About TG Therapeutics

TG Therapeutics, Inc. operates as a fully-integrated, commercial stage biopharmaceutical company. The company focuses on the acquisition, development and commercialization of novel treatments for B-cell diseases. In addition to an active research pipeline, including five investigational medicines across these therapeutic areas, the company has received accelerated approval from the U.S. Food and Drug Administration (FDA) for UKONIQ (umbralisib), for the treatment of adult patients with relapsed or refractory marginal zone lymphoma who have received at least one prior anti-CD20-based regimen and relapsed or refractory follicular lymphoma who have received at least three prior lines of systemic therapies. In addition to a research pipeline including several investigational medicines, the company has received approval from the U.S. Food and Drug Administration (FDA) for BRIUMVI (ublituximab-xiiy) for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. The company also actively evaluate complementary products, technologies and companies for in-licensing, partnership, acquisition and/or investment opportunities. FDA Approval and the U.S. Launch of BRIUMVI In December 2022, the company announced that the FDA granted approval of ublituximab, referred to as BRIUMVI, for the treatment of RMS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. BRIUMVI is an anti-CD20 monoclonal antibody approved for patients with RMS that can be administered in a one-hour infusion following the starting dose. Approval was granted for this indication based on data from the ULTIMATE I & II Phase 3 trials, which demonstrated superiority over teriflunomide in significantly reducing the annualized relapse rate (ARR, the primary endpoint), the number of T1 Gd-enhancing lesions and the number of new or enlarging T2 lesions. Results from the ULTIMATE I & II trials were recently published in August 2022 in The New England Journal of Medicine. In January 2023, the company announced the commercial launch of BRIUMVI, making it available to physicians and patients. UNITY-CLL Phase 3 Trial & Withdrawal of the BLA/sNDA Submission for U2 to Treat Patients with CLL/SLL and Withdrawal of UKONIQ (umbralisib) from Sale In February 2021, the company announced that the FDA granted accelerated approval of umbralisib, the company’s PI3K delta inhibitor, then commercially referred to as UKONIQ, for the treatment of adult patients with relapsed or refractory Marginal Zone Lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and adult patients with relapsed or refractory Follicular Lymphoma (FL) who have received at least three prior lines of systemic therapy. To further expand the use of UKONIQ and to obtain the approval of ublituximab, the company’s anti-CD20 monoclonal antibody under development, it conducted the UNITY-CLL study, a global, Phase 3, randomized, controlled clinical trial, that compared the combination of ublituximab, and UKONIQ, (combination referred to as U2), to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial met its primary endpoint, and based on those results, a Biologics License Application (BLA) and supplemental New Drug Application (sNDA) were submitted to the U.S. Food and Drug Administration (FDA) for U2 to treat patients with CLL/small lymphocytic lymphoma (SLL). In November 2021, the company received notification from the FDA that it planned to host an Oncologic Drug Advisory Committee (ODAC) meeting in connection with its review of the pending BLA/sNDA and to discuss the benefit risk of UKONIQ in its approved indications. While the FDA identified a number of concerns, the FDA’s desire to host an ODAC appeared to stem from an early ad hoc analysis of overall survival (OS) from the UNITY-CLL trial. In April 2022, based on newly updated OS data from the UNITY-CLL study, which showed a negative survival benefit, the company decided to withdraw the pending BLA/sNDA for U2 to treat CLL/SLL. In April 2022, the company also announced the voluntary withdrawal of UKONIQ from sale for its approved indications. The company’s decision to withdraw UKONIQ from sale was primarily based on the withdrawal of the BLA and sNDA for U2 in CLL. In June 2022, the FDA withdrew its approval of UKONIQ. As a result of these withdrawals, the company closed or are in the process of closing all studies related to umbralisib +/- ublituximab in oncology. Products BRIUMVI (ublituximab-xiiy) Overview BRIUMVI is the first and only anti-CD20 monoclonal antibody approved for the treatment of RMS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults, that can be administered in a one-hour infusion following the starting dose. Late-Stage Clinical Development of Ublituximab-xiiy ULTIMATE I & II Trials Evaluating Single Agent Ublituximab in RMS: ULTIMATE I and ULTIMATE II are two independent Phase 3 trials. Each trial is a global, randomized, multi-center, double-blinded, double-dummy, active-controlled study evaluating the efficacy and safety/tolerability of ublituximab-xiiy (450mg dose administered by one hour intravenous infusion every six months, following a Day 1 infusion of 150mg over four hours, and a Day 15 infusion of 450mg over one hour) to teriflunomide (14mg oral tablets taken once daily) in subjects with RMS. The primary endpoint for each study was ARR following 96 weeks of treatment. This program was led by Lawrence Steinman, MD, George A. Zimmermann Professor and Professor of Pediatrics, Neurology and Neurological Sciences at Stanford University. In December 2020, the company announced positive topline results from the ULTIMATE I & II trials. Both studies met their primary endpoint of significantly reducing ARR over a 96-week period (p<0.005 in each study) with ublituximab-xiiy demonstrating an ARR of <0.10 in each of the studies. Relative reductions of approximately 60% and 50% in ARR over teriflunomide were observed in ULTIMATE I & II, respectively. Key secondary MRI endpoints were also met. In August 2022, the full results from the ULTIMATE I & II trials were published in the New England Journal of Medicine. Commercialization of BRIUMVI (ublituximab-xiiy) In December 2022, the company announced the FDA approval of BRIUMVI (ublituximab-xiiy) for the treatment of RMS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults, primarily based on results from the ULTIMATE I & II Phase 3 trials, and in January 2023, the company announced the U.S. commercial launch of BRIUMVI, making it available to physicians and patients. A marketing authorization application (MAA) has been submitted to the European Medicines Agency (EMA) for ublituximab to treat adult patients with relapsing forms of MS. The company expects a decision to be made on this application in the second half of 2023. The company will continue to evaluate options for commercialization outside the U.S., either alone or with a partner, that maximizes the potential return on investment. TG-1701 (BTK inhibitor) Overview TG-1701 is a novel, orally available and covalently-bound Bruton’s tyrosine kinase (BTK) inhibitor that exhibits strong selectivity to BTK in in vitro kinase screening. B-cell receptor (BCR) signaling is crucial for normal B-cell development and supports the survival and growth of malignant B-cells in patients with B-cell leukemias or lymphomas. Targeting BTK, an essential element of BCR signaling pathway which regulates the survival, activation, proliferation, and differentiation of B lymphocytes, has shown remarkable efficacy with an acceptable safety profile in B-cell malignancies. The company is evaluating TG-1701 in a Phase 1, multi-center, dose-escalation clinical trial in patients with B-cell malignancies. Key secondary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity. Data from this trial was presented at the 2021 American Society of Hematology (ASH) annual meeting. TG-1801 (anti-CD47/anti-CD19 bispecific monoclonal antibody) Overview TG-1801 is a first-in-class, bispecific CD47 and CD19 antibody. It is the first therapy to target both CD19, a B-cell specific market widely expressed across B-cell malignancies, and CD47, the ‘don’t eat me’ signal used by both healthy and tumor cells to evade macrophage mediated phagocytosis. CD47 is expressed ubiquitously on normal cells, including red blood cells and platelets. CD19 is a specific B-cell marker, expressed early during pre-B cell ontogeny and until terminal differentiation into early plasma cells. The majority of B-cell lineage malignancies (more than 90%) express CD19, including NHL, CLL and acute lymphoblastic leukemia (ALL). Tumor B-cells that have lost the expression of CD20 after anti-CD20 mAb therapy, have been found to maintain the expression of CD19, making CD19 an attractive target in the treatment of B cell malignancies. In the first quarter of 2019, the company commenced a Phase 1 first-in-human, dose-escalation study of TG-1801. This study is evaluating escalating doses of TG-1801 in patients with B-Cell lymphoma. The primary objective of the study is to determine the recommended Phase 2 dose and to characterize the safety profile of TG-1801. Key secondary objectives are to evaluate the pharmacokinetics of TG-1801 and its preliminary anticancer activity. In December 2022, preliminary results from this first-in-human Phase 1 study were presented at the 64th American Society of Hematology (ASH) Annual Meeting & Exposition. TG-1801 was well tolerated as monotherapy and in combination with ublituximab with no MTD identified and exhibited preliminary signs of efficacy in a variety of relapsed or refractory B-cell lymphomas. In the first half of 2021, the company commenced a second Phase 1 study of TG-1801 in the U.S. to continue dose optimization as monotherapy and in combination with ublituximab. Enrollment in this study is ongoing. Intellectual Property and Patents BRIUMVI (ublituximab-xiiy) Pursuant to the company’s license for ublituximab with LFB Biotechnologies, GTC Biotherapeutics, and LFB/GTC LLC, it has the exclusive commercial rights to a series of patents and patent applications in the U.S. and in multiple countries around the world, as well as a non-exclusive license to additional background patent rights. The composition of matter patent for ublituximab has been issued in the U.S., Europe and other jurisdictions, including Australia, Canada, China, Japan, Korea, and India. The expected expiration for the composition of matter patent is 2029 in the U.S. and 2025 in Europe and other non-U.S. jurisdictions, exclusive of patent term extensions, which could result in later expiration dates. The company also has a method of use patent on the combination of UKONIQ and ublituximab, which has been issued in the U.S., Europe, and other jurisdictions, including Australia, China, Korea, and Japan, and is pending in other territories. The expected expiration of the method of use patent for the combination of UKONIQ and ublituximab is 2033. In the U.S., the Biologics Price Competition and Innovation Act provides that BRIUMVI is eligible for 12 years of market exclusivity from the date of BRIUMVI’s U.S. approval. During this 12 year period a biosimilar product that references the company’s BRIUMVI product, cannot be approved. TG-1701 (BTK inhibitor) Pursuant to the company’s license agreement with Jiangsu