TD-8236 / Theravance Biopharma - LARVOL DELTA

The Safety, Pharmacokinetics, and Pharmacodynamics of TD-8236, an Inhaled pan-JAK Inhibitor: Results from Part C of a First-in-Human Study in Participants with Moderate to Severe Asthma (ATS 2022) - "In Part C of this FIH study, inhaled TD-8236 dosed at 1500 μg had a favorable safety profile and was generally well tolerated by participants with moderate to severe T2-dominant and non-T2-dominant asthma. No effect was observed on FeNO levels in participants with non-T2-dominant asthma. However, in participants with T2-dominant asthma, treatment with TD-8236 vs placebo was associated with reduced FeNO levels, consistent with FeNO changes observed in Part B."

Clinical • P1 data • PK/PD data • Asthma • Immunology • Inflammation • Pain • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Safety, pharmacokinetics, and pharmacodynamics of TD-8236, an inhaled pan-JAK inhibitor, following single- and multiple-ascending doses in healthy volunteers and mild asthmatics (ERS 2021) - "TD-8236 was generally well tolerated in healthy participants and those with mild asthma. TD-8236 administration resulted in dose-dependent target engagement in the lung as demonstrated by reductions in FeNO with minimal systemic exposure."

Clinical • PK/PD data • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Pharmacokinetics of TD-8236, a Lung-Selective pan-JAK Inhibitor, Following Single-Dose Administration in Mice, Rats, and Dogs (ATS 2021) - "TD-8236 exhibits a lung-selective pharmacokinetic profile after inhalation dosing characterized by low systemic plasma exposures and sustained lung retention. The preclinical TD-8236 PK profile supports once-daily clinical evaluation of this inhaled, lung-selective, JAK inhibitor in patients with inflammatory lung conditions, including moderate to severe asthma."

PK/PD data • Preclinical • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Lung-Selective Pan-JAK-Inhibition with TD-8236 Has Broad Anti-Inflammatory Effects on Eosinophilic and Neutrophilic Airway Inflammation in WT and IL-4Rα Deficient Mice (ATS 2021) - "In these models TD-8236 demonstrated inhibition of eosinophilic airway inflammation, and airway neutrophilia induced by T2-associated allergens and non-T2 triggers, respectively. The anti-inflammatory activity of TD-8236 is evident even on a Background of selective IL-4 and IL-13 deficiency as measured by reduction of molecular and cellular mediators of inflammation across the two phenotypes. These data suggest that TD-8236 may provide benefit to asthma patients across T2-high and T2-low phenotypes."

Preclinical • Asthma • Eosinophilia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IFNG • IL13 • IL4R • IL5 • IL6

Theravance Biopharma Inc (TBPH) Q4 2020 Earnings Call Transcript (The Motley Fool) - P1, N=94; NCT03652038; Sponsor: Theravance Biopharma; "...we completed the additional analysis on TD-8236...taking a deep dive into the gene signature and biomarker data from the Phase 1c study. The gene pathway analysis and biomarker data are consistent with target engagement in the lung....We've decided to pause that clinical program for TD-8236 in its current form and apply our 8236 and 0903 learnings by refining the form of 8236...The full dataset for TD-8236 will be presented at future scientific meetings....One or two of these 15 parameters that we think can be further optimized, either with a different form of 8236 or with one of the other JAK inhibitors that we've got coming out of the research efforts."

Biomarker • Discontinued • P1 data • Asthma • Respiratory Diseases

Theravance Biopharma, Inc. Reports Third Quarter 2020 Financial Results and Provides Business Update (PRNewswire) - P1, N=94; NCT03652038; P2, N=24; NCT04150341; Sponsor: Theravance Biopharma; "YUPELRI (revefenacin)...First and only once-daily, nebulized bronchodilator approved in the U.S. for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), reimbursed by Part B Medicare program...We completed the TD-8236 Phase 1 Part C and Phase 2a Lung Allergen Challenge (LAC) study...We met our primary objectives with the Phase 1 Part C study in moderate-to-severe asthmatics dosing TD-8236 with an inhaled corticosteroid...Gene expression and cytokine data from the Phase 1 Part C is still under analysis. While we are still reviewing the full data set, TD-8236 as a single agent did not meet the primary objective of the Phase 2a LAC study."

P1 data • P2a data • Reimbursement • Asthma • Respiratory Diseases

Effect of Inhaled TD-8236 on Allergen-induced Asthmatic Response (clinicaltrials.gov) - P2; N=24; Completed; Sponsor: Theravance Biopharma; Recruiting ➔ Completed

Clinical • Trial completion • Asthma • Respiratory Diseases

TD-8236: Data from P2 trial (NCT04150341) for allergen-induced asthma in Q4 2020 (Theravance) - Investor Presentation

P2 data • Asthma

[VIRTUAL] Identification of mechanism-specific biomarkers to guide development of the lung-selective inhaled pan-JAK inhibitor TD-8236 (ERS 2020) - "TD-8236 resulted in durable inhibition of cytokine-induced pSTAT when administered to mice 1 or 6 hours prior to BALF collection. Conclusions : These data support methods to evaluate target engagement and anti-inflammatory activity in the BALF of asthmatic patients dosed with TD-8236."

