izencitinib (TD-1473) / Theravance Biopharma - LARVOL DELTA

Izencitinib induction treatment in patients with moderately-to-severely-active Crohn's Disease: A phase 2 double-blind, randomized, placebo-controlled study (ECCO-IBD 2023) - "Conclusion In patients with moderately-to-severely active Crohn's Disease, izencitinib treatment for 12 weeks did not demonstrate a statistically significant reduction in CDAI or endoscopic severity. Izencitinib at both doses was well tolerated without a new safety signal."

Clinical • P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease

Theravance Biopharma, Inc. Reports Third Quarter 2022 Financial Results, Provides Business Update and Extends Tender Offer (PRNewswire) - "YUPELRI® (revefenacin) inhalation solution, the first and only once-daily, nebulized bronchodilator approved in the US for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), with net sales increasing by 35% year-over-year (Q3 2022 vs Q3 2021) – its strongest quarter to date and increased its share of the long-acting nebulized COPD market, increasing to 26.3% through August 2022, up from 25.6% in Q2 2022....Revenue: Total revenue for the third quarter of 2022 was $12.5 million, primarily comprised of $12.4 million in Viatris collaboration revenue. Total revenue for the third quarter represents a $0.7 million decrease over the same period in 2021 primarily driven by the completion of the recognition of non-cash Janssen collaboration revenue in 2021, resulting from the planned close-out of the izencitinib program."

Commercial • Chronic Obstructive Pulmonary Disease • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

EFFICACY AND SAFETY OF ADVANCED ORAL THERAPIES FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2022) - "Patients were randomised to placebo (n=1685), a JAK inhibitor (tofacitinib, n=1879; peficitinib n=176; upadacitinib, n=732; TD-1473, n=31; SHR0320, n=123; filgotinib, n=1199; ritlecitinib, n=150; brepocitinib, n=152) or an S1P receptor modulator (ozanimod, n=928; etrasimod, n=214; amiselimod, n=40; and KRP203, n=17). JAK inhibitors and S1P receptor modulators are effective for inducing clinical and endoscopic remission in UC. Filgotinib, upadacitinib, ozanimod, and etrasimod are also associated with improved histological outcomes in UC. JAK inhibitors are effective for inducing clinical remission in CD but may not provide a benefit for maintenance of remission."

Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

IZENCITINIB INDUCTION TREATMENT IN PATIENTS WITH MODERATELY-TO-SEVERELY ACTIVE ULCERATIVE COLITIS: A PHASE 2B RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY (DDW 2022) - "There were numerically small dose-dependent improvements in clinical response as well as dose-dependent reductions in CRP. Izencitinib at all doses was well tolerated, and no new safety signals were identified."

Clinical • P2b data • Anemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Bowel Disease • Ulcerative Colitis • CRP

"Novel targets in earlier stages of clinical testing: • TD-1473 (Izencitinib; a gut specific pan-JAKi) • SHR0302 (JAK1i) • PF-06700841 (Brepocitinib; JAK1/TYK2i) • PF-06651600 (Ritlecitinib; JAK3i) • BMS-9861165 (Deucravacitinib; TYK2i) • ABX464 (cap-binding complex)" (@charlie_lees)

Clinical • JAK1 • JAK3

"Looks like TD-1473 stopped - https://t.co/DHoa6VqaSa" (@ibddoctor)

JAK inhibitors in crohn's disease: ready to go? (PubMed, Expert Opin Investig Drugs) - "PubMed database and ClinicalTrials.gov website were consulted in order to find the clinical trials evaluating the efficacy and safety profiles of JAK-inhibitors in CD patients, including the following compounds: tofacitinib, filgotinib, upadacitinib, TD-1473, and Pf-06651600/Pf-06700841. JAK-inhibitors are a promising class of oral compounds in moderate-severe CD. Further clinical trials are necessary in order to implement the available knowledge, especially on their long-term safety issues."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Gut-Selective Design of Orally-Administered Izencitinib (TD-1473) Limits Systemic Exposure and Effects of Janus Kinase Inhibition in Nonclinical Species. (PubMed, Toxicol Sci) - "Izencitinib did not affect embryonic development in rats and rabbits as commonly reported with systemic JAK inhibition, consistent with low maternal systemic concentrations (2-6X plasma Cave: JAK IC50 ratio, 10-33X nonclinical: clinical AUC margin) and negligible fetal exposures. In conclusion, the izencitinib gut-selective approach resulted in minimal systemic findings in nonclinical species at pharmacologic, clinically-relevant systemic exposures, highlighting the impact of organ-selectivity in reducing systemic safety findings."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

DIONE: Efficacy and Safety of TD-1473 in Crohn's Disease (clinicaltrials.gov) - P2 | N=167 | Terminated | Sponsor: Theravance Biopharma | Trial completion date: Jan 2023 ➔ Dec 2021 | Active, not recruiting ➔ Terminated; The decision was made following the planned review of trial data by the independent data monitoring committee who determined that, while there are no safety concerns, there are concerns about the ongoing benefit-risk of continuing the trial.

Trial completion date • Trial termination • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Janssen Cuts Ties with Theravance After IBD Program Flop (BioSpace) - "J & J’s Janssen Pharmaceutical says goodbye to San Francisco’s Theravance Biopharma after a disappointing performance from a drug the two companies were developing together. Three years ago, the two entered into a collaboration for izencitinib...to treating ulcerative colitis and Crohn’s disease. Theravance scored $100 million in 2018, with another $900M potential on the line with milestone payments and royalties. Janssen has now opted to terminate the deal in the wake of recent events."

