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Item 1. Business

2024-02-29 compared with 2023-03-01 · 132 added, 88 removed, 390 unchanged (36% of the section changed)

TG Therapeutics is a fully-integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell diseases.

TG Therapeutics is a fully-integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell mediated diseases.

In addition to a research pipeline including several investigational medicines, TG 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.

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, as well as approval by the European Commission (EC) and the Medicines and Healthcare products Regulatory Agency (MHRA) for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features in Europe and the United Kingdom (UK), respectively.

We also actively evaluate complementary products, technologies and companies for in-licensing, partnership, acquisition and/or investment opportunities.

Business Updates

Business Highlights

FDA Approval and U.S.

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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.

Results from the ULTIMATE I & II trials were published in August 2022 in The New England Journal of Medicine.

On January 26, 2023, we announced the commercial launch of BRIUMVI, making it available to physicians and patients.

We are committed to helping patients access BRIUMVI through the BRIUMVI Patient Support Program, which we launched following the approval, additional information can be found at www.briumvi.com.

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

On February 5, 2021, we 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, our anti-CD20 monoclonal antibody under development, we 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, we 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.

On April 15, 2022, based on newly updated OS data from the UNITY-CLL study, which showed a negative survival benefit, we decided to withdraw the pending BLA/sNDA for U2 to treat CLL/SLL.

On April 15, 2022, we also announced the voluntary withdrawal of UKONIQ from sale for its approved indications.

Our decision to withdraw UKONIQ from sale was primarily based on the withdrawal of the BLA and sNDA for U2 in CLL.

On June 1, 2022, the FDA withdrew its approval of UKONIQ.

As a result of these withdrawals, we closed or are in the process of closing all studies related to umbralisib +/- ublituximab in oncology.

Commercialization of BRIUMVI

On June 1, 2023, we announced that the EC granted approval of BRIUMVI for the treatment of adult patients with RMS who have active disease defined by clinical or imaging features.

On August 1, 2023, we announced an agreement with Neuraxpharm Pharmaceuticals, S.L.

(Neuraxpharm), a leading European specialty pharmaceutical company focused on the treatment of central nervous system (CNS) disorders, for the ex-U.S.

commercialization of BRIUMVI.

On November 1, 2023, we announced that we also received approval by the MHRA for BRIUMVI to treat adult patients with RMS with active disease defined by clinical or imaging features in the UK.

On February 26, 2024, we announced the commercial launch of BRIUMVI in the European Union (EU) by Neuraxpharm, with BRIUMVI made available for commercial sale in Germany, with additional EU markets expected to follow.

Pipeline Expansion

On January 9, 2024, we entered into an agreement with Precision BioSciences, Inc.

(Precision) to acquire a worldwide license to Precision’s Azercabtagene Zapreleucel (azer-cel), an allogeneic CD19 CAR T cell therapy program for autoimmune diseases and all other non-oncology indications.

Azer-cel is an allogeneic (off the shelf) CAR T program, and the Company has near term plans to evaluate the program in multiple autoimmune indications.

CORPORATE INFORMATION

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Our telephone number is 1-877-575-TGTX(8489), and our e-mail address is info@tgtxinc.com.

We maintain a website with the address www.tgtherapeutics.com and maintain various social media accounts, including but not limited to Twitter and LinkedIn.

We maintain a website with the address www.tgtherapeutics.com and maintain various social media accounts, including but not limited to X (formerly Twitter ) and LinkedIn.

We also maintain websites related to BRIUMVI, including but not limited to www.BRIUMVI.com, and www.BRIUMVIPATIENTSUPPORT.com.

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social media channels listed on our website.

As a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B cell diseases, our key corporate objectives include:

As a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B cell mediated diseases, our key corporate objectives include:

Successfully commercializing BRIUMVI in the U.S.

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Our Approach and Platform

Our approach to drug development is centered on developing therapies for b cell diseases.

Our process begins by identifying validated targets against B-cell diseases, and then searching for and, ideally, acquiring what we believe to be “best-in-class” compounds with complementary mechanisms against these targets.

Our preference is to identify targets for which there is human clinical proof of concept that the mechanism is active in B-cell diseases and then to identify drug candidates that effectively modulate the desired molecular target.

Our approach to drug development is centered on developing therapies for B- cell mediated diseases.

Our process begins by identifying validated targets against B-cell mediated diseases, and then searching for and, ideally, acquiring what we believe to be “best-in-class” compounds with complementary mechanisms against these targets.

Our preference is to identify targets for which there is human clinical proof of concept that the mechanism is active in B-cell mediated diseases and then to identify drug candidates that effectively modulate the desired molecular target.

We identify these drug candidates at academic centers of excellence or in development at biotech companies or pharmaceutical companies globally.

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This approach enables us to minimize target risk while looking for the best available drug candidates around the world.

By focusing on B-cell diseases and targets with a known activity profile, we believe that we can quickly identify the patients most likely to respond, resulting in a more efficient development path with the potential for a greater likelihood of success.

Our approach is enabled by our clinical development platform which includes an internal team with a deep understanding of B-cell diseases and significant experience successfully obtaining FDA approval for innovative treatments for these complex diseases.

By focusing on B-cell mediated diseases and targets with a known activity profile, we believe that we can quickly identify the patients most likely to respond, resulting in a more efficient development path with the potential for a greater likelihood of success.

Our approach is enabled by our clinical development platform which includes an internal team with a deep understanding of B-cell mediated diseases and significant experience successfully obtaining FDA approval for innovative treatments for these complex diseases.

AUTOIMMUNE DISEASE OVERVIEW

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These antibodies cannot discriminate “self” from “non-self,” and inadvertently mount a disabling immune response against normal organs.

Examples of common and very debilitating autoimmune disorders for which abnormally functioning B-cells have been implicated include MS and rheumatoid arthritis (RA).

Some of these diseases may not be antibody mediated but may still result from aberrant activity of B-cells.

Examples of common and very debilitating autoimmune disorders for which abnormally functioning B-cells have been implicated include multiple sclerosis (MS) and rheumatoid arthritis (RA).

The Company’s current focus is on MS.

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We currently license worldwide development and commercial rights, subject to certain limited geographical restrictions, for all of our products under development.

The following table summarizes the current clinical trial status for our lead drug candidates as of February 2023.

The following table summarizes the current status for our lead drug candidates as of February 2024.

Clinical Drug Candidate:

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Initial Target Disease

Stage of Development

Stage of Development (trial name)

Ublituximab (anti-CD20 mAb)

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Phase 1 trial

Auto-immune disorders

Phase 1 (pending)

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

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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.

Key secondary magnetic resonance imaging (MRI) endpoints were also met.

On August 22, 2022, the full results from the ULTIMATE I & II trials were published in the New England Journal of Medicine.

ENHANCE Phase 3b Trial:

On October 11, 2023, we presented the first data from the ENHANCE Phase 3b trial evaluating BRIUMVI in patients with RMS who switch from another anti-CD20 therapy to BRIUMVI.

The presentation occurred at the 2023 European Committee for Treatment and Research in Multiple Sclerosis Annual Meeting.

In this study, patients with low levels of B-cells as pre-specified in the protocol are eligible to proceed directly to a full dose of BRIUMVI 450mg without receiving a 150 mg loading dose.

As of the presentation, 13 patients switched from Ocrevus to BRIUMVI 450mg as a 2-hour infusion with no infusion related reactions reported and no unexpected side effects.

An additional 2 patients switched from Ocrevus to BRIUMVI 450mg as a 1-hour infusion again with no infusion related reactions reported and no unexpected side effects.

The study has continued to enroll patients at 450mg as a 1-hour infusion and additional data is expected to be reported during the course of 2024.

Commercialization of BRIUMVI (ublituximab-xiiy)

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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.

We expect a decision to be made on this application in the second half of 2023.

We will continue to evaluate options for commercialization outside the U.S., either alone or with a partner, that maximizes the potential return on investment.

On July 1, 2023, the permanent J-Code for BRIUMVI (J2329) became effective.

