NEW YORK – Following the announcement last week of a planned merger with special purpose acquisition company Phoenix Biotech Acquisition, Cero Therapeutics is gearing up to become a publicly traded and clinical-stage company.
The South San Francisco, California-based firm plans to file an investigational new drug application with the US Food and Drug Administration in early 2024 and take its autologous cell therapy, CER-1236, into a Phase I clinical trial involving patients with blood cancers, such as myeloid malignancies lacking treatment options and relapsed or refractory acute myeloid leukemia.
The therapy, which Cero Founder and Chief Technology Officer Daniel Corey began working on when he was a physician scientist at Stanford University, is similar to the autologous CAR T-cell therapies that have gained a foothold in blood cancers. It involves harvesting patients' immune cells, engineering them to express a receptor meant to target cancer cells, and then reinfusing them as a one-time, bespoke therapy.
The main difference with Cero's cell therapies, however, has to do with the receptor that these immune cells are engineered to express and, accordingly, the way they're meant to target and attack patients' cancer cells. While CAR T-cell therapies are engineered to express a chimeric antigen receptor, or CAR, Cero's therapy is engineered to express a receptor that the firm invented, called a chimeric engulfment receptor, or CER.
"The T cell we have engineered has the ability to both 'eat,' as well as to 'kill,'" Corey said, explaining that by 'eat,' he means phagocytosis, a natural process that the body uses to eliminate dead or unwanted cells. "With the CER T cell, you're merging both innate effector function as well as classic adaptive cell killing into a single cell. … You're bringing in the favorable aspects of dendritic cells and myeloid biology into and on top of classic T-cell killing."
Through years of laboratory and preclinical research leading up to where the firm is today, Corey said this CER technology has demonstrated what could be a number of advantages over CAR T-cell therapy. One possible advantage lies in the target it's going after.
The CER T-cell therapy is built to bind to what Corey called the "eat me signal," a receptor called phospholipid phosphatidylserine that remains inside the cell membrane but presents on the cell surface when a cell is infected, under stress, or cancerous.
"There's a history of targeting phosphatidylserine, and there's a large body of literature that shows it can be upregulated on various subsets of tumors," he said. "It's not a lineage-specific target like CD19 or BCMA, which is unique to the B-cell lineage or the plasma blast lineage. … This is more tissue- and indication-agnostic, so that allows us to potentially target various malignancies."
When Corey was at Stanford, he was involved in research developing anti-CD47 approaches, and he said that's where he became interested in innate immunology and using tumor cell phagocytosis as an anti-tumor immunotherapy approach. "This is taking that understanding and building it into a cell therapy platform. That's the inspiration behind it."
The target itself isn't new or novel, Corey said. Antibody-based therapies have taken this route, going after phosphatidylserine, but Cero is, Corey believes, the first to turn it into a cell therapy.
According to Corey, Cero has all the data it needs for its IND filing but is just ironing out the final details. Through pre-IND meetings with the FDA last year, the firm disclosed its development roadmap and manufacturing plans. "We're basically just checking the boxes at this point," he said, adding that since this therapy is an autologous T-cell therapy, existing processes used for CAR T-cell therapies can be replicated easily in the CER T-cell therapy.
"The advantage here is that we can use the road that has been paved, which is a real advantage from the manufacturing perspective as well as an IND-enabling perspective," he said. "That was strategic. We wanted to leverage 20 years of manufacturing experience engineering and administering T cells. We don't have to reinvent the wheel here." According to Corey, manufacturing the CER T cells is expected to take roughly seven to nine days.
While it's not possible to truly know CER-1236's safety or efficacy until first-in-human studies begin, Corey is expecting, based on data from animal models, that the CER T-cell therapy won't attack healthy tissue and cause toxicities in patients.
"Because it's a lipid, it's not species-specific, so when we're putting our cells into a mouse, our cells also recognize the mouse 'eat me' signal," he explained. "If we were to see the cells getting aberrantly activated or attacking the tissues they're not supposed to, we would see that in the mouse."
The Phase I trial will include patients with various blood cancers, but down the line, Corey said he hopes to evaluate the CER T-cell therapy in solid tumors as well, including subsets of patients with non-small cell lung cancer and high-grade epithelial ovarian cancer. Preclinical studies have suggested that the target is upregulated in both of these tumor types. The tumor microenvironment surrounding solid tumors has posed a significant barrier hindering CAR T-cell therapy efficacy, but Cero believes its CER T-cell therapy can help overcome these barriers.
"It restores some of the deficits that exist, where you have dysfunctional dendritic cells or tumor-associated myeloid cells, macrophages that are dysfunctional in antigen presentation or making bad cytokines or things like that," Corey said. "Now we're bringing that functionality in and restoring some of that to address the issues in solid tumors."
Additionally, although the first clinical trial will be focused on evaluating the treatment's safety when administered as a monotherapy, Cero has ambitions to combine the treatment with other therapies to enhance efficacy.
"Because you can elicit and augment the signal with combinations, you can drive the target up when you add various small molecules," he said. "Once we dose 10 or 20 patients, the vision would be that we could expand into various combination cohorts and get really unique synergies … but we have to first get the single-agent safety data."
Cero Therapeutics started off in Johnson & Johnson's incubator, J Labs, in 2018, where it developed the technology, drafted the patents, and showed proof of concept. Then, the firm went on to secure more formal financing, build out its team, and generate the animal data. In the last 18 months, Cero has focused on building out manufacturing capabilities. Now, Corey said Cero is poised for its next phase as a clinical-stage company.
But getting to this point has been tremendously resource-intensive, which is part of why the firm decided to go public on the Nasdaq through a SPAC merger.
Based on a pre-money equity value of $50 million, Cero expects the SPAC deal will have a pro forma equity capitalization value of $145 million. The deal could bring in up to $13.7 million held in trust, barring redemptions from Phoenix's existing stockholders and added capital raised. The deal is contingent on a cash condition of $30 million, which Cero and Phoenix Biotech Acquisition anticipate bringing in through their trust account and additional financing, including a private placement.
Corey said the firm is looking forward to growing its team to include people with experience in management and business development as well as clinical-stage development.
For all of the excitement Corey has about the technology's potential to address unmet needs in a wide range of cancer types, "you just don't know [what could happen] until you get into the clinic," he said. "But there's enough here to give this therapy a chance. It deserves clinical translation."