INT-2104 / Gilead - LARVOL DELTA

INVISE: A Study to Investigate Safety of INT2104 Infusions in Participants Aged 18 Years of Age and Older Who Have B-cell Cancers That Came Back After Previous Treatment (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Kite, A Gilead Company | Trial completion date: Jul 2026 ➔ Oct 2026 | Trial primary completion date: Jul 2026 ➔ Oct 2026

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

In vivo CAR T-cell engineering in B-cell malignancies: A systematic review of emerging clinical and translational evidence. (ASCO 2026) - " We performed a literature search of peer-reviewed publications, conference proceedings (ASH, ASCO, EHA), and registered clinical trials (2018–2025) evaluating in vivo CAR T. Identified platforms included KLN-1010 (in vivo anti-BCMA CAR), INT2104 (CD20 CAR), Umoja CD22 CAR, Capstan CD8-targeted LNP CD19 CAR, and Orna circular RNA CD19 CAR systems... In vivo CAR T engineering has now demonstrated clinical proof-of-concept with deep molecular responses, robust in vivo CAR expansion, and manageable toxicity. Translational and preclinical CD19-, CD20-, and CD22-directed platforms show potent activity in aggressive lymphoma models, supporting direct applicability to DLBCL and HGBCL. Compared with ex vivo CAR T, in vivo systems offer elimination of leukapheresis, no manufacturing delays, outpatient feasibility, repeat dosing, and substantially reduced cost, potentially enabling earlier-line and broader access to CAR-T–level therapy."

CAR T-Cell Therapy • First-in-human • IO biomarker • Preclinical • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20 • CD22 • CD8

INVISE: A Study to Investigate Safety of INT2104 Infusions in Participants Aged 18 Years of Age and Older Who Have B-cell Cancers That Came Back After Previous Treatment (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Kite, A Gilead Company | Recruiting ➔ Active, not recruiting | N=34 ➔ 10 | Trial completion date: Mar 2031 ➔ Jul 2026 | Trial primary completion date: Mar 2028 ➔ Jul 2026

Enrollment change • Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Targeted In Vivo Generation of CAR T and NK Cells Utilizing an Engineered Lentiviral Vector Platform (ASH 2023) - "Taken together, these data suggest that intravenous delivery of INT2104 will be both safe and effective, providing a faster, cheaper, and more accessible option for treatment of B cell malignancies. Ongoing efforts include a GLP Toxicology study to enable IND submission in 2Q2024."

Preclinical • Viral vector • CD34 • CD7 • CD8

Targeted in vivo delivery of genetic medicines utilizing an engineered lentiviral vector platform results in CAR T and NK cell generation. (PubMed, Mol Ther) - "Preclinical data generated in mouse and cynomolgus macaque models indicate INT2104 results in both CAR T cells (CD4+ and CD8+) and CAR NK cells with subsequent depletion of CD20+ B cells following a single intravenous administration. Thus, INT2104 could potentially provide a more accessible, off-the-shelf treatment option for patients who may benefit from CAR therapies."

Journal • Preclinical • Oncology • CD20 • CD4 • CD7 • CD8

Interius BioTherapeutics to Present at Upcoming Scientific Meetings (GlobeNewswire) - "Interius BioTherapeutics...today announced that it will present at several upcoming scientific meetings."

Preclinical • Hematological Malignancies

Interius BioTherapeutics Announces Regulatory Approval to Expand Phase 1 Clinical Trial of INT2104 into Europe (GlobeNewswire) - "Interius BioTherapeutics...announced that the German regulatory agency, the Paul Ehrlich Institute (PEI), has approved expansion of the INVISE first-in-human Phase 1 clinical trial evaluating INT2104 for the treatment of B-cell malignancies to Europe. INVISE is the first clinical trial to announce clearance to evaluate in vivo CAR gene therapy in Europe....INVISE interim safety and proof-of-concept data to be presented at a scientific meeting in 2H 2025."

P1 data • Trial status • Non-Hodgkin’s Lymphoma

Interius BioTherapeutics Doses First Patient with in vivo Chimeric Antigen Receptor (CAR) Gene Therapy for B-cell Malignancies (GlobeNewswire) - "Interim safety and proof-of-concept data to be presented at a scientific meeting in 1H 2025...Interius BioTherapeutics...announced that the first study participant has been dosed in INVISE, its first-in-human Phase 1 clinical trial of INT2104, a first-in-class gene therapy that delivers a CAR transgene to generate effector CAR-T and CAR-NK cells in vivo for the targeting of CD20-positive B cells for the treatment of B-cell malignancies."

P1 data • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

INVISE: Safety of INT2104 in Participants Aged 18 Years and Older Who Have B-cell Cancer That Came Back After Prior Treatment (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Interius BioTherapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

INVISE: Safety of INT2104 in Participants Aged 18 Years and Older Who Have B-cell Cancer That Came Back After Prior Treatment (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Interius BioTherapeutics Inc.

