Pulmonary Arterial Hypertension

About Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH) is a type of a broader condition known as pulmonary hypertension, which means high blood pressure in the lungs.

PAH is characterized by scarring and narrowing of the small arteries in the lung, which increases pressure and the resistance to blood flow through the lungs.
Preclinical studies have shown that an mTOR inhibitor can reverse or control the disease, including the scarring in the small arteries that are indicated in PAH. [1]

AADi is conducting a phase 1b trial to evaluate the optimal dose and utility use of ABI-009 in the treatment of severe (NCT02587325). Activation of the mTOR pathway has been implicated in the development and progression of PAH and anecdotal clinical data supports the investigation of an mTOR inhibitor to treat PAH [2, 3]. No approved PAH drug addresses ‘proliferative’ component of disease (arterial wall thickening and hyper-proliferaton of smooth muscle and endothelial cells). ABI-009 can achieve high target tissue levels not possible with oral mTOR agents and can be combined with standard therapy in PAH.

You can check out more info about our PAH study and eligibility in our dedicated website here: http://pulmonaryhypertension001.com/

  1. Houssaini et al., Am J Respir Cell Mol Biol 2013 48(5):568-577.
  2. Wessler et al. Chest 2010 138, 991-993.
  3. Seyfarth et al. Pulmonary circulation 2013: 3, 632-638.
  4. AADi, LLC, Data on file


~ 30,000 patients in US (orphan indication)
Only 50% 3 year survival
Current therapies offer only symptomatic relief
No disease modifiers on market
First-in-class opportunity
Can be added to conventional therapy
Opportunity for IV or inhalational route of administration

Pulmonary Arterial Hypertension

January, 3 2019, Aadi Bioscience, Inc. (Aadi), a clinical stage biopharmaceutical company focused on treating diseases driven by mTOR activation, today announced that its drug TARZIFYX™ (sirolimus albumin-bound nanoparticles for injectable suspension, ABI-009) has received Breakthrough Therapy Designation status from the FDA for the indication of Advanced (metastatic or locally advanced) Malignant PEComa (perivascular epithelioid cell tumor). The designation was granted based on data provided to the FDA from Aadi’s ongoing phase 2 registration trial (NCT02494570) in Advanced Malignant PEComa. In October 2018, Aadi also received Fast Track Designation from the FDA for TARZIFYX™ for the same indication. Aadi received orphan drug designation for TARZIFYX™ for the treatment of PEComa in December 2017. Aadi’s Phase 2 registration trial for Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT), a rare form of sarcoma, has completed enrollment. Aadi previously received agreement from the FDA that this open label study in 30 efficacy evaluable patients with a primary endpoint of overall response rate could support the submission of an NDA for approval to treat this rare disease. mTOR inhibition is relevant in a number of disease states and has not been fully exploited in oncology, cardiovascular disease, CNS diseases, mitochondrial disease, diseases of ageing, etc. Due to the unique properties of Aadi’s drug including effective CNS penetration, it is being tested in nine ongoing clinical studies across these indications with encouraging results even outside of oncology in early studies in pulmonary hypertension and surgically refractory epilepsy. Aadi’s ongoing and planned clinical trials include Oncology (pediatric tumors, advanced sarcoma, first-line treatment of advanced colorectal cancer, newly diagnosed and recurrent glioblastoma, advanced neuroendocrine tumors), Cardiovascular indications (pulmonary arterial hypertension), CNS indications (surgically refractory epilepsy) and Mitochondrial disease (Leigh Syndrome). About Aadi and TARZIFYX™ (ABI-009) Aadi is a clinical stage biopharmaceutical company led by Dr. Neil Desai, an inventor of ABRAXANE®, TARZIFYX™ and the nab® technology platform. Aadi’s lead product TARZIFYX™ (sirolimus albumin-bound nanoparticles for injectable suspension, ABI-009) is an mTOR inhibitor complexed with human albumin that has significantly higher tumor accumulation and improved efficacy over other mTOR inhibitors in preclinical models. mTOR as a therapeutic target is well recognized in oncology, however Aadi aims to develop the full potential of albumin-bound sirolimus in therapeutic areas and diseases that are driven by mTOR activation and where the mTOR inhibitors have not or cannot be effectively exploited due to problems of pharmacology, effective drug delivery, safety or effective targeting to the disease site. These indications include oncology, cardiovascular, CNS, mitochondrial disease and diseases of ageing. About PEComa Perivascular epithelioid-cell tumors, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle markers,’ are a rare subset of soft-tissue tumors, with an undefined cell of origin. The PEComa family of tumors include lymphangioleiomyomatosis (LAM), angiomyolipoma (AML), clear-cell ‘sugar’ tumor of the lung (CCST), and a variety of morphologically and immunophenotypically similar tumors, which may arise in almost any body site (typically the uterus, retroperitoneum, genitourinary, and gastrointestinal tract), collectively termed PEComa-NOS. Malignant PEComas can have an aggressive clinical course including distant metastases and ultimate death. They have been shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTORC1 pathway. Therefore, mTORC1 signaling is a promising therapeutic target for malignant PEComa, and anecdotal case reports have suggested clinical benefits of mTOR inhibitors in patients with malignant PEComas.   See original News Broadcast here: Businesswire.com/Aadi