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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On April 25, 2025 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported preclinical data demonstrating the anti-tumor activity of OP-3136, a novel small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), in prostate, ovarian, and non-small cell lung cancer (NSCLC) models (Press release, Olema Oncology, APR 25, 2025, View Source [SID1234652148]). These findings are being presented in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data showcase the potential of OP-3136 for the treatment of challenging cancers beyond breast cancer," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "OP-3136 has shown inhibition across all models explored, and we were excited to observe potent tumor growth inhibition and sustained tumor regression with OP-3136 as a monotherapy in ovarian cancer models. We are actively recruiting the Phase 1 trial of OP-3136 in multiple solid tumor types and will continue to explore its potential in other indications of high unmet need."

Poster Presentation Details
Title: OP-3136, a selective KAT6 inhibitor, demonstrates anti-tumor activity in prostate, ovarian, and non-small cell lung cancer preclinical models
Poster/Abstract: LB166
Session: Late-Breaking Research: Tumor Biology 2
Date/Time: April 28, 2025, from 9:00am-12:00pm CT / 10:00am-1:00pm ET
Presenter: Dr. Gopinath S. Palanisamy, DVM, Ph.D.

Key findings include:

OP-3136 showed potent anti-proliferative activity in multiple ovarian, NSCLC, and prostate cell lines in vitro.
OP-3136 showed activity that was independent of KAT6 amplification or over expression.
OP-3136 monotherapy demonstrated anti-tumor activity in in vivo xenograft models of ovarian (OVCAR3), NSCLC (LCLC-97TM1), and prostate (22Rv1) cancers.
In the OVCAR3 model, OP-3136 monotherapy demonstrated sustained tumor regression across the 28-day study period and robust tumor growth inhibition.
In the LCLC-97TM1 model, OP-3136 monotherapy demonstrated tumor growth inhibition comparable to ribociclib and, when combined with ribociclib, demonstrated synergy and enhanced anti-tumor activity.
In the 22Rv1 model, OP-3136 inhibited tumor growth in a dose-dependent manner and, when combined with docetaxel, resulted in enhanced anti-tumor activity.
These data indicate OP-3136 may be effective in treating ovarian, lung, and prostate cancer indications in addition to breast cancer.
A copy of this poster is available on the Publications page of Olema’s website. Additional information can be found on the AACR (Free AACR Whitepaper) Annual Meeting website, including abstracts.

About OP-3136
OP-3136 is a novel, orally available small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), an epigenetic target that is dysregulated in breast and other cancers. In preclinical studies, OP-3136 has demonstrated significant anti-proliferative activity in ER+ breast cancer models and is combinable and synergistic with endocrine therapies, including palazestrant and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The Investigational New Drug (IND) application for OP-3136 was cleared by the U.S. Food and Drug Administration (FDA) in December 2024 and patients are currently enrolling in the Phase 1 clinical trial.

On April 25, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported multiple preclinical presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting supporting several programs, each with different drug targets for indications with central nervous system (CNS) involvement (Press release, Nurix Therapeutics, APR 25, 2025, View Source [SID1234652147]). The AACR (Free AACR Whitepaper) Annual Meeting is being held from April 25-30, 2025, in Chicago, IL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data we are presenting at AACR (Free AACR Whitepaper) highlight the power of our DEL-AI platform to design and create potent, orally available degraders that overcome the limitations of inhibitors, target difficult to treat mutations, and access the CNS, a feature which is particularly important for patients whose tumor has metastasized to the brain," said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. "We look forward to advancing these programs in pursuit of novel therapeutic options for the benefit of patients living with cancer."

In a poster titled: "NX-5948 is a CNS-penetrant catalytic Bruton’s tyrosine kinase (BTK) degrader that breaks established design rules for CNS drugs," data were presented that highlight the unique physico-chemical properties of NX-5948, now called bexobrutideg, that differentiate it from traditional brain penetrant drugs. Bexobrutideg exhibits CNS exposure in several preclinical models and, most importantly, is detectable in the cerebrospinal fluid of patients where it has demonstrated clinically meaningful responses in patients with primary CNS lymphoma or chronic lymphocytic leukemia with CNS involvement. An important feature of protein degraders compared to small molecule inhibitors is their catalytic nature. In vitro experiments enabled calculation of the catalytic efficiency of bexobrutideg, demonstrating that a single molecule can degrade approximately 10,000 copies of BTK protein per hour at clinically relevant concentrations, which means that activity and efficacy can be achieved at much lower concentrations of a degrader as compared to an inhibitor.

In a second poster titled: NRX-0305: a pan-mutant BRAF degrader with broad preclinical efficacy, brain penetrance, and synergistic potential with MEKi across class 1/2/3 BRAF-mutant cancers, preclinical data were presented from Nurix’s differentiated BRAF degrader, NRX-0305, which degrades all three classes of mutant oncogenic BRAF proteins while sparing wildtype BRAF in healthy cells. Mutations in BRAF, a key component of the mitogen-activated protein kinase (MAPK) pathway, drive oncogenic transformation and are commonly found in a variety of cancers including melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). BRAF mutations are categorized into three mutational classes (Class 1-3). While approved BRAF inhibitors (BRAFi) provide survival benefit to Class 1 patients, drug durability and efficacy are limited by the emergence of primary and acquired resistance. Furthermore, patients who have progressed on BRAFi, especially in melanoma, frequently present with brain metastases, for which there are limited treatment options due to poor CNS penetrance of available drugs. New data demonstrate that BRAF degradation correlates with reduced tumor cell viability across a panel of clinically relevant BRAF mutations, supporting the role of degradation in driving antiproliferative effects. In disease models, data demonstrated broad anti-tumor efficacy of NRX-0305 across all three BRAF mutation classes and in tumors that are resistant to existing therapies. Specifically, NX-0305 demonstrated superior anti-tumor efficacy in a xenograft (PDX) model derived from a patient with a class 1 BRAF mutation whose tumor was resistant to both pembrolizumab + BRAFi compared to a competitor BRAF degrader CFT1946. In addition, the data showed anti-tumor efficacy as a single agent and in combination with MEKi in class 3 (G466V) NSCLC cell-derived xenograft (CDX) models.

