Oncology Pipeline and Product Candidates - Apollomics has built a pipeline of nine product candidates across 11 programs focusing on oncology, with six candidates currently in the clinical stage[392] - The leading product candidates, vebreltinib (APL-101) and uproleselan (APL-106), are in registration trials and have shown promising initial clinical results[392] - Uproleselan has received breakthrough therapy designation from both the NMPA and FDA for the treatment of relapsed or refractory acute myeloid leukemia (AML), with a global Phase 3 study fully enrolled with 388 patients[401] - Vebreltinib has received conditional approval from the NMPA for the treatment of non-small cell lung cancer (NSCLC) with MET genomic tumor aberrations, and is being investigated in clinical trials for advanced tumors[396] - APL-102 is currently in a Phase 1 dose escalation clinical trial in China, with no dose-limiting toxicity observed as of the latest report[397] - APL-122 is in Phase 1 dose escalation in Australia, targeting ErbB1/2/4 signaling pathways and showing potential to treat brain cancers[398] - Apollomics aims to advance the global development of vebreltinib and other tumor inhibitor candidates to address different c-Met alterations across various tumors[409] Clinical Trials and Results - Uproleselan has completed Phase 3 enrollment in 388 subjects with r/r AML outside Greater China, with topline results expected in Q2 2024; a bridging Phase 3 study in China has enrolled 140 patients[415] - Vebreltinib has shown a 48% reduction in the risk of death in patients with r/r glioblastoma multiforme compared to the active comparator arm[417] - Among 37 subjects in the Phase 1 trial, the overall objective response rate (ORR) for c-Met overexpression was 35.7%, and the disease control rate (DCR) was 92.9%[433] - In patients with MET amplification and exon 14 skipping, the ORR was 100% and the DCR was also 100%[433] - The ongoing Phase 2 SPARTA study has over 250 subjects enrolled across approximately 90 study sites in more than 10 countries[449] - The primary endpoint of the SPARTA study is objective response rate (ORR) per blinded independent review committee (BIRC) for NSCLC and other solid tumors[450] - Vebreltinib shows an overall response rate (ORR) of 75% in patients with NSCLC harboring Met Exon 14 skipping mutations, with a median duration of response (DOR) of 15.9 months[452] Safety and Efficacy - The safety profile of vebreltinib showed that 40.5% of patients experienced an increase in ALT, and 35.1% reported peripheral edema[436] - Vebreltinib has been administered to over 500 patients and 170 healthy volunteers, demonstrating an acceptable safety profile[430] - The drug concentration in cerebrospinal fluid (CSF) was about 5% of the steady-state plasma concentration, indicating effective central nervous system penetration[440] - The addition of uproleselan was associated with lower than expected rates of severe Grade 3–4 mucositis, reported at 3% compared to a historical incidence of 20–25%[509] Market Opportunities and Projections - The incidence of AML in China was 26,900 in 2019, projected to rise to 29,000 by 2024 and 31,400 by 2030[415] - Global incidence of NSCLC is projected to increase from 1.0 million cases in 2019 to 1.3 million by 2030, with the U.S. incidence expected to rise from approximately 178,300 cases in 2019 to 221,200 in 2030[478] - The market size for single-targeted c-Met inhibitors in NSCLC is expected to grow to $1.5 billion by 2025 and $3.1 billion by 2030, representing a CAGR of 14.8% from 2025[479] - Approximately 34% of GBM patients exhibit c-Met dysregulation, indicating a significant market opportunity for targeted therapies[481] Collaborations and Agreements - The company entered into a collaboration agreement with GlycoMimetics for the development and commercialization of uproleselan and APL-108 in Greater China[559] - GlycoMimetics received an upfront cash payment of $9.0 million and is eligible for up to approximately $180.0 million based on specified development, regulatory, and commercial milestones[563] - The company has exclusive rights to APL-501 outside of China, with Genor holding the rights within China[548] - The company has obtained development and commercialization rights for vebreltinib, APL-501, APL-502, and APL-102 outside of China, Hong Kong, and Macau[540] Research and Development Focus - The company focuses on developing novel therapies for difficult-to-treat cancers, aiming to improve response rates and reduce treatment resistance and toxicity[392] - The company is committed to leveraging its R&D capabilities to enrich its oncology-focused early-stage pipeline through internal discovery and collaborations[411] - Drug discovery research targets next-generation cancer therapies focusing on the immunosuppressive tumor microenvironment (TME)[586] - The company aims to improve cure rates for various cancers by engaging the immune system in a coordinated, personalized approach[586]
APOLLOMICS INC.(APLM) - 2023 Q4 - Annual Report