TIVDAK® (tisotumab vedotin) Approved by Japan Ministry of Health, Labour and Welfare for the Treatment of Advanced or Recurrent Cervical Cancer that has Progressed on or after Chemotherapy

On March 27, 2025 Genmab A/S (Nasdaq: GMAB) reported that the Japan Ministry of Health, Labour and Welfare has approved TIVDAK (tisotumab vedotin) for the treatment of advanced or recurrent cervical cancer that has progressed on or after cancer chemotherapy (Press release, Genmab, MAR 27, 2025, View Source [SID1234651522]). TIVDAK is the first and only ADC to be approved for people living with cervical cancer in Japan.

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In recent years, cervical cancer incidence and mortality rates have increased in Japan, particularly among women under age 50.i,ii,iii Moreover, patients with recurrent or metastatic cervical cancer whose disease has progressed after first-line therapy have limited treatment options.

"Patients with advanced or recurrent cervical cancer, in general, have a poor prognosis. The advent of new treatment options, especially for second-line or later treatment, is much needed," said Aikou Okamoto, M.D., Ph.D., Chief Professor, Department of Obstetrics and Gynecology at The Jikei University School of Medicine. "Cervical cancer treatment has advanced in recent years, but it is very meaningful that the approval of tisotumab vedotin as an ADC has increased the number of treatment options with a new mechanism of action that is expected to prolong overall survival. This is good news for patients and healthcare professionals."

The approval is based on data from the randomized, open-label, global Phase 3 innovaTV 301 clinical trial 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 included 502 patients, 101 of which were Japanese. 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.

Adverse drug reactions occurred in 219 (87.6%) of 250 patients (including 50 Japanese patients) treated with TIVDAK. The most common (≥20%) adverse reactions included conjunctivitis (n=76; 30.4%), nausea (n=73; 29.2%), peripheral sensory neuropathy (n=67; 26.8%), alopecia (n=61; 24.4%), and epistaxis (n=57; 22.8%), at the data cutoff date of July 24, 2023.

"As a company, we understand the urgent need for patients with advanced cervical cancer whose disease has progressed," said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. "This approval marks an important step forward in transforming the treatment paradigm in Japan, ultimately bringing new hope and possibility to patients and their loved ones."

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 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.

Plus Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights

On March 27, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported financial results for the fourth quarter and full year ended December 31, 2024, and provides an overview of recent and upcoming business highlights (Press release, Plus Therapeutics, MAR 27, 2025, View Source [SID1234651521]).

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"Over the last twelve months, Plus has reported very promising safety and efficacy data for our lead drug REYOBIQ administered in our two most advanced CNS cancer programs," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "The recently raised capital, coupled with existing grant support, enables us to progress both our therapeutic programs to key clinical and regulatory milestones as well as commercially launch our CNSide diagnostic platform. The year 2025 has the potential to be transformational at Plus as we anticipate transitioning to an operational revenue generating company with the launch of CNSide. We are highly appreciative of our investors, partners and other stakeholders for their continued commitment to Plus as we deliver on our objectives and drive value."

Q4 2024 & RECENT HIGHLIGHTS AND MILESTONES

Corporate


Raised $15.0 million in a private placement financing, enabling the Company to regain compliance with Nasdaq minimum stockholders’ equity requirement and extending runway into 2026

Obtained a $2.0 million grant award advance from the Company’s existing $17.6 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to accelerate the development of REYOBIQ for our leptomeningeal metastases (LM) program

Strengthened management team with key leadership appointments:
o
Dr. Michael Rosol as Chief Development Officer – Dr. Rosol will lead the Company’s clinical, pre-clinical, and biomarker development activities
o
Mr. Russell Bradley as President and General Manager of Plus Therapeutics’ wholly owned subsidiary, CNSide Diagnostics, LLC ("CNSide Diagnostics") – Mr. Bradley will provide leadership at CNSide with an immediate focus on commercialization of the diagnostic platform
o
Dr. Jonathan Stein as Medical Director, CNSide Diagnostics – Dr. Stein will provide technical leadership to support CNSide Diagnostics, having experience in all aspects of diagnostic operations, compliance and regulatory affairs

REYOBIQ


Received U.S. FDA agreement for the brand name REYOBIQ (Rhenium Re186 Obisbemeda) for the Company’s lead radiotherapeutic

