About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, Japan, Latin
America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle
East, and Africa, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific
antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects
associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each
of its intended targets with multifold higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF
in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s
tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding
interactions) in the TME with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and
over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC, 2023). This
tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single
bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue
versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days (Zhong, et al, SITC, 2023),
2 is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles
associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III
clinical trials. Over 1,800 patients have been treated with ivonescimab in clinical studies globally.

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing
enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, with a plan to initiate
HARMONi-7 in early 2025.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy
compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nonsquamous
NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy
compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

HARMONi-7 is a planned Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared
to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1
expression (PD-L1 TPS > 50%).

In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical
trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to
placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC
who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab
in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS > 1%).

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license
territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China
in May 2024.