- CEO Arthur Tzianabos
- Total raised $70 million
- Headquarters Burlington, MA
As a young scientist, Jay Rothstein asked fellow immunologists what they thought the biggest unsolved problem in the field was. “Give me a non-toxic steroid and we’re done,” they told him.
Corticosteroids have been used for decades. The drugs powerfully suppress runaway immune systems, but their side effects can be brutal. Chronic use can break down bone and muscle, weaken the skin, impair eyesight and increase the risk of diabetes, forcing most patients to stop taking them.
Over the years, chemists have tried, and largely failed, to separate the benefits of steroids from their many limitations. “That’s been the holy grail,” Rothstein said.
The problem is that steroid receptors are found not just in immune cells, but in pretty much every cell of the body. It’s a drug delivery problem. And Rothstein’s solution was to have steroids hitch a ride on an antibody that selectively targets immune cells.
That antibody-drug conjugate, or ADC, approach is a hot technology in cancer, where companies are attaching potent chemotherapies to antibodies that target tumors. But apart from a brief effort to turn AbbVie’s drug Humira into an ADC, the idea has gained little traction in immunology.
Rothstein developed an ADC that carries the powerful steroid budesonide at ImmuNext, a small New Hampshire company that was spun out of Dartmouth professor Randolph Noelle’s lab. ImmuNext successfully licensed experimental drugs to Eli Lilly and Sanofi, but when its leaders decided they wanted to retire and wind down the company’s research operations, Rothstein began searching for a new home for his ADC program.
Last year, he called Steve Gillis, a managing partner at ARCH Venture Partners who trained as an immunologist at Dartmouth. Gillis was fascinated by the possibility of using steroids without side effects “for the first time in history,” he said.
“There is nothing more prescribed for autoimmune disease than steroid hormones. The problems are, nobody likes taking them, nobody likes prescribing them,” Gillis said. “We really do have the opportunity here to essentially bring steroids back to a frontline therapy that people will really want to have.”
Gillis recruited Bruce Booth from Atlas Venture and Arthur Tzianabos from 5AM Ventures to form the new company, Lifordi Immunotherapeutics. Tzianabos, the startup’s CEO, told Endpoints News in an exclusive interview that Lifordi raised a $70 million Series A from those three firms last fall and is on track to start testing its drug in a clinical trial next year.
Lifordi’s name is an allusion to the New Hampshire motto, “Live Free or Die,” proudly emblazoned on the state’s license plates. The company licensed its ADC drug and technology from ImmuNext for a stake in the startup and undisclosed financial terms “back-loaded” in milestones and royalties, Tzianabos said. Lifordi also subsumed ImmuNext’s roughly 10-person research group, which Rothstein continues to lead.
The startup’s drug targets an immune protein called VISTA, which was discovered in Noelle’s lab at Dartmouth. It’s widely found on the surface of both adaptive immune cells (like B cells and T cells) and innate immune cells (like dendritic cells and macrophages), but not in other parts of the body.
Once the drug binds to VISTA, it gets rapidly pulled into the cell where each antibody unloads eight steroid molecules. The company hasn’t published its preclinical data yet, but Tzianabos said that in monkey experiments, a subcutaneous injection of the ADC given every other week delivered similar efficacy as a daily dose of steroids, and without the side effects.
“We’re not hitting the immune system constantly, and that’s why we can see this drug potentially being used for the lifetime of the patient,” Tzianabos said.
But ADCs are expensive drugs. Even if Lifordi’s compound is successful, the company may struggle to convince doctors and payers to switch from cheap steroids.
Tzianabos wouldn’t name the specific condition Lifordi is going after first, but he said it’s a “very large autoimmune disorder” with “multiple cytokines involved” in the disease. “And if you show efficacy and safety in that disease, there’s no reason to think that you couldn’t go after other large autoimmune disorders as well,” he added.
This pipeline-in-a-product potential, which is already common among immune disease programs, is especially pronounced at Lifordi.
“It would be a true panacea,” Rothstein said. “IBD, asthma, psoriasis, all these diseases get treated with steroids. And Lifordi’s goal would be that almost all of these diseases would be a space for this drug.”
Key backers: 5AM Ventures, ARCH Venture Partners, Atlas Venture
Find the full list of 2024 Endpoints 11 winners here.