Quentis Nets $48M For Cancer Drugs, Building Buzz For NY Bio Startups

Xconomy New York — 

After a string of announcements a few years back, there’s been few new, high-profile biotech startups taking shape in New York. But that quiet period might be coming to an end this morning with the arrival of Quentis Therapeutics, a cancer immunotherapy startup born from the lab of former Weill Cornell Medicine dean and immunologist Laurie Glimcher. The company makes its debut today with a $48 million Series A round.

Quentis has been incubating for a few years within Highline Therapeutics, the New York biotech creator Versant Ventures formed in late 2015. Versant is one of the venture firms to plant a flag in New York amidst the city’s multi-year push to spur on its life sciences industry and compete with more established biotech hubs elsewhere. Since its inception, Highline has formed three companies, though only two of them—Kyras Therapeutics and now Quentis—are based in New York, according to Versant partner Carlo Rizzuto.

Since late 2016, city and state governments have committed more than $1 billion to growing New York’s biotech industry. Several startup incubators have sprouted up, or soon will, and startup creators like Versant, Accelerator Corp., and Flagship Ventures (which, along with Arch Venture Partners, co-manages a still-unused $150 million biotech fund from the New York City Economic Development Corp.) have arrived.

This effort—which will likely take decades—is still early. New York has nowhere near the number of high-profile biotech startups that Boston and San Francisco regularly churn out. Kallyope, Petra Pharma, and Lodo Therapeutics came along in quick succession in late-2015 and early 2016 and raised $109 million combined in separate Series A rounds. Since then though, similar announcements have been few and far between. As Erik Lium, the senior vice president of Mount Sinai Innovation Partners said at an Xconomy event in December, the area needs “a number of really noteworthy, breakthrough startup companies” to generate bigger buzz.

Some momentum has gathered over the past month. The NYCEDC put up $100 million to draw outside investors in to help develop a biotech campus. Roche bought Flatiron Health, a New York life sciences/tech hybrid company that amasses data on cancer patients, for $1.9 billion. Kallyope last week reloaded with a $66 million financing, one of the largest for a privately held New York drug developer in years. And now here comes Quentis.

“You’re going to see more [companies],” says Quentis CEO Michael Aberman. “Science, like everything else, comes in fits and starts.”

Aberman has long been on the New York life sciences scene. Formerly a biotech analyst at Morgan Stanley and Credit Suisse, he ran investor relations for Regeneron Pharmaceuticals (NASDAQ: REGN) for seven years before stepping down in June to run Quentis. Citing the influx of investors to New York and progress made building lab space, he decided to leave New York’s preeminent biotech for a startup. “I do feel like there’s this community growing,” Aberman says.

Quentis’s scientific founders are Glimcher, who now runs the Dana-Farber Cancer Institute in Boston, and two former post-docs from Glimcher’s lab: Juan Cubillos-Ruiz and Sarah Bettigole. The company’s work comes from new insights into a method cells use to sense and cope with stressful environments.

When a cell is stressed, it switches on an internal program to survive. This program is called the “endoplasmic reticulum (ER) stress response,” and it can help a cell deal with a variety of problems. If a bunch of misfolded proteins abnormally build up within a cell, the ER stress response kicks in and clears up the mess. In cancer, however, this cellular machinery gets hijacked, allowing tumors to grow, survive, and resist attacks from the immune system. Quentis’s approach is to find drugs that counteract this stress response in cancer, making tumors more vulnerable to attack.

Researchers and companies over many years have tried to do the same: block a molecular stress sensor that’s involved to the ER stress response called inositol requiring enzyme 1 (IRE1a). So far, no drugs have come from it. Amgen looked into it a few years ago, but a team of its scientists wrote in this 2014 paper that IRE1a activity “is not essential for viability” in most tumors, and that interfering with the cell’s response to the buildup of misfolded proteins “may not be an effective strategy” to stop the formation of tumors. Other efforts previously disclosed by Mannkind Corp. and Ruga Corp. (now known as Aravive Biologics) are no longer mentioned in either company’s pipeline.

Glimcher and Aberman say there are a few key reasons why some of the earlier efforts fizzled. One is that those compounds weren’t “potent or selective” enough to be effective and safe in humans. Another, they say, is that previous efforts only studied whether these drugs would kill cancer cells. It turns out blocking IRE1a has another possible benefit that hadn’t been measured, they say: weakening a tumor’s defense against the immune system, making the approach potentially useful for cancer immunotherapy. Previous efforts were “pre-immunotherapy thinking,” Aberman says.

The foundation for Quentis’ technology is based on a 2015 paper published in the journal Cell by Weill Cornell scientists, including Quentis’s three founders. They showed that inhibiting IRE1a in animals provoked an immune response against ovarian cancer—a type of cancer that immunotherapy has yet to crack. Glimcher says her company has developed “a series of highly potent [IRE1a-blocking] molecules that are much more selective” than previous attempts.

Quentis now plans to get in on the ultra-competitive mix-and-match game of combination cancer immunotherapy. Despite all the progress made using drugs to stimulate an immune attack against cancer, immunotherapy’s reach remains limited to a fraction of patients with certain types of tumors. There are more than 1,000 trials underway testing immunotherapy drugs in combination with chemotherapy, other immunotherapies and more, in the hopes of expanding the benefit of immunotherapy to more patients.

Quentis isn’t disclosing its clinical plan as of yet, though Aberman says there are a variety of cancers—ovarian, triple-negative breast, pancreatic, and brain—where unusually high IRE1a activity is linked to to poor outcomes. The hope is to start clinical tests in 2019, at which point Quentis will try to prove it can stand out in a fast-moving, highly competitive field.

Versant, Polaris Partners, and its affiliated LS Polaris Innovation Fund led the financing. AbbVie Ventures, Alexandria Venture Investments, Taiho Pharmaceutical, Yonghua Capital, and New York Ventures, the investment arm of Empire State Development, also participated.