ATL 001 / Achilles Therap - LARVOL DELTA

CHIRON: ATL001 in Patients with Advanced Unresectable or Metastatic NSCLC (clinicaltrials.gov) - P1/2 | N=27 | Terminated | Sponsor: Achilles Therapeutics UK Limited | N=50 ➔ 27 | Trial completion date: Jul 2027 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Sep 2024; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

THETIS: ATL001 in Patients With Metastatic or Recurrent Melanoma (clinicaltrials.gov) - P1/2 | N=13 | Terminated | Sponsor: Achilles Therapeutics UK Limited | N=40 ➔ 13 | Trial completion date: Jul 2027 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Sep 2024; Sponsor decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Melanoma • Oncology • Solid Tumor • BRAF • IL2 • PD-L1

Achilles Therapeutics Announces Strategic Update (GlobeNewswire) - "Achilles Therapeutics plc (NASDAQ: ACHL) today announced the discontinuation of its TIL-based cNeT program and closure of the Phase I/IIa CHIRON and THETIS clinical trials. The Company will refocus its strategy to explore further engagement with third parties who are developing alternative modalities to target clonal neoantigens for the treatment of cancers, such as neoantigen vaccines, ADCs, and TCR-T therapies...The full clinical data generated from the Phase I/IIa CHIRON trial in patients with advanced non-small cell lung cancer (NSCLC) and the Phase I/IIa THETIS trial in patients with recurrent or metastatic melanoma will be presented in an upcoming forum."

Discontinued • Trial termination • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Achilles Therapeutics Reports Fourth Quarter and Year-End 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "2024 Focus and Upcoming Events: Clinical Data: Report clinical activity and translational science data from patients in CHIRON and THETIS Cohort C, evaluating the benefit of enhanced host conditioning, with a meaningful data update expected in 2H 2024; Translational Science: Leverage the Company’s world-class translational science platform to define the features associated with clinical response and to pursue rational design of the final cNeT product; Clinical Activity: Drive additional confirmed responses in CHIRON and THETIS patients on cNeT therapy by delivering higher cNeT doses with enhanced host conditioning; Manufacturing Development: Continue VELOS and PELEUS development to optimize cNeT dose and functionality."

Commercial • P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Achilles Therapeutics Provides Interim Phase I/IIa Update on Clonal Neoantigen Reactive T Cells in Advanced NSCLC and Melanoma Including First Patients Dosed with Enhanced Host Conditioning (GlobeNewswire) - P1/2a | N= 50 | CHIRON (NCT04032847) | N=40 | THETIS (NCT03997474) | Sponsor: Achilles Therapeutics UK Limited | "Achilles Therapeutics...announced interim Phase I/IIa data on the use of clonal neoantigen reactive T cells (cNeT) from the CHIRON study in advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and the THETIS study in recurrent or metastatic malignant melanoma...'The next step is to evaluate cNeT persistence and clinical activity in patients with enhanced host conditioning, and we plan to report a meaningful data update in the second half of 2024.'...'Emerging translational data from the three patients dosed with the enhanced conditioning show improved cNeT engraftment levels and persistence.'....25% of higher dose (>100M cNeT) patients in CHIRON and THETIS (3 of 12) demonstrated stable disease with some reduction in tumor volume; No new objective responses were observed..."

P1/2 data • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

THETIS: ATL001 in Patients With Metastatic or Recurrent Melanoma (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Achilles Therapeutics UK Limited | Trial completion date: Dec 2027 ➔ Jul 2027

Metastases • Trial completion date • Melanoma • Oncology • Solid Tumor • BRAF • IL2 • PD-L1

Long-Term Follow-Up Study of Patients Receiving ATL001 (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Achilles Therapeutics UK Limited | N=90 ➔ 1 | Trial completion date: Jul 2028 ➔ Oct 2023 | Not yet recruiting ➔ Terminated | Trial primary completion date: Jul 2028 ➔ Oct 2023; The long-term follow-up of patients is being migrated to the original (parent) study protocols (Trial ID: ATX-NS-001 / NCT: NCT04032847;Trial ID: ATX-ME-001 / NCT: NCT03997474). Consequently, the ATX-LTFU-001 study is being terminated by the Sponsor.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Achilles Therapeutics Reports Third Quarter 2023 Financial Results and Recent Highlights (GlobeNewswire) - "...'Our Phase I/IIa clinical trials evaluating cNeT therapy for the treatment of advanced NSCLC (CHIRON) and metastatic malignant melanoma (THETIS) continue to progress and we are on track to dose patients in line with our previous guidance. We look forward to sharing our next clinical and translational data update in Q1 2024'."

