TAVT-135 / Tavanta Therap - LARVOL DELTA

Primary pharmacology and toxicology of TAVT-135, a novel chloride ion transporter in development for the treatment of cystic fibrosis (NACFC 2023) - "The electrophysiologic effects of acute (1–7 μM) and chronic (3 μM) exposure to TAVT-135 and highly effective CFTR modulator therapy (elexacaftor-tezacaftor-ivacaftor [ETI]) were evaluated on primary CF human bronchial epithelial (hBE) cells (F508del/F508del) using a modified Ussing chamber system. Collectively, these in vitro and in vivo data indicate that TAVT- 135 localizes to cell membranes without disrupting cellular integrity, increases Isc to a magnitude similar to that of ETI, is well tolerated in animals, and remains in the lungs after inhalation. Thus, TAVT-135 has the potential to address significant unmet needs in people with CF, including those who are ineligible or not responding to CFTR modulators."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • CFTR

In Vitro Pharmacological Characterization of TAVT-135, a Novel Chloride Ion Transporter for Pan-genotypic Treatment of Cystic Fibrosis (ATS 2023) - "Short circuit current (ISC) following amiloride-induced sodium channel suppression and transepithelial electrical resistance (TEER) were measured. TAVT-135 was also associated with increased ASL height, which is a relevant marker of mucosal hydration. TAVT-135 has the potential to address significant unmet needs in patients with CF who are ineligible or not responding to CFTR modulators."

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Tavanta Therapeutics Announces New Preclinical Data for its Cystic Fibrosis Candidate TAVT-135 at Two Prominent Scientific Conferences (PRNewswire) - "Tavanta Therapeutics...today announced presentations of new preclinical data for TAVT–135, a novel inhaled chloride ion transporter in development for pan-genotypic treatment of cystic fibrosis (CF). Data was shared at both the 2023 American Thoracic Society (ATS) International Conference, held May 19-24, in Washington, DC and at the European Cystic Fibrosis Foundation (ECFS) Basic Science Conference..."

Preclinical • Cystic Fibrosis

In vitro evaluation of TAVT-135, an artificial pan-genotypic chloride ion transporter (NACFC 2022) - "TA VT-135 (0,1, 10, 100 µM) was delivered to the apical side of the cultures, and theimpact of acute or chronic (24-hour) exposure on short-circuit current (Isc)was measured with amiloride-induced suppression of sodium channels.Responses were studied in the presence of Cl–transport agonists (forskolin, uridine triphosphate [UTP]) and an antagonist (CFTR inhibitor-172).Mucus-penetration times for diffusion of fluorescently labeled TA VT-135through 100-µm mucus layers (harvested from human bronchial epithelialcell cultures) were calculated. Initial investigations show promising signs of a CFTR-independent effect of this candidate on Isc and Cl –transport and evidence of it penetrating CF-like mucus. These data suggest that TA VT-135 couldalleviate symptoms associated with highly viscous mucus by increasingelectrolyte levels of the airway surface liquid layer and facilitating watertransport out of epithelial cells. Additional studies of this novel artificial Cl −..."

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Tavanta Therapeutics to Present Preclinical Data for TAVT-135 at the North American Cystic Fibrosis Conference (PRNewswire) - "Tavanta Therapeutics...announced that it will present preclinical data on TAVT-135, a cell-penetrating peptide conjugate, at the Cystic Fibrosis Foundation's North American Cystic Fibrosis Conference (NACFC). The conference will take place November 3-5, 2022, at the Pennsylvania Convention Center in Philadelphia."

Preclinical • Cystic Fibrosis • Genetic Disorders