Published Phase 1 clinical trial results for REYOBIQ in the peer-reviewed publication Nature Communications, demonstrating safety and potential efficacy in treating recurrent glioblastoma (GBM), with patients receiving a radiation dose >100 Gy achieving a median overall survival of 17 months, more than double the standard of care. Additional details can be found here

Granted U.S. FDA Orphan Drug Designation for REYOBIQ for the treatment of LM in patients with lung cancer


Completed ReSPECT-LM Phase 1 single dose administration trial and determined the maximum feasible and recommended Phase 2 doses. Additional details can be found here

Presented positive ReSPECT-LM Phase 1 interim data for LM at the 2024 SNO Annual Conference. Additional details can be found here

Presented positive ReSPECT-LM Phase 1 interim data for breast cancer patients with LM at the 2024 San Antonio Breast Cancer Symposium. Additional details can be found here

Expanded strategic agreement with Telix IsoTherapeutics Group, securing a reliable supply of cGMP Rhenium-186 for late-stage clinical trials and future commercialization of REYOBIQ. Additional details can be found here

CNSide


Presented positive FORESEE clinical trial summary demonstrating utility of the CNSide Cerebrospinal Fluid Assay Platform ("CNSide") in diagnosis and clinical management of patients with LM. Additional details can be found here

Presented real world, multi-institutional, longitudinal data showing the commercial utility of CNSide at the 2024 Society for Neuro-Oncology Annual Meeting. Additional details can be found here

UPCOMING EXPECTED EVENTS AND MILESTONES


Full commercial launch of CNSide on track for 2025

Presentations planned for the following upcoming medical conferences:
o
Nuclear Medicine and Neuro-oncology Symposium (NMN) in Vienna, Austria (May 9-10, 2025); Title: "Diagnostic and Therapeutic Innovations in the Era of Precision Medicine – Nuclear Medicine Meets Neuro-Oncology" on May 9, 2025 by Dr. Andrew Brenner, M.D, Ph.D.
o
Society for Neuro-Oncology/American Society of Clinical Oncology (SNO/ASCO) CNS Metastases Conference in Baltimore, Maryland (August 14-16, 2025): Corporate Key Opinion Leader symposium, title to be determined

Complete enrollment of Cohort 1 in the ReSPECT-LM Phase 1 multiple dose administration trial in 2025

Complete end of Phase 1 meeting with the U.S. FDA for the ReSPECT-LM trial and determine next clinical steps in 2025

Complete ReSPECT-GBM Phase 2 enrollment in 2025

Obtain IND approval for the ReSPECT-PBC Phase 1/2 trial of REYOBIQ for pediatric ependymoma and high-grade glioma in H2 2025

FULL YEAR 2024 FINANCIAL RESULTS


The Company’s cash and investments balance was $3.6 million at December 31, 2024 compared to $8.6 million at December 31, 2023.

The Company recognized $5.8 million in grant revenue in the year ending December 31, 2024 and $4.9 million for the year ending December 31, 2023, which in both periods represents CPRIT’s share of the costs incurred for REYOBIQ development for the treatment of patients with LM

Total operating loss for the year ending December 31, 2024 was $14.7 million versus $13.3 million for the year ending December 31, 2023. The increase is primarily due to increased expenditures related to the ReSPECT-LM trial


Net loss for the year ending December 31, 2024 was $13.0 million, or $(1.95) per basic share versus $13.3 million, or $(4.24) per basic share, for the year ending December 31, 2023
FOURTH QUARTER & FULL YEAR 2024 RESULTS CONFERENCE CALL

The Company will hold a conference call and live audio webcast at 5:00 pm Eastern Time today to discuss its financial results and provide a general business update.

The live audio webcast will be available at ir.plustherapeutics.com/events.

Participants may also pre-register any time before the call here. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Please dial in 15 minutes prior to the start time.

Following the live call, a replay will be available on the Company’s website under the ‘For Investors’ section. The webcast will be available on the Company’s website for 90 days following the live call.

Boundless Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Business Highlights

On March 27, 2025 Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported financial results and business highlights for the fiscal quarter and full year ended December 31, 2024 (Press release, Boundless Bio, MAR 27, 2025, View Source [SID1234651520]).

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"We made important strides in 2024 as we became a public company and continued to advance BBI-355, our oral, selective CHK1 inhibitor in the Phase 1/2 POTENTIATE trial in patients with oncogene amplified cancers, and we look forward to reporting preliminary proof-of-concept data in the second half of this year," said Zachary Hornby, President and CEO of Boundless Bio. "Additionally, we have continued to identify new targets and are advancing an oral degrader of a novel kinesin identified by our Spyglass platform. We are on track to nominate a development candidate for our Kinesin program by mid-year, with the intention to submit an IND in the first half of 2026. We look forward to the year ahead as we continue to advance our pipeline to address the significant unmet need in patients with oncogene amplified cancers."

Research and Development Highlights and Upcoming Milestones

BBI-355, a novel, oral, potent CHK1 inhibitor designed to target replication stress in oncogene-amplified cancers


Enrollment in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a monotherapy and combination agent in patients with locally advanced or metastatic solid tumors with oncogene amplifications is ongoing.

ECHO, a proprietary diagnostic for the detection of ecDNA amplified oncogenes, is in use in the POTENTIATE trial.

Boundless expects to report preliminary clinical proof-of-concept safety and antitumor activity data in the second half of 2025.

Novel Kinesin program targeting ecDNA segregation and inheritance


Boundless is advancing a preclinical program targeting a previously undrugged kinesin that is essential for proper ecDNA segregation and inheritance during cell division.

Boundless expects to nominate a development candidate by mid-2025 and submit an investigational new drug application (IND) to the FDA in the first half of 2026.

Recent Corporate Highlights


In February 2025, Boundless appointed Robert Doebele, M.D., Ph.D., as Chief Medical Officer. Dr. Doebele is a medical oncologist and previously served as Chief Medical Officer and Chief Scientific Officer at Rain Oncology, where he led the early and late-stage development of multiple oncology programs using biology-based, tumor-agnostic strategies.

Fourth Quarter and Full Year 2024 Financial Results


Cash Position: Cash, cash equivalents, and short-term investments totaled $152.1 million as of December 31, 2024.

Research and Development (R&D) Expenses: R&D expenses were $13.3 million for the fourth quarter of 2024 and $55.3 million for the full year 2024, compared to $10.4 million and $42.6 million for the same periods in 2023.

General and Administrative (G&A) Expenses: G&A expenses were $5.0 million for the fourth quarter of 2024 and $18.0 million for the full year 2024, compared to $3.4 million and $12.2 million for the same periods in 2023.

Net Loss: Net loss totaled $16.4 million for the fourth quarter of 2024 and $65.4 million for the full year 2024, compared to $12.1 million and $49.4 million for the same periods in 2023.

BeyondSpring Reports 2024 Year-End Financial Results and Highlights Key Clinical & Strategic Milestones

On March 27, 2025 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a global clinical-stage biopharmaceutical company developing innovative cancer therapies, reported its financial results for the year ended December 31, 2024, and provided a business update on key clinical and corporate developments (Press release, BeyondSpring Pharmaceuticals, MAR 27, 2025, View Source;utm_medium=rss&utm_campaign=beyondspring-reports-2024-year-end-financial-results-and-highlights-key-clinical-strategic-milestones [SID1234651519]).

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"2024 was a pivotal year for BeyondSpring, with significant clinical progress for our first-in-class agent Plinabulin and strategic advancements for SEED Therapeutics (SEED), which BeyondSpring co-founded and owns an equity stake in. We believe these developments create value benefiting all stakeholders," said Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring.

"Plinabulin demonstrated a statistically significant survival benefit in patients with second- and third-line non-small cell lung cancer (NSCLC) (EGFR wild-type), a setting where no new therapies have been approved in over a decade. This Phase 3 data, now published in The Lancet Respiratory Medicine, strengthens our regulatory strategy as we prepare for submission to the Chinese National Medical Products Administration (NMPA) and potentially regulatory authorities in other jurisdictions."

"BeyondSpring is also advancing Plinabulin’s potential as a next-generation immuno-oncology agent, with its potent effect in dendritic cell maturation. An ongoing Phase 2 study showed that Plinabulin, in combination with a PD-1 inhibitor and docetaxel, produced promising efficacy in patients with metastatic NSCLC who had progressed on prior PD-1/PD-L1 inhibitors with good tolerability. While PD-1 and PD-L1 antibody annual sales have exceeded $50 billion, with most sales coming from lung cancer, 60% of patients across multiple cancer indications develop acquired resistance to checkpoint inhibitors, which we believe represents a significant opportunity for Plinabulin to impact the treatment landscape and create substantial value."

"SEED also made significant progress in 2024, securing a strategic research collaboration with Eisai Co., Ltd. ("Eisai"), a second global pharma partnership in addition to the Eli Lilly and Company ("Lilly") partnership. Under this collaboration, SEED will be eligible to receive upfront payments and potential preclinical, clinical, regulatory and sales milestone payments of up to $1.5 billion, plus tiered royalties on net sales. In parallel, SEED is advancing its internal lead oncology asset, RBM39 degrader, toward clinical development. SEED’s recognition in two Nature review papers as a leader in targeted protein degradation (TPD), along with recent granting of Rare Pediatric Disease and Orphan Drug Designations by the FDA for its RBM39 degrader ST-01156, further underscore its unique platform and reinforce its leadership in this emerging field."

"With strongly anchored pipelines, key global partnerships and deliberate plans to navigate regulatory pathways, we believe BeyondSpring and SEED are well-positioned to drive transformative advancements in oncology and TPD in 2025," Dr. Lan Huang concluded.

Recent Clinical and Business Updates
Plinabulin Clinical Updates
Plinabulin Phase 3 Data Published in The Lancet Respiratory Medicine and Presented at the IASLC 2024 conference
Demonstrated a statistically significant overall survival, PFS and ORR benefit in second- and third-line NSCLC (EGFR wild-type) compared to standard-of-care docetaxel.
Supports planned regulatory submissions to NMPA and potentially regulatory authorities in other jurisdictions.
Plinabulin Combination Therapy in multiple cancers which failed PD-1/PD-L1 therapies at MD Anderson Cancer Center
Phase 1 investigator-initiated study of Plinabulin + PD-1/PD-L1 inhibitor + radiation showed encouraging data in re-sensitizing NSCLC, Head and Neck cancer, and Hodgkin’s Lymphoma.
Responding patients showed dendritic cell maturation.
Plinabulin Combination Therapy in NSCLC
Ongoing Phase 2 investigator-initiated study (Study 303) of Plinabulin + PD-1 inhibitor + Docetaxel showed encouraging efficacy and safety outcomes in metastatic NSCLC patients who had progressed on prior PD-1/PD-L1 inhibitors.
Supports Plinabulin’s potential to resensitize tumors to checkpoint inhibitors.
Other Ongoing Clinical Trial
Enrolled first patient in a Phase 2 investigator-initiated study (Study 302) of Plinabulin + PD-1 inhibitor + Etoposide/Platinum (EP) for first-line extensive-stage small-cell lung cancer (ES-SCLC).d
BeyondSpring Business Update
Entered into definitive agreements to sell a portion of BeyondSpring’s Series A-1 Preferred Shares of SEED for gross proceeds of approximately $35.4 million to advance late-stage clinical development of Plinabulin. First closing of approximately $7.35 million completed in February 2025.
SEED Updates
Strategic Collaborations & Financing
Research collaboration with Eisai to develop molecular glue degraders for oncology and neurodegenerative diseases with potential payments to SEED of up to $1.5 billion.
$24 million Series A-3 financing first close, led by Eisai.
Achieved third milestone with Lilly R&D collaboration.
Industry Recognition & FDA Designations
SEED was recognized in two Nature review articles as a leading company in TPD.
Received Rare Pediatric Disease and Orphan Drug Designations from the FDA for RBM39 degrader ST-01156, reinforcing its potential as a breakthrough therapy for hard-to-treat cancers.
Full-Year 2024 Financial Results1
Continuing operations:

R&D expenses: $2.6 million (vs. $7.3 million in 2023), reflecting completion ofPlinabulin Dublin-3 and Protective Studies.
G&A expenses: $6.1 million (vs. $7.8 million in 2023), driven by cost optimization measures.
Net loss: $8.9 million (vs. $14.0 million in 2023).
Cash, cash equivalents, and short-term investments: $2.9 million as of December 31, 2024.

Discontinued operations:

Net loss: $7.8 million (vs. $7.9 million in 2023).
Current assets: $25.3 million as of December 31, 2024.

Expected 2025 Milestones
Plinabulin
1H 2025: Updated data from Phase 2 of Study 303 in metastatic NSCLC progressed on PD-1/PD-L1 inhibitors.
2H 2025: Preliminary data from Phase 2 of Study 302 in 1L ES-SCLC.
SEED
Mid-2025: Expected IND filing of RBM39 degrader.
2H 2025: RBM39 degraderexpected to begin patient enrollment.
2H 2025: Tau degraderexpected to achieve in vivo efficacy.
Note: 1. As a result of BeyondSpring entering into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED, SEED’s operations met the criteria as discontinued operations under ASC 205-20 for financial reporting purposes.

Arbutus Reports Fourth Quarter and Year End 2024 Financial Results and Provides Corporate Update

On March 27, 2025 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company focused on infectious disease, reported fourth quarter and year end 2024 financial results and provided a corporate update (Press release, Arbutus Biopharma, MAR 27, 2025, View Source [SID1234651518]).

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"With my recent appointment as CEO of Arbutus, I am excited to lead the company into its next chapter," said Lindsay Androski, President and CEO of Arbutus. "Along with Arbutus’ new directors, my focus is on evaluating strategies to accelerate the development and potential approval of imdusiran, alongside several subject matter experts being retained to assist with this evaluation. As part of this review, we have implemented a reduction in our workforce of 57%, retaining a core team well-positioned to advance imdusiran into a Phase 2b trial, and have taken additional related steps to improve our financial and operational efficiency. We will provide an update on our pipeline and development timeline upon completion of our review of our chronic hepatitis B virus (cHBV) programs."

Ms. Androski continued, "I am also excited to welcome Tuan Nguyen to our leadership team as Chief Financial Officer. Tuan’s appointment reinforces our renewed focus on advancing our pipeline efficiently and delivering value to patients and our stakeholders. In addition, the Company announced today the departure of David Hastings, Karen Sims and Christopher Naftzger, and I would like to thank them for their valuable contributions over the past years.

We will continue to consult closely with and support our exclusive licensee Genevant Sciences to protect and defend our intellectual property, including through recently filed international lawsuits against Moderna for patent infringement in the development of its COVID-19 and RSV vaccines. We expect 2025 to be a transformative year for Arbutus."

2024 Clinical Development Milestones

Imdusiran (AB-729)

At the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting in November 2024, the Company presented new data from its IM-PROVE I Phase 2a clinical trial showing that six doses of imdusiran and 24 weeks of pegylated interferon alfa-2α (IFN), a standard-of-care immunomodulator, added to ongoing nucleos(t)ide analogue (NA) therapy led to a functional cure rate of 50% (3/6) in HBeAg-negative patients with baseline HBsAg levels less than 1000 IU/mL, and an overall functional cure rate of 25% (3/12). Those patients that achieved a functional cure also seroconverted with high anti-HBs antibody levels. The data from this trial indicated that the combination of imdusiran, IFN and NA therapy was generally safe and well-tolerated.
The Company also presented data from its IM-PROVE II Phase 2a clinical trial at AASLD showing that the addition of low dose nivolumab increased rates of HBsAg loss in cHBV patients that were first treated with imdusiran, ongoing NA therapy and Barinthus Biotherapeutics’ VTP-300, an HBV antigen-specific immunotherapy. In this clinical trial, 23% (3/13) of patients that received imdusiran, VTP-300, NA therapy and nivolumab achieved HBsAg loss by week 48. The Company is evaluating functional cure in these patients.
The Company is reviewing development plans for a Phase 2b clinical trial of imdusiran, including potential ways to accelerate the development timeline. To assist with its review, the Company is currently retaining experts in virology, hepatitis B, and in the clinical development and approval of antiviral treatments. The Company will provide a further update once its review is complete.
AB-101 (oral PD-L1 inhibitor)

AB-101-001 is a Phase 1a/1b double-blind, randomized, placebo-controlled clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses of AB-101, the Company’s oral PD-L1 inhibitor, in healthy subjects and patients with cHBV.
Based on data from Part 2 of this clinical trial reported in November 2024 showing that AB-101 was generally well-tolerated with evidence of dose-dependent receptor occupancy in healthy subjects, Arbutus has moved into Part 3 which evaluates repeat doses of AB-101 for 28 days in patients with cHBV. Next steps for AB-101 will be determined upon completion of the Company’s review of its cHBV programs.
LNP Litigation

