On March 25, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported it will host an investor call at 8:00 am ET that will feature KOL Dr. Ehab Atallah, Professor of Medicine at the Medical College of Wisconsin and principal investigator of the Actimab-A + CLAG-M combination trial in patients with relapsed/refractory acute myeloid leukemia (r/r AML) (Press release, Actinium Pharmaceuticals, MAR 25, 2025, View Source [SID1234651422]). Dr. Atallah will discuss Actimab-A clinical results to date including recently published long-term survival outcomes and the planned pivotal Phase 2/3 clinical trial in r/r AML and trials to be conducted under Actinium’s cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI). In addition, Actinium’s management will detail its recently announced Actimab-A solid tumor program, which is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA versus KEYTRUDA alone, and Actimab-A with OPDIVO versus OPDIVO alone initially in patients with head and neck squamous cell carcinoma and non-small cell lung cancer with a separate trial for each indication.

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Actinium’s company update will highlight the 3 separate potential multi-billion-dollar blockbuster market opportunities being pursued with its targeted radiotherapies including the following:

– Actimab-A as a mutation agnostic, backbone therapy for myeloid malignancies including AML and myelodysplastic syndromes (MDS) across multiple treatment settings

– Actimab-A as a pan solid tumor therapy in combination with PD-1 inhibitors including KEYTRUDA and OPDIVO by depleting myeloid derived suppressor cells (MDSCs)

– Iomab-ACT as a universal targeted conditioning agent to increase patients access to cell & gene therapies and improve patient outcomes

To register for the KOL Call & Company Update please use the following link:

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On March 25, 2025 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, reported the presentation of new data from the Phase 2 portion of its Phase 1/2 clinical trial of AU-007 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Aulos Bioscience, MAR 25, 2025, View Source [SID1234651438]). The presentation will focus on promising results for AU-007 in second-line treatment of melanoma.

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AU-007 is a human IgG1 monoclonal antibody designed with the assistance of artificial intelligence to harness the power of interleukin-2 (IL-2) to eradicate solid tumors in patients with unresectable locally advanced or metastatic cancers. The AACR (Free AACR Whitepaper) Annual Meeting is being held April 25-30, 2025, in Chicago, Illinois.

Details of the poster presentation are as follows:

Poster Title: AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update
Abstract: CT178
Session Title: Phase II Clinical Trials 1
Date and Time: Tuesday, April 29, 2025, 9:00 a.m.-12:00 p.m. CDT

The poster will be presented in Poster Section 49 at McCormick Place. An electronic version will also be available on the AACR (Free AACR Whitepaper) 2025 virtual meeting platform.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

To learn more about the AU-007 Phase 1/2 clinical trial program, including study locations in the United States and Australia, please visit ClinicalTrials.gov (identifier: NCT05267626), www.solidtumorstudy.com (U.S.) and www.solidtumourstudy.com (Australia).

On March 25, 2025 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company, reported that the ARTISTRY-7 phase 3 trial of nemvaleukin alfa in combination with Merck’s (known as MSD outside the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer (PROC) will not continue to final analysis and the company will cease development of nemvaleukin for PROC (Press release, Mural Oncology, MAR 25, 2025, View Source [SID1234651408]). In the pre-specified interim analysis conducted by the independent data monitoring committee, nemvaleukin in combination with pembrolizumab did not achieve a statistically significant improvement in overall survival versus investigator’s choice chemotherapy alone and the company believes the study is highly unlikely to achieve success at the final analysis. Median overall survival was 10.1 months for patients treated with nemvaleukin in combination with pembrolizumab and 9.8 months for patients treated with investigator’s choice chemotherapy (hazard ratio: 0.98).

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"We are disappointed for ovarian cancer patients desperately lacking new treatment options. There has been a great deal of work across the industry in this immunologically cold tumor, yet there are still few treatment options that improve survival in this very difficult-to-treat tumor type. We are still on track to report topline data from our potentially registrational trial in mucosal melanoma later next quarter and will assess all available data to inform our next steps," said Caroline Loew, Ph.D., CEO of Mural Oncology.

Nemvaleukin has a well characterized and favorable safety profile, both as a monotherapy and in combination with pembrolizumab, with over 800 patients treated across the broader clinical program. In the interim analysis of ARTISTRY-7, the safety profile was generally consistent with previously reported data.

Nemvaleukin is currently being evaluated in a potentially registrational, phase 2 trial, ARTISTRY-6, cohort 2 in mucosal melanoma, with a topline data readout expected in Q2 2025. Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 of ARTISTRY-6 (monotherapy) and the second half of 2025 for cohort 4 of ARTISTRY-6 (combination therapy), subject to patient enrollment.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the ARTISTRY-7 Trial

ARTISTRY-7 is a phase 3 trial comparing nemvaleukin in combination with pembrolizumab vs. investigator choice single agent chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, with a primary endpoint of overall survival. This four-arm trial also contains two smaller single agent arms, a pembrolizumab and a nemvaleukin arm, to assess contribution of components. A total of 456 patients were enrolled over the four arms of the trial in an approximate 3:1:1:3 randomization. Only arms 1 (nemvaleukin in combination with pembrolizumab) and 4 (investigator’s choice chemotherapy) were designed to be assessed for statistical comparisons. The pre-specified interim analysis was conducted at 77% events (219 events) needed for the final analysis.

About Nemvaleukin

Nemvaleukin alfa (nemvaleukin) is an engineered fusion protein designed to leverage IL-2’s antitumor effects while mitigating the hallmark toxicities that limit its use. Nemvaleukin selectively binds to the intermediate-affinity IL-2 receptor (IL-2R) and is sterically occluded from binding to the high-affinity IL-2R. Because of this molecular design, nemvaleukin treatment leads to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. Nemvaleukin is currently being evaluated in a potentially registrational trial, ARTISTRY-6, cohort 2 in mucosal melanoma, with a topline readout expected in Q2 2025. Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 of ARTISTRY-6 (monotherapy) and the second half of 2025 for cohort 4 of ARTISTRY-6 (combination therapy), subject to patient enrollment.

On March 25, 2025 CStone reported that it will showcase its latest preclinical studies on five internally developed innovative candidates, including the trispecific antibody CS2009, the bispecific antibody CS2011, and three novel antibody-drug conjugates (ADCs) developed from CStone’s proprietary ADC platform: CS5006, CS5007, and CS5005 (Press release, CStone Pharmaceauticals, MAR 25, 2025, View Source [SID1234651423]). The abstracts will be published in Cancer Research, the official journal of AACR (Free AACR Whitepaper), on April 11 (ET).

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CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4. Its innovative molecular design is expected to enhance anti-tumor efficacy by preferentially targeting PD-1/CTLA-4 double positive T cells in tumor microenvironment (TME) while reducing systemic toxicity by sparing CTLA-4 single positive cells, making it a potential first-in-class (FIH) or best-in-class (BIC) next-generation immuno-oncology backbone. Preclinical studies have demonstrated that CS2009 induces more potent tumor growth inhibition (TGI) than its potential competitors, such as PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies, along with an outstanding safety profile. CS2009 is currently evaluated in a global multicenter Phase I clinical trial in patients with late-stage cancers, including non-small cell lung cancer (NSCLC), ovarian cancer (OC), renal cell carcinoma (RCC), cervical cancer (CC), hepatocellular carcinoma (HCC), gastric adenocarcinoma (GAC), etc.
CS5006 is a first-in-class ADC targeting the novel antigen ITGB4, whose expression pattern holds broad application potential in solid tumors, including NSCLC, squamous cell carcinoma of the head and neck (SCCHN), and esophageal squamous cell carcinoma (ESCC). Preclinical studies demonstrated that ITGB4 ADCs were potent to inhibit tumor growth in multiple animal models and well tolerated, thus supporting further preclinical development toward clinical evaluation of this promising FIC molecule.
CS2011 (EGFR/HER3 bispecific antibody) is the bispecific antibody backbone of CS5007 (EGFR/HER3 bispecific ADC). CS2011 enables synergistic blocking of EGFR and HER3 signaling for enhanced therapeutic effects, while minimizing toxicity in normal tissues. CS5007 is built on CStone’s proprietary ADC platform, demonstrating best-in-class potential. Both CS2011 and CS5007 target indications include NSCLC, SCCHN, and colorectal cancer (CRC).
CS5005 is a first-in-class ADC targeting SSTR2, enabling precise targeting of SSTR2-positive tumors, including small cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), and neuroendocrine tumors (NETs). CS5005 is composed of CStone’s proprietary anti-SSTR2 antibody with high affinity and selectivity, CStone’s proprietary hydrophilic beta-glucuronide linker, and potent TOP1 inhibitor. It has demonstrated encouraging anti-tumor activity in vitro and in vivo. Meanwhile, leveraging CStone’s proprietary ADC platform, we are accelerating the development of a bispecific ADC targeting SSTR2/DLL3 (CS5008). By simultaneously targeting SSTR2 and DLL3 that frequently co-express in SCLC, NECs, NETs and others, CS5008 aims to overcome tumor heterogeneity, a challenge faced by mono-specific therapies.
Detailed information on the research topics and poster presentations selected for AACR (Free AACR Whitepaper) 2025 are as follows:

Title: CS2009: A first-in-class trispecific antibody targeting PD-1, CTLA-4, and VEGFA with potential to be a next-generation backbone therapy with combined checkpoint inhibition and anti-angiogenesis
Session Title: Overcoming Checkpoint Inhibition and Tumor Suppression
Presentation Type: Poster
Abstract Number: 7299
Time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM ET
Location: Poster Section 39, Board #14
Key Findings: In the proof of mechanism studies, CS2009 demonstrated strong synergy between the PD-1 and CTLA-4 arms, and the checkpoint inhibitory activity from the PD-1/CTLA4 arms was also greatly enhanced through crosslinking between its anti-VEGF arms with VEGFA dimers. DMPK/toxicology study in cynomolgus monkeys demonstrated that the highest non-severely toxic dose (HNSTD) and the no observed adverse effect level (NOAEL) of CS2009 were 100 mg/kg. CS2009 exhibited a PK profile comparable to those of monoclonal antibodies and demonstrated dose-dependent T-cell activation in cynomolgus monkeys.

Title: CS5006: A novel integrin β4-targeted antibody-drug conjugate (ADC) with robust antitumor activity in preclinical studies
Session Title: Growth Factor Receptors and Other Surface Antigens as Targets for Therapy 2
Presentation Type: Poster
Abstract Number: 2953
Date & Time: Monday, April 28, 2025, 2:00 PM – 5:00 PM ET
Location: Poster Section 18, Board #5
Key Findings: CS5006 (ITGB4 ADC) demonstrated promising therapeutic potential by effectively killing tumor cells in both in vivo and in vitro studies, while maintaining a PK profile comparable to those of monoclonal antibodies.

Title: CS2011: A novel bispecific antibody targeting EGFR and HER3 that demonstrates promising antitumor activity in preclinical evaluation
Session Title: Growth Factor Receptors and Other Surface Antigens as Targets for Therapy 1
Presentation Type: Poster
Abstract Number: 2927
Date and Time: Monday, April 28, 2025, 2:00 PM – 5:00 PM ET
Location: Poster Section 17, Board #1
Key Findings: CS2011 (an EGFR/HER3 bispecific antibody), composed of anti-EGFR and anti-HER3 arms with balanced affinity, effectively and synergistically inhibits EGFR/HER3 downstream signaling, leading to further inhibition of tumor growth. Its lead compound demonstrated favorable stability and a PK profile comparable to those of monoclonal antibodies.

Title: CS5007: A novel EGFR and HER3 dual-targeted antibody-drug conjugate (ADC) with potent antitumor activity in preclinical studies
Session Title: Growth Factor Receptors and Other Surface Antigens as Targets for Therapy 2
Presentation Type: Poster
Abstract Number: 2954
Date and Time: Monday, April 28, 2025, 2:00 PM – 5:00 PM ET
Location: Poster Section 18, Board #6
Key Findings: CS5007 (EGFR/HER3 ADC) inhibited tumor growth by blocking downstream EGFR/HER3 signaling and releasing chemotherapeutic molecules in a target-dependent manner. Its lead compound demonstrated favorable stability and a PK profile comparable to those of monoclonal antibodies.

Title: CS5005: A novel SSTR2-targeted antibody-drug conjugate (ADC) with robust antitumor activity in preclinical studies
Session Title: Molecular, Preclinical, and Clinical Endocrinology
Presentation Type: Poster
Abstract Number: 4751
Date & Time: Tuesday, April 29, 2025, 9:00 AM – 12:00 PM ET
Location: Poster Section 35, Board #18
Key Findings: CS5005 (SSTR2 ADC) demonstrated promising therapeutic potential by effectively killing tumor cells in both in vivo and in vitro studies, while maintaining a PK profile comparable to those of monoclonal antibodies. Additionally, a dual-target ADC against DLL3 and SSTR2 also exhibited potential as a therapeutic agent.

On March 25, 2025 AN2 Therapeutics, Inc. (Nasdaq: ANTX), a biopharmaceutical company focused on discovering and developing novel small molecule therapeutics derived from its boron chemistry platform, reported financial results for the fourth quarter and year ended December 31, 2024 (Press release, AN2 Therapeutics, MAR 25, 2025, View Source [SID1234651439]).

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"Epetraborole demonstrated potential proof-of-concept in Phase 2, achieving nominal statistical significance on two patient-reported outcome measures in patients with treatment-refractory MAC lung disease. Building on these encouraging findings, we updated our statistical analysis plan to select QOL-B as the primary efficacy endpoint for the Phase 3 part of the study, for which we plan to unblind and announce topline results in the second quarter. Should the Phase 3 data support the findings from Phase 2, we plan to engage with the FDA to explore potential registrational pathways for this highly refractory population with limited treatment options," said Eric Easom Co-Founder, Chairman, President and Chief Executive Officer. "Our robust pipeline, including upcoming clinical trials in Chagas disease and melioidosis, highlights our commitment to advancing innovative treatments. We also anticipate our first oncology development candidate later this year and are excited about the potential of our pipeline to address unmet medical needs and improve patient outcomes."

Fourth Quarter & Recent Business Updates:

Epetraborole Phase 2/3 Clinical Study in TR-MAC Lung Disease

In February 2025, the Company submitted an amended statistical analysis plan to the FDA selecting the Quality of Life – Bronchiectasis (QOL-B) respiratory domain patient reported outcome (PRO) instrument as the primary efficacy endpoint for the Phase 3 part of the EBO-301 trial. The Company believes that this approach aligns with current FDA Guidance for Industry on NTM drug development regarding the use of a symptom-focused clinical outcome measure as the sole primary endpoint and it also follows the precedent established by Insmed’s ongoing confirmatory study of Arikayce in treatment-naïve patients, where Insmed has reported the same QOL-B instrument as the primary efficacy measure.

The Company intends to announce topline Phase 3 results in the second quarter of 2025, subject to the timing of any potential FDA feedback with respect to the trial or amended statistical analysis plan. Ninety-seven subjects had completed treatment in Phase 3 when the trial was terminated in August 2024 (2:1 epetraborole+optimized background regimen (OBR) vs. placebo+OBR), the data for which remains blinded and available for analysis as a Phase 3 dataset. If the Phase 3 data align with the potential efficacy signal observed in Phase 2, the Company plans to review both Phase 2 and Phase 3 results with the FDA and discuss potential registrational pathways.

Chagas Disease

During the quarter, the Company conducted Phase 1-enabling activities for AN2-502998, a candidate for chronic Chagas disease, which affects an estimated 6-7 million people worldwide, including approximately 300,000 in the U.S., and can cause severe cardiac disease and death. The Company plans to initiate a Phase 1 clinical study in mid-2025.

Melioidosis

The Company completed enrollment in a 200-patient observational trial in acute melioidosis in October 2024. These data will inform a potential Phase 2 proof of concept study of epetraborole that is planned to initiate start up activities in the second half of 2025. Melioidosis is a deadly bacterial infection and global bioterrorism threat with a 90-day mortality rate of approximately 50% using standard of care drugs ceftazidime or meropenem. The aim of the program is to meaningfully lower the expected mortality rate by dosing epetraborole on top of standard of care.

Boron Chemistry Pipeline

Additional development programs are underway and focused on targets in infectious diseases and oncology with high unmet needs. The Company anticipates delivering development compound(s) in 2025, including the first oncology targets using its boron chemistry platform.

Global Health

In October 2024, the Company announced that it received a second-year continuation of a research grant from the Gates Foundation to discover novel boron containing small molecules for the treatment of tuberculosis and malaria. The Company will continue its efforts to tackle global health disease through non-dilutive funding.

Selected Fourth Quarter and Full Year 2024 Financial Results

Research and Development (R&D) Expenses: R&D expenses for the full year 2024 were $40.5 million, compared to $54.9 million in the prior year. R&D expenses for the fourth quarter of 2024 were $5.4 million, compared to $14.9 million for the same period during 2023 due to decreased clinical trial expenses, personnel-related expenses, consulting and outside services, chemistry manufacturing and controls expenses, and allocated facilities and miscellaneous expenses, primarily related to termination of the EBO-301 clinical study and corporate restructuring activities, and a decrease in licensing fees, partially offset by an increase in preclinical and research expenses.
General and Administrative (G&A) Expenses: G&A expenses for the full year 2024 were $14.1 million, compared to $14.8 million in the prior year. G&A expenses for the fourth quarter of 2024 were $3.2 million, compared to $3.9 million for the same period during 2023 due to decreased personnel-related expenses, professional services expenses and allocated facilities and miscellaneous expenses, partially offset by increased D&O insurance expenses.
Restructuring Charges: Restructuring charges for the full year 2024 were $2.2 million due to severance payments and other employee termination expenses.
Interest Income: Interest income for the full year 2024 was $5.5 million, compared to $4.9 million in the prior year. Interest income for the fourth quarter of 2024 was $1.1 million, compared to $1.9 million for the same period in 2023 due to higher interest rates despite lower cash, cash equivalents and investment balances in 2024 as compared to 2023.
Net loss: Net loss for the full year 2024 was $51.3 million, compared to $64.7 million in the prior year. Net loss for the fourth quarter of 2024 was $7.5 million, compared to $16.9 million for the same period during 2023.
Cash Position: The Company had cash, cash equivalents and investments of $88.6 million at December 31, 2024.