Isocel (ALEXIS-ISO-1) / Kiromic - LARVOL DELTA

AUC FLUDARABINE AND PRODUCT CHOICE ARE MAIN PREDICTORS OF CRS/ICANS AFTER CAR T CELL THERAPY: GENERATION OF AN IMPROVED MODEL (EHA 2025) - "Additionally, previous studies only comprised patients treated with tisacel or axi-cel, and a few experimental products...After exclusion of gender, patient weight and brexu-cel as predictors, mEASIX, AUC fludarabine, age, liso-cel, and MM were included as predictors for ICANS>=°II... Elevated AUC fludarabine was significantly associated with severe CRS/ICANS. In contrast, lisocel and MM were associated with decreased risk. The previously reported association of mEASIX with CRS/ICANS was less pronounced in our models."

CAR T-Cell Therapy • Chronic Kidney Disease • Hematological Malignancies • Multiple Myeloma • Oncology

PERSISTING THROMBOCYTOPENIA AFTER CD19-DIRECTED CAR-T CELL THERAPY IS A PREDICTOR OF WORSE SURVIVAL IN RELAPSED / REFRACTORY LBCL PATIENTS (EHA 2025) - "The administered CAR-T cell products were as following: Axicel (n=79; 87%), Tisacel (n=11; 12%) and Lisocel (n=1; 1%).Cytopenias ≥ grade 3 were a frequent event in follow-up in our cohort with a maximum at d+30 (Granulocytopenia 37%, Anemia 8%, Thrombocytopenia 48%). Cytopenias are a frequent event in post-CAR-T phase in r/r LBCL. Of all scenarios, persisting Thrombocytopenia CTC ≥ 2 at d+90 after CAR-T cell therapy was a strong predictor for worse survival. Patients with thrombocytopenia grade ≥ 2 should be monitored carefully in post-CAR-T follow-up."

CAR T-Cell Therapy • Clinical • Agranulocytosis • Anemia • B Cell Lymphoma • Granulocytopenia • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

Theoretical Analysis of Power-Law Stress Relaxation and Calcium-Dependent Passive Mechanics in Cardiac Muscle. (PubMed, bioRxiv) - "By providing a unified basis for the observed viscoelastic and preconditioning effects, calcium dependency, and power-law stress relaxation phenomena, this study offers a novel theoretical basis for understanding and simulating the role of titin in striated muscle mechanics. 1Passive stress relaxation of cardiac muscle follows a power-law decay, a phenomenon that is explained using a theoretical model of dynamic unfolding of globular domains along polymer chain.The theoretical model simulates the behavior of titin, a giant sarcomere protein linking myosin thick filaments to the Z disk and providing passive restoring force during muscle stretch.The theoretical model is able to account the observed effects of calcium on the effective viscoelastic passive mechanics of cardiac muscle.This model provides a theoretical basis for understanding passive visocelastic properties and titin's role in striated muscle mechanics."

Journal • TTN

Low Symmetry Face-Capped Fe(II) Tetrahedra Through Anisotropic Ligand Extension. (PubMed, Angew Chem Int Ed Engl) - "The use of 'isoceles' ligands (two arms the same, one different) gives tetragonal disphenoid structures, while a 'scalene' ligand (all three arms different) gives a rhombic disphenoid structure...More distorted cages were more prone to loss of structural integrity upon introduction of highly coordinating dimethyl sulfoxide solvent into the cage in acetonitrile solution. As well, increasing distortion was shown to increase the ease of oxidation from Fe(II) to Fe(III) within the cages."

