Nobel laureate David Baltimore throws his weight behind I/O startup looking to craft off-the-shelf CAR therapies
In the insular world of biotech, names matter — and no names shine brighter than those luminaries with a Nobel Prize on their record. Now, a Los Angeles startup working at the furthest frontiers of cell therapeutics is standing on the shoulders of a laureate of its own and looking to rewrite the fight against solid tumors.
On Tuesday, Appia Bio launched with $52 million in Series A financing led by 8VC and a platform focused on what are called invariant natural killer T cells (iNKT), an extremely rare immune cell the biotech hopes to reengineer to bust malignant tumors through a “best of both worlds” attack plan, the company said.
Appia’s work is founded on science from UCLA professor Lili Yang alongside a management team of Kite Pharma veterans and a first-time CEO all gravitating around one man — David Baltimore, the 83-year-old Nobel laureate and president emeritus at CalTech.
Baltimore’s work on human viruses earned him the prize for physiology and medicine back in 1975, and since then his labs have mostly been involved in non-translational bench science. But in recent years, his CalTech research team has propped up a translational wing focusing on the use of AAV-based gene transfer for use in stem cells.
Yang, a 13-year veteran of Baltimore’s lab who moved up from graduate research assistant to postdoc to lead scientist on engineered immunity, moved to UCLA in 2013 as an assistant department head in microbiology, immunology and molecular genetics, where she started working on the potential for therapeutic iNKTs in oncology, this time using lentiviral gene transfer instead of AAV. In September 2019, her team published in Cell Stem Cell proof of concept for an “off-the-shelf,” engineered iNKT proliferated in vivo through stem cells.
After showing some success in mice without any serious safety flags, Yang and collaborators Baltimore and Pin Wang, a professor of chemical engineering and materials science and biomedical engineering at USC, saw a path to a potential product and kickstarted Appia last year.
The promise of an allogeneic cell therapy has been a hot area of investment in recent years, but researchers have had a hard time showing that reengineered T cells that don’t come from patients’ own bodies can pass the immune system without heinous side effects. But with iNKTs, which co-express NK and T cell markers, the Appia team thinks it can evade the graft vs. host disease endemic to allogeneic cell therapies and engineer multiple routes of attack on tumors using the innate and active immune system.
Joining the scientific braintrust is JJ Kang, a former partner at The Column Group who received her doctorate in chemical biology at CalTech before a stint as president at Tenaya Therapeutics from 2016 to 2018 — what she told Endpoints News was like “running a company with training wheels.” Baltimore was instrumental in introducing Kang to the Column team, and when she got the chance to head Appia, she jumped.
“It’s so much about people and the way that things mesh together,” she said. “In the academic collaboration that led up to it, you already had the founders that worked together, and adding on the management founders, we all kind of meshed well and it made sense to build a company.”
For Baltimore, who helped Kang arrange the CEO role, he told Endpoints that despite her lack of experience in immunology, Kang has taken to the platform and was ready to lead a biotech with big ambitions.
“I think she’s in the perfect position to now move into a responsible managerial role,” Baltimore said of Kang’s preparation for the job. “She has every other form of experience, she knows the people and the moves to get a company going, and she’s really devoted to the technology.”
The rest of the founding team is comprised of Jeff Wiezorek, the former head of cell therapy development at Kite Pharma who will take on the CMO role, and Edmund Kim, Appia’s chief operating officer and former VP of corporate development at Kite. Wiezorek actually shared a bench with Yang while at CalTech — starting to see the bonds formed here? — while Kim is the odd man out looking to bring his experience at a marketed cell therapy to bear at the fledgling firm.
Having that development experience will bode well as the Appia team hopes to translate its winning preclinical data into a successful human trial, which Kang said the company hopes to enter by late 2023. Baltimore said the platform holds promise, but it’s still too early to say whether it will eventually prove effective.
“There’s a strong likelihood it will work, but you don’t know until you test it,” he said. “There will be surprises, there will be annoyances, but I feel confident that this is the right moment to try.”
The Series A was joined by Two Sigma Ventures among others, with participation from seed investors Sherpa Healthcare Partners and Freeflow Ventures.