NXC-201 / Immix Biopharma - LARVOL DELTA

2025 Update of Cellular Immunotherapy for Plasma Cell Disorders. (PubMed, Turk J Haematol) - "Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM based on the Phase 2 KarMMa and CARTITUDE trials, respectively...Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in-vivo proliferation capability, are regarded as very efficacious...The development of academic CAR-Ts such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness...To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized..."

Journal • Amyloidosis • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • SLAMF7

High Rate of Cytokine Release Syndrome-Related Coagulopathy with Low Incidence of Bleeding and Thrombosis in Patients Treated with B-Cell Maturation Antigen (BCMA)-Targeted Chimeric Antigen Receptor T-Cells (CAR-T). (PubMed, Cancers (Basel)) - P1 | " We conducted a prospective analysis of 108 adult patients with multiple myeloma or light chain amyloidosis treated with the academic anti-BCMA CAR-T HBI0101 in a single-center trial (NCT04720313)...Laboratory markers, tocilizumab and blood product use, and thrombotic and bleeding complications were recorded. Patients received a short (3-day) or extended course of enoxaparin thromboprophylaxis as well as fresh frozen plasma in cases of severe coagulopathy... CRS-related coagulopathy is common following BCMA-targeted CAR-T treatment and correlates closely with CRS severity. Despite the high rate of laboratory coagulopathy, thrombosis and bleeding events were infrequent, suggesting the benefit of the prophylactic strategies used."

IO biomarker • Journal • Cardiovascular • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombosis

Talquetamab induces deep responses in heavily pre-treated patients with systemic light-chain amyloidosis (ASH 2025) - "All were refractory to daratumumab, bortezomib, cyclophosphamide, and pomalidomide; four were refractory to lenalidomide and belantamab mafodotin; one patient with t(11; 14) was refractory to venetoclax. Three relapsed after anti-BCMA academic CAR-T (HBI0101). Additional therapies included ixazomib (2), carfilzomib (1), elotuzumab (1), and melphalan (1)... Talquetamab produced deep and durable hematologic responses in heavily pretreated patients with R/R AL amyloidosis. Assessment of organ response potential was limited by irreversible organ dysfunction at baseline and short follow-up. Treatment was feasible, including in end-stage renal disease, and the safety profile was manageable without unexpected toxicities."

Clinical • Amyloidosis • Cardiovascular • Congestive Heart Failure • Dental Disorders • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Renal Disease • Septic Shock • Thrombocytopenia • Xerostomia

Prospective predictors of toxicity of BCMA‑directed CART therapy in multiple myeloma (ASH 2025) - P1 | "While risk factors forthese toxicities are established in lymphoma, often reflecting high tumor burden and pro-inflammatorystatus, their relevance in MM is unclear, and current evidence is largely limited to retrospective series.Identifying MM-specific predictors may inform patient selection, mitigate toxicity, and aid next-generationCART design.We included all patients with R/R MM enrolled in the NCT04720313 phase 1a/b study using the academicanti‑BCMA CART product HBI0101 who received the target dose of 800×10⁶ CART cells. ECOG >0, older age, anemia, and high involved FLC levels predicted severe inflammatory toxicities afteranti‑BCMA CART. Prior anti‑BCMA therapy (mostly belantamab mafodotin in our cohort) appearedprotective, an observation that may reflect differences in immune milieu or CART expansion kinetics andwarrants further investigation. These predictors outperformed the CAR‑HEMATOTOX score, and appearto have some similarities to what is known in..."

Clinical • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Rare Diseases • B2M • CD4 • CD8

First 20-patient safety and efficacy data from nexicart-2, the first u.S. trial of CAR-T in R/R light chain (AL) amyloidosis, nxc-201 (ASH 2025) - P1/2 | "Pts must have been exposed to bortezomib and anti-CD-38 antibodywith persistent or relapsed disease with measurable disease (dFLC >5mg/dl or dFLC >2mg/dl withabnormal k:l ratio, or serum M-spike >0.5g/dl). Lymphodepletion was with fludarabine andcyclophosphamide... In this first 20-patient reported U.S. CAR-T clinical trial experience in RR AL Amyloidosis, wedemonstrate that NXC-201 can be given safely and resulted in rapid and deep hematologic responses inall pts treated. Our data suggests that the novel anti-BCMA CAR-T NXC-201 may become a valuabletreatment option for RR AL pts."