Commercialization of BRIUMVI

On June 1, 2023, we announced that the EC granted approval of BRIUMVI for the treatment of adult patients with RMS who have active disease defined by clinical or imaging features.

With this approval, the centralized marketing authorization is valid in all EU member states, Iceland, Norway and Liechtenstein.

On August 1, 2023, we announced an agreement with Neuraxpharm, a leading European specialty pharmaceutical company focused on the treatment of CNS disorders, for the Ex-US commercialization of BRIUMVI.

Under the terms of the commercialization agreement, we received an upfront payment of $140 million, and are eligible to receive an additional $12.5 million upon launch in the first EU country and up to an additional $492.5 million in milestone-based payments on achievement of certain launch and commercial milestones.

The total deal is valued at up to $645 million in upfront and milestone payments.

In addition, we will receive tiered double-digit royalties on net product sales up to 30%.

In exchange, Neuraxpharm will have the exclusive right to commercialize BRIUMVI in certain territories outside the United States, Canada and Mexico, the commercialization rights for which had been previously retained by TG, thus excluding certain Asian countries subject to previously existing partnerships.

We retain an option to buy back all rights under the commercialization agreement for a period of two years in the event of a change in control of TG.

On November 1, 2023, we announced that we also received approval by the MHRA for BRIUMVI to treat adult patients with RMS with active disease defined by clinical or imaging features in the UK.

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.

B-cell receptor (BCR) signaling is crucial for normal B-cell development and supports the survival and growth of B-cells.

We are currently 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.

Data from this trial was last 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, we 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.

TG-1801 is a potentially first-in-class, bispecific CD47 and CD19 antibody.

It is the first therapy to target both CD19, a B-cell specific marker 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.

In the first quarter of 2019, we commenced a Phase 1 first-in-human, dose-escalation study of TG-1801 in patients with B-cell lymphoma.

In December 2022, preliminary results from this first-in-human Phase 1 study were presented at the 64 th 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, we commenced a second Phase 1 study of TG-1801 in the US to continue dose optimization as monotherapy and in combination with ublituximab.

Enrollment in this study is ongoing.

TG-1801 was well tolerated as monotherapy and in combination with ublituximab with no maximum tolerable dose (MTD) identified and exhibited preliminary signs of efficacy in a variety of relapsed or refractory B-cell lymphomas.

In the first half of 2021, we commenced a second Phase 1 study of TG-1801 in the U.S.

to continue dose optimization as monotherapy.

Azercabtagene Zapreleucel (azer-cel)

Azer-cel is an allogeneic (off-the-shelf) CD19 CAR T cell therapy program for autoimmune diseases and all other non-oncology indications.

Made from donor-derived T cells modified using a proprietary ARCUS genome editing technology, azer-cel recognizes the well characterized B-cell surface protein CD19, an important and validated target in several B-cell cancers and autoimmune diseases.

Azer-cel is designed to avoid graft-versus-host disease (GvHD), a significant complication associated with other donor-derived, cell-based therapies.

The Company has near term plans to evaluate the program in autoimmune indications.

INTELLECTUAL PROPERTY AND PATENTS

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Litigation would involve substantial costs.

Moreover, physicians may prescribe such a competitive identical product for indications other than the one for which the product has been approved, or off-label indications, that are covered by the applicable patents.

Although such off-label prescriptions may directly infringe or contribute to or induce infringement of method of use patents, such infringement is difficult to prevent or prosecute.

Patent Term Restoration and Marketing Exclusivity

Depending upon the timing, duration and specifics of any FDA approval of our drug candidates, some of our U.S.

patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act.

The Hatch-Waxman Act permits restoration of the term of certain types of patents for up to five years as compensation for patent term lost during the FDA regulatory review process.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The patent term restoration period is generally one-half the time between the effective date of an Investigational New Drug (IND) application and the submission date of a New Drug Application (NDA) or BLA plus the time between the submission date of an NDA or BLA and the approval of that application.

The calculation is subject to several subtractions for any portion of the regulatory review process that occurred before the date the patent was issued and any portion during which the FDA determined a lack of due diligence.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent, and within 60 days of a product’s approval.

