Issuu

Program Speakers Joseph Mikhael, MD, MEd, FRCPC, FACP, FFASCO International Myeloma Foundation Chief Medical Officer Donna Catamero, ANP-BC, OCN, CCRC Myeloma Translational Research, The Mount Sinai Health System, New York, NY Sagar Lonial, MD, FACP, FASCO Winship Cancer Institute, Emory University, Atlanta, GA Tom Martin, MD University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA

Thank you to our speakers & our sponsors!

Heather Cooper Ortner President & CEO International Myeloma Foundation “I am humbled to serve alongside so many who are making a difference every day for patients and families affected by myeloma, and I look forward to building on the IMF’s legacy of impact”

ASH Orlando 2025 – Fast Facts

Over 9000 abstracts submitted (over 1000 more than last year) - over 1500 related to myeloma! - including over 100 oral abstracts and 2 late breaking abstracts Approximately 27, 500 in person attendees and another 3500 virtual

OUTLINE – Top 15 Abstracts 1. Frontline Therapy 2. Early Relapse (1-3 prior lines) 3. Late Relapse

Frontline Therapy 1. Smoldering MM – AQUILA (#372) 2. BENEFIT Trial – Isa-VRD (#368) 3. Teclistamab-Daratumumab (#367) 4. Dual target fastcar frontline (#258) 5. Linvoseltamab post induction (#248)

Sustained minimal residual disease in BENEFIT phase 3 randomized study of Isatuximab plus Lenalidomide and Dexamethasone with Bortezomib (Isa-VRd) versus IsaRd in newly diagnosed transplant ineligible Multiple Myeloma (IFM 2020-05) Arthur Bobin, Jerome Lambert, Jill Corre, Salomon Manier, Aurore Perrot, Lionel Karlin, Murielle Roussel, Noemie Bigot, Omar Benbrahim, Olivier Allangba, Philippe Rey, Véronique Dorvaux, Marguerite Vignon, Virginie Roland, Réda Garidi, Jean-Noel Bastie, Marie-Lorraine Chretien, Sophie Godet, Lydia Montes, Brieuc Chere, Souhila Ikhlef, Anne Vekhoff, Thomas Chalopin, Borhane Slama, Kamel Laribi, Claire Dingremont, Christophe Roul, Valentine Richez-Olivier, Clara Mariette, Sophie Rigaudeau, Claire Calmettes, Mamoun Dib, Mourad Tiab, Laure Vincent, Jacques Delaunay, jean-Pierre Marolleau, Pascal Godmer, Sabrina Maheo, Anais, Schavgoulidze, Laurent Frenzel, Ronan Le Calloch, Emilie Chalayer, Helene Gardeney, Margaret Macro, Bruno Royer, Stephanie Harel, Olivier Decaux, Bertrand Arnulf, Karim Belhadj, Cyrille Touzeau, Mohamad Mohty, Aurelie Gontier, Philippe Moreau, Thierry Facon, Cyrille Hulin, Xavier Leleu

Presented at the 67th Annual American Society of Hematology Meeting, Orlando, USA, December 6-9, 2025 FOR USE BY SANOFI MEDICAL AFFAIRS FOR SCIENTIFIC EXCHANGE DISCUSSIONS ONLY. DO NOT COPY, PHOTOGRAPH, OR DISTRIBUTE.

Study design: Isa-VRd vs Isa-Rd in TI NDMM

†Cycle 1 only. CR, complete response; Cy, cycle; d, dexamethasone; D, day; Isa, isatuximab; M, month; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; NGS, next generation sequencing; OS, overall survival; PD, progressive disease; PFS,

progression-free survival; PR, partial response; R, lenalidomide; SPM, second primary malignancy; Ti, transplant-ineligible; V, bortezomib; VGPR, very good partial response.

Leleu, X. et al. Nat. Med. 30, 2235–2241 (2024).

FOR USE BY SANOFI MEDICAL AFFAIRS FOR SCIENTIFIC EXCHANGE DISCUSSIONS ONLY. DO NOT COPY, PHOTOGRAPH, OR DISTRIBUTE.

112 2

Depth of response at 12, 18 and 24 months - ITT Population

84%

95%

Isa-VRd resulted in deep response rates, including ≥CR rate, at all timepoints CI, confidence interval; CR, complete response; GCS, international genomic staging consensus; IMWG, International myeloma working group; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next generation sequencing; no., number; OR, odds ratio; ORR, overall response rate; %, percentages; PR, partial response; VGPR, very good partial response. .

MRD– rate at 12, 18 and 24 months – ITT population

Isa-VRd resulted in a significant improvement in the MRD at 24 months at 10–5 and 10–6 in the ITT population MRD was performed on bone marrow aspiration in patients at least in ≥PR for the primary endpoint timepoint at 18 months. In ITT analysis, the patients with primary refractory disease, stable disease and minor response, along with patients failing MRD analysis, will be considered as patients with MRD positive at 10-5. The MRD test was centrally and primarily determined by next generation sequencing (NGS) with a 10-5 sensitivity (Pr Avet Loiseau / Pr Corre, Toulouse Oncopole, France). In case of failure to perform MRD by NGS, MRD assessment was then performed centrally using multiparametric flow cytometry (MFC) with a 10-5 sensitivity (Dr Francois Vergez, Toulouse Oncopole, France) 21. Next Generation Sequencing was performed using the Food and Drug Administration-approved Clonoseq 2.0 assay in accordance with IMWG guidelines on assessment of MRD 20. Limit of Detection (LOD) and MRD status were determined using Adaptive’s validated algorithms for the clonoSEQ V2.0 assay. MRD was assessed on the basis of IMWG recommendations. MRD results are compared between treatment groups and treatment effect is assessed by odds ratio and 95% confidence interval using a mixed logistic regression with treatment as the explanatory variable and adjusting for randomization stratification factors. Interaction test are maximum likelihood test of an interaction term included in a logistic regression model. Square represents the estimated OR, and horizontal bars correspond to 95% CI. All statistical test used are two-sided with no correction for multiple comparisons. HRMM definition according to the GCS. Fourteen patients (Isa-VRd n=6 and IsaRd n=7) failed to have cytogenetic analyzed and were classified as non-HR in the ITT analysis. Sustained negative MRD ≥12 months (12-24 months). MRD negative at 12, 18 and 24 months. Sustained negative MRD 18-24 months. MRD negative at 18 and 24 months. CI, confidence interval; FISH, fluorescence in situ hybridization; GCS, international genomic staging consensus; HR, high-risk; IMS, international myeloma society; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next generation sequencing; no., number; %, percentages; s., sustained.

sMRD– rate ≥12 months – ITT population

Isa-VRd resulted in a significant improvement in the sMRD ≥12 months at 10–5 and 10–6 in the ITT population

MRD was performed on bone marrow aspiration in patients at least in ≥PR for the primary endpoint timepoint at 18 months. In ITT analysis, the patients with primary refractory disease, stable disease and minor response, along with patients failing MRD analysis, will be considered as patients with MRD positive at 10-5. The MRD test was centrally and primarily determined by next generation sequencing (NGS) with a 10-5 sensitivity (Pr Avet Loiseau / Pr Corre, Toulouse Oncopole, France). In case of failure to perform MRD by NGS, MRD assessment was then performed centrally using multiparametric flow cytometry (MFC) with a 10-5 sensitivity (Dr Francois Vergez, Toulouse Oncopole, France) 21. Next Generation Sequencing was performed using the Food and Drug Administration-approved Clonoseq 2.0 assay in accordance with IMWG guidelines on assessment of MRD 20. Limit of Detection (LOD) and MRD status were determined using Adaptive’s validated algorithms for the clonoSEQ V2.0 assay. MRD was assessed on the basis of IMWG recommendations. MRD results are compared between treatment groups and treatment effect is assessed by odds ratio and 95% confidence interval using a mixed logistic regression with treatment as the explanatory variable and adjusting for randomization stratification factors. Interaction test are maximum likelihood test of an interaction term included in a logistic regression model. Square represents the estimated OR, and horizontal bars correspond to 95% CI. All statistical test used are two-sided with no correction for multiple comparisons. HRMM definition according to the GCS. Fourteen patients (Isa-VRd n=6 and IsaRd n=7) failed to have cytogenetic analyzed and were classified as non-HR in the ITT analysis. Sustained negative MRD ≥12 months (12-24 months). MRD negative at 12, 18 and 24 months. Sustained negative MRD 18-24 months. MRD negative at 18 and 24 months. CI, confidence interval; FISH, fluorescence in situ hybridization; GCS, international genomic staging consensus; HR, high-risk; IMS, international myeloma society; ITT, intention-to-treat; MRD, minimal residual disease; NGS, next generation sequencing; no., number; %, percentages; s., sustained.

A phase 2 study of teclistamab in combination with daratumumab in elderly patients with newly diagnosed multiple myeloma: the IFM2021-01 TecLille trial, cohort A S. Manier, J. Lambert, M. Macro, T. Chalopin, M. Dib, A. Rumpler, J. Gay, J.-N. Bastie, C. Jacquet, C. Sonntag, L. Vincent, A. Perrot, C. Mariette, L. Montes, S. Rigaudeau, N. Bigot, M. Doyle, D. Santra, P. Smirnov, C. Albrecht, C. Touzeau, J. Corre, P. Moreau, H. Avet-Loiseau, C. Hulin, X. Leleu, T. Facon Abstract #367

ASH 2025, Orlando

IFM 2021-01 TecLille - Study design Phase 2 study of Tec-Dara and Tec-Len in TNE NDMM (n = 74) Cohort A (n=37)

Primary endpoint

Teclistamab 2 step-up dose then 1.5mg/kg D8 and D15 then 3mg/kg Q4W thereafter NDMM Age > 65yo TNE ECOG 0-2

Daratumumab 1800 mg SC, QW for 8 weeks, Q2W for 16 weeks, Q4W thereafter

Pre-specified safety and efficacy analysis after 18 patients have received ≥ 2 cycles

•

Secondary endpoints •

Cohort B (n=37) Teclistamab 2 step-up dose then 1.5mg/kg D8 and D15 then 3mg/kg Q4W thereafter Lenalidomide 25mg per day 21/28 MRD evaluation

M18

M30

Pre-specified safety and efficacy analysis after 10 and 18 patients have received ≥ 2 cycles

Rate of VGPR or better after 4 cycles

• • • • • •

Rate of responses (PR, VGPR, CR, sCR) PFS OS TTNT MRD 10-6 at 6 months Sustained MRD 10-6 Treatment-emergent adverse events

M42

Current amendment: Teclistamab 3mg/kg Q8W after C13 if CR or better and treatment interruption if 2-years sustained MRD -

NCT05572229

IFM 2021-01 TecLille – cohort A: Tec-Dara Response rates VGPR rate after 4 cycles* ORR = 95% 100

Best response rate

CR PR

sCR

ORR = 100%

VG PR

100

VGPR

76%

≥ VGPR = 79%

Patients, %

59%

≥ VGPR = 100%

8% 32% 16% 0

* primary endpoint

Tec-Dara n=37

All patients achieved VGPR or better at best response

IFM 2021-01 TecLille – cohort A: Tec-Dara PFS and OS Median follow up time = 10.3 months PFS

No event of progression or death occurred

Publication Number: 258

A Dual Targeting BCMA and CD19 FasTCAR-T (GC012F/AZD0120) as First-line Therapy for Newly Diagnosed Multiple Myeloma Juan Du,*1 Wanting Qiang,1 Jing Lu,1 Yanchun Jia,1 Haiyan He,1 Jin Liu,1 Pei Guo,1 Ying Yang,1 Zhongyuan Feng,1 Lina Jin,1 Xiaoqiang Fan,1 Nina Shah,2 Qi Zhang,3 Lianjun Shen,3 Jia Liu3 1Department of Hematology, Myeloma & Lymphoma Center, Shanghai Changzheng Hospital, Shanghai, China 2AstraZeneca, Gaithersburg, MD, USA

3Gracell Biotechnologies Ltd., Shanghai, China

Juan Du, MD, PhD

67th ASH Annual Meeting December 6–9, 2025

Study design

Two Phase 1 studies in NDMM Key eligibility criteria • • • • •

Key endpoints

Diagnosed with MM per IMWG criteria ECOG PS ≤3 Measurable disease Study 1 (NCT04935580): high risk (HR)* transplant eligible (TE) NDMM (N=22) Study 2 (NCT05840107): transplant ineligible (TI) NDMM (N=8)

Screening

Leukapheresis

GC012F/AZD0120 infusion

Lymphodepletion

Day -5 to -3 2 cycles of induction therapy RVd (lenalidomide + bortezomib + dexamethasone) could be given before or after apheresis

Fludarabine 30mg/m2/day Cyclophosphamide 300mg/m2/day

Day 0

Dose levels: ＜2x105 cells/kg (n=4) 2x105 cells/kg (n=4) 3x105 cells/kg (n=22)

• • • •

Safety: incidence and severity of Aes Efficacy: ORR, per 2016 IMWG criteria CRR; MRD negativity rate DoR, OS, PFS

Efficacy & safety assessment

Long-term follow-up

24 months Lenalidomide maintenance was permitted to be administered post infusion per investigator’s discretion

15 years

* High-risk was defined as meeting at least one of the following: a) R-ISS stage II or III; b) High-risk cytogenetics: del17p, t(4;14), t(14;16), or 1q21 ≥4 copies; c) Extramedullary disease; d) IgD or IgE

subtype; e) High-risk definition according to mSMART3.0; f) LDH > the upper limit of normal. IMWG: International Myeloma Working Group; ECOG PS: Eastern Cooperative Oncology Group Performance Status; AE: A22erse events; ORR: Overall response Rate; CRR: Complete Response Rate; MRD: Minimal Residual Disease; PFS: Progression Free Survival; DOR: Duration of Response: OS: Overall Survival. 67th ASH Annual Meeting

Juan Du, MD, PhD

December 6–9, 2025

Safety profile: TEAEs • GC012F was well tolerated and mostly low-grade CRS • Grade 1 CRS: 30% (9/30), grade 2 CRS: 3% (1/30), grade ≥3 CRS: 0

TEAEs, n (%)

All Grades All grades

Grade≥3 Grade ≥3

Neutropenia

24 (80)

15 (50)

Leukopenia

24 (80)

13 (43)

Lymphopenia

19 (63)

16 (53)

Four patients with CRS were treated with tocilizumab

LDH increased

12 (40)

Median time to onset: 8 days (range, 6–18 days)

Thrombocytopenia

11 (37)

Hypoalbuminemia

10 (33)

Anemia

10 (33)

Infection

10 (33)

6 (20)

CRS

10 (33)

Hypocalcemia

7 (23)

Median duration: 2 days (range, 1–8 days)

• No ICANS or IEC-HS or IEC-EC observed • No delayed neurotoxicities or secondary primary malignancies observed to date

Juan Du, MD, PhD

Grade 1–2 ≥Grade 3

33 23

0 AEs were graded according to CTCAE v5.0. AE, adverse event; ASTCT, American society for transplantation and cellular therapy; CRS, cytokine release syndrome, graded by ASTCT consensus; CTCAE, common terminology criteria for adverse events; ICANS, immune effector cell-associated neurotoxicity syndrome, graded by ASTCT consensus; IEC-EC, immune effector cell–associated encephalopathy; IEC-HS, immune effector cell–associated hemophagocytic syndrome; LDH, lactase dehydrogenase; TEAE, treatment-emergent adverse event.

40 60 Patients (%)

67th ASH Annual Meeting December 6–9, 2025

100

100% ORR in both cohorts 3%

≥VGPR 100%

97%

ALL (N=30)

sCR 97%

Fast and deep responses were achieved in both groups

•

As of October 15, 2025, the median follow-up time since diagnosis was 36.5 months (19.6–53.9)

•

ORR=100% (30/30): 100% ≥VGPR

100%

95%

TE HR NDMM (N=22) sCR

•

97% (29/30) sCR (1 VGPR patient still in response)

•

is still in response)

•

Median time to first response post infusion was 28 days

•

Median time to best response post infusion was 68 days

TI NDMM (N=8)

VGPR

HR, high risk; NDMM, newly diagnosed multiple myeloma; ORR, overall response rate; sCR, stringent complete response; TE, transplant eligible; TI, transplant ineligible; VGPR, very good partial response.

Juan Du, MD, PhD

67th ASH Annual Meeting December 6–9, 2025

Efficacy profile: PFS & OS

100

PFS

96.7% (95% CI, 78.7–99.5)

OS 89.2% (95% CI, 70.1–96.4)

75 50 25 0

Number at risk All patients 30

50 25

Number at risk All patients 30

Months after infusion

• •

No patients died within 12 months of AZD0120 infusion 23 patients (77%) received lenalidomide maintenance (median time to initiation was 6 months post infusion)

•

7 patients did not receive lenalidomide maintenance, 5 of them remain in disease-free survival.

•

Two patients progressed and then died

• •

One experienced PD and subsequently died One died without documented PD

OS, overall survival; PD, progressive disease; PFS, progression-free survival.

89.2% (95% CI, 70.2–96.4)

100

Overall Survival, %

Progression-Free Survival, %

Median study follow-up: 36.5 months

Juan Du, MD, PhD

67th ASH Annual Meeting December 6–9, 2025

A Phase 2 Trial of Abbreviated Fixed-Duration (Default 4 Cycles) Linvoseltamab ImmunoConsolidation to Deepen Responses Post Newly Diagnosed Multiple Myeloma Combination Therapy for Minimal Residual Disease Positivity (NCT06376526): The IMMUNOPLANT Study Dickran Kazandjian*, Benjamin Diamond, James Hoffman, Abhishek Pandey, David Coffey, Marcella Kaddoura, Brian Walker, David Lessen, Yaharini, Rodriguez, Caterine Diaz, Stephanie Mompoint, Sindy Gutierrez, Jennifer Chapman, Yi Zhou, Mike Georgiou, Russ Kuker, Kellye Koubek, Andrew Kowalski, Leslie Gallardo, Stephanie Fernandes, Fiorela Flores, Rabia Bukhari, Sunwoo Han, Michelle Armogan, Ola Landgren

*Email: dkazandjian@miami.edu

Study Design: Schema Immuno-consolidation for newly diagnosed Multiple Myeloma Using lack of MRD Negativity after initial cOmbination therapy to Pursue deeper responses with Linvoseltamab ANd delay Transplant: The Phase 2 IMMUNOPLANT Study)

Baseline/ Screening Evaluation

Linvoseltamab Cycles 1-4

MRD x10-6 Assessment

NDMM: ≥4 Cycles SoC Novel Combination

≥ VGPR & MRD+

Study Start

MRD(-)

Linvoseltamab Cycles 5-6

MRD(+)

Cycle 1 only

D1 D8 D15 D22

Cycle 5-6

D15

Linvoseltamab 5 mg IV Linvoseltamab 25 mg IV Linvoseltamab 200 mg IV

Cycle 2-3

D1 D8 D15 D22

Cycle 4

D15

Dexamethasone 40/10 mg IV/PO (Subsequent dosing only if CRS,etc.)

Key Eligibility –PI/IMiD/anti-CD38 triplet/quad –≥4 cycles with MRD+ ≥VGPR –adequate organ function

Statistical Hypothesis:

Response Assessment

EoT & 30-day safety/MRD follow up

• Simon Minimax 2-Stage Design: Target MRD(-) Rate: 30%; null MRD(-) Rate: 10% • Stage I: ≥2 of 15 patients with response--> continue enrollment • Stage II: total ≥6 of 25 patients with response reject null hypothesis • One sided alpha = 0.05; Power = 80%

• SoC, e.g. maintenance, HDM-ASCT, etc. • Follow-up for MRD(-) duration, PFS & OS

Endpoints: Primary: MRD- 10-6conversion rate Secondary: Safety, sustained MRD negativity, PFS, OS

Dr. Joe’s Take On Frontline Therapy 1. Single agent daratumumab is a legitimate option in high risk smoldering using the 20/2/20 criteria 2. Quadruplets remain the standard of care in frontline MM with sustained responses 3. Teclistamab can be feasibly and effectively given in frontline myeloma in combination with daratumumab 4. CAR T cell therapy frontline is still early in development but with remarkable efficacy and safety 5. Novel approaches to achieve MRD negativity include adding fixed duration bispecific antibody therapy post induction

Audience Q&A With Panel

Open the Q&A window, allowing you to ask questions to the host and panelists. If we do not answer your questions today, please reach out to our Infoline: U.S. & Canada: 800-452 CURE (2873) Worldwide: 1-818-487-7455

Early Relapse 1. Teclistamab-Dara in early relapse (LBA-6) 2. Long term follow up cilta-cel (#94) 3. Enhancing safety of cilta-cel (#1034) 4. Elranatamab plus Iberdomide (#100) 5. Functional High Risk Definition (#1037)

Long-Term Progression-Free Survival Benefit With Ciltacabtagene Autoleucel in Standard-Risk Relapsed/Refractory Multiple Myeloma Luciano Costa1, Albert Oriol2, Dominik Dytfeld3, Salomon Manier4, Peter Voorhees5, Yi Lin6, Myo Htut7, Wilfried Roeloffzen8, Phoebe Joy Ho9, Urvi Shah10, Man Zhao11, Quanlin Li12, Agnes Balogh13, Katherine Li14, Ana Slaughter15, Nina Benachour13, Carolina Lonardi16, Arnab Ghosh17, Huabin Sun17, Nikoletta Lendvai17, Tamar Lengil17, Nitin Patel18, Mythili Koneru18, Erika Florendo18, Octavio Costa18, Vrinda Mahajan18, Paula Rodríguez-Otero19, Christopher Strouse20, A. Keith Stewart21, Surbhi Sidana22

https://www.congresshub.com/ASH2025/ Oncology/Cilta-cel/Costa The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way.

1University of Alabama at Birmingham, Birmingham, AL, United States; 2Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain;

3Poznan University of Medical Sciences, Poznań, Poland; 4University of Lille, CHU Lille, Lille, France; 5Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, United States; 6Mayo Clinic, Rochester, MN, United States; 7Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States; 8Department of Hematology, University Medical Center Groningen, Groningen, Netherlands; 9Royal Prince Alfred Hospital, Sydney, Australia; 10Myeloma Service, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, NY, United States; 11IQVIA, Shanghai, China; 12Johnson & Johnson, Apex, NC, United States; 13Johnson & Johnson, Beerse, Belgium; 14Johnson & Johnson, Spring House, PA, United States; 15Johnson & Johnson, Zug, Switzerland; 16Johnson & Johnson, Buenos Aires, Argentina; 17Johnson & Johnson, Raritan, NJ, United States; 18Legend Biotech USA Inc, Somerset, NJ, United States; 19Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain; 20Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA, United States; 21University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada; 22Stanford University School of Medicine, Stanford, CA, United States

Presented by L Costa at the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, Florida, USA

Add QR code here on slide master 2.16” x 2.16”

CARTITUDE-4: Study Design1 Screening Key inclusion criteria:

SOC arm

1:1 randomization

PVd or DPda,b

• Age ≥18 years with MM • 1–3 prior LOT (including PI + IMiD) • Lenalidomide refractory • ECOG PS ≤1 Key exclusion criteria: • Prior CAR-T or BCMA-targeting therapy

Stratified by: • Choice of PVd/DPd • ISS stage • Number of prior LOT

Bridging PVd or DPda ≥1 cycle

Day 1:

Cilta-cel infusion

(Target: 0.75 × 106 CAR+ T cells/kg)

Cilta-cel arm

Follow-up

Day 1–112: Collect safety, efficacy,c PK/PD data every 28 days

Apheresis Lymphodepletion (start of study treatment) T-cell transduction and expansion

Primary endpoint • PFSd

Secondary endpoints • Efficacy: ≥CR, ORR, MRD negativity, OS • Incidence and severity of AEs

aPhysician’s choice. bAdministered until disease progression. cEfficacy data were collected after Day 112 every 28 days. dTime from randomization to disease progression/death. AE, adverse event; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CTCAE, Common Terminology Criteria for Adverse Events; DPd, daratumumab, pomalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; IMiD, immunomodulatory drug; ISS, International Staging System; ORR, overall response rate; PD, pharmacodynamics; PI, proteasome inhibitor; PK, pharmacokinetics; PVd, pomalidomide, bortezomib, and dexamethasone. 1. San-Miguel J, et al. N Engl J Med 2023;389:335-47.

Presented by L Costa at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

Add QR code here on slide master 0.75” x 0.75“

100

CARTITUDE-4 ITT population 33.6 months median follow-up

1 1 PFSPFS

100

1 1 OSOS

Standard-risk cyto, cilta-cel

High-risk cyto, cilta-cel

Standard-risk cyto, SOC 30-month rate

20 Standard-risk cyto High-risk cyto Cilta-cel 71.0% SOC 43.2% 0.43 0 HR

High-risk cyto, SOC

Cilta-cel 52.3% SOC 17.5% HR 0.38

37 31 28 23 20 84 76 73 70 55 35 32 32 29 27 49 49 49 49 46

7 3 31 14 18 9 27 9

0 7 1 2

0 2 1 1

0 0 0 0

Standard-risk cyto, cilta-cel High-risk cyto, cilta-cel

Standard-risk cyto, SOC High-risk cyto, SOC

40 30-month rate

20 0

9 12 15 18 21 24 27 30 33 36 39 42 45 PFS, months

Patients at risk High risk, SOC 132 111 79 65 52 42 High risk, cilta-cel 123 106 102 96 92 87 Standard risk, SOC 70 58 50 47 41 36 Standard risk, cilta-cel 69 59 58 57 53 51

Patients alive, %

Patients progression free and alive, %

PFS and OS in Patients With High-Risk and Standard-Risk Cytogenetics (ITT)

Standard-risk cyto Cilta-cel 79.7% SOC 69.6% HR 0.62

High-risk cyto Cilta-cel 75.5% SOC 62.1% HR 0.54

9 12 15 18 21 24 27 30 33 36 39 42 45 OS, months

Patients at risk High risk, SOC 132 130 126 116 110 103 96 91 84 81 75 38 14 High risk, cilta-cel 123 121 115 111 105 103 102 98 95 93 83 50 23 Standard risk, SOC 70 69 62 61 57 55 54 52 49 48 48 29 18 Standard risk, cilta-cel 69 65 61 59 57 57 56 56 56 55 52 35 13

6 14 5 5

0 5 3 2

0 0 0 0

In CARTITUDE-4, cilta-cel improved PFS and OS in prespecified subgroups with standard- and high-risk cytogenetics1 Add QR code here on slide master 0.75” x 0.75“

1. Sidana S, et al. J Clin Oncol 2025;43:7539. Presented by L Costa at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

CARTITUDE-4 and CARTITUDE-1: PFS and OS in Patients With Standard-Risk Cytogenetics (As-Treated) PFS 100

71.7% 50

CARTITUDE-4 std risk + gain/amp(1q)

59.9% CARTITUDE-1 std risk [includes gain/amp(1q)]

No. at risk C-1 std risk: incl. gain/amp(1q) 68

Months 66

30-month OS

100

C-4 std risk: + gain/amp(1q) 105 103 101

Patients alive, %

Patients progression free and alive, %

30-month PFS

86.1% CARTITUDE-4 std risk

+ gain/amp(1q)

70.6% CARTITUDE-1 std risk

[includes gain/amp(1q)]

No. at risk C-1 std risk: 68 incl. gain/amp(1q)

Months 68

C-4 std risk: + gain/amp(1q) 105 103 101

Survival rates were higher when cilta-cel was used earlier in standard-risk disease Add QR code here on slide master 0.75” x 0.75“

Presented by L Costa at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

Summary of Cilta-cel Outcomes in Standard-Risk Myeloma (As-Treated Population) 30-month PFS rate, %

30-month OS rate, %

Cilta-cel

80.5

87.3

Cilta-cel

71.7

86.1

59.9

70.6

CARTITUDE-4 (median 2 prior lines) Standard-risk cytogenetics per protocol

Standard-risk cytogenetics per protocol + gain/amp(1q)

CARTITUDE-1 (median 6 prior lines) Cilta-cel

Standard-risk cytogenetics per protocol including gain/amp(1q)

Earlier use of cilta-cel in standard-risk RRMM led to higher survival rates Add QR code here on slide master 0.75” x 0.75“

Presented by L Costa at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

Enhancing the safety of ciltacabtagene autoleucel in relapsed multiple myeloma (MM): Identification of potentially modifiable risk-factors associated with delayed neurotoxicity and non-relapse mortality Surbhi Sidana*, Brett Reid*, Danai Dima*, Lauren C. Peres, Mahmoud Gaballa, Rahul Banerjee, Oren Pasvolsky, Aimaz Afrough, Christen Dillard, Christopher Ferreri, Shebli Atrash, Cindy Varga, Andrew Portuguese, Masooma Rana, Hitomi Hosoya, Lekha Mikkilineni, Vanna Hovanky, Saurabh Zanwar, Nilesh Kalariya, Damian Mikulski, Charlotte Wagner, Christopher R. Cahoon, Omar Castaneda Puglianini, Gabe De Avila, Christian Gordillo, Eli Zolotov, Jenny Bhurtel, Ariel Grajales-Cruz, Utkarsh Goel, Aishwarya Sannareddy, Jeries Kort, Rafaella Cassano, Shonali Midha, James Davis, Rebecca Gonzalez, Megan Herr, Zhuoer Xie, Hamza Hassan, Sneha Purvey, Marcus Geer, Kimberly Green, Fabiana Perna, Hien Liu, Taiga Nishihori, Jack Khouri, Shahzad Raza, Faiz Anwer, Susan Bal, Omar Nadeem, Ciara L. Freeman, Leyla Shune, Ran Reshef, Kenneth Shain, Melissa Alsina, Rachid Baz, Doug Sborov, Saurabh Dahiya, Frederick L. Locke, David Miklos, Peter Voorhees, Larry Anderson, Luciano Costa, Noa Biran, Shaji Kumar, Yi Lin*, Krina K. Patel* , Doris Hansen*

* contributed equally ASH 2025, Abstract #1034

Toxicities with Cilta-cel Early (Days/Weeks)

Delayed (Weeks/Months)

Long-term (Years)

Cytokine Release Syndrome (CRS)

Delayed neurotoxicity (Parkinsonism, cranial nerve palsy)

Second cancers

Neurotoxicity (ICANS)

IEC-Colitis

Unknown long-term effects

IEC-HS Cytopenias and infections

Study Design Population

Definitions

Analysis

•

Patients with relapsed MM receiving standard of care cilta-cel

•

Sites: 15 U.S centers

•

N=761 (May 2022 to December 2024)

•

Delayed neurotoxicity (DNT) or Non-ICANS neurotoxicity (NINT): Neurotoxicity events except ICANS including Parkinsonism, cranial nerve palsy, neuropathy, etc

•

NRM was defined as death due any cause except myeloma progression

•

Risk factors for Parkinsonism and NRM were evaluated by univariable and multivariable analysis.

•

Any NRM events occurring after disease progression were censored for analysis, except second primary malignancies Sidana et al. ASH 2025, Abstract #1034

Summary 

Non-response to bridging therapy was associated with 10x risk of Parkinsonism and a higher NRM with cilta-cel



Effective tumor debulking with bridging is critical to decrease the risk of Parkinsonism and NRM with cilta-cel



Peak ALC was significantly higher in patients who developed Parkinsonism, with peak ≥ 3000/uL associated with 12% risk of Parkinsonism.



Peak ALC ≥ 3000/uL can serve as a biomarker to identify patients for preemptive interventions and risk mitigation measures

Sidana et al. ASH 2025, Abstract #1034

100

Safety and Efficacy of Elranatamab in Combination With Iberdomide in Patients With Relapsed or Refractory Multiple Myeloma: Results from the Phase 1b MagnetisMM-30 Trial Attaya Suvannasankha,1 Jonathan L. Kaufman,2 Ashraf Badros,3 Michel Pavic,4 Hock-Choong Lai,5 Muhammad S Raza,6 Parth S Shah,7 Patrick Y. Muller,8 Jorge Acosta,8 Margaret Hoyle,9 Erik R Vandendries,10 Jay Cheng,11 Alexander Lesokhin12 1Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN, USA; 2Winship Cancer Institute, Emory University, Atlanta, GA,

USA; 3Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA; 4Centre Intégré Universitaire de Santé et de Services Sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke, Quebec, QC, Canada; 5Icon Cancer Centre Townsville, Queensland, AU; 6Dr. Everett Chalmers Hospital, Halifax, NS, Canada; 7Dartmouth Hitchcock Medical Center, Hanover, NH, USA; 8Bristol Myers Squibb, Boudry, Switzerland; 9Pfizer Inc, Milan, Italy; 10Pfizer Inc, Cambridge, MA, USA; 11Pfizer Inc, Bothell, WA, USA; 12Memorial Sloan Kettering Cancer Center, New York, NY, USA

Presented at the 67th ASH Annual Meeting and Exposition | December 6-9, 2025 | Orlando, FL

MagnetisMM-30 Study Design • MagnetisMM-30 (NCT06215118) is a phase 1b, open-label, multicenter, prospective study • Part 1 (dose escalation) primary objective was to assess the tolerability and safety of elranatamab in combination with iberdomide to determine the recommended doses of the combination for evaluation in Part 2 (randomized dose optimization) – A BOIN approach was used to guide dose escalation/de-escalation in Part 1 Patients with RRMM Key inclusion criteria • Age ≥18 years with MM per IMWG criteria • ECOG PS 0-1 • 2-4 prior LOTs, including ≥1 IMiD and ≥1 PIa • Relapsed or refractory to last LOT Key exclusion criterion • Stem cell transplant ≤12 weeks prior to enrollment or active GVHD • Ongoing grade ≥2 peripheral sensory or motor neuropathy; history of grade ≥3 peripheral motor polyneuropathy

Dose Level 2

Dose Level 1b

Primary endpoint • DLTs during DLT observation period

Elranatamab 76 mg QW + iberdomide 1.0 mg QD

Elranatamab 76 mg Q2W + iberdomide 1.3 mg QD

Dose Level –1b Elranatamab 76 mg Q2W + iberdomide 1.0 mg QD

Secondary endpoints • AEs and laboratory abnormalities • ORRc • CR ratec • Time-to-event endpointsc • PK • MRD negativity ratec • Immunogenicity

Dose Level –2 Elranatamab 76 mg Q2W + iberdomide 0.75 mg QD a All patients must have received ≥2 consecutive cycles of an IMiD-containing regimen and ≥2 consecutive cycles of a PI or PI-containing regimen; b All patients received an initial 14-day cycle of elranatamab (12 mg on day 1, 32 mg on day

4, 76 mg on day 8) without iberdomide. Iberdomide was dosed at 21 out of 28 days for subsequent cycles; c Per IMWG criteria AE=adverse event; BOIN=Bayesian Optimal Interval Design; CR rate=complete response rate; DLT=dose-limiting toxicity; ECOG PS=Eastern Cooperative Oncology Group performance status; GVHD=graft vs host disease; IMiD=immunomodulatory drug; IMWG=International Myeloma Working Group; LOT=line of therapy; MM=multiple myeloma; MRD=minimal residual disease; ORR=objective response rate; PI=proteasome inhibitor; PK=pharmacokinetics; QD=once daily; QW=once weekly; Q2W=once every 2 weeks

ORR • Overall, the confirmed ORR by investigator was 95.5% (95% CI, 77.299.9)

DL1

76 mg ELRA QW + 1.0 mg IBER 9.4 months (range, 0.7-11.3)

Median follow-upa

100%

• Responses occurred early

90%

– Median time to response was 1.4 months (range, 0.5-2.7) Patients, %

60%

≥CR: 46.2%

46.2%

40% 30%

7.8 months (range, 0.7-11.3)

ORR, 100.0% (95% CI, 66.4-100.0)

ORR, 95.5% (95% CI, 77.2-99.9)

11.1% ≥CR: 44.4%

4.5% ≥CR: 45.5%

33.3%

≥VGPR: 69.2%

50%

Overall

76 mg ELRA Q2W + 1.0 mg IBER 5.2 months (range, 4.5-6.4)

ORR, 92.3% (95% CI, 64.0-99.8)

80% 70%

DL–1

40.9% ≥VGPR: 77.3%

≥VGPR: 88.9%

23.1%

31.8%

44.4%

20% 10% 0%

23.1%

18.2%

11.1%

DL1 (n=13)

DL–1 (n=9) PR

VGPR

Overall (N=22)

sCR

a Simple median of observation times.

CR=complete response; DL=dose level; ELRA=elranatamab; IBER=iberdomide; ORR=objective response rate; PR=partial response; sCR=stringent complete response; VGPR=very good partial response

Redefining Functional High-Risk (FHR) Multiple Myeloma (MM) in the Context of Upfront Quadruplet (QUAD) Therapy and Autologous Stem Cell Transplantation (ASCT) Luciano Costa1, Susan Bal1, Kelly Godby1, Gayathri Ravi1, Eva Medvedova2, Natalie Callander3, Rebecca Silbermann2, Bhagi Dholaria4, Forest Huls5, Baylie Mullinax1, Laura Joiner1, Caitlin Hagedorn1, Binod Dhakal6. 1 University of Alabama at Birmingham, Division of Hematology and Oncology, Birmingham, AL; 2 Oregon Health Sciences University, Portland, OR; 3 University of Wisconsin, Madison, WI, United States; 4 Vanderbilt University, Nashville, TN; 5 University of Alabama at Birmingham, Department of Pathology, Birmingham, AL; 6 Medical College of Wisconsin, Milwaukee, WI.

Results

FHR12 = 2.6% FHR18 = 6.2% FHR24 = 10.1% FHR36 = 16.4% FHR36 FHR24 FHR18 FHR12

Conclusions In NDMM treated with QUAD + ASCT : FHR36 identifies a population with expected OS ~24 months= New Definition FHR36 is associated with worse response, 2PFS and OS in patients with progression after QUAD + ASCT TCRT in 2nd line is associated with improved 2PFS in patients with progression after QUAD + ASCT

Dr. Joe’s Take On Early Relapse 1. The combination of Teclistamab and Daratumumab in early relapse is remarkable and will likely be available soon - but infectious concerns must be mitigated 2. Long term outcomes with cilta-cel in standard risk are excellent with 30 month PFS 80% in early line and 60% in late line 3. Key toxicities with cilta-cel can be mitigated with bridging therapy and ALC monitoring 4. Combining Elranatamab and Iberdomide is both feasible and effective 5. The definition of Functional High Risk could reset to 36 months due to better outcomes in frontline therapy

Audience Q&A With Panel

Late Relapse 1. in vivo CAR T (LBA-1) 2. Anito-cel in relapsed MM (#256) 3. AZD0120 CAR T (#269) 4. Teclistamab-Talquetamab in EMD (#698) 5. Etentamig plus pomalidomide (#247) 5. Cevostamab post CAR T (#699)

LBA-1 MRD-negative outcomes following a novel, in vivo gene therapy generating anti-BCMA CAR-Tcells in patients with RRMM: Preliminary results from inMMyCAR, the first-in-human Phase 1 study of KLN-1010 Simon Harrison1, P. Joy Ho2, Sueh-li Lim3, Stephanie Talam2, Hannah Pahl1, Dharmesh Dingar4, Scott Currence4, Travis Quigley4, Andrew Spencer3 1Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; 2Royal Prince Alfred Hospital,

Sydney, New South Wales, Australia; 3The Alfred Hospital, Melbourne, Victoria, Australia; 4Kelonia Therapeutics, Inc., Boston, Massachusetts, United States.

Presented at the 67th ASH Annual Meeting and Exposition; December 6-9, 2025; Orlando, FL, USA.

Expanding the reach of CAR-Tcells with in vivo gene delivery1,2

In vivo CAR Twith KLN-1010 lentiviral particles

Ex vivo CAR T

Expansion

CAR-T engineering

Formulation

Release testing

Preparative chemotherapy

Eliminates preconditioning lymphodepletion Greatly simplified logistics to expand access

In vivo CAR-T generation

No ex vivo culture may increase T-cell fitness Collection of T cells

Infuse CAR-Tcells into patient

Direct infusion

Reduced cost of goods and manufacturing

CAR, chimeric antigen receptor. 1. Bot A et al. Nat Rev Drug Discov. 2025 Sep 30. doi: 10.1038/s41573-025-01291-5; 2. Najibi AJ. Tcell-specific in vivo transduction with preclinical candidate KLN-1010 generates BCMA-directed CAR-Tcells with potent anti-multiple myeloma activity (abstract #48). Poster presented at: AACR Annual Meeting; April 5-10, 2024.

Deep, ongoing MRD-negative responses were observed across first 4 patients Months post treatment 1

Patient 1

VGPR

Patient 2

MRD negative 10-6

Patient 3

MRD negative 10-5

Patient 4

*Most sensitive result from next generation flow cytometry or sequencing

Post-infusion

Soluble BCMA sBCMA (pg/mL)

sFLC (mg/L)

Post-infusion

M-spike levels M-spike (g/L)

Involved sFLC

Post-infusion

BCMA, B-cell maturation antigen; BL, baseline; CR, complete response; D, study day; M, study month; M-spike, monoclonal protein spike; MRD, minimal residual disease; PR, partial response; SCR, screening; sFLC, serum free light chain; u, unconfirmed response; VGPR,very good partial response.

Patient 1, DL1 Patient 2, DL1 Patient 3, DL1 Patient 4, DL-1

Abstract 256 Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM): Updated Results from iMMagine-1 Krina Patel, MD, MSc; Binod Dhakal, MD; Gurbakhash Kaur, MD; Richard T. Maziarz, MD; Natalie S. Callander, MD; Adam S. Sperling, MD, PhD; Carolina Schinke, MD; Andrzej J. Jakubowiak, MD, PhD; Noa Biran, MD; Douglas W. Sborov, MD, MS; Cindy Varga, MD; Larry D. Anderson, Jr., MD, PhD; Abhinav Deol, MD; Abraham S. Kanate, MD; Mehmet Hakan Kocoglu, MD; Melhem Solh, MD; Kamalika C. Banerjee, MS, MA; Krishna Rana, PharmD; Ana Kostic, MD; Enrique Granados, MD; Carolyn C. Jackson, MD, MPH; Christopher R. Heery, MD; Tim Welliver, MD, PhD; Ciara L. Freeman, MD, PhD; and Matthew J. Frigault, MD, MS

Anitocabtagene autoleucel (anito-cel/CART-ddBCMA)

Autologous BCMA-directed CAR T-cell therapy using a novel, D-Domain binder1,2 D-Domain Attributes:

Non-Antibody Derived Synthetic Protein1,2

scFv (~25 kDa)

Bivalent camelid VHH (~30 kDa)

D-Domain (~8 kDa)

Size

Small D-Domain construct facilitates high transduction efficiency and CAR positivity2-4 resulting in a low total cell dose

Structure & Stability

D-Domain CARs are stable and lack tonic signaling4,6 due to the rapid folding, lack of disulfide bonds, and hydrophobic core5,6 of the D-Domain

Binding

The D-Domain binder has a fast off-rate4 and high CAR surface expression4. This combination may allow optimal tumor cell killing without prolonged inflammation

1Rotte, et al. Immuno-Oncology Insights 2022; 3(1), 13–24; 2Frigault, et al. Blood Adv. 2023; 7(5):768-777; 3Cante-Barrett, et al. BMC Res. Notes 2016; 9:13; 4Buonato, et al. Mol. Cancer Ther. 2022; 21(7):1171-1183; 5Zhu, et al. Proc. Nat. Acad. Sci.

2003; 100(26): 15486-15491; 6Qin, et al. Mol. Ther. 2019; 27(7): 1262-1274.

Patel et al, American Society of Hematology 2025, Abstract 256

iMMagine-1: Overall Response Rate and Depth of Response Efficacy Evaluable Patients, N=117 ORR=96% 8%

 Responses continue to deepen over time

15%

 At a median follow-up of 15.9 months, IRC-assessed ORR was 96% and sCR/CR rate was 74% ≥VGPR 88%

74%

sCR/CR 74%

N=117 Best Response:

sCR/CR

VGPR

Median (months)

Interquartile Range

Min, Max

Time to first response

1.0

1.0, 1.9

0.9, 13.8

Time to best response

4.8

2.1, 9.0

0.9, 23.8

Time to sCR/CR

3.2

2.0, 9.2

0.9, 23.8

Responses are per IMWG criteria and are IRC assessed; ORR defined as partial response or better. CR, complete response; IRC, independent review committee; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response Patel et al, American Society of Hematology 2025, Abstract 256

iMMagine-1: PFS and OS Rates Estimated by Kaplan-Meier Median PFS and OS were not reached

N=117

PFS Rate (%) (95% CI)

OS Rate (%) (95% CI)

6-Month

93.1 (86.7, 96.5)

95.7 (90.0, 98.2)

12-Month

82.1 (73.6, 88.1)

94.0 (87.8, 97.1)

18-Month

67.4 (55.4, 76.8)

88.0 (78.8, 93.4)

24-Month

61.7 (48.0, 72.8)

83.0 (70.7, 90.5)

Median follow-up of 15.9 months (range: 0.3 – 33.1 months) PFS, progression-free survival; OS, overall survival Patel et al, American Society of Hematology 2025, Abstract 256

iMMagine-1: Safety Update CRS, Maximum Grade (N=117) 80 (68%)

No CRS

4-day median onset (range: 1-17 days) 2-day median duration (range: 1-9 days)

19 (16%)

17 (15%) Grade 1

ICANS, Maximum Grade (N=117)

Grade 2

0 (0%)

1 (1%)

Grade 3

Grade 4

Grade 5

7-day median onset (range: 2-9 daysa) 5-day median duration (range: 2-10 daysb)

108 (92%)

3 (3%)

5 (4%)

1 (1%)

0 (0%)

No ICANS Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

 95% (111/117) of patients had either no CRS or CRS that resolved by ≤10 days of anito-cel infusion  No new treatment-related or treatment-emergent deaths have occurred since the previous May 1, 2025 datacut  No secondary primary malignancies of T-cell origin have occurred  No replication competent lentivirus detected No delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis have been observed to date at ≥10 months since anito-cel infusion aWith the exception of n=1 Grade 1 ICANS (confusion) on day 31 post infusion that rapidly resolved. bWith the exception of n=1 max Grade 2 ICANS with 29-day duration to resolution

Note: Updates to data resulting from ongoing data review; CRS and ICANS assessed per American Society for Transplantation and Cellular Therapy criteria CRS, cytokine release syndrome; ICANS, immune-effector cell-associated neurotoxicity syndrome Patel et al, American Society of Hematology 2025, Abstract 256

P269

Safety and Efficacy of AZD0120, a BCMA/CD19 Dual-Targeting CART-cell Therapy, in Relapsed/Refractory Multiple Myeloma: Preliminary Results From the DURGA-1 Phase 1b/2 Study

Shambavi Richard, MD1, Mahmoud Gaballa, MMBCh2, Tara Gregory, MD3, Saurabh Chhabra, MD, MS4, Larry D. Anderson Jr, MD, PhD5, Luciano J. Costa, MD, PhD6, Caitlin Costello, MD7, Scott R. Goldsmith, MD8, Doris K. Hansen, MD9, Sridevi Rajeeve, MD10, Shaji Kumar, MD11, Aravind Ramakrishnan, MD12, Minoo Battiwalla, MD, MS13, Ajay K. Nooka, MD, MPH14, Hira Shaikh, MBBS15, Meiyue G. Hong, MD16, Steven Wang, MS17, Patricia Cheung, PhD18, Liang Li, PhD19, Binod Dhakal, MD20 1Icahn School of Medicine at Mount Sinai, New York, NY; 2The University of Texas MD Anderson Cancer Center, Houston, TX; 3Colorado Blood Cancer Institute, Denver, CO; 4Mayo Clinic Arizona, Phoenix, AZ; 5Hematologic Malignancies

and Cellular Therapy Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX; 6University of Alabama at Birmingham, Birmingham, AL; 7University of California San Diego Moores Cancer Center, San Diego, CA; 8City of Hope Comprehensive Cancer Center, Duarte, CA; 9Moffitt Cancer Center, Tampa, FL; 10Memorial Sloan Kettering Cancer Center, New York, NY; 11Mayo Clinic, Rochester, MN; 12Sarah Cannon Transplant and Cellular Therapy, St. David’s South Austin Medical Center, Austin, TX; 13Sarah Cannon Transplant and Cell Therapy Network, Nashville, TN; 14Winship Cancer Institute of Emory University, Atlanta, GA; 15University of Iowa Hospital & Clinic, Iowa City, IA; 16AstraZeneca, Boston, MA; 17AstraZeneca, Mississauga, Canada; 18AstraZeneca, South San Francisco, CA; 19AstraZeneca, Gaithersburg, MD; 20Medical College of Wisconsin, Milwaukee, WI

Presented at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, Florida

AZD0120: A Novel BCMA/CD19 Dual CART Dual Target

Next-Generation Manufacturing

BCMA/CD19 Dual CAR T

Faster to Patients Manufactured in

a-CD19 BCMA

a-BCMA CD19

CD19 (low expression)

\ MM cell

<3 days

Better T Cells Younger, fitter naive T cells Safety profile enabling outpatient administration and monitoring

Making cell therapy available to more patients

MM progenitor

AZD0120 was formerly named GC012F, and next-generation manufacturing refers to the FasTCARplatform. BCMA, B-cell maturation antigen; CART, chimeric antigen receptor T-cell therapy; MM, multiple myeloma.

CRSand ICANS DL1 (n=12)

DL2 (n=14)

ICANS, overall

1 (7%)

15 (58%)

Grade 1

1 (7%)

1 (4%)

Grade 2

Grade 3+

Onset time, median (range), days

9 (2–11)

9 (8–10)

9 (2–11)*

Onset time, days

Duration, median (range), days

1 (1–4)

2 (1–2)

1.5 (1–4)

Duration, day

Tocilizumab

7 (58%)

5 (36%)

12 (46%)

Dexamethasone

1 (8%)

2 (14%)

3 (12%)

1 (7%)

1 (4%)

CRS

DL1 (n=12) DL2 (n=14) Total (n=26)

ICANS

CRS,overall

9 (75%)

7 (50%)

16 (62%)

Grade 1

9 (75%)

6 (43%)

Grade 2

Grade 3+

CRSmanagement

Anakinra

•

No grade 3+ CRSreported

•

*CRS onset on day 8–11 for 15 of 16 patients

•

No delayed neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome reported

•

No IEC-associated colitis reported

•

Only one grade 1 ICANS event

•

One patient with IEC-HS(DL1, grade 2); resolved within 7 days

CRS, cytokine release syndrome; DL, dose level; IEC, immune effector cell; IEC-HS, immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome; ICANS, immune effector cell–associated neurotoxicity syndrome; NA, not applicable.

Efficacy: 96% ORR, 78% CR 100

ORRa: 96%

• Median follow-up time = 3.9 months • Median time to first response = 28 days

80 %of Patients

• Responses deepened over time 60

78.3%

Total (n=23)

BCMACAR T Exposed (n=5)

ORR

96%

100%

sCR/CR

78%

80%

3.9 (0.9–19.7)

3.9 (3.0–4.0)

20 17.4% 0

Total (n=23) sCR/CR

Follow-up, median (range), months

Efficacy-evaluable population defined as all patients who received conformed AZD0120 infusion at the targeted DL with measurable disease at baseline and at least one post-baseline efficacy assessment. aResponse as assessed by study investigator using IMWG criteria. BCMA, B-cell maturation antigen; CART, chimeric antigen receptor T-cell therapy; CR, complete response; DL, dose level; IMWG, International Myeloma Working Group; ORR, objective response rate; PR, partial response; sCR, stringent complete response.

Efficacy and Safety of Talquetamab + Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma and Extramedullary Disease: Updated Phase 2 Results From the RedirecTT-1 Study With Extended Follow-Up Saad Z Usmani1*, Shaji Kumar2*, María-Victoria Mateos3, Jing Christine Ye4, Shebli Atrash5, Hila Magen6, Hang Quach7, Michael P Chu8, Suzanne Trudel9, Joshua Richter10, Paula Rodríguez-Otero11, Hun Chuah12, Moshe Gatt13, Eva Medvedova14, Shahzad Raza15, Dok Hyun Yoon16, Tadao Ishida17, Jeffrey V Matous18, Laura Rosiñol19, Koichi Onodera20, Carmela Maffucci21, Emma Scott22, Christoph Heuck22, Jenny Zhang22, Todd Henninger21, Lisa O’Rourke22, Payal Thakkar21, Mariacristina Festa23, Guoqiang Zhang22, Sheetal Khedkar24, Lin Huang22, Jiangxiu Zhou22, Mikihiro Takamoto25, Lixia Pei21, Jiashen Lu26, Nicholas Au22, Maria Krevvata22, Yael C Cohen27

https://www.congresshub.com/ASH2025/ Oncology/Talquetamab/Usmani The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way.

1Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Mayo Clinic Rochester, Rochester, MN, USA; 3University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain;

4MD Anderson Cancer Center, University of Texas, Houston, TX, USA; 5Levine Cancer Institute-Atrium Health, Charlotte, NC, USA; 6Chaim Sheba Medical Center, Ramat-Gan, Faculty of Medical and Health Sciences,

Tel Aviv University, Tel Aviv, Israel; 7University of Melbourne, St Vincent’s Hospital, Melbourne, VIC, Australia; 8Alberta Health Services, Edmonton, AB, Canada; 9Princess Margaret Cancer Centre, Toronto, ON, Canada;

10Mount Sinai Medical Center, New York, NY, USA; 11Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain; 12Royal Perth Hospital, Perth, WA, Australia; 13Hadassah Medical Cener, Hebrew University of

Jerusalem, Jerusalem, Israel; 14Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; 15Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA; 16Asan Medical Center, University of

Ulsan College of Medicine, Seoul, Republic of Korea; 17Japanese Red Cross Medical Center, Tokyo, Japan; 18Colorado Blood Cancer Institute and Sarah Cannon Research Institute, Denver, CO, USA; 19Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain; 20Tohoku University Hospital, Sendai shi, Miyagi, Japan; 21Johnson & Johnson, Raritan, NJ, USA; 22Johnson & Johnson, Spring House, PA, USA; 23Johnson & Johnson, Leiden, Netherlands; 24Johnson & Johnson, Horsham, PA, USA; 25Johnson & Johnson, Tokyo, Japan; 26Johnson & Johnson, Shanghai, China; 27Tel Aviv Sourasky (Ichilov) Medical Center, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel *Contributed equally.

Presented by S Usmani at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, Florida, USA

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RedirecTT-1 Phase 2 EMD (Tal + Tec): Largest Dedicated Study in Patients With True EMD Screening

Treatment

Endpoints

Eligibility criteria • Triple-class exposed RRMMa • True EMD, defined as ≥1 nonradiated bone-independent soft tissue plasmacytoma ≥2 cm in greatest dimension confirmed by central review of PET-CT scansb,c • Prior CAR-T and non-BCMA/GPRC5D bispecific antibody therapies were permitted • Nonsecretory and oligosecretory disease were permitted

Tal 0.8 mg/kg Q2W SCd,e + Tec 3.0 mg/kg Q2W SCd,e

Primary endpoint: ORRf

Option to switch to monthly dosing after 4 cycles and ≥VGPR, or after 6 cycles (irrespective of response)

Secondary endpoints: • DORf • PFSf • OS • Safety

Step-up dosingd 2–4 days apart (Tal + Tec) SUD1: 0.01 mg/kg + 0.06 mg/kg SUD2: 0.06 mg/kg + 0.3 mg/kg SUD3: 0.4 mg/kg + 1.5 mg/kg

aIncludes prior exposure to a proteasome inhibitor, immunomodulatory drug, anti-CD38 monoclonal antibody. bPatients may have had paramedullary plasmacytomas in addition to true EMD. cWhole-body MRI permitted with sponsor approval. dTal and Tec administered on the same day, 30 (±10) minutes apart, for all step-up and full treatment doses. eUntil disease progression. fResponse and PFS were assessed by an independent review committee per IMWG criteria; EMD response was assessed by PET-CT or MRI whole-body scans. CAR, chimeric antigen receptor; DOR, duration of response; MRI, magnetic resonance imaging; PET-CT, positron emission tomography–computed tomography; Q2W, every other week; SC, subcutaneous; SUD, step-up dose; VGPR, very good partial response. Kumar S, et al. N Engl J Med 2025; doi:10.1056/NEJMoa2514752.

Presented by S Usmani at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

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RedirecTT-1 Phase 2 EMD (Tal + Tec): Deep, Durable Responses at 16.8 Months Median Follow-up

80 60

79% (69–87) ≥CR: 53%

40 9 20 0

17 9 Tal + Tec (N=90)

62.1%

sCR CR VGPR PR

Median (range) time to: • First response, 2.6 (1.0–5.8) months • Best response, 5.1 (1.0–16.6) months

Patients, % (95% CI)

ORR (95% CI), %a,b

100

DOR

100

(49.0–72.7) 60

Patients at risk

Median DOR (95% CI)c: NR (11.5–NE) 0

9 10 11 12 13 14 15 16 17 18 19 20 21 22 DOR, months

71 69 69 62 62 57 52 51 50 44 40 39 29 24 22 17 12

With additional ~4 months of median follow-up, ORR approached 80%; 62% of responders remained in response at 1 year Data cut-off date: July 18, 2025. aORR was assessed by independent review committee per IMWG criteria. bDue to rounding, individual response rates may not sum to the ORR. cAt time of data cut-off, 43 (60.6%) patients were censored. NE, not estimable; NR, not reached; sCR, stringent complete response. Presented by S Usmani at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

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RedirecTT-1 Phase 2 EMD (Tal + Tec): PFS and OS at 16.8 Months Median Follow-up 100

PFS 57.5%

(46.4–67.1) 60

Patients at risk

(63.3–81.8)

Median (95% CI) PFSa: 15.0 (10.3–NE)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 PFS, months 90 83 79 72 68 65 64 61 54 52 52 47 45 42 38 32 23 21 14 8

73.8%

80 Patients, % (95% CI)

Patients. % (95% CI)

100

Patients at risk

Median (95% CI) OSb: NR (19.7–NE) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 OS, months 90 84 82 80 80 80 80 76 74 70 68 64 59 58 51 45 34 27 22 16 8

With over 1 year of median follow-up, median PFS was 15 months and median OS was not reached Data cut-off date: July 18, 2025. aAt time of data cut-off, 45 (50.0%) patients were censored for PFS. bAt time of data cut-off, 59 (65.6%) patients were censored for OS. Presented by S Usmani at the 67th American Society of Hematology (ASH) Annual Meeting; December 6–9, 2025; Orlando, FL, USA

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247

Etentamig Plus Pomalidomide-Dexamethasone Combination Therapy in Relapsed or Refractory Multiple Myeloma: 1b Dose-Escalation and Safety Title AofPhase Presentation, Title Case Expansion Study Peter Voorhees1, Anita D’Souza2, Hang Quach3, Sabine Gaerditz4, Estrella Carrillo Cruz5, Michał Mielnik6, Tomasz Wrobel7, Matthew J. Pianko8, Dickran Kazandjian9, M Hasib Sidiqi10, Valerio De Stefano11, Cesar Rodriguez12, Shonali Midha13, Ariel F. Grajales-Cruz14, Hideki Goto15, Satoshi Ito16, Claudio Cerchione17, Ziyi Jin18, Shane Lee18, Akshanth R. Polepally18, Sneha Rathi18, Ross La Motte-Mohs18, Kristin D’Amico18, Thomas Doerr18, Chetasi Talati18, Leanne Lash Fleming18, Linda Ho18, Katja Weisel19, Marek Hus6, Joaquin Martinez Lopez20 1Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, USA; 2Division of Hematology/Oncology, Department of Medicine, Froedtert &

Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA; 3St Vincent’s Hospital Melbourne, University of Melbourne, Melbourne, Vic, Australia; 4Department of Hematology and Oncology, University Hospital of Regensburg, Regensburg, Germany; 5Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS)/CSIC, Universidad de Sevilla, Sevilla, Spain; 6Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 7Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland; 8Division of Hematology/Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; 9Myeloma Division, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; 10Fiona Stanley Hospital, Perth, WA, Australia; 11Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; 12Division of Hematology-Oncology, Department of Internal Medicine, Mount Sinai, New York, NY, USA; 13Division of Myeloma, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 14Malignant Hematology, Myeloma Section, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 15Department of Hematology, Hokkaido University Hospital, Sapporo, Japan; 16Department of Hematology, Yamagata University Hospital, Yamagata, Japan; 17IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola (FC), Italy; 18AbbVie Inc., North Chicago, IL, USA; 19Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 20Hospital Universitario 12 de Octubre, University Complutense, CIBER-ONC CB16/12/00369, CNIO, Madrid, Spain, Spain.

Presented at the 2025 67th American Society of Hematology (ASH) Annual Meeting, December 6–9, 2025; Orlando, FL, United States of America [DV-017508]

Etentamig is a next-generation differentiated BCMA x CD3 bispecific T-cell engager Long-term results from 2 ongoing Phase 1 studies (NCT03933735/NCT05650632) of Etentamig in heavily pretreated patients with RRMM demonstrate1,2: • 30% overall CRS rate • Grade 1: 26% • Grade 2: 4% • No Grade 3+ events • Deep and durable responses with 66% ORR • Convenient treatment schedule, including Q4W dosing Preclinical data demonstrate enhanced Etentamig activity when used in combination with antimyeloma regimens, including IMiD agents3,4

Bivalent BCMA-Binding Domain With High Avidity to Promote T-Cell Mediated Killing and Activation5

Silenced Fc Tail for Extended HalfLife Enabling Convenient (Q4W) Dosing5

Low-Affinity CD3-Binding Domain Potentially Reducing CRS5 Clinical correlation of the molecular properties is under ongoing investigation

Here we present data on Etentamig in combination with Pom + dex from Arm A (safety and efficacy) and Arm E (safety) of the Kilimanjaro study (NCT05259839) in patients with RRMM BCMA, B-cell maturation antigen; CRS, cytokine release syndrome; dex, dexamethasone; IMiD, immunomodulatory drug; ORR, overall response rate; Pom, pomalidomide; Q4W, every 4 weeks; RRMM, relapsed or refractory multiple myeloma. 1. Baljevic M, et al. J Clin Oncol. 2024;43(16_suppl):7527. 2. Baljević M, et al. Presented at: EHA2025 Congress; June 13, 2025. Poster number: PF722. 3. Meermeier E, et al. Cancer Res. 2020;80(16_Suppl):5630. 4. Cho SF, et al. Blood Adv. 2020;4(17):4195 –4207. 5. D'Souza A, et al. J Clin Oncol. 2022;40(31):3576–3586.

Arm A: Etentamig combined with Pom + dex led to deep responses in heavily pretreated RRMM patient population Proportion of patients (%)

100 80

≥CRa: 57%

40 20 0

ORR: 83%

ORR: 81%

≥VGPRb:

69%

7 12 12

20 mg (n=42)

MRD-neg <10−5: 75% (15/20)

75%

VGPR CR

≥CRa: 55%

MRD-neg <10−5: 73% (11/15)

18 ≥VGPRb:

ORR: 82%

20 8

40 mg (n=40)

sCR ≥CRa: 56%

≥VGPRb:

72%

20 mg + 40 mg (n=82)

Arm A: Etentamig + Pom + dex Months (range)

20 mg (n=44)

40 mg (n=41)

20 mg + 40 mg (N=85)

Median follow up

27 (1–33)

19 (1–26)

23 (1–33)

Median time to first responsec

1 (1–19)

1 (1–9)

1 (1–19)

Median time to CR

7.0 (3, 21)

6 (3, 16)

7 (3, 21)

Responses in the 40 mg cohort may deepen further with continued follow-up a≥CR: sCR+CR. b≥VPGR: VGPR+CR+sCR. cTime to response is the time from the date of first dose to the date of first documented PR or better determined by 2016 IMWG criteria. CR, complete response; dex,

dexamethasone; IMWG, International Myeloma Working Group; MRD, minimal residual disease; ORR, overall response rate; Pom, pomalidomide; PR, partial response; RRMM, relapsed or refractory multiple myeloma; sCR, stringent complete response; VGPR, very good partial response. Data cutoff: September 3, 2025

Dr. Joe’s Take On Late Relapse 1. in vivo CAR T holds promise for effective CAR T therapy more easily and safely delivered in MM 2. Anitocel and AZD0120 are novel CAR T products with high efficacy and lower risk of neurological toxicities 3. The combination of teclistamab and talquetamab is very potent in EMD 4. Etentamig is a novel bispecific antibody that may be delivered more easily in the clinic

The Evolution of Myeloma Therapy – MORE to come!

Now

VTD VRD KRD D-VMP DRD D-VRD SCT +/- More induction D-KRD Isa-KRD Front line treatment

Induction

New

Belantamab or Bispecifics?

Bortezomib Panobinostat Lenalidomide Daratumumab Carfilzomib Ixazomib Pomalidomide Elotuzumab Lenalidomide Selinexor Isatuximab Bortezomib Idecabtagene autoleucel Ixazomib Ciltacabtagene autoleucel Lenalidomide + PI Teclistamab Talquetamab Carfilzomib Elranatamab Linvoseltamab Dara + Lenalidomide Belantamab Combinations Maintenance

Consolidation

Post consolidation

CAR T or Bispecifics?

Iberdomide, Belanatamab or Bispecifics?

ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib. Speaker’s own opinions.

Relapsed

Rescue

Novel CAR T Cell Therapies Bispecific/Trispecific Antibodies Iberdomide and Mezigdomide Venetoclax/Sonrotoclax for t(11;14)? Multiple small molecules ++++++++

Thank you to our speakers & our sponsors!

IMF Core Values:

These are the core values we bring to accomplishing our mission each day. Patient Centric The patient experience is the focus of everything we do. Every interaction is an opportunity to establish a personal connection built on care and compassion which is the basis for continued support. Respect All As a team, we value honesty and transparency while creating a culture of mutual respect. We foster a myeloma community built on sincerity, authenticity, and kindness. Excellence and Innovation We value accountability, personal responsibility, and a steadfast commitment to excellence. We respect the legacy and reputation of our organization while seeking new solutions and advancements to improve outcomes, quality of life, and access to the best available resources for everyone impacted by myeloma. Honor differences We recognize each team member's skills and talents through collaboration and cooperation. Our programs aim to celebrate and support the diversity of our patients and their communities. 75

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