BEQALZI

1 INDICATIONS AND USAGE BEQALZI is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s) [see Clinical Studies (14.1) ] . BEQALZI is a BCL-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. ( 1 ) This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION Recommended dosage: 320 mg orally once daily following completion of a 4-week dose ramp-up schedule. ( 2.2 ) Swallow tablets whole with food and water. Do not break, chew, or crush tablets. ( 2.5 ) Provide prophylaxis for tumor lysis syndrome. ( 2.1 , 2.3 ) See Full Prescribing Information for dosage modifications. ( 2.2 , 2.3 , 2.4 ) 2.1 Important Safety Information BEQALZI can cause tumor lysis syndrome (TLS), especially during the ramp-up phase or during restart after a dosage interruption [see Warnings and Precautions (5.1) ] . Initiate BEQALZI with a dose ramp-up. For dose interruption lasting greater than 7 days, adjust the restart BEQALZI dose as instructed [see Dosage and Administration (2.3) and (2.4) ] . Assess patient risk for TLS and whether hospitalization for monitoring is warranted. Initiate prophylactic hydration and anti-hyperuricemics before the first dose of BEQALZI and continue as appropriate. Correct pre-existing electrolyte abnormalities before the first dose. Monitor blood chemistries closely [see Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage for Mantle Cell Lymphoma BEQALZI dosing begins with a 4-week ramp-up. The ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS. 4-Week Dose Ramp-Up Schedule Administer BEQALZI orally once daily, according to the ramp-up dosing schedule shown in Table 1. Table 1: Dosing Schedule for 4-Week Ramp-Up Phase Week Number Days Daily Dose Number of Tablets per Dose Week 1 Days 1 to 3 1 mg One 1 mg tablet Days 4 to 7 2 mg Two 1 mg tablets Week 2 Days 1 to 3 5 mg One 5 mg tablet Days 4 to 7 10 mg Two 5 mg tablets Week 3 Days 1 to 3 20 mg One 20 mg tablet Days 4 to 7 40 mg Two 20 mg tablets Week 4 Days 1 to 3 80 mg One 80 mg tablet Days 4 to 7 160 mg Two 80 mg tablets The Starter Pack provides the first 4 weeks of BEQALZI according to the ramp-up schedule [see How Supplied/Storage and Handling (16) ] . Target Dose Week 5 and Beyond After completion of the 4-week ramp-up phase, the recommended dosage of BEQALZI is 320 mg (four 80 mg tablets) taken orally once daily until disease progression or unacceptable toxicity. Dosing after treatment interruption greater than 7 days is described in Table 3 [see Dosage Modifications for Adverse Reactions (2.3) ] . 2.3 Dosage Modifications for Adverse Reactions Table 2 provides recommended BEQALZI dosage modifications for adverse reactions. Table 3 provides temporary dose modifications upon restart after dose interruptions lasting more than 7 days. Table 4 provides recommended modifications to the target dose after adverse reactions are resolved. Table 2: Recommended BEQALZI Dosage Modifications for Adverse Reactions Adverse Reaction Adverse reactions were graded using NCI CTCAE version 5.0. Occurrence Dosage Modification Tumor Lysis Syndrome Any blood chemistry changes or symptoms suggestive of TLS [see Warnings and Precautions (5.1) ] Any Interrupt BEQALZI. Upon resolution of lab abnormalities, resume BEQALZI. For interruptions lasting 7 days or less, resume planned dosing. For interruptions lasting more than 7 days, see Table 3 for dosage when resuming treatment. Hematologic Toxicity Grade ≥3 febrile neutropenia First Interrupt BEQALZI. Resume BEQALZI at the same dose upon recovery. Second and subsequent Interrupt BEQALZI. A maximum of 2 dose reductions is recommended. Upon recovery to Grade 1 or baseline level, resume BEQALZI and follow dose reduction guidelines in Table 3 and Table 4. Platelet count <50,000/mm 3 with significant bleeding Platelet count <25,000/mm 3 Neutrophil count <500/mm 3 lasting greater than 7 consecutive days First Interrupt BEQALZI. Resume BEQALZI at the same dose upon recovery to Grade 1 or baseline level. Second and subsequent Interrupt BEQALZI. Upon recovery to Grade 1 or baseline level, resume BEQALZI and follow dose reduction guidelines in Table 3 and Table 4. Nonhematologic Toxicity Grade 3 nonhematologic toxicity Pa …

