September 2025 Letter to Shareholders

Core Insights - CytoDyn Inc. is making significant progress with leronlimab as a treatment for oncology, particularly in addressing unmet needs in solid tumor oncology, supported by both preclinical and clinical evidence [1][3][4] - The company has appointed Robert E. Hoffman as the new Chief Financial Officer to enhance its financial and strategic capabilities [2] - Leronlimab's novel mechanism of action shows promise in increasing PD-L1 expression, potentially allowing for better synergy with immune checkpoint inhibitors [3][24] Clinical Development - Leronlimab has shown prolonged survival in patients with Metastatic Triple-Negative Breast Cancer (mTNBC), with a 5-year survival rate around 15% [4] - A Phase II proof of concept protocol for PD-L1-negative mTNBC patients will be submitted, combining leronlimab with standard chemotherapy and an immune checkpoint inhibitor [4][5] - The company is also advancing leronlimab in metastatic Colorectal Cancer (mCRC), with ongoing enrollment in a Phase II study [6] Scientific Progress - Data presented at the European Society for Medical Oncology (ESMO) meeting indicates that leronlimab induces PD-L1 expression, which could transform treatment approaches for solid tumors [3][24] - In a study, 76% of patients showed increased PD-L1 expression after starting leronlimab, suggesting a shift from a "cold" to a "hot" tumor microenvironment [24] - The company is preparing to submit a comprehensive manuscript detailing the clinical and PD-L1 data from the ESMO presentation [31][32] Regulatory Matters - CytoDyn has successfully resolved investigations by the SEC and DOJ, indicating a positive compliance standing [9] - The company maintains a collaborative relationship with the FDA, focusing on responsible pathways for oncology development [10] Commitment to Shareholders - The company expresses gratitude for shareholder support and emphasizes the importance of maintaining respectful communication with industry partners [11] - CytoDyn is actively pursuing collaborations to maximize the potential of leronlimab [11] Future Directions - The company is exploring the use of leronlimab in glioblastoma, with funding secured for an investigator-initiated study [28] - Ongoing projects include studies on Alzheimer's disease and HIV, with recent approvals and funding arrangements in place [29][30]