Arbutus will continue to consult closely with and support our exclusive licensee Genevant Sciences to protect and defend Arbutus’s intellectual property, which is the subject of on-going lawsuits against Moderna and Pfizer/BioNTech. The Company, together with Genevant, is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of Arbutus’s patented LNP technology that was developed with great effort and at a great expense, and without which Moderna’s and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful.
The claim construction hearing for the lawsuit against Pfizer/BioNTech occurred in December 2024. The court is expected to provide its ruling on the claim construction and issue a further scheduling order in 2025.
The jury trial in the Moderna U.S. litigation is currently scheduled for September 2025. Expert discovery continues in this lawsuit. On March 3, 2025, the Company announced that alongside Genevant Sciences, it filed five international lawsuits seeking to enforce patents protecting their innovative LNP technology across 30 countries.
Corporate Updates

In March 2025, the Company’s Board took action to reduce the Company’s workforce by 57% resulting in a total workforce after reductions of 19 employees. The Board also decided to exit the Company’s corporate headquarters in Warminster, PA, and to discontinue in-house scientific research. In connection with these actions, the Company expects to incur a one-time restructuring charge in the first quarter of 2025 of approximately $11 million to $13 million.
Also in March 2025, the Board appointed Tuan Nguyen as Chief Financial Officer effective March 28, succeeding David C. Hastings. Additionally, the Company announced the departure of J. Christopher Naftzger as General Counsel and Chief Compliance Officer and Dr. Karen Sims as Chief Medical Officer.
Tuan Nguyen has almost two decades of experience in biopharma working on small molecules and AAV gene therapies. Most recently, he served as Chief Financial Officer of Kinevant Sciences, a subsidiary of Roivant Sciences, dedicated to treating rare inflammatory and autoimmune diseases with significant unmet need. Prior to that he held various senior finance leadership roles at Adverum, Intarcia Therapeutics, Fibrogen, and UCB. He has helped raise over $2 billion in dilutive and non-dilutive capital. Mr. Nguyen earned his MBA with dual concentrations in Finance and Entrepreneurship, Innovation, & Change from Emory University. Mr. Nguyen will report directly to Lindsay Androski, President and CEO.
Financial Results

Cash, Cash Equivalents and Investments

As of December 31, 2024, the Company had cash, cash equivalents and investments in marketable securities of $122.6 million compared to $132.3 million as of December 31, 2023. During the year ended December 31, 2024, the Company used $64.9 million in operating activities, which was partially offset by $44.1 million of net proceeds from the issuance of common shares under its "at-the-market" (ATM) offering program and $7.5 million of proceeds from the exercise of employee stock options. The Company expects to significantly reduce its net cash burn in 2025 when compared to 2024. Given the Company’s review of its pipeline and development plans for its cHBV programs and refocused operations, the Company has terminated its ATM offering program.

Revenue

Total revenue was $6.2 million for the year ended December 31, 2024, compared to $18.1 million for the same period in 2023. The decrease of $11.9 million was due primarily to a $9.3 million decrease in revenue recognition of the upfront license fee received in 2022 from Qilu, the Company’s collaboration partner in China, Hong Kong, Macau and Taiwan, as less effort was required from the Company in 2024 compared to 2023 to support Qilu’s progress towards achieving its own imdusiran manufacturing capability. Additionally, license royalty revenues decreased $2.6 million in 2024 compared to 2023 due to a decrease in Alnylam’s sales of ONPATTRO.

Operating Expenses

Research and development expenses were $54.0 million for the year ended December 31, 2024 compared to $73.7 million for the same period in 2023. The decrease of $19.7 million was due primarily to: i) a decrease in clinical expenses related to the discontinuation of the Company’s coronavirus and AB-161 programs during the fourth quarter of 2023; ii) a decrease in research activities and preclinical study costs for AB-101 which is now in a Phase 1a/1b clinical trial; and iii) cost savings from the Company’s decision in August 2024 to streamline the organization to focus its efforts on advancing the clinical development of imdusiran and AB-101, which included ceasing all discovery efforts, discontinuing its IM-PROVE III clinical trial and reducing its workforce by 40%. These actions in August 2024 resulted in the Company incurring a one-time restructuring charge of $3.7 million in the third quarter of 2024.

