AMD Disease Overview - AMD (Age-related Macular Degeneration) affects one in eight people 60 years or older and is the most common cause of blindness in developed countries [8] - An estimated 200 million people worldwide have AMD, projected to reach nearly 300 million by 2040 [8] - Wet AMD is characterized by abnormal blood vessel growth and leakage in the retina, damaging the macula and distorting central vision [7] Current Treatment & Limitations - Current gold standard treatment is anti-VEGF therapy, requiring direct eye injections every 4-6 weeks for 2 years or longer [16][23] - Anti-VEGF therapy, while effective in slowing vision loss and sometimes restoring sight, presents a significant treatment burden on patients, families, physicians, and the healthcare system [14][16][17] - Anti-VEGF drugs have a short half-life in the eye, necessitating repeated injections [17][18] Novel Drug Delivery System - The company is developing a biodegradable microsphere hydrogel composite system for sustained release of anti-VEGF drugs [19] - This system aims to maintain a relatively constant anti-VEGF level in the eye, potentially extending the duration between injections to 6-7 months [19][22] - The system is designed to be injectable using the same procedure, minimizing the need for physicians to adapt to new techniques [20] - Preclinical studies have demonstrated the safety and effectiveness of the drug delivery system [21]

Market Overview - The global branded anti-VEGF market for retinal neovascular/exudative diseases is approximately $14 billion in 2023 and is projected to grow to approximately $18 billion by 2029[8, 16, 24] - Branded anti-VEGF therapies accounted for approximately 70% of the global anti-VEGF units in retinal disease in 2023, while compounded bevacizumab accounted for approximately 30%[25] TH103 Development - TH103 is a fusion protein targeting VEGF, engineered for longer-lasting and increased anti-VEGF activity, invented by VEGF pioneer Dr Napoleone Ferrara[6, 8, 38] - Preclinical studies demonstrated TH103 achieved 100% inhibition of VEGF-induced endothelial cell proliferation in vitro, compared to 80% by aflibercept[57] - TH103 demonstrated increased retention in the retina compared to aflibercept at two weeks in rabbit retina cross-sections[64] - In a mouse laser CNV model, TH103 demonstrated increased duration of action in reducing mean CNV area after administration at Day -14 compared to aflibercept[72] Clinical Program & Intellectual Property - Kalaris received IND clearance from the FDA in June 2024 for a Phase 1 clinical trial of TH103 for nAMD[84] - Initial clinical data from the Phase 1 trial of TH103 for nAMD is expected in Q4 2025[8, 84, 86] - Kalaris holds US exclusivity for TH103 compositions of matter through the early 2040s[92]