durcabtagene autoleucel (PHE885) / Novartis - LARVOL DELTA

EVALUATION OF COGNITIVE IMPAIRMENT AND NEUROTOXIC EFFECTS IN ADULT PATIENTS UNDERGOING CAR-T CELL THERAPY (EBMT 2025) - "Axicabtagene Ciloleucel was infused to 20 patients, Brexucabtagene Autoleucel to 4 patients, Tisagenlecleucel to 2 patients, Cilta-cel to 2 patients and PHE 885 to 2 patients according to disease indications. The lowest scores were identified 3 months after infusion irrespective of disease response or severe toxicities, indicating that further long-term studies are needed in this population."

CAR T-Cell Therapy • Clinical • Alzheimer's Disease • Cognitive Disorders • Hematological Malignancies • Oncology

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=147 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Feb 2025 ➔ Jun 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Prolonged Persistence and Functional Activity of Anti-BCMA CAR-T Durcabtagene Autoleucel (PHE885) Manufactured Using the T-Charge™ Platform (ASH 2024) - P1 | "In summary, BCMA CAR-T cells manufactured using the T-Charge process exhibit robust expansion in vivo and long-term polyclonal persistence for >6 months in 48% of patients. Long-term persisting CAR-T cells remain functionally active against BCMA expressing target cells in vivo and in vitro, and the IL-7/IL-7R pathway appears to have an important role in promoting long-term persistence of memory CD4+ CAR-T cells."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8 • IL15 • IL7 • IL7R

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=146 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ Feb 2025 | Trial primary completion date: Dec 2025 ➔ Feb 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Durcabtagene Autoleucel Yields High Response Rates in R/R Myeloma (OncLive) - P2 | N=146 | NCT05172596| Sponsor: Novartis Pharmaceuticals | "The BCMA-directed CAR T-cell therapy durcabtagene autoleucel (PHE885) generated responses, including high minimal residual disease (MRD)–negative responses, with a tolerable safety profile in patients with relapsed/refractory multiple myeloma, according to interim findings from a phase 2 trial...shared at the 21st International Myeloma Society Annual Meeting....In 94 patients who received 10 x 106 CAR T cells, the overall response rate (ORR) was 89% as assessed by independent review committee (IRC), including 61% of patients with a stringent complete response (sCR)/CR, 20% with a very good partial response (VGPR), and 9% with a partial response (PR). These results met the primary end point of the study. Additionally, 10% of patients were classified as having an unknown response."

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Interim phase 2 study results of durcabtagene autoleucel (PHE885), a T-Charge™ manufactured BCMA-directed CAR-T cell therapy in patients (pts) with r/r multiple myeloma (RRMM) (IMW 2024) - P2 | "T-Charge™-manufactured PHE885 produces high response rates with a manageable safety profile in RRMM. Efficacy thus far has appeared comparable between doses, with a trend toward better safety at the 5e6 dose. Longer follow-up is needed to fully assess durability and response rates as late conversions to CR/sCR have been observed."

CAR T-Cell Therapy • Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

SOLUBLE BCMA AND BCMA-CONTENT IN CIRCULATING EXTRACELLULAR VESICLES TO EVALUATE RESPONSE IN MULTIPLE MYELOMA RECEIVING BCMA-DIRECTED CARTS (EHA 2024) - " Nineteen RRMM patients received different anti-BCMA CART products (PHE885, ARI0002h, Ide-cel and Cilta-cel) in clinical trials conducted at the University Hospital of Salamanca. Overall, median sBCMA levels reached minimum values at day +100 after CAR-T infusion and increased at thetime of progression. sBCMA levels before lymphodepletion and CAR-T infusion may be predictable of early/lateprogression. In addition, most patients showed dynamics of sBCMA similar to those of EV-BCMA."

Hematological Malignancies • Multiple Myeloma • Oncology

THE DIVERSITY AND COMPOSITION OF THE T CELL REARRANGEMENT REPERTOIRE IS ASSOCIATED WITH PROGNOSIS IN MULTIPLE MYELOMA PATIENTS TREATED WITH CAR-T CELL THERAPIES (EHA 2024) - " Nineteen patients treated with four different CAR-T products (ARI0002h, PHE885, ide-cel and cilta-cel) wererecruited. Two main features may be associated with inferior responses and progression: presence of low-diversityrepertoires at screening (before apheresis), most probably as a result of a degenerated immune system, and astatic TRB profile over time, probably a consequence of ineffective CAR-T cell expansion."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=136 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=136 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma (clinicaltrials.gov) - P1 | N=96 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

T-Charge™ Manufacturing of the Anti-BCMA CAR-T, Durcabtagene Autoleucel (PHE885), Promotes Expansion and Persistence of CAR-T Cells with High TCR Repertoire Diversity (ASH 2023) - P1 | "Our findings demonstrate that the T-Charge™ manufacturing platform successfully maintains highly heterogeneous transduced Tscm clones with self-renewal potential in durcabtagene autoleucel products. Maintenance of Tscm in manufactured products contributes to robust CAR-T expansion and long-term persistence of CAR-T cells with a highly diverse TCR repertoire after infusion."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8

CAR-T: PRESENT AND FUTURE (SIE 2023) - P1 | "Conventional therapy yields unsatisfactory results in patients with refractory triple-class (IMiDs, PIs, anti-CD38 mAbs) and penta-drug (lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab) multiple myeloma (R/R MM)1...Two BCMA-directed CAR-T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved by the FDA and EMA for patients with R/R MM after at least four prior lines of therapy.2 In the phase 2 KarMMA trial, 128 R/R MM infused with ide-cel obtained complete response (CR) in 33% of patients and a median progression-free survival (PFS) of 8.8 months...All grade CRS and neurotoxic events were observed in 76.1% and 4.5% of the patients infused with cilta—cel, respectively.7 (Table 1) Those impressive results on PFS and CR were confirmed also in reallife experiences.8-10 Novel CAR-T products are under investigations: PHE885 CAR-T cells, based on T-Charge, a rapid manufacturing platform for BCMAtargeted..."

Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology

PHE885 CAR T Cells Show Expansion and Persistence in Multiple Myeloma (Targeted Oncology) - P1 | N=96 | NCT04318327 | Sponsor: Novartis Pharmaceuticals | "Durcabtagene autoleucel (PHE885) chimeric antigen receptor (CAR) T cells were produced in under 2 days, showed response, and demonstrated rapid expansion in vivo and long-term persistence in patients with relapsed/refractory multiple myeloma, according to data presented at the International Myeloma Society 20th Annual Meeting and Exposition....All patients responded except for 1 patient who received the lowest dose level, for an overall response rate of 97% including a stringent complete response rate of 38.7%, very good partial response rate of 38.7%, and partial response rate of 19.4%."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Robust in vivo expansion and long-term persistence of anti-BCMA CAR T cells, PHE885, manufactured in <2 days on the T-Charge platform (IMW 2023) - P1 | "The T-charge rapid manufacturing platform successfully preserved TSCM clones in the FP leading to a highly heterogeneous and proliferative CAR-T expansion with durable persistence."

CAR T-Cell Therapy • Preclinical • Oncology • IFNG • IL6 • TNFA

Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM). (ASCO 2023) - P1 | "Pts received fludarabine and cyclophosphamide (or bendamustine) for lymphodepletion (LD) prior to PHE885 infusion. T-Charge manufactured PHE885 produced high response rates with no unexpected safety findings in heavily pretreated RRMM pts with aggressive disease. PHE885 expanded rapidly and showed durable persistence in vivo. Since conversion to CR/sCR has occurred as late as 18 months after infusion in this study, longer follow-up is ongoing to identify a recommended dose for future development."

CAR T-Cell Therapy • Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

"#ASCO23 The New T-Charged CAR on the Block: PHE885 #mmsm https://t.co/YYc6QbDyCx" (@MyelomaTeacher)

Hematological Malignancies • Multiple Myeloma

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=136 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Dec 2023 ➔ Dec 2025

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=56 ➔ 96 | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

CAR T-Cell Therapy • Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Identification and Development of PHE885: A Novel and Highly Potent Fully Human Anti-BCMA CAR-T Manufactured with a Novel T-ChargeTM Platform for the Treatment of Multiple Myeloma (ASH 2021) - P1 | "In addition to its unique phenotype, PHE885 secretes up to 25 fold more target specific IL-2 and ~7 fold more IFN gamma in vitro , when comparing to the TM products either using the same lentiviral vector (TM_PHE885) or a clinically validated anti-BCMA vector (MCM998) . Based on these results, a Phase 1, open-label trial assessing PHE885 in patients with r/r MM (NCT04318327) was initiated. Initial data from the dose escalation portion of the Phase 1 study will be presented separately."

IO biomarker • Graft versus Host Disease • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Multiple Myeloma • Oncology • CCR7 • IFNG • IL2RA • TNFRSF9

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=136 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2025 ➔ Dec 2025 | Trial primary completion date: Aug 2023 ➔ Dec 2023

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Phase I Study of PHE885, a Fully Human BCMA-Directed CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma Manufactured in <2 Days Using the T-ChargeTM Platform (ASH 2021) - P1 | "Pts received fludarabine and cyclophosphamide for lymphodepletion prior to a single PHE885 intravenous injection...All pts received at least 1 dose each of steroids and tocilizumab; 3 pts received anakinra to manage CRS...The trial is ongoing and updated data will be presented at the annual meeting. Clinical trial information: NCT04318327"

CAR T-Cell Therapy • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

PHASE I STUDY DATA UPDATE OF PHE885, A FULLY HUMAN BCMA-DIRECTED CAR-T CELL THERAPY MANUFACTURED USING THE T-CHARGETM PLATFORM FOR PATIENTS WITH RELAPSED/REFRACTORY (R/R) MULTIPLE MYELOMA (MM) (EHA 2022) - P1 | "Pts received fludarabine and cyclophosphamide for lymphodepletion prior to a single PHE885 intravenous injection...Tocilizumab (n=13, 87%), steroids (n=11, 73%), anakinra (n=4, 27%), and pressors (n=3, 20%) were used to manage CRS...Conclusion Low doses of PHE885 manufactured by T-Charge TM in <2 d have a manageable safety profile and encouraging clinical activity in pts with r/r MM. PHE885 expands rapidly in vivo, persists for prolonged periods, and demonstrates a relatively naive T-cell phenotype."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

TRIAL-IN-PROGRESS: PHASE II STUDY OF PHE885, A B-CELL MATURATION ANTIGEN-DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN ADULTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (EHA 2022) - P2 | "Conclusion This Phase II trial of PHE885 will help further determine efficacy and safety outcomes in pts with r/r MM who failed ≥3 prior lines of therapy. The trial will be initiated in February 2022 and is estimated to treat 100 pts across 40 trial sites."

CAR T-Cell Therapy • Clinical • P2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

BCMA-directed CAR-T Cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2024 ➔ Mar 2025 | Trial primary completion date: Oct 2024 ➔ Mar 2025

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology