On April 28, 2025 Plexium, Inc. (Plexium), a leading next-generation targeted protein degradation company, reported multiple presentations with the Company’s selective monovalent degrader programs for SMARCA2, IKZF2 and CDK2 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, Plexium, APR 28, 2025, View Source [SID1234652243]).

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 highlight the clinical and preclinical progress we’ve made across our portfolio, including the use of a novel E3 ligase DCAF16, in our SMARCA2 program—an industry first that reinforces the differentiated potential of our monovalent degrader platform," said Jorge F. DiMartino, MD, PhD, Chief Medical Officer at Plexium. "We are also excited to share initial clinical data from PLX-4545, which demonstrated clinical proof of mechanism and intended pharmacological immunophenotypic effects."

Oral Presentation Details:

Title: "Discovery and characterization of novel, potent and selective CDK2 molecular glue degrader against CCNE1-amplified tumors"
Session: MS.ET09.01 – Degraders and Glues
Abstract Number: 6375
Date and Time: April 29, 2:55 PM – 3:10 PM
Presenting Author: Leenus Martin, PhD

Title: "PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy"
Session: MS.ET09.01 – Degraders and Glues
Abstract Number: 6380
Date and Time: April 29, 4:10 PM – 4:25 PM
Presenting Author: Peggy Thompson, PhD

Poster Presentation Highlights:

Title: "Mechanistic characterization of selective monovalent direct degraders of SMARCA2″
Session: PO.ET09.04 – Degraders and Glues 1
Abstract Number: 404
Section: 18
Date and Time: April 27, 2025, 2:00 PM – 5:00 PM
Presenting Author: Julia Toth, PhD

Plexium’s SMARCA2 degraders function by bromodomain binding and covalent modification
A CRISPR knockout screen identified DCAF16 as being required for PLX-61639 mediated SMARCA2 degradation
MOA studies demonstrate PLX-61639-mediated SMARCA2:DCAF16 protein interactions and the requirement of covalent binding to a specific DCAF16 cysteine to support a stable ternary complex and subsequent SMARCA2 degradation
Title: "Preclinical characterization of PLX-61639, a potent and orally bioavailable SMARCA2-selective monovalent direct degrader"
Session: PO.ET09.10 – Degraders and Glues 2
Abstract Number: 1653
Section: 18
Date and Time: April 28, 2025, 9:00 AM – 12:00 PM
Presenting Author: Gregory Parker, PhD

Plexium has designed PLX-61639, a potent and selective direct degrader of SMARCA2, and nominated it as a development candidate
Daily oral dosing of PLX-61639 results in deep and sustained SMARCA2 degradation, eliciting robust tumor growth inhibition and regression in SM4mut CDX and PDX models, no tumor growth inhibition is observed in a control SM4wt CDX model
PLX-61639 is currently advancing through IND-enabling studies
Title: "A first in human trial of PLX-4545, a molecular glue degrader of IKZF2, in healthy volunteers, shows pharmacologic modulation of Tregs at well-tolerated doses"
Session Title: PO.CT01.02. First-in-Human Phase I Clinical Trials 2
Abstract Number: CT150
Section: 48
Date and Time: April 29, 2025, 9:00 AM – 12 PM
Presenting Author: Jorge DiMartino, MD, PhD

PLX-4545 an oral, CRBN molecular glue degrader of IKZF2, a lineage-defining transcription factor for Tregs was tested in healthy adult volunteers
With repeated daily dosing for 14 days, all dose levels achieved complete degradation of IKZF2 in PBMCs by Day 2 leading to conversion of Tregs into effector-like T cells and an increase in activated T effector cells
TEAEs were mostly Grade 1 or 2 (mild or moderate) in severity and no Dose Limiting Toxicities were encountered. All AEs were reversible with discontinuation of dosing
The AACR (Free AACR Whitepaper) 2025 posters will be made available on the Plexium website.

On April 28, 2025 PharmaMar (MSE:PHM), global leader in research, development and commercialization of marine-derived oncology treatments, reported that it is once again participating in the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), being held in Chicago from April 25th to 30th, 2025 (Press release, PharmaMar, APR 28, 2025, View Source [SID1234652242]). On this occasion, the Company is presenting eleven new studies with results on the activity of its compounds: lurbinectedin (Zepzelca), ecubectedin, PM54, PM534, and trabectedin (Yondelis).

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!

This reinforces PharmaMar’s ongoing commitment to innovation and cancer research. "We continue to advance the study of the therapeutic potential of marine-derived molecules, both in well-established compounds and in those in earlier stages of development. Our participation this year in the world’s leading oncology research congress reflects our firm commitment to scientific innovation and the path we are building to provide potential therapeutic alternatives for patients," says Carmen Cuevas, VP of R&D at PharmaMar.

The main conclusions from the presented studies highlight the potential of two novel transcription inhibitors, PM54 and ecubectedin as innovative antitumor agents. Ecubectedin has demonstrated encouraging antitumor efficacy in both gastric and neuroendocrine-prostate cancer models. In collaboration with KU Leuven University (Belgium), data also confirm promising antitumor activity of both ecubectedin and PM54 in representative models of soft tissue sarcomas (STS).

Additionally, data on PM534 are being presented. PM534 is a novel tubulin-targeting agent, that may bypass the most common resistance mechanisms, limiting the effectiveness of standard microtubule-binding drugs.

Finally, the studies also show the antitumor activity of lurbinectedin in NUT carcinoma—a rare type of cancer that forms in the head, neck and lungs. Furthermore, new insights into the mechanism of action of trabectedin will also be shared.

The full list of all presentations supported by PharmaMar or its collaborators at the AACR (Free AACR Whitepaper) 2025 Annual Meeting is as follows:

COMPOUND TITLE LEAD AUTHOR ABSTRACT
Ecubectedin (PM14) Ecubectedin’s role in targeting transcriptional regulators in neuroendocrine prostate cancer. Laura Almalé, PhD Location: Section 22
Board Number: 23
Published Abstract Number: 1771 April 28, 2025
Ecubectedin as a promising therapeutic agent against gastric cancer through Wnt/β-Catenin modulation. Alejandro Losada, PhD Location: Section 21
Board Number: 8
Published Abstract Number: 5630 April 29, 2025
The novel transcriptional inhibitor ecubectedin demonstrates strong antitumor activity in patent-derived xenograft models of soft tissue sarcoma. Daniël Gorgels, PhD Location: Section 21
Board Number: 1
Published Abstract Number: 6857 April 30, 2025
PM534 Overcoming resistance to tubulin-targeting drugs with PM534: an innovative microtubule-targeting compound. Pablo M. Aviles, PharmD, PhD Location: Section 21
Board Number: 8
Published Abstract Number: 6864 April 30, 2025
PM54 PM54, a novel transcription inhibitor with promising broad spectrum antitumor activity. Marcelo Lima Ribeiro, PhD Location: Section 22
Board Number: 25
Published Abstract Number: 1773 April 28, 2025
The next generation transcriptional inhibitor PM54 demonstrates strong antitumor activity in patient-derived xenograft models of soft tissue sarcoma. Daniël Gorgels, PhD Location: Section 21
Board Number: 2
Published Abstract Number: 6858 April 30, 2025
Pan-inhibition of super-enhancer-driven oncogenic transcription by novel synthetic ecteinascidins yields potent anti-cancer activity Julian Obid, PhD Location: Section 21
Board Number: 13
Published Abstract Number: 1738 April 28, 2025
Trabectedin (Yondelis) Redefining the Molecular Target for Trabectedin (ET743) as Stable Covalent Bonding to N2 of Guanine in Duplex Stem-Loops of G-Quadruplexes. Laurence H. Hurley, PhD Location: Section 19
Board Number: 2
Published Abstract Number: 2972 April 28, 2025
Lurbinectedin (Zepzelca) New therapeutic approaches in NUT Carcinoma: an unmet need. María Virgina Sáchéz-Becerra, PhD Location: Section 34
Board Number: 23
Published Abstract Number: 5996 April 29, 2025
Lurbinectedin-Induced Transcriptional Reprogramming: A Pathway to Sensitise SCLC to Immunotherapy J.S. Russo-Cabrera, PhD Location: Section 23
Board Number: 13
Published Abstract Number: 5837 April 29, 2025
Lurbinectedin Irinotecan as a new therapeutic combination for Small Cell Lung Cancer Miguel Ruiz-Torres, PhD Location: Section 34
Board Number: 13
Published Abstract Number: 5986 April 29, 2025

On April 28, 2025 Orum Therapeutics, Inc. ("Orum" or the "Company") (KRX: 475830), a public biotechnology company pioneering the field of degrader-antibody conjugates (DACs), reported a strategic update to its pipeline (Press release, Orum Therapeutics, APR 28, 2025, View Source [SID1234652241]). Orum has discontinued further clinical development of ORM-5029, a HER2-targeted GSPT1 degrader-antibody conjugate (DAC). This decision follows an internal assessment of the program’s clinical progress and incorporates information previously disclosed. Concurrently, Orum announced the nomination of a new drug candidate, ORM-1153, in development for the treatment of hematologic malignancies.

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!

ORM-1153 is a novel DAC engineered using Orum’s proprietary Dual-Precision Targeted Protein Degradation (TPD²) approach, which combines the catalytic protein degradation mechanism of TPDs with the tumor-targeting capabilities of therapeutic antibodies. The candidate targets GSPT1, a translation termination factor highly relevant in hematologic malignancies, and an undisclosed tumor-associated antigen to enhance selectivity and broaden the therapeutic window.

In preclinical studies, ORM-1153 demonstrated potent anti-tumor activity and a favorable safety profile, including in non-human primate models. ORM-1153 demonstrated picomolar potency in target-expressing cell lines and showed greater potency than existing small molecule GSPT1 degraders. In vivo, a single dose of ORM-1153 led to strong anti-tumor activity in relevant xenograft models. Orum plans to advance the program into IND-enabling studies and anticipates presenting additional data at a scientific conference later this year.

"After careful review of available clinical and preclinical data, we have concluded clinical development of ORM-5029," said Sung Joo (SJ) Lee, Ph.D., Founder and CEO of Orum Therapeutics. "This decision reflects our continued commitment to patient safety and our strategic focus on advancing the next generation of degrader-antibody conjugates with a clearly defined risk-benefit profile. We look forward to advancing next-generation programs emerging from our proprietary platform, like ORM-1153."

Dr. Lee continued, "ORM-1153 leverages learnings from all our programs and clinical experience to build potent, selective, and tumor-targeted protein degrader therapeutics that address serious unmet needs in oncology. We remain confident in the promise of our Dual-Precision Targeted Protein Degradation GSPT1 platform and are excited to progress this new candidate toward the clinic."

About Orum’s TPD² Approach

Orum’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach builds novel targeted protein degraders combined with the precise cell delivery mechanisms of antibodies to generate innovative, first-in-class, cell-selective TPDs for the treatment of cancer. Orum has developed new targeted protein degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to target cells and precisely degrade the intracellular target protein of interest.

On April 28, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the presentation of a poster at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, highlighting preclinical data on ORIC-944, a potent, highly selective, orally bioavailable allosteric inhibitor of PRC2, which demonstrated synergistic activity and improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in models of prostate cancer (Press release, ORIC Pharmaceuticals, APR 28, 2025, View Source [SID1234652240]).

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!

"We are excited by the potential of ORIC-944 to be a best-in-class PRC2 inhibitor for the treatment of prostate cancer," said Lori Friedman, PhD, chief scientific officer. "The data presented at AACR (Free AACR Whitepaper) demonstrate the strong synergy of ORIC-944 when combined with standards of care, reversing the evolution of prostate cancer, and improving progression-free survival in both castration-resistant and castration-sensitive prostate cancer models – validating the clinical exploration of ORIC-944 across the continuum of prostate cancer."

Poster presentation:

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

Key findings of the presentation:

ORIC-944 increased progression-free survival (PFS) when combined with ARPIs in both castration-sensitive and castration-resistant prostate cancer models.
ORIC-944 demonstrated transcriptional synergy and antitumor synergy when combined with ARPIs in prostate cancer cells.
In preclinical prostate cancer models, ORIC-944 demonstrated robust inhibition of PRC2, enhanced luminal cell state, and consistently restricted lineage transcription factor accessibility through chromatin remodeling, ​thereby reenforcing the luminal state and preventing access to plasticity programs.
Results position ORIC-944 as a potential best-in-class PRC2 inhibitor that, through both transcriptional and chromatin mechanisms, blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPIs.
ORIC-944 is currently being evaluated in combination with ERLEADA (apalutamide) and in combination with NUBEQA (darolutamide) in an ongoing Phase 1b trial for prostate cancer.
About ORIC-944
ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the embryonic ectoderm development (EED) subunit that demonstrates best-in-class drug properties in preclinical studies, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including clinical half-life of approximately 20 hours, robust target engagement and a favorable safety profile. ORIC-944 is currently being evaluated in combination with ERLEADA (apalutamide) and in combination with NUBEQA (darolutamide) in an ongoing Phase 1b trial for prostate cancer (NCT05413421).

On April 28, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported data that demonstrate the potential of its DEL Foundation Model to enable the rapid in silico identification of novel binders for a broad range of therapeutically relevant proteins, addressing a key barrier in the discovery and development of small molecule drugs (Press release, Nurix Therapeutics, APR 28, 2025, View Source [SID1234652239]). These results were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL, which is being held from April 25-30, 2025.

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!

"Nurix’s DEL-AI platform has the potential to accelerate the discovery of breakthrough small molecule drugs—whether they be protein degraders, molecular glues, or inhibitors—by enabling ready-access to tractable chemical matter for an expansive set of proteins, especially those previously considered beyond the reach of drug discovery organizations," said Gwenn M. Hansen, Ph.D., chief scientific officer of Nurix. "Our team has leveraged the rich datasets generated from rigorously controlled screenings of our customize collection of over five billion unique DEL compounds against hundreds of disease targets and E3 ligase proteins to construct a powerful suite of machine learning models and tools. By directly integrating the sampling density provided by DEL compound repertoires with primary protein sequence information, our model can learn a generalizable structure activity relationship capable of predicting novel binders for nearly any disease-relevant protein target."

"Our DEL-AI engine is a potential game changer, allowing us to substantially accelerate drug discovery workflows and efficiently identify therapeutic candidates for our wholly owned pipeline and our current and future discovery partnerships," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "This powerful research engine is a result of our significant expertise and strategic investments in DEL methodology and our machine learning platform."

Nurix’s presentation at the AACR (Free AACR Whitepaper) 2025 Annual Meeting, titled: "DEL-AI: Proteome-wide in silico screening of multi-billion compound libraries using machine learning foundation models," described the development of a first-in-class foundation model that was trained on the Company’s high quality, proprietary DEL data. Nurix’s DEL Foundation Model is able to perform virtual DEL experiments on prospective protein target sequences to accurately predict novel binders to a large proportion of therapeutically relevant targets, including many targets considered undruggable. In plots of virtually predicted vs. experimentally-derived DEL screens against therapeutically relevant proteins, Nurix’s DEL Foundation Model demonstrated the ability to accurately predict the experimental results, including experimentally validated binders. Success of the DEL Foundation Model was found to correlate to the degree of similarity of query sequences to proteins within the DEL training set, and data demonstrated that the current model requires as little as 50% amino acid sequence similarity of a query protein to training data to enable binder prediction. Nurix’s model was also capable of inferring binders from chemical space not represented in the training set, suggesting that the model is capable of both protein sequence and chemical structure generalizations.

The development of the DEL Foundation Model was led by Nurix in collaboration with Loka, a Silicon Valley-based software development firm, and supported by Amazon Web Services (AWS), leveraging AWS SageMaker and AWS managed MLflow to provide enterprise-grade reliability and scalable infrastructure.

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, Nurix’s DEL-AI platform can prospectively identify binders as starting points for drug discovery for virtually any pharmaceutically relevant target.