Clinical • IO biomarker • Amyloidosis • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Febrile Neutropenia • Heart Failure • Hematological Disorders • Infectious Disease • Inflammation • Nephrology • Neutropenia • Renal Disease

Summary analysis of the phase 1a/b study with HBI0101, an academic anti-BCMA chimeric antigen receptor T-cell (CART) for relapsed/refractory multiple myeloma (ASH 2025) - P1 | "HBI0101 anti-BCMA CART results demonstrate high efficacy and safety in a more difficult-to-treat population as compared with the registrational studies with commercial products. These data notonly support further utilization of HBI0101 CART therapy, but also demonstrate the feasibility of CARTproduction in an academic setting, ensuring a sufficient CART supply in light of the increasing demand.This study completed enrollment in February 2025, and was immediately followed by a phase 2 study,including R/R MM and AL amyloidosis patients at earlier stages."

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

BCMA-targeted CAR T-cell therapy in refractory autoimmune diseases: Initial Results from a Phase 1 clinical trial (ASH 2025) - "We conducted a phase 1, open-label, single-centertrial to evaluate the safety and preliminary efficacy of BCMA-targeted CAR T-cell therapy (HBI0101) inpatients with severe, treatment-refractory autoimmune diseases. HBI0101 is an autologous BCMA-targeted CAR T-cell product generated via retroviraltransduction of patient-derived T cells...Tocilizumab was administered to 4 patients, with high dose corticosteroidsneeded in one patient... BCMA-targeted CAR T-cell therapy demonstrated a favorable safety profile in this early-phase trial, with no dose-limiting toxicities or unexpected adverse events. No intervention from the DataSafety Monitoring Board was required. Among four patients with adequate follow-up, all showed signs ofsignificant clinical improvement across diverse autoimmune phenotypes."

CAR T-Cell Therapy • Clinical • P1 data • Amyloidosis • Fibrosis • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Multiple Myeloma • Myositis • Nephrology • Neutropenia • Renal Disease • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

At ASH 2025 Oral Presentation, Immix Biopharma Reports Positive Phase 2 NXC-201 Results, Advancing Toward BLA Submission as a Potentially First- and Best-in-Class Therapy for relapsed/refractory AL Amyloidosis (GlobeNewswire) - "After NXC-201 treatment, complete responses (CRs) were observed in 75% (15 out of 20 patients) (at s/u IFE(-) level) by independent review committee. In four out of five pending patients, minimum residual disease (MRD) negativity in bone marrow predicts future complete response, potentially increasing the future CR rate to 95%. Downstream clinical improvement, including organ responses, were observed in 70% of evaluable patients (7/10)....NEXICART-2 final readout and BLA submission are planned for 2026."

FDA filing • P2 data • Amyloidosis

Safety and Efficacy of a Locally Produced Novel Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) (HBI0101) for the Treatment of Relapsed and Refractory Multiple Myeloma (ASH 2023) - P1 | "BACKGROUND: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM), with recent phase 3 studies showing clear advantage of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) over standard-of-care...Lymphodepletion included fludarabine 25mg/m2 and cyclophosphamide 250mg/m2 on days -5 to -3 before infusion (bendamustine 90mg/m2 and on days -4 and -3 for patients with creatinine clearance <30ml/min)...Twenty patients (40%) were penta-refractory and 10 (20%) were refractory to the anti-BCMA antibody drug conjugate belantamab mafodotin...Tocilizumab was used in 40/48 patients with CRS (median of 1 dose, range 1-4) and corticosteroids in 8/48... Our findings demonstrate the manageable safety and high efficacy profiles of HBI0101 also in high-risk patients. Fast production time enabled the timely treatment of 98% of..."

CAR T-Cell Therapy • Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Rare Diseases • Thrombocytopenia

Efficacy of HBI0101, an Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) for Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1 | "Most patients (73/84, 87%) were triple refractory, 32/84 (38%) were penta-refractory and 14/84 (17%) had received prior anti-BCMA therapy, mostly belantamab mafodotin. CONCLUSION : HBI0101 BCMA CART results demonstrate high efficacy and manageable safety in a frailer and higher risk population as compared with the registrational studies with commercial products. This data not only supports further utilization of HBI0101 CART therapy, but also of CART production at an academic setting in general, ensuring a sufficient CART supply in the light of the increasing demand."

