On March 31, 2025 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for TIVDAK (tisotumab vedotin), an antibody-drug conjugate (ADC), as monotherapy treatment for adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy (Press release, Genmab, MAR 31, 2025, View Source [SID1234651675]). TIVDAK is the first and only ADC to be granted European Union (EU) marketing authorization for people living with recurrent or metastatic cervical cancer.

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Despite progress in cervical cancer prevention and early detection, there remains a high need for new treatment options, particularly in advanced forms of the disease. In fact, cervical cancer is the fourth most common cause of cancer death among women globally.i In the European Union, cervical cancer is the 11th most frequently occurring cancer among women.ii Up to 15% of adults with cervical cancer present with metastatic disease at diagnosisiii,iv and, for those diagnosed at earlier stages who receive treatment, up to 61%v will experience disease recurrence. For these patients, the prognosis can be poor.vi

"Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options," said Ignace Vergote, M.D., Ph.D., University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial. "In clinical trials, TIVDAK demonstrated a superior overall survival benefit and manageable safety profile compared to chemotherapy, supporting its position to become a potential new standard of care in this setting with a novel mechanism of action. This approval is an important step forward in the treatment landscape for advanced cervical cancer."

The approval is supported by data from the global, randomized, Phase 3 innovaTV 301 trial (NCT04697628) that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met, further validating its clinical benefit. PFS results were statistically significant, with TIVDAK demonstrating a 33% reduction in the risk of disease progression compared with chemotherapy (HR: 0.67 [95% CI, 0.54-0.82], p<0.0001). Data from the innovaTV 204 (NCT03438396) pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as monotherapy in patients with previously treated recurrent or metastatic cervical cancer was also included in the marketing authorization application (MAA).

The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving tisotumab vedotin were peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anaemia (27%), and diarrhoea (25%).

"We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer," said Brad Bailey, Executive Vice President and Chief Commercial Officer of Genmab. "The European Commission approval of TIVDAK marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in Europe independently, we’re committed to bringing this important option to as many patients in Europe with previously treated recurrent or metastatic cervical cancer as possible."

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin
Tisotumab vedotin (approved under the brand name TIVDAK in the EU, U.S. and Japan) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

On March 31, 2025 Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics") reported that Merck has exercised the global commercialization option for pimicotinib (ABSK021), with an option exercise fee of USD85.0 million, under the licensing agreement signed in December 2023 (Press release, Merck & Co, MAR 31, 2025, View Source [SID1234651694]). The development represents further deepening of the collaboration, underscoring the unwavering commitment and confidence that both parties possess for the ongoing advancement of pimicotinib.

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In December 2023, Abbisko Therapeutics entered into an exclusive licensing agreement (the "Agreement") with Merck regarding pimicotinib, a CSF-1R inhibitor. Under the terms of the Agreement, Merck initially had an exclusive license to commercialize pimicotinib for all indications in the Chinese mainland, Hong Kong, Macau and Taiwan with an exclusive option for global commercial rights of pimicotinib. Merck now has exercised such option and has the exclusive license to commercialize pimicotinib worldwide. Abbisko Therapeutics has already received the one-time, non-refundable upfront payment of USD70.0 million in February 2024, and is now entitled to receive the additional option exercise fee of USD85.0 million. Additionally, Merck has the option to co-develop pimicotinib for additional indications under certain conditions. In total, Abbisko Therapeutics is eligible to receive up to USD605.5 million in payments, including upfront, development, and commercial milestones, as well as double-digit percentage royalties on annual net sales.

Pimicotinib is a novel, orally administered, highly selective, and potent small molecule CSF-1R inhibitor, independently developed by Abbisko Therapeutics. Pimicotinib’s positive topline results from the Global Phase III MANEUVER Study in tenosynovial giant cell tumor ("TGCT") were successfully released in November 2024, where MANEUVER met the primary endpoint with an objective response rate ("ORR") at Week 25 of 54.0% for pimicotinib compared with 3.2% for placebo (p<0.0001), and treatment with oral, once-daily pimicotinib was well-tolerated with very low rates of discontinuation due to treatment-related adverse events, and with no evidence of cholestatic hepatotoxicity.

Yao-Chang Xu, Chairman and CEO of Abbisko Therapeutics, said, "Pimicotinib represents a key advancement within the emerging class of CSF-1R inhibitors, demonstrating a meaningful clinical efficacy and safety profile that positions it as an innovative treatment option for worldwide TGCT patients. We look forward to deepening our collaboration with the Merck team to expedite the registration process of pimicotinib to bring benefits to patients as quickly as possible."

