Candidate: TXA127

Type: Pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in lung injury, TXA127 has shown therapeutic activity in animal models of chronic stroke, Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa.

The binding of SARS-CoV-2 to ACE2 down-regulates the activity of the enzyme, leading to a loss of angiotensin-(1-7). Constant reasons that replacing the peptide with TXA127 will restoe the protective nature of the ACE2/Ang-(1-7)/Mas axis.

2021 Status: Selected for ACTIV-4d Trial—Constant said May 12 that TXA127 had been been selected for the NIH’s ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) 4d RAAS trial. ACTIV-4d RAAS is designed to evaluate treatments targeting the RAAS and to determine whether modulation of the RAAS is an effective strategy for preventing progression to critical illness, multiorgan failure, or mortality in hospitalized COVID-19 patients.

ACTIV-4d RAAS is expected to enroll approximately 1,600 patients at more than 50 sites, including members of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, supported by the NIH’s National Heart, Lung, and Blood Institute. In addition to TRV027, ACTIV-4d RAAS is also expected to evaluate Trevena’s TRV027, and Apeiron Biologics’ APN01.

NHLBI has awarded Vanderbilt Institute for Clinical and Translational Research (VICTR) a $60 million grant to lead the trial.

2020 Status: Multiple Phase II Trials—Constant said July 8 that TXA127 will be evaluated in a series of Phase II clinical trials in hospitalized COVID-19 patients who are not in the ICU. The trials will be conducted at medical centers in the U.S., including the Brigham and Women’s Hospital in Boston, Massachusetts; Policlinico S. Orsola-Malpighi Hospital in Bologna, Italy; and at sites in Israel affiliated with Bar-Ilan University and Technion Israel Institute of Technology. More than 400 patients are expected to be recruited.

TXA127 has been shown in preclinical models of acute lung injury to reduce fibrosis, stabilize endothelial and epithelial barrier function and reduce inflammation, Constant said.

COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types: