TP-6076 / Innoviva - LARVOL DELTA

An Analysis of the Novel Fluorocycline TP-6076 Bound to Both the Ribosome and Multidrug Efflux Pump AdeJ from Acinetobacter baumannii. (PubMed, mBio) - "We then compare the differences in binding modes between TP-6076 and the related tetracycline antibiotic eravacycline in both targets. In this work, we use cryo-EM to show how AdeJ recognizes the experimental tetracycline antibiotic TP-6076 and prevents this drug from interacting with the A. baumannii ribosome. Since AdeJ and the ribosome use different binding modes to stabilize interactions with TP-6076, exploiting these differences may guide future drug development for combating antibiotic-resistant A. baumannii and potentially other strains of MDR bacteria."

Journal • Infectious Disease

Phase 1, Safety and Bronchopulmonary PK Study in Healthy Volunteers (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Tetraphase Pharmaceuticals, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

In-vitro activity of the novel fluorocycline TP-6076 against carbapenem-resistant Acinetobacter baumannii. (PubMed, Int J Antimicrob Agents) - "The susceptibility of 323 non-duplicate CRAB isolates to TP-6076, amikacin, ampicillin/sulbactam (SAM), cefepime, colistin, doxycycline, eravacycline, imipenem, levofloxacin, meropenem, minocycline, rifampicin, sulbactam, tigecycline, tobramycin and trimethoprim/sulfamethoxazole (SXT) was determined by the broth microdilution method. Compared to other compounds, TP-6076 was the most active antimicrobial against carbapenem-resistant A. baumannii, including isolates that were resistant to other anti-Acinetobacter reference drugs including ampicillin/sulbactam, colistin, amikacin/tobramycin, and levofloxacin. TP-6076 is a promising new agent that may offer a useful addition to the limited armamentarium of drugs targeting this problem pathogen."

Journal • Preclinical

In vivo efficacy of TP-6076 in murine thigh and lung infection models challenged with Acinetobacter baumannii (ECCMID 2019) - "Female CD-1 mice (22 ± 2 g) were rendered neutropenic by intraperitoneal injection of cyclophosphamide at 150 mg/kg (Day -4) and 100 mg/kg (Day -1) pre-infection. TP-6076 demonstrated potent in vivo efficacy in murine neutropenic thigh/lung infection models challenged with carbapenem-resistant A. baumannii. Further PK/PD modeling to predict percentage of target attainment (PTA) in patients is warranted.e"

Preclinical • Neutropenia

Phase 1, Safety and Bronchopulmonary PK Study in Healthy Volunteers (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Tetraphase Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar

TP-6076, a Fully Synthetic Tetracycline Antibacterial Agent, is Highly Potent against a Broad Range of Pathogens, Including Carbapenem-Resistant Enterobacteriaceae (ASM Microbe 2018) - "Fully synthetic tetracycline analogs with novel substitutions at C4, C7, and C8 were designed and synthesized using the total synthesis approach, and their antibacterial activity-structure relationships were systematically studied. A number of these new tetracyclines displayed high in vitro potency against a broad range of clinically important pathogens, including carbapenem-resistant Enterobacteriaceae (CRE). TP-6076, a lead compound from this novel chemical series, is currently being evaluated in phase 1 clinical studies."

Biosimilar

BAL: Phase 1, Safety and Bronchopulmonary PK Study in Healthy Volunteers (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: Tetraphase Pharmaceuticals, Inc.

New P1 trial • Biosimilar

Phase 1, Safety and Bronchopulmonary PK Study in Healthy Volunteers (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: Tetraphase Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting; N=20 ➔ 8; Trial completion date: May 2019 ➔ Feb 2020; Trial primary completion date: Mar 2019 ➔ Jun 2019

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