BMPR2

AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today the initiation of a Phase 2 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 2 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). About LAM-001 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 high speed “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 Angel™ 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. The content above comes from the network. if any infringement, please contact us to modify.

GUILFORD, Conn., Aug. 31, 2023 (GLOBE NEWSWIRE) -- AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today the initiation of a Phase 2 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 2 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 (NCT05798923). About LAM-001 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 high speed “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 Angel™ 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. MEDIA CONTACT: info@ai-thera.com

Reports emerged late Wednesday afternoon that Merck emerged as the winning suitor with a deal valued at about $11 billion. Kena Betancur/Getty Images The question of which pharma giant will acquire rare disease-focused Acceleron Pharma appears to be over. Reports emerged late Wednesday afternoon that Merck emerged as the winning suitor with a deal valued at about $11 billion. Bloomberg Law reported Merck and Acceleron came to terms at a price of $180 per share. Although no formal announcement from either company has been made public, Bloomberg said the deal could be announced as early as Thursday morning. If the early report is accurate, that means Merck beat out Bristol Myers Squibb, which already owns about 11.5% of the company. BMS gained the stake in Acceleron when it acquired Celgene, which struck multiple collaboration agreements with the company in 2008 and 2011. That partnership netted approval of Reblozyl in 2019 for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. With the acquisition, Merck will gain control of Acceleron’s portfolio of treatments for rare disease, including its Phase III pulmonary arterial hypertension (PAH) drug sotatercept. The Acceleron drug is an investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily. The drug is designed to rebalance BMPR2 signaling, which is a key molecular driver of PAH, a rare progressive disorder characterized by the constriction of pulmonary arteries and elevated blood pressure in the pulmonary circulation. In 2019, sotatercept received Orphan Drug Designation for PAH from the U.S. Food and Drug Administration. Sotatercept will bolster Merck’s existing PAH pipeline that includes Adempas, which it gained in a licensing deal with Bayer. Earlier this year, Merck initiated a Phase II/III PAH study of MK-5475, an inhaled soluble guanylate cyclase (sGC) stimulator. Merck’s acquisition places the company in a leading position among rare disease-focused companies. And, if Sotatercept is approved, it will lessen the company’s dependence on its blockbuster cancer drug, Keytruda, which is on track to becoming the top-selling drug in the world and provides about half of Merck’s revenue stream. Analysts peg Sotarcept sales at about $2 billion if it is approved. The asset is currently in an ongoing Phase III study. Daina Graybosch, Senior Research Analyst at SVB Leerink, told BioSpace hours ahead of the deal report that Merck’s new head of research and development Dean Li has a feel for the PAH space given his background as a cardiologist. Graybosch said the company has a “long, rich history of understanding this type of biology.” Although she does not see something like Sotatercept becoming an asset that can replace a drug like Keytruda, she said having multiple assets for PAH could be a firm foundation for long-term growth. “I think if Merck does a deal, they just truly have some ability to analyze it and they see something that could really be a meaningful step change,” Graybosch said. The analyst added that Merck has been consistent with its strategic focus, which includes multiple acquisitions over the past few years. Some of those buys include the $425 million in upfront cash to acquire OncoImmune, as well as a $1.85 billion deal for autoimmune-focused Pandion Therapeutics. While terms of the deal have not been formally announced, Graybosch speculated that Merck could be required to dump its Phase II/III PAH asset due to concerns of potential market monopoly. Although both drugs have different forms of mechanisms, the Federal Trade Commission could raise that concern.