3 DOSAGE FORMS AND STRENGTHS Tablet Strength Description 1 mg Purple, oval, film-coated tablets with 1 debossed on one side. 5 mg Purple, oval, film-coated tablets with 5 debossed on one side. 20 mg Purple, oblong, film-coated tablets with 20 debossed on one side. 80 mg Purple, oval, film-coated tablets with 80 debossed on one side. Tablets: 1 mg, 5 mg, 20 mg, and 80 mg. ( 3 )

4 CONTRAINDICATIONS Concomitant use of sonrotoclax with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients due to the potential for increased risk of tumor lysis syndrome [see Drug Interactions (7.1) ]. Concomitant use of sonrotoclax with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated. ( 2.4 , 4 , 7.1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Tumor Lysis Syndrome [see Warnings and Precautions (5.1) ] Serious Infections [see Warnings and Precautions (5.2) ] Neutropenia [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥15%) are pneumonia and fatigue. The most common Grade 3-4 laboratory abnormalities (≥15%) are decreases in lymphocytes and neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BeOne Medicines at 1-877-828-5596 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. Mantle Cell Lymphoma The safety of BEQALZI was evaluated in 115 adult patients with previously treated MCL in a single-arm, multicenter clinical trial, BGB-11417-201 (NCT05471843) [see Clinical Studies (14.1) ] . The trial required prior receipt of anti-CD20–based therapy and a BTK inhibitor. The trial excluded patients on moderate or strong CYP3A inhibitors or strong CYP3A inducers and required an absolute neutrophil count (ANC) ≥1000/mm 3 ; platelets ≥75,000/mm 3 ; creatinine clearance ≥50 mL/min; AST and ALT ≤3 × upper limit of normal (ULN); and serum total bilirubin ≤2 × ULN. Patients received BEQALZI 320 mg orally once daily following completion of a 4-week ramp-up dosing schedule. Of the 115 patients who received BEQALZI, 52% were exposed for at least 6 months and 34% were exposed for at least 1 year. Serious adverse reactions were reported in 37% of patients who received BEQALZI, most frequently (≥2%) from pneumonia (10%). Fatal adverse reactions occurred in 4.3% of patients, including from pneumonia (2.6%) and sudden death (1.7%). Adverse reactions led to dose interruption of BEQALZI in 27% of patients, dose reduction in 0.9%, and permanent discontinuation in 8%. The most common reasons for dose interruption were infections (10%) and neutropenia (5%). The most common adverse reaction leading to treatment discontinuation was infection (1.7%). Table 7 summarizes select adverse reactions in Study BGB-11417-201, excluding laboratory terms. Table 7: Adverse Reactions (≥10%) in Patients with MCL Who Received BEQALZI in BGB-11417-201 Adverse Reaction BEQALZI (N=115) All Grades (%) Grade 3 or 4 (%) Infections Pneumonia Includes pneumonia, COVID-19 pneumonia, pneumonia bacterial, and other related terms. 16 Additionally includes three fatal cases (2.6%) of pneumonia. 10 Upper respiratory tract infection Includes upper respiratory tract infection, pharyngitis, sinusitis, and other related terms. 12 1.7 General Disorders Fatigue Includes fatigue and asthenia. 16 0.9 Edema Includes edema peripheral, generalized edema, and other related terms. 14 0 Pyrexia 10 0.9 Gastrointestinal Disorders Diarrhea 14 1.7 Constipation 10 0 Skin and Subcutaneous Tissue Disorders Rash Includes rash, dermatitis, drug eruption, and other related terms. 10 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Includes musculoskeletal pain, back pain, bone pain, and other related terms. 10 0 Clinically relevant adverse reactions in <10% of patients who received BEQALZI included: TLS, headache, nausea, vomiting, mucositis, peripheral sensory neuropathy, febrile neutropenia, pneumonitis, herpes zoster infection, and sepsis. Table 8 summarizes new or worsening laboratory abnormalities throughout treatment. Grade 4 laboratory abnormalities in ≥2% of patients included decreases in neutrophils (6%) and platelet count (3.5%). Table 8: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with Previously Treated MCL Who Received BEQALZI Laboratory Abnormality The denominator used to calculate the rate varied from 103 to 115 based on the number of pat …

