IO Summit EU 2023 - Personalised Neoantigen Therapies: State of the Art Neoantigen Immunogenicity Prediction

Personalised Neoantigen Therapies: State of the Art Neoantigen Immunogenicity Prediction

IO Summit EU - 21 June 2023 Andrew Craig, SVP Bioinformatics and Data Science, Achilles Therapeutics

Non-Confidential

© Achilles Therapeutics plc 2023

TRACERx: the largest longitudinal real-world NSCLC patient dataset

•

•

•

•

Over 9 years, 815 patients enrolled with adv/ NSCLC Extensive multi-region sequencing of >4,000 biopsy samples 250 investigators based at 19 hospital sites in UK

25+ publications with ~6000 citations

Non-Confidential	© Achilles Therapeutics plc 2023	1. Rosenthal et al Nature, 2019	3. Chemi et al Nat. Med, 2019; Joshi et al Nat. Med 2019	1
2. Ghorani et al Nat. Cancer, 2020	4. Abbosh et al Nature, 2017

The landmark TRACERx study demonstrated that clonal neoantigens are on all tumour cells

Clonal neoantigens remain as genetic diversity increases

Tumours	Original, clonal
constantly evolve	mutations passed
and acquire new	down and remain in
mutations	all tumour cells1-4

Sub-clonal neoantigens

Clonal neoantigens

Achilles can identify clonal mutations for each patient & target multiple antigens only on tumour cells2-4

Non-Confidential	© Achilles Therapeutics plc 2023	1. Gerlinger et al., NEJM, 2012	3. Jamal-Hanjani et al. NEJM,	2
2. Jamal-Hanjani et al., Plos Biol, 2014	4. Abbosh et al., Nature, 2017

Fundamentals of branched tumour evolution

TRACERx played a significant role in furthering our understanding of tumour evolution and heterogeneity, revealing the importance of clonal neoantigens as targets for treating solid tumours

• Clonal mutations occur early in tumour evolution and are present in all tumour cells including metastases1
• • Clonal neoantigen reactive T cells are found in all tumour regions in NSCLC2
• Subclonal mutations occur later in the tumour evolution and so are found only in a subset of tumour cells
• • Subclonal neoantigens can be detrimental to immune response through subclonal distraction3

Non-Confidential	© Achilles Therapeutics plc 2023	1. Al Bakir et al. 2023 Nature	3. Wolf et al., 2019, Cell	3
2. McGranahan et al. 2016 Science

Critical relevance of clonal neoantigens demonstrated clinically

Sub-clonal neoantigens Clonal neoantigens

Clonality is the driver of disease-free survival

• Patients with high clonal neoantigen burden have an improved disease-free survival
• This is not seen in patients with high sub-clonal neoantigen burden

The higher the number of clonal neoantigens, the greater the chance of immune recognition and successful elimination of all cancer cells

Non-Confidential	© Achilles Therapeutics plc 2023	Rosenthal et al 2019 Nature	4
McGranahan et al. 2016 Science