Journal

Real World Outcomes of CAR T-Cell Therapy for B-Cell Lymphoma in Adults Age ≥ 65: A Referral Center Experience (TCT-ASTCT-CIBMTR 2025) - "CAR T products included: 36 Axicel, 12 Brexucel, 10 Lisocel, and 3 Tisacel. Among the 61 patients, 49 had DLBCL/HGBL and 12 had MCL; the median age was 72 years old (range 65-84) and 38 patients were male. Median prior lines of therapy were 2 (range 1-11) including 9 prior autologous transplants. The pre-CAR T Karnofsky performance score (KPS) was 90 - 100 in 26 patients and ≤ 80 for 35 patients."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases

Real World Comparison of Axicabtagene Ciloleucel and Lisocabtagene Maraleucel in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ASH 2024) - "Background : Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19, such as Axicabatagene ciloleucel (axicel) and Lisocabtagene maraleucel (lisocel), have shown efficacy with a tolerable safety profile in the treatment of relapsed or refractory diffuse large B-cell lymphoma (RR DLBLC) in clinical trials. Although comparisons for OS cannot be made due to published trial's data maturity, this study provides real-world evidence for pts with RR DLBCL who underwent treatment with either axicel or lisocel. Further maturation of data from clinical trials is needed to better guide treatment for these groups, but comparison data from our analysis looks promising and doesn't show any significant difference between the two products."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

State of knowledge of the ladybird beetle (Coleoptera, Coccinellidae) fauna of Armenia and other Transcaucasian countries, including two new country records. (PubMed, Zookeys) - "Two of them, Anatisocellata (Linnaeus, 1758) and Tytthaspissedecimpunctata (Linnaeus, 1761), have not been reported in the literature but were present in our field samples, so they can be considered species new to Armenia, and signify new country records...The recognized Coccinellidae fauna of Armenia is slightly poorer than the faunas of other Transcaucasian countries (Azerbaijan and Georgia): there are 92 species currently known to occur in Azerbaijan and 90 species in Georgia. Interestingly, the Armenian fauna contains more Caucasian endemics (10 species) and fewer non-natives (1 species) than the faunas of Azerbaijan (4 endemics and 2 non-natives) and Georgia (6 endemics and 6 non-natives)."

Journal

Kiromic BioPharma Announces Settlement of Previously Disclosed SEC Investigation (Businesswire) - "Kiromic BioPharma, Inc...today announced that it has entered into a settlement agreement with the U.S. Securities and Exchange Commission (the 'SEC'), resolving the previously disclosed SEC investigation arising from the non-disclosure by Kiromic’s prior executive management of the clinical holds placed on the investigational new drug ('IND') applications the Company filed with the U.S. Food and Drug Administration (the 'FDA') in May 2021. The IND applications pertained to ALEXIS-PRO-1 (Procel) and ALEXIS-ISO-1 (Isocel). In light of the Company’s self-reporting, prompt remediation and cooperation, the SEC has determined not to impose a civil penalty on the Company and there are no ongoing undertakings in connection with the settlement."

Commercial • Oncology • Solid Tumor

CAR-T cells in second-line large B-cell lymphoma (LBCL): Is the ZUMA-7 approach practical? (DGHO 2024) - "19 patients proceeded to CART infusion (axicel 15, lisocel 4): 15 patients of 25 evaluable patients (60%) were dosed in 2L, whereas 10 patients progressed through holding/bridging and were infused in 3 rd -line (n=4) or could not be dosed due to rapid disease progression (n=6). Only about 60% of all patients with high-risk LBCL failure intended to receive 2L CARTs can actually be infused in 2L. Nevertheless, these first real-world results obtained in an intent-to-treat fashion suggest that a 2L CART strategy is feasible and may improve the poor outcome of high-risk LBCL failure for a meaningful proportion of patients including those deeming transplant-ineligible."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology

Mantle Cell Lymphoma: Next Steps (SOHO 2024) - "The most commonly used agents are the Bruton tyrosine kinase (BTK) inhibitors, with ibrutinib becoming Food and Drug Administration (FDA)-approved in 2013, acalabrutinib in 2017, and zanubrutinib in 2019...Excitingly, pirtobrutinib, a BTK inhibitor that binds noncovalently and reversibly to BTK, is also now FDA-approved and is providing acceptable results even in many patients with prior relapse to covalent BTK inhibitors...Brexucabtagene autoleucel (brexu-cel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the FDA in 2020...Most excitingly, a second anti-CD19 CAR T-cell therapy, lisocabtagene maraleucel (lisocel), was approved a week ago...The most advanced ones include glofitamab (CD20/CD3) and epcoritamab (CD20/CD3), both of which are approved for diffuse large B-cell lymphoma and are currently being tested for mantle cell lymphoma as well...In this phase 3 trial, ibrutinib plus venetoclax produced a high complete response (CR)..."

Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • ROR1

Impact of Bridging Therapy (BT) on Lisocabtagene Maraleucel (liso-cel) as Second-Line (2L) or Later (2L+) Treatment of R/R Follicular Lymphoma (FL) in the Phase 2, Open-Label TRANSCEND FL Study (SOHO 2024) - P2 | " Consented patients with 2L+ FL received lisocel; patients with 2L FL had progression of disease ≤24 months from diagnosis after treatment with anti-CD20+alkylator ≤6 months of FL diagnosis and/or met mGELF criteria. Liso-cel showed similar efficacy and safety (low rates of severe CRS/NEs/infections) in both subgroups, suggesting BT may slow disease progression (despite higher baseline disease burden), potentially improving outcomes in this high-risk population. Safety in the outpatient setting was consistent with the overall population and with liso-cel in OUTREACH (NCT03744676; LBCL outpatient setting), with no new safety signals."

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Real-World Outcomes of Lisocabtagene Maraleucel (liso-cel) in Patients With Richter Transformation (RT) From the Center for International Blood and Marrow Transplant Research (CIBMTR) (SOHO 2024) - "Median time from leukapheresis to lisocel infusion was 35 days (range, 28-63)...Overall, 70% of patients had CRS (grade 3, 0; grade 4, 3%; grade 5, 3% [patient also had hemophagocytic lymphohistiocytosis]); the most common CRS treatments were corticosteroids and tocilizumab (23%) and tocilizumab (20%)... Patients with RT have poor prognosis and high unmet need. Here, we show that liso-cel provided meaningful clinical benefit and manageable safety, with low incidences of grade ≥3 CRS. The high CR rate is promising in this difficult-to-treat population, and longer follow-up in a larger cohort is needed."

Clinical • Real-world • Real-world evidence • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Oncology • Richter's Syndrome

CAR-T CELL TREATMENT OF LARGE B-CELL LYMPHOMA (LBCL): DO PROGRAM DURATION AND TREATMENT LINE MATTER? (EBMT 2024) - " Eligible for this retrospective analysis were all adult patients who received commercial or experimental CD19 CARTs at the University of Heidelberg...Axicabtagene ciloleucel (axicel), tisagenelecleucel (tisacel), lisocabtagen maraleucel (lisocel), and experimental CARTs were used in 73%, 18%, 6%, and 3% of patients, respectively... Despite constant response rates, PFS and NRM of >2L CARTs seem to improve with longer CART program duration. This might be partly explained with better patient selection, earlier use of CARTs, and more effective bridging strategies. The advent of 2L CARTs associates with a strong reduction, but not a complete abrogation of >2L indications."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CAR-T CELL TREATMENT OF LARGE B-CELL LYMPHOMA (LBCL): DO PROGRAM DURATION AND TREATMENT LINE MATTER? (EBMT 2024) - " Eligible for this retrospective analysis were all adult patients who received commercial or experimental CD19 CARTs at the University of Heidelberg...Axicabtagene ciloleucel (axicel), tisagenelecleucel (tisacel), lisocabtagen maraleucel (lisocel), and experimental CARTs were used in 73%, 18%, 6%, and 3% of patients, respectively... Despite constant response rates, PFS and NRM of >2L CARTs seem to improve with longer CART program duration. This might be partly explained with better patient selection, earlier use of CARTs, and more effective bridging strategies. The advent of 2L CARTs associates with a strong reduction, but not a complete abrogation of >2L indications."

CAR T-Cell Therapy • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Impact of Response to Systemic Bridging Therapy on Clinical Outcomes and Cytokine Profiles in Patients Receiving CD19- CAR T-Cell Therapy for B-Cell Lymphoma (ASH 2023) - "BT was classified as Polatuzumab (pola) based, intensive chemotherapy, lenalidomide/ Bruton tyrosine kinases inhibitors (len/BTKi), or others...Among all pts, 86 (47%) received Axicel, 49 (27%) Tisacel, 36 (20%) Lisocel and, 11 (6%) Brexucel... Our findings suggest that achieving a response to BT is associated with reduced tumor burden and inflammatory markers pre-LD, reflecting inherent disease biology and treatment-refractoriness. Further studies are required to evaluate which BT strategies may optimize the inflammatory cytokine environment for improved outcomes after CD19 CAR T cell therapy."

CAR T-Cell Therapy • Clinical • Clinical data • IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL6

Past and present: changes in the Odonata fauna of small lowland watercourses. (PubMed, Biodivers Data J) - "However, a diverse Odonata assemblage (1,277 individuals of 27 species) was observed at the 14 sampling sites of the three watercourses, containing protected and sensitive species (Somatochloraflavomaculata, Orthetrumbrunneum, Aeshnaisoceles, Libellulafulva). However, the low abundance of larval and exuvial forms (59 individuals of 13 species) suggests that the majority of the observed adults were developed in other watercourses. While recolonisation from nearby habitats is still possible, a parallel degradation of adjecent waterbodies could lead to an irreversible biodiversity loss."

Journal

IMPACT OF RESPONSE TO SYSTEMIC BRIDGING THERAPY ON CLINICAL OUTCOMES AND CYTOKINE PROFILE IN PATIENTS RECEIVING CAR T-CELL THERAPY FOR AGGRESSIVE B-CELL LYMPHOMA (ICML 2023) - "BT was classified as Polatuzumab- (pola) based, intensive chemotherapy, lenalidomide/ Bruton tyrosine kinases inhibitors (len/BTKi), or other...Among all pts, 77 (52%) received Axicel, 42 (28%) received Tisacel and 29 (20%) received Lisocel... Our findings indicate that response to CAR T therapy is more frequent in pts responding to BT. Ferritin, LDH, and other inflammatory cytokine levels at the time of LD differ according to the type and response to systemic BT. Higher levels may reflect inherent disease biology and treatment-refractoriness."

CAR T-Cell Therapy • Clinical • Clinical data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP • IL10 • IL6

"TRANSCEND #CLL 004 Of 137 leukapher 117->lisocel 53 (DL1=4; DL2=49) in primary efficacy ax (PAS) median 5 lines All BTKi exp CR/CRi in PAS 18% ORR 43% uMRD PB 63% mDOR 35m PFS 12m Responders->✅DOR CRS 85% G3 8.5% NE 45% G3 18% Effective in v high risk but notable tox #ASCO2023" (@tobyeyre82)

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

HOW I TREAT DOUBLE-HIT LYMPHMOMA AND HGBL, NOS (EHOC 2022) - "Albeit with a small number of patients, the three main products (axi-cell, tisa-cell and lisocell), used for rescue of DLBCL patients, had shown activity against HGBL. HGBL is an aggressive form of lymphoma, with tendency of a worst prognosis with conventional treatment. Intensive regimens seem to fare better than RCHOP, although with more toxicity and no randomize studies supporting this indication. New treatments, mainly CAR T-cells and bispecifics, are very promising and possibly will became standard of care for such patients but were in the therapy algorithm is still to be decide."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • BCL2 • BCL6

"Now updated to include the TRANSFORM lisocel data + small edits/fixes" (@drjgauthier)