P1/2 data • Melanoma • Non Small Cell Lung Cancer

CHIRON: ATL001 in Patients With Advanced Unresectable or Metastatic NSCLC (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Achilles Therapeutics UK Limited | Trial completion date: Dec 2023 ➔ Jul 2027 | Trial primary completion date: Jul 2023 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Achilles Therapeutics Reports First Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "Clinical Data: Report clinical and translational science data from 15 to 20 additional patients treated with cNeT monotherapy in NSCLC and melanoma, and with a cNeT/anti-PD-1 checkpoint inhibitor combination in melanoma, in the fourth quarter of the year....Clinical Activity: Drive the potential for additional confirmed responses in CHIRON and THETIS patients by delivering higher cNeT doses and improved product design."

P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

THETIS: ATL001 in Patients With Metastatic or Recurrent Melanoma (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Achilles Therapeutics UK Limited | Trial completion date: Dec 2023 ➔ Dec 2027 | Trial primary completion date: Jul 2023 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF • IL2 • PD-L1

Achilles Therapeutics Presents Encouraging Phase I/IIa Update on Clonal Neoantigen Reactive T Cells in Advanced NSCLC and Melanoma at ESMO IO Congress 2022 (GlobeNewswire) - P1/2a | N=50 | CHIRON (NCT04032847) | P1/2a | N=40 | THETIS (NCT03997474) | Sponsor: Achilles Therapeutics UK Limited |"Additional monotherapy data and initial anti-PD-1 combination data expected in 2023...Confirmed partial response and stable disease achieved with low doses of cNeT and reduced dose lymphodepletion and IL-2 in NSCLC. 1 partial response (PR, 56% tumor reduction maintained at week 36) and 6 patients with stable disease (SD) with overall durable clinical benefit at 12 weeks in 71% of evaluable patients (5/7) with advanced NSCLC. cNeT driven anti-tumor activity in the partial responder is supported by T cell engraftment and cytokine profiles. Stable disease in 50% of evaluable patients (3/6) with melanoma. cNeT product characterization supports a polyfunctional active component."

P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Achilles Therapeutics to Present Early Proof of Concept of Safety and Clinical Activity of Clonal Neoantigen Reactive T Cells at the ESMO Immuno-Oncology Annual Congress 2022 (GlobeNewswire) - P1/2a | N=50 | CHIRON (NCT04032847) | P1/2a | N=40 | THETIS (NCT03997474) | Sponsor: Achilles Therapeutics UK Limited | "Data on 14 heavily pre-treated patients (eight patients from CHIRON with advanced NSCLC and six patients from THETIS with recurrent melanoma) that received cNeT as monotherapy and had completed at least one post-treatment scan six weeks following dosing by the abstract cut-off date will be presented....The best clinical response was a partial response (ongoing at week 33) in a NSCLC patient that showed an investigator-reported 57% total tumor reduction at week 24. Translational science analysis shows that peak expansion of cytokine-secreting cNeT at day 21 was coincident with signs of systemic immune activation including increased serum IL-6. Stable disease was observed in five NSCLC patients through week 12, with two patients remaining stable beyond weeks 15 and 26."

P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

Sensitive quantification and tracking of the active components of a Clonal Neoantigen T cell (cNeT) therapy: From manufacture to peripheral circulation (SITC 2021) - P1/2 | "Conclusions These data underscore our ability to sensitively detect, quantify and track the patient-specific cNeT component of ATL001 – during manufacture and post dosing. As the dataset matures, these metrics of detection and expansion will be correlated with product, clinical and genomic characteristics to determine variables associated with peripheral cNeT dynamics and clinical response."

Tumor-specific neoantigens • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG • TNFA

A first-in-human clinical trial in adult patients with metastatic or recurrent melanoma of a personalised therapy targeting specific mutations that occur in all cancer cells within a single patient. Primer estudio en humanos en pacientes adultos con melanoma metastásico o recurrente, para la evaluación de una terapia personalizada que se dirige a mutaciones específicas que ocurren e (clinicaltrialsregister.eu) - P1/2 | N=40 | Ongoing | Sponsor: Achilles Therapeutics UK Limited

New P1/2 trial • Melanoma • Oncology • Solid Tumor • BRAF • IL2

Achilles Therapeutics Doses First Patient with Higher-dose cNeT in Phase I/IIa CHIRON Trial in Advanced NSCLC and Initiates Enrollment in Cohort B of the THETIS Trial (cNeT + PD-1 checkpoint inhibitor) in Metastatic Malignant Melanoma (GlobeNewswire) - "Achilles Therapeutics plc...announced that the first patient has been dosed with personalized clonal neoantigen-reactive T cells, or cNeT, manufactured with the Company’s higher-dose VELOS Process 2 in the ongoing Phase I/IIa CHIRON clinical trial for the treatment of advanced non-small cell lung cancer (NSCLC). Additionally, following a positive review by an Independent Data Safety Monitoring Committee, the Company has initiated enrollment in Cohort B of the THETIS clinical trial to evaluate cNeT in combination with a PD-1 checkpoint inhibitor for the treatment of metastatic malignant melanoma....'We...look forward to reporting clinical data in the second half of 2022'."

Clinical data • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

Achilles Therapeutics Announces Manufacturing Expansion in the UK and Partnership for Manufacturing in the US (GlobeNewswire) - "Achilles Therapeutics...announced clinical manufacturing expansion in the United Kingdom (UK) and the United States (US)....The Company has entered into a partnership agreement for clinical manufacturing with the Center for Breakthrough Medicines (CBM), a contract development and manufacturing organization in King of Prussia, Pennsylvania. The additional peak annual capacity of up to 600 doses of the Company’s personalized clonal neoantigen-reactive T cell product candidates, known as cNeT, will support clinical manufacturing in the two ongoing Phase I/IIa CHIRON and THETIS clinical trials in advanced non-small cell lung cancer and recurrent or metastatic melanoma, respectively."

Commercial • Licensing / partnership • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

Achilles Therapeutics Reports Fourth Quarter and Year-End 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "2022 Milestones and Upcoming Events: (i) Patient Dosing: Dose first patients with higher dose (Process 2) cNeT monotherapy and cNeT in combination with a PD-1 inhibitor in 2Q 2022; (ii) Higher-dose Monotherapy: Report additional patient data from higher-dose cohort (Process 2) of cNeT monotherapy for the treatment of NSCLC and melanoma in 2H 2022; (iii) cNeT Combination: Report initial patient data from cNeT in combination with a PD-1 inhibitor for the treatment of melanoma in 2H 2022."

P1/2 data • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Long-Term Follow-Up Study of Patients Receiving ATL001 (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Achilles Therapeutics UK Limited | Initiation date: Jul 2021 ➔ Jun 2022

Trial initiation date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Achilles Therapeutics Presents Positive Data at ESMO I-O Congress 2021 on High-Dose Manufacturing Process for Precision T Cell Therapies Targeting Clonal Neoantigens (GlobeNewswire) - P1/2a, N=50; NCT04032847; Sponsor: Achilles Therapeutics UK Limited; "We anticipate dosing patients with high-dose Process 2 cNeT in the first half of 2022, with 6-week clinical and translational science data available in the second half 2022'...Key highlights from the presentation entitled 'Achilles VELOS Process 2 generates a >10-fold improvement in cNeT dose over Process 1 with a highly potent polyclonal phenotype and has been successfully validated at GMP scale for clinical use in solid cancer,” include: Reporting that GMP validation of VELOS Process 2 has successfully been completed and transferred into clinical manufacture in Achilles’ ongoing Phase I/IIa CHIRON and THETIS clinical trials. ..Demonstrating the quantification of the active cNeT drug component with Achilles’ proprietary potency assay which further underlines the strength of the Achilles platform."

