β and IL-18 was observed throughout the 14 days of treatment in the multiple-dose study. The safety profile, rapid absorption, marginal accumulation, and significant inhibition of IL-1β and IL-18 level support its development for the management of inflammatory disorders."

Journal • P1 data • PK/PD data • Inflammation • IL18 • IL1B • NLRC5 • NLRP3

A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS) (clinicaltrials.gov) - P2a | N=3 | Completed | Sponsor: Cadila Healthcare Limited | Recruiting ➔ Completed | Trial completion date: Nov 2022 ➔ Jul 2022 | Trial primary completion date: Sep 2022 ➔ Jul 2022

Trial completion • Trial completion date • Trial primary completion date • IL6 • NLRP3

A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS) (clinicaltrials.gov) - P2a | N=3 | Recruiting | Sponsor: Cadila Healthcare Limited | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2022 ➔ Apr 2022

Enrollment open • Trial initiation date • IL1B • IL6 • NLRP3

A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS) (clinicaltrials.gov) - P2a; N=3; Not yet recruiting; Sponsor: Cadila Healthcare Limited

Clinical • New P2a trial • IL1B • IL6 • NLRP3

A Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: Cadila Healthcare Limited; Recruiting ➔ Completed

Clinical • Trial completion

A Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Cadila Healthcare Limited

Clinical • New P1 trial

Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers (clinicaltrials.gov) - P1; N=30; Completed; Sponsor: Cadila Healthcare Limited; Recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Jun 2021; Trial primary completion date: Oct 2021 ➔ Jun 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date

Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Cadila Healthcare Limited

Clinical • New P1 trial

Zydus announces Phase I trials of ZYIL1, a novel oral small molecule NLRP3 inflammasome inhibitor (Zydus Cadila Press Release) - "Zydus has secured a Strong IP portfolio with multiple patents filed in all major countries...Zydus...today announced that it has received permission to initiate the Phase 1 clinical trial of ZYIL1...'We will study the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYIL1 in this Phase I clinical trial in healthy human volunteers.'"

New P1 trial • Patent • Acute Respiratory Distress Syndrome • Cardiovascular • CNS Disorders • Inflammatory Bowel Disease • Metabolic Disorders • Renal Disease