Callio Therapeutics Launches with US$187 Million Series A to Advance Multi-Payload Antibody-Drug Conjugate Platform Through Clinical Proof-of-Concept

On March 3, 2025 Callio Therapeutics, a biotechnology company focused on realizing the promise of multi-payload antibody-drug conjugates (ADCs) to improve cancer therapy, reported its launch with the closing of a $187.0 million Series A financing round (Press release, Callio Therapeutics, MAR 3, 2025, View Source [SID1234650850]). This financing was led by Frazier Life Sciences with significant participation from Jeito Capital alongside other life sciences investors, including Novo Holdings A/S, Omega Funds, ClavystBio, Platanus, Norwest, Pureos Bioventures, SEEDS Capital and EDBI. The newly formed company, with headquarters in Seattle and Singapore, intends to use the proceeds from the Series A financing to achieve clinical proof-of-concept for its HER2-targeted dual-payload ADC and a second undisclosed ADC program.

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In conjunction with the financing, Callio Therapeutics has entered into an exclusive worldwide license agreement with Hummingbird Bioscience for its multi-payload ADC platform in oncology, and associated intellectual property and pipeline assets, in exchange for equity, potential milestone payments and royalties.

"We are delighted to be launching Callio Therapeutics with the support of Frazier Life Sciences and this syndicate of investors. Multi-payload ADCs have the potential to enable the targeted delivery of rational drug combinations to cancer cells, and may provide significantly enhanced efficacy," said Piers Ingram, PhD, co-founder and Chief Executive Officer of Callio Therapeutics. "This new generation of ADC therapies may meaningfully improve outcomes for patients."

Leadership Team

The founding Callio Therapeutics management team comprises individuals with extensive experience from leading biotechnology and biopharmaceutical companies including ProfoundBio, Silverback Therapeutics, SeaGen, Medarex, Hummingbird Bioscience and Genentech:

Piers Ingram, PhD, Chief Executive Officer
Jerome Boyd-Kirkup, PhD, Chief Scientific Officer
Naomi Hunder, MD, Chief Medical Officer
Angèle Maki, PhD, Chief Business Officer
"The multi-payload ADCs being developed at Callio Therapeutics have the potential to address large unmet medical needs by overcoming many of the limitations of existing ADCs," said Adam Simpson, Executive Board Chair of Callio Therapeutics and Venture Partner at Frazier Life Sciences. "With the expertise of the Callio Therapeutics team, together with access to the innovative multi-payload ADC technology, we believe that Callio Therapeutics will be the first company to show the clinical benefit of this exciting new multi-payload ADC approach and is well positioned to transform cancer therapy."

TYPE D MEETING OUTCOME WITH US FOOD AND DRUG ADMINISTRATION

On March 3, 2025 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported a regulatory update on its planned US clinical trial following its Type D meeting with the United States Food and Drug Administration (FDA) (Press release, Amplia Therapeutics, MAR 3, 2025, View Source [SID1234650784]).

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The Company has previously disclosed plans for a clinical trial in the US of its best-in-class FAK inhibitor narmafotinib, in combination with the chemotherapy regime FOLFIRINOX, in advanced pancreatic cancer patients. FOLFIRINOX, which is a mixture of four different drugs, is the preferred first-line treatment option for advanced pancreatic cancer in the US. The Company has previously reported1 that narmafotinib enhances the activity of FOLFIRINOX in preclinical models of pancreatic cancer.

A Type D meeting is an opportunity for a company to seek feedback from the FDA for specific questions regarding clinical development activities. The Company sought the FDA’s feedback regarding modifications to the clinical trial protocol previously submitted as part of the Investigational New Drug application cleared by the FDA in January 20242 . Specifically, the Company was seeking commentary regarding changes to the dose-escalation and dose-optimization phase of the study and concerning removal of a pharmacokinetic assessment of FOLFIRINOX in the trial. In the written response received by the Company, the FDA noted that the proposed changes ‘appear reasonable’ clearing the way for the Company to finalise the study protocol and initiate the final stages of trial planning prior to commencing the study.

Amplia CEO and MD Dr Chris Burns commented: "We are grateful for the thoughtful input from the FDA regarding the modifications to our clinical trial protocol. These changes will allow the Company to progress the trial in a more time-efficient and capital-efficient manner, and we are now in the final planning stages to start the trial in the coming months."

Dr Burns continued: "Positive data from this clinical study, combined with promising data from the current ACCENT trial – where narmafotinib is combined with gemcitabine and Abraxane – will position narmafotinib as the preferred drug to combine with the two main chemotherapy regimes used for the treatment of pancreatic cancer across the globe."

EMERGENT BIOSOLUTIONS REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS

On March 3, 2025 Emergent BioSolutions Inc. (NYSE: EBS) reported financial results for the quarter and year ended December 31, 2024 (Press release, Emergent BioSolutions, MAR 3, 2025, View Source [SID1234650833]).

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"As we close out 2024, I’m proud to share we delivered favorable full-year financial results driven by our core products, all the while, completing a series of strategic stabilization actions to strengthen our financial position ahead of plan," said Joe Papa, president and chief executive officer of Emergent. "This strong foundation enables Emergent to focus on profitable revenue growth and cash generation as we move forward with turnaround activities, a critical phase in our multi-year transformation plan. Our results and progress are a testament to the hard work and dedication of our entire team, and we believe Emergent’s future will be defined by the durability of our business, opportunities for new markets and innovation, and a steadfast commitment to protecting and saving lives."

FINANCIAL HIGHLIGHTS(1)
Q4 2024 vs. Q4 2023
($ in millions, except per share amounts) Q4 2024 Q4 2023 % Change
Total Revenues $ 194.7 $ 276.6 (30) %
Net Loss $ (31.3) $ (49.5) 37 %
Net Loss per Diluted Share $ (0.58) $ (0.95) 39 %
Adjusted Net Income (Loss)(2)
$ 2.6 $ (40.0) 107 %
Adjusted Net Income (Loss) per Diluted Share(2)
$ 0.05 $ (0.77) 106 %
Adjusted EBITDA(2)
$ 21.0 $ 3.4 518 %
Total Segment Gross Margin %(2)
29 % 25 %
Total Segment Adjusted Gross Margin %(2)
40 % 32 %

Year to Date ("YTD") 2024 vs. YTD 2023
($ in millions, except per share amounts) YTD 2024 YTD 2023 % Change
Total Revenues $ 1,043.6 $ 1,049.3 (1) %
Net Loss $ (190.6) $ (760.5) 75 %
Net Loss per Diluted Share $ (3.60) $ (14.85) 76 %
Adjusted Net Loss(2)
$ (12.1) $ (319.0) 96 %
Adjusted Net Loss per Diluted Share(2)
$ (0.23) $ (6.23) 96 %
Adjusted EBITDA(2)
$ 183.1 $ (22.3) 921 %
Total Segment Gross Margin %(2)
26 % 25 %
Total Segment Adjusted Gross Margin %(2)
45 % 33 %

1

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SELECT 2024 FULL YEAR BUSINESS UPDATES
•Appointed industry leader Joseph C. Papa as President, CEO and Director
•Appointed Dr. Simon Lowry as Chief Medical Officer and Head of Research and Development
•Received approximately $550 million of Medical Countermeasure Contract Modification Awards
•Awarded procurement contract valued up to $235.8 million to supply BioThrax (Anthrax Vaccine Adsorbed) to the U.S. Department of Defense
•FDA approved sBLA for expansion of the indication for ACAM2000 to include prevention of mpox disease in individuals determined to be at high risk

•Repaid $168 million of debt and extended maturities to 2029 with new $250 million secured term loan and $100 million asset-backed revolving credit facility
•Completed $117 million of targeted asset divestitures and streamlined manufacturing footprint
•Resolved legacy legal disputes including receipt of $50 million settlement payment from Janssen
•Received $30 million in development milestone payments from Bavarian Nordic as part of the sale of the Travel Health Business
•Returned to strong, positive operating cash flow
FOURTH QUARTER 2024 FINANCIAL PERFORMANCE(1)
Revenues
The Company uses the following categories in discussing product/service level revenues:
•NARCAN — comprises contributions from NARCAN Nasal Spray
•Anthrax MCM — comprises contributions from CYFENDUS, previously known as AV7909, BioThrax, Anthrasil and Raxibacumab
•Smallpox MCM — comprises contributions from ACAM2000, VIGIV CNJ-016 and TEMBEXA
•Other Products — comprises contributions from BAT and RSDL
•Bioservices — comprises service and lease revenues from the Bioservices business
($ in millions) Q4 2024 Q4 2023 % Change
Product sales, net:(3)
NARCAN
$ 65.1 $ 111.0 (41) %
Anthrax MCM 32.5 111.6 (71) %
Smallpox MCM 76.5 11.5 565 %
Other Products 7.8 15.0 (48) %
Total Product sales, net $ 181.9 $ 249.1 (27) %
Bioservices:
Services $ 6.8 $ 20.6 (67) %
Leases 0.6 0.2 200 %
Total Bioservices revenues $ 7.4 $ 20.8 (64) %
Contracts and grants $ 5.4 $ 6.7 (19) %
Total revenues $ 194.7 $ 276.6 (30) %

2

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Product Sales, net
NARCAN
For Q4 2024, revenues from NARCAN (naloxone HCl) Nasal Spray decreased $45.9 million, or 41%, as compared with Q4 2023. The decrease was primarily driven by lower sales of over-the-counter ("OTC") NARCAN, coupled with lower revenues for Canadian retail sales.
Anthrax MCM
For Q4 2024, revenues from Anthrax MCM products decreased $79.1 million, or 71%, as compared with Q4 2023. The decrease reflects the impact of timing of sales related to CYFENDUS, Anthrasil, and BioThrax. Anthrax vaccine product sales are primarily made under annual purchase options exercised by the U.S. government (the "USG"). Fluctuations in revenues result from the timing of USG purchases and the exercise of annual purchase options, the availability of governmental funding and the Company’s delivery of orders that follow.
Smallpox MCM
For Q4 2024, revenues from Smallpox MCM products increased $65.0 million, or 565%, as compared with Q4 2023. The increase was primarily due higher ACAM2000 sales to non-U.S. customers and timing of USG purchases of VIGIV CNJ-016. Fluctuations in revenues result from the timing of USG purchases and the exercise of annual purchase options in existing procurement contracts, the availability of governmental funding and Company delivery of orders that follow.
Other Products
For Q4 2024, revenues from Other Product sales decreased $7.2 million, or 48%, as compared with Q4 2023. The decrease was due to lower sales of RSDL, which was sold to SERB during the third quarter of 2024, and lower product sales of BAT, due to timing of deliveries.
Bioservices Revenues
Services
For Q4 2024, revenues from Bioservices services decreased $13.8 million, or 67%, as compared with Q4 2023. The decrease was primarily attributable to the sale of the Camden facility to Bora Pharmaceuticals Injectables Inc., a subsidiary of Bora Pharmaceuticals Co., Ltd ("Bora"), during the third quarter of 2024, coupled with lower revenue from the Company’s Bayview facility as a result of the prior year resolution of a customer’s outstanding obligation, partially offset by higher production from the Company’s Winnipeg facility.
Leases
For Q4 2024, revenues from Bioservices leases increased $0.4 million, or 200%, as compared with Q4 2023. The increase was attributable to an increase in lease revenue associated with SERB at our Winnipeg facility.
Contracts and Grants
For Q4 2024, revenues from contracts and grants decreased $1.3 million, or 19%, as compared with Q4 2023. The decrease was primarily attributable to the wind-down of various development initiatives.

Biond Biologics to Regain Full Rights to BND-22, a Novel Immune Checkpoint Inhibitor Targeting the ILT2 Receptor

On March 3, 2025 Biond Biologics Ltd. ("Biond" or the "Company"), a private clinical-stage biopharmaceutical company developing novel therapies for cancer, reported that it would regain full rights to BND-22 (SAR444881) from Sanofi (Press release, Biond Biologics, MAR 3, 2025, View Source [SID1234650851]). Sanofi is returning the rights of BND-22 as part of their broader R&D prioritization to focus on programs that support the company’s strategy. Biond and Sanofi, are working together to complete full transfer of the BND-22 program to Biond.

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In January 2021, Biond entered into an exclusive worldwide license agreement with Sanofi for the development and commercialization of BND-22. As part of the agreement, Biond collaborated with Sanofi to initiate a first-in-human Phase 1 study (BND-22-001, NCT04717375), designed to evaluate the safety and tolerability of BND-22, both as a monotherapy and in combination with the approved cancer therapies cetuximab and pembrolizumab. The Phase 1 dose-escalation study was successfully completed and demonstrated a favorable safety profile across all patient groups. More specifically, data showed that BND-22 was well-tolerated and exhibited anti-tumor activity in heavily pretreated patients. Consistent with preclinical findings, a dose-dependent upregulation of activation markers was observed in monocytes and ILT2-expressing T and natural killer (NK) cell subsets. Notably, several confirmed clinical responses to both monotherapy and combination therapies regimens, were reported during the dose-escalation phase. These findings highlight the potential of BND-22 to address critical unmet needs in oncology.

Building on these encouraging results, Sanofi initiated enrollment for a Phase 2 dose-optimization and expansion study (BND-22-001, NCT04717375). The study was designed to evaluate BND-22 as monotherapy for patients with cholangiocarcinoma and in combination with cetuximab for patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC). For more information about the trial, please visit View Source (Trial Identifier: NCT04717375).

"As part of the agreement between Biond and Sanofi, Biond will regain full rights to BND-22, including access to the clinical data generated by Sanofi," said Dr. Tehila Ben Moshe, Biond’s CEO and co-founder. "Sanofi has been an outstanding partner, and together, we have made remarkable progress in advancing the clinical development of BND-22. We remain committed to the continued development of BND-22 program, whether independently or in partnership with strategic collaborators".

"We are encouraged by the data demonstrated so far for BND-22 in the dose-escalation and dose-expansion study", said Dr. Natalia Ashtamker, Biond’s VP of Clinical Development. "We intend to continue treating patients who are benefiting from BND-22 treatment in the BND-22-001 study and are looking forward to the initiation of a Phase 2 biomarker study of BND-22 in combination with anti-PD-1 therapy".

About BND-22

BND-22 is a humanized IgG4 antagonist antibody targeting the ILT2 receptor, developed for the treatment of solid tumors. ILT2 is an inhibitory immuno-modulating receptor expressed on both innate and adaptive immune cells. It binds to major histocompatibility complex (MHC) class I molecules, including HLA-G, an immunosuppressive protein expressed by various tumor types.

Preclinical studies have demonstrated that BND-22 exerts broad anti-tumor effects by disrupting ILT2-mediated "do not eat me" signals in macrophages and activating NK and CD8+ lymphocytes.

BND-22-001, a Phase 1/2 multicenter, open-label, dose-escalation, dose-expansion and dose optimization study enrolled patients with advanced solid tumors known to express HLA-G. The study included evaluations of BND-22 as monotherapy in cholangiocarcinoma and in combination with cetuximab in patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Additionally, a future Phase 2 biomarker trial will explore BND-22 in combination with an anti-PD-1 agent in NSCLC, CRC and ovarian cancers.

TG Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results

On March 3, 2025 TG Therapeutics, Inc. (NASDAQ: TGTX) (the Company or TG Therapeutics) reported its financial results for the fourth quarter and full year ended December 31, 2024, along with recent company developments (Press release, TG Therapeutics, MAR 3, 2025, View Source [SID1234650832]).

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Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, stated, "2024 was a year of significant outperformance and growth for TG, highlighted by the strong adoption of BRIUMVI for adult patients with relapsing forms of multiple sclerosis, which surpassed our initial expectations. Additionally, we made meaningful progress in strengthening our BRIUMVI patent portfolio through 2042, launching new clinical trials, including for subcutaneous BRIUMVI, and advancing our pipeline. These accomplishments provide a solid foundation as we look toward continued success in 2025."

2024 Highlights & Recent Developments

BRIUMVI (ublituximab-xiiy) Commercialization

BRIUMVI United States (U.S.) net product revenue of $103.6 million and $310 million for the fourth quarter and full year of 2024, respectively, representing approximately 250% growth year over year

Obtained three additional patents from the United States Patent and Trademark Office (USPTO) for BRIUMVI, extending patent protection through 2042

BRIUMVI launched in Europe with our partner, Neuraxpharm, which is now commercially available in several additional countries in the European Union and United Kingdom

BRIUMVI Data Presentations

Presented five-year data from the open-label extension study of the ULTIMATE I & II Phase 3 trials evaluating BRIUMVI in adult patients with relapsing forms of multiple sclerosis (RMS) which demonstrated that 92% of patients were free from disability progression after five years of treatment, an annualized relapse rate of 0.02 during year 5 of treatment (equivalent to one relapse occurring every fifty years of patient treatment), and an overall safety profile that remained consistent over 5 years of continuous treatment, with no new safety signals emerging with prolonged treatment.

