On March 25, 2025 Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, reported that it will present new data on its first-in-class oral DHX9 inhibitor, ATX-559, and its potentially best-in-class KIF18A inhibitor, ATX-295, at the 2025 AACR (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois (Press release, Accent Therapeutics, MAR 25, 2025, View Source [SID1234651425]).

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Data presented at the meeting will reinforce Accent’s approach focused on precision oncology for large patient populations in a poster highlighting the therapeutic potential of lead candidate ATX-559 and in an oral presentation for lead candidate ATX-295.

Preclinical data supporting continued clinical evaluation of ATX-559 will characterize the compound’s activity across in vivo models of cancers exhibiting genomic instability and replication stress, including in dMMR/MSI-H colorectal cancer and BRCA altered triple negative breast cancer. An oral presentation will discuss the preclinical activity of ATX-295 across a panel of ovarian cancer cell lines and provide rationale for whole genome doubling as a viable enrichment biomarker of ATX-295 sensitivity in ovarian cancer models.

"We are excited to present foundational preclinical data supporting our clinical-stage ATX-559 program and our soon-to-be clinical-stage ATX-295 program. These data include key mechanistic, biological and pharmacological underpinnings that help to guide our current or future clinical development plans for these programs. For both programs, we are also excited to have uncovered significant patient opportunities in additional undisclosed indications, and we are evaluating opportunities to explore them in the clinic during our current or future studies " said Serena Silver, Chief Scientific Officer at Accent Therapeutics.

ATX-559 is currently under investigation in a first-in-human, Phase 1/2, open-label, dose-escalation and expansion study (NCT06625515), with a focus on advanced or metastatic patients with BRCA-1 and/or BRCA-2-deficient breast cancer or MSI-H and/or dMMR solid tumors. Additional undisclosed solid tumor indications under replicative stress and representing significant patient populations have the potential to be explored either in parallel to the initial indications or in subsequent studies.

Accent’s potentially best-in-class KIF18A inhibitor, ATX-295, is anticipated to enter the clinic in the first half of 2025.

AACR presentations details are as follows:

Presentation Title: Activity of the Novel KIF18A Inhibitor, ATX-295, is Enriched in Whole Genome Doubled Ovarian Cancer Pre-Clinical Models

Abstract Number: 3784
Session Type: Minisymposium
Session Title: Novel Antitumor Agents
Session Date and Time: Monday, April 28: 2:30 PM – 4:30 PM
Presenter: Maureen Lynes, Ph.D.
Poster Title: ATX-559, a First in Class DHX9 Inhibitor, and Targeted Therapeutic for Molecularly Defined Tumors with Genomic Instability and Replicative Stress

Abstract Number: 1758
Session Title: Novel Antitumor Agents 1
Session Date and Time: Monday, April 28: 9:00 AM – 12:00 PM
Location: Poster Section 22
Poster Board Number: 10
Presenter: Jennifer Castro
About ATX-559
ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.

About ATX-295
Accent’s second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to the KIF18A program, which is anticipated to enter the clinic in 1H 2025.

On March 25, 2025 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported that it will present preclinical data for its novel HER3 ADC, EO-1022, in a late-breaking poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, being held April 25-30 in Chicago, Illinois (Press release, Elevation Oncology, MAR 25, 2025, View Source [SID1234651424]).

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EO-1022 is an antibody drug conjugate (ADC) containing seribantumab, a fully human IgG2 anti-HER3 monoclonal antibody (mAb), which is site-specifically conjugated at glycan to the monomethyl auristatin E (MMAE) payload with a drug-to-antibody ratio (DAR) of 4. Elevation Oncology designed EO-1022, leveraging the advanced site-specific conjugation technology platform licensed from Synaffix B.V. Elevation Oncology is developing EO-1022 for the treatment of solid tumors that express HER3, including breast cancer and non-small cell lung cancer, and expects to file an IND application in 2026.

"We are eager to share the first preclinical data for EO-1022 at the AACR (Free AACR Whitepaper) Annual Meeting," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "With EO-1022, we are combining the most advanced site-specific conjugation technology platform with the clinically validated MMAE payload, which is widely used across ADC programs but has yet to be introduced into a HER3-targeting ADC in the clinic. We believe this unique combination will enable us to provide a new treatment option to patients with HER3-expressing solid tumors, including those who are refractory to other HER3-targeting agents in development. We look forward to advancing EO-1022 into clinical development next year."

Details of the poster presentation at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Preclinical discovery and characterization of EO-1022, a site-specific glycan-conjugated anti-HER3 vc-MMAE ADC for treating solid tumors

Abstract Presentation Number: LB004
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1
Session Date and Time: Sunday, April 27, from 2 p.m. to 5 p.m. CT (3 p.m. to 6 p.m. ET)
Location: Poster Section 50
The late-breaking abstract will become available on the AACR (Free AACR Whitepaper) website beginning at 12:00 noon CT (1:00 p.m. ET) on April 25, 2025, and published in an online-only supplement to Cancer Research.

About EO-1022

Elevation Oncology is developing EO-1022, a potentially differentiated HER3 ADC for the treatment of HER3-expressing solid tumors, including breast cancer and non-small cell lung cancer. EO-1022 consists of seribantumab, a fully human IgG2 anti-HER3 antibody, site-specifically conjugated at glycan to the MMAE payload with a DAR of 4. It leverages seribantumab’s desirable internalization properties and advanced site-specific ADC technology which makes possible the use of the potent cytotoxic MMAE payload. Elevation Oncology expects to file an IND application in 2026.

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 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 Oncotelic Therapeutics, Inc (OTCQB:OTLC) ("Oncotelic", the "Company" or "We" or "Our"), "), a leader in RNA-based therapeutics, reported the successful completion of a Phase 1 clinical trial evaluating OT-101, in combination with IL-2 for advanced or metastatic solid tumors (Press release, Oncotelic, MAR 25, 2025, View Source [SID1234651421]). These results set the stage for new studies that combine OT-101,an antisense therapeutic targeting Transforming Growth Factor Beta 2 (TGFβ2), with checkpoint inhibitors ("CKIs") and recombinant IL-2 (aldesleukin) ("IL-2").

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The announcement coincides with a presentation delivered by Vuong Trieu, Ph.D., Chairman & CEO of Oncotelic, at the 5th Symposium on World Cancer Research (SWCR) 2025. In his talk, titled "Transforming Growth Factor Beta 2 in Aging, Cancer, Lupus, and Immuno-Oncology: A Convergence of Disease Pathways and Therapeutic Potential," Dr. Trieu described the central role of TGFβ2 in immune suppression across multiple diseases, and outlined the ongoing development of OT-101 in pancreatic cancer (Phase 3 STOP-PC study), gliomas, and combination regimens with immunotherapies.

Phase 1 Trial of OT-101 (TASO) and IL-2 Successfully Completed

The Phase 1 trial (ClinicalTrials.gov ID: NCT04862767) investigated the safety and tolerability of OT-101 in combination with recombinant IL-2 in patients with advanced or metastatic solid tumors.
The combination showed a tolerable safety profile at the planned dosing schedule, with no unexpected safety signals identified.
Based on the favorable safety data, Oncotelic plans to advance OT-101 plus IL-2 into further clinical studies, exploring synergies with CKIs such as PD-1 blockers.
Key Highlights From the Kyoto 2025 Presentation

TGFβ2’s Central Role in Cancer and Beyond:
Dr. Trieu presented evidence that TGFβ2 is a critical driver of immunosuppression, fueling tumor progression by promoting an M2-like macrophage phenotype and blunting antitumor immunity.
OT-101’s Clinical Progress and Versatility:
In pancreatic ductal adenocarcinoma (PDAC), OT-101 is currently in a Phase 3 clinical trial (the STOP-PC study) combined with mFOLFIRINOX.
OT-101 has shown encouraging activity in gliomas, where high intratumoral TGFβ2 expression correlates with poor prognosis.
Combination regimens with CKIs and IL-2 address multiple pathways of immune evasion, potentially amplifying therapeutic benefits.
Next Studies Targeting TGF β2 and Beyond:
With the newly completed OT-101 and IL-2 Phase 1 trial, Oncotelic is poised to begin further combination trials to determine the added efficacy of OT-101, IL-2, and CKIs in solid tumors such as lung cancer, melanoma, and colorectal cancer.
Next wave of clinical trials aiming to knock down TGF β 2 (e.g., with OT-101) paired with intervention with a complementary therapy, checkpoint blockade, IL-2, interferon-based regimens, or standard-of-care chemo, depending on the tumor indication
"We are thrilled to announce the completion of our Phase 1 study evaluating OT-101 with IL-2, a key milestone that sets the stage for next-generation immunotherapy combinations," said Dr. Vuong Trieu, Chairman & CEO of Oncotelic. Our findings reinforce that OT-101’s specific inhibition of TGFβ2 can significantly enhance the immune response, and we are eager to test these synergies with checkpoint inhibitors and IL-2 to maximize therapeutic potential for patients with hard-to-treat cancers."

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