GUILFORD,CT, May 9, 2023 — AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today Dr Antje Prasse of Fraunhofer ITEM and Hannover Medical School, Germany, will present a scientific poster, sponsored and co-authored by the Company, at the upcoming 2023 American Thoracic Society (ATS) International Conference, taking place May 19-24, 2023 in Washington, DC.
The abstract information is provided below:
Thematic Poster Session C34: Sarcoidosis, Fibrosis, and Proteinosis
Date: May 23, 2023
Presentation Time: 11:30a-1:15p
Location: Area F, Hall C (Lower Level) Walter E. Washington Convention Center
Abstract P649: High mTOR Activity in Bronchoalveolar Lavage Cells from Patients with Sarcoidosis
Multiple studies in humans and in animals have implicated mTOR signaling in the pathogenesis of sarcoidosis. Knock out of the TSC2 gene (an upstream regulator of mTOR) in mice leads to the formation of granulomas very similar to those seen in human sarcoidosis[1]. These studies suggest that mTOR activation and subsequent activation of inflammatory immune responses involving innate immune cells, such as monocytes, macrophages and dendritic cells, is a key contributor to sarcoidosis. Treatment in a sarcoidosis animal model with an mTOR inhibitor has been shown to resolve the granuloma formation.
In humans, there are case reports describing similar resolution of sarcoidosis with oral rapamycin[2],[3],[4]. Furthermore, studies of patients with progressive pulmonary sarcoidosis demonstrated alterations in genes affecting the mTOR pathway[5] and analysis of patient tissues demonstrated activated mTOR signaling[6].
About LAM-001
LAM-001 is a proprietary, investigational, inhaled formulation of sirolimus, also known as rapamycin. LAM-001 inhibits the mTOR pathway which has been implicated in multiple pulmonary indications. By delivering the drug directly to the lung, LAM-001 has the potential to deliver the benefits of sirolimus while reducing systemic exposure and the toxicities associated with oral sirolimus administration. AI Therapeutics is developing LAM-001 for the treatment of pulmonary sarcoidosis, pulmonary arterial hypertension (PAH) and bronchiolitis obliterans syndrome (BOS) post lung transplant.
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.
[1] Linke M, Pham HT, Katholnig K, Schnöller T, Miller A, Demel F, Schütz B, Rosner M, Kovacic B, Sukhbaatar N, Niederreiter B, Blüml S, Kuess P, Sexl V, Müller M, Mikula M, Weckwerth W, Haschemi A, Susani M, Hengstschläger M, Gambello MJ, Weichhart T. Chronic signaling via the metabolic checkpoint kinase mTORC1induces macrophage granuloma formation and marks sarcoidosis progression. Nat Immunol. 2017 Mar;18(3):293-302.doi:10.1038/ni.3655. Epub 2017 Jan 16. PMID: 28092373.
[2] Manzia TM, Bellini MI, Corona L, Toti L, Fratoni S, Cillis A, Orlando G, Tisone G. Successful treatment of systemic de novo sarcoidosis with cyclosporine discontinuation and provision of rapamune after liver transplantation. Transpl Int. 2011 Aug;24(8):e69-70. doi:10.1111/j.1432-2277.2011.01256.x. Epub 2011Apr 19. PMID: 21504488
[3] Kelleher, K. J., Russell, J., Killeen, O. G.,& Leahy, T. R. (2020).Treatment-recalcitrant laryngeal sarcoidosis responsive to sirolimus. BMJ Case Reports, 13(8), e235372. doi:/10.1136/bcr-2020-235372
[4] Gupta N, Bleesing JH, McCormack FX. Successful Response to Treatment with Sirolimus in Pulmonary Sarcoidosis. Am J Respir Crit Care Med. 2020 Nov 1;202(9):e119-e120. doi:10.1164/rccm.202004-0914IM. PMID:32730705.
[5] Calender A, Lim CX, Weichhart T, Buisson A, Besnard V, Rollat-Farnier PA, Bardel C, Roy P, Cottin V, Devouassoux G, Finat A, Pinson S, Lebecque S, Nunes H, Israel-Biet D, Bentaher A, Valeyre D, Pacheco Y; in the frame of GSF (Group Sarcoidosis France). Exome sequencing and pathogenicity-network analysis of five French families implicate mTOR signaling and autophagy in familial sarcoidosis. Eur Respir J. 2019 Aug 1;54(2):1900430.doi:10.1183/13993003.00430-2019. PMID: 31023854.
[6] Linke M, Pham HT, Katholnig K, Schnöller T, Miller A, Demel F, Schütz B, Rosner M, Kovacic B, Sukhbaatar N, Niederreiter B, Blüml S, Kuess P, Sexl V, Müller M, Mikula M, Weckwerth W, Haschemi A, SusaniM, Hengstschläger M, Gambello MJ, Weichhart T. Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression. Nat Immunol. 2017 Mar;18(3):293-302.doi:10.1038/ni.3655. Epub 2017 Jan 16. PMID: 28092373.
