Results From the Phase 1 Study of the Novel BCL2 Inhibitor
Sonrotoclax in Combination with Zanubrutinib for
Relapsed/Refractory CLL/SLL Show Deep and Durable Responses
Stephen Opat,1 Mary Ann Anderson,2,3 Alessandra Tedeschi,4 Emma Verner,5,6 Masa Lasica,7Alejandro Arbelaez,8 Stephan Stilgenbauer,9 Peter Browett,10 Sophie Leitch,11 Eva Gonzalez-Barca,12Mazyar Shadman,13,14 Jing-Zhou Hou,15 Herbert Eradat,16 Shuo Ma,17 David Westerman,18,19 Yiqian Fang,20James Hilger,21 Sheel Patel,21 Wei Ding,21 Haiyi Guo,22 Constantine S. Tam231Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia; 2Royal Melbourne Hospital and Peter MacCallum

Cancer Centre, Melbourne, VIC, Australia; 3The Walter and Eliza Hall Institute, Melbourne, VIC, Australia; 4ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy;

5Concord Repatriation General Hospital, Concord, NSW, Australia; 6University of Sydney, Sydney, NSW, Australia; 7St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia;
8Pindara Private Hospital, Benowa, QLD, Australia; 9Division of CLL, Internal Medicine III, Ulm University, Ulm, Germany; 10Auckland City Hospital, Grafton, Auckland,New Zealand; 11Te Whatu Ora, Health New Zealand, Waitemata, Auckland, New Zealand; 12Institut Català d’Oncologia Hospitalet, Universitat de Barcelona, IDIBELL,Barcelona, Spain; 13Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 14University of Washington, Seattle, WA, USA; 15University of Pittsburgh Medical Center,Pittsburgh, PA, USA; 16David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 17Robert H. Lurie Comprehensive Cancer Center,Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 18Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 19University of Melbourne,Melbourne, VIC, Australia; 20BeiGene (Beijing) Co, Ltd, Beijing, China; 21BeiGene USA, Inc, San Mateo, CA, USA; 22BeiGene (Shanghai) Co, Ltd, Shanghai, China;
23Alfred Hospital and Monash University, Melbourne, VIC, Australia

Presented at the EHA2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain

Disclosures for Stephen Opat
• AbbVie (consulting fees, research funding, honoraria, membership on an entity’s board ofdirectors or advisory committees); Antengene (consulting fees); AstraZeneca (consulting fees,research funding, honoraria, membership on an entity’s board of directors or advisorycommittees); BeiGene (consulting fees, research funding, honoraria, membership on an entity’sboard of directors or advisory committees); BMS (consulting fees, research funding, honoraria,
membership on an entity’s board of directors or advisory committees);
CSL Behring (consulting fees); Gilead (consulting fees, research funding, honoraria,membership on an entity’s board of directors or advisory committees); Janssen (consulting fees,research funding, honoraria, membership on an entity’s board of directors or advisorycommittees); Merck (consulting fees, research funding, honoraria, membership on an entity’sboard of directors or advisory committees); Novartis (consulting fees, research funding,honoraria, membership on an entity’s board of directors or advisory committees); Pharmacyclics(research funding); Roche (consulting fees, research funding, honoraria, membership on anentity’s board of directors or advisory committees); Takeda (consulting fees, research funding,honoraria, membership on an entity’s board of directors or advisory committees)2

Introduction• CLL/SLL remains incurable as many treated patients experience relapse,1 necessitating furthertreatment with novel agents• Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective andpharmacologically potent inhibitor of BCL2 than venetoclax with a shorter half-life and no drug
accumulation2• Zanubrutinib is a next-generation BTK inhibitor approved globally for 5 indications, including
CLL3,4– Zanubrutinib has shown superior PFS and safety/tolerability compared with ibrutinib,including fewer cardiac AEs, in patients with R/R CLL/SLL5• Here, updated safety and efficacy data are presented for patients with R/R CLL/SLL treatedwith sonrotoclax + zanubrutinib in the ongoing BGB-11417-101 study (NCT04277637)
1. Hillmen P, et al. J Clin Oncol. 2019;37(30):2722-2729. 2. Hu N, et al. AACR 2020. Abstract 3077. 3. Brukinsa. Prescribing information. BeiGene, Ltd; 2024.
4. Brukinsa. Summary of product characteristics. BeiGene, Ltd; 2021. 5. Brown JR, et al. N Engl J Med. 2023;388(4):319-332.

3

BGB-11417-101 Study Design• BGB-11417-101 is a global phase 1/1b study evaluating sonrotoclax as monotherapy,or in combination ± zanubrutinib, and ± obinutuzumab in patients with B-cell malignancies ​• The primary endpoints were safety per CTCAE v5.0, MTD, and RP2D
• Treatment consisted of 8-12 weeks of zanubrutinib lead-in (320 mg QD or 160 mg BID), then incombination with sonrotoclax (with weekly or daily ramp-up to target dose) until diseaseprogression
Sonrotoclax + zanubrutinib dosefindinga (weekly ramp-up)

Sonrotoclax + zanubrutinib expansion(daily or weekly ramp-up)

R/R CLL/SLL, R/R MCL, TN CLL/SLL

R/R CLL/SLL, R/R MCL, TN CLL/SLL

320 mg

40 mg

80 mg

640 mg

160 mg

320 mg selected
for expansion

320 mgMedian follow-up (range):19.3 months (0.4-35.7)
a The safety monitoring committee reviewed dose-level cohort data before dose escalation.

4Baseline Characteristics and Demographics
Characteristic
Study follow-up, median (range),monthsAge, median (range), years
Male sex, n (%)
ECOG PS01
Risk status, n/tested (%)adel(17p)del(17p) and/or TP53 mutation
IGHV status, n/tested (%)
Unmutated
Prior therapy
No. of lines of prior therapy,
median (range)
Prior BTK inhibitor, n (%)bPrior BTK inhibitor duration,
median (range), months

Sonro 40 mg+ zanu (n=4)
34.0(10.2-35.7)
60 (50-71)
4 (100)

Sonro 80 mg+ zanu (n=9)
27.7(10.0-34.5)
62 (55-75)
8 (89)

Sonro 160 mg+ zanu (n=6)
29.2(28.3-30.8)
62 (41-76)
3 (50)

Sonro 320 mg+ zanu (n=22)
6.8(0.4-26.9)
67 (36-76)
18 (82)

Sonro 640 mg+ zanu (n=6)
18.1(10.9-22.6)
60 (53-69)
2 (33)

All(N=47)
19.3(0.4-35.7)
65 (36-76)
35 (75)4 (100)05 (56)
3 (33)

4 (67)
2 (33)

11 (50)10 (46)

4 (67)
2 (33)

28 (60)17 (36)

3/4 (75)
3/4 (75)

4/8 (50)
7/9 (78)

1/6 (17)
2/6 (33)

3/18 (17)
13/22 (59)00

11/42 (26)
25/47 (53)

1/3 (33)

6/6 (100)

3/6 (50)

3/4 (75)013/19 (68)

1.5 (1-2)

1 (1-2)

1 (1-2)

1 (1-3)

1 (1-1)1 (1-3)

1 (25)
86.6(86.6-86.6)

1 (11)
1.6(1.6-1.6)

1 (17)
18.5(18.5-18.5)

3 (14)
38.1(34.2-49.1)

1 (17)
24.0(24.0-24.0)

7 (15)
34.2(1.6-86.6)

Data cutoff: February 4, 2024.
a TP53 mutations defined as >0.1% variant allele frequency. b BTK inhibitor was the last prior therapy for 7 patients: all discontinued due to toxicity.

5TEAE Summary• No DLTs occurred and MTD was not reached; the 320 mg sonrotoclax + zanubrutinib cohort
was expanded as RP2D
• Sonrotoclax in combination with zanubrutinib was well tolerated, with very low rates of treatment
discontinuation and dose reductions; no deaths were observed

Patients, n (%)
Any TEAEs
Grade ≥3
Serious TEAEs
Led to zanu discontinuation
Led to zanu dose reduction
Treated with sonro, n (%)
TEAEs leading to sonro
discontinuation
TEAEs leading to sonrodose reduction

Sonro 40 mg+ zanu(n=4)
4 (100)1 (25)
1 (25)
004 (100)

Sonro 80 mg+ zanu(n=9)
9 (100)5 (56)
1 (11)
1 (11)a0
9 (100)

Sonro 160 mg+ zanu(n=6)
6 (100)3 (50)
3 (50)
006 (100)

Sonro 320 mg+ zanu(n=22)
20 (91)13 (59)7 (32)
01 (4.5)b
19 (86)dSonro 640 mg+ zanu(n=6)
5 (83)
2 (33)
1 (17)
1 (17)c06 (100)

All(N=47)
44 (94)24 (51)
13 (28)2 (4)1 (2)44 (94)0000

1 (17)c1 (2)000000a 1 patient discontinued zanu due to intracranial hemorrhage. b 1 patient dose reduced zanu (during lead-in) due to neutropenia. c 1 patient discontinued both sonro and zanu due to plasma cellmyeloma. d 3 patients are still in the zanu lead-in phase.
6TEAEs Observed With Sonrotoclax + Zanubrutinib Were Mostly
Low Grade and Transient
TEAEs in ≥5 patients of all patients and those treated at sonrotoclax RP2D of 320 mga,bAll cohorts (N=47)
Median follow-up (range): 19.3 (0.4-35.7) months• No TLS•••Contusion
32
cNeutropenia 621
COVID-1926
No atrial fibrillationDiarrhea
28
Fatigue
26
No febrile
Nausea23
neutropenia
URTI
23
Cough21
No dose reductions Constipation
215Headache17
due to diarrhea
Hypertension 4 9
Back pain
13
Sinusitis
11d d
Thrombocyto.
11
Thrombocytopenia

01020

Sonrotoclax 320 mg + zanubrutinib (n=22)Median follow-up (range): 6.8 (0.4-26.9) months
Neutropenia

2c

536

URTI

Grade 1/2
Grade ≥330

Patients, %405032Contusion

23

Diarrhea

23

Constipation

180

Grade 1/2
Grade ≥352040

Patients, %a Grade is listed as worst grade experienced by patient on any drug. b Hematologic AEs were graded per iwCLL criteria; nonhematologic AEs were graded per CTCAE v5.0 criteria.

60

c Neutropenia combines preferred terms neutrophil count decreased and neutropenia. d Thrombocytopenia combines preferred terms platelet count decreased and thrombocytopenia.

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Sonrotoclax + Zanubrutinib Achieves Deep Responses Across All
Dose Levels• With a median study follow-up of 19.3 months, the ORR was 97%, with a 57% CR/CRi rate across all doses•

In the 320 mg cohort, the ORR was 100%, with a 73% CR/CRi rate

• The median time to CR or CRi was 9.8 months (range, 5.3-22.8 months)• Of 6 evaluable patients with prior BTK inhibitor therapy, 4 achieved PR and 1 achieved CR
100100%Patients, %80
80%
6060%
40
40%
2020%
00%

Follow-up timed,median (range), months

ORRa,b75%

ORRa,b100%

ORRa,b100%

ORRa,b100%

ORRa,b100%

ORRa,b97%

2550
2567

50
7357CR/CRi25350
253327

Sonro 40 mg+ zanu (n=4)

Sonro 80 mg+ zanu (n=8)

Sonro 160 mg+ zanu (n=6)

Sonro 320 mg+ zanu (n=11)

34.0(10.2-35.7)

27.7(10.0-34.5)

29.2(28.3-30.8)

6.8(0.4-26.9)

50c,eSonro 640 mg+ zanu (n=6)

18.1(10.9-22.6)

37
Efficacy-evaluable
population(N=35)

nPR
PR
SD

3

19.3
(0.4-35.7)

a Responses were assessed per 2008 iwCLL criteria and percentage of response is based on number of patients who had at least one post-baseline tumor assessment after dosing

sonrotoclax. b ORR was defined as PR-L or better. c One patient achieved CRi. d For all patients as treated (n=47). e 1 patient previously exposed to venetoclax was included and achieved CR. 8

Sonrotoclax + Zanubrutinib Achieved High Rates of uMRD in
Peripheral Blood• Data shows evidence of
responses deepening over time
• All patients in the 160 mg,
320 mg and 640 mg cohorts
who reached week 48
achieved uMRD

100%
1008080%
Patients, %• Of 33 MRD-evaluable patients,
28 (85%) had uMRD at time ofdata cutoff

6060%

Best MRDaby Week 24b333317224040%
2020%0%05044

Sonro 160 mg+ zanu
(n=6)

Sonro 320 mg+ zanu
(n=9)

uMRD4Best MRDa
by Week 48bOverallBest MRDa
15

100100

Sonro 160 mg+ zanu
(n=6)

Sonro 320 mg+ zanu
(n=5)

MRD4+Not available

85All(N=33)

Data cutoff: February 18, 2024.
a Measured by an ERIC-approved flow cytometry method with 10-4 sensitivity. uMRD4 defined as <10-4 CLL cells of total WBCs. MRD4+ defined as ≥10-4 CLL cells of total WBCs. MRD isbest reported within a 2-week window following the week 24/week 48 day 1 MRD assessments. b Week 24 or 48 of treatment at target dose, following zanu monotherapy and sonro ramp-up
to target dose.

9Progression-Free Survival• With a median study follow-up of 19.3 months, only 1 PFS event occurred in the 40 mg cohort

10Data of Sonrotoclax + Zanubrutinib Demonstrates an Encouraging
Safety and Efficacy Profile in Patients With R/R CLL• Sonrotoclax + zanubrutinib combination treatment had a tolerable safety profile in patients with
R/R CLL/SLL at all dose levels tested up to 640 mg–46/47 of patients remain on study treatment with a median follow-up of 19.3 months–

No TLS and no cardiac toxicity, including atrial fibrillation, were observed–

The most commonly reported hematologic TEAE was neutropenia, which was mostly transitory, with nocases of febrile neutropenia, and did not require sonrotoclax dose reductions• Efficacy was promising in this R/R CLL/SLL population, including patients with high-riskfeatures–

The combination of sonrotoclax + zanubrutinib demonstrated a 97% ORR, with a CR/CRi rate of 57%
across all dose levels and 100% ORR with a CR/CRi rate of 73% at 320mg–Responses deepened over time with high blood MRD negativity observed by week 48 of combinationtherapy–At 19.3 months of median study follow-up, only 1 PFS event occurred in the lowest tested dose (40 mg)• Follow up is ongoing with this promising combination therapy
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Acknowledgments• The authors thank the patients and their families, investigators, co-investigators, and the study
teams at each of the participating centers• This study was sponsored by BeiGene, Ltd• Medical writing support was provided by Kendall Foote, PhD, of Nucleus Global, an Inizio
company, and supported by BeiGene12