Licensing / partnership • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

RHEA: Efficacy & Safety of TD-1473 in Ulcerative Colitis (clinicaltrials.gov) - P2b; N=243; Terminated; Sponsor: Theravance Biopharma; Trial completion date: Jul 2025 ➔ Oct 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Jun 2025 ➔ Oct 2021; Stopped early due to company decision. Company decision based on interim analysis results in TD-1473-0157.

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

TD-1473 Long-Term Safety (LTS) Ulcerative Colitis (UC) Study (clinicaltrials.gov) - P2/3; N=46; Terminated; Sponsor: Theravance Biopharma; Trial completion date: Sep 2028 ➔ Oct 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Sep 2028 ➔ Oct 2021; Stopped early due to company decision. Company decision based on interim analysis results in TD-1473-0157.

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

"$TBPH 8K only - Discontinues Phase 2 study of Izencitinib (gut-selective oral pan-JAK inhibitor for inflammatory intestinal diseases) in Crohn’s disease" (@BioStocks)

P2 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Theravance Biopharma, Inc. Reports Third Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Theravance Biopharma, Inc...today reported financial results for the third quarter of 2021....Q1 2022: Izencitinib...Phase 2 in Crohn's disease (Study 0173) – top-line results expected in Q1 2022."

P2 data • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease

DIONE: Efficacy and Safety of TD-1473 in Crohn's Disease (clinicaltrials.gov) - P2; N=167; Active, not recruiting; Sponsor: Theravance Biopharma; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

RHEA: Efficacy & Safety of TD-1473 in Ulcerative Colitis (clinicaltrials.gov) - P2b; N=243; Active, not recruiting; Sponsor: Theravance Biopharma; Recruiting ➔ Active, not recruiting; N=880 ➔ 243

Clinical • Enrollment change • Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

TD-1473 Long-Term Safety (LTS) Ulcerative Colitis (UC) Study (clinicaltrials.gov) - P2/3; N=46; Active, not recruiting; Sponsor: Theravance Biopharma; Recruiting ➔ Active, not recruiting; N=500 ➔ 46

Clinical • Enrollment change • Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Theravance Biopharma, Inc. Announces Strategic Actions to Focus on Respiratory Disease Portfolio (PRNewswire) - "Theravance Biopharma, Inc...announced strategic actions to focus on leveraging its expertise in developing and commercializing respiratory therapeutics in order to maximize shareholder value....In order to implement this plan, the Company will halt the development of all non-respiratory disease related programs except that it will close-out the izencitinib Phase 2 Crohn's disease Study 0157 (NCT03758443)..."

Discontinued • Crohn's disease • Immunology • Inflammatory Bowel Disease

Izencitinib: "No statistically significant difference at any dose in the change in total Mayo score at Week 8 relative to placebo"; Ulcerative colitis (Theravance) - Investor Conference Call and Webcast

P2b data • Inflammatory Bowel Disease • Ulcerative Colitis

Theravance Biopharma, Inc. Announces Top-line Results from Phase 2b Dose-Finding Induction Study of Izencitinib in Patients with Ulcerative Colitis (PRNewswire) - P2b/3, N=880; RHEA (NCT03758443); Sponsor: Theravance Biopharma; "Theravance Biopharma...announced top-line results from its Phase 2b dose-finding induction study of izencitinib, an orally administered, gut-selective pan-Janus kinase (JAK) inhibitor in development for the treatment of ulcerative colitis. The study did not meet its primary endpoint of change in the total Mayo score or the key secondary endpoint of clinical remission at week 8, relative to placebo...The Company plans to present study results at a scientific forum...Forthcoming ulcerative colitis data will include results from the 16-week extended induction portion of the study and the 44-week maintenance study. The Company reiterates timing of the top-line results of the Crohn's Phase 2 study in late fourth quarter 2021 or early first quarter 2022."

P2 data • P2b data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

DIONE: Efficacy and Safety of TD-1473 in Crohn's Disease (clinicaltrials.gov) - P2; N=160; Recruiting; Sponsor: Theravance Biopharma; Trial completion date: Aug 2022 ➔ Jan 2023; Trial primary completion date: Aug 2021 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Theravance Biopharma, Inc. Announces Proposed Public Offering of Ordinary Shares (PRNewswire) - "Theravance Biopharma, Inc...announced today that it intends to offer its ordinary shares in an underwritten public offering. Theravance Biopharma also intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of ordinary shares in the offering...Theravance Biopharma intends to use the net proceeds from this offering for general corporate purposes, including further development of...its gut-selective pan-Janus kinase inhibitor izencitinib, which is in a Phase 2b/3 clinical program for ulcerative colitis and Phase 2 clinical program for Crohn's disease."

Financing • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Theravance Biopharma, Inc. Reports First Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Upcoming Clinical Milestones:...Q3 2021: Izencitinib (gut-selective oral pan-JAK inhibitor for inflammatory intestinal diseases) Phase 2b in ulcerative colitis (study 0157) – enrollment complete and topline results expected in Q3. Q4 2021/Q1 2022: Izencitinib (gut-selective oral pan-JAK inhibitor for inflammatory intestinal diseases) due to enrollment challenges, Phase 2 in Crohn's disease (study 0173) – enrollment ongoing and topline results now expected in late Q4 2021/early Q1 2022."

Enrollment status • P2 data • P2b data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

TD-1473: Data from P2 DIONE trial (NCT03635112) for Crohn’s disease in late Q4 2021 (Theravance) - Investor Presentation

P2 data • Crohn's disease • Inflammatory Bowel Disease

Single Dose Bioavailability and Ethnobridging PK Study in Healthy Subjects (clinicaltrials.gov) - P1; N=58; Completed; Sponsor: Theravance Biopharma; Recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease