On April 28, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported preclinical results with ATNM-400 in prostate cancer models presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, APR 28, 2025, View Source [SID1234652253]). ATNM-400 is a novel, non-PSMA targeting, first in class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that Actinium is evaluating in prostate cancer models prior to and following treatment with Pluvicto. Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed radiotherapy radiolabeled with the beta-particle emitter, Lutetitium-177 (Lu-177) is approved for patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024.

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In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Key Data and Highlights From the ATNM-400 AACR (Free AACR Whitepaper) Presentation

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.

Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working

ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option

ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400

Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver

ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo
Sandesh Seth, Actinium’s Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR (Free AACR Whitepaper), continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR (Free AACR Whitepaper) and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".

The ATNM-400 AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578

On April 28, 2025 AVEO Oncology, an LG Chem company ("AVEO"), a biopharmaceutical company committed to providing differentiated solutions to improve cancer patients lives, reported that three abstracts were accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 annual meeting this May 30-June 3, 2025, in Chicago, IL (Press release, AVEO, APR 28, 2025, View Source [SID1234652269]).

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Presentation Details

Title: Efficacy of second line (2L) treatment with tivozanib (Tivo) as monotherapy or with nivolumab (Nivo) in patients (pts) with metastatic renal cell carcinoma (mRCC) previously treated with an immune checkpoint inhibitor (ICI) combination of ipilimumab (Ipi)/Nivo or vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)/ICI in the Phase 3 TiNivo-2 study
First Author: Alexander Chehrazi-Raffle, MD, City of Hope Cancer Center
Abstract Number: 4540
Poster Session: Genitourinary Cancer—Kidney and Bladder
Poster Board: 340
Date and Time: Monday, June 2, 2025, 9:00am – 12:00 PM CDT

Title: FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET Mab) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC)
First Author: Julie E. Bauman, MD, MPH, George Washington University Cancer Center
Abstract Number: TPS6115
Poster Session: Head and Neck Cancer
Poster Board: 520a
Date and Time: Monday, June 2, 2025, 9:00 AM – 12:00 PM CDT

Title: A phase1b dose escalation study of AV-380 (anti-GDF15 monoclonal antibody) in combination with standard-of-care therapy in cancer patients with cachexia
First Author: Eric Roeland, MD, FAAHPM, Oregon Health & Science University
Abstract Number: TPS12142
Poster Session: Symptom Science and Palliative Care
Poster Board: 159a
Date and Time: Monday, June 2, 2025, 1:30-4:30 PM CDT

On April 28, 2025 Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T-cell engagers (TCEs), reported dosing of the initial patient in the GUARDIAN-101 phase 1 trial of CLSP-1025, the first tumor-specific TCE to enter clinical development. CLSP-1025 exclusively targets cancer cells expressing the p53R175H mutation, a mutation associated with a wide range of solid tumors, including colorectal, pancreatic, lung, gastric, esophageal, gynecological, and prostate cancers (Press release, Clasp Therapeutics, APR 28, 2025, View Source [SID1234652285]).

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Unlike first-generation TCEs that target proteins present on both tumor and normal cells, Clasp’s TCEs target tumor-specific peptides derived from cancer driver mutations, ensuring absolute specificity and minimizing risk of toxicity to healthy tissues. Truncal mutations like p53R175H occur early in tumorigenesis and are present in every tumor cell, making them ideal targets for immune system attack. Moreover, these pHLAre molecules (precise HLA redirecting engagers) are designed to mimic the natural T cell receptor interface between a cancer cell and T cell, maximizing anti-cancer activity.

"Treating the first patient in the GUARDIAN-101 trial marks a pivotal milestone in Clasp’s mission to transform patient outcomes through precision immunotherapy," said Dr. Lauren Harshman, M.D., SVP of Clinical Development at Clasp Therapeutics. "Advancing CLSP-1025 into the clinic is an important step in validating the potential of our pHLAre platform to overcome the limitations of current T-cell engagers and offer a breakthrough treatment option for patients."

At the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting this week, Clasp also presented nonclinical data supporting the clinical development of CLSP-1025, including data supporting the therapeutic candidate’s selectivity, activity, pharmacokinetics and safety profile.

About GUARDIAN-101 and CLSP-1025

Clasp’s Phase 1 GUARDIAN-101 dose escalation study evaluates the safety and initial anti-tumor activity of CLSP-1025. CLSP-1025 is a bispecific antibody-like molecule that directs a patient’s T cells to the tumor, generating a precise immune response to selectively and potently eliminate cancer cells. CLSP-1025 is designed to target the p53R175H peptide in the context of HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have an advanced solid tumor that harbors the p53R175H mutation. This Phase 1 study will identify the dose of CLSP-1025 for use in future studies. Visit clinicaltrials.gov (NCT06778863) for more details.

On April 28, 2025, BeiGene, Ltd. (the "Company") reported its 2024 Annual Report (the "STAR Annual Report") with the Science and Technology Innovation Board (the "STAR Market") of the Shanghai Stock Exchange, which was prepared in accordance with the listing rules of the STAR Market and the applicable securities laws and regulations of the Peoples’ Republic of China (the "PRC" and the "PRC Securities Laws") (Press release, BeiGene, APR 28, 2025, View Source [SID1234652221]). The STAR Annual Report is available to the public in Chinese language only on the website maintained by the Shanghai Stock Exchange at www.sse.com.cn.

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As required by the PRC Securities Laws, the STAR Annual Report contains additional financial information of the Company’s gross profit margin ratio, research and development expenses allocated by key products and other research and development projects and production, sales and inventory stock units for the year ended December 31, 2024 (the "Reporting Period"), prepared in accordance with the China Accounting Standards for Business Enterprises – Basic Standard ("CAS") and other applicable PRC accounting rules, guidance and interpretations (together with CAS, "PRC GAAP"), including but not limited to the China Securities Regulatory Commission’s Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 15 – General Rules for Financial Statement (2023 revised), and Compilation Rule for Information Disclosure by Companies Offering Securities to the Public No. 24-Special Provisions on Information Disclosure in Financial Statements of Pilot Innovative Red-chip Companies on the Sci-Tech Innovation Board. The key differences between such financial information prepared in accordance with PRC GAAP and those prepared in accordance with accounting principles generally accepted in the United States ("U.S. GAAP") for the Reporting Period, which was previously filed with the U.S. Securities and Exchange Commission, are summarized below.

Key Differences between PRC GAAP and U.S. GAAP

Share-based Compensation

Under U.S. GAAP, the Company elects to recognize share-based compensation expenses using the straight-line method for all employee equity awards granted with graded vesting based on service conditions, provided that the amount of compensation cost recognized at any date is at least equal to the portion of the grant-date value of the options that are vested as of that date.

Under PRC GAAP, the Company recognizes share-based compensation expense using the accelerated method for all employee equity awards granted with graded vesting.

Under PRC GAAP, the excess tax benefit resulting from the pre-tax deductible amount arising from U.S. employee share-based payments over the cumulative share-based payment-related expenses recognized for accounting purposes should be recorded in shareholders’ equity rather than in current income tax expenses/benefits under U.S. GAAP.

Leasing

Under U.S. GAAP, as a lessee, the Company recognizes a lease liability based on the present value of the total remaining lease payments, and a corresponding right-of-use assets. The Company subsequently recognizes operating lease expenses on a straight-line basis over the lease term.

PRC GAAP requires lessees to present interest expenses on the lease liability and depreciation on the right-of-use assets separately in the statements of operations. The combination of a straight-line depreciation of the right-of-use assets and the effective interest rate method applied to the lease liability will result in a higher total charge to profit or loss in the initial years of the leases and decreasing expenses during the latter part of the lease term.

Gross Profit Margin Ratio

As required by the PRC Securities Laws, the 2024 STAR Annual Report contained financial information regarding gross profit margin ratio by region, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.

For the year ended December 31, 2024
For the year ended December 31, 2023
By Region Revenue COGS Gross Margin ratio Revenue COGS Gross Margin ratio
China 1,411,307
524,220
62.9%
1,101,951 352,706 68.0%
Ex-China 2,398,934
69,869
97.1% 1,356,828 27,214 98.0%
Total 3,810,241 594,089 - 2,458,779 379,920 -

Research and Development Expenses Allocated by Key Products and Other R&D Projects

As required by the PRC Securities Laws, the 2024 STAR Annual Report contains financial information regarding the research and development ("R&D") expenses allocated by key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below. Amounts reported herein are stated in thousands of U.S. dollars.

Pipeline Products/ Projects
For the year ended December 31, 2024
For the year ended December 31, 2023
Zanubrutinib 129,226 158,051
Tislelizumab 68,684 83,799
Bcl-2 (BGB-11417) 99,939 52,548
CDAC (BGB-16673) 20,380 3,584
CDK4 (BGB-43395) 6,078 1,734
Other R&D projects 215,139 251,701
R&D collaboration projects 189,214 100,115
Subtotal of external R&D expenses 728,660 651,532
Subtotal of internal R&D expenses 1,224,635 1,127,062
Total 1,953,295 1,778,594

Production, Sales and Inventory Stock Units

As required by the PRC Securities Laws, the 2024 STAR Annual Report contained financial information regarding the production, sales and inventory stock units of key products, which was prepared in accordance with PRC GAAP. The corresponding financial information prepared in accordance with U.S. GAAP is presented below.

Item Unit
Production or purchase quantity for the year ended December 31, 2024
Sales quantity for the year ended December 31, 2024
Stock quantity as of December 31, 2024
Key products vials
5,011,100
5,037,600
2,639,900

On April 28, 2025 Nerviano Medical Sciences S.r.l. (NMS), a clinical-stage oncology company developing targeted therapies across DNA damage response and kinase pathways, reported the initiation of two Phase 1 clinical trials evaluating its unique non-trapping, highly specific and brain penetrant PARP1 inhibitor NMS-293 in combination therapies for relapsed small cell lung cancer (SCLC) and BRCA wild-type ovarian cancer (Press release, Nerviano Medical Sciences, APR 28, 2025, View Source [SID1234652238]). NMS-293 represents a third generation of PARP1 inhibitor using non-trapping as a way to combine with DNA-damaging therapies while preserving bone marrow safety. In this way, NMS-293 addresses tumors outside of BRCA or homologous recombination (HR) repair mutations which is unique. BRCA/HR mutation therapies represent only a small minority of tumors, mainly subsets of pancreatic, breast, prostate and ovarian cancers. Thus, therapies that leverage DNA damage response but are not limited to synthetic lethality of BRCA/HR mutations such as NMS-293 combinations with DNA damaging agents could address many tumor types in the future.

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PARPA-293-004: NMS-293 with Temozolomide in Relapsed SCLC

This open-label, single-arm Phase 1 trial will enroll approximately 10 patients with relapsed SCLC who have progressed after platinum-based chemotherapy, immunotherapy and other standards of care. The objectives include safety and preliminary anti-tumor activity. This regimen is similar to the ongoing Phase 2 -002 study in relapsed high-grade glioma. Boosting temozolomide activity in this relapsed setting of SCLC could lead to accelerated registration pathways and future early line combination study options with a variety of DNA-damage modalities.

ClinicalTrials.gov Identifier: NCT06931626

PARPA-293-003: NMS-293 with Topotecan in BRCA Wild-Type Ovarian Carcinoma
This open-label Phase 1 study will enroll approximately 24 patients with recurrent ovarian cancer who have received platinum-based treatments and other standards of care, including patients with platinum resistance. The objectives include safety, dose-finding and preliminary anti-tumor activity. Boosting topotecan activity in patients with relapsed ovarian cancer could lead to accelerated registration pathways as well as various DNA-damaging modality combination options for future early line studies.

ClinicalTrials.gov Identifier: NCT06930755

The rationale for initiating these trials is supported by both preclinical evidence and emerging clinical data from temozolomide combination studies which revealed an unprecedented combination safety profile coupled with preliminary antitumor efficacy in high grade gliomas (Mahnke, DDR Summit 2025 and Guerts et al, AACR (Free AACR Whitepaper)-NCI-EORTC 2023) including glioblastoma (unpublished). NMS-293 is a highly novel third generation PARP1 inhibitor distinguished by non-trapping as shown preclinically with high potency, selectivity and brain penetrance. Taken together, the profile improves on poor bone marrow features of first and second generation trapping PARP1 inhibitors (Yap et al AACR (Free AACR Whitepaper) 2024) and thus removes traditional barriers of combining a DNA damage repair inhibitor with a DNA damaging agent to address non-BRCA mutation tumors.

"These trials represent our focused, mechanism-driven approach to improving treatment outcomes in areas of high unmet medical need including relapsed small cell lung and BRCA wild type ovarian cancers," said Lisa Mahnke, MD, PhD, Chief Medical Officer of NMS. "NMS-293 has the potential to establish a new third generation of PARP1 inhibitor and which is not being developed as a classical PARP1 inhibitor due its unique chemotype. NMS-293 is a highly potent, highly selective, non-trapping PARP1, inhibitor which is highly brain penetrant and which can be developed across many tumor types including brain tumors like GBM or others with or without brain metastases in combination with a variety of DNA-damaging modalities such as chemotherapies or ADC payloads to reach many non-BRCA-mutation tumors in the future."