Presented data from the ENHANCE Phase 3b trial evaluating BRIUMVI in patients with RMS which demonstrated that:


o

Rapid 30-minute BRIUMVI infusions are well tolerated in over 80 patients with RMS, and


o

RMS patients who were already B-cell depleted from a prior anti-CD20 therapy were able to switch directly to a full 450 mg dose of BRIUMVI administered in 1 hour, without a 150 mg initial dose, with 97% of infusions being completed without interruption or slowing.

Pipeline

Launched a Phase 1 trial evaluating subcutaneous ublituximab in patients with relapsing forms of multiple sclerosis (MS)

Enrolled patients with Myasthenia Gravis (MG) into a Phase 1 trial with subcutaneous ublituximab

Entered into a global license agreement with Precision BioSciences, Inc. (Precision) for the development and commercialization of Precision’s allogeneic CD19 CAR T therapy program, azercabtagene zapreleucel (azer-cel), for the treatment of autoimmune disorders and launched a Phase 1 trial in primary progressive multiple sclerosis

2025 Financial Guidance

Full Year 2025 target total global revenue of approximately $540 million, including BRIUMVI U.S. net product revenue of approximately $525 million

Full year 2025 target operating expense of approximately $300 million (excluding non-cash compensation)

2025 Development Pipeline Anticipated Milestones

Commence pivotal program of subcutaneous ublituximab

Commence a pivotal program based on data from the ENHANCE trial with the goal of enhancing the patient experience on intravenous BRIUMVI

Enroll participants into the ongoing trial evaluating BRIUMVI in autoimmune diseases outside of MS

Enroll participants into the Phase 1 azer-cel trial in autoimmune disease, beginning with progressive forms of MS

Present updated data at major medical conferences throughout the year

Financial Results for Fourth Quarter and Full Year 2024

Product Revenue, net: Product revenue, net was approximately $107.3 million and $313.7 million for the three and twelve months ended December 31, 2024, respectively, compared to $43.1 million and $92.0 million for the three and twelve months ended December 31, 2023, respectively. Product revenue, net consists primarily of net product sales of BRIUMVI in the United States, which totaled $103.6 million and $310.0 million during the three and twelve months ended December 31, 2024, respectively. Also included in product revenue, net during the three months ended December 31, 2023 and 2024 is approximately $3.2 million and $3.7 million, respectively, for product sold to our partner Neuraxpharm to support the Ex-US commercialization of BRIUMVI.

License, milestone, royalty and other revenue: License, milestone, royalty and other revenue was approximately $0.8 million and $15.3 million for the three and twelve months ended December 31, 2024, respectively, compared to $0.8 million and $141.7 million for the three and twelve months ended December 31, 2023, respectively. License, milestone, royalty and other revenue for the twelve months ended December 31, 2024, is predominantly comprised of a $12.5 million milestone payment under the Neuraxpharm Commercialization Agreement for the first key market commercial launch of BRIUMVI in the European Union (EU) which occurred in the first quarter of 2024. License, milestone, royalty and other revenue for the twelve months ended December 31, 2023 is predominantly comprised of recognition of the one-time $140.0 million non-refundable upfront payment under the Commercialization Agreement with Neuraxpharm.

R&D Expenses: Total research and development (R&D) expense was approximately $23.9 million and $94.3 million for the three and twelve months ended December 31, 2024, respectively, compared to $17.4 million and $76.2 million for the three and twelve months ended December 31, 2023, respectively. The increase in R&D expense during the three and twelve months ended December 31, 2024 was primarily attributable to manufacturing and development costs incurred in connection with our ublituximab subcutaneous development work, as well as license and milestone expense related to the license agreement with Precision BioSciences, Inc., during the period.

SG&A Expenses: Total selling, general and administrative (SG&A) expense was approximately $39.0 million and $154.3 million for the three and twelve months ended December 31, 2024, respectively, compared to $31.2 million and $122.7 million for the three and twelve months ended December 31, 2023, respectively. The increase in both periods was primarily due to other selling, general and administrative costs, including personnel and consultants, associated with the commercialization of BRIUMVI during the period ended December 31, 2024.

Net Income (Loss): Net income was $23.3 million and $23.4 million for the three and twelve months ended December 31, 2024, respectively, compared to a net loss of ($14.4) million for the three months ended December 31, 2023 and net income of $12.7 million for the twelve months ended December 31, 2023, respectively.

Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $311.0 million as of December 31, 2024. We anticipate that our cash, cash equivalents and investment securities as of December 31, 2024, combined with the projected revenues from BRIUMVI, will be sufficient to fund our business based on our current operating plan.

CONFERENCE CALL INFORMATION
The Company will host a conference call today, March 3, 2025, at 8:30 AM ET, to discuss the Company’s financial results from the fourth quarter and full year ended December 31, 2024.

To participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for a period of 30 days after the call.

ABOUT BRIUMVI (ublituximab-xiiy) 150 mg/6 mL Injection for IV
BRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of autoimmune disorders, such as RMS. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses.

BRIUMVI is indicated in the U.S. for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease and in the EU and UK for the treatment of adult patients with RMS with active disease defined by clinical or imaging features.

A list of authorized specialty distributors can be found at www.briumvi.com.

IMPORTANT SAFETY INFORMATION

Contraindications: BRIUMVI is contraindicated in patients with:

Active Hepatitis B Virus infection

A history of life-threatening infusion reaction to BRIUMVI

WARNINGS AND PRECAUTIONS

Infusion Reactions: BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction. In MS clinical trials, the incidence of infusion reactions in BRIUMVI-treated patients who received infusion reaction-limiting premedication prior to each infusion was 48%, with the highest incidence within 24 hours of the first infusion. 0.6% of BRIUMVI-treated patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe treated patients for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer the recommended pre-medication to reduce the frequency and severity of infusion reactions. If life-threatening, stop the infusion immediately, permanently discontinue BRIUMVI, and administer appropriate supportive treatment. Less severe infusion reactions may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections: Serious, life-threatening or fatal, bacterial and viral infections have been reported in BRIUMVI-treated patients. In MS clinical trials, the overall rate of infections in BRIUMVI-treated patients was 56% compared to 54% in teriflunomide-treated patients. The rate of serious infections was 5% compared to 3% respectively. There were 3 infection-related deaths in BRIUMVI-treated patients. The most common infections in BRIUMVI-treated patients included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved.

Consider the potential for increased immunosuppressive effects when initiating BRIUMVI after immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HB surface antigen (HBsAg) and anti-HB tests. For patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment.

Progressive Multifocal Leukoencephalopathy (PML): Although no cases of PML have occurred in BRIUMVI-treated MS patients, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

If PML is suspected, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms; monitoring for signs consistent with PML may be useful. Further investigate suspicious findings to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis.

If PML is confirmed, treatment with BRIUMVI should be discontinued.

Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines, at least 4 weeks and, whenever possible, at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines. BRIUMVI may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines during or following administration of BRIUMVI has not been studied. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with BRIUMVI During Pregnancy: In infants of mothers exposed to BRIUMVI during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. Inactivated or non-live vaccines may be administered prior to B-cell recovery. Assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted.

Fetal Risk: Based on data from animal studies, BRIUMVI may cause fetal harm when administered to a pregnant woman. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. A pregnancy test is recommended in females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception during BRIUMVI treatment and for 6 months after the last dose.

Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 0.6% of BRIUMVI-treated patients compared to none of the patients treated with teriflunomide in RMS clinical trials. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy, until B-cell repletion. Consider discontinuing BRIUMVI therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections.

Physicians, pharmacists, or other healthcare professionals with questions about BRIUMVI should visit www.briumvi.com.

The full Summary of Product Characteristics approved in the European Union (EU) for BRIUMVI can be found here Briumvi | European Medicines Agency (europa.eu).

ABOUT BRIUMVI PATIENT SUPPORT in the U.S.
BRIUMVI Patient Support is a flexible program designed by TG Therapeutics to support U.S. patients through their treatment journey in a way that works best for them. More information about the BRIUMVI Patient Support program can be accessed at www.briumvipatientsupport.com.

ABOUT MULTIPLE SCLEROSIS
Relapsing multiple sclerosis (RMS) is a chronic demyelinating disease of the central nervous system (CNS) and includes people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses. RRMS is the most common form of multiple sclerosis (MS) and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS.1,2 The majority of people who are diagnosed with RRMS will eventually transition to SPMS, in which they experience steadily worsening disability over time. Worldwide, more than 2.3 million people have a diagnosis of MS.