TG-1801 / Light Chain Biosci, TG Therap - LARVOL DELTA

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=21 | Terminated | Sponsor: TG Therapeutics, Inc. | N=60 ➔ 21 | Trial completion date: Dec 2024 ➔ Jun 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Jun 2024; Strategic/Business Decision

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: TG Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: TG Therapeutics, Inc.

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: TG Therapeutics, Inc.

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: TG Therapeutics, Inc. | Phase classification: P1b ➔ P1

Combination therapy • Phase classification • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b | N=60 | Recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Novel agents in relapsed/refractory diffuse large B-cell lymphoma (ICML 2023) - "In recent years, numerous agents have been approved specifically for patients with DLBCL (RED) including tafasitamab, loncastuximab tesirine, polatuzumab vedotin, selinexor, rituximab, and pembrolizumab (for patients with Primary Mediastinal B-cell lymphoma)...Significant grade 3-4 toxicities were neutropenia and thrombocytopenia with 48.6% of patients requiring dose modifications, and 22.9% discontinuing treatment for toxicity.12 Ongoing and planned trials with loncastuximab include a phase III trial with rituximab, gemcitabine, and oxaliplatin (R-GemOx) (Tables 1 and 3)...Encouraging clinical activity, without unanticipated toxicities was observed when polatuzumab was combined with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) with an ORR of 89% (CR 61%).24 Combination of polatuzumab with lenalidomide and rituximab (R2) in 49 patients demonstrated an ORR of 35% (CR 29%), with median DOR, PFS, and OS of 8.1, 6.3, and 10.9 months, respectively...One notable..."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CARD11 • CD79B • CDKN1A • CRBN • CTLA4 • EZH2 • IKZF1 • IRAK4 • LYN • MALT1 • MCT1 • MYC • MYD88 • NF-κβ • PD-L1 • ROR1 • SIRPA • SYK • XPO1

First-in-Human (FIH) Study of the Fully-Human Kappa-Lambda CD19/CD47 Bispecific Antibody TG-1801 in Patients with B-Cell Lymphoma (ICML 2023) - P1 | " The primary objectives of this phase I 3+3 study were to characterize the safety profile and determine the recommended phase 2 dose (RP2D) as monotherapy and in combination with ublituximab. TG-1801 monotherapy and combination therapy demonstrates clinical activity, particularly in R/R DLBCL, with an acceptable preliminary safety profile. This study (NCT03804996) has completed enrollment."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

G protein-coupled receptor 183 mediates the sensitization of Burkitt lymphoma tumors to CD47 immune checkpoint blockade by anti-CD20/PI3Kδi dual therapy. (PubMed, Front Immunol) - "Cell response to TG-1801 alone or combined with the U2 regimen associating ublituximab to the PI3Kδ inhibitor umbralisib, was analyzed by proliferation assay, western blot, transcriptomic analysis (qPCR array and RNA sequencing followed by gene set enrichment analysis) and/or quantification of antibody-dependent cell death (ADCC) and antibody-dependent cell phagocytosis (ADCP). Genetic depletion and pharmacological inhibition of GPR183 impaired ADCP initiation, cytoskeleton remodeling and cell migration in 2D and 3D spheroid B-NHL co-cultures, and disrupted macrophage-mediated control of tumor growth in B-NHL CAM xenografts. Altogether, our results support a crucial role for GPR183 in the recognition and elimination of malignant B cells upon concomitant targeting of CD20, CD47 and PI3Kδ, and warrant further clinical evaluation of this triplet regimen in B-NHL."

Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • Burkitt Lymphoma • Hematological Malignancies • Immune Modulation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • GPR183 • PIK3CD • SIRPA

NI-2601, an Fc-active CD47xPD-L1 bispecific antibody that selectively targets CD47 on PD-L1-positive tumors (AACR 2022) - P1, P1b | "The latter is also used in our CD47xCD19 bispecific antibody NI-1701/TG-1801, currently in phase I clinical trials (NCT03804996, NCT04806035)...NI-2601 demonstrated effective blockade of PD-1/PD-L1 interaction, and T-cell activation in vitro, similar to the anti-PD-L1 clinical benchmarks atezolizumab and avelumab...Thus, NI-2601 is able to harness Fc-effector function to eliminate PD-L1-positive tumor cells while sparing PD-L1-negative cells, such as RBC or platelets. Pharmacokinetic and tolerability studies in non-human primate are planned for 2022."