New P1 trial • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Interius BioTherapeutics Receives HREC Approval and CTN Clearance from the TGA to Commence a Phase 1 Clinical Trial for Its First-in-Class In Vivo CAR Therapeutic for B Cell Malignancies (PRNewswire) - "Interius BioTherapeutics... announced that it has been granted Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) to commence a first-in-human Phase 1 clinical trial of INT2104, its lead in vivo CAR candidate for treatment of B-cell malignancies....The CTN clearance was granted based on HREC approval in Australia which included extensive review of Interius's preclinical data and study protocol. Interius intends to begin the trial in the fourth quarter of 2024..."

New P1 trial • Hematological Malignancies

Interius BioTherapeutics to Present In Vivo CAR Data in Oncology and Autoimmunity Programs at the American Society of Gene and Cell Therapy 27th Annual Meeting (PRNewswire) - "Interius BioTherapeutics...today announced the presentation of preclinical data across six abstracts at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting to be held on May 7-11 in Baltimore, MD....'Data from humanized mice and cynomolgus macaques demonstrate that a single i.v. administration of INT2104 transduces both T and NK cells that are then reprogramed to become functional chimeric antigen receptor (CAR) cells.' Biodistribution and immunohistochemical analyses confirmed vector targeting specificity. The in vivo generated autologous CAR cells targeted CD20 positive cells leading to B cell depletion in both animal models. One macaque had persistent B cell aplasia for one year, and at autopsy, had no detectable B cells in the peripheral circulation, spleen, bone marrow, or lymph nodes."

Preclinical • Hematological Malignancies • Oncology

In Vivo Generation of Both CAR T Cells and CAR NK Cells Using a CD7 Targeted Lentiviral Vector (ASGCT 2024) - ""Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors." The New England Journal of Medicine. 382(6) (2020): 545-553."

CAR T-Cell Therapy • IO biomarker • Preclinical • Viral vector • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD34 • CD7 • CD8 • IL15 • KLRC1

Pharmacokinetics and Vector Shedding in NHPs Following a Single Intravenous Infusion of a CD20-Targeted Engineered Lentiviral Vector (ASGCT 2024) - "Shedding of vector RNA genomes into feces, saliva and urine was detectable in some animals at very low levels in the first 3 days following vector administration, suggesting very limited and transient LVV shedding. Taken together these data demonstrate rapid clearing of an in vivo-administered replication-incompetent LVV, with limited shedding in animal excreta indicating low risk of environmental contamination."

PK/PD data • Viral vector • CD20

Rational Design of a Detargeted Vesiculovirus Fusogen to Enable Targeted In Vivo Gene Delivery (ASGCT 2024) - """Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein."" Nature Communications 9.1 (2018): 1029.2Hwang, B-Y., and D. V. Schaffer. ""Engineering a serum-resistant and thermostable vesicular stomatitis virus G glycoprotein for pseudotyping retroviral and lentiviral vectors."" Gene Therapy 20.8 (2013): 807-815."

Preclinical • Gene Therapies • Oncology • CD7

Targeted in vivo generation of CAR T and NK cells utilizing an engineered lentiviral vector platform (SITC 2023) - "INT2104 administration to mice bearing an established B cell tumor also resulted in B cell aplasia, with complete tumor ablation seen in all treated mice across a 15-fold range in dosing, including a dose matching the proposed first-in-human dose in TU/kg. Conclusions These preclinical data suggest that intravenous delivery of INT2104 will be both safe and effective, supporting plans to continue development and transition into the clinic."

Preclinical • Viral vector • Oncology • CD34 • CD7 • CD8

Interius BioTherapeutics Highlights Strong Preclinical Data Supporting In Vivo Chimeric Antigen Receptor (CAR) Vector Evaluation in Clinic (PRNewswire) - "Interius BioTherapeutics...announced the presentation of compelling preclinical data at the Cellicon Valley 2023 Meeting in Philadelphia, PA. The data demonstrates the potential of Interius Bio's lead program (INT2104) to generate biologically active CAR cells directly in vivo for the treatment of B-cell malignancies. The company will also be unveiling non-human primate data from multiple studies at the In Vivo Engineering of Therapeutic Cells Summit in Boston, MA on July 10-12, 2023. In mouse models of systemic lymphoma, complete tumor clearance occurs across a wide dose range after a single intravenous infusion of Interius Bio's targeted cell-specific lentiviral vector....Significant B cell depletion is observed with no toxicity and has been sustained in one animal for over 6 months....'We continue to maintain our timeline to IND with initial human data expected in 2024'."

IND • Preclinical • Hematological Malignancies • Lymphoma • Oncology

Interius BioTherapeutics Announces Successful Manufacturing Partnership with WuXi Advanced Therapies (PRNewswire) - "Interius BioTherapeutics...announced a manufacturing partnership with WuXi Advanced Therapies (WuXi ATU), a global Contract Testing, Development and Manufacturing Organization (CTDMO). Interius has developed a process to manufacture INT-2104, an off the shelf lentivector product designed to create autologous chimeric antigen receptor (CAR) T cells directly in vivo in a patient's body for the treatment of B cell malignancies. Through this partnership, Interius will leverage WuXi ATU's CTDMO platform for Good Manufacturing Process (GMP) manufacturing of Phase I clinical product."

Licensing / partnership • Hematological Malignancies • Oncology