On October 24, 2025 Parabilis Medicines, a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported preliminary clinical and preclinical findings across its Helicon peptide pipeline at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, Massachusetts.

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The findings reinforce the broad potential of FOG-001, the company’s lead investigational therapy and the first-ever direct Wnt/β-catenin:TCF inhibitor, to act across a range of rare and more prevalent solid tumors linked by the same dysregulated biology of the Wnt/β-catenin pathway. Single-agent activity resulting in tumor shrinkage by at least 30% (partial response (PR)) was observed in five low-complexity tumor types, with strong scientific support as well for FOG-001’s potential in combination therapy for more complex tumors, including microsatellite-stable colorectal cancer (MSS CRC).

Together with positive preclinical read-outs demonstrating pharmacologic proof of concept for the company’s discovery-stage Helicon peptides in prostate cancer targeting the ERG and active androgen receptor (ARON) targets, these data highlight how the company’s Helicon platform can repeatably target high-impact "undruggable" targets long considered inaccessible to conventional therapeutic approaches.

"Just one week after presenting the first clinical proof that β-catenin:TCF can be drugged, we are showing the breadth of what this breakthrough could mean for science and for patients," said Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines. "FOG-001 is demonstrating meaningful signs of clinical activity across multiple Wnt/β-catenin-driven tumors, supporting its continued development in both simpler and more biologically complex Wnt-driven cancers through both monotherapy and combination therapy approaches."

He added, "Together with our preclinical advances in prostate cancer, the data illustrate the potential of Helicons to take on some of the toughest problems in oncology and bring forward transformative medicines that could meaningfully improve outcomes for patients."

FOG-001 Clinical and Preclinical Findings

The Wnt/β-catenin pathway — first identified as a key cancer driver over 30 years ago — is implicated in millions of cancer cases annually, spanning many rare and prevalent solid tumors as well as diseases like familial adenomatous polyposis (FAP) that predispose individuals to certain cancers, including colorectal cancer and desmoid tumors. Despite its central role in cancer biology, the pathway’s critical β-catenin:TCF transcription complex has long been considered "undruggable."

Preliminary data from the ongoing Phase 1/2 trial of FOG-001 (NCT05919264), as of mid-August 2025, show that the therapy is well tolerated with no Grade 4/5 treatment-related adverse events or discontinuations and exhibits a favorable pharmacokinetic profile. As of this early data cut, an objective response rate (ORR) of 43% and a disease control rate (DCR) of 73%, per RECIST 1.1, were observed in non-CRC patients with Wnt pathway activating mutations (WPAM). Evidence of single-agent activity was observed across numerous Wnt/β-catenin–driven tumors, particularly in those with low mutational burden, including desmoid, adamantinomatous craniopharyngioma (ACP), ameloblastoma, salivary gland cancer, and solid pseudopapillary neoplasm (SPN).

In MSS CRC, a 50% DCR was achieved within the efficacious monotherapy dose range, with molecular data confirming on-target pathway inhibition and reprogramming of the tumor microenvironment toward a more immune-active state. Complementary preclinical studies demonstrated that FOG-001 enhances the effects of standard and emerging therapies for MSS CRC—showing in these preclinical models additive or synergistic activity with each of 5-fluorouracil and anti-VEGF regimens, synergy with anti–PD-1 therapy, and combination benefit with pan-RAS and KRAS G12D inhibitors.

Together, these findings highlight FOG-001’s broad pipeline potential — warranting continued development in Wnt pathway–activated low-complexity tumors, and as a backbone for rational combination regimens in more complex cancers. The Phase 1/2 study remains ongoing across a wide range of Wnt-driven rare and common cancers, with additional data readouts expected over the coming months.

Prostate cancer pipeline expansion

Parabilis also presented preclinical data advancing its prostate cancer franchise, focused on two long-standing oncogenic drivers that currently lack effective therapies. ERG-degrading Helicon peptides potently and durably reduced ERG protein levels —overexpressed in 40–50% of prostate cancers — showing in vivo pharmacologic proof-of-concept demonstrating tumor growth inhibition and efficacy comparable to or exceeding standard of care in challenging prostate cancer models.

In parallel, allosteric ARON Helicon degraders that bind a conserved site distinct from the androgen ligand pocket, were designed to selectively target the active, agonist-bound androgen receptor. These Helicon degraders block proliferation in AR-amplified prostate cancer cells, offering a strategy to overcome resistance driven by AR mutations or amplification. Importantly, this approach also allows for effective combinations with approved and emerging treatments that target the testosterone ligand pocket. Together, these data demonstrate the repeatability of the Helicon platform in addressing high-value, historically undruggable targets in oncology.

"Our Helicons are delivering against three of the most challenging and compelling targets in oncology, from β-catenin:TCF to ERG to ARON," said Fawzi Benzaghou, M.D., Chief Medical Officer of Parabilis Medicines. "By pursuing bold science that makes the undruggable druggable, we’re opening new therapeutic possibilities for patients with few or no options. These data reinforce the power of our α-helical peptide platform to repeatedly unlock difficult targets and advance medicines with the potential for extraordinary patient impact."

About the Phase 1/2 trial of FOG-001
FOG-001 is being evaluated in a first-in-human Phase 1/2 multicenter, open-label study (NCT05919264) assessing its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The trial includes dose-escalation and dose-expansion phases and is testing FOG-001 both as a monotherapy and in combination with other anticancer agents in patients with advanced or metastatic solid tumors likely or known to harbor a Wnt pathway–activating mutation (WPAM).

About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors and is currently in clinical development. By directly targeting the β-catenin:TCF protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and β-catenin mutations that typically drive disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the key downstream node, disrupting the interaction between β-catenin and the TCF transcription factors, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis.

FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

(Press release, Parabilis Medicines, OCT 24, 2025, View Source [SID1234656994])

On October 24, 2025 ChemDiv reported the extension of its discovery and early development partnership with Mondego Bio to advance the company’s best-in-class immuno-oncology program targeting PTPN2. The announcement follows Mondego Bio’s successful Series A financing led by Biovance Capital with participation from OrbiMed Advisors and Torrey Pines Investment, underscoring strong momentum behind Mondego’s strategy.
ChemDiv previously supported the accelerated discovery of a drug candidate by Eilean Therapeutics LLC in the U.S., which preceded the establishment of

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Mondego Bio in Portugal in 2025. Leveraging rational drug design across reversible, covalent, and allosteric inhibitors, the collaboration established a differentiated selectivity profile that delivers high oral bioavailability, robust in vivo efficacy, and strong safety and tolerability—hallmarks of potentially best-in-class cancer therapeutics.

Medicinal chemistry and scale-up were led by ChemDiv’s group in Germany, while pharmacology and translational biology were supported by ChemDiv facilities in the U.S. and Portugal. Together, these efforts advanced Mondego’s pre-IND program, supported by its European venture capital–backed launch.

Looking ahead, ChemDiv will continue to provide:

Medicinal chemistry and discovery biology for backup series,
CMC process research and large-scale manufacturing of the lead candidate for non-GLP and GLP animal studies,
Computational and wet-lab pharmacology to accelerate clinical readiness.
These efforts build on ChemDiv’s deep expertise in designing selective kinase and phosphatase inhibitors, leveraging its extensive kinase and phosphatase chemical libraries, and applying parallel lead optimization supported by AI/ML-enabled rational design, ADME/DMPK, and translational capabilities.

"We’re moving fast with Mondego to translate PTPN2 biology into medicines," said Ilya Baimetov, COO and Head of Digital Platforms at ChemDiv.
"By combining our advanced rational design, medchem horsepower, and focused tool libraries with Mondego’s cutting-edge immuno-oncology platform, we are advancing the next generation of phosphatase inhibitors with best-in-class potential."

(Press release, ChemDiv, OCT 24, 2025, View Source [SID1234656993])

On October 24, 2025 Whitehawk Therapeutics, Inc. (Nasdaq: WHWK), an oncology therapeutics company applying advanced technologies to established tumor biology to efficiently deliver improved antibody drug conjugate (ADC) cancer treatments, reported data from a real-world analysis of Protein Tyrosine Kinase 7 (PTK7) at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). As part of a collaboration between Whitehawk and Tempus AI, the analysis evaluated real-world data from the Tempus AI database and the Clinical Proteomic Tumor Analysis Consortium to, for the first time, robustly characterize PTK7 expression.

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PTK7 is an oncofetal transmembrane pseudokinase that drives early embryonic development, has restricted expression in adult tissues and frequent overexpression in a wide range of cancers. There are no approved PTK7-directed ADCs.

This large-scale RNA analysis of >157,000 tumor samples, nearly half from metastatic lesions, confirms PTK7 as one of the most broadly and highly expressed targets across solid tumors, reinforcing its potential as a clinically meaningful pan-tumor ADC target, and further support development of HWK-007, Whitehawk’s PTK7-directed ADC candidate.

Key findings include:

PTK7 is expressed in ~70% of solid tumors.
PTK7 is the third most highly expressed tumor marker among clinically validated and emerging ADC targets, after HER2 and HER3.
Highest median PTK7 mRNA expression1 observed in endometrial (7.4), ovarian (7.2), head and neck (7.1), non-small cell lung cancer (NSCLC) (6.9) and breast (6.7) tumors.
Stable expression across disease stages and metastatic status, underscoring relevance in both early- and late-stage disease.
Expression levels comparable to or exceeding clinically validated and emerging ADC targets:
Lung cancer: Comparable to HER2, HER3, Trop-2 and cMET.
Ovarian cancer: Comparable to HER2 and FRα; markedly higher than CDH6, B7-H4 and CLDN6.
Endometrial cancer: Comparable to Trop-2; markedly higher than FRα, B7-H4 and HER2.
"These results emphasize the translational potential of PTK7 as a broadly expressed and stable target across solid tumors," said Grace Dy, MD, Chief, Thoracic Oncology, Professor of Oncology, Department of Medicine, Roswell Park Comprehensive Cancer Center. "By demonstrating consistent expression across histologies, disease stages and sample types, this analysis builds on the foundational rationale for developing next-generation ADCs that have the potential to reach a wide range of patients."

Whitehawk is advancing HWK-007, a PTK7-targeting ADC that leverages an advanced ADC technology platform which consists of a highly stable yet cleavable linker that delivers a Topoisomerase I (TOPO1) inhibitor payload. The Company plans to submit an Investigational New Drug application to the U.S. Food and Drug Administration for HWK-007 by year-end, with initial clinical evaluation planned in NSCLC, ovarian and endometrial cancers.

"These findings reinforce PTK7’s promise as one of the most compelling and underexplored ADC targets in oncology," said Dave Lennon, PhD, President and Chief Executive Officer, Whitehawk Therapeutics. "As the third most abundant tumor marker across all cancer patients – present in approximately 70% of solid tumors – the opportunity for HWK-007 has never been clearer. We believe we are well positioned to develop a differentiated ADC that could have a meaningful impact for the nearly 750,0002 patients in the US with PTK7-expressing cancers."

The analysis was conducted as part of a previously announced collaboration between Whitehawk and Tempus AI. The abstract is available as a freely available supplement in the AACR (Free AACR Whitepaper) journal Molecular Cancer Therapeutics.

(Press release, Whitehawk Therapeutics, OCT 24, 2025, View Source [SID1234656992])

On October 24, 2025 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics, Triclonics and ADClonics), reported interim clinical data as of a July 29, 2025 data cutoff from the ongoing phase 2 trial of the bispecific antibody petosemtamab in combination with standard of care FOLFOX/FOLFIRI in 1L and 2L metastatic colorectal cancer (mCRC), and petosemtamab monotherapy in 3L+ mCRC. These data will be presented in a plenary session oral presentation by Dr. Moh’d Khushman M.D., Washington University School of Medicine, St. Louis, MO, at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on Friday, October 24 at 10:20 a.m. ET.

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"Petosemtamab’s unique mechanism of action, including targeting both EGFR and LGR5, and potential to safely combine with FOLFOX/FOLFIRI, represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer," said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. "These data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma. We are encouraged that petosemtamab has the potential to become a transformational treatment and new standard of care for patients across a range of solid tumors."

"Metastatic colorectal cancer remains a formidable challenge with limited effective therapies. The promising early results with petosemtamab offer hope for advancing care and bringing new treatment possibilities to patients facing this difficult disease," added Dr. Khushman.

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics)

Presentation title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial
Observations in the presentation include:
As of a July 29, 2025 data cutoff date:

54 patients (pts) with left- and/or right-sided, KRAS, NRAS, and BRAF wildtype microsatellite stable mCRC received petosemtamab 1500 mg every two weeks, in combination with FOLFOX/FOLFIRI or as monotherapy
Pts treated in 1L or 2L had no prior anti-EGFR therapy
Pts treated in 2L received 1 prior chemotherapy regimen in the metastatic setting
Pts treated in 3L+ received at least 2 prior regimens in the metastatic setting, including a prior anti-EGFR therapy
Efficacy evaluable population consisted of patients with ≥1 dose of petosemtamab who had opportunity for ≥8 weeks follow up and ≥1 post baseline tumor assessment or discontinued petosemtamab early due to disease progression, symptomatic deterioration and/or death
1L petosemtamab with FOLFOX/FOLFIRI
14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI)
10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment
80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs)
88% (7 of 8) response rate in left-sided: 1 confirmed complete response, 6 PRs (3 unconfirmed, 1 unconfirmed response confirmed post data cutoff); 1 SD
One SD observed to be an unconfirmed PR post data cutoff leading to 100% (8/8) response rate left-sided and 90% (9/10) response rate overall in 1L
All unconfirmed PRs remained on treatment without disease progression
2L petosemtamab with FOLFOX/FOLFIRI
14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI)
13 were efficacy evaluable; 10 (77%) remained on treatment
62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan
All unconfirmed PRs and SDs remained on treatment without disease progression
3L+ petosemtamab monotherapy:
26 pts were treated
20 were efficacy evaluable, 6 (30%) remained on treatment
10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment)
Safety:
Petosemtamab safety profile in mCRC observed thus far, appears consistent with its established safety profile in recurrent/metastatic head and neck squamous cell carcinoma
No significant overlapping toxicities identified in combination with FOLFOX/FOLFIRI
No new safety signals identified
Infusion related reactions (IRRs) were managed with premedication and prolonged infusion on cycle 1 day 1; no discontinuations due to IRRs
Presentation:
Title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial
Session Title: Plenary Session 4: Clinical Trials Plenary Session
Date and Time: Friday, October 24, 10:20 a.m. ET
The same data will also be available in a poster:
Session Title: Poster Session B
Session Date and Time: Friday, October 24, 12:30-4:00 p.m. ET

As full presentations become available at the conference, they will contemporaneously be available on the Merus website.

(Press release, Merus, OCT 24, 2025, View Source [SID1234656991])

On October 24, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of differentiated targeted radiotherapies, reported new preclinical data for ATNM-400, its novel, first-in-class antibody radioconjugate armed with the potent alpha-emitter Actinium-225 (Ac-225) at the 32nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat being held October 23 – 25, 2025 in Carlsbad, CA.

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ATNM-400, which targets a non-PSMA antigen associated with prostate cancer progression and treatment resistance, demonstrated superior tumor control and improved overall survival compared with the active agents in key standard-of-care therapies including enzalutamide (the active agent in Xtandi, Astellas/Pfizer) and 177Lu-PSMA-617 (the active agent in Pluvicto, Novartis), as well as 225Ac-PSMA-617 across multiple preclinical prostate cancer models.

These data further reinforce ATNM-400’s potential as a paradigm changing, PSMA-independent Ac-225 alpha radiotherapy, offering opportunities for use as a monotherapy, in combination regimens, and in patients relapsing after ARPI or PSMA-directed treatments. ATNM-400 data has now been presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), Society for Nuclear Medicine and Molecular Imaging (SNMMI) and PCF annual conferences in 2025 demonstrating its growing potential in various treatment settings in prostate cancer. In addition, data highlighting its potential in non-small cell lung cancer will be presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on Saturday, October 25, 2025.

Key Findings in Prostate Cancer Treatment Settings:

Potent and Durable Tumor Control, Increased Overall Survival and Synergistic Activity in Enzalutamide Resistant Prostate Cancer

Studies were performed in 22Rv1 prostate cancer models, which are known to be resistant to enzalutamide

ATNM-400 demonstrated superior and 5-times more durable anti-tumor efficacy extending to 100 days compared to approximately 20 days with enzalutamide alone

Given that ARPI therapies like enzalutamide are known to increase the ATNM-400 target antigen expression, combination treatment with ATNM-400 and enzalutamide was synergistic, resulting in complete tumor eradication in 40% of treated animals and significantly prolonged survival, whereas enzalutamide alone provided no durable disease control
Potent and Durable Tumor Control, Increased Overall Survival and Synergistic Activity in Enzalutamide Resistant Prostate Cancer

In models that progressed on enzalutamide, subsequent treatment with ATNM-400 achieved robust tumor control and extended survival, highlighting its potential in post-enzalutamide settings
Subsequent treatment with ATNM-400 achieved robust tumor control and extended survival, highlighting its potential in post-enzalutamide settings

Highly Effective and Increased Overall Survival in 177Lu-PSMA-617 Resistant Prostate Cancer

22Rv1 prostate cancer models are also resistant to 177Lu-PSMA-617

ATNM-400 overcame 177Lu-PSMA-617 resistance with approximately 5-times long tumor control and 2-times longer overall survival in tumor bearing animals
Highly Effective and Increased Overall Survival in 177Lu-PSMA-617 Resistant Prostate Cancer

Potent Therapeutic Activity Independent of PSMA Expression Levels

ATNM-400 targets a highly differentiated, non-PSMA antigen associated with the development and progression of prostate cancer, exhibiting potent therapeutic activity independent of PSMA expression levels

The expression of the ATNM-400 antigen target was not altered post-177Lu-PSMA-617
Potent Therapeutic Activity Independent of PSMA Expression Levels

22Rv1 cell lines are low-PSMA expressing and LNCaP cell lines are high-PSMA expressing
Addressing Critical Unmet Needs in mCRPC

Prostate cancer patients who progress to mCRPC face limited treatment options. While ARPI therapies like enzalutamide and PSMA-targeted radiotherapies like Pluvicto have extended survival, resistance and disease progression remain major challenges. In addition, a significant number of patients do not respond to PSMA-targeted radiotherapy as approximately 25%-30% of patients with mCRPC have low or no detectable PSMA and approximately 60% of patients have at least one PSMA-negative prostate cancer lesion.

By targeting a distinct, non-PSMA antigen associated with treatment resistance and poor outcomes, ATNM-400 represents a mechanistically differentiated alpha-radiotherapy approach that has potential in various treatment settings in prostate cancer. Its combination of a high-affinity antibody and potent alpha-emitting Ac-225 payload provides a path to overcome therapeutic resistance and extend patient survival beyond current standards of care.

Differentiation and Potential Clinical Impact

Sandesh Seth, Chairman and Chief Executive Officer, Actinium Pharmaceuticals, Inc., stated, "Since unveiling ATNM-400 earlier this year at AACR (Free AACR Whitepaper), our enthusiasm for this program only continues to grow commensurate with the promising results generated supporting its potential in various treatment settings in prostate cancer. ATNM-400 combines the precision of antibody targeting with the unparalleled potency of Ac-225 alpha particles, and importantly, it does so through a biologically distinct, PSMA-independent mechanism. These new preclinical data presented at PCF provide further validation for ATNM-400 and positions it as a candidate capable of transforming the treatment paradigm for patients with mCRPC. We are thrilled by the positive reactions to our ATNM-400 data and its differentiated non-PSMA approach."

Mr. Seth added, "As we have recently announced, beyond prostate cancer, we are also advancing ATNM-400 into non-small cell lung cancer (NSCLC), where it has shown the ability to overcome resistance to osimertinib (TAGRISSO, AstraZeneca) an EGFR-TKI therapy in preclinical models. Together, these data highlight Actinium’s innovate approach to R&D that leverages our radiochemistry expertise and strong translational biology capabilities to create first-in-class, multi-indication radiotherapeutics."

Actinium Pharmaceuticals envisions multiple clinical applications for ATNM-400 in prostate cancer, including:

Monotherapy in earlier disease settings prior to PSMA-directed radiotherapy.

Combination therapy with ARPI’s to enhance and prolong treatment responses.

Sequential therapy for patients relapsing after ARPI or PSMA-targeted radioligand treatments.
Summary of Preclinical Highlights of ATNM-400

Novel Mechanism: First-in-class Ac-225-based antibody radioconjugate against a non-PSMA target, overexpressed in advanced and resistant prostate cancer.

Superior Efficacy: Outperformed 177Lu-PSMA-617, Ac225-PSMA-617 and enzalutamide in direct head-to-head preclinical comparisons.

Durable Responses: A single 40 µCi/kg dose produced strong tumor inhibition; multi-dose regimens yielded long-term tumor control exceeding both enzalutamide and 177Lu-PSMA-617.

Overcomes Resistance: ATNM-400 maintained potent anti-tumor activity in models resistant to both enzalutamide and 177Lu-PSMA-617.

Combination Synergy: Synergized with enzalutamide, achieving complete tumor regressions in 40% of treated animals and markedly extending survival.

Favorable Biodistribution: Demonstrated selective and durable tumor uptake and rapid clearance from normal tissues, supporting a strong therapeutic index.
About ATNM-400

ATNM-400 is a highly innovative, first-in-class, and multi-indication Actinium-225 (Ac-225) targeted radiotherapy candidate in development for prostate cancer and non-small cell lung cancer (NSCLC). ATNM-400 is highly differentiated in prostate cancer as it targets a distinct non-PSMA antigen strongly implicated in prostate cancer progression and treatment resistance. Unlike 177Lu-PSMA-617, the active agent in Pluvicto and the majority of radiotherapies under development, which rely on PSMA targeting, ATNM-400 is designed to maintain efficacy in low-PSMA or PSMA-resistant disease, a major unmet clinical need. Ac-225 delivers high-linear-energy-transfer alpha particles that induce irreparable double-strand DNA breaks, offering superior potency over beta emitters like Lutetium-177 (177Lu), and has a shorter tissue path length that may reduce off-target toxicity. The receptor specifically targeted by ATNM-400 continues to be expressed at a high level even after androgen receptor inhibitor (ARPI) and ATNM-400 has shown to overcome resistance to the ARPI therapy enzalutamide and work synergistically in combination with enhanced tumor control including complete tumor regression. In NSCLC, ATNM-400 has shown to overcome resistance to osimertinib, an EGFR tyrosine kinase inhibitor (TKI) that is a standard of care therapy.

Prostate cancer is the most commonly diagnosed cancer in men, with ~1.5 million new cases globally and over 313,000 cases expected in the U.S. in 2025. While early-stage disease is typically managed with surgery, radiation, and ARPI therapy, up to 20% of cases progress to mCRPC – a lethal stage with limited treatment options. Targeted radiotherapy is a growing field in prostate cancer, dominated by PSMA-targeting agents like Pluvicto, which had sales of over $1.3 billion in 2024, yet many patients either lack PSMA expression or develop resistance to Pluvicto. In the U.S., 40,000 to 60,000 mCRPC patients annually progress after ARPI therapy that as a class generated sales of over $10.0 billion in 2024 including enzalutamide (Xtandi), which led the ARPI class with sales of over $5.9 billion in 2024, highlighting a significant unmet need. Lung cancer is the leading cause of cancer deaths and there are there are over 200,000 new cases expected in the U.S. in 2025. NSCLC accounts for approximately 85% of all lung cancer cases. The EGFR TKI Osimertinib (TAGRISSO, AstraZeneca) generated sales of $6.6 billion in 2024. Across prostate cancer and NSCLC, there are approximately 500,000 new cases in the U.S. alone.

(Press release, Actinium Pharmaceuticals, OCT 24, 2025, View Source [SID1234656990])