P1/2 data • Trial status • Oncology • Solid Tumor

Achilles Therapeutics Presents Data at the Society for Immunotherapy of Cancer (SITC) Annual Meeting Demonstrating the Ability to Detect, Quantify and Track Patient-specific cNeT and Significant Increase in cNeT Dose from VELOS™ Process 2 Manufacturing (GlobeNewswire) - P1/2, N=40; THETIS (NCT03997474); P1/2, N=50; CHIRON (NCT04032847); Sponsor: Achilles Therapeutics UK Limited; "At the data cut-off for this presentation, five patients with melanoma (THETIS) and three patients with NSCLC (CHIRON) had received their cNeT infusion....In these seven products, the number of individual reactivities ranged from two to twenty-eight and cNeT were detected in the blood of 71% (5 of 7) of the patients following infusion at time points up to six weeks post dosing. Best response in the eight dosed patients was stable disease in 63% (5 of 8) in this initial, low-dose cohort generated using VELOS Process 1."

P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] An open-label, multicenter phase I/IIa study evaluating the safety and clinical activity of clonal neoantigen reactive T cells in patients with advanced non-small cell lung cancer (CHIRON). (ASCO 2021) - P=N/A, P1/2 | "Patients in Cohort A receive cyclophosphamide/fludarabine on days -6 to -4, followed by a single dose of ATL001 and 10 daily doses of subcutaneous IL-2; Patients in Cohort B will additionally receive one dose of pembrolizumab between days -13 and -6 before receiving ATL001, then restart pembrolizumab 2 weeks after receiving ATL001 and continue for up to 12 months . Correlative studies will investigate the effects of cNeT dose and engraftment kinetics on clinical activity . The study began enrolling patients in Cohort A in August 2019."

Clinical • IO biomarker • P1/2 data • Tumor-specific neoantigens • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL2

Achilles Therapeutics Enrolls First US Patient in Ongoing Phase I/IIa Study in Advanced Non-small Cell Lung Cancer (GlobeNewswire) - “Achilles Therapeutics plc…announced that the first patient in the United States (US) has been enrolled in the Company’s ongoing Phase I/IIa CHIRON clinical trial….CHIRON is expected to recruit approximately 40 patients with advanced unresectable or metastatic NSCLC.”

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Achilles Therapeutics Details Phase I/IIa Clinical Trial Design of CHIRON in Patients with Advanced Non-Small Cell Lung Cancer at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - P1/2, N=50; CHIRON (NCT04032847); Sponsor: Achilles Therapeutics; "All patients enrolled in CHIRON will have been treated with at least one prior systemic therapy, inclusive of a checkpoint inhibitor unless contraindicated, have Eastern Cooperative Oncology Group (ECOG) Status 0-1, have locally advanced or metastatic disease, and have accessible sites for collection of adequate tissue. Patients requiring regular immunosuppression (including steroids at a dose equivalent to prednisolone 10 mg/day or greater) or that have previously received any investigational cell or gene therapies are not eligible."

Clinical protocol • Lung Cancer • Non Small Cell Lung Cancer • Oncology

[VIRTUAL] Characterization of a novel clonal neoantigen reactive T cell (cNeT) product through a comprehensive translational research program (AACR 2021) - "An approach that targets multiple clonal neoantigens with specific T cells has the potential to demonstrate high specificity and efficacy whilst mitigating the risk of immune escape.Achilles Therapeutics is developing a personalized ACT product, ATL001, to target clonal neoantigens, which are identified using tumor exome sequencing and the PELEUS™ bioinformatics platform...The amalgamation of diverse streams of data requires the development of robust processes and systems for data collection, processing and storage. Furthermore, the evaluation of multiple exploratory endpoints will require integration and modelling of baseline covariates, time-series immune-monitoring and efficacy data, all of which will be described"

Tumor-specific neoantigens • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor