On March 25, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that a preclinical abstract highlighting the potential of ORIC-944, a potent and selective allosteric inhibitor of PRC2 to treat prostate cancer, has been accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30, 2025 in Chicago, IL (Press release, ORIC Pharmaceuticals, MAR 25, 2025, View Source [SID1234651410]).

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Poster presentation details:

Title: ORIC-944, a PRC2 inhibitor with best-in-class properties, restores luminal features and restricts adaptation in prostate cancer models, conferring synergy with AR pathway inhibitors
Abstract Number: 452
Date & Time: Sunday, April 27, 2025, 2:00 – 5:00 p.m. CT
Session Category: Experimental and Molecular Therapeutics
Session Title: Epigenetic Targets
Location: Poster Section 20

Abstract Highlights
ORIC-944 is a potent, highly selective, orally bioavailable, allosteric inhibitor of PRC2 that demonstrates best-in-class drug properties, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. In preclinical prostate cancer models, ORIC-944 demonstrated robust inhibition of PRC2, enhanced luminal cell state, and increased androgen receptor (AR) signaling. Analysis of chromatin revealed that ORIC-944 specifically restricts accessibility to lineage-associated transcription factors known to impart cellular plasticity in prostate cancer. This plasticity-restricted luminal state conferred by PRC2 inhibition is dependent on AR, leading to antitumor activity either in the hormone-depleted context or in the combination setting with an AR pathway inhibitor (ARPI). Together these data indicate that ORIC-944 reinforces a luminal cell state and, notably, restricts access to plasticity genes leading to a highly AR-dependent state in prostate models. This mechanism supports the observed preclinical synergy between PRC2 inhibition and ARPIs in both ARPI-sensitive and ARPI-resistant settings. These results position ORIC-944 as a potential best-in-class PRC2 inhibitor that blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPIs. A phase 1b trial of ORIC-944 in combination with ARPIs is ongoing in metastatic prostate cancer (NCT05413421).

On March 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 that company scientists will present preclinical data from its proprietary DEL-AI platform and several degrader programs in two oral presentations and two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, which will be held from April 25-30, 2025, in Chicago, IL (Press release, Nurix Therapeutics, MAR 25, 2025, View Source [SID1234651409]).

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Oral Presentation Details:

Title: DEL-AI: Proteome-wide in silico screening of multi-billion compound libraries using machine learning foundation models
Presenting author: Paul Novick, Ph.D.
Session title: Innovative Approaches in Drug Discovery: Novel Leads, Degraders, and AI-Driven Solutions
Session date and time: Monday, April 28, 2025, 2:30 PM – 4:30 PM CST
Abstract ID: 3762

Title: Identification of selective, orally bioavailable Aurora A degraders for treatment of pediatric and adult cancers
Presenting author: Ryan Rountree, Ph.D.
Session title: Degraders and Glues
Session date and time: Tuesday, April 29, 2025, 2:30 PM – 4:30 PM CST
Abstract ID: 6379

Poster Presentation Details:

Title: 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
Presenting authors: Alexandra ‘Sasha’ Borodovsky, Ph.D.
Session title: Degraders and Glues 2
Session date and time: Monday, April 28, 2025, 9:00 AM – 12:00 PM CST
Abstract ID: 1651

Title: NX-5948 is a CNS-penetrant catalytic Bruton’s tyrosine kinase (BTK) degrader that breaks established design rules for CNS drugs
Presenting authors: Wylie Palmer, Ph.D.
Session title: Targeted Protein Degradation
Session date and time: Wednesday, April 30, 2025, 9:00 AM – 12:00 PM CST
Abstract ID: 7003

About DEL-AI
DEL-AI is Nurix’s discovery platform which employs advanced machine learning to enable all aspects of Nurix’s discovery engine, starting with DNA encoded library (DEL) hit-finding and degrader design, followed by automated chemistry synthesis and direct-to-biology screening and optimization, to rapidly generate degraders and degrader antibody conjugates (DACs) as new chemical entity drug candidates. By leveraging hundreds of billions of DEL compound binding signatures derived from thousands of DEL affinity screens collected from a diverse set of highly validated protein targets, our DEL-AI platform can prospectively identify binders as starting points for drug discovery for virtually any pharmaceutically relevant target.

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

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

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

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

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

About the ARTISTRY-7 Trial

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

About Nemvaleukin

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

On March 25, 2025 Eli Lilly and Company (NYSE: LLY) reported that preclinical data for agents targeting SMARCA2 (BRM) and multiple KRAS mutations will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25 – 30 in Chicago (Press release, Eli Lilly, MAR 25, 2025, View Source [SID1234651407]).

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In an oral presentation, Lilly, in collaboration with Foghorn Therapeutics, will present new preclinical data for LY4050784, a selective inhibitor of SMARCA2, in combination with chemotherapy, pembrolizumab, and KRAS inhibitors in preclinical models of SMARCA4 mutant cancers. Preclinical data for LY4066434, a pan-KRAS inhibitor that is highly selective over HRAS and NRAS, will also be presented. Both programs are currently enrolling Phase 1 studies.

Details on presentations are below:

Presentation Title: LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors
Abstract Number: 3779
Session Date & Time: Monday, April 28, 2:30-4:30 p.m. CST
Session Title: Continuum of Innovation: Biological Therapeutic Agents
Presenter: Nathan Brooks

Presentation Title: LY4066434, an oral small molecule pan-KRAS inhibitor, demonstrates robust anti-tumor activity in KRAS-mutant models, including in the CNS
Abstract Number: 4375
Session Date & Time: Tuesday, April 29, 9 a.m.-12 p.m. CST
Session Title: RAS Inhibitors
Presenter: Hong Gao

On March 25, 2025 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported that it will present new data for its lead asset EVX-01 at a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Chicago April 25-30, 2025 (Press release, Evaxion Biotech, MAR 25, 2025, View Source [SID1234651403]). Designed with Evaxion’s AI-Immunology platform, EVX-01 is a personalized cancer vaccine currently being evaluated as a treatment for advanced melanoma (skin cancer).

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Evaxion will present new biomarker and immune data obtained from the ongoing phase 2 trial. These will further add to EVX-01’s already strong clinical data package.

"We are proud to be selected by the AACR (Free AACR Whitepaper)’s scientific committee to present new data at this very renowned and important scientific meeting. This is a testament of the high scientific value of the EVX-01 clinical program, and we are excited to get the chance to present and discuss the data with a big audience in the field of melanoma research", says Birgitte Rønø, Chief Scientific Officer of Evaxion.

The trial previously yielded strong interim one-year clinical data and remains on track for readout of two-year clinical data in the second half of 2025. Additionally, the trial has been extended with a third year, allowing for a more comprehensive assessment of the full potential of EVX-01.

AACR presentation details:
Abstract title: T-cell immunogenicity and biomarker profiling in advanced melanoma patients receiving the personalized vaccine EVX-01 in combination with pembrolizumab
Abstract#: 4538
Poster#: 9
Session (category): Immune responses to therapies including chemotherapy and radiotherapy (Clinical research)
Location: Poster section 28
Date/Time: April 29, 2025, at 9am-12pm CST/16-19 CET
Presenter: Mads Lausen Nielsen, PhD, Project Manager at Evaxion

The phase 2 trial investigates EVX-01 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced melanoma (skin cancer). Each patient enrolled in the trial has received a unique vaccine designed and manufactured based on their individual biology. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About EVX-01
EVX-01 is a personalized peptide-based cancer vaccine intended for first-line treatment of multiple advanced solid cancers. It is Evaxion’s lead clinical asset.

EVX-01 is designed with our AI-Immunology platform and is tailored to target the unique tumor profile and immune characteristics of each patient. It engages the patient’s immune system to fight off cancer by mounting a targeted response against tumors.

In clinical trials, EVX-01 has demonstrated 69% and 67% Overall Response Rates in patients with advanced melanoma. Further, significant correlations between clinical responses and AI-Immunology predictions have been observed, underlining the predictive power of the platform.