Kiromic BioPharma Pipeline to Prioritize a New Gamma Delta T-cell Product Candidate (Businesswire) - "Kiromic BioPharma, Inc...announces a strategic pipeline shift to prioritize its allogeneic, non-engineered off-the-shelf product candidate, Deltacel/KB-GDT™....These three IND applications will expand Kiromic’s therapeutic pipeline to five allogeneic GDT clinical trials...including: New IND #1: Deltacel™ in combination with a standard antitumor modality, with clinical activation expected to begin by the end of the fourth quarter of 2022; New IND #2: Procel™ in combination with a standard antitumor modality, with clinical activation expected to begin by the end of the second quarter of 2023; ALEXIS – PRO-1 Procel™ as a monotherapy, with clinical activation expected to begin by the end of second quarter 2023; New IND #3: Isocel™ in combination with a standard antitumor modality, targeting clinical activation to begin by the end of the fourth quarter of 2023; ALEXIS – ISO-1 Isocel™ as a monotherapy, targeting clinical activation to begin by the end of the fourth quarter of 2023."

IND • New trial • Pipeline update • Oncology

Kiromic BioPharma Significantly Expands Gamma Delta T cell Product Pipeline with New Sponsored Research Agreement (Businesswire) - "Kiromic BioPharma, Inc...announces it has entered into a sponsored research agreement (SRA) with Principal Investigator James W. Welsh, M.D. of The University of Texas MD Anderson Cancer Center. Under the two-year SRA, in vivo preclinical data will be generated from Kiromic’s Gamma Delta T cell (GDT) allogeneic therapies. This SRA is intended to evaluate efficacy and patient safety outcomes to support three new investigational drug (IND) applications to the U.S. Food and Drug Administration (FDA)....'The first of these three new IND submissions - the Deltacel™ - is expected to be submitted during the second half of the year', stated Pietro Bersani, Chief Executive Officer of Kiromic BioPharma. 'Importantly, we expect to begin the activation of the Deltacel clinical trial by the end of this year.' In addition to Deltacel/KB-GDT...the second IND is expected to focus on Procel/KB-PD1...The third IND is expected to focus on Isocel/KB-ISO..."

IND • Licensing / partnership • Oncology

Kiromic BioPharma Announces Strategic Collaboration with Gemelli Teaching Hospital to Accelerate the Analysis of Allogeneic CAR-T Clinical Trial Candidate Alexis ISO-1 in Solid Cancers (Businesswire) - "Kiromic BioPharma, Inc...announces it has engaged in a strategic collaboration with Gemelli Teaching Hospital IRCCS to accelerate the analysis of the Company’s first allogeneic CAR-T clinical trial candidate Alexis ISO-1...The Company is anticipating being granted a Type A meeting with the FDA by the first half of 2022 to discuss the clinical hold and the clinical development path forward of its previously submitted IND. Following the Type A meeting, the Company plans to resubmit the investigational new drug (IND) application, and will continue to coordinate closely with the FDA to meet all regulatory requirements."

FDA event • Licensing / partnership • Oncology • Solid Tumor

Kiromic BioPharma Reports Second Quarter 2021 Financial Results and Operating Highlights (Businesswire) - "The company's plans to submit the prepared response..[to FDA]...by the first half of September 2021. The commencement of the dosing of its first in human clinical trial is expected to be delivered in the first quarter of 2022."

FDA event • New trial • Oncology

Kiromic BioPharma Provides Update on IND Filings on its Off-the-Shelf, Allogeneic CAR-T for Solid Tumors (PRNewswire) - "Two INDs were submitted to the FDA in May 2021 for the first-in-human off-the-shelf allogeneic CAR-T for Solid Tumors. FDA returned with comments on the Company’s allogeneic CAR-T products with respect to: (i) Tracing of all reagents used in manufacturing; (ii) Flow chart of manufacturing processes; (iii) Certificate of Analysis (COA) for the Company’s CAR-T products (allogeneic CAR-T)...The company's timeline for commencement of the dosing of its first in human clinical trial is expected to be tighter but we still plan on delivering in 3Q 2021."

IND • Trial status • Oncology • Solid Tumor