Many new drugs for cancer work by targeting the genetic make-up of patients' tumors. A new startup debuting Wednesday, Esker Therapeutics, has raised $70 million in venture fundraising to make similarly precise treatments for autoimmune diseases.
The San Francisco, California-based startup is starting out with a program that could rival an experimental medicine from Bristol Myers Squibb known as deucravacitinib, which recently succeeded in a Phase 3 study. Like Bristol Myers's drug, Esker's medicine targets a protein called tyrosine kinase 2, or TYK2, which triggers cell signaling pathways that are involved in inflammation. Esker claims its drug is more selective and potentially safer.
Founder and CEO June Lee has experience studying specific groups of patients and targeted drugs to treat them from her tenure as an executive at MyoKardia. That biotech successfully developed a drug for a genetic form of heart disease using a clinical trial that enrolled only 250 patients to test the treatment's effectiveness — a departure from typical late-stage cardiovascular trials that often require thousands or tens of thousands of participants. Bristol-Myers bought MyoKardia for $13 billion after the positive finding.
"We had to develop a novel endpoint, because the traditional cardiovascular measures weren't really appropriate for this population," Lee said in an interview. "We had to come up with a new way of identifying these patients."
Lee called her experience "compelling" because of MyoKardia's clear focus on "committing to precision drug development." With Esker, she's now aiming to bring similar types of treatments to autoimmune disease.
Esker's isn't starting with a drug it developed, however. While being incubated within San Francisco startup incubator Foresite Labs, Esker came across the TYK2 inhibitor, now dubbed ESK-001, and decided to acquire its developer, Fronthera.
ESK-001 was attractive due to its selectivity, Lee said. TYK2 comes from the same family of proteins as Janus kinases, or JAKs, which are the targets of a group of autoimmune drugs from Pfizer, Eli Lilly and AbbVie. Concerns have grown, however, about the safety of JAK inhibitors, which come with warnings for malignancies, infections and blood clots. More recently, the FDA appears to be increasing scrutiny of the drug class, delaying reviews of Pfizer and Lilly's drugs.
The leading TYK2-targeting drug, Bristol-Myers' deucravacitinib, is being tested in patients with psoriasis. Though it doesn't appear to be as effective as injectable biologic drugs like AbbVie's Skyrizi, the treatment has been shown in testing to clear patients' skin better than another oral drug, Amgen's Otezla. So far, deucravacitinib appears safer than JAK inhibitors, heightening interest in targeting the pathway.
Pfizer, Galapagos and privately held Nimbus Therapeutics are also developing TYK2 inhibitors.
Apart from ESK-001, Esker's efforts are very early, centered around analytics technology that's meant to aid development of multiple "discovery-stage" programs. The company aims to study specific biomarkers and biological pathways that could improve treatment responses across different autoimmune diseases.
"In spite of the fact that we've been developing and approving drugs for the better part of the last two decades or so, it's not very good, our ability to actually alleviate the suffering for patients," she said.
The data drawn from genetic, clinical and patient records hasn't been well-connected in the past, Lee said, and Esker aims to correct that. "The answer is probably somewhere out there," Lee said. "Have we found that yet? No, but we have the tools to start looking right now."