


Xconomy Boston — 

Genetic engineering a patient’s own immune cells to make them better cancer fighters is the latest tool in oncology, following FDA approvals of two such therapies this year. But executives at Torque Therapeutics say cell therapy can be further improved by enlisting T cells to carry a drug payload that prompts a more targeted and durable tumor-killing immune response.

Torque’s approach is based on 10 years of research on how to affix to T cells drugs that direct and boost the T cells’ activity against cancer. Today, the Cambridge, MA, biotech is coming out of stealth with $25 million in financing. The Series A funding comes from venture capital firm Flagship Pioneering, Torque’s sole institutional investor. The company’s lead drug candidate, Deep IL-15, is expected to begin clinical trials in 2018 in a yet-to-be-determined cancer.

Cell therapy has been in the headlines in recent months following the approvals of cancer treatments developed by Novartis (NYSE: NVS) and Gilead Sciences (NASDAQ: GILD). These “CAR T” treatments involve removing a patient’s T cells, the soldiers of the immune system, and engineering them to produce receptors on their surface (chimeric antigen receptors or CAR) that recognize and attach to antigens on the surface of cancer cells. These souped-up T cells are then infused into the patient to treat the cancer.

But these treatments come with safety issues, such as cytokine release syndrome, when the immune system goes into overdrive. Torque uses T cells in a different way, with the aim of avoiding some of these safety problems. The company has developed a way to attach to these cells drugs that can boost immune attack of tumors. These “deep-primed” T cells carry the immunomodulating drugs to the tumors, where they prompt an immune response that’s local and targeted to the tumor, rather than one that happens throughout the body, says Bart Henderson, CEO and co-founder of Torque. This initial wave of activity then triggers a second response by the body’s innate immune system, which keeps fighting the cancer cells over time for a longer-lasting effect.

“You can’t do that with gene editing or genetic engineering technologies,” Henderson says.

Torque’s deep priming approach is based on the research of Darrell Irvine, a professor of materials science, and engineering and biological engineering at MIT. His work involved developing cell therapies that can overcome a tumor’s mechanisms for suppressing an immune response. Henderson founded Rhythm Pharmaceuticals (NASDAQ: RYTM), and is the former president of that Boston peptide drug developer.

Torque isn’t the only company targeting the body’s innate immune system. Cambridge-based IFM Therapeutics is developing drugs in the form of a pill that are meant to trigger an immune response to cancer. IFM says its drug aims to stimulate one of two molecular targets, NLRP3 or STING. Doing so would trigger the innate immune system to fight cancer cells.

The work of IFM, which was incubated within Boston venture capital firm Atlas Venture, is still preclinical. But Bristol-Myers Squibb (NYSE: BMY) saw enough potential in the approach to acquire IFM in August for $300 million up front, and potentially more than $1 billion for each of the company’s two drugs, should those programs hit development and sales milestones.

Ulrik Neilsen, president and co-founder of Torque, says that an immunotherapy drug given as a pill could trigger an immune response throughout the body—which risks a broad toxic effect. Neilsen says preclinical studies of drugs that work systemically showed that they act on cells in the blood, rather than the tumor.

Torque’s preclinical studies of its own infused cell therapy showed that the drug acted on the tumor and did not have toxic effects throughout the body, Neilsen says. He adds that the approach more closely mimics how the immune system responds to bodily injury, with local rather than systemic responses.

Henderson says that Torque’s approach would complement rather than compete with CAR T treatments, and could work with all immune cell therapeutics as a way to more specifically target immune cells to tumors. The Torque therapy could be added to CAR T treatments approved for blood cancers, potentially producing a longer-lasting response with less toxicity, Henderson says. The company says its approach could apply to solid tumors as well.

“It can be added to a cell therapy or a TCR (T cell receptor therapy) and go beyond what those technologies can do on their own,” he says.

Torque still has to test its approach in humans, of course. Henderson says the $25 million in funding will support the work needed to start clinical trials for Torque’s lead drug. The company’s three other drug programs will need additional financing before the company can begin testing them in humans.
