RG6421 / Roche - LARVOL DELTA

Randomized, phase I studies to evaluate the safety, tolerability, and pharmacokinetics of an inhaled, TMEM16A potentiator, GDC-6988, in healthy subjects. (PubMed, Ther Adv Respir Dis) - P1 | "Inhaled GDC-6988 was safe and well tolerated across all dose levels. The plasma PK of GDC-6988 was low and generally dose-proportional with a relatively short half-life."

Clinical • Journal • P1 data • PK/PD data • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Feb 2026 ➔ Jul 2027 | Trial primary completion date: Feb 2026 ➔ Jul 2027 | Phase classification: P1/2 ➔ P1

Phase classification • Trial completion date • Trial primary completion date • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1/2 | N=128 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Sep 2026 ➔ Feb 2026

Trial completion date • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Mechanistic Physiologically Based Pharmacokinetic Modeling of Dry Powder and Nebulized Formulations of Orally Inhaled TMEM16A Potentiator GDC-6988. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The sensitivity analyses showed that the systemic Cmax depended on the ratio of airway to alveolar deposition, but this did not impact the AUC. This novel mechanistic lung PBPK modeling framework could be applied to predict plasma and regional lung exposure and inform the early clinical development of inhaled molecules (e.g., dose selection)."

Journal • PK/PD data

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: Genentech, Inc. | Phase classification: P1/2 ➔ P1

Phase classification • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1/2 | N=128 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Mar 2026 ➔ Sep 2026

Trial completion date • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1/2 | N=128 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1/2 | N=128 | Not yet recruiting | Sponsor: Genentech, Inc. | Phase classification: P1 ➔ P1/2

Phase classification • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test the Safety and Effects of Inhaled GDC-6988 in Participants With Muco-Obstructive Disease (clinicaltrials.gov) - P1 | N=128 | Not yet recruiting | Sponsor: Genentech, Inc.

New P1 trial • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Phase-1 multiple ascending dose healthy volunteer study to evaluate the safety, tolerability, and pharmacokinetics of GDC-6988, a dry powder formulation of a selective inhaled potentiator of TMEM16A (ECFS 2023) - "GDC-6988 was generally safe and well-tolerated at 11.2 mg BID. Systemic exposure levels of GDC-6988 were low. Additional cohorts at higher doses are ongoing, and a Phase 2 study in patients with CF is planned."

Clinical • P1 data • PK/PD data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A first in human study to evaluate the safety, tolerability, and pharmacokinetics of GDC-6988 (ETD002), a selective inhaled potentiator of the TMEM16A chloride channel (NACFC 2022) - P1 | "GDC-6988 is generally safe and well tolerated at doses of upto 75 mg BID by nebulized inhalation. Reductions in FEV 1are self-limited and can be mitigated with pretreatment albuterol. As expected, systemicexposure levels of GDC-6988 are low."

Clinical • P1 data • PK/PD data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pain • Pulmonary Disease • Respiratory Diseases

A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Inhaled ETD002 in Healthy Subjects (clinicaltrials.gov) - P1; N=80; Completed; Sponsor: Enterprise Therapeutics Ltd; Recruiting ➔ Completed

Clinical • Trial completion

A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Inhaled ETD002 in Healthy Subjects (clinicaltrials.gov) - P1; N=96; Recruiting; Sponsor: Enterprise Therapeutics Ltd; Active, not recruiting ➔ Recruiting

Enrollment open

A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Inhaled ETD002 in Healthy Subjects (clinicaltrials.gov) - P1; N=88; Active, not recruiting; Sponsor: Enterprise Therapeutics Ltd; Recruiting ➔ Active, not recruiting; Trial completion date: Feb 2021 ➔ Jun 2021; Trial primary completion date: Feb 2021 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

Enterprise Therapeutics’ First-in-Class TMEM16A potentiator program for treatment of cystic fibrosis and other respiratory diseases acquired by Roche (Businesswire) - "Enterprise Therapeutics...today announced its novel TMEM16A potentiator portfolio has been fully acquired by Roche and will be developed by Genentech, a member of the Roche Group. The portfolio includes ETD002 which recently entered Phase 1 trials. Enterprise’s shareholders received an upfront payment of £75 million and are eligible to receive additional contingent payments."

M&A • Cystic Fibrosis • Respiratory Diseases

Enterprise Therapeutics Doses First Subjects in Phase 1 Trial for First-in-Class Cystic Fibrosis Therapy ETD002 (Businesswire) - "Enterprise Therapeutics...today announced it has successfully dosed the first subjects in a Phase 1 trial for its novel inhaled cystic fibrosis therapy, ETD002. The first-in-man safety study is being conducted in healthy participants with ETD002, a TMEM16A potentiator aimed at treating all people with cystic fibrosis (CF)."

Trial status • Cystic Fibrosis

A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Inhaled ETD002 in Healthy Subjects (clinicaltrials.gov) - P1; N=88; Recruiting; Sponsor: Enterprise Therapeutics Ltd

Clinical • New P1 trial