7 DRUG INTERACTIONS Strong CYP3A inhibitors: Contraindicated at initiation and during the ramp-up phase. Reduce target dose after ramp-up. ( 2.4 , 7.1 ) Moderate CYP3A inhibitors: Avoid concomitant use at 1 mg and 2 mg doses of BEQALZI and reduce all other doses. ( 7.1 ) Strong or moderate CYP3A inducers: Avoid coadministration. ( 7.1 ) 7.1 Effects of Other Drugs on BEQALZI Strong or Moderate CYP3A Inhibitors Concomitant use of strong CYP3A inhibitors during the initiation and ramp-up phase with BEQALZI is contraindicated. After the ramp-up phase, reduce the target dose of BEQALZI as in Table 5 [see Dosage and Administration (2.4) ] . For dose modifications of sonrotoclax with moderate CYP3A inhibitors, see Dosage and Administration (2.4) . Sonrotoclax is a CYP3A substrate [see Clinical Pharmacology (12.3) ] . Concomitant use with strong and moderate CYP3A inhibitors increase sonrotoclax exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of BEQALZI adverse reactions. Strong or Moderate CYP3A Inducers Avoid concomitant use of strong or moderate CYP3A inducers with BEQALZI. Sonrotoclax is a CYP3A substrate [see Clinical Pharmacology (12.3) ] . Concomitant use with strong CYP3A inducers decreases sonrotoclax exposure [see Clinical Pharmacology (12.3) ] , which may reduce effectiveness of sonrotoclax.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology (12.1) ] , BEQALZI can cause embryo-fetal harm when administered to pregnant women. There are no available data on BEQALZI use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of sonrotoclax to pregnant mice and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including structural abnormalities and altered fetal growth, at maternal exposures approximately ≥2 times the human exposure (AUC) at the recommended dose of 320 mg daily (see Data ). Advise patients of the potential risk to a fetus. 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. Data Animal Data Sonrotoclax was administered orally to pregnant mice at doses of 100, 300, and 1000 mg/kg/day during organogenesis (gestation days 6-15). Decreased fetal body weight and crown-rump length were noted at all doses. At the dose of 100 mg/kg/day in mice, the maternal exposure was approximately 8 times the human exposure at the recommended dose of 320 mg once daily. Sonrotoclax was administered orally to pregnant rabbits at doses of 15, 75, and 300 mg/kg/day during organogenesis (gestation days 6-19). Fetal external (absent or open eye, cleft lip, misshapen mouth, acephalostoma) malformations were noted at 300 mg/kg/day. At the dose of 300 mg/kg/day in rabbits, the maternal exposure was approximately 2 times the human exposure at the recommended dose of 320 mg once daily. 8.2 Lactation Risk Summary There are no data on the presence of sonrotoclax or its metabolites in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with BEQALZI and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential Based on findings in animals and its mechanism of action, BEQALZI can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating BEQALZI. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with BEQALZI and for 1 week after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with BEQALZI and for 1 week after the last dose. Infertility Based on findings in animals, BEQALZI may impair male and female fertility. Fertility findings were reversible in animals [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of BEQALZI in pediatric patients have not been established. 8.5 Geriatric Use Of the 115 patients with MCL who were treated with BEQALZI, 74 (64%) were 65 years old or older and 26 (23%) were 75 years old or older. Patients aged 65 years and older experienced higher rates of serious adverse reactions (42%) compared to younger patients (29%). Clinical studies of BEQALZI did not include sufficient numbers of patients to determine whether efficacy differs in patients 65 years of age or older compared to younger patients. 8.6 Renal Impairment No dose adjustments are recommended for patients with mild or moderate renal impairment (estimated glomerular filtration rate (eGFR) ≥30 mL/min). BEQALZI has not been studied in patients with severe renal impairment (eGFR 3 × ULN and any AST) [see Clinical Pharmacology (12.3) ] .