"Today marks a significant milestone in our partnership with Abbisko as we work together to deliver a potentially best-in-class therapy for patients with TGCT around the world," said Andrew Paterson, Chief Marketing Officer for the Healthcare business sector of Merck. "This collaboration underscores our commitment to advancing new treatment options in rare oncology for patients who need them. With this important step forward, we aim to transform the treatment landscape and offer hope to those living with TGCT, who today have very limited treatment options."

On March 31, 2025, Atara Biotherapeutics, Inc., (the "Company") entered into an Amendment (the "Amendment") to the Amended and Restated Commercialization Agreement dated October 31, 2023 (the "Agreement") with Pierre Fabre Medicament ("Pierre Fabre") (Filing, 8-K, Atara Biotherapeutics, MAR 31, 2025, View Source [SID1234651804]). Under the terms of the Amendment, as of March 31, 2025, the Company has completed the transfer of all manufacturing responsibility to Pierre Fabre and Pierre Fabre will be, at its cost, responsible for manufacturing and supplying tabelecleucel for development and commercialization worldwide. Pierre Fabre has also agreed to assume the costs related to remediation of the third-party manufacturing facility to address the U.S. Food and Drug Administration’s (the "FDA") requests to support resubmission of the BLA for tab-cel.

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In exchange for accelerating the transfer of all manufacturing responsibility and assumption of such remediation costs by Pierre Fabre, among other things, the Company agreed to reduce the amount of certain potential future regulatory and commercial milestone payments under the Agreement. The Amendment did not change any of the royalties the Company is eligible to receive under the Agreement. Pursuant to the Amendment, the Company is now entitled to receive an aggregate of up to $550.0 million in additional potential milestone payments upon achieving certain regulatory and commercial milestones relating to tab-cel, including up to $40.0 million in potential regulatory milestones in connection with the approval by the FDA of a BLA for tab-cel under the terms of the Agreement (as amended by the Amendment).

The foregoing summary of the Amendment does not purport to be complete and is qualified in its entirety by reference to the Amendment, a copy of which will be filed with the Company’s Quarterly Report on Form 10-Q for the period ended March 31, 2025.

On March 31, 2025 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing innovative treatments for patients with unmet medical needs, reported fourth quarter and full-year 2024 financial results and summarized recent developments (Press release, Monopar Therapeutics, MAR 31, 2025, View Source [SID1234651636]).

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"2024 was a productive year for Monopar, with the in-licensing of ALXN1840, the initiation of two first-in-human radiopharma Phase 1 clinical trials, and the strengthening of our balance sheet with net proceeds of over $55 million from financings," said Chandler Robinson, MD, Chief Executive Officer of Monopar. "We are especially grateful to the Wilson disease patients. Their testimonies and support are what provided the opportunity for Monopar to progress ALXN1840 toward an NDA filing."

Recent Program Developments

ALXN1840 – Plan to Submit NDA with FDA for Wilson Disease in Early 2026

Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised, leading to damage from toxic copper build-up in tissues and organs such as the liver and brain. ALXN1840 is a potent binder and mobilizer of copper, as demonstrated in a Phase 3 clinical trial that met its primary endpoint. In October 2024, Monopar announced the execution of a worldwide exclusive license to ALXN1840 with Alexion, AstraZeneca Rare Disease ("AZ"). As part of this transaction, AZ received a total cash payment of $4.0 million, was issued 9.9% ownership of Monopar’s outstanding common stock, and is entitled to receive regulatory approval and sales milestones along with a tiered royalty based on net sales

MNPR-101 – Currently Enrolling Phase 1 Imaging and Therapeutic Oncology Trials

Imaging agent MNPR-101-Zr (MNPR-101 conjugated to zirconium-89) and therapeutic agent MNPR-101-Lu (MNPR-101 conjugated to lutetium-177) target the urokinase plasminogen activator receptor ("uPAR"), which is expressed in numerous aggressive cancers such as triple-negative breast, colorectal, and pancreatic cancers

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Initiated Phase 1a clinical trial for novel therapeutic radiopharmaceutical MNPR-101-Lu in patients with advanced cancers

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Dosed first patient with MNPR-101-Lu in December 2024

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Presented encouraging human clinical imaging and dosimetry data of MNPR-101-Zr at the European Association of Nuclear Medicine ("EANM") 2024 Annual Congress

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uPAR expression, as detected by MNPR-101-Zr, has been seen to date in breast, colorectal, pancreatic, adrenocortical carcinoma, and ovarian cancer patients

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Filed a patent application covering new therapeutic radiopharmaceuticals based on a novel family of linkers used to connect radioisotopes with targeting agents, including Monopar’s uPAR targeting antibody MNPR-101

Recent Financings

In Q4 2024, we raised net proceeds of over $55 million from the following financings:

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On October 30, 2024, pursuant to a placement agent agreement with Rodman & Renshaw LLC, we sold 1,181,540 shares of our common stock at $16.25 in a public offering, yielding net proceeds of approximately $17.8 million.

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On December 23, 2024, pursuant to an underwriting agreement with Piper Sandler & Co., we sold 798,655 shares of our common stock at $23.79 per share in a public offering. Concurrently with the public offering, we completed a private placement of 882,761 pre-funded warrants to purchase shares of common stock to an institutional investor at a purchase price of $23.789 per pre-funded warrant. The net proceeds of the December 23, 2024, public offering and private placement were approximately $37.4 million.

Results for the Fourth Quarter and Year Ended December 31, 2024, Compared to the Fourth Quarter and Year Ended December 31, 2023

Cash and Net Loss

Cash, cash equivalents and short-term investments as of December 31, 2024, were $60.2 million. Monopar expects that its current funds will be sufficient to continue operations at least through December 31, 2026, in order to: (1) assemble a regulatory package and file an NDA for ALXN1840; (2) continue to conduct and conclude its first-in-human imaging and dosimetry clinical trial with MNPR-101-Zr; (3) continue to conduct its first-in-human therapeutic clinical trial of MNPR-101-Lu; (4) advance its preclinical MNPR-101-Ac program into the clinic; and (5) invest in internal research and development projects to expand its radiopharma and rare disease pipeline.

Net loss for the fourth quarter of 2024 was $10.9 million or $2.23 per share compared to $1.8 million or $0.60 per share for the fourth quarter of 2023. Net loss for the year ended December 31, 2024, was $15.6 million or $4.11 per share compared to $8.4 million or $3.04 per share for the year ended December 31, 2023.

Research and Development ("R&D") Expenses

R&D expenses for the fourth quarter of 2024 were $9.9 million compared to $1.0 million for the fourth quarter of 2023. This increase of $8.9 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840 and (2) an increase of $0.4 million in R&D salaries, partially offset by a net decrease of $0.1 million in other R&D expenses.

R&D expenses for the year ended December 31, 2024, were $13.0 million compared to $5.6 million for the year ended December 31, 2023. This increase of $7.4 million was primarily due to: (1) an increase of $8.6 million related to the in-licensing of ALXN1840; (2) an increase of $0.3 million in R&D personnel expenses; and (3) a net increase of $0.1 million in other R&D expenses, partially offset by a decrease of $1.6 million in trial closure related expenses.

General and Administrative ("G&A") Expenses

G&A expenses for the fourth quarter of 2024 were $1.2 million, compared to $0.9 million for the fourth quarter of 2023. This increase of $0.3 million was primarily due to: (1) an increase of $0.1 million in G&A personnel salaries; (2) an increase of $0.1 million in G&A consulting fees; and (3) an increase of $0.1 million in Delaware franchise taxes.

G&A expenses for the year ended December 31, 2024, were $3.2 million, compared to $3.2 million for the year ended December 31, 2023.

On March 31, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies for cancer and autoimmune diseases, reported a poster presentation on its potentially breakthrough next generation γδ T cell-based T cell engager (TCE) platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, taking place April 25-30, 2025 in Chicago, IL (Press release, In8bio, MAR 31, 2025, View Source [SID1234651676]).

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"T cell engagers are an exciting area of immunotherapy that remains in the early innings of development. We believe gamma-delta T cells offer unique properties, including tissue residence, phagocytosis and low IL-6 secretion, representing a powerful modality with the potential to overcome the limitations of current CD-3 based engager therapies," said William Ho, CEO, and co-founder of IN8bio. Our novel gamma-delta T cell engager platform, presented for the first time at AACR (Free AACR Whitepaper) 2025, demonstrates how we can combine the innate tumor-recognition capabilities of gamma-delta T cells with the capacity for significant cell expansion and the specificity of bispecific engagers to drive a potent, targeted immune response against multiple target antigens. These early findings in AML and B-ALL support our broader strategy to harness the unique biology of these cells across a range of cancers."

AACR Poster Presentation Details

Poster Title: A novel gamma-delta T cell engager platform for cancer immunotherapy

Abstract Presentation Number: 7321 (Poster Board 7)

Session Title: Immunology/T Cell Engagers and Novel Antibody-Based Therapies

Session Date and Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM CT

For more details visit: www.aacr.org/meeting/aacr-annual-meeting-2025/abstracts.