Hengrui Medicine Co. (Hengrui), it has the exclusive commercial rights in the treatment of hematologic cancers to a patent family which covers the composition of matter and proposed methods of use for various therapeutic indications in the U.S. and certain other countries. Patents directed to the compound have granted in the U.S., Europe, and other jurisdictions, including Australia, Canada, Japan, China, and Korea and are expected to expire no sooner than October 2034. Applications are pending in other jurisdictions. TG-1801 (anti-CD47/anti-CD19 bispecific antibody) Pursuant to the company’s joint venture and license option agreement with Novimmune SA (Novimmune), it maintains an exclusive option, exercisable at specific times during development, to license the commercial rights to a series of global patent applications and patents, and the non-exclusive right to certain technology patent applications. Patents directed to a bispecific antibody have issued in Australia, China, Europe, Japan, and Russia and are pending in other jurisdictions including the U.S. Any patents maturing from these pending applications are expected to expire no sooner than December 2033. Licensing Agreements and Collaborations The company has formed strategic alliances with a number of companies for the manufacture and commercialization of its products. The company’s key strategic alliances are discussed as follows. BRIUMVI (ublituximab-xiiy) LFB Biotechnologies S.A.S, GTC Biotherapeutics, LFB/GTC LLC. In January 2012, the company entered into an exclusive license agreement with LFB Biotechnologies, GTC Biotherapeutics and LFB/GTC LLC, all wholly-owned subsidiaries of LFB Group, relating to the development of ublituximab (the LFB License Agreement). Under the terms of the LFB License Agreement, the company has acquired the exclusive worldwide rights (exclusive of France/Belgium) for the development and commercialization of ublituximab. Ildong Pharmaceutical Co. Ltd.(Ildong) In November 2012, the company entered into an exclusive (within the territory) sublicense agreement with Ildong relating to the development and commercialization of ublituximab in South Korea and Southeast Asia. Under the terms of the sublicense agreement, Ildong has been granted a royalty bearing, exclusive right, including the right to grant sublicenses, to develop and commercialize ublituximab in South Korea, Taiwan, Singapore, Indonesia, Malaysia, Thailand, the Philippines, Vietnam, and Myanmar. TG-1701 (BTK inhibitor) In January 2018, the company entered into a global exclusive license agreement with Jiangsu Hengrui Medicine Co., to acquire worldwide intellectual property rights, excluding Asia but including Japan, and for the research, development, manufacturing, and commercialization of products containing or comprising of any of Hengrui’s Bruton’s Tyrosine Kinase inhibitors containing the compounds of either TG 1701 (SHR1459 or EBI1459) or TG1702 (SHR1266 or EBI1266). TG-1801 (anti-CD47/anti-CD19 bispecific antibody) In June 2018, the company entered into a Joint Venture and License Option Agreement with Novimmune to collaborate on the development and commercialization of Novimmune’s novel first-in-class anti-CD47/anti-CD19 bispecific antibody known as TG 1801 (previously NI 1701). The companies will jointly develop the product on a worldwide basis, focusing on indications in the area of hematologic B-cell malignancies. The company serves as the primary responsible party for the development, manufacturing and commercialization of the product. UKONIQ (umbralisib) In September 2014, the company exercised its option to license the global rights to umbralisib, thereby entering into an exclusive licensing agreement (the Umbralisib License) with Rhizen Pharmaceuticals, S A (Rhizen) for the development and commercialization of umbralisib. Cosibelimab In March 2015, the company entered into a global collaboration (the Collaboration Agreement) with Checkpoint Therapeutics, Inc. (Checkpoint) for the development and commercialization of Checkpoint’s anti-PD-L1 and anti-GITR antibody research programs in the field of hematological malignancies with an option to acquire rights in autoimmune diseases. Supply and Manufacturing The company has established a contract manufacturing relationship for the commercial supply of BRIUMVI with Samsung Biologics. Government Regulation Before marketing in the U.S., any drug that the company develops must undergo rigorous pre-clinical testing and clinical trials and an extensive regulatory review and approval process implemented by the FDA under the FDCA and, in the case of biologics, the Public Health Service Act. The company is required to submit extensive pre-clinical and clinical data and supporting information to the FDA for each indication or use to establish a drug candidate’s safety and efficacy before it can secure FDA approval to market or sell a product in the U.S. Any products for which the company receives FDA approval are subject to continuing regulation by the FDA and other federal and state regulators on a wide range of matters, including, among other things current Good Manufacturing Practices (cGMPs) and product quality, pharmacovigilance and reporting of adverse events, product distribution requirements, fulfilling post-marketing or confirmatory study or Risk Evaluation and Mitigation Strategy (REMS) commitments, and complying with FDA promotion and advertising requirements. Research and Development The company’s research and development expenses were $112.1 million for the year ended December 31, 2022. History TG Therapeutics, Inc. was incorporated in Delaware in 1993.