edralbrutinib (TG-1701) / TG Therap, Jiangsu Hengrui Pharma - LARVOL DELTA

TG-1701-101: Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies (clinicaltrials.gov) - P1 | N=172 | Terminated | Sponsor: TG Therapeutics, Inc. | Active, not recruiting ➔ Terminated; Strategic/Business Decision

Trial termination • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TG-1701-101: Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies (clinicaltrials.gov) - P1 | N=172 | Active, not recruiting | Sponsor: TG Therapeutics, Inc.

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

TG-1701-101: Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies (clinicaltrials.gov) - P1 | N=172 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

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

Extended Abstract: New BTKi (SOHO 2022) - "It has also been studied in combination with idelalisib or entospletinib in CLL and other B-cell lymphomas though without clear benefi t for the combinations over monotherapy16,17. Tirabrutinib is approved in Japan for WM, lymphoplasmacytic lymphoma (LPL), and RRPCNSL, and in South Korea for RR-PCNSL18. TG-1701 is a selective covalent BTKi that has been studied as a monotherapy and in combination with ublituximab and umbralisib with preliminary results suggesting both effi cacy and manageable safety19. Orelabrutinib, another selective covalent BTKi, has been studied as a monotherapy in CLL in addition to other B-cell malignancies, also with favorable safety and effi cacy20,21 and it is approved in China for rel/ref CLL and MCL22. Finally, DTRMWXHS-12 is a covalent BTKi that uniquely is being studied in combination with everolimus and pomalidomide (triplet referred to as DTRM-555), given that this combination was determined to lead to synthetic lethality in both in vivo..."

IO biomarker • Chronic Lymphocytic Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • FLT3 • IL2 • ITK • PLCG2

Evaluate the Efficacy and Safety of SHR1459 Tablets in Patients With Primary Membranous Nephropathy (clinicaltrials.gov) - P2 | N=61 | Active, not recruiting | Sponsor: Reistone Biopharma Company Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • Renal Disease

An Open Label Study of the Effects of SHR1459 in NMOSDs Patients (clinicaltrials.gov) - P2 | N=10 | Completed | Sponsor: Reistone Biopharma Company Limited | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

A Trial of DDI Between SHR1459 and Efavirenz With Healthy Subjects (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Oncology

A Trial of DDI Between SHR1459 and Efavirenz With Healthy Subjects (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor (clinicaltrials.gov) - P1 | N=86 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Trial completion date: Sep 2022 ➔ Dec 2024 | Trial primary completion date: Jun 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Mantle Cell Lymphoma • Oncology

The Selective Bruton Tyrosine Kinase (BTK) Inhibitor TG-1701 As Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with B-Cell Malignancies (ASH 2021) - P1 | "Treatment with a more selective BTK inhibitor could result in improved efficacy and safety outcomes compared with ibrutinib (ALPINE study, EHA 2021), and we hypothesized that dual blockade of the B-cell receptor (BCR) pathway through combination of TG-1701 with U2 may confer greater depth of response compared to either regimen alone. TG-1701 exhibits an encouraging safety and efficacy profile as monotherapy in patients with CLL and additionally shows promising activity and a manageable tolerability profile in combination with U2. Future registration trials are being planned in CLL with TG-1701. Recruitment to this study (NCT03671590) continues."

Clinical • Combination therapy • IO biomarker • Monotherapy • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Thrombocytopenia • Ventricular Tachycardia • IGH • PIK3CD • TP53

A Bioavailability Study of SHR1459 on Healthy Chinese Volunteers (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Unknown status ➔ Completed

Trial completion

A Trial of DDI Between SHR1459 and Efavirenz With Healthy Subjects (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1 trial • Oncology

TG Therapeutics Announces Data from a Phase 1 Study Evaluating TG-1701 as a Monotherapy and as a Triple Combination with Ublituximab and UKONIQ at the 2021 American Society of Clinical Oncology Annual Meeting (GlobeNewswire) - P1, N=50; NCT03671590; Sponsor: TG Therapeutics, Inc.; "TG Therapeutics...announced data from TG-1701...as a monotherapy and as a triple therapy in combination with ublituximab...and UKONIQ® (umbralisib), the Company’s once-daily, inhibitor of PI3K-delta and CK1-epsilon in patients with front line or relapsed/refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL)...We look forward to continuing to enroll on this trial and presenting additional data.'...At a median follow up of 12.2 months in the 200 mg QD monotherapy expansion cohorts, overall response rates (ORR) were: 95% (19/20) in CLL, 65% (13/20) in mantle cell lymphoma (MCL), and 95% (19/20) in Waldenstrom macroglobulinemia (WM)...100% ORR observed at a median follow up of 8.6 months in the 300 mg CLL monotherapy cohort (n=19)."

P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

TG-1701-101: Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: TG Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

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

Evaluate the Efficacy and Safety of SHR1459 Tablets in Patients With Primary Membranous Nephropathy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Reistone Biopharma Company Limited | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Oct 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Glomerulonephritis • Renal Disease

Study to Evaluate the Mass Balance and Biotransformation of [14C]SHR1459 in Healthy Adult Male Volunteers (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting | Trial completion date: Feb 2022 ➔ Jul 2022 | Trial primary completion date: Feb 2022 ➔ Jul 2022

Enrollment closed • Trial completion date • Trial primary completion date

Antitumor activity of the novel BTK inhibitor TG-1701 is associated with disruption of Ikaros signaling in patients with B-cell non-Hodgkin lymphoma. (PubMed, Clin Cancer Res) - "These data validate phosphoproteomic as a valuable tool for the early detection of response to BTK inhibition in the clinic, and for the determination of drug mechanism of action."

Clinical • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IKZF1

TG Therapeutics Announces Data Presentations at the 63rd American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - P1, N=200; NCT03671590; Sponsor: TG Therapeutics, Inc.; "Efficacy Overall Response Rate (ORR) and Complete Response (CR) Outcomes: 100% ORR observed in the CLL 300 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 13.8 months (n=19); 95% ORR observed in the CLL 200 mg QD TG-1701 monotherapy expansion cohort at a median follow up of 20 months (n=20); 86% ORR, including 19% CR rate, observed in the 1701+U2 dose escalation cohort (using doses of 100 mg to 300 mg QD of TG-1701) at a median follow up of 20.2 months (n=21); 83% ORR, including 6% CR rate, observed in the 1701+U2 dose expansion cohort (using 100 mg QD of TG-1701 and 400 mg QD of umbralisib) at a median follow up of 2.7 months (n=18)."

P2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Evaluate the Efficacy and Safety of SHR1459 Tablets in Patients With Primary Membranous Nephropathy (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Reistone Biopharma Company Limited

Clinical • New P2 trial • Glomerulonephritis • Renal Disease

TG Therapeutics Provides Business Update and Reports Third Quarter 2021 Financial Results (GlobeNewswire) - "Generated $4.3M in total net UKONIQ revenue from launch through the end of Q3 2021, approximately seven months; Continue the commercialization of UKONIQ in R/R MZL and FL and expand commercialization capabilities in preparation for a potential launch of U2 in CLL and ublituximab in RMS. Seek to obtain U.S. FDA approval of U2 in CLL and SLL by the PDUFA goal date of March 25, 2022. Continue to enroll patients into the newly launched ULTRA-V Phase 3 trial evaluating the triple combination of U2 plus venetoclax. Continue to advance our early pipeline candidates including TG-1501 (cosibelimab) our PDL1 inhibitor, TG-1701 our BTK inhibitor and TG-1801 our CD47/CD19 bispecific antibody."

PDUFA date • Sales • Trial status • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology • Small Lymphocytic Lymphoma

TG Therapeutics Highlights Data Selected for Presentation at the 63rd American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "TG Therapeutics...announced the release of six abstracts that will be presented at the upcoming 63rd American Society of Hematology (ASH) annual meeting and exposition, to be held December 11 – 14, 2021....'Specifically, we are pleased to share new data from the UNITY-NHL Phase 2b trial showing the U2 combination in patients with relapsed or refractory marginal zone lymphoma and diffuse large b-cell lymphoma. We are also excited to share two novel analyses from the UNITY-CLL Phase 3 trial....We will also share two presentations from studies evaluating U2 triplet regimens with a BTK, namely TG-1701 and ibrutinib'."

Clinical data • P2 data • P3 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

An Open Label Study of the Effects of SHR1459 in NMOSDs Patients (clinicaltrials.gov) - P2; N=10; Active, not recruiting; Sponsor: Reistone Biopharma Company Limited; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • MRI

A Phase I Study of SHR1459 in Healthy Subjects (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: Jiangsu HengRui Medicine Co., Ltd.; Not yet recruiting ➔ Completed

Clinical • Trial completion

SHR1459-II-201: SHR1459 in Combination With YY-20394 in Recurrent and Refractory B-cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2; N=102; Recruiting; Sponsor: Jiangsu HengRui Medicine Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Could a combo TG-1701 with either CC-200 or CC-92480 in #mmsm be considered @SagarLonialMD @TGTherapeutics ? @ScienceAtBMS @JoeSzustakowski" (@Biotech2050)

Hematological Malignancies • Multiple Myeloma