The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension.

Moreover, a patent can only be extended once, and thus, if a single patent is applicable to multiple products, it can only be extended based on one product.

Following the approval of BRIUMVI in the U.S., we have applied for patent term extensions for certain of our issued U.S.

patents covering our product and/or their methods of use.

Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug and have been filed for in certain European Patent (EP) countries.

Also, under the Hatch-Waxman Act, drugs that are new chemical entities (NCEs) are eligible for a five-year period of marketing exclusivity in the United States.

During the exclusivity period, the FDA may not accept for review an abbreviated new drug application (ANDA) or a 505(b)(2) NDA submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovator drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The Hatch-Waxman Act also provides three years of marketing exclusivity for a drug product that contains an active moiety that has been previously approved, if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations.

During this period, FDA will not approve an application filed by a third party for the protected conditions of use that relies on any of the data from the new clinical investigations that was submitted by the innovator company.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA that does not rely on the innovator company’s data.

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created an abbreviated pathway for companies to bring biologic drugs to market that are biosimilar to previously approved branded reference products by relying on clinical studies that were performed by the reference product sponsor.

The BPCIA also created a 12-year period of data exclusivity for innovator biologics, whereby the FDA cannot approve a biological license application (BLA) for a biosimilar product relying on data for a specific reference product until 12 years after the reference product is first licensed.

BLA supplements are not eligible for any additional exclusivity.

The objectives of the BPCIA are conceptually similar to those of the Hatch-Waxman Act described above.

The implementation of an abbreviated approval pathway for biosimilar products is under the direction of the FDA.

Since the enactment of the BPCIA, the FDA has issued guidance on biosimilars, addressing scientific, quality and procedural issues relevant to an abbreviated application for a biosimilar product.

As of December 2022, the FDA had approved 40 biosimilar products.

Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.

This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.

We, or those companies from which we have licensed our drug candidates, file patent applications directed to our drug candidates in an effort to establish intellectual property positions regarding these new chemical entities as well as uses of these new chemical entities in the treatment of diseases.

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These patents and patent applications include composition of matter patents relating to the structure and mechanism of action for ublituximab, as well as method of use patents which cover use of ublituximab in combination with various agents and for various therapeutic indications.

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.

Our earliest in time patent families relate to compositions of matter for ublituximab , which 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-US jurisdictions, exclusive of patent term extensions, which could result in later expiration dates.

and 2025 in Europe and other non-U.S.

jurisdictions, exclusive of patent term extensions, which could result in later expiration dates.

We also have 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.

Our most recently filed patent family relates to compositions of matter comprising ublituximab, methods of manufacturing those compositions and methods for treating multiple sclerosis using those compositions.

This family includes three issued U.S.

patents and one recently allowed U.S.

We also have patent applications pending in this family in the U.S., Argentina, the EU and Taiwan.

The Patent Cooperation Treaty application , from which further national phase applications may be filed, is also pending.

Patents issuing from this family may first begin to expire as early as 2042.

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.

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Any patents maturing from these pending applications are expected to expire no sooner than December 2033.

Azer-Cel (allogeneic CD19 CAR T)

Pursuant to our license agreement with Precision, we have an exclusive license to develop and commercialize Precision’s azer-cel for the treatment of autoimmune and other non-oncology diseases and conditions as well as a non-exclusive license to manufacture azer-cel.

The license agreement includes non-exclusive rights to a series of patents and patent applications in the U.S.

and in multiple countries around the world, as well as non-exclusive rights to additional background patent rights.

These patents and patent applications include composition of matter patents relating to azer-cel, as well as method of use patents which cover use of azer-cel.

Limitations on Patent Rights and Trade Secrets

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Additionally, proof that a competitor contributes to or induces infringement of a patented method of use by another can also prove difficult because an off-label use of a product could prohibit a finding of contributory infringement, and inducement of infringement requires proof of intent by the competitor.

Although such off-label prescriptions may directly infringe or contribute to or induce infringement of method of use patents, such infringement is difficult to prevent or prosecute.

