Nicole Paulk's Siren Bio is building a gene therapy delivery vehicle against cancer

Nicole Paulk's "dream" job was to be an assistant professor at UCSF in the biochemistry and biophysics departments. As her lab began to explore a delivery system for gene therapy that was one-size fits all, and how to use it to target cancer, Nicole Paulk realized she had to start a business.

After two years in stealth mode, Paulk’s Siren Biotechnology revealed an undisclosed amount of financial support from Peter Thiel Founders Fund and Lux Capital, as well as a new gene therapy for cancer.

Siren's core approach relies on a "universal adeno-associated viral," which is a copy and paste version of an adenovirus shelled out. This virus delivers a good-copy of a gene that corrects aberrant genetic instructions. Paulk explained that this could be used to deliver cytokine-immunotherapy, small proteins that trigger the immune system’s inflammatory response against an invader, which can lead to an antitumor response.

Paulk stated that "we weren't interested oncology, but rather a universal genetherapy to treat multiple indications."

As members of her laboratory at the University of California San Francisco's Mission Bay Campus pushed for a universal AAV they realized that there was a compelling case in cancer. Drug development has struggled to deliver cytokine-based immunotherapies that can fight large tumors. They have a short-lived half-life and are not able to stay around long. Higher doses, in order compensate for this, often lead dangerous side effects. They thought a universal AAV could act as a FedEx delivery vehicle for cytokines and selectively target those proteins to tumors.

Paulk stated that the truck could be used to treat a variety of diseases. This includes Alzheimer's Disease, cancer and rare genetic diseases like X linked myotubular disease. The vehicle's universality could lead to shorter timelines for gene therapy development and more standardized, cheaper manufacturing.

Paulk stated, "Everything remains the same, including the FedEx truck and the outer protein shell that delivers therapy, as well as the medical backpacks that are delivered." "There is no change to the drug product."

Siren spun out of her laboratory in September 2021 and presented its first preclinical data on mice with brain tumors at the American Society of Gene & Cell Therapy Conference in Los Angeles this week. Paulk, who said that the eight-person firm will have 25 employees by this time next year has established itself in a space located across Third Street from UCSF Mission Bay Campus.

Paulk says that a universal AAV-delivery cytokine immunotherapy will probably not be ready for human testing until 2025 at the earliest, due to the unique approach and efficacy questions that regulators and peers are likely to want to investigate.

Other Siren investors include former Google CEO Eric Schmidt's Innovation Endeavors (formerly known as ARTIS Ventures), Civilization Ventures, Savantus Ventures and Savantus Ventures.

Siren is currently raising Series A funding.

Paulk explained that, given the lengthy timeline of Siren's project, it would be normal for a founder to spin out their technology, join the scientific advisory board of the new company, and stop working on the project. This is to avoid any conflicts.

She said, "We had phenomenal data and thought of spinning it out to stop work in the laboratory." "It broke my heart that I had to give away the coolest thing that I've done in 17 years of research, to someone else. I couldn't.

This is an opportunity that will only come around once in a lifetime. Paulk stated that this may never happen again. This is my next chapter.