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

Feasibility of a Novel Academic Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis (ASH 2023) - P1 | "Patients with creatinine clearance ≥30ml/min (n=7) received lymphodepletion with fludarabine 25mg/m2 and cyclophosphamide 250mg/m2 on days -5 to -3 before infusion, and patients with creatinine clearance <30ml/min (n=2) received lymphodepletion with bendamustine 90mg/m2 and on days -4 and -3 before infusion...All patients were triple refractory to PI, IMiD and anti-CD38 antibody, 6 were penta-refractory and 5 were refractory to the anti-BCMA antibody drug conjugate belantamab mafodotin... In the largest cohort of AL patients treated with CART reported to date, we demonstrated acceptable toxicity in this frail population, with a remarkable hematologic efficacy, leading to organ responses in most participants. Our data suggests that anti-BCMA CART modality may become a powerful clinical tool to improve organ function and survival, even in advanced AL patients."

CAR T-Cell Therapy • IO biomarker • Amyloidosis • Anemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Efficacy and Safety of Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) for the Treatment of Relapsed and Refractory AL Amyloidosis (ASH 2024) - P1 | "In a phase Ia-b/2 study (NCT04720313), HBI0101 has demonstrated manageable safety with therapeutic efficacy in over 90 MM patient...Patients with creatinine clearance ≥30ml/min (n=13) received lymphodepletion with fludarabine 25mg/m2 and cyclophosphamide 250mg/m2 on days -5 to -3 before infusion, and patients with creatinine clearance <30ml/min (n=3) received lymphodepletion with bendamustine 90mg/m2 and on days -4 and -3 before infusion...RESULTS : Sixteen AL patients with relapsed/refractory disease were included, with a median of 4 prior lines of therapy (range : 3-10), all except one were refractory to their last line of therapy, 14/16 (88%) were triple refractory to PI, IMiD and anti-CD38 antibody and 6/16 (38%) were refractory to the anti-BCMA antibody drug conjugate belantamab mafodotin...Cytokine release syndrome (CRS) was observed in 14/16 (grade 1-2- 11 patients; grade 3- 3 patients; no grade 4 or 5 CRS), and was manageable with frequent use of..."

CAR T-Cell Therapy • Clinical • Acute Kidney Injury • Amyloidosis • Anemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatology • Inflammation • Liver Failure • Multiple Myeloma • Myelodysplastic Syndrome • Nephrology • Neutropenia • Oncology • Renal Disease • Thrombocytopenia

B Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy in Refractory Autoimmune Diseases (KIDNEY WEEK 2025) - "Methods This Phase I, single-center, dose-escalation trial evaluates HBI0101, an autologous BCMA-directed CAR T-cell product developed at Hadassah Medical Center and validated in MM...Conclusion BCMA CAR T-cell therapy induced rapid, substantial improvement in three patients with refractory autoimmune diseases and was well tolerated. These findings underscore the potential of this strategy to redefine treatment in autoimmunity and justify its continued exploration as a targeted, durable, and disease-modifying intervention."

CAR T-Cell Therapy • IO biomarker • Glomerulonephritis • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Multiple Myeloma • Myositis • Nephrology • Renal Disease • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Efficacy and Safety of Chimeric Antigen Receptor T-Cell Therapy in Relapsed and Refractory Multiple Myeloma – a Meta-Analysis (ASH 2024) - "We included 7 trials each of Ciltacabtagene autoleucel (cilta-cel) and Idecabtagene vicleucel (ida-cel) while 21 trials used different CAR-T cell therapies including GPRC5D, HDS269B, C-CAR088, HBI0101, CART-ddBCMA, ALLO-715, ARI0002h. This analysis has limitations with significant heterogeneity among studies. There were different CAR T-cell therapies with diverse designs of studies which limit the generalization of results."

CAR T-Cell Therapy • Retrospective data • Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Immix Biopharma…announced that Phase 1/2 interim results from its U.S. NXC-201 NEXICART-2 trial in relapsed/refractory AL Amyloidosis has been selected for oral presentation at the upcoming American Society of Hematology 2025 Annual Meeting (ASH 2025)… (GlobeNewswire) - "Oral presentation Sunday, December 7, at ASH 2025."

P1/2 data • Amyloidosis

Immix Biopharma…announced that it will present a NXC-201 abstract at the upcoming American Society of Hematology (ASH) 67th Annual Meeting… (GlobeNewswire)

Clinical data • Amyloidosis

Immix Biopharma Announces 50% Enrollment Milestone Surpassed in its ongoing relapsed/refractory AL Amyloidosis Clinical Trial, NEXICART-2 (GlobeNewswire) - "Immix continues to enroll expediently toward BLA submission."

Enrollment status • Amyloidosis

Phase 1 Study of HBI0101 CAR-T in Refractory B-Cell Autoimmune Diseases (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Polina Stepensky

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Myositis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Immix Biopharma Announces Other Serious Diseases Strategy (GlobeNewswire) - "Immix Biopharma, Inc...announced important updates about its plan to address other serious diseases with its sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy NXC-201 with a 'digital filter' that filters out non-specific activation. The Company plans to release forthcoming clinical data at upcoming scientific forums."

Clinical data • Amyloidosis

Immix Biopharma Announces Class-Leading Safety Profile, Allowing Potential Future Indication Expansion (GlobeNewswire) - "Immix Biopharma...announced a class-leading safety profile for sterically-optimized CAR-T NXC-201, including absence of neurotoxicity of any grade in low-volume disease to-date, laying a foundation for potential future indication expansion."

Trial status • Amyloidosis

NEXICART-2: Study of NXC-201 CAR-T in Patients With Light Chain (AL) Amyloidosis (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Nexcella Inc. | Phase classification: P1 ➔ P1/2

Phase classification • Amyloidosis • Multiple Myeloma

Immix Biopharma Announces Accelerated NEXICART-2 Clinical Trial Progress in relapsed/refractory AL Amyloidosis (GlobeNewswire) - "Immix Biopharma, Inc...announced accelerated U.S. NEXICART-2 clinical trial progress in relapsed/refractory AL Amyloidosis. NEXICART-2 now includes 18 clinical trial sites in its national footprint....'These additional new sites further accelerate our path to BLA submission for FDA approval.'"

Trial status • Amyloidosis

Immix Biopharma Announces Primary Endpoint Met in positive NXC-201 Interim Results Presented at ASCO, Enabling Path to Best-in-Class Therapy for relapsed/refractory AL Amyloidosis (GlobeNewswire) - P1/2 | N=40 | NEXICART-2 (NCT06097832) | Sponsor: Nexcella Inc. | "After NXC-201 treatment, all patients normalized pathological disease markers. Complete responses (CRs) were observed in 70% (7 out of 10) of patients treated with NXC-201. The remaining 3 patients are bone marrow minimum residual disease (MRD) negative (10-6), predicting future CR (Immix believes remaining three MRD negative (10-6) patients could be confirmed as CRs in the coming weeks and months). Downstream clinical improvement, including cardiac and renal organ responses, were recorded after CRs. There have been no relapses recorded to-date and no safety signals identified. No neurotoxicity has been observed....Immix plans Biologics License Application (BLA) for FDA approval."

FDA filing • P1/2 data • Amyloidosis

Safety and efficacy data from Nexicart-2, the first US trial of CAR-T in R/R light chain (AL) amyloidosis, Nxc-201. (ASCO 2025) - P1 | "Pts must have been exposed to bortezomib and anti-CD-38 antibody with persistent or relapsed disease. Lymphodepletion was with fludarabine and cyclophosphamide...CRS was observed in 5 pts (grade 1 (N=4), grade 2 (N=1)); onset day 1 (N=3) or 3 (N=2), lasting <24 hours following 1 dose of tocilizumab in all pts... In this first reported U.S. CAR-T clinical trial experience in RR AL Amyloidosis, we demonstrate that NXC-201 can be given safely and resulted in rapid and deep hematologic responses in all pts treated. Our data suggests that the novel anti-BCMA CAR-T NXC-201 may become a valuable treatment option for RR AL pts."

Clinical • IO biomarker • Amyloidosis • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Febrile Neutropenia • Heart Failure • Hematological Disorders • Infectious Disease • Nephrology • Neutropenia • Oncology • Renal Disease

Immix Biopharma Announces Positive Results for NXC-201 at ASCO Oral Presentation, Enabling Pathway to Best-in-Class Therapy for relapsed/refractory AL Amyloidosis (GlobeNewswire) - P1b/2 | N=40 | NEXICART-2 (NCT06097832) | Sponsor: Nexcella Inc. | "The abstract summarizes positive results from the U.S. multi-site NEXICART-2 trial evaluating NXC-201 in relapsed/refractory AL Amyloidosis with a data cutoff of January 28, 2025....Complete responses (CRs) were observed in 71% (5 out of 7) of patients treated with NXC-201. The remaining 2 patients are bone marrow minimum residual disease (MRD) negative (10-6), predicting future CR (Immix believes remaining two MRD negative (10-6) patients could be confirmed as CRs in the coming weeks and months). Downstream clinical improvement, including cardiac and renal organ responses, were recorded after CRs. There have been no relapses recorded to-date and no safety signals identified."

P1/2 data • Amyloidosis