Pharmaceutical firm ready for breakthrough

Loxo Oncology could soon see cancer drug approved by FDA

Five years after its launch, a Stamfordbased biotech firm is on the verge of its biggest milestone.

Loxo Oncology, which is developing cancer treatments focused on genetic mutations, could gain within the next week the U.S. Food & Drug Administration’s approval of its lead drug, Larotrectinib. The endorsement would pave the way for Loxo to put Larotrectinib on the market, making the treatment accessible to thousands of patients with rare cancers and reflecting the increasing use of genetic testing.

“When modern science opens the door and points the way to a new target that a great drug can be made against, we want to be the ones to make it,” Loxo CEO Josh Bilenker said in a recent interview at the firm’s headquarters at 281 Tresser Blvd., in downtown Stamford. “We’re constantly on the hunt for these new vulnerabilities that are revealed about certain cancers.”

Moving toward the market

Founded in 2013, Loxo takes its name from a term in Greek mythology referring to the trajectory of an arrow. The metaphor describes its approach to developing its drugs, which would be mainly pills.

Larotrectinib would treat “locally advanced” and metastatic solid tumors in adult and pediatric patients, who have either progressed with previous treatments or have no acceptable alternatives. It would target the “TRK fusion” mutation found in small percentages — sometimes less than 1 percent — of cases involving about 20 tumor types, including those in the lungs, thyroid, breasts, colon and pancreas. The firm estimates only 2,500 to 3,000 cancer patients in the U.S. carry the TRK fusion.

A “cousin” drug, Loxo-195, would treat patients who might become resistant to Larotrectinib.

“It doesn’t matter the site of origin of the tumor,” Bilenker said. “It doesn’t matter if it was a lung cancer or a thyroid cancer. … (Larotrectinib) was instead developed around the DNA-specific abnormality.”

Last December, the firm started its application to the FDA for Larotrectinib. In May, the agency granted a “priority review” to the submission.

Now, the FDA is scheduled to decide by Nov. 26 on whether to approve the drug. Securing the endorsement would clear the last major regulatory hurdle for Loxo to sell Larotrectinib.

At the same time, the firm is forging ahead with clinical testing for another drug, Loxo-292, which targets the “RET” mutation in lung and thyroid cancers. In September, Loxo announced that it had gained Breakthrough Therapy Designation from the FDA to accelerate the review of Loxo-292, a classification also awarded to Larotrectinib.

“It has been helpful,” Jacob Van Naarden, Loxo’s chief business officer, said of Breakthrough Therapy. “We’re happy to engage closer with the FDA.”

The company aims to gain FDA approval for Loxo-292 in 2020.

Another drug under development, Loxo-305, would treat blood-borne cancers such as leukemia and lymphoma in patients who have developed resistance to existing drugs.

Clinical testing for Loxo-305 could start by the end of this year.

Gene-focused testing

Loxo’s business model relies on advanced testing to identify the genetic abnormalities that its drugs would treat.

“We’re increasingly using DNA as the thing that is studied in these diagnostic tests,” Bilenker said. “It’s the DNA of the tumor — it’s not the DNA we inherit from our parents — that matters. We all inherit DNA, but the way a tumor with cancer arises is something goes wrong.”

As the cost of genetic testing for cancer has plummeted in recent years — from millions of dollars to hundreds of dollars, for some patients — such assessments have become a crucial part of treatment at a number of Connecticut hospitals.

Since 2010, the Western Connecticut Health Network — which includes Norwalk, Danbury and New Milford hospitals — has carried out oncological genetic testing.

At Norwalk Hospital, Dr. Richard Frank, a medical oncologist-hematologist and WCHN’s director of clinical cancer research, referred a patient with aggressive lung cancer to a Loxo-292 trial at Memorial Sloan Kettering Cancer Center in Manhattan. The patient’s response to the drug has been “excellent” during her first few months of treatment, according to Frank.

“I don’t think oncologists are uniformly doing full genomic profiling,” Frank said. “But now with so many genetic mutations that we can target, it speaks to the need to do a full genomic profile, especially for lung cancer and any patients with incurable cancers.”

In the Stamford Health system, which includes Stamford Hospital, doctors prescribe a number of drugs to treat mutations in cancers, including those in lungs and breasts as well as melanoma.

“We need more drugs to target the many different driver mutations in cancer,” said Dr. Steve Lo, a medical oncologist at Stamford Hospital’s Bennett Cancer Center. “Hopefully, Loxo-292 will help us treat cancers that have the RET mutation. For those 2 percent of lung-cancer patients with the RET mutation, Loxo-292 could be a magic drug that will help to prolong their lives.”

R&D progress

Without any products on the market yet, Loxo is still operating in the red — typical of biotech startups of its age.

But the company’s financial prognosis is promising in light of a deal last year with pharmaceutical giant Bayer that could be worth more than $1 billion to Loxo.

The agreement stipulated that Loxo receive a $400 million upfront payment. The firm would then be eligible to receive $450 million in payments tied to Larotrectinib’s regulatory approvals and first sales in certain markets and an additional $200 million linked to regulatory progress and initial sales of Loxo-195.

Among other funding infusions, Loxo received in June 2017 about $261 million from a public offering. It is using the proceeds for commercialization work related to Larotrectinib; research-and-development initiatives for other drugs and additional uses that could include acquisitions or investments.

“A lot of biotech companies, even a lot of large pharma companies, think about the blockbuster, a mega product that sells a lot because there are a lot of patient customers for it,” Bilenker said. “We don’t think of it that way. We want to build very selective drugs for very specific purposes. It just means that we have to build more of them in succession.”

As the company pushes ahead with research and development, it continues to grow its roster. It employs approximately 125, about half of whom are based at the Stamford headquarters. It recently expanded to a second floor at 281 Tresser.

Other employees work at an office in South San Francisco, Calif., and a new laboratory in Boulder, Colo.