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.

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

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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

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

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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

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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.

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

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

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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

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

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

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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

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

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

2025 Development Pipeline Anticipated Milestones

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Commence pivotal program of subcutaneous ublituximab

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

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

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

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Present updated data at major medical conferences throughout the year

Financial Results for Fourth Quarter and Full Year 2024

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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.

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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.

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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.

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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.

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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.

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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:

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Active Hepatitis B Virus infection

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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.

On March 3, 2025 Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, reported a review of recent accomplishments and anticipated upcoming developments and reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Biohaven Pharmaceutical, MAR 3, 2025, View Source [SID1234650852]).

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Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "We have made considerable progress this past year in advancing our innovative and diversified portfolio. Most notably, we oversaw the advent of our groundbreaking degrader or MoDE technology continue to advance into the clinic, with today’s added news that multiple doses of BHV-1300 lowered serum IgG by up to 84% from baseline. Modulation of IgG has proven to be an exciting and growing market in the treatment of autoimmune disease, and BHV-1300 has the potential to further advance the field. Our next generation TRAP degraders offer the additional advantage of selectively removing antigen-specific targets while sparing off-target effects to allow continued healthy immune functioning. The selectivity of MoDE and TRAP degraders demonstrated to date has the potential to redefine the immune-modulating treatment paradigm. The implications and applications of this selective targeting could be multi-organ, multi-disease and we are eager to continue unlocking the vast potential afforded by our innovative degrader technology."

Dr. Coric continued, "Thanks to focused execution across the balance of our portfolio, we believe we are poised to deliver important milestones in 2025 and beyond, starting with the FDA accepting our troriluzole NDA filing resubmission and granting Priority Review. An approval in this indication could profoundly impact the outlook for nearly 40,000 patients living with spinocerebellar ataxia across the globe and we are making commercial plans in earnest as we await final regulatory outcomes; we separately await the results of critical Phase 3 data in each of our 2 identical ongoing studies in OCD. Our ion channel platform expects to report topline pivotal results with our Kv7.2/7.3 potassium channel activator, BHV-7000, in major depressive disorder in 2H 2025 and in focal epilepsy in 1H 2026. Furthering our expansion of knowledge for our ion channel platform, we expect to report data from the laser-evoked hyperalgesia and proof-of-concept migraine studies with TRPM3 antagonist, BHV-2100, in 1H 2025. With taldefgrobep alfa, our anti-myostatin agent, we likewise look forward to working with appropriate regulatory bodies to establish a potential path forward in spinal muscular atrophy as we work in tandem to initiate our Phase 2 study in obesity. Regarding our brain-penetrant TYK2/JAK1 Inhibitor, we are eager to initiate our Phase 2/3 study in Parkinson’s disease in the first half of the year as we advance programs in Alzheimer’s, MS, and ARIA in parallel. Finally, we are significantly advancing our ADC portfolio as new strategic collaborations and ongoing clinical and non-clinical work has invigorated our oncology franchise, with several milestones anticipated in 2025, including interim Phase 1 data with our lead clinical Trop-2 ADC program, BHV-1510 and a Phase 1 initiation with our novel FGFR3 ADC, BHV-1530, for patients with urothelial cancer & other tumors; we are also advancing multiple ADCs through our newly announced collaborations with Merus and GeneQuantum."

"An exciting year awaits us to be sure, and as we move forward, I’m confident our strong momentum will continue thanks to the unwavering dedication of our talented team, underpinned by our relentless desire to innovate, serve patients, and generate value in lockstep."

Full Year and Recent Business Highlights

Glutamate Modulation Platform – Milestones and Next Steps:
Troriluzole is a novel glutamate modulator currently in Phase 3 development for all-genotype spinocerebellar ataxia (SCA) and obsessive-compulsive disorder (OCD). The FDA has accepted for review the Company’s NDA for troriluzole for the treatment of adult patients with SCA and has granted Priority Review; troriluzole previously received Orphan Drug and Fast-Track designations. EU marketing authorization application is also under review for troriluzole in all SCA genotypes. There are no FDA-approved treatments for SCA. Additionally, two Phase 3 trials with troriluzole in OCD are ongoing.

