SOTYKTU

1 INDICATIONS AND USAGE SOTYKTU is a tyrosine kinase 2 (TYK2) inhibitor indicated for: • the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. ( 1.1 ) Limitations of Use : Not recommended for use in combination with other potent immunosuppressants. • the treatment of active psoriatic arthritis in adults. ( 1.2 ) 1.1 Plaque Psoriasis SOTYKTU is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Limitations of Use : SOTYKTU is not recommended for use in combination with other potent immunosuppressants. 1.2 Psoriatic Arthritis SOTYKTU is indicated for the treatment of active psoriatic arthritis in adults.

2 DOSAGE AND ADMINISTRATION • For recommended evaluation prior to SOTYKTU initiation, see Full Prescribing Information. (2.1) • Recommended dosage is 6 mg orally once daily, with or without food. (2.2) 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Evaluate patients for active and latent tuberculosis (TB) infection prior to initiating treatment with SOTYKTU. Do not administer SOTYKTU to patients with active TB. Start treatment for latent TB prior to initiation of SOTYKTU use [see Warnings and Precautions (5.3) ]. Complete all immunizations according to current immunization guidelines [see Warnings and Precautions (5.7) ] . 2.2 Recommended Dosage The recommended dosage of SOTYKTU is 6 mg taken orally once daily, with or without food. Do not crush, cut, or chew the tablets. 2.3 Recommended Dosage in Patients with Hepatic Impairment SOTYKTU is not recommended in patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. No dosage adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions: Hypersensitivity reactions, such as angioedema, have been reported. Discontinue if a clinically significant hypersensitivity reaction occurs. (5.1) • Infections: SOTYKTU may increase the risk of infection. Avoid use in patients with active or serious infection. If a serious infection develops, discontinue SOTYKTU until the infection resolves. (5.2) • Tuberculosis: Evaluate for latent or active TB prior to initiating treatment with SOTYKTU. (5.3) • Malignancy: Malignancies including lymphomas were observed in clinical trials with SOTYKTU. Consider the benefits and risks prior to initiating or continuing SOTYKTU in patients with a malignancy. (5.4) • Rhabdomyolysis and Elevated CPK: Discontinue SOTYKTU if markedly elevated CPK levels occur or myopathy is diagnosed or suspected . (5.5) • Laboratory Abnormalities: Periodically evaluate serum triglycerides. Evaluate liver enzymes at baseline and during SOTYKTU treatment in patients with known or suspected liver disease. (5.6) • Immunizations: Avoid use of SOTYKTU with live vaccines. (5.7) • Potential Risks Related to JAK Inhibition: It is not known whether TYK2 inhibition may be associated with the observed or potential adverse reactions of JAK inhibition. Higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with a JAK inhibitor compared to those treated with TNF blockers in patients with rheumatoid arthritis (RA). SOTYKTU is not approved for use in RA. (5.8) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, such as angioedema, have been reported in subjects receiving SOTYKTU. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue SOTYKTU [see Contraindications (4) ]. 5.2 Infections SOTYKTU may increase the risk of infections. Serious infections have been reported in subjects who received SOTYKTU. The most common serious infections reported with SOTYKTU included pneumonia and COVID-19 [see Adverse Reactions (6.1) ] . Avoid use of SOTYKTU in patients with an active or serious infection. Consider the risks and benefits of SOTYKTU prior to initiating treatment in patients: • with chronic or recurrent infection • who have been exposed to tuberculosis • with a history of a serious or an opportunistic infection • with underlying conditions that may predispose them to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SOTYKTU. Patients who develops a new infection during treatment with SOTYKTU should undergo prompt and complete diagnostic testing, have appropriate antimicrobial therapy be initiated, and be closely monitored. Interrupt SOTYKTU if a serious infection occurs. Do not resume SOTYKTU until the infection resolves or is adequately treated. Viral Reactivation Herpes virus reactivation (e.g., herpes zoster, herpes simplex) was reported in clinical trials with SOTYKTU [see Adverse Reactions (6.1) ] . In the 16‑week placebo-controlled period of Trials PSO-1 and PSO-2, herpes simplex infections were reported in 17 subjects (6.8 per 100 patient‑years) treated with SOTYKTU, and 1 subject (0.8 per 100 patient-years) treated with placebo. Multidermatomal herpes zoster was reported in an immunocompetent subject who received SOTYKTU. The clinical implications of SOTYKTU on viral hepatitis reactivation are unknown. Subjects with positive screening tests for hepatitis B or C, or chronic hepatitis B, or untreated hepatitis C were excluded from clinical trials or closely monitored for evidence of reactivation. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with SOTYKTU. If signs of reactivation occu…

4 CONTRAINDICATIONS SOTYKTU is contraindicated in patients with a history of hypersensitivity reaction to deucravacitinib or to any of the excipients in SOTYKTU [see Warnings and Precautions (5.1) ] . History of hypersensitivity reaction to deucravacitinib or any of the excipients in SOTYKTU. ( 4 , 5.1 )

8.1 Pregnancy Risk Summary Available data from case reports on SOTYKTU use during pregnancy are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no effects on embryo-fetal development were observed with oral administration of deucravacitinib to rats and rabbits during organogenesis at doses that were at least 72 times the maximum recommended human dose (MRHD) of 6 mg once daily (see Data ) . All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Report pregnancies to the Bristol-Myers Squibb Company’s Adverse Event reporting line at 1-800-721-5072. Data Animal data Deucravacitinib was administered orally during the period of organogenesis at doses of 5, 15, or 75 mg/kg/day in rats and 1, 3, or 10 mg/kg/day in rabbits. Deucravacitinib was not associated with embryo-fetal lethality or fetal malformations in either species. These doses resulted in maternal exposures (AUC) that were 211 times (rat) or 72 times (rabbit) the exposure at the MRHD. In a pre- and post-natal development study in rats, deucravacitinib was administered orally from gestation day 6 through lactation day 20, at doses of 5, 15, or 50 mg/kg/day. At 50 mg/kg/day, F1 offspring had reduced body weight gains during the pre-weaning period. After weaning, body weights of affected F1 offspring gradually normalized to control levels. No maternal effects were observed at 50 mg/kg/day (87 times the MRHD based on AUC comparison). No deucravacitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring were noted at doses up to 15 mg/kg/day (15 times the MRHD based on AUC comparison).

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of labeling: • Infections [see Warnings and Precautions (5.2) ] • Malignancy including Lymphomas [see Warnings and Precautions (5.4) ] • Elevated CPK [see Warnings and Precautions (5.5) ] • Laboratory Abnormalities [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥ 1%) are: upper respiratory infections, blood creatine phosphokinase increased, herpes simplex, mouth ulcers, folliculitis, and acne. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Plaque Psoriasis Clinical Trials The safety of SOTYKTU was evaluated in two placebo- and active-controlled trials (Trial PSO-1 and Trial PSO-2) and an open-label extension trial in which subjects who completed Trial PSO-1 or Trial PSO-2 could enroll [see Clinical Studies (14.1) ]. In these clinical trials, a total of 1,519 subjects with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy received SOTYKTU 6 mg orally once daily. Of these, 1,141 subjects were exposed to SOTYKTU for at least one year. In Trials PSO-1 and PSO-2, 1,681 subjects were randomized to receive SOTYKTU 6 mg once daily (840 subjects), placebo (419 subjects), or apremilast 30 mg twice daily (422 subjects). All subjects randomized to placebo switched to SOTYKTU at Week 16. All other subjects remained in their original treatment group until Week 24, at which point subjects could have continued on the same treatment or be switched to SOTYKTU or placebo. The mean age of subjects was 47 years. The majority of subjects were White (87%) and male (67%). In the 16-week placebo-controlled period of the pooled clinical trials (Trials PSO-1 and PSO-2), discontinuation of therapy due to adverse reactions in subjects who received SOTYKTU was 2.4%, compared to 3.8% for placebo. Table 1 summarizes the adverse reactions that occurred in at least 1% of subjects in the SOTYKTU group and at a higher rate than the placebo group during the 16-week controlled period. Table 1: Adverse Reactions that Occurred in ≥ 1% of Subjects with Plaque Psoriasis in the SOTYKTU Group and More Frequently than in the Placebo Group in Trials PSO-1 and PSO-2 through Week 16 a Includes upper respiratory tract infection (viral, bacterial, and unspecified), nasopharyngitis, pharyngitis (including viral, streptococcal, and unspecified), sinusitis (includes acute, viral, bacterial), rhinitis, rhinotracheitis, tracheitis, laryngitis, and tonsillitis (including bacterial, streptococcal) b Includes oral herpes, genital herpes, herpes simplex, and herpes virus infection c Includes mouth ulceration, aphthous ulcer, tongue ulceration, and stomatitis d Includes acne, acne cystic, and dermatitis acneiform Adverse Reaction SOTYKTU 6 mg once daily Placebo N=840 n (%) N=419 n (%) Upper respiratory infections a 161 (19.2) 62 (14.8) Blood creatine phosphokinase increased 23 (2.7) 5 (1.2) Herpes simplex b 17 (2) 1 (0.2) Mouth ulcers c 16 (1.9) 0 (0.0) Folliculitis 14 (1.7) 0 (0.0) Acne d 12 (1.4) 1 (0.2) Adverse reactions that occurred in < 1% of subjects in the SOTYKTU group were herpes zoster. Specific Adverse Reactions Exposure adjusted incidence rates are reported for all the adverse reactions presented below. Infections In the 16-week placebo-controlled period, infections occurred in 29% of subjects in the SOTYKTU group (116 events per 100 patient-years) compared to 22% of subjects in the placebo group (83.7 events per 100 patient-years). The majority of infections were non-serious and mild to moderate in severity and did not lead t…