Constant Therapeutics will be initiating several clinical trials to test the effect of its peptide, TXA127, as a treatment for COVID-19 patients who are hospitalized, but not in the intensive care unit (ICU). TXA127 is a pharmaceutical formulation of the natural human peptide, angiotensin-(1-7). Angiotensin-(1-7) is produced in the body by the action of the enzyme angiotensin converting enzyme 2 (ACE2), which degrades angiotensin II to produce angiotensin-(1-7). The COVID-19 virus binds to ACE2, and inactivates the enzyme, leading to a deficiency in angiotensin-(1-7) and the loss of the normal beneficial biologic effects of the peptide. Those effects include maintaining barrier function in the lung and reducing inflammation. TXA127 will be given as treatment to restore angiotensin-(1-7) levels and improve pulmonary function.
There are 1 million new strokes annually in the U.S. and more than 10 million people living with disability from stroke. Acute stroke therapeutics have been universal failures with the exception of tPA, which is only given to 5-10% of stroke patients. In contrast, Constant will focus on the opportunity to enhance neurological function at weeks or months after stroke. TXA127 has shown striking efficacy in animal models of stroke recovery when treatment was initiated four weeks after the stroke. TXA127 has the potential to transform the treatment of stroke. Constant is planning a Phase 2 clinical trial in stroke recovery which will begin in 2019.
Cardiomyopathy in DMD
Cardiomyopathy is the most common cause of death as children with DMD age, and it represents a large unmet medical need. In three genetically distinct models of muscular dystrophy (Duchenne MD Limb Girdle MD, Congenital MD), TXA127 shows improvements in skeletal muscle fibrosis, muscle strength, and ambulation, and in the LGMD model, TXA127 reversed cardiac dysfunction.
Epidermolysis Bullosa (EB)
Recessive Dystrophic EB is a severe genetic Collagen VII deficiency that affects children and is characterized by skin blistering, fibrosis, and premature death from aggressive skin cancers. Its pathophysiology is mediated through the TGF-beta pathway, and there are no approved therapies for RDEB. TXA127 showed positive effects in two mouse models of RDEB. Constant is collaborating with with four EB charities – DEBEA (Austria), Cure-EB, EBRP, and EBMRF – to develop an oral formulation of TXA127 and to use that formulation in a Phase 2 trial in EB.