IO biomarker • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD47 • SIRPA

First-in-Human (FIH) Study of the Fully-Human Kappa-Lambda CD19/CD47 Bispecific Antibody TG-1801 in Patients (pts) with B-Cell Lymphoma (ASH 2022) - P1 | "Combination of CD47 blockade with the anti-CD20 antibody rituximab has resulted in encouraging clinical activity (Advani 2018), and CD19 is also an established target of multiple B-NHL therapies...A 3+3 design was also utilized to evaluate two dose levels of TG-1801 (300 mg and 400 mg) with a standard dose of ublituximab (900 mg)... TG-1801 monotherapy and combination therapy demonstrates clinical activity, particularly in relapsed and refractory DLBCL, with an acceptable preliminary safety profile. This study (NCT03804996) has completed enrollment."

Clinical • P1 data • Anemia • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Richter's Syndrome • Thrombocytopenia • Transplantation • CD19 • CD47 • SIRPA

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | N=16 ➔ 50

Enrollment change • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CD47xCD19 bispecific antibody triggers recruitment and activation of innate immune effector cells in a B-cell lymphoma xenograft model. (PubMed, Exp Hematol Oncol) - P1b | "The study described the mechanisms afforded by the CD47xCD19 bispecific antibody, NI-1701, at controlling tumor growth in lymphoma mouse model. NI-1701 is currently being evaluated in a Phase I clinical trial for the treatment of refractory or relapsed B-cell lymphoma (NCT04806035)."

Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD8 • IFNG • SIRPA

The Ublituximab-Umbralisib (U2) Drug Regimen Potentiates the Activity of the Novel CD47-CD19 Bispecific Antibody, TG-1801, through the Activation of the G Protein-Coupled Receptor EBI2/GPR183 (ASH 2021) - "The data presented here set the preclinical rationale and support a combination strategy of the novel CD47-CD19 bispecific antibody TG-1801 in B-NHL with other B-cell targeted mechanisms, including umbralisib and ublituximab."

Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PIK3CD • SIRPA

"Looking forward to interesting data results @ASH_hematology on TG-1801 in #CD47 space! #hematology #oncology #cancertherapy #ASH2021 #abstract" (@Uday39788790)

Hematological Disorders • Oncology

"#TGTherapeutics reported milestone reached in the clinical development of #TG1801 (#NI1701) https://t.co/oW4UDhKmDc" (@1stOncology)

Clinical

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b; N=60; Recruiting; Sponsor: TG Therapeutics, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

TG Therapeutics Provides Business Update and Reports Fourth Quarter and Year-End 2020 Financial Results (GlobeNewswire) - "Key Objectives for 2021; Continue the commercialization of UKONIQ in relapsed/refractory MZL and FL and expand commercialization capabilities in preparation for a potential launch of ublituximab; Present results from the ULTIMATE I & II Phase 3 trials evaluating ublituximab in RMS and prepare a BLA submission; Complete the rolling BLA submission of ublituximab, in combination with umbralisib, for the treatment of patients with CLL; Complete enrollment in the ULTRA-V Phase 2b trial and begin a Phase 3 trial evaluating the triple combination of U2 plus venetoclax; Continue to advance our early pipeline candidates including TG-1501 (cosibelimab), TG-1701 and TG-1801."

BLA • Enrollment status • Launch • New P3 trial • P3 data • Trial status • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P1b; N=60; Not yet recruiting; Sponsor: TG Therapeutics, Inc.

Clinical • Combination therapy • New P1 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

Study of TG-1801 in Subjects With B-Cell Lymphoma (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: TG Therapeutics, Inc.; Trial completion date: Aug 2021 ➔ Dec 2022; Trial primary completion date: Feb 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TG Therapeutics provides business update and reports first quarter 2020 financial results (GlobeNewswire, TG Therapeutics, Inc.) - "Key Objectives for 2020: Complete rolling NDA submission for umbralisib in patients with previously treated MZL and FL, in the first half of 2020; Present full data from the UNITY-CLL Phase 3 trial and present full data from the FL and MZL umbralisib monotherapy cohorts of the UNITY-NHL trial at a major medical meeting, by year-end 2020; Target an NDA/Biologics Licensing Application (BLA) submission of U2 for the treatment of patients with CLL (including both previously untreated and relapsed/refractory patients), by year end 2020; Continue to advance our early pipeline candidates including our anti-PD-L1 monoclonal antibody, cosibelimab (TG-1501), our covalently-bound Bruton’s Tyrosine Kinase (BTK) inhibitor, TG-1701, and our anti-CD47/CD19 bispecific antibody, TG-1801."

BLA • NDA • P2/3 data • P3 data • Pipeline update • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology