Despite scoring a historic FDA approval last year, Adaptimmune Therapeutics is expressing concerns about its own longevity, cutting funding for two preclinical programs and evaluating strategic options.
Last August, the FDA granted accelerated approval to Adaptimmune’s afami-cel, sold as Tecelra, for metastatic or unresectable synovial sarcoma. Tecelra is the first engineered cell therapy for a solid tumor to ever snag the agency's approval, and it's the first TCR-T therapy to enter the market. In its own indication, Tecelra is the first new treatment in more than a decade.
Despite Tecelra’s novelty, Adaptimmune has had to implement cost-saving measures to prioritize the cell therapy’s launch and will be discontinuing funding for two preclinical programs, according to a March 20 press release.
One asset, dubbed ADP-600, is designed to target indications that express PRAME—a protein coding gene—such as synovial sarcoma, breast cancer, non-small cell lung cancer and various other tumor types.
The other program is a CD70 program known as ADP-520 meant to go after hematological malignancies such as acute myeloid leukemia, lymphoma and renal cell carcinoma.
The efforts are expected to save up to $100 million over the next four years, according to Adaptimmune.
The cuts build off a 29% workforce reduction announced in November and completed in the first quarter of this year. The layoffs were part of an overarching savings drive designed to cut costs by about $300 million over four years.
Furthermore, Adaptimmune has now hired a bank to assess strategic options for the biotech and its programs.
“In the context of the current capital markets, we are assessing all strategic options to enable us to achieve these goals,” Adaptimmune CEO Adrian Rawcliffe said in the release.
The company expects to release its annual report next Monday, in which it will detail “substantial doubt” about the company’s viability, according to the release.
Since market open, Adaptimmune’s stock has oscillated violently, ultimately falling 31% from 43 cents at market open to 31 cents as of 1:30 p.m. ET on March 20.
The need to assess strategic options in not wholly unexpected.
After receiving the FDA green light for Tecelra, Adaptimmune’s stock fell, perhaps at the prospect of going at the launch alone.
A few months later, after 42% of patients with sarcoma responded to its investigational cell therapy lete-cel in a pivotal phase 2 trial, the biotech announced plans for another FDA submission. While Adaptimmune expects to start a rolling biologics licensing application later this year, another approval may mean another solo commercial launch.
Previously, the cell therapy biotech had been buoyed by a $3 billion biobucks partnership with Genentech until the Roche subsidiary terminated it last April. Just seven weeks later, Adaptimmune was able to secure a $665 million deal with Galapagos for uza-cel, a MAGE-4A TCR T-cell therapy.
However, enrollment in two clinical trials for the cell therapy has been discontinued, according to Adaptimmune’s updated pipeline. It’s unclear if treatment is continuing for already enrolled patients.
“This concerns uza-cel produced using ADAP’s production platform,” a Galapagos spokesperson told Fierce Biotech. “This is not related to the ongoing collaboration we have with ADAP for uza-cel produced on the Galapagos’ cell therapy manufacturing platform.”
Galapagos is pursuing head and neck cancer with Adaptimmune’s uza-cel, with clinical development expected to start next year, according to Galapagos’ 2024 annual financial report. The company presented preclinical data last year demonstrating “that Galapagos’ decentralized cell therapy manufacturing platform can produce uza-cel with features that may result in improved efficacy and durability of response in the clinic compared with the existing manufacturing procedure.”
The collaboration is ongoing, according to the Galapagos spokesperson. The two trials—dubbed Surpass and Surpass-3—that are discontinuing enrollment are not related to Galapagos, according to the spokesperson.
The studies, along with another dubbed Surpass-2, are all "no longer active," an Adaptimmune spokesperson told Fierce Biotech via a March 21 email.
Surpass was a dose-escalating phase 1 trial for patients with MAGE-A4 positive tumors, according to ClinicalTrials.gov. The study launched in 2019 and had a primary completion date slated for the end of this year.
"Data with uza-cel from our Surpass (phase 1) trial has demonstrated compelling early results in ovarian, bladder, and head and neck cancers," the spokesperson said. "That data prompted the initiation of Surpass-2 (phase 2) in esophageal or esophagogastric junction and Surpass-3 (phase 2) in ovarian."
Surpass-2 was terminated in the fall due to “difficulty recruiting subjects and lack of efficacy," according to ClinicalTrials.gov.
Surpass-3 was a phase 2 ovarian cancer study that was launched in 2023 and had an expected enrollment of 66 patients, according to an entry in the federal clinical trial database. The decision to discontinue the mid-stage trial was "based on the financial investment needed relative to clinical timelines," the Adaptimmune spokesperson said.
Trial activities, including long-term follow-up, are ongoing for patients enrolled before the three studies were terminated, according to the spokesperson.
"The decisions on the Surpass family of trials are unrelated to the ADAP production platform," the Adaptimmune spokesperson said.
The Surpass trials used uza-cel manufactured on the Adaptimmune production platform, according to the spokesperson, while the Galapagos collaboration uses uza-cel manufactured on the Galapagos cell therapy manufacturing platform.
The Galapagos deal, which included $100 million upfront, was used to help fund Adaptimmune’s launch of Tecelra.
So far, the launch has experienced successful insurance reimbursement, with no denials to date, plus a 100% success rate in manufacturing, according to Adaptimmune. The company expects to open 30 authorized treatment centers by the end of the year, with 20 currently open and accepting referrals.
"2025 is the year of commercial execution for Tecelra, as we begin to generate value from our promising sarcoma franchise,” Rawcliffe said. “These results give us confidence in our strategy to build value from our sarcoma franchise and our path to profitability in 2027.”
The company is focused on U.S. commercialization, with timing on any potential European regulatory filing for Tecelra up in the air, pending additional clinical data and partnering discussions, according to Adaptimmune.
The company is also running a pediatric phase 1/2 basket study testing Tecelra in patients up to the age of 21 with MAGE-A4 positive tumors. However, the trial’s enrollment was under a temporary suspension "in collaboration with the FDA as per protocol in the trial," the Adaptimmune spokesperson said. The company would not elaborate further on the hold.
Analysts at Mizhuo were “encouraged” by the information on the Tecelra launch but said their bigger focus is now centered around the company’s sustainability.
While the biotech didn’t share financials for the fourth quarter of 2024 or the year as a whole, Adaptimmune said it had a total liquidity of $151.6 million at the end of last year.
It's been a rough week for cell therapy companies, with Cargo Therapeutics suspending development of its allogeneic platform and laying off 90% of its workforce. Meanwhile, Century Therapeutics discontinued a phase 1 cancer study to instead pursue autoimmune diseases, and cell programming company bit.bio cut a quarter of its workforce to focus on its biomedical tool offerings.
Editor's note: This article was updated at 4:30 p.m. ET to include comment from Galapagos. The story was updated twice on March 21 to include Adaptimmune comment and clarify that funding to the preclinical programs was terminated, though the company still lists the programs in its pipeline.