Disposal of expired or unused product will be returned to the manufacturer or disposed of according to standard site procedures based on agreement between the manufacturer and the site. 81 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 14.3.2 Toxicity In patients receiving the 10 mcg/kg subcutaneous injection, the following were reported grade 1 and 2 toxicities: worsening anemia, diarrhea, anorexia, nausea/vomiting, constipation, fatigue, fever, peripheral IV infiltration, injection site reactions, pain/aches, sinusitis, hypoalbuminemia, hypocalcemia, hypophosphatemia, decreased iron, headaches, dysgeusia, atrial fibrillation, and cough. Grade 3 hypertension, atrial fibrillation, neutropenia, and decreased lymphocyte count were also reported. 14.3.3 Formulation and preparation N-803 is a soluble complex consisting of two protein subunits of a human IL-15 variant associated with high affinity to a dimeric human IL-15 receptor α (IL-15Rα) sushi domain/human IgG1 Fc fusion protein. The IL-15 variant is a 114 aa polypeptide comprising the mature human IL-15 cytokine sequence with an Asn to Asp substitution at position 72 of helix C (N72D). The human IL-15Rα sushi domain/human IgG1 Fc fusion protein comprises the sushi domain of the human IL-15 receptor α subunit (IL-15Rα) (aa 1-65 of the mature human IL-15Rα protein) linked with the human IgG1 CH2-CH3 region containing the Fc domain (232 amino acids). Aside from the N72D substitution, all of the protein sequences are human. Based on the amino acid sequence of the subunits, calculated molecular weight of complex comprising two IL-15N72D polypeptides and a disulfide linked homodimeric IL-15RαSu/IgG1 Fc protein is 92.4 kilodaltons (kDa). Each IL-15N72D polypeptide has a calculated molecular weight of approximately 12.8 kDa and the IL-15RαSu/IgG1 Fc fusion protein has a calculated molecular weight of approximately 33.4 kDa. Both the IL-15N72D and IL-15RαSu/IgG1 Fc proteins are glycosylated resulting in an apparent molecular weight of N-803 as approximately 113 kDa by size exclusion chromatography. The isoelectric point (pI) determined for N-803 ranges from approximately 5.5 to 6.5. Thus, the fusion protein is negatively charged at pH 7. The calculated molar extinction coefficient at A280 for N-803 is 116,540 M-1, or 1.26 OD280 for a 1 mg/mL solution of N-803, or one OD280 is equivalent to 0.79 mg/mL solution of N-803. The biological drug product, N-803, is formulated in a phosphate buffered saline solution. The drug substance is produced by a recombinant mammalian cell line and is manufactured using protein-free media. N-803 is supplied in a 2-mL single-dose/single-use vial containing 0.6 mL of N-803 (extractable volume is 0.5 mL) at a concentration of 1 mg/mL or 2 mg/mL. 14.3.4 Stability and storage Study medication is provided in a 2mL vial containing 0.6 mL of ALT 803 at a concentration of 2 mg/mL. Study medication must be maintained at a temperature between 2℃ and 8℃. The duration of time during which the product remains stable at room temperature will be obtained from ImmunityBio (previously NantCell). 14.3.5 Administration procedures N-803 is administered subcutaneously. See section 3.2.4 82 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 14.3.6 Incompatibilities None known 83 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 15 REFERENCES 1. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C et al: Human papillomavirus and survival of patients with oropharyngeal cancer.