Summit Therapeutics (SMMT) investor relations material

Study design and background

• HARMONI is a global Phase III trial evaluating ivonescimab plus chemotherapy versus chemotherapy alone in EGFR-mutant non-small cell lung cancer (NSCLC) patients who progressed after 3rd generation EGFR-TKI therapy.

• 438 patients were randomized 1:1, with stratification by region and brain metastases; the study included both Asian and Western patients, with sequential and global enrollment.

• Key endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints including response rate, duration of response, and safety.

• Ivonescimab is a bispecific antibody targeting PD-1 and VEGF, designed for enhanced tumor targeting and efficacy.

• Additional Phase III trials and positive results from China-based studies support global development; ivonescimab received Fast Track designation from the US FDA and is approved in China as of May 2024.

Efficacy and survival outcomes

• Ivonescimab plus chemotherapy significantly improved PFS: median 6.8 vs 4.4 months, HR=0.52, p<0.0001; benefit was consistent across all pre-specified subgroups, including those with and without brain metastases.

• OS showed a favorable trend: median 16.8 vs 14.0 months (ITT), HR=0.79, p=0.0570; in Western patients, median OS was 17.0 vs 14.0 months, HR=0.78, p=0.0332.

• Overall response rate was higher (45% vs 34%) and median duration of response longer (7.6 vs 4.2 months) for ivonescimab plus chemotherapy.

• PFS and OS benefits were consistent across age, sex, region, brain metastases, EGFR mutation subgroups, and PD-L1 status.

• No subgroup showed a detrimental effect; differences in response rates between regions were attributed to timing and maturity of data.

Safety and tolerability

• Ivonescimab plus chemotherapy was well tolerated; grade ≥3 treatment-related adverse events occurred in 50% (ivonescimab) vs 42% (control/placebo).

• Discontinuation due to adverse events was 7.3% (ivonescimab) vs 5% (control); death due to TRAEs was 1.8% vs 2.3%.

• Most immune- and VEGF-related adverse events were low-grade; grade ≥3 hemorrhage was under 1%.

• Most common adverse events included lab abnormalities, nausea, decreased appetite, and anemia.

• Safety profile was consistent globally and manageable, with no new safety signals.