Achilles Therapeutics: Biomanufacturing platform for personalized autologous T cell therapies

Achilles Therapeutics (UK) is pushing the frontier of personalized adoptive T cell therapies. In the first round of the 2022 EIC Pathfinder program, an Achilles-led consortium was awarded €4 million from the “Emerging technologies in cell & gene therapy” Challenge, to develop a proof-of-concept, first-in-class, smart bioprocessing manufacturing platform. We spoke with Dr Gioia Cherubini, Senior Scientific Partnerships Manager at Achilles, to learn more about this momentous success, and the partnership with Catalyze.

Image used with permission from Achilles Therapeutics.

Summary: Achilles Therapeutics SMARTER

The project, SMARTER (grant agreement ID: 101071054), will build on Achilles’ innovative manufacturing process, VELOSTM, which generates a personalized, precision T cell product for each cancer patient. The new platform will allow the consortium to address potential bottlenecks in the existing biomanufacturing process. Catalyze is proud to have supported Achilles Therapeutics towards their winning EIC application, in what is another successful collaboration after our previous support on their €3M FET Open win in 2020, DECOD-Ag (grant agreement ID: 964998).

Leading the next wave in immune-oncology drug development

Achilles was founded on technology initially developed by University College London and the Francis-Crick Institute (UK) after the groundbreaking TRACERx study into the evolution of lung cancer – led by Achilles co-founder Professor Charlie Swanton. This study supported the theory that tumors are clonal in origin, meaning that a single cell starts the entire tumor.

Based on these findings, Achilles developed a bioinformatics platform to identify ‘clonal’ neoantigens that arise early in cancer development and are retained as each tumor continues to grow and mutate. By directing T cell therapies against clonal neoantigens, which are present on all cancer cells and are completely absent from normal cells, Achilles aims to target every cancer cell without attacking healthy tissue for the first time.

Achilles believes that clonal neoantigens represent the ultimate targets with the potential to treat hardest-to-treat solid tumors, where current cell therapies (e.g. CAR-T) still fail.

Gioia highlights, “With our platform, we enrich a population of tumor-infiltrating lymphocytes (TIL) that can target multiple clonal neoantigens, whereas in CAR-T a single neoantigen is targeted.”

Achilles Therapeutics’ EIC Pathfinder project

In the €4 million SMARTER project, Achilles and consortium partners Leibniz University Hannover (DE) (project coordinator), Health Research Institute Hospital La Fe (ES), and Cell Therapy Catapult Limited (UK), aim to develop a first-in-class, smart bioprocessing manufacturing platform for personalized autologous cell therapies, implementing for the first-time inline process analytical technologies and smart process control systems.

Through implementing such continuous monitoring technologies, Achilles can overcome certain bottlenecks in the manufacturing of personalized adoptive cell therapies:

Gioia explains, “With a personalized therapy, it is important to understand the issues of scalability, variability in patient tumor samples, and the current reliance on human intervention, contamination etc. These interventions also take time with current processes, limiting the amount of patient treatments that can be produced.”

Finishing, Gioia adds, “To optimize this process, automated, real-time sensing of the established parameters would be optimal, using sensors that are suitable and scalable for cell therapy. The SMARTER consortium will address these technological challenges as we develop the proof-of-concept platform.”

Dr Gioia Cherubini, Senior Scientific Partnership Manager at Achilles Therapeutics.

Exploiting breakthrough discoveries for adaptive process control

Together, the consortium comprises complementary expertise in cancer immunotherapy, bioinformatics, cell therapy bioprocess engineering, metabolomics and advanced sensor development. Utilizing this combined expertise, SMARTER will exploit breakthrough discoveries of novel T cell expansion process biomarkers and newly developed fluorescence spectroscopy sensors for real-time monitoring of critical process parameters, to enable adaptive process control of the precision TIL biomanufacturing process.

The impact of creating such a smart biomanufacturing platform goes beyond Achilles.  After the EIC Pathfinder project, the prototype R&D platform will be ready for follow-up development into a commercial-scale bioreactor.

Gioia explains, “Once the consortium reaches proof-of-principle, the process could be applied to any other cell therapy. It is something that other companies could potentially take on and develop to be applied on a larger scale.”

Collaborating with Catalyze for the application

In a highly collaborative process, Achilles partnered with Catalyze for the development of the successful application to EIC Pathfinder – and for project management and science communication during execution of the project.

Gioia says, “We decided early on in the collaboration that Catalyze would focus on the grant writing.”

With a clear plan in place and transparency over the respective roles Achilles and Catalyze would play, the collaboration was a success.

Gioia remarks, “The Catalyze consultants were very responsive and very professional. It has been a productive collaboration and, in particular, the team has always been available for discussion or to answer questions, which helped to build trust.”

Continuing the partnership: project management and dissemination

Soon after the news of the successful application, Achilles brought Catalyze onboard to deliver project management and dissemination for the duration of SMARTER. Gioia explains what led Achilles to this decision:

“We had always planned to outsource project management to a group experienced in managing interactions with the EU. Catalyze had this experience and offered the best value.”

Gioia continues, “The project hasn’t started yet, but we are already having a very positive experience with a very responsive, very competent and very professional team at Catalyze.”

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