A new West Coast biotech has emerged into the busy in vivo cell therapy space, this time with the backing of Nobel Prize-winning CRISPR pioneer Jennifer Doudna, Ph.D. Azalea Therapeutics has bloomed with $82 million in funding and a dual-vector approach that the company hopes can enable permanent genome editing with a single dose.
The funding total includes a $65 million series A that was led by Third Rock Ventures, with RA Capital Management, Yosemite and Sozo Ventures joining the financing bouquet.
The newly sprouted biotech will use the funds to push an in vivo CAR-T therapy for B-cell malignancies into the clinic within the next 12 to 18 months, co-founder and CEO Jenny Hamilton, Ph.D., told Fierce Biotech in an interview. The company will also maintain work on a platform that it believes could have much broader applications.
Azalea’s crown jewel is its enveloped delivery vehicle (EDV) technology, the development of which was spearheaded in Doudna’s lab by Hamilton.
EDVs are viruslike particles that encircle DNA-cutting Cas9 enzymes and are dotted with antibody fragments that target specific cells, Hamilton explained in the interview. She began working on the particles in 2018, and Azalea began taking shape in 2023 after she met Andrea van Elsas, Ph.D., a partner at Third Rock Ventures.
As he became acquainted with Hamilton and Azalea’s science, van Elsas “saw a pattern recognition of something that could look like a real drug,” he told Fierce in an interview. “The other thing I saw was a highly motivated founder team that really wanted to stay involved and try to build this into the best possible company.”
In addition to Hamilton and Doudna, Azalea’s founding team includes Stanford bioengineer Michael Fischbach, Ph.D., and Justin Eyquem, Ph.D., who contributed the second vector to Azalea’s in vivo CAR-T approach.
Eyquem approached Hamilton after a talk she gave at the University of California, San Francisco, where he is a professor, and proposed teaming her EDVs with his adeno-associated viruses (AAV), which can carry genes to insert into a highly specific place in the genome.
Eyquem’s approach, first published in 2017, targets the T-cell receptor alpha constant (TRAC) locus in the T cell genome. TRAC is only active in T cells, and combined with Hamilton’s T cell-targeting EDVs, that reduces the chance for editing errors for Azalea’s in vivo approach.
“What we are so excited about is that by having these two components, a way to specifically deliver the editor and a way to deliver the template, you can turn this into just a single injection,” Hamilton explained, with the engineered T cells mimicking “how your T cells normally behave.”
Azalea’s goal is to develop single-dose treatments that can permanently engineer a patient’s T cells to target their disease. The Berkeley-based outfit will present proof-of-concept mouse data for a suite of tumor models at the ASGCT Breakthroughs in Targeted In Vivo Gene Editing meeting in San Diego later this month, and experiments in primate models are currently underway.
Though Azalea’s first focus is on in vivo CAR-T, their tech could conceivably be reworked to target any other cell type; Hamilton said the company is expanding the approach to engineer hematopoietic stem cells and B cells, too.
“The application space is so massive that we just have to focus and show that this works in patients first, before we start to think too big,” van Elsas said. “At the same time, I do think there’s currently no limitation that we’re aware of.”
In vivo cell therapy has been booming this year. Gilead’s Kite inked an in vivo CAR-T deal with China’s Pregene Biopharma worth up to $1.64 billion in October, while Bristol Myers Squibb paid $1.5 billion to pull in Orbital Therapeutics, an in vivo biotech with a preclinical autoimmune program, the same month. And the federal government has gotten involved, too, with the Advanced Research Projects Agency for Health unveiling a slew of new grants for in vivo cell therapy work.
“There are always these points in time where science just comes together,” van Elsas said. “About a year and a half ago, even people at the FDA talked about being very excited about in vivo gene editing, especially in CAR-T application, because it solves for huge accessibility problems.”
But as all these players compete for sunlight in the ever-growing in vivo space, Hamilton believes Azalea stands apart.
“To the best of our knowledge, we’re the only ones who currently have the ability to program where we can drop a gene in the genome,” Hamilton said. “We really think that’s a major advantage.”
Editor’s note: This article's headline was updated at 11 a.m. ET on Nov. 4 to reflect the entirety of Azalea’s investigational work.