On Tuesday, April 29, 2025, Nurix scientists will also present data from the company’s ongoing collaboration sponsored by Alex’s Lemonade Stand Foundation (ALSF), a leading funder of pediatric cancer research, to develop a drug to potentially treat aggressive childhood cancers including neuroblastoma and medulloblastoma. As part of the collaboration, Nurix has identified a panel of selective, orally bioavailable degraders of Aurora A kinase (AURKA), an oncogene frequently overexpressed in these pediatric cancers and in adult solid tumors and hematologic malignancies. While several AURKA inhibitors are effective in preclinical tumor models, this activity has failed to translate into clinical efficacy, which may be explained by recent studies that found that AURKA has kinase-independent scaffolding functions that are not effectively blocked through enzymatic inhibition. In an oral presentation titled "Identification of selective, orally bioavailable Aurora A degraders for treatment of pediatric and adult cancers," Nurix will highlight preclinical data from studies of NRX-4972, an orally bioavailable and highly selective brain penetrant AURKA degrader. The data demonstrate that daily oral administration of NRX-4972 resulted in downregulation of MYCN as well as induction of DNA damage, apoptosis, and G2/M arrest, the latter set of effects being more pronounced in the context of degradation rather than AURKA inhibitor, which translated into significant efficacy in a model of neuroblastoma. Data comparing AURKA degradation to inhibition in a second efficacy model will be included in the upcoming oral presentation on Tuesday, April 29, 2025.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. Bexobrutideg is currently being evaluated in a Phase 1a/b clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

About NRX-0305
NRX-0305 is a potent, selective, and orally bioavailable mutant-specific BRAF degrader that Nurix is exploring for use in oncology. Nurix has reported preclinical data demonstrating potent anti-tumor activity in multiple cell line-derived and patient-derived xenograft disease models representing Class I, Class II and Class III B-RAF mutations. Anti-tumor activity was also observed in the setting of CNS disease and treatment-resistance, suggesting the potential for utility across a broad range of solid tumor types.

About Aurora A Kinase
Aurora A kinase (AURKA) is an oncogene frequently overexpressed in adult solid tumors, hematologic malignancies, and pediatric cancers. Several AURKA inhibitors are effective in preclinical tumor models, but this activity has failed to translate into clinical efficacy. To address the limitations of inhibitors, Nurix has designed bifunctional targeted protein degraders of AURKA that enable removal of both enzymatic and scaffolding functions.

On April 25, 2025 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, reported that its Phase 1/2 clinical trial of NDI-219216, the company’s investigational non-covalent Werner syndrome helicase (WRN) inhibitor, is actively enrolling and dosing patients with advanced solid tumors (Press release, Nimbus Therapeutics, APR 25, 2025, View Source [SID1234652146]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initiation of this clinical trial marks an important milestone in advancing our novel WRN inhibitor program," said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Head, Oncology at Nimbus. "We are excited to be evaluating NDI-219216 in patients with advanced disease, who currently have limited treatment options when they experience disease progression on standard of care therapies. The trial is actively enrolling across multiple clinical sites, and we look forward to generating important additional safety and efficacy data as we advance this promising candidate through clinical development."

The Phase 1/2 clinical trial (NCT06898450) is an open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced cancer. The study will be conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion).

Nimbus presented promising preclinical data on NDI-219216 (previously NTX-452) at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October 2024. The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses observed at low doses in MSI-H tumor models refractory to immunotherapy and chemotherapy.

The company will present new findings comparing covalent versus non-covalent WRN inhibition mechanisms and demonstrating NDI-219216’s superior efficacy across multiple preclinical MSI-H tumor models compared with other clinical-stage WRN inhibitors in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 25-30, 2025 in Chicago. The poster entitled "NDI-219216: a non-covalent, potent, selective and highly efficacious WRN inhibitor with best-in-class potential for the treatment of MSI-H tumors" highlights key preclinical findings related to NDI-219216, including:

Demonstration of activity against a potential resistance mutation at Cysteine 727 that could significantly reduce the efficacy of covalent WRN inhibitors
Robust tumor regression across multiple MSI-H tumor models, including those that are refractory to existing standard of care agents
Superior efficacy at lower doses and in less responsive MSI-H tumor models compared to other clinical-stage WRN inhibitors
"The data we are presenting at AACR (Free AACR Whitepaper) 2025 highlight several important features of our non-covalent WRN inhibitor," said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. "NDI-219216 has the potential for more durable target engagement than covalent inhibitors and maintains potency against potential resistance mutations. Its superior efficacy across multiple MSI-H tumor models, including those less sensitive to other WRN inhibitors and those refractory to current therapies, reinforces our belief that NDI-219216 represents a best-in-class opportunity with broad potential across multiple MSI-H tumor types with significant unmet need."

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.