On April 25, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported it will present preclinical data of FL-501 in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois (Press release, Leap Therapeutics, APR 25, 2025, View Source [SID1234652153]).

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FL-501 is a potential best-in-class monoclonal antibody targeting growth differentiation factor 15 (GDF-15), a cytokine that is implicated in multiple diseases and therapeutic areas, including cancer cachexia.

"Cancer cachexia is a devasting and potentially life-threatening condition characterized by significant weight loss, muscle wasting, fatigue, and severely reduced quality of life. It is a major contributor to cancer-related mortality, and unfortunately there are no effective treatment options available to patients," said Jason Baum, PhD, Chief Scientific Officer of Leap. "These data not only demonstrate that FL-501 is a novel and potential best-in-class anti-GDF-15 antibody, but also capable of fully restoring body composition in preclinical models that is comparable or better than other, clinical-stage antibodies. We look forward to progressing the development of FL-501 and bringing the asset into the clinic in 2026."

Key Findings:

In humanized FcRn mouse studies, FL-501 demonstrated a 2-3-fold longer half-life and 50% reduced clearance compared to its wild-type precursor and ponsegromab
In mouse cachexia models using GDF-15-overexpressing colorectal cancer cells, FL-501 fully restored body composition, comparably or better than clinical-stage antibodies visugromab and ponsegromab
In a non-small cell lung cancer patient-derived xenograft model, FL-501 effectively countered cisplatin-induced weight loss, restoring body weight, composition, and condition scores
These findings confirm GDF-15’s role in cachexia and support FL-501’s advancement in development
Poster Details:

Title: FL-501 is a potential best in class GDF-15 inhibitor with extended half-life and potent anti-cachexia activity in preclinical models
Presenter: Roma Kaul, PhD, Leap Therapeutics
Session Category: Experimental and Molecular Therapeutics
Session Title: New and Emerging Cancer Drug Targets
Date and Time: Tuesday, April 29, 2025, 9:00 a.m. – 12:00 p.m. CT
Poster Board Number: 15
Published Abstract Number: 4258

About FL-501
FL-501 is a potential best-in-class monoclonal antibody in preclinical development that targets growth differentiation factor-15 (GDF-15), a cytokine that is produced at elevated levels in response to various stresses, including chronic inflammation, obesity, cardiovascular diseases, cancers, and chemotherapy treatment. High GDF-15 expression is associated with cancer cachexia including loss of appetite, nausea and weight loss. FL-501 was engineered for higher affinity to GDF-15 and longer plasma half-life compared to competing therapies. In addition to cachexia, FL-501 may be able to reverse immunosuppression in cancers where elevated GDF-15 is correlated with poor survival, as well as play a role in treating other GDF-15-related diseases. FL-501 is being developed through a collaboration agreement with Adimab.

On April 25, 2025 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (NASDAQ: ALLR), a Phase 2 clinical-stage pharmaceutical company dedicated to developing stenoparib—a differentiated, dual PARP and WNT pathway inhibitor—as a personalized cancer treatment using its proprietary, drug-specific Drug Response Predictor (DRP) patient selection technology reported the presentation of a poster containing data on a new DRP for the monoclonal antibody drug daratumumab (Press release, Allarity Therapeutics, APR 25, 2025, View Source [SID1234652152]). The poster is to be presented during a session at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25–30, 2025, in Chicago, IL. This novel predictor is designed to identify multiple myeloma patients most likely to benefit from daratumumab.

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The daratumumab DRP was developed by correlating gene expression patterns with sensitivity to daratumumab-induced antibody-dependent cellular cytotoxicity (ADCC), based on published in vitro data from multiple myeloma and B-cell lymphoma cell lines. From this analysis, the Company identified a total of 53 genes—27 associated with sensitivity and 26 with resistance—which form the basis of this drug-specific DRP. Using single-cell RNA sequencing data and overall response information from bone marrow samples collected in the KYDAR trial (a study of multiple myeloma patients treated with daratumumab in combination with carfilzomib, lenalidomide, and dexamethasone), the DRP was able to predict treatment outcomes and survival. These findings support the test’s potential as a patient enrichment tool.

"This is yet another successful application of our DRP technology beyond our internal clinical program pipeline," said Thomas Jensen, CEO of Allarity Therapeutics. "We already offer an extensive portfolio of DRPs for research use, and the addition of a DRP for daratumumab—our first developed for an antibody therapy—further demonstrates the versatility and flexibility of our DRP platform. Until now, our DRPs have been developed exclusively for small-molecule drugs. This new predictor expands the reach of our technology and positions us even better as a potential strategic partner for any third party seeking to target the right patients with existing cancer therapies. The data to be presented mark another important step toward potential future collaborations aimed at bringing precision diagnostics to more patients."

Poster Details

Poster Title: An mRNA-based predictor of response to daratumumab in multiple myeloma
Session Category: Clinical Research
Session Title: Predictive Biomarkers 2
Session Time: April 27, 2025 | 2:00 PM – 5:00 PM CT
Location: Poster Section 31
Poster Board Number: 10
Abstract Number: 725
Daratumumab is approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of multiple myeloma and marketed under the brand name Darzalex.

Allarity has already developed DRPs for investigational or research use for dozens of anticancer drugs covering a wide range of cancer types. This includes the company’s lead program, stenoparib, which is currently in Phase 2 development for advanced, recurrent, platinum-resistant or platinum-ineligible ovarian cancer, as well as in a combination study with temozolomide for recurrent small cell lung cancer.

The poster will be made available on Allarity’s website later today, following 1:00 p.m. ET, in the Scientific Publications section.

About Stenoparib
Stenoparib is an orally available, small-molecule dual-targeted inhibitor of PARP1/2 and tankyrase 1/2. At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in regulating the WNT signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of numerous cancers. By inhibiting PARP and blocking WNT pathway activation, stenoparib’s unique therapeutic action shows potential as a promising therapeutic for many cancer types, including ovarian cancer. Allarity has secured exclusive global rights for the development and commercialization of stenoparib, which was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121.

About the Drug Response Predictor – DRP Companion Diagnostic
Allarity uses its drug-specific DRP to select those patients who, by the gene expression signature of their cancer, may have a high likelihood of benefiting from a specific drug. By screening patients before treatment, and only treating those patients with a sufficiently high, drug-specific DRP score, the therapeutic benefit rate may be enhanced. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including transcriptomic information from cell lines, combined with clinical tumor biology filters and prior clinical trial outcomes. DRP is based on messenger RNA expression profiles from patient biopsies. The DRP platform has shown an ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients across dozens of clinical studies (both retrospective and prospective). The DRP platform, which may be useful in all cancer types and is patented for dozens of anti-cancer drugs, has been extensively published in the peer-reviewed literature.

On April 25, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that it has entered into a securities purchase agreement with certain institutional and accredited investors for a private placement of approximately $24 million of shares of its common stock at a price of $7.00 per share and, in lieu of common stock to certain investors, $51 million of pre-funded warrants to purchase shares of its common stock at a price of $6.9999 per pre-funded warrant (Press release, Verastem, APR 25, 2025, View Source [SID1234652151]). The exercise price of each pre-funded warrant will equal $0.0001 per share. Verastem expects to receive gross proceeds from the offering of approximately $75 million, before deducting placement agent fees and other offering expenses.

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The private placement was led by RTW Investments, with participation from other new and existing investors, including BVF Partners, Nantahala Capital, Octagon Capital, OrbiMed and Stonepine Capital Management.

The private placement is expected to close on or about April 28, 2025, subject to the satisfaction of customary closing conditions.

Proceeds from the financing are expected to fund the potential launch of avutometinib and defactinib in recurrent low-grade serous ovarian cancer, continued clinical research and development of product candidates including VS-7375, and for working capital and other general corporate purposes.

Guggenheim Securities is acting as the lead placement agent for the private placement. RBC Capital Markets, BTIG, Mizuho and B. Riley Securities are acting as co-placement agents for the private placement (together with Guggenheim Securities, the "Placement Agents"). The Company has agreed to pay customary placement fees and reimburse certain expenses of the Placement Agents.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state or other applicable jurisdictions’ securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. Verastem has agreed to file a registration statement with the United States Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued in the private placement and the shares of common stock issuable upon the exercise of the pre-funded warrants issued in the private placement, no later than 30 days after the closing of the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

On April 25, 2025 Veracyte, Inc. (Nasdaq: VCYT), a leading genomic diagnostics company, reported the launch of its Decipher Prostate Metastatic Genomic Classifier for use in patients whose prostate cancer has spread beyond the primary tumor (Press release, Veracyte, APR 25, 2025, View Source [SID1234652150]). The Decipher Prostate test, already widely used for patients with localized disease, is now the only gene expression test available and covered by Medicare to inform treatment decisions for patients across the full continuum of prostate cancer risk.

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Veracyte has begun making the Decipher Prostate Metastatic test available to select clinical sites through an early access program and will begin taking orders for the test more broadly in June 2025.

Prostate cancer is the second-leading cause of cancer deaths among men in the United States and the rate of men diagnosed with advanced disease has been growing in recent years.1 Veracyte estimates that approximately 10% (or about 30,000) of all prostate cancers diagnosed annually in the United States are metastatic.2

"A number of treatment options are now available to increase survival for patients whose prostate cancer has metastasized," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "Until now, however, clinicians had limited ways to determine which of these patients will likely benefit from these therapies and which will not and may thus avoid their toxic side effects. We believe the Decipher Prostate Metastatic test will provide an important new tool to help clinicians make more-informed treatment recommendations for their patients with metastatic prostate cancer."

The Decipher Prostate test’s clinical validity and clinical utility for use in patients with metastatic prostate cancer have been demonstrated in multiple, prospective, Phase 3 clinical studies.3-6 These studies have shown that such patients with high Decipher scores are likely to have more-aggressive tumor biology compared to those with lower scores, informing the absolute benefit from treatment intensification. These findings build upon extensive data already established for the Decipher Prostate test’s use in patients with localized prostate cancer, where it is the only gene expression test to achieve "Level I" evidence status in the most recent NCCN Guidelines* for prostate cancer.

"Our expansion into metastatic prostate cancer underscores the power of the Veracyte Diagnostics Platform to uncover novel insights that can enable us to further help patients," said Philip Febbo, M.D., Veracyte’s chief scientific officer and chief medical officer.

About Decipher Prostate

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients across the full spectrum of prostate cancer. The test is performed on biopsy or surgically resected samples and conveys the aggressiveness of the cancer. For patients with localized or regional prostate cancer, the Decipher score indicates a patient’s risk of metastasis, helping to determine treatment timing and intensity. For patients with metastatic prostate cancer, the Decipher score indicates the likelihood of cancer progression and survival benefit with treatment intensification. Armed with this information, physicians can better personalize their patients’ care. The Decipher Prostate test’s performance and clinical utility has been demonstrated in over 85 studies involving more than 200,000 patients. It is the only gene expression test to achieve "Level I" evidence status and inclusion in the risk-stratification table in the most recent NCCN Guidelines* for prostate cancer.

On April 25, 2025 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported the presentation of new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting for its highly selective IV SMARCA2 degrader and its highly selective KAT6A degraders (Press release, Prelude Therapeutics, APR 25, 2025, View Source [SID1234652149]).

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Peggy Scherle, Ph.D., Chief Scientific Officer of Prelude, stated, "We are pleased to provide further preclinical data on the discovery of our lead selective SMARCA2 degrader PRT3789, currently advancing in early clinical development for patients with SMARCA4 mutated cancers. We are also delighted to report initial preclinical data from our selective KAT6A degrader discovery program. These data demonstrate that selectively degrading KAT6A results in robust anti-cancer activity in various pre-clinical models of breast cancer and other solid tumors. We believe that our first-in-class, highly potent KAT6A selective degraders have the potential to expand the therapeutic reach of KAT6A/B inhibitors currently advancing in the clinic, while addressing safety challenges associated with non-selective approaches to this clinically validated target."

Details on the presentations are as follows:

Title: Elucidating the Molecular Mechanism of Action of the First-in-Human SMARCA2 Selective Degrader PRT3789

Summary:

•
PRT3789 is a first-in-human SMARCA2 degrader that selectively induces deep and sustained SMARCA2 degradation in preclinical and clinical studies.
•
PRT3789 achieves high selectivity by inducing a more stable ternary complex between SMARCA2 and VHL than SMARCA4 and VHL.

•
K1405 loop in SMARCA2 provides a unique lysine residue to enable selective ubiquitination and also stabilizes the SMARCA2:PRT3789:VHL complex.
•
SMARCA2 resynthesis rate is 2-3 times slower than SMARCA4 thereby enhancing the selectivity profile and contributing to the broad therapeutic index and favorable safety profile observed with PRT3789 in clinical studies to date.
•
PRT3789 is currently under evaluation in Phase 1 and Phase 2 studies in patients with advanced solid tumors with loss of SMARCA4 (NCT05639751 and NCT06682806).

Link: Publications – Prelude Therapeutics (preludetx.com)

Title: Discovery of First-in-Class Potent and Selective Oral Degraders of KAT6A that Demonstrate Anti-cancer Activity in Pre-clinical Models

Summary:

•
KAT6A expression is associated with cancer growth and is recurrently amplified in breast, lung, ovarian and other cancers.1
•
KAT6 is a clinically validated target with a dual KAT6A/B inhibitor recently demonstrating promising efficacy in heavily pre-treated patients with ER+/HER2- breast cancer, albeit with potential on-target safety considerations including neutropenia.2
•
Prelude hypothesized that a targeted protein degradation approach could enable discovery of KAT6A selective candidates with potential for improved hematological safety and more robust single agent activity relative to other KAT6-targeted approaches.
•
Prelude believes that it has identified a series of first-in-class, sub-nanomolar, selective and readily orally bioavailable KAT6A degraders now advancing to candidate nomination.
•
Pre-clinical data presented demonstrate that Prelude’s selective KAT6A degraders:
o
Drive significantly deeper anti-cancer responses compared to non-selective KAT6A/B inhibitors across multiple KAT6A-amplified tumors.
o
Disrupt the histone acetyltransferase (HAT) complex resulting in a deeper biological effect on ERα expression.
o
Show sustained activity in ESR1- and Pi3Kalpha-mutated cells, as well as endocrine therapy- and CDK4/6i-resistant cells.
o
Exhibit robust combination benefit with SoC and potential synergy with next generation breast cancer therapies.
o
Deliver robust in vivo target engagement and deep tumor regressions, including complete regressions, in breast and lung cancer xenografts as a monotherapy at low oral daily doses.
o
Display reduced hematologic toxicity compared to KAT6A/B inhibitors.