The first agreement facilitated by Oak Ridge National Laboratory's COVID-19 Rapid Access Licensing Program is now helping a small biotechnology company attempt to do what larger companies have yet to achieve--heal the injured lungs of patients hospitalized with severe COVID-19 disease and those whose severe symptoms persist for six months or longer.
Cymbeline "Bem" Culiat, the former ORNL molecular geneticist who founded Knoxville, TN-based NellOne Therapeutics, told Friends of ORNL (FORNL) recently that her company is pursuing a fast-track path toward obtaining approval of the new drug for human clinical trials through the Food and Drug Administration’s Coronavirus Treatment Acceleration Program.
While at ORNL, Culiat discovered the role of the NELL1 signaling protein in directing the growth and maturation of musculoskeletal and cardiovascular tissues in mice, suggesting that the protein could trigger healing of damaged hard and soft tissues.
“A decade of work on various animal and cultured human tissue models by NellOne and other groups worldwide is documented in more than 200 publications,” Culiat told her FORNL audience. “This scientific foundation demonstrated the activity of the NELL1 protein in promoting key processes in tissue healing such as survival under adverse conditions such as inflammation and low oxygen, blood vessel formation, control of immune system responses, recruitment of stem cells into injured sites, cell growth and differentiation. This activity is manifested in major organs such as bone, cartilage, skeletal and heart muscle, skin, lungs and the brain. It is indeed a very talented protein."
Culiat said her company has made a new, patented drug called NV1 (for NELL1 Variant, Protein 1), which is a recombinant “shortened form of the NELL1 protein that is much easier to manufacture as a drug and that has a higher efficacy in soft tissues than the longer, more complex, protein found in nature.”
She added that multiple studies done by her company and independent organizations have shown that NV1 is effective in soft-tissue healing.
Under ORNL's COVID-19 Rapid Access Licensing Program, launched in June 2020, the lab issued a no-cost license to NellOne for a drug delivery system that transports therapeutic drugs directly into cells infected by the COVID-19 virus. The system incorporates the virus’ spike protein — the part of the virus that enables it to latch onto and infect cells — into the structure of nanoparticles that are filled with doses of an anti-COVID drug. These nanoparticles then bind only to COVID-infected cells and deliver their therapeutic payloads through the cell membrane.
“We’re working with NellOne to adapt the delivery system to transport the NELL1 protein directly to the hearts and lungs of patients whose organs have been damaged as a result of a COVID exposure," said Mike Paulus, director of technology transfer at ORNL.
NellOne Therapeutics seeks to win approval of NV1 as a “first-in-class” drug, a therapeutic that addresses a disease problem in a different way because its mechanism of action is new and unique. Big Pharma, she said, has been testing old drugs adapted for use in targeting a single molecule partly responsible for the aggressive inflammatory response to the novel coronavirus that has damaged the lungs of severely ill COVID-19 patients.
NellOne has completed and published a proof-of-concept study showing that NV1 increased survival and control of the “cytokine storm,” or hyperinflammation, in mice infected with human SARS-CoV-2, the virus that causes the COVID-19 disease.
Culiat said NellOne Therapeutics aims to produce drugs that will improve patients’ quality of life and reduce the burden on healthcare systems of patients suffering from acute respiratory distress syndrome (ARDS), especially COVID-19-associated ARDS, called CARDS. Such patients have lungs so damaged from aggressive, body-harming inflammation that they are often put on ventilators to get sufficient oxygen. Their chances of dying are as high as 40%.
"Intravenous administration of NV1 in the hospital might prevent COVID patients from going into intensive care or it might shorten ventilator time,” Culiat said. “It could be administered by IV to recovering COVID long haulers to heal ongoing tissue damage.”
NellOne Therapeutics is funded by private, state and federal sources such as angel investors, the National Science Foundation and Tennessee Small Business Innovation Research grant matching funds (through LaunchTN).