NEW YORK – When the US Food and Drug Administration approved Tecelra (afamitresgene autoleucel) in August 2024 for certain patients with advanced sarcoma, Adaptimmune became the second company to ever net approval for an autologous cell therapy for a solid tumor.
Now, the firm is riding that wave toward regulatory approval for its second autologous engineered T-cell receptor (TCR) T-cell therapy, letetresgene autoleucel (lete-cel). Adaptimmune CEO Adrian Rawcliffe said during the JP Morgan Healthcare Conference on Tuesday that the firm expects to begin the process of submitting a rolling biologics license application to the FDA for lete-cel in advanced synovial sarcoma and myxoid/round cell liposarcoma in 2025 and that, just this week, the agency granted breakthrough therapy designation to the treatment. The application will include data from the Phase II IGNYTE-ESO trial in which 42 percent of patients responded to lete-cel and the median duration of response was 12.2 months.
Although Tecelra and lete-cel are similar therapies that intend to treat sarcoma patients, they are designed to go after different targets: MAGE-A4 and NY-ESO-1, respectively. To be eligible for Tecelra, patients' sarcoma cells must express MAGE-A4, and to be eligible for lete-cel, they must express NY-ESO-1. For both treatments, patients must test positive for one of several specific human leukocyte antigen types: for Tecelra, HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P, and for lete-cel, HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06.
Adaptimmune estimates that 400 new sarcoma patients per year are currently eligible for Tecelra, and that closer to 1,000 new sarcoma patients per year would be eligible for either Tecelra or lete-cel, should it net approval. The firm is approaching the two therapies as a sarcoma franchise, which it collectively anticipates will bring in up to $400 million in annualized peak sales.
Although there would theoretically be what Rawcliffe called "significant overlap" among sarcoma patients eligible for both Tecelra and lete-cel, he said these therapies could also end up as sequential options.
"Probably 40 to 50 percent of patients express both MAGE-A4 and NY-ESO-1 at high levels," he said. "Some of our physicians are saying they'd really love to think about them in sequence … it would be lovely to have an option for those patients … when they relapse, to go on the second therapy against the other target."
But in terms of the sales projections, Rawcliffe emphasized that the team has only factored in patients who'd receive one therapy or the other, not both.
"The approval of Tecelra was just the first step in building our sarcoma franchise," Rawcliffe said, noting that lete-cel could take a nearly identical path toward its approval and launch. "There are tremendous commercial synergies because these effectively go through exactly the same commercial footprint."
Having both sarcoma treatments on the market would help the firm to reach its current goal of breaking even with its cash flow by 2027.
This goal recently led Adaptimmune to undertake a restructuring plan, announced in November 2024, which involved laying off one-third of its employees and committing to reducing operating expenses by $300 million over the course of four years.
In making these cuts, Adaptimmune said it was prioritizing not only its commercial sarcoma franchise but also the pipeline programs that have the highest potential for return on investment and benefit to patients. This meant halting an ongoing trial of another cell therapy, uzatresgene autoleucel (uza-cel), in certain patients with platinum-resistant ovarian cancer. The firm is still, however, developing uza-cel for patients with head and neck cancer. For this, Adaptimmune has partnered with Galapagos so as to tap into its existing decentralized manufacturing platform.
"We thought this was the best possible place to use the distributed manufacturing that Galapagos has, which offers a potential of a seven-day vein-to-vein period," Rawcliffe said. The firm plans to begin a proof-of-concept trial using Galapagos' platform during 2025.
Beyond its sarcoma franchise and the Galapagos uza-cel partnership program, Adaptimmune is also focused on advancing two additional TCR T-cell therapies toward the clinic: one targeting PRAME and the other targeting CD70.
According to Rawcliffe, the firm's PRAME candidate, which could potentially treat an estimated 29,000 eligible patients, has the potential to be approximately 10 times more sensitive than competitor PRAME-targeting cell therapies. PRAME is highly expressed in solid tumors, including endometrial, breast, lung, and uterine cancer. Adaptimmune is planning to submit an investigational new drug application to the FDA to begin trials of its PRAME candidate in 2025.
Other companies, including Immunocore and Immatics, are also developing PRAME-targeted cell therapies.
Adaptimmune is aiming to submit an investigational new drug application in 2026 for its CD70-targeting cell therapy product candidate. Approximately 72,000 patients, including those with hematologic malignancies and solid tumors like renal cell carcinoma, could potentially be eligible for the CD70 candidate, Rawcliffe said.
While the firm is preparing to develop this next crop of cell therapies, its immediate focus is on the sarcoma franchise, including expanding access to Tecelra in the wake of its approval. The firm expects sales of the autologous therapy — which has a list price of $727,000 per infusion — to grow each quarter of this year as Adaptimmune brings on additional authorized treatment centers across the country to administer the therapy.
The firm believes that its success as a company lies in its highly specialized focus rather than its scale. "This is why I think large companies aren't going to be successful at [solid tumor cell therapies]," Rawcliffe said. "The answers to the problems of cell therapies are specialization and specificity. You've got to be dedicated and committed, and you've got to design everything that you do to deliver cell therapies … this is [our] real advantage."