Boulevard Bio has exited stealth mode with plans to develop several next-generation therapies targeting B-cell-driven autoimmune disease. The New York City start-up has a pipeline of two bispecific and one trispecific antibody-based therapies; the lead candidate is already in Phase 1 trials for treatment of the rare autoimmune kidney disease Immunoglobulin A (IgA) nephropathy.
The company was founded by Georg Schett, who is credited with pioneering the use of chimeric antigen receptor (CAR) T-cell therapy for treatment of severe autoimmune disease, and Frank Nestle, an immunologist whose work helped clarify immune mechanisms in psoriasis and other inflammatory skin disorders.
Boulevard was incubated by Deerfield Management a large, specialist US health-care investment firm and the start-up’s sole funder to date. Nestle is CEO of Deerfield’s discovery and development unit, 3DC, which helped develop Boulevard’s pipeline.
Boulevard CEO Mahesh Karande previously led the messenger RNA–based epigenomic biotech Omega Therapeutics and also spent a number of years at Novartis. “Our approach is really grounded in a very deep understanding of B-cell biology to really understand the key mechanisms that drive different autoimmune diseases,” he says.
The company’s lead candidate, BLVD101, is in early Phase 1 trials. It is a bispecific antibody designed to neutralize BAFF and APRIL, two related immune-signaling proteins that support the production of disease causing abnormal IgA antibodies, seen in people with IgA nephropathy.
“You need to inhibit both of them,” Karande says. “You can have only APRIL inhibitors that will give you inhibition of IgA, which actually drives to proteinuria resolution as well as eGFR [estimated glomerular filtration rate] resolution. But BAFF is important for long-term protection.”
In July, the US Food and Drug Administration approved atacicept, a similar BAFF-APRIL bispecific therapy developed by Vera Therapeutics, to treat IgA nephropathy. But atacicept is dosed once weekly, and Boulevard hopes to dose once every 12 weeks with BLVD101.
“If you are a young person in your 20s needing to take this medicine for the next 50 years, a weekly medicine is 52 doses a year versus . . . what we are coming with, 4 doses a year for 50 years. Imagine the changing game here for a patient,” Karande says.
BLVD201, Boulevard’s second therapeutic candidate, is a next-generation trispecific T-cell engager designed to induce an immune reset and potential cure in severe autoimmune disease. The company in-licensed it from the Chinese firm METiS TechBio for an up-front payment of $20 million in June, and the product is currently in preclinical trials.
Karande says that Boulevard has not yet decided on a specific indication for BLVD201 but that it will be aimed at more-severe B-cell diseases.
“For some of the severe diseases, if you do immune reset of the entire B-cell population so that the new B cells that grow are ‘normal,’ your disease resolves. That was what was demonstrated by CAR Ts by one of our founders, Georg Schett,” Karande explains.
“CAR Ts come with a lot of baggage. . . . T-cell engagers actually give you a much better handle that could be as potent but could have dosing flexibility and convenience, and a better safety profile than CAR Ts.”
The company also has a third candidate—a bispecific antibody known as BLVD301—in development for treatment of what it says is a B-cell-driven autoimmune disease, though it has not released specific details.
“We have an incredible management team that has been at the helm of public and private biotechs,” Karande says. “Our company’s approach is grounded in B-cell biology and creating products that make sense for those target types of diseases with patient interest and patient benefit in mind. That’s really what is exciting about this company.”
