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Achilles Therapeutics presents data to the Society for

LONDON, Nov. 12, 2021 (GLOBE NEWSWIRE) – Achilles Therapeutics plc (NASDAQ: ACHL), a clinical-stage biopharmaceutical company that develops precision T-cell therapies to treat solid tumors, today presented two posters at The Society for Immunotherapy of Cancer (SITC) Annual Meeting Demonstrating the Ability to Detect, Quantify, and Track Patient-Specific Clonal Neoantigens (cNeT) Reactive T cells and generate increased doses of cNeT from the manufacture of VELOS ™ Process 2. cNeT targets clonal neoantigens, which are unique targets expressed on every cancer cell in a patient but not on healthy tissue.

Samra Turajlic, MD, PhD, lead investigator of the THETIS Phase I / IIa Achilles trial for metastatic malignant melanoma at the Royal Marsden NHS Foundation Trust in London, UK, presented poster 543, titled ‘Sensitive quantification and monitoring of the active components of a clonal therapy based on T neoantigens (cNeT): from manufacture to peripheral circulation ” which shows Achilles’ ability to detect, quantify and monitor patient-specific cNeTs before and after infusion in the ongoing PI / IIa CHIRON and THETIS clinical trials for non-small cell lung cancer (NSCLC) and melanoma metastatic malignant, respectively. Joseph Robinson, PhD, Senior Scientist, Process Development at Achilles Therapeutics, presented poster 193, ‘Achilles VELOS ™ Process 2 increases dose of highly functional, neoantigen-responsive clonal T cells for personalized, precision cell therapy‘highlighting data from a proof-of-concept study showing an 18-fold increase in the median cNeT generated by the VELOS ™ 2 process compared to process 1.

“The data we presented today continues to illustrate the differentiated profile of our cNeT product and our overall platform which leverages standard TIL therapy by leveraging the targeting of clonal neoantigens to deliver a more efficient product. precise and more powerful, ”said Dr Iraj Ali, Managing Director of Achilles. “The ability to reliably detect and quantify our active component is a key differentiator of our world-class technology which is unique in the field and which we believe will be critical to the successful development of TIL-based therapies. “

Kinetics of engraftment, quantification and monitoring of cNeT in CHIRON and THETIS

The data presented on the first eight patients assayed in the framework of the first PI / IIa clinical trials CHIRON and THETIS confirm the ability of the Achilles VELOS manufacturing process to generate a suitable polyclonal cNeT that can target several cancer neo-antigens present on all tumor cells. The Achilles platform can detect, quantify, and track patient-specific cNeT during manufacturing and post-patient administration, enabling in-depth product characterization and immune monitoring.

At the data cut-off date for this presentation, five melanoma patients (THETIS) and three patients with NSCLC (CHIRON) had received their cNeT infusion. The median age of the cohort was 57 years and patients had received a median of 2.5 lines of prior treatment. 88% (7 out of 8) of the cNeT products assayed targeted several clonal neo-antigens present on all tumor cells. In these seven products, the number of individual reactivities ranged from two to twenty-eight and cNeTs were detected in the blood of 71% (5 of 7) of patients after infusion up to six weeks after administration. The best response in the eight treated patients was stable disease in 63% (5 of 8) in this initial low dose cohort generated using the VELOS 1 method. The safety profile was generally similar to that of standard TIL products. which were not fortified for cNeT reactivity, none of the higher grade adverse events most commonly associated with the use of higher doses of interleukin-2 (IL-2). No suspicious unexpected serious adverse reactions have been reported since the last update on the first six patients earlier in 2021. Overall, in the cohort, there were three cytokine release syndrome events and one ICANS event considered possibly related to cNeT treatment. A previously disclosed case of encephalopathy was subsequently deemed unlikely to be related to cNeT treatment following review by an independent data safety oversight committee.

“The encouraging data from this low-dose cohort is important because it shows how the Achilles platform can answer questions of potency, provides a first insight into the mechanism of action of a TIL product, and adds confidence to move on now. at higher cellular doses, “said Dr Samra Turajlic, THETIS Chief Researcher, Royal Marsden NHS Foundation Trust, London, UK. “I look forward to exploring higher median doses from the manufacturing of VELOS Process 2 that are expected to be more predictably within the expected therapeutic range, based on work done with other cell therapies. As we move to higher doses of cNeT, I expect improved cell engraftment, both in terms of maximum expansion and durability, and hope to see more evidence of it. anti-tumor activity.