Announced FDA acceptance and Priority Review of troriluzole NDA for the treatment of spinocerebellar ataxia: The FDA’s decision regarding the NDA is expected within 6 months of filing (during 3Q 2025). Based on FDA Priority Review timelines and, if ultimately approved, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025.
The Company had previously achieved positive topline results in a pivotal study of troriluzole in SCA. Troriluzole 200 mg dosed orally, once daily, in patients with SCA met the study’s primary endpoint on the change from baseline in the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) at 3 years in all study population genotypes. Troriluzole also showed statistically significant superiority after both 1 and 2 years of treatment. Troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period.
Upcoming milestones:

Following FDA acceptance of the troriluzole all-genotype SCA NDA filing resubmission with Priority Review status and a 3Q 2025 PDUFA date, the Company is preparing for commercial launch in SCA in 2025, pending approval.
Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively.
Inflammation and Immunology Platform – Milestones and Next Steps:

Targeted Extracellular Protein Degradation
Biohaven’s novel immune-modulating extracellular degrader platform harnesses selectivity, rapidity, and patient-friendly self-administration to remove disease-causing proteins from the body to potentially treat a wide range of diseases; MoDEs (Molecular Degraders of Extracellular Proteins) uniquely harness the hepatic asialoglycoprotein receptor (ASGPR) for efficient and safe removal of circulating pathogenic targets. BHV-1300 and BHV-1310 are IgG degraders; Biohaven introduced next generation TRAPTM (Targeted Removal of Aberrant Protein) degraders, which are highly selective, each targeting a specific disease-causing protein for proteolysis; BHV-1400 is a TRAP degrader targeting Gd-IgA1. BHV-1600 is a TRAP degrader targeting β1-AR autoantibodies.

Announced multiple advancements across MoDE and TRAP platforms:

IgA Nephropathy (IgAN) program: First-in-human (FIH) dosing with BHV-1400 achieved rapid, deep, and selective lowering of only aberrant galactose-deficient IgA1 (Gd-IgA1).The first and lowest dose tested (125 mg) of BHV-1400 in the ongoing Phase 1 trial achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immunity.
Peripartum cardiomyopathy (PPCM) program: FIH dosing with BHV-1600 was initiated and has been well-tolerated to date after the first two dosing cohorts without clinically significant changes in innate or adaptive immunity. Held INTERACT meeting with FDA in 4Q 2024.
IgG degrader programs: BHV-1300: Advanced optimized subcutaneous formulation with deep reductions of total IgG exceeding 80% with 1,000 mg weekly dosed over four weeks in the ongoing Phase 1 study. Doses of up to 2,000 mg have been safe and well-tolerated. There were no clinically significant reductions in IgG3, IgA, IgE, IgM, or albumin, nor clinically significant increases in AST, ALT, bilirubin, or cholesterol.
Upcoming milestones:

IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 with the optimized subcutaneous formulation expected completion in 1H 2025. BHV-1310 completion of preclinical testing prior to anticipated first-in-human study initiating 1H 2025. Phase 2 study in Graves’ disease expected to initiate mid-2025 and additional programs in rheumatoid arthritis and myasthenia gravis continue to be pursued.
Phase 1 study with BHV-1400 and BHV-1600 expected to be completed in 1H 2025.
Four additional degraders advancing including: IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader.
TYK2/JAK1 Inhibition
BHV-8000 is an oral, brain-penetrant, selective TYK2/JAK1 inhibitor with broad potential for neuroinflammatory and neurodegenerative disorders.

Completed Phase 1 study with BHV-8000: In the Phase 1 SAD/MAD study in healthy participants, BHV-8000 was generally safe and well-tolerated while producing significant reductions in inflammatory biomarkers relative to placebo. Biohaven completed interactions with FDA enabling registrational programs for Parkinson’s disease and the prevention of ARIA.
Upcoming milestones:

Initiate BHV-8000 Phase 2/3 study in Parkinson’s disease in 1H 2025.
Advance Alzheimer’s, MS and ARIA programs in 2025.
Ion Channel Platform – Milestones and Next Steps:

Kv7 Activation: Epilepsy & Neuropsychiatric Indications
BHV-7000, the lead asset from the Kv7 platform, is a selective activator of Kv7.2/Kv7.3 potassium channels. Kv7 activation is a clinically validated target for treating mood disorders and epilepsy. Four registrational studies are ongoing in major depressive disorder, focal epilepsy, and generalized epilepsy.

BHV-7000 once-daily extended-release formulation data presented: Reported expanded safety results from BHV-7000 Phase 1 MAD studies at the American Epilepsy Society (AES) 2024 Annual Meeting, including the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies, demonstrating excellent tolerability at all doses evaluated without central nervous system (CNS) adverse effects typically associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. BHV-7000 was safe and well-tolerated at dose levels up to 120 mg daily for 15 days with no dose-limiting toxicities; 120 mg exceeds the doses being evaluated in ongoing Phase 2 and 3 clinical studies of up to 75 mg daily in focal epilepsy, idiopathic generalized epilepsy, and major depressive disorder.
Completed a focused topline analysis of treatment with BHV-7000 in the acute treatment of manic episodes associated with bipolar disorder in a 3-week trial: BHV-7000 did not statistically differentiate from the comparator arm on the primary efficacy endpoint of improvement from Baseline to Day 21 on the Young Mania Rating Scale. Additional analyses are ongoing, and complete study results will be presented at an upcoming scientific meeting. BHV-7000 75 mg once daily, the highest dose of BHV-7000 being evaluated in Phase 2/3 trials, was safe and well-tolerated in this study. No adverse trends in vital signs, ECGs, or labs were noted. There were no treatment emergent serious adverse events. Most adverse events were mostly mild in intensity and resolved spontaneously. This offers a highly favorable and differentiated profile compared to other antiseizure medicines and is consistent with lack of GABA effects.
Upcoming milestones:

Pivotal major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026.
TRPM3 Ion Channel Antagonism: Migraine & Neuropathic Pain
BHV-2100 is an oral, selective TRPM3 antagonist potentially offering a novel, non-addictive treatment for migraine and neuropathic pain

Phase 1 study data supports evaluation in migraine and pain: Based on favorable PK and safety data from Phase 1 studies in healthy subjects, a Phase 1b laser-evoked hyperalgesia trial completed and a proof-of-concept in the acute treatment of migraine is ongoing. Preliminary data from the laser-evoked hyperalgesia study demonstrated that BHV-2100 reduced laser heat-induced pain and brain evoked potentials in healthy volunteers, providing the first indication of potential clinical efficacy in pain with the novel TRPM3 mechanism recapitulating antinociceptive preclinical efficacy across a spectrum of pain models.
Upcoming milestones:

Data from the laser-evoked potential study and migraine proof-of-concept in 1H 2025.
Myostatin Platform – Milestones and Next Steps:
Taldefgrobep is a novel myostatin inhibitor that is optimized to block signaling of myostatin and other activin II receptor ligands, key regulators of muscle and fat metabolism. Biohaven is studying taldefgrobep in a global Phase 3 expansion study in Spinal Muscular Atrophy (SMA), as an adjunctive therapy to enhance muscle mass and function in patients treated with standard-of-care therapies.

Provided update on Phase 3 taldefgrobep alfa program for spinal muscular atrophy: In November 2024, the Company presented analyses of prespecified subgroups by race and ethnicity demonstrating that the largest study population (87% Caucasian; n=180) showed clinically meaningful improvements on the MFM-32 at all timepoints, including Week 48, compared to the corresponding placebo+SOC group (p < 0.05), though the overall primary endpoint was not met. Additionally, robust target engagement (myostatin reduction) and beneficial impacts on body composition parameters (fat mass, lean muscle mass, and bone density) were noted, offering a potential paradigm shift in the treatment of obesity with opportunity to improve quality of weight loss; lower total body weight by specifically reducing fat mass while also preserving or increasing lean muscle mass.
Upcoming milestones :

Expect FDA meeting to discuss SMA registrational path in 1H 2025
Initiate taldefgrobep Phase 2 study in obesity in 1H 2025
Next-Generation ADC Platform – Milestones and Next Steps:
Biohaven’s antibody drug conjugate (ADC) technology is focused on novel, modular site-specific conjugation chemistry approaches, with the potential to drive superior clinical profiles compared to current industry standard maleimide and lipophilic click chemistries.

BHV-1510, a clinical-stage TROP2 directed ADC with a highly differentiated preclinical efficacy and safety profile, has demonstrated early Phase 1 clinical activity and a tolerable safety profile of the novel topoisomerase 1 inhibitor (TopoIx) payload in early cohorts, with no payload associated interstitial lung disease, gastrointestinal toxicities or significant hematological toxicities. Dose escalation and optimization are ongoing as monotherapy and in combination with Libtayo (R) (cemiplimab), an anti-PD1 checkpoint inhibitor, through a clinical supply agreement with Regeneron.
Based on the preclinical profile and encouraging early results with BHV-1510, Biohaven has entered into an expanded collaboration agreement with GeneQuantum, which provides broad target exclusivity for up to 18 ADC targets incorporating the TopoIx payload
The next ADC program positioned to enter clinic, BHV-1530, is a novel FGFR3 ADC that incorporates the TopoIx payload. Similar to BHV-1510, this program has demonstrated a differentiated efficacy and safety profile in preclinical studies, including synergistic in vivo efficacy in combination with a checkpoint inhibitor. Potential indications include urothelial cancer and other FGFR3-driven solid tumors.
In January 2025, Biohaven also announced a multi-target collaboration with Merus N.V. to co-develop three novel dual-targeted ADCs, leveraging Merus’ Biclonics technology platform, and Biohaven’s next-generation ADC conjugation and payload technologies.
Expected Upcoming Milestones:

We believe Biohaven is well positioned to achieve significant milestones in 2025 and 2026 across numerous programs:

MoDE Platform

IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 with the optimized subcutaneous formulation completing in 1H 2025. BHV-1310 completion of preclinical testing prior to anticipated FIH study initiating 1H 2025. Expect to initiate Phase 2 study in Graves’ disease in mid-2025, and additional programs in rheumatoid arthritis and myasthenia gravis continue to be pursued.
Phase 1 with BHV-1400 and BHV-1600 expected to be completed in 1H 2025.
Four additional degrader molecules advancing including: IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader.
Kv7 Activator (BHV-7000):

Pivotal major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026.
Glutamate Modulator (Troriluzole):

Preparing for commercial launch in all-genotype SCA in 2025, following FDA filing acceptance and 3Q 2025 PDUFA date.
Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively.
Myostatin (Taldefgrobep alfa):

Expect FDA meeting to discuss SMA registrational path in 1H 2025.
Initiate taldefgrobep Phase 2 study in obesity in 1H 2025.
TRPM3 Antagonist (BHV-2100):

Continue advancing enrollment in proof of concept trial with BHV-2100 in acute migraine; data from the laser-evoked potential study expected in 1H 2025.
TYK2/JAK1 Inhibitor (BHV-8000):

Initiate BHV-8000 Phase 2/3 study in Parkinson’s disease in 1H 2025.
Advance Alzheimer’s, MS and ARIA programs.
Next Generation ADC Platform:

Interim Phase 1 data with BHV-1510 and dose optimization as monotherapy and combination therapy with Libtayo in epithelial tumors in 2025.
Initiate Phase 1 trial of BHV-1530 in 1H 2025.
Advance Merus collaboration ADCs (undisclosed targets) and TopoIx ADCs in 2025.
Capital Position:

Cash, cash equivalents, marketable securities and restricted cash as of December 31, 2024 totaled approximately $489 million.

Fourth Quarter 2024 Financial Highlights:

Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $167.5 million for the three months ended December 31, 2024, compared to $134.8 million for the three months ended December 31, 2023. The increase of $32.7 million was due to additional and advancing clinical trials, including late Phase 3 and Phase 2/3 studies, and preclinical research programs in 2024, as compared to the same period in the prior year. Non-cash share-based compensation expense was $7.1 million for the three months ended December 31, 2024, a decrease of $2.0 million as compared to the same period in 2023. Non-cash share-based compensation expense was lower in the fourth quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 with no new annual equity incentive awards granted in the fourth quarter of 2024.

General and Administrative (G&A) Expenses: G&A expenses were $22.5 million for the three months ended December 31, 2024, compared to $18.9 million for the three months ended December 31, 2023. The increase of $3.6 million was primarily due to increased personnel and legal costs for the three months ended December 31, 2024 as compared to the same period in 2023. Non-cash share-based compensation expense was $5.6 million for the three months ended December 31, 2024, a decrease of $1.1 million as compared to the same period in 2023. Non-cash share-based compensation expense was lower in the fourth quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 with no new annual equity incentive awards granted in the fourth quarter of 2024.

Other Income, Net: Other income, net was $3.1 million for the three months ended December 31, 2024, compared to other income, net of $7.7 million for the three months ended December 31, 2023. The decrease of $4.6 million was primarily due to non-cash changes in the fair value of our forward contract and derivative liabilities recorded in connection with the amendment to our Membership Interest Purchase Agreement with Knopp Biosciences LLC in May 2024 (the Knopp Amendment) and decreased service revenue from the Transition Service Agreement we entered into with Biohaven Pharmaceutical Holding Company Ltd. (the "Former Parent").

Net Loss: Biohaven reported a net loss for the three months ended December 31, 2024 of $186.8 million, or $1.85 per share, compared to $144.8 million, or $1.81 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended December 31, 2024 was $173.3 million, or $1.71 per share, compared to $128.9 million, or $1.61 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

Full Year 2024 Financial Highlights

R&D Expenses: R&D expenses, including non-cash share-based compensation, were $795.9 million for the year ended December 31, 2024, compared to $373.3 million for the year ended December 31, 2023. The increase was largely due to non-cash expense of $171.9 million paid to Knopp for a milestone and royalty buyback related to BHV-7000 and the broader Kv7 platform that was recognized during the three months ended June 30, 2024. The buyback reduced our potential future milestone payments by $867.5 million, and replaced the scaled high single digit to low teens royalty payment obligations with a flat royalty payment in the mid-single digits for the Kv7 programs. The increase in R&D expenses was also related to advancing our clinical platforms including four Phase 3 study starts and one Phase 2 study start for BHV-7000, follow-on Kv7 assets, preclinical research programs, and increases in direct program spend for additional multiple clinical development programs in 2024, as compared to the same period in the prior year. The increase was also due to a $40.2 million increase in personnel costs, primarily due to increased non-cash share based compensation expense and increased headcount to support our expanding clinical and preclinical research programs. Non-cash share-based compensation expense was $42.6 million for the year ended December 31, 2024, an increase of $26.6 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the year ended December 31, 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and first quarter of 2024.

G&A Expenses: G&A expenses, including non-cash share-based compensation costs, were $89.2 million for the year ended December 31, 2024, compared to $62.8 million for the year ended December 31, 2023. The increase of $26.5 million was primarily due to increased non-cash share-based compensation costs and increased legal costs. Non-cash share-based compensation expense was $29.4 million for the year ended December 31, 2024, an increase of $16.6 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in 2024 primarily due to our annual equity incentive awards being partially granted in the fourth quarter of 2023 with a greater portion granted in the first quarter of 2024, partially offset by the subsequent year annual equity incentive awards being granted in the first quarter of 2025 and no partial grants from such annual equity incentive awards in the fourth quarter of 2024.

Other Income (Expense), Net: Other income (expense), net was income of $39.4 million for the year ended December 31, 2024, compared to income of $26.5 million for the year ended December 31, 2023. The increase of $12.9 million was primarily due to non-cash changes in the fair value of our forward contract and derivative liabilities recorded in connection with the Knopp Amendment as well as increased investment income. The increases were partially offset by a decrease in other income recognized during the year ended December 31, 2024 as compared to 2023 related to the Transition Services Agreement entered into with the Former Parent.

Net Loss: The Company reported a net loss attributable to common shareholders for the year ended December 31, 2024 of $846.4 million, or $9.28 per share, compared to $408.2 million, or $5.73 per share for the same period in 2023. Non-GAAP adjusted net loss for the year ended December 31, 2024 was $790.6 million, or $8.67 per share, compared to $379.4 million, or $5.33 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

On March 3, 2025 Intra-Cellular Therapies, Inc. ( the "Company") reported that as previously announced, on January 10, 2025, it has entered into an Agreement and Plan of Merger (the "Merger Agreement") with Johnson & Johnson, a New Jersey corporation ("Parent"), and Fleming Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of Parent ("Merger Sub"), pursuant to which, subject to the terms and conditions thereof, Merger Sub will merge with and into the Company (the "Merger"), with the Company surviving the Merger as a wholly owned subsidiary of Parent (Filing, 8-K, Intra-Cellular Therapies, MAR 3, 2025, View Source [SID1234650831]). Capitalized terms used herein and not otherwise defined herein have the meanings set forth in the Merger Agreement.

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The closing of the Merger is conditioned upon, among other things, the expiration or termination of the waiting period applicable to the Merger under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended (the "HSR Act"). The required waiting period under the HSR Act with respect to the Merger expired at 11:59 p.m., Eastern Time on February 26, 2025.

The expiration of the waiting period under the HSR Act satisfies one of the conditions to the closing of the Merger. The closing of the Merger remains subject to the satisfaction or waiver of other customary closing conditions, including, without limitation, the adoption of the Merger Agreement and approval of the Merger by the affirmative vote of the holders of a majority of the outstanding Company Shares. As previously disclosed, the Company has scheduled the special meeting of stockholders for March 27, 2025 to vote on the adoption of the Merger Agreement and approval of the Merger.

For more information about the proposed transaction, including the Merger Agreement, the Merger and the special meeting of the Company’s stockholders, please see the definitive proxy statement filed with the Securities and Exchange Commission (the "SEC") by the Company on February 18, 2025 (the "Definitive Proxy Statement").

On March 3, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy in oncology and autoimmune diseases, reported that Ipsen (Euronext: IPN; ADR: IPSEY) has nominated a second drug candidate (DC) under its multi-year strategic oncology collaboration with Marengo (Press release, Marengo Therapeutics, MAR 3, 2025, View Source [SID1234650853]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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This nomination marks the successful advancement of the second STAR bispecific T cell activator program included in the partnership between Ipsen and Marengo since it began in August 2022. The first DC nomination under the collaboration was announced in April 2024.

"This second DC nomination is a testament to our strong collaboration with Ipsen and once again underscores the dedication and ingenuity of Marengo’s research team in advancing innovative immunotherapy candidates to clinical trials," said Andrew Bayliffe Ph.D., Chief Scientific Officer of Marengo. "Our novel, first in class TCRVβ-targeted dual T cell agonists drive the revitalization of anti-tumor T cell responses in immunotherapy refractory tumor models, and we look forward to working with Ipsen as we translate this potential into people living with cancer."

Under the terms of the agreement, Marengo will receive a milestone payment for this pre-defined pre-clinical milestone. Per the agreement, Marengo has led research and preclinical development efforts in partnership with Ipsen. Ipsen will assume responsibilities for IND filing, regulatory submissions, clinical development and commercialization.