Pioneering Advances in Regenerative Medicine: NellOne Therapeutics

Three Roots Capital is committed to working with forward-thinking organizations to help fuel their growth for future discoveries and developments. One of these companies, NellOne Therapeutics (NellOne), located in Knox County’s Fairview Technology Center, is an early-stage biopharmaceutical company pioneering advances in regenerative medicine.

In 2008, NellOne was co-founded by Dr. Cymbeline (Bem) Culiat and Tracy Warren, an investor, executive, and entrepreneur. Serial entrepreneur and valued Three Roots partner, Bill Malkes, joined NellOne as its Chief Executive Officer in April 2020.

Dr. Culiat, who serves as NellOne’s Chief Science Officer, spent a decade as a senior scientist at Oak Ridge National Laboratory. At ORNL, she discovered NELL1, a naturally occurring secreted human protein, which triggers multiple processes for tissue growth and maturation. NELL1’s basic biology and regenerative effects on tissue injury (physical, chemical, inflammation, low oxygen conditions, etc.) have been studied for more than a decade, with Dr. Culiat arguably being at the pioneering forefront in understanding NELL1. This formidable collective of attributes empowers the use of NELL1 as a prospective therapeutic for a plethora of severe injuries and disorders, including virally induced lung damage caused by COVID-19.

Malkes refers to NELL1 as a “very talented protein” that has immense potential. Malkes and Dr. Culiat feel they “have been given stewardship of this protein for a greater good and have an obligation to make it available.”

“I felt very called to be here. It’s a phenomenally important product in so many ways that needs to be on the market,” said Malkes. “Not only do we want to make a difference in the world, but we want to make this product accessible to everybody.”

In August 2020, NellOne secured a utility patent to protect its breakthrough work on creating a shorter version (NV1) of the naturally occurring NELL1 protein. This patent allows the startup to fast-forward its effort to create multiple clinical applications for the NV1 novel variant and pursue large-scale production.

Earlier in the year, NellOne filed a provisional patent application to use the NELL1 signaling protein in the treatment of respiratory viral infections, particularly COVID-19. The patent application, Methods and Compositions for Treating Tissue Damage Resulting from Viral Infections, is an extension of the startup’s current research. In November 2020, NellOne partnered with ORNL on a COVID-19 drug delivery system that is designed to transport therapeutics directly to cells infected by SARS-CoV-2, the virus that causes COVID-19.

“We were headed down a particular path when COVID broke out, but what we understood pretty quickly was that while NELL1 can’t prevent COVID, it’s a prospective therapeutic with the potential to reverse tissue damage and regulate the inflammatory response linked with COVID and other virally induced lung disease,” said Malkes.

In October 2020, Three Roots made an investment in NellOne. Three Roots wanted to put “fuel in the tank” to fund the company’s progress and wanted to create an opportunity to contribute to the company’s success by providing technical and operational assistance in areas where Three Roots can add value. This approach to investing is illustrated by the three roots of Three Roots Capital: Access to (1) capital, (2) coaching, and (3) connections.

“Three Roots is enthusiastic about supporting NellOne,” said Grady Vanderhoofven, President and CEO. “NellOne is a team of brilliant and dedicated people who truly want to make a difference in the world around them. We’ve had an awareness of the company for quite some time. We believe the addition of Bill Malkes to the team, coupled with the company’s recent advances and recent market dynamics, creates a scenario where Three Roots can help the company accomplishes its goals.”

Looking ahead, NellOne is seeking U.S.-based partners to complement their current overseas partners to help produce the NELL1 protein. They will also continue to validate their studies regarding the efficacy of the protein and conduct Food and Drug Administration safety and toxicity studies.

“I also cannot say enough of how proud I am to be a part of NellOne,” said Malkes. “It’s a company founded by two women, one of whom is a minority, and that’s where I get to work. This is not what Knoxville looked like in 2000, but it’s happening today, and it’s real. I truly believe these are the things that take a community to the next level. That’s what people should know: There’s momentum, come join us.”