Comment from Mohammad Zaman

COMMENT ON COMMISIONER’s NATIONAL PRIORITY VOUCHER (CNPV) PILOT PROGRAM I respectfully submit this comment in support of consideration of ANKTIVA and related ImmunityBio immunotherapy programs under the Commissioner's NPV Program. 1.Significant Unmet Medical Need Significant unmet medical needs remain in: 1.BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) 2.Advanced lung cancer 3.Pancreatic cancer 4.Colorectal cancer 5.Head and neck cancers 6.Lymphoma and other hematologic malignancies Patients facing these diseases urgently need innovative therapies capable of restoring effective anti-tumor immunity while maintaining acceptable safety profiles. 2.ANKTIVA Represents an Innovative IL-15 Immunotherapy Platform Interleukin-15 is widely recognized as one of the most important cytokines involved in activation, proliferation, and persistence of natural killer (NK) cells and CD8+ cytotoxic T cells. Unlike IL-2, which can stimulate regulatory T cells and contribute to significant toxicity, IL-15 preferentially promotes anti-tumor immune effector cells while supporting long-term immune memory. 3.Robust Expansion of NK Cells, CD8+ T Cells, and Absolute Lymphocyte Counts One of ANKTIVA's most compelling attributes is its demonstrated ability to expand and activate immune effector populations essential for cancer surveillance and tumor elimination. Clinical studies have reported: 1.Significant expansion of NK cells 2.Increased NK-cell cytotoxic activity 3.Expansion of CD8+ T cells 4.Increased memory T-cell populations 5.Sustained immune activation 6.Increased absolute lymphocyte counts (ALC) These findings are particularly important because cancer-associated lymphopenia has consistently been associated with poorer clinical outcomes across multiple malignancies. Restoration of lymphocyte populations may enhance anti-tumor immune responses and improve responsiveness to other therapeutic interventions. 4.Potential Importance in Lymphoma and Other Hematologic Malignancies The biologic rationale for ANKTIVA is particularly compelling in lymphoma and other hematologic cancers. NK cells play a central role in antibody-dependent cellular cytotoxicity, a major mechanism through which monoclonal antibodies such as rituximab exert anti-tumor effects. 5.Importance of Expedited Review of the Pending Papillary NMIBC Application The pending supplemental application warrants particular consideration because of the substantial unmet need faced by patients with BCG-unresponsive papillary NMIBC. Publicly reported QUILT 3.032 Cohort B results demonstrated: 1.Approximately 58% disease-free survival at 12 months 2.Approximately 83% progression-free survival at 36 months 3.Approximately 82% cystectomy-free survival at 36 months 4.Approximately 96% disease-specific survival at 36 months 5.These outcomes are particularly significant because radical cystectomy remains the standard recommendation for many patients with BCG-unresponsive disease. A therapy capable of preserving the bladder while maintaining durable disease control may provide substantial benefits to patients, caregivers, and healthcare systems. 6.Consideration of Accelerated Regulatory Pathways for BioShield Programs The Commissioner may also wish to consider whether existing FDA accelerated regulatory mechanisms could be appropriate for BioShield-related programs should the Agency determine that available evidence demonstrates a favorable benefit-risk profile for serious conditions associated with national health preparedness, biodefense, infectious disease response, radiation exposure, or other public-health emergencies. 7.Alignment with the Goals of the Commissioner's National Priority Voucher Program ANKTIVA appears strongly aligned with the objectives of the CNPV Program because it: 1.Addresses serious and life-threatening diseases 2.Targets significant unmet medical needs 3.Is supported by a scientifically validated mechanism of action 4.Demonstrates robust activation of NK cells and CD8+ T cells 5.Increases lymphocyte populations and may restore immune competence 6.Shows promise in both solid tumors and hematologic malignancies 7.Has already achieved FDA approval 8.Is currently under active FDA review for an expanded bladder cancer indication 9.May have substantial public-health impact across multiple disease areas Based on the totality of currently available scientific, clinical, and regulatory evidence, ANKTIVA represents a uniquely promising immunotherapy platform with demonstrated immune-restorative properties, robust activation of NK cells and CD8+ T cells, expansion of lymphocyte populations, and potential applicability across multiple malignancies. I respectfully encourage FDA to give favorable consideration to ANKTIVA-related oncology programs under the Commissioner's NPV Pilot Program.