On January 13, 2025 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, reported its 2025 corporate objectives and provided a financial update (Press release, Arbutus Biopharma, JAN 13, 2025, View Source [SID1234649716]).

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"We enter 2025 with solid financial footing and strong momentum in achieving our mission of developing a functional cure for cHBV, a disease that affects more than 250 million people worldwide and is a leading cause of liver cancer," said Michael J. McElhaugh, Interim President and Chief Executive Officer of Arbutus. "The data we reported late last year from our IM-PROVE I Phase 2a clinical trial showed a meaningful functional cure rate and immune activation in cHBV patients that were treated with our RNAi therapeutic, imdusiran, interferon and nucleos(t)ide analogue (NA) therapy. These data support our belief that imdusiran is differentiated from other RNAi therapeutics in development for HBV. Therefore, we plan to initiate a Phase 2b clinical trial combining imdusiran, interferon and NA therapy in the first half of 2025."

Imdusiran (RNAi therapeutic)

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 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 combination of imdusiran, IFN and NA therapy was generally safe and well-tolerated.
Based on this data, the Company is planning to initiate a placebo-controlled Phase 2b clinical trial with this treatment regimen in the first half of 2025. Subject to regulatory approval, the clinical trial is anticipated to enroll approximately 170 HBeAg-negative cHBV patients with baseline HBsAg ≤1000 IU/mL. Additional details will be provided by the Company after regulatory approval.
The Company also presented data from its IM-PROVE II Phase 2a clinical trial 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. 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 and anticipates reporting data in the first half of 2025.
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 (PK), and pharmacodynamics (PD) 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, Arbutus has moved into Part 3 which evaluates repeat doses of AB-101 for 28 days in patients with cHBV. Data from the 10 mg cohort is expected in the first half of 2025. Next steps for AB-101 will be determined after Arbutus evaluates data from Part 3 of this clinical trial.
LNP Litigation

Arbutus will continue to protect and defend its intellectual property, which is the subject of the on-going lawsuits against Moderna and Pfizer/BioNTech. The Company is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of its patented LNP technology that was developed with great effort and at a great expense, 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 on December 18, 2024. The court is expected to provide its ruling on the claim construction and issue the scheduling order in the first half of 2025.
The Moderna trial date is scheduled for September 24, 2025, and is subject to the court’s availability. Expert reports and expert depositions continue in this lawsuit.
Financial Update:

The Company had cash, cash equivalents and investments in marketable securities totaling approximately $123 million as of December 31, 2024 (unaudited).
The Company expects to significantly reduce its net cash burn in 2025 when compared to 2024. Net cash burn is expected to range from $47 to $50 million in 2025 versus a 2024 net cash burn of approximately $65 million (unaudited). The Company believes its cash, cash equivalents, investments in marketable securities and anticipated contractual milestones from Qilu Pharmaceutical, its strategic partner in Greater China, are sufficient to fund its operations through the first quarter of 2028. This includes fully funding the imdusiran Phase 2b clinical trial.
The preliminary cash, cash equivalents and investments as of December 31, 2024 and the estimated 2024 net cash burn were calculated prior to the completion of an audit by Arbutus’ independent registered public accounting firm and are therefore subject to adjustment.
With its current cash balance and anticipated 2025 net cash burn, the Company does not anticipate utilizing its "at-the-market" program (ATM) this year.
About Imdusiran

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. In the first half of 2025, the Company is planning to initiate a Phase 2b clinical trial of imdusiran combined with IFN and NA therapy.

About AB-101

AB-101 is our oral PD-L1 inhibitor candidate that we believe will 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. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in patients chronically infected with HBV. 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.

On January 13, 2025 Aptose biosciences presented its corporate presentation (Presentation, Aptose Biosciences, JAN 13, 2025, View Source [SID1234649635]).

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On January 13, 2025 Eli Lilly and Company (NYSE: LLY) and Scorpion Therapeutics, Inc. ("Scorpion"), a private biotechnology company developing small molecule precision oncology therapies, reported a definitive agreement for Lilly to acquire Scorpion’s PI3Kα inhibitor program STX-478 (Press release, Eli Lilly, JAN 13, 2025, View Source [SID1234649652]). STX-478 is a once-daily oral, mutant-selective PI3Kα inhibitor currently being evaluated in a Phase 1/2 clinical trial for breast cancer and other advanced solid tumors.

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STX-478 could represent the next generation of PI3Kα targeting agents by selectively targeting the pathway in cancerous but not healthy cells, thus overcoming a key limitation of currently available medicines that target the PI3Kα pathway. This approach could potentially offer better disease control through deeper pathway inhibition, as well as improved tolerability.

"PI3Kα mutations occur in a meaningful proportion of hormone-positive breast cancers, and there is significant unmet need for new treatment options that effectively and safely target this pathway," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "The selectivity profile of STX-478 has led to a differentiated clinical profile, enabling use in combinations with standard-of-care therapies to potentially deliver meaningful impact in earlier treatment settings when there is the best opportunity to improve outcomes for patients. We look forward to leveraging the great work of the Scorpion team to date, along with Lilly’s deep expertise in breast cancer, to further advance STX-478 with speed and focus."

Under the terms of the agreement, Lilly will acquire Scorpion and Scorpion shareholders could receive up to $2.5 billion in cash, inclusive of an upfront payment and subsequent payments upon achievement of certain regulatory and sales milestones. Additionally, as part of the transaction, Scorpion will spin out a new entity to hold its employees and non-PI3Kα pipeline assets. The new, independent company would be owned by Scorpion’s current shareholders with Lilly holding a minority equity interest. The new company will be led by Dr. Friedman and members of the current Scorpion management team and will focus on discovering and delivering a portfolio of precision medicines to patients, accelerated by Scorpion’s discovery capabilities and non-PI3Kα pipeline of medicines.

"Lilly has advanced scientific breakthroughs for some of the most difficult-to-treat cancers," said Adam Friedman, M.D., Ph.D., president and chief executive officer of Scorpion. "We believe Lilly’s global capabilities and strategic commitment to patients with breast cancer will accelerate our goal of developing STX-478 to improve outcomes for the many patients with solid tumors driven by PI3Kα mutations. This acquisition is a testament to the expertise of the Scorpion team and our drug discovery capabilities, which will become the foundation of our new company."

The transaction is subject to customary closing conditions. Lilly will determine the accounting treatment of this transaction in accordance with Generally Accepted Accounting Principles (GAAP) upon closing. This transaction will thereafter be reflected in Lilly’s financial results and financial guidance.

For Lilly, Citi is acting as exclusive financial advisor and Ropes & Gray LLP is acting as legal counsel. For Scorpion, Centerview Partners LLC is acting as lead financial advisor with additional financial advisory from Morgan Stanley, and Kirkland & Ellis LLP is acting as legal counsel.

On January 13, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that the company has entered into a supply agreement with Janssen Research & Development, LLC, a Johnson & Johnson company, to evaluate ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, in combination with subcutaneous (SC) amivantamab, Johnson & Johnson’s fully-human EGFR-MET bispecific antibody, for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (Press release, ORIC Pharmaceuticals, JAN 13, 2025, View Source [SID1234649668]).

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Under the terms of the agreement, ORIC will conduct and sponsor the trial and Johnson & Johnson will provide SC amivantamab. ORIC maintains development and commercial rights to ORIC-114 and is free to expand the program in combination with other agents.

"ORIC-114 has already demonstrated encouraging systemic and intracranial activity in heavily pre-treated patients with EGFR/HER2 mutated NSCLC," said Jacob M. Chacko, MD, chief executive officer. "Given the prevalence of brain metastases across all lines of EGFR exon 20 NSCLC, we aim to further explore ORIC-114’s emerging profile in the first-line setting both as a monotherapy and in combination with SC amivantamab."

ORIC expects to initiate the combination Phase 1b trial to evaluate the safety and tolerability of ORIC-114 in combination with SC amivantamab for the first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations in the first quarter of 2025. The primary objectives are to determine the provisional recommended Phase 2 dose (RP2D) for the combination, and additional objectives include assessment of efficacy and further characterization of the safety profile of ORIC-114 in combination with SC amivantamab. The company expects to report initial data from the trial in mid-2026.

In 2024, the company announced the completion of the monotherapy dose escalation portion of the Phase 1b trial of ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications. Based upon these data, ORIC selected the two provisional RP2D levels of ORIC-114 at 80 mg and 120 mg QD, which are being further evaluated in three dose expansion cohorts for dose optimization and final RP2D selection in patients with NSCLC with EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, or EGFR atypical mutations as well as an extension cohort for the treatment of patients with first-line, treatment-naïve EGFR exon 20 mutated NSCLC.

About ORIC-114

ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.

On January 13, 2025 SciTech Development, a clinical-stage pharmaceutical company specializing in oncology, reported the initiation of the next stage of its clinical trial for their lead drug candidate, ST-001 nanoFenretinide (ST-001) (Press release, SciTech Development, JAN 13, 2025, View Source [SID1234649684]). This milestone follows the successful completion of the accelerated safety and dose-escalation stage, where ST-001 demonstrated exceptional safety, tolerability, and pharmacokinetic performance.

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Advancing the Phase 1a Trial with Clear Clinical Objectives

The continuation of the ST-001 clinical trial aims to achieve several critical clinical objectives:

Confirm that ST-001 achieves previously reported clinical response rates.
Determine the pharmacological profile of intravenous fenretinide delivered using SciTech’s novel nanoparticle delivery system, designed for drugs with poor water solubility.
Determine the recommended treatment dose (RTD) to evaluate disease activity and response rates in the follow-on Phase 1b trial and the planned trial in Small Cell Lung Cancer.
"The success of our accelerated Phase 1a trial marks a pivotal milestone, driving ST-001 into the next critical stage of development," said Earle Holsapple, CEO of SciTech Development. "We are thrilled about the potential of ST-001 nanoFenretinide and its promise to transform treatment outcomes for patients battling cancers such as T-cell Non-Hodgkin Lymphoma."

About ST-001 nanoFenretinide

ST-001 nanoFenretinide is a patented nanoparticle IV formulation that combines the drug fenretinide with biocompatible phospholipids. This groundbreaking new investigational drug overcomes bioavailability challenges, enhances therapeutic efficacy, and minimizes toxicity in cancer patients. Powered by SciTech’s advanced delivery platform, ST-001 enables rapid delivery of effective doses of fenretinide to cancer cells, marking a breakthrough in hard-to-treat cancers.

Encouraging Early Results in Phase 1a Accelerated Trial

During the accelerated stage of the trial, ST-001 achieved significant milestones:

Patient Enrollment is Complete for the accelerated stage of the clinical trial marking a significant accomplishment for patients with this rare disease.
Therapeutic Responses Observed: Patients demonstrated partial responses and stable disease, marking an important step for trial advancement.
Excellent Tolerability for ST-001 across all dose levels to date.
Outstanding Pharmacokinetics: The nanoparticle delivery platform overcame longstanding bioavailability challenges, ensuring efficient delivery of fenretinide to tissues.
Future Direction for ST-001 nanoFenretinide

Building on the success of the accelerated Phase 1a stage, the trial begins detailed evaluation of clinical activity and response rates in T-cell lymphomas. The trial is actively underway at nine renowned medical centers across the country. Click here to learn more about the locations and patient trial criteria. Additionally, a separate trial targeting Small Cell Lung Cancer utilizing ST-001 is scheduled to begin in Q2 2025.