Biomarker • Asthma • Respiratory Diseases • IFNG • IL13 • IL6 • Mucin 5 • POSTN

Single and Multiple Ascending Dose Study of TD-8236 by Inhalation (clinicaltrials.gov) - P1; N=94; Completed; Sponsor: Theravance Biopharma; Recruiting ➔ Completed

Clinical • Trial completion • Asthma • Respiratory Diseases

TD-8236: Data from P1 trial (NCT03652038) for moderate-to-severe asthma in H2 2020 (Theravance) - Q1 2020 Results: Data from P2 trial (NCT04150341) for allergen-induced asthma in H2 2020

P1 data • P2 data • Asthma • Respiratory Diseases

TD-8236: Data from P1 trial (NCT03652038) for asthma in mid-2020 (Theravance, Cowen & Co. 40th Annual Health Care Conference 2020) - Data from P2 trial (NCT04150341) for allergen-induced asthma in 2020 or later

P1 data • P2 data • Asthma • Respiratory Diseases

TD-8236: Data from P1 trial (NCT03652038) for asthma in mid-2020 (Theravance, Cowen & Co. 40th Annual Health Care Conference 2020) - Data from P2 trial (NCT04150341) for allergen-induced asthma in 2020 or later

P1 data • P2 data • Asthma • Respiratory Diseases

Single and Multiple Ascending Dose Study of TD-8236 by Inhalation (clinicaltrials.gov) - P1; N=124; Recruiting; Sponsor: Theravance Biopharma; Trial completion date: Mar 2020 ➔ Jun 2020; Trial primary completion date: Mar 2020 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date • Asthma • Immunology • Respiratory Diseases

Theravance Biopharma Inc (TBPH) Q4 2019 earnings call transcript (The Motley Fool) - "In mid-2020, data from both Phase 1 biomarker study of 8236...in moderate-to-severe asthma...Positive data from these studies would lay the groundwork for advancing to a formal Phase 2b study....As reported last year, initial results from the Phase 1 multiple and single ascending dose studies were encouraging. 8236 was generally well tolerated."

New P2b trial • P1 data

Pharmacokinetics of TD-8236, A Lung-Selective pan-JAK Inhibitor, Following Single-Dose Administration in Mice, Rats, and Dogs (ATS 2020) - "Abstract embargoed at this time."

PK/PD data • Preclinical

Lung-Selective Pan-JAK-Inhibition with TD-8236 Has Broad Anti-Inflammatory Effects on Eosinophilic and Neutrophilic Airway Inflammation in Wild Type and Interleukin-4 Receptor Alpha Deficient Mice (ATS 2020) - "Abstract embargoed at this time."

Preclinical • IL4R

TD-8236, a lung-selective inhaled pan-JAK inhibitor, inhibits gene expression related to severe asthma and exhaled nitric oxide (FeNO), in 3-D airway epithelium liquid interface (ALI) cultures derived from asthmatic donors. (AAAAI 2020) - "T2-high and T2-low asthma-associated genes and pathways are inhibited by TD-8236 projecting broad activity in moderate to severe asthma. These findings could translate into potential biomarkers for future clinical studies."

IL13 • IL4 • IL5 • IL6

Effect of Inhaled TD-8236 on Allergen-induced Asthmatic Response (clinicaltrials.gov) - P2; N=21; Recruiting; Sponsor: Theravance Biopharma; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Single and Multiple Ascending Dose Study of TD-8236 by Inhalation (clinicaltrials.gov) - P1; N=124; Recruiting; Sponsor: Theravance Biopharma; Trial primary completion date: Jul 2019 ➔ Mar 2020

Clinical • Trial primary completion date

Effect of Inhaled TD-8236 on Allergen-induced Asthmatic Response (clinicaltrials.gov) - P2; N=21; Not yet recruiting; Sponsor: Theravance Biopharma

Clinical • New P2 trial

The potent and lung-selective inhaled pan JAK inhibitor TD-8236 limits airway inflammation without affecting systemic immunity in mice (ERS 2019) - "These data suggest that TD-8236, when delivered locally to the mouse lung, provides anti-inflammatory activity without measurable systemic immunosuppression. The importance of JAK/STAT cytokines in asthma warrants further investigation of TD-8236 as a novel inhaled non-steroidal therapy for this disease."

Preclinical

In vitro pharmacological characterization of the potent, lung selective pan-JAK inhibitor TD-8236 (ERS 2019) - "Collectively, these data show that TD-8236 is a potent pan-JAK inhibitor that blocks multiple asthma-relevant cytokine pathways in vitro . This profile supports further development of TD-8236 as a novel inhaled non-steroidal therapy to address the needs of asthma patients."

Preclinical

Single and Multiple Ascending Dose Study of TD-8236 by Inhalation (clinicaltrials.gov) - P1; N=124; Recruiting; Sponsor: Theravance Biopharma; Trial completion date: Jul 2019 ➔ Mar 2020

Clinical • Trial completion date