GUILFORD, CT, May 23, 2023 — AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today the initiation of a Phase II study for its novel inhaled form of sirolimus, LAM-001, for the treatment of pulmonary arterial hypertension (PAH). PAH is a rapidly progressive cardiopulmonary disease that affects an estimated 30,000 patients in the United States with a five-year survival rate of approximately 57%.
“Currently available therapies for PAH provide relief to patients predominantly through the reversal of vasoconstriction, but do not directly address the cellular remodeling that constitutes the underlying pathophysiology of the disease,” said Dr. Aaron Waxman, Director of the Pulmonary Vascular Disease Program at Brigham and Women’s Hospital, and Principal Investigator of the trial. “By modulating both the mTOR and BMPR2 pathways, LAM-001 has the potential to reduce smooth muscle cell hyperproliferation and ameliorate endothelial cell dysfunction in the pulmonary vasculature, thereby altering the long-term course of disease. Even as new disease modifying agents become available, because of its unique mechanism of action, LAM-001 may become an important addition to our growing armamentarium of drugs used to treat this devastating disease.”
“LAM-001 offers an innovative solution to delivering sirolimus directly to diseased lungs, thereby potentially minimizing systemic exposure. Systemic toxicities have heretofore precluded the widespread adoption of oral sirolimus in certain promising indications despite strong signals of clinical benefit. PAH represents one such orphan pulmonary disorder,” said Dr. Brigette Roberts, Chief Executive Officer of AI Therapeutics. “Recognizing that there is still an acute need to offer additional treatments for this population, we are excited to have begun dosing in our Phase II LAM-001 study in PAH.”
The 24-week, single-arm, open label, exploratory study is designed to evaluate the safety, tolerability and activity of LAM-001 in 15 adults with advanced PAH (classified as WHO functional class III) who are symptomatic despite background therapy. The primary endpoint of the trial is safety and tolerability, as well as the change from baseline in peak oxygen uptake (VO2 max) at week 24 as recorded by invasive cardiopulmonary exercise testing (iCPET). Secondary endpoints include additional hemodynamic metrics as determined by iCPET including change in VE/VCO2 slope (ventilatory efficiency), cardiac output (CO), cardiac index (CI), mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), pulmonary arterial distensibility, CavO2 (arteriovenous O2 content difference) at 24 weeks. Assessments of cardiac structure and function will be collected by cardiac magnetic resonance (MR) imaging. Further assessments will include change from baseline in 6-minute walk distance (6MWD), change from baseline in WHO functional class, time to clinical worsening, and LAM-001 pharmacokinetics. The first 24 weeks of therapy will be followed by a 12 month extension period. Additional information is available at www.clinicaltrials.gov (NCT05798923).
LAM-001 is a proprietary, investigational, inhaled formulation of sirolimus, also known as rapamycin. Rapamycin’s potential in PAH stems from its ability to both inhibit mTOR-mediated pulmonary arterial smooth muscle cell proliferation and to improve BMPR2-mediated endothelial cell function. The mTOR pathway has been shown to be activated in small pulmonary arteries in PAH patients and enhanced smooth muscle cell proliferation in vitro can be inhibited with rapamycin. Similarly, BMPR2 signaling dysfunction can be rescued by rapamycin treatment. Rapamycin reverses occlusion and improves lung function in an animal model of PAH.
About AI Therapeutics
AI Therapeutics was founded by Dr. Jonathan Rothberg, serial entrepreneur and Recipient of the National Medal of Technology and Innovation for inventing highspeed “Next-Gen” DNA sequencing, with the goal of utilizing artificial intelligence to accelerate the clinical development of drugs for rare diseases. The company is building out an expansive rare disease pipeline with the help of its Guardian AngelTM Platform, a suite of artificial intelligence tools that use deep learning to understand complex disease biology and the action of potential new therapeutics. To learn more, visit: AI Therapeutics.com.