The median dose of cNeT in patients in this low dose process 1 cohort was 14.2 million cNeT, which is consistent with previous updates. The production of VELOS Process 1 generated doses of between 0.1 million and 287 million cNeT. The cNeT reactivity, defined as the percentage of clonal cells reactive to neoantigens in the final assay products, ranged from 5% to 77%. As the dataset expands and matures, these detection and expansion metrics will be correlated with product, clinical, and genomic characteristics to determine variables associated with peripheral cNeT dynamics and response. clinical.

VELOS ™ Process 2 manufacturing

The manufacture of the Achilles VELOS Process 2 generated an 18-fold increase in cNeT over Process 1 in this proof-of-concept study. The increased cNeT contained multiple polyclonal reactivities and key phenotypic characteristics associated with high cell aptitude and reduced cell depletion. The VELOS 2 process improves on process 1 by introducing additional culture medium supplementation and an expansion stimulating cocktail during the co-culture period, without adding time to the overall manufacturing process. Additional manufacturing data at the GMP scale of process 2 will be presented at the ESMO immuno-oncology congress to be held from December 8 to 11, 2021. This manufacturing at the GMP scale is identical to the study process Achilles clinics and formed the basis for the company’s regulatory submissions. move ongoing clinical studies to process 2.

“We are delighted to see that our Process 2 generated such a large increase in cell count while maintaining a highly functional phenotype and we look forward to treating patients with higher doses manufactured using the VELOS 2 process” , said Dr Sergio Quezada, Scientific Director of Achilles. “Based on our experience with other cell therapies, we are confident that Process 2 will provide doses capable of eliciting detectable clinical activity. “

The proprietary Achilles activity test quantified the proportion of tumor-reactive cNeT in the larger TIL population. Both processes generated CD4 + and CD8 + cells capable of recognizing clonal neoantigens. Process 2 provided a polyclonal product with a median of five neoantigen reactivities (range 3-18) detected per patient. The cNeT immunophenotype generated by process 1 and 2 was broadly similar, with the majority of cells carrying an effector memory phenotype. Cells generated from the two processes are also functionally similar, as determined by their ability to secrete INF-γ, IL-2, and TNF-α in response to a polyclonal stimulus.

Poster presentations are available in the Events and Presentations section of the Company’s website.

Webcast and conference call details
The company will host a live webcast and conference call today, Friday, November 12, 2021 at 8:30 a.m.ET / 1:30 p.m. UK to review the SITC presentations and provide a company update. A slide presentation accompanying today’s webcast and conference call will be available on the webcast and in the Events and Presentations section of the Company’s website. The live webcast is available in the Events and Presentations section of the Company’s website. The conference call for investors and analysts is (833) 732-1204 (toll free within the US), 0800 0288438 (toll free within the UK) or (720) 405-2169 (outside the US ) with access code 4795875.

About Achilles Therapeutics
Achilles is a clinical-stage biopharmaceutical company developing precision T-cell therapies targeting clonal neoantigens: individual-unique protein markers that are expressed on the surface of every cancer cell. The Company has two ongoing Phase I / IIa trials, the CHIRON trial in patients with locally advanced and metastatic unresectable non-small cell lung cancer (NSCLC) and the THETIS trial in patients with recurrent or metastatic melanoma. Achilles uses each patient’s DNA sequencing data, along with its proprietary PELEUS ™ bioinformatics platform, to identify patient-specific clonal neoantigens, then develop precision T-cell-based product candidates specifically targeting these patients. clonal neoantigens.

Forward-looking statements
This press release contains express or implied forward-looking statements which are based on the beliefs and assumptions of our management and on information currently available to our management. Although we believe that the expectations reflected in these forward-looking statements are reasonable, these statements relate to future events or our future operational or financial performance, and involve known and unknown risks, uncertainties and other factors that may cause our results, performances or achievements are materially different from the future results, performances or achievements expressed or implied by these forward-looking statements. The forward-looking statements contained in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will change our perspective. However, although we may choose to update these forward-looking statements at any time in the future, we currently have no intention of doing so, except to the extent required by applicable law. You should therefore not rely on any such forward-looking statements as representing our views as of a date subsequent to the date of this press release.

More information :

Lee M. Stern – Vice-President, IR and External Communications
+1 (332) 373-2634
l.stern@achillestx.com

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