AI Therapeutics Seeks Partner to Advance Testing of LAM-001, its Candidate Inhaled Therapy for PAH

Ana Pena, PhD avatar

by Ana Pena, PhD |

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AI Therapeutics is seeking to advance the development of its candidate treatment LAM-001 for patients with lymphangioleiomyomatosis (LAM) and pulmonary arterial hypertension (PAH), two rare lung disorders.

Specifically, the company is looking for a collaborator with commercial expertise to advance LAM-001 in a registrational trial for LAM disease and a Phase 2 trial for PAH.

LAM-001 is the first inhaled formulation of rapamycin, also known as sirolimus, to reach the clinical stage testing in humans. Rapamycin is used to prevent organ transplant rejection due to its ability to suppress the immune system. It is approved for the treatment of LAM disease.

LAM is a rare lung disease almost exclusively found in women, and is characterized by non-cancerous overgrowths of abnormal muscle-like cells in the lungs. This results in the formation of cysts and the destruction of lung tissue, and can lead to difficulty in breathing (dyspnea), episodes of collapsed lung, or respiratory failure.

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At the molecular level, rapamycin couples to another factor and the two together inhibit the mammalian target of rapamycin (mTOR), an enzyme fundamental for the growth, proliferation, and function of cells. By inhibiting mTOR, rapamycin can prevent the excessive proliferation of cells, including muscle cells that make up the blood vessels of the lungs, and of immune T-cells — thereby producing its immunosuppressive effect.

According to AI Therapeutics, inhalation of low doses of LAM-001 has the potential to deliver therapeutic doses of rapamycin into the lung, while leading to fewer side effects compared with oral rapamycin, which has a widespread effect on the body. Common side effects of oral rapamycin include fever, cold symptoms, mouth sores, nausea, diarrhea, headache, muscle aches, chest pain, and dizziness.

So far, LAM-001 has been tested in clinical trials with healthy volunteers, and in patients with LAM disease.

“LAM-001 may offer an opportunity for women with LAM disease to stabilize their lung function, and reduce the side effects associated with oral rapamycin,” Simon Johnson, professor of respiratory medicine at the University of Nottingham, in the U.K., said  in a press release.

Lewis Rubin, MD, professor at the University of California, San Diego School of Medicine, added: “I also see tremendous potential for LAM-001 as a new mechanistic approach to treat pulmonary arterial hypertension since rapamycin has effects on two pathways — mammalian target of rapamycin and bone morphogenetic protein receptor type II (BMPR2) that are involved in the pathogenesis [disease mechanism] of PAH.”

Of note, more than 350 BMPR2 gene mutations have been linked to PAH.

LAM-001 was named an orphan drug in the U.S. for the treatment of LAM disease and PAH. In Europe, it gained this status as a candidate treatment for LAM disease.

AI Therapeutics, which belongs to 4Catalyzer, owns an artificial intelligence algorithm called Guardian Angel, which integrates public and proprietary data to find therapeutic candidates for any indication. Guided by this technology, the company has pushed four compounds into clinical stage development, including LAM-001 and candidates to treat cancer and amyotrophic lateral sclerosis.