Toragen Explores ‘Novel’ Treatment for HPV-Induced Cancer

Sometimes drug discovery involves taking a closer look at drugs that have already been discovered.

That is the story behind San Diego-based Toragen, Inc., a company pursuing treatments for human papilloma virus (HPV) and the cancers it causes with a drug originally developed to treat influenza.

In 2018, Toragen founder Dr. Andrew Sharabi MD, PhD was researching the flu drug in his lab at UC San Diego when he discovered it causes direct inhibition of a protein that the HPV virus produces when it infects human cells.

"That was transformational because it's a mechanism of action that's a novel one to treat HPV induced cancer," said Toragen CEO Dr. Sandra Coufal, MD.

The discovery soon began attracting talent to the new company, such as Toragen Director of R&D Richard Lumpkin, PhD – a 30-year veteran of developing and commercializing early stage biotechs – who helped Sharabi develop the science behind how the drug works on HPV.

After raising an initial $1.3 million seed round, Coufal was hired as CEO, bringing 22 years of biotech and venture capital experience to the company. In September, she led Toragen in closing a $5.4 million Seed Series B round to fund expanding the company's talent and begin preparing for clinical trials of the drug, TGN S-11.

"It is a privilege for me to join an early-stage company that is focused on developing a treatment to address such a large unmet medical need," said Cheryl Collett, a 20-year biotech veteran who joined Toragen as CFO in June.

HPV Infection

HPV is a sexually transmitted infection that studies show 85% of the U.S. population has contracted at one time or another. There is a vaccine available for young people but for the population over 25 years old, it wasn't available.

"Most people clear the virus from their bodies, but a certain percentage don't clear the virus," Coufal said, adding that the virus infects and lies dormant in cells before it can cause cancer in some people. HPV is the cause of 70% of head and neck cancers; 90% of cervical cancers; and high percentages of cancers in other genitourinary organs.

"HPV is something hidden in the cells and there is not a diagnostic test for it," Coufal said, adding that the only way to discover an HPV infection is through tissue sample, pap smear or a tumor biopsy.

How It Works

Sharabi discovered TGN S-11's effect on HPV while studying how HPV hides from the body's immune system after infecting a cell. He found HPV makes cells produce an abnormal protein that shields infected cells from the immune system's ability to detect infection.

"What our drug does is it inhibits the activity of the abnormal protein that the HPV gene produces," Coufal said. "Cells are then able to produce the signals that tell the immune system to attack the infected cell."

Toragen is currently developing a Phase 1 clinical trial for TGN S-11 that will begin in the early part of 2023. The trial will target patients with HPV-induced cancers who have failed current treatment with a group of drugs called checkpoint inhibitors.

Toragen anticipates a Phase 2 trial for efficacy will prove the drug effective in treating patients who have HPV induced cancer, have already been treated with checkpoint inhibitors, and in tandem with continued checkpoint inhibitor therapy.

"Checkpoint inhibitors have a different mechanism of action, and we believe our drug can help checkpoint inhibitors work better by allowing our own immune system to identify the virally infected cells," Coufal said, adding that checkpoint inhibitors work well with other cancers but have a low success rate (14%) with head and neck cancers.

"We will probably focus on head and neck cancers in our Phase 2 studies because that's where the greatest unmet need is," she said.

Preventive Medicine?

Because of the unique mechanism of TGN S-11 to expose HPV to the body's immune system, there is potential for using the drug to prevent cancers from developing.

"We have not proven that yet, but that is where we're going because we would like to have no patients with HPV-induced cancers," Coufal said. "We would rather eliminate the virus so it can't produce this abnormal protein and changes the cells that then mutate further and become cancer cells."

Even though there are vaccines for HPV, they do not target all HPV strains – other HPV mutants are on the rise, though HPV does not mutate as fast as influenza or some other viruses. The vaccines are also not universally adopted.

"As an internist, my favorite therapy is a preventative one including vaccines," Coufal said. "Even if 100% of eligible people got the HPV vaccine, there is still a patient population that became sexually active when we didn't have the vaccine approved that could have retained HPV and in the future produce HPV-induced cancer."

In an "ideal world," Coufal said, there would be a test for the presence of HPV and then people would take a treatment to get rid of the virus. "We're not there yet, but we're hoping to get there," she added.

Toragen, Inc.

Founded: 2018
CEO: Dr. Sandra Coufal, MD
Headquarters: San Diego
Business: Drug development company
Funding: $6.7 million total seed funding
Employees: 7
Website: www.toragen.com
Notable: Toragen was founded after discovering a flu drug had a novel mechanism of action on HPV.

What is HPV