General and administrative expenses were $22.1 million for the year ended December 31, 2024, compared to $22.5 million for the same period in 2023. This decrease was due primarily to decreases in employee compensation-related expenses, partially offset by an increase in litigation-related legal fees.

Net Loss

For the year ended December 31, 2024, our net loss was $69.9 million, or a loss of $0.38 per basic and diluted common share, as compared to a net loss of $72.8 million, or a loss of $0.44 per basic and diluted common share, for the year ended December 31, 2023.

Outstanding Shares

As of December 31, 2024, the Company had 190.0 million common shares issued and outstanding, as well as 16.9 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 20% of the Company’s outstanding common shares as of December 31, 2024.

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(in thousands, except share and per share data)

Year Ended December 31,
2024 2023
Revenue
Collaborations and licenses $ 3,919 $ 14,274
Non-cash royalty revenue 2,252 3,867
Total revenue 6,171 18,141
Operating expenses
Research and development 54,037 73,700
General and administrative 22,108 22,475
Change in fair value of contingent consideration 2,625 69
Restructuring costs 3,720 —
Total operating expenses 82,490 96,244
Loss from operations (76,319 ) (78,103 )
Other income (loss)
Interest income 6,585 5,688
Interest expense (137 ) (459 )
Foreign exchange gain (49 ) 25
Total other income 6,399 5,254
Net loss $ (69,920 ) $ (72,849 )
Net loss per common share
Basic and diluted $ (0.38 ) $ (0.44 )
Weighted average number of common shares
Basic and diluted 185,608,874 165,960,379

UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands)

December 31, 2024 December 31, 2023
Cash, cash equivalents and marketable securities, current $ 122,623 $ 126,003
Accounts receivable and other current assets 4,693 6,024
Total current assets 127,316 132,027
Property and equipment, net of accumulated depreciation 3,309 4,674
Investments in marketable securities, non-current — 6,284
Right of use asset 1,048 1,416
Other non-current assets 34 —
Total assets $ 131,707 $ 144,401

Accounts payable and accrued liabilities $ 7,564 $ 10,271
Deferred license revenue, current 7,571 11,791
Lease liability, current 483 425
Total current liabilities 15,618 22,487
Liability related to sale of future royalties 4,829 6,953
Deferred license revenue, non-current 2,863 —
Contingent consideration 10,225 7,600
Lease liability, non-current 806 1,343
Total stockholders’ equity 97,366 106,018
Total liabilities and stockholders’ equity $ 131,707 $ 144,401

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)

Twelve Months Ended December 31,
2024
2023
Net loss $ (69,920 ) $ (72,849 )
Non-cash items 7,899 5,146
Change in deferred license revenue (1,357 ) (10,664 )
Other changes in working capital (1,472 ) (7,569 )
Net cash used in operating activities (64,850 ) (85,936 )
Net cash provided by investing activities 22,948 50,773
Issuance of common shares pursuant to the Open Market Sale Agreement 44,123 29,852
Cash provided by other financing activities 7,873 795
Net cash provided by financing activities 51,996 30,647
Effect of foreign exchange rate changes on cash and cash equivalents (49 ) 25
Increase/(decrease) in cash and cash equivalents 10,045 (4,491 )
Cash and cash equivalents, beginning of period 26,285 30,776
Cash and cash equivalents, end of period 36,330 26,285
Investments in marketable securities 86,293 106,002
Cash, cash equivalents and marketable securities, end of period $ 122,623 $ 132,287

About Imdusiran (AB-729) 

Imdusiran is an RNAi therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. In a Phase 2a clinical trial, imdusiran achieved meaningful functional cure rates in patients with cHBV when combined with pegylated interferon (IFN) alfa-2α and nucleos(t)ide analogue (NA) therapy. Clinical data generated thus far has shown imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. The Company is currently reevaluating plans for a Phase 2b clinical trial of imdusiran combined with IFN and NA therapy.

About AB-101 

AB-101 is an oral PD-L1 inhibitor candidate that is designed to allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates re-activation of exhausted HBV-specific T-cells from cHBV patients. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial.

About HBV 

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2 million people in the United States suffer from chronic HBV infection. Approximately 1.1 million people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.