12.1 Mechanism of Action Sonrotoclax is an inhibitor of B-cell lymphoma 2 (BCL-2) protein. Overexpression of BCL-2 in various cancers mediates cell survival and has been associated with chemotherapeutic resistance. Sonrotoclax binds to the BCL-2 protein, displacing pro-apoptotic proteins, thereby inducing apoptosis of cells. In nonclinical studies, sonrotoclax demonstrated cytotoxicity in cancer cells overexpressing BCL-2, with a series of intrinsic apoptotic events, including caspase activation.

11 DESCRIPTION BEQALZI tablets contain sonrotoclax, a B-cell lymphoma 2 (BCL-2) inhibitor. The molecular formula of sonrotoclax is C 49 H 59 N 7 O 7 S and the chemical name is N -[4-({[(1 r ,4 r )-4-hydroxy-4-methylcyclohexyl]methyl}amino)-3-nitrobenzene-1-sulfonyl]-4-(2-{(2 S )-2-[2-(propan-2-yl)phenyl]pyrrolidin-1-yl}-7-azaspiro[3.5]nonan-7-yl)-2-[(1 H -pyrrolo[2,3- b ]pyridin-5-yl)oxy]benzamide. The molecular weight of sonrotoclax is 890.11 Daltons. Sonrotoclax has the following structure: BEQALZI tablets for oral use contain 1, 5, 20, or 80 mg of sonrotoclax. Each tablet contains the following inactive ingredients: anhydrous dibasic calcium phosphate, colloidal silicon dioxide (20 and 80 mg only), croscarmellose sodium, hydroxypropyl methylcellulose acetate succinate, magnesium stearate, microcrystalline cellulose, talc (20 and 80 mg only). The tablet film coating contains FD&C Blue No. 1/brilliant blue FCF aluminum lake, FD&C Red No. 40/allura red ac aluminum lake, polyethylene glycol, polyvinyl alcohol, soy lecithin, talc, and titanium dioxide. Chemical Structure

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Package Number of Tablets NDC Number Starter pack carton Each starter pack carton contains 4 weekly blister pack wallets: Week 1 (11 × 1 mg tablets) Week 2 (11 × 5 mg tablets) Week 3 (11 × 20 mg tablets) Week 4 (11 × 80 mg tablets) 72579-015-04 Individual restart packs 1 mg wallet in carton (Week 1 wallet) 11 × 1 mg tablets 72579-020-01 5 mg wallet in carton (Week 2 wallet) 11 × 5 mg tablets 72579-017-01 20 mg wallet in carton (Week 3 wallet) 11 × 20 mg tablets 72579-025-01 80 mg wallet in carton (Week 4 wallet) 11 × 80 mg tablets 72579-022-01 Additional packs 20 mg wallet in carton 14 × 20 mg tablets 72579-025-02 80 mg bottle in carton 120 × 80 mg tablets 72579-022-08 BEQALZI 1 mg film-coated tablets are purple, oval, and debossed with 1 on one side. BEQALZI 5 mg film-coated tablets are purple, oval, and debossed with 5 on one side. BEQALZI 20 mg film-coated tablets are purple, oblong, and debossed with 20 on one side. BEQALZI 80 mg film-coated tablets are purple, oval, and debossed with 80 on one side. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Storage of blister wallets: Store tablets in the original blister package; do not transfer the tablets to a different container.