Patent Term Restoration and Marketing Exclusivity

Depending upon the timing, duration and specifics of any FDA approval of our drug candidates, some of our U.S.

patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act.

The Hatch-Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

Also, under the Hatch-Waxman Act, drugs that are new chemical entities (NCEs) are eligible for a five-year period of marketing exclusivity in the United States.

This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA that does not rely on the innovator company’s data.

The Biologics Price Competition and Innovation Act of 2009 2009 (BPCIA) created an abbreviated pathway for companies to bring biologic drugs to market that are biosimilar to previously approved branded reference products by relying on clinical studies that were performed by the reference product sponsor.

BLA supplements are not eligible for any additional exclusivity.

The objectives of the BPCIA are conceptually similar to those of the Hatch-Waxman Act described above.

The implementation of an abbreviated approval pathway for biosimilar products is under the direction of the FDA.

Since the enactment of the BPCIA, the FDA has issued guidance on biosimilars, addressing scientific, quality and procedural issues relevant to an abbreviated application for a biosimilar product.

As of December 2022, the FDA had approved 40 biosimilar products.

Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.

LICENSING AGREEMENTS AND COLLABORATIONS

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The license will terminate on a country by country basis upon the expiration of the last licensed patent right or 15 years after the first commercial sale of a product in such country, unless the agreement is earlier terminated (i) by Ildong if the Company challenges any of the licensed patent rights, (ii) by either party due to a breach of the agreement, or (iii) by either party in the event of the insolvency of the other party.

In August 2023, we entered into an agreement with Neuraxpharm, for the ex-U.S.

commercialization of BRIUMVI.

Under the terms of the commercialization agreement, we received an upfront payment of $140 million and are eligible to receive an additional $12.5 million upon launch in the first EU country and up to an additional $492.5 million in milestone-based payments on achievement of certain launch and commercial milestones.

The total deal is valued at up to $645 million in upfront and milestone payments.

In addition, we will receive tiered double-digit royalties on net product sales up to 30%.

We retain an option to buy back all rights under the commercialization agreement for a period of two years in the event of a change in control of TG.

TG-1701 (BTK inhibitor)

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Royalty payments in the low double digits are due on net sales of licensed products and revenue from sublicenses.

Additionally, before we can license, sell, develop, or commercialize ublituximab within China, we must notify Hengrui, giving Hengrui the right of first offer.

The agreement allows combinations of TG-1701 or TG-1702 with umbralisib, ublituximab, or U2.

Additional combinations may be undertaken under the agreement subject to additional pre-specified payments to Hengrui.

The term of the agreement expires after the expiration of the last royalty term to expire with respect to any of the patent rights under the agreement.

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The Company and Novimmune will each maintain an exclusive option, exercisable at specific times during development, for the Company to license the rights to TG 1801, in which case Novimmune is eligible to receive additional milestone payments totaling approximately $185 million as well as tiered royalties on net sales in the high single to low double digits upon and subject to the achievement of certain milestones.

Azer-Cel (allogeneic CD19 CAR T)

In January 2024, we, through our wholly-owned subsidiary, TG Cell Therapy, Inc., entered into a global exclusive license agreement with Precision to develop and commercialize azer-cel for autoimmune diseases and all other non-oncology indications.

Pursuant to such license Agreement, the Company made an upfront payment to Precision of $7.5 million, consisting of (i) $5.25 million in cash and (ii) $2.25 million as an equity investment.

The Company will make an additional deferred payment of $2.5 million to Precision as an equity investment to Precision within 12 months at a pre-specified premium.

Upon achievement of certain near-term clinical or time-based milestones, the Company will make a further $7.5 million payment to Precision, a portion of which will also be an equity investment in Precision’s common stock at a pre-specified premium.

Precision will be eligible to receive up to $288 million in additional milestone payments based on the achievement of certain clinical, regulatory and commercial milestones.

In addition, the Company is obligated to pay Precision high-single-digit to low-double-digit royalties on net sales of the licensed product on a country-by-country basis until the latest to occur of patent expiration, loss of regulatory exclusivity or a period of ten years following the first commercial sale of the licensed product in such country.

