Akeso's 2024 First Half Interim Results: Expanding Global Lead in IO Bispecific Antibodies, Advancing New Therapies, and Accelerating Commercialization

• Approval of ivonescimab for 2L+ EGFRm NSCL; HARMONi-A is the only phase III study that demonstrates significant benefit across all subgroups for PFS, and is also the only study to achieve the primary endpoint while showing a positive trend in OS benefit; HARMONi-A study presented in an oral presentation at ASCO 2024 and published in JAMA.
• Ivonescimab vs. pembrolizumab for 1L PD-L1 positive NSCLC showed significant positive results; sNDA prioritized by NMPA; HARMONi-2 study featured as Late-Breaking Abstract-Plenary Oral at WCLC 2024. Ivonescimab to become the new standard treatment for first-line lung cancer, offering patients a novel and superior "chemotherapy-free" option.
• The Phase III trial of ligufalimab (CD47, AK117) for first-line head and neck squamous cell carcinoma (vs. pembrolizumab) has begun, making it the first CD47 mAb to enter Phase III for solid tumors.
• Phase III trial of pulocimab (AK109, VEGFR-2) plus cadonilimab for PD-1/L1-resistant gastric cancer underway, cadonilimab aims to provide a new option for IO-resistant cancers, showcasing its potential as next-generation cancer immunotherapy.
• Cadonilimab's sNDAs for advanced gastric and cervical cancers accepted, showing broad benefit and addressing the need for effective treatments in tumors with low or negative PD-L1 expression.
• 12 products are in Phase lll clinical trials or commercial stage; 17 pivotal/Phase III trials for cadonilimab and ivonescimab completed/ongoing.
• 6 new phase III trials added, including ivonescimab for first-line biliary tract cancer (vs. durvalumab), head and neck squamous cell carcinoma (vs. pembrolizumab), pancreatic cancer, and cadonilimab for IO-resistant gastric cancer.
• IND application received for AK138D1, the first differentiated ADC product.
• H1 net product sales recorded RMB939.4 million.

HONG KONG, Aug. 29, 2024 /PRNewswire/ -- Akeso, Inc. (9926.HK) reported its interim results, highlighting the Company's continued innovation and commercial execution. The Company has solidified its lead in cancer immunotherapy bispecific antibodies with the successful market approval of cadonilimab(PD-1/CTLA-4) and ivonescimab(PD-1/VEGF). In the first half of 2024, 4 new drugs were launched, and applications for market approval were submitted for 7 indications across 5 new drugs, and 12 products are in Phase lll clinical trials or commercial stage. Over 20 phase III clinical trials have been completed or are in progress.

Akeso is propelling forward with innovative therapies to drive global oncology treatment advancements: 6 novel bispecific antibodies have entered clinical trials, and the Company's first differentiated ADC, AK138D1, is now in clinical development. Upcoming are new drugs featuring ADCs, bispecific ADCs, trispecific antibodies, and other novel targets and mechanisms.

In the first half of the year, Akeso achieved strong commercial growth with innovative drug sales reaching RMB939.4 million, representing an increase of 23.96% for the same period last year. Cadonilimab remained strong and recorded approximately RMB705.7 million, representing an increase of 16.5% for the same period last year, despite having only one 2/3 line cervical cancer indication. Ivonescimab was successfully approved on May 24, 2024 with achieved net product sales exceeding RMB100 million. The Company's total cash and short-term financial assets, including time deposits, are RMB5.69 billion.

Dr. Michelle Xia, Founder, Chairwoman, President, and CEO of Akeso, said: "In 2024, Akeso has become a major contributor to the field of cancer immunotherapy, outperforming our goals for the year's first half. The approval of cadonilimab has affirmed our innovative strategy and efficiency in bispecific antibody development, setting a strong foundation for drug commercialization. The success of ivonescimab's approval further demonstrates our consistent ability to innovate, providing essential support for its international launch and our global drug commercialization efforts.

We've launched over 50 clinical trials for combination therapies leveraging the clinical potential of cadonilimab and ivonescimab. Our ongoing exploration includes integrating our two cornerstone bispecific assets with ADCs/bispecific ADCs and innovative treatment approaches for multiple tumor types. This drive will enhance global cancer treatment standards and fuel our sustained, high-quality global expansion over the next five years.

In addition, we're rapidly advancing research and clinical development across a diverse range of targets including ADCs, bispecific ADCs, tri-specific antibodies, and other innovative therapeutic modalities. Our robust clinical pipeline enhances our product portfolio, maximizes the clinical impact of our key offerings, and establishes a strong base for Akeso's medium to long-term global growth."

Global Leading Bispecific Antibodies Achieve Major Breakthroughs

Ivonescimab (PD-1/VEGF Bispecific Antibody)

In May 2024, following the HARMONi-A study, ivonescimab was approved in China for the treatment of epidermal growth factor receptor ("EGFR") mutated locally advanced or metastatic non-squamous non-small cell lung cancer ("nsq-NSCLC"). HARMONi-A is the only phase III study that demonstrates significant benefit across all subgroups for PFS, and is also the only study to achieve the primary endpoint while showing a positive trend in OS benefit. Ivonescimab became the world's first approved PD-1/VEGF bi-specific antibody.

Following the HARMONi-2 study's positive interim analysis results, which demonstrated that ivonescimab monotherapy decisively beats pembrolizumab monotherapy head-to-head in patients with PD-L1 positive (TPS≥1%) locally advanced or metastatic NSCLC, ivonescimab has been recognized as the only drug to achieve this milestone in this setting. The interim analysis results have led to the NMPA's priority review of the sNDA for ivonescimab for this indication. The ongoing Phase III studies are strengthening confidence in the HARMONi and HARMONi-3 trials' outcomes and global market potential.Ivonescimab will become the new standard treatment for first-line lung cancer, offering patients a novel and superior "chemotherapy-free" option.

Currently, ivonescimab has 1 approved lung cancer indication in China, 1 under priority review, and 6 Phase III lung cancer trials completed or ongoing, including 4 head-to-head studies with PD-1. In addition, Akeso has launched or is about to launch 3 Phase III clinical trials for ivonescimab:

• Ivonescimab combined with ligufalimab (CD47) for first-line treatment of PD-L1 positive head and neck squamous cell carcinoma (vs. pembrolizumab).
• Ivonescimab combination therapy for first-line treatment of biliary tract cancer (vs. durvalumab combination ).
• Ivonescimab combination therapy for first-line treatment of pancreatic cancer.

Ivonescimab has been involved in more than 25 clinical trials across 17 indications, including lung, pancreatic, breast, hepatocellular, colorectal, and other cancers.

Cadonilimab（PD-1/CTLA-4 Bispecific Antibody)

Since approval, cadonilimab has received widespread clinical and patient acclaim in cancer immunotherapy, backed by strong clinical evidence. Its role as a cornerstone drug in next-gen immunotherapy is becoming more apparent. Besides its approved use for 2/3 line cervical cancer, submissions for first-line advanced gastric and cervical cancer treatments are under regulatory review. Ongoing Phase III trials reveal substantial benefits for diverse PD-L1 expressing patients, offering new options to address critical unmet need in this patient population.

Additionally, cadonilimab has been involved in 8 ongoing or completed pivotal/Phase III clinical trials: Trials for postoperative adjuvant therapy in hepatocellular carcinoma, intermediate-stage hepatocellular carcinoma, and unresectable NSCLC are swiftly progressing. Trials for gastric cancer that has progressed after PD-1/L1 treatment and first-line treatment for PD-L1 negative NSCLC are also steadily enrolling patients, showcasing cadonilimab's potential to offer unique clinical advantages and address the limitations of single-target antibody therapies. To date, cadonilimab as a monotherapy or in combination has been engaged in over 23 clinical trials for 16 indications, including gastric, lung, liver, cervical, and pancreatic cancers.

Ligufalimab (CD47 Monoclonal Antibody, AK117)

The Phase III trial of ligufalimab for first-line head and neck squamous cell carcinoma (vs. pembrolizumab) has begun, making it the first CD47 mAb to enter Phase III for solid tumors. The international multi-center Phase II trial of ligufalimab, AK117 for treating myelodysplastic syndromes (MDS) is also underway as part of AK117's global approval process. Ligufalimab is also being investigated for acute myeloid leukemia (AML), and Phase I/II trials have also been initiated for ligufalimab combined with AK129 (PD-1/LAG-3) in classic Hodgkin lymphoma (cHL). Additionally, several clinical studies for solid tumors are underway.

The Phase III clinical trial for AK109, a novel VEGFR-2 monoclonal antibody, has been initiated in combination with cadonilimab for PD-1/L1-resistant gastric cancer. Clinical trials of other self-developed new drugs in combination with AK109 are also progressing efficiently.

Pursuing More Innovative Therapies

In the first half of the year, Akeso advanced over 10 new therapies into clinical trials, including bispecific antibodies like ivonescimab, cadonilimab, AK129 (PD-1/LAG-3), and AK130 (TIGIT/TGF-β), either in combination with each other or with other high-potential therapies. The Company also introduced its first differentiated ADC product, AK138D1 (HER3 ADC), as well as other innovative therapies into clinical research. Development is ongoing for preclinical candidates such as bispecific antibody AK137 (CD73/LAG-3), bispecific ADC trispecific antibody AK150, and new drug AK135 (IL-1RAP) for chemotherapy-induced peripheral neuropathy. Additionally, multiple candidates in ADC, mRNA, and cell therapies are actively advancing in development.

Non-Oncology Business Enters Commercialization Phase on a Large Scale

Ebdarokimab(IL-12/IL-23) for moderate to severe plaque psoriasis, ebronucimab (PCSK9) for primary hypercholesterolemia and mixed hyperlipidemia, and heterozygous familial hypercholesterolemia (HeFH), have been accepted by NMPA, with anticipated approvals in 2024-2025. Following positive Phase III outcomes, gumokimab (AK111, IL-17) for plaque psoriasis is ready for an NDA submission. Additionally, Phase III trials for gumokimab in ankylosing spondylitis and manfidokimab (AK120, IL-4R) for atopic dermatitis are progressing, with the latter having enrolled its first patient.