A multi-disciplinary NIAID team has received an Excellence in Technology Transfer Award for work that led to the treatment of the rare disease known as PASLI/APDS. The Federal Laboratory Consortium for Technology Transfer (FLC) award honors outstanding work by federal laboratories that collaborate with industry, academia or other labs to bring technologies from the bench to the marketplace.
In 2013, NIAID researchers, as well as an independent team of scientists in the United Kingdom, identified a rare genetic primary immunodeficiency disease, PASLI (p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency). Also known as APDS (activated PI3 Kinase delta syndrome), it is a rare primary immunodeficiency disease, estimated to affect up to 2 people per million worldwide. APDS is characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections, childhood onset chronic benign lymphoproliferation, increased risk of lymphoma and/or autoimmune disease. APDS can only be cured via successful bone marrow transplant. Available treatment options include relieving the symptoms using immunoglobulin replacement therapy, empirical use of biologicals like Rituximab, immunomodulatory drugs such as mTOR inhibitors, and treatments targeting infections, such as antibiotic and antiviral therapy. Discovery of the genetic basis of the disease led to treating the patients with specific PI3 kinase inhibitors that can provide more effective, targeted treatment with fewer long-term side effects.
In 2015, the pharmaceutical company Novartis approached NIAID with an oral, investigational small molecule PI3 kinase-delta inhibitor, CDZ173 (leniolisib), it had in its pipeline to treat autoimmune diseases. NIAID entered a Cooperative Research and Development Agreement (CRADA) with Novartis to determine the dose and then test the safety and efficacy of the experimental drug in patients with APDS. This CRADA combined NIAID’s clinical and research experience regarding APDS patients with Novartis’s interest in developing inhibitors of the PI3K delta pathway designed to correct the underlying pathophysiology in this patient population with an orphan disease. NIAID’s Technology Transfer and Intellectual Property Office (TTIPO) facilitated the collaborative relationship between NIAID and Novartis, navigating complex variables to successfully coordinate the tech transfer efforts. TTIPO played a crucial role in formalizing the collaboration with Novartis through the CRADA.
In 2015, a clinical trial began, recruiting 6 patients (4 patients at NIH; 2 in Europe) to determine the correct dosage. The interim data from this trial determined the dosage of leniolisib and successfully demonstrated that the treatment was welltolerated with improved laboratory outcomes in APDS patients. Based on these findings, the experimental treatment advanced to a Phase 2/3 clinical trial that provided further evidence of leniolisib’s safety and efficacy with findings published in 2023. The commercialization rights to the clinical development of leniolisib were transferred from Novartis to Pharming Group N.V. (Pharming) in August 2019. The Food and Drug Administration approved the drug in March 2023 for the treatment of APDS in patients 12 years of age and older. Leniolisib is the first and only drug approved in the U.S. to treat this condition.
TTIPO’s significant efforts enabled this successful technology transfer, bringing a new effective and targeted treatment option for APDS patients and fulfilling an unmet medical need for a rare orphan disease.
Members of the NIAID team that received the FLC Excellence in Technology Transfer Award included:
- Yogikala Prabhu, Ph.D., Senior Technology Transfer Patent Specialist, TTIPO, NIAID
- Michael Lenardo, M.D., Laboratory of Immune System Biology (LISB), NIAID
- V. Koneti Rao, M.D., Laboratory of Clinical Immunology and Microbiology (LCIM), NIAID
- Gulbu Uzel, M.D., LCIM, NIAID
- Sharon Webster, R.N., Former Protocol coordinator, LISB, NIAID
- Alan Orpia, R.N., Protocol coordinator, LISB, NIAID
- Cecilia Pazman, Ph.D., Team Lead, TTIPO, NIAID
- Peter Tung, Ph.D., M.B.A., Senior TTPS, TTIPO, NIAID
- Cosimo Fuda, Ph.D., J.D., Branch Chief, TTIPO, NIAID