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FDA approval of cell therapies made from a patient’s own immune cells provided another treatment option for the most serious cases of blood cancer. But this type of treatment, called CAR-T therapy, is cumbersome to manufacture and still hasn’t proven effective in solid tumors.
A different type of cell therapy called tumor infiltrating lymphocytes (TIL) could offer yet another alternative, plus the potential to address solid tumors. Several biotechs have TILs in clinical development. Achilles Therapeutics aims to best them all.
The London-based biotech has one TIL in clinical testing. It now has $175.5 million from its IPO to continue that research and continue building its TIL therapy pipeline. Late Tuesday, Achilles priced its offering of 9.75 million American depositary shares at $18 apiece, which was the midpoint of the $17 to $19 per share range it had previously set. Those shares began trading on the Nasdaq Wednesday under the stock symbol “ACHL.”
The CAR-T therapies marketed by Novartis and Gilead Sciences are made by harvesting a patient’s T cells and engineering them in a lab to recognize a patient’s cancer. Those cells are multiplied, then infused back into the patient. The entire manufacturing process takes weeks. TIL therapy is similar, but the immune cells that are harvested come from the patient’s tumor, so they already recognize the cancer. That means this type of therapy doesn’t require the engineering that’s key to CAR-T treatments.
In its IPO filing, Achilles noted that clinical testing in the field of TIL research has shown significant responses to TIL therapies, including complete responses in studies in melanoma, cervical carcinoma, and non-small cell lung cancer (NSCLC). But the company added that this approach still has limitations, including an inability to target the therapy and a lack of T cell “fitness” to attack tumors. Other drawbacks to TILs include toxicity to the patient and the challenges of manufacturing these therapies.
Achilles aims to overcome limitations to TILs by developing therapies that target a cancer antigen the company believes is the most specific tumor antigen found on solid tumor cells. The biotech said that its proprietary PELEUS technology identifies mutations formed early in the development of cancer that give rise to these antigens, called clonal antigens. These antigens are found on the surface of cancer cells but are absent on healthy tissue.
The next step is to use the patient’s T cells and dendritic cells to create what Achilles describes as a clonal neoantigen targeting T cell therapy (cNeT). This cell therapy seeks out clonal neoantigens, specifically directing its killing activity to cancer cells. In addition to being more targeted, Achilles contends its approach could also overcome the ability of cancer to evade an immune response, which is referred to as “immune escape.”
“We believe that targeting clonal neoantigens is the key to unlocking immunotherapy in solid tumors and have developed our platform to specifically address these targets,” Achilles said in its filing. “By targeting multiple clonal neoantigens, we have the potential to reduce the likelihood of immune escape by tumor cells, thereby enhancing long-term tumor control, while also reducing the potential for off target toxicity.”
Lead Achilles drug candidate ATL001 is being tested in advanced NSCLC and metastatic or recurrent melanoma. Both clinical trials are open-label Phase 1/2a studies. The company expects to report interim data from the two studies in the second half of next year.
Achilles has its eye on other types of cancers, as well. The company said it is collecting tissue samples from other tumor types, including head and neck squamous cell carcinoma, renal cell carcinoma, triple negative breast cancer, and bladder cancer. Achilles is using its PELEUS technology to identify clonal neoantigens in these tumors. The head and neck squamous cell carcinoma program is expected to become the lead program from this research and could start clinical testing in the second half of 2022.
Though the Achilles TIL therapies could offer a more targeted approach, manufacturing TILs still takes a long time, which is characteristic of many cell therapies. Achilles has designed an automated, fully closed cell manufacturing system. The company said in the IPO filing that the system should be scalable for commercial production and has the potential to overcome many of the manufacturing challenges associated with standard TIL therapies. The company added that it is working to improve the system, turning what takes roughly nine weeks into a six- to eight-week manufacturing process.
Other TIL therapy developers are also trying to improve their manufacturing processes. Dallas-based Instil Bio, which priced its $320 million IPO in mid-March, has a proprietary process that cryopreserves a patient’s tissue sample near a clinical site. That sample is them then transported to one of two manufacturing facilities for processing. Additional competitors in the TIL therapy field include San Carolos, California-based Iovance Biotherapeutics and Adaptimmune Therapeutics, which is based in the U.K.
Achilles said that its IPO proceeds, combined with its existing capital, will be directed toward its TIL pipeline. About $79 million is set aside for its lead TIL candidate through the completion of Phase 1/2a clinical testing in NSCLC and melanoma. Another $36 million is planned for advancing the head and neck squamous cell carcinoma and renal cell carcinoma programs through the completion of the preclinical testing needed to proceed to Phase 1. Achilles also plans to spend about $32 million to continue to further develop its TIL technology and the manufacturing process; $67 million is planned for continued automation and expansion of manufacturing capabilities.
Achilles launched in 2016. Two years ago, the company raised £100 million (about $120 million) in a Series B round of funding led by RA Capital. The company said at the time that it planned to use the cash to begin clinical testing in NSCLC and melanoma. Prior to the IPO, Achilles had raised about $231 million, the company said in the prospectus. The document shows that Syncona is the largest shareholder with a 27.3% post-IPO stake. RA Capital is the next largest stakeholder, owning 8.9% after the IPO.
Image by Flickr user Ed Uthman via a Creative Commons license

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