The Company has also agreed to make certain payments to Precision’s licensors during the term of our license agreement with Precision.

UKONIQ (umbralisib)

In September 2014, we exercised our 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.

Rhizen is eligible to receive approval and sales-based milestone payments in the aggregate of approximately $175 million payable.

Rhizen is eligible to receive approval and sales-based milestone payments in the aggregate of approximately $175 million.

Additionally, Rhizen receives tiered royalties that escalate from high single digits to low double digits on any net sales of umbralisib.

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(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.

Under the terms of the agreement, we will make development and sales-based milestone payments up to an aggregate of approximately $110 million and will pay a tiered low double-digit royalty on net sales.

The royalty term will terminate on a country by country basis upon the later of (i) ten years after the first commercial sale of any applicable licensed product in such country, or (ii) the expiration of the last-to-expire patent containing a valid claim to any licensed product in such country.

In September 2023, we terminated this agreement and have no remaining obligations or commitments under the Collaboration Agreement.

Competition in the pharmaceutical and biotechnology industries is intense.

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In addition, while we believe not directly competitive, there is also a subcutaneous anti-CD20 monoclonal antibody approved for MS, ofatumumab (Novartis AG).

TG-1701 and TG-1801 if approved will also face competition from drugs on the market and under development in the same therapeutic class as each of those drugs.

TG-1701, TG-1801 and azer-cel, if approved will also face competition from drugs on the market and under development in the same therapeutic class as each of those drugs.

Additional information can be found under Item “1A - Risk Factors – Other Risks Related to Our Business” within this report.

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None of our product candidates, except BRIUMVI, are approved for sale in any market in which we have marketing rights.

Before marketing in the U.S., any drug that we develop 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.

Before marketing in the U.S., any drug that we develop must undergo rigorous pre-clinical testing and clinical trials and an extensive regulatory review and approval process implemented by the FDA under the Federal Food, Drug, and Cosmetic Act (FDCA) and, in the case of biologics, the Public Health Service Act.

The FDA regulates, among other things, the pre-clinical and clinical testing, safety, efficacy, approval, manufacturing, quality control and assurance, record keeping, pharmacovigilance and adverse event reporting, packaging, labeling, storage, advertising, promotion, import and export, sale and distribution of biopharmaceutical products.

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ineffectiveness of the drug candidates.

For clinical trials that are intended to form the basis of a new drug or biologics license application for approval, sponsors of drugs may apply for an SPA from the FDA, by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols.

In December 2022, with the passage of Food and Drug Omnibus Reform Act, Congress required sponsors to develop and submit a diversity action plan (DAP) for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

Specifically, DAPs must include the sponsor’s goals for enrollment, the underlying rationale for those goals and an explanation of how the sponsor intends to meet them.

In addition to these requirements, the legislation directs the FDA to issue new guidance on diversity action plans.

For clinical trials that are intended to form the basis of a new drug or biologics license application for approval, sponsors of drugs may apply for a Special Protocol Assessment (SPA) from the FDA, by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols.

While obtaining an SPA provides some assurance the design of a trial should be sufficient for approval, the final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 trial.

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On August 16, 2022, President Biden signed into law the Inflation Reduction Act of 2022 (the Act), which, among other provisions, included several measures intended to lower the cost of prescription drugs and related healthcare reforms.

Specifically, the Act authorizes and directs the Department of Health and Human Services (the DHHS) to set drug price caps for certain high-cost Medicare Part B and Part D qualified drugs, with the initial list of drugs to be selected by September 1, 2023, and the first year of maximum price applicability to begin in 2026.

Specifically, the Act authorizes and directs the Department of Health and Human Services (the DHHS) to set drug price caps for certain high-cost Medicare Part B and Part D qualified drugs, with the initial list of drugs selected on August 29, 2023, and the first year of maximum price applicability to begin in 2026.

The Act further authorizes the DHHS to penalize pharmaceutical manufacturers that increase the price of certain Medicare Part B and Part D drugs faster than the rate of inflation.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business