On October 9, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that it will present four posters with clinical and preclinical data from RVU120 (CDK8/19 inhibitor), RVU305 (MTA-cooperative PRMT5 inhibitor), WRN and novel synthetic lethality programs at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (ENA), October 23-25, Barcelona, Spain (Press release, Ryvu Therapeutics, OCT 9, 2024, View Source [SID1234647114]).

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 thrilled to showcase our latest advancements on RVU120, RVU305, and other synthetic lethality projects at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium this year. The strong preclinical data from our PRMT5 synthetic lethality program is highly encouraging as we target IND/CTA filing and continue to advance our project toward clinical studies." – said Krzysztof Brzózka, Ph.D., Chief Scientific Officer.

Poster highlights:

Abstract Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers
Abstract Number: ENA24-0205
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a potentially best-in-class MTA-cooperative PRMT5 inhibitor, RVU305, demonstrating favorable drug-like properties and effective PRMT5 inhibition dependent on MTA binding. Structure-based optimization has resulted in a compound exerting selective efficacy in MTAP-deleted cell lines and a DMPK profile suitable for oral administration. RVU305 exhibits robust antiproliferative activity in MTAP-null cancer models, with a favorable safety margin in MTAP wild-type cells. Comparative studies against other clinical-stage PRMT5 inhibitors confirmed RVU305’s favorable antitumor activity in vitro and in vivo. Overall, the findings highlight the potential of RVU305 as a promising therapeutic option for patients with MTAP-deleted cancers.

Abstract Title: Discovery of WRN inhibitors as targeted therapy in the treatment of microsatellite unstable (MSI-H) tumors
Number: ENA24-0364
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu is developing a series of potent and selective WRN helicase inhibitors that demonstrate pronounced efficacy in tumors with high microsatellite instability (MSI-H). These compounds show nanomolar potency in viability assays in MSI-H cell lines, with excellent selectivity over microsatellite-stable (MSS) cells. In in vivo studies, RVU305 strongly suppressed tumor growth in an MSI-H model (SW48) while not impacting the MSS model (SW620). Additionally, the compounds exhibit favorable pharmacokinetics, achieving optimal exposure and target engagement, further enhancing their therapeutic potential in MSI-H cancers.

Abstract Title: Exploring synthetic lethality and novel drug combinations in patient-derived cells
Poster Number: ENA24-0395
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

Ryvu has developed a proprietary platform, ONCO Prime, to discover novel synthetic lethal (SL) inhibitors targeting key oncogenic drivers such as KRAS and other mutations. Initial data are presented in colorectal cancer (CRC), but the platform has the potential to discover novel SL targets across all tumor types. ONCO Prime uses human intestinal stem cell (hISC)-derived cancer model cells, patient-derived xenografts (PDXs), and clinical samples to conduct genomic and functional analyses. By integrating CRISPR/Cas9 technology and machine learning, Ryvu generated isogenic cancer models, performed high-throughput screenings, and validated the findings through transcriptomic profiling of clinically relevant samples. This approach enabled the identification of essential and tumor suppressor genes critical for CRC and other cancers, focusing on SL targets specific to transformed cells.

Abstract Title: Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor in patients with relapsed/refractory metastatic or advanced solid tumors
Number: 34
Session date and time: Wednesday, October 23 (12:00-19:00 CEST)

RVU120 is being tested in patients with solid tumors in an ongoing Phase I/II clinical trial, AMNYS-51. RVU120 has demonstrated a manageable safety profile across multiple dose levels and dosing schedules in patients with advanced or metastatic solid tumors. No dose-limiting toxicities (DLTs) were observed, and most treatment-emergent adverse events (TEAEs) were mild to moderate, with nausea and vomiting being the most common. Stable disease (SD) was achieved in multiple patients, with tumor size reductions in three patients with adenoid cystic carcinoma (AdCC). The recommended phase 2 dose (RP2D) for the QOD schedule was identified as 250 mg, with dose escalation continuing for the QD schedule. These promising safety and preliminary efficacy results support further clinical investigation of RVU120.

Investor Event:
Ryvu Therapeutics will host a webinar to discuss new data from our latest poster presentations. The date and time of the webinar will be announced soon.

On October 9, 2024 Arbele, a leading innovator in biopharmaceutical & biotechnology focused on targeting cadherin-17 (CDH17), reported strategic collaborations in precision oncology using artificial intelligence (AI) to advance targeted immunotherapeutics of bispecific T-cell engagers (TCEs) and antibody-drug conjugates (ADCs) (Press release, ARBELE, OCT 9, 2024, View Source [SID1234647113]). These partnerships, aimed at advancing the quantification and prognostic prediction of CDH17 expression in tumor tissue and the surrounding tumor immune microenvironment, are expected to accelerate the development of precise companion diagnostics and effective clinical trials for the treatment of advanced cancer patients.

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!

Collaboration with BioAI: Development of IHC-Based Quantification Algorithm

Arbele enters a strategic alliance with BioAI Health to develop a prototype of an immunohistochemistry (IHC)-based quantification algorithm. Leveraging the PredictX platform to develop AI-based models using Arbele’s clinical trial data on colorectal cancer (CRC) biomarker screening, we join force to establish a gold standard companion diagnostic test for anti-CDH17 therapies for patient selection and prediction of clinical outcomes.

"By partnering with Arbele, we are excited to apply our novel AI platform and expertise to accelerate the development of innovative treatment options for gastrointestinal cancers," said Thomas Colarusso, CEO of BioAI. "This partnership underscores our commitment to revolutionizing personalized medicine through cutting-edge machine learning."

"BioAI’s machine learning capabilities offer a transformative approach to biomarker identification and patient stratification through predicting CDH17 expression and its spatial interaction with immune cells in tumor microenvironment," said Dr John Luk, CEO of Arbele. "This collaboration is a critical step in guiding us the uses of the right treatment modalities and/or therapeutic regimens, thereby improving outcomes for patients with high mortality cancers."

Collaboration with Chime Biologics: Accelerated CMC Process Development of novel ADC and TCE

Arbele has entered a strategic alliance with Chime Biologics to accelerate chemistry, manufacturing and control (CMC) process development of the novel designs of ADCs and TCEs. The partnership supports multiple pipelines of about 10 first-in-class and best-in-class immunotherapeutics, including monoclonal, bispecific/biparatopic and TriAx antibodies within the coming 3 years. The collaboration will ensure Arbele continues to have at least 1-2 new molecular entities (NMEs) successfully filing for investigational new drug (IND) application and entering clinical studies in the next 5 years without any technical and supply-chain interruptions. The first deliverable will be anti-CDH17 ADC (ARB102A), for IND submission in early 2025.

"Chime Biologics has partnered Arbele for several years, with our advanced biologics development supporting key milestones such as previous IND filings for multinational clinical trials," said Dr. Jimmy Wei, President of Chime Biologics. "We adopt the Quality-by-Design (QbD) strategy for process development to yield optimal outcomes cost-effectively, delivering innovative immunotherapeutics to enhance the global accessibility of these treatments."

On October 9, 2024 Harbour BioMed (the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on oncology and immunology, reported the online publication of the results from its phase I clinical trial of porustobart (HBM4003), the Company’s first-in-class fully human heavy chain antibody targeting CTLA-4 (Press release, Harbour BioMed, OCT 9, 2024, View Source [SID1234647111]). The trial evaluated porustobart in combination with the anti-PD-1 antibody toripalimab for the treatment of advanced solid tumors, with a particular focus on melanoma. These results were published in the Journal for ImmunoTherapy of Cancer (IF=10.3, 2023).

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 multicenter, open-label phase I trial was led by Dr. Jun Guo, Chief Physician of the Department of Melanoma and Soft Tissue Sarcoma at Beijing Cancer Hospital. The data demonstrated that the combination of porustobart and toripalimab had a manageable safety profile with no new safety signals in the treatment of solid tumors. Initial results also indicated promising antitumor activity, particularly in PD-1 treatment-naïve mucosal melanoma.

Dual immunotherapy combining anti-CTLA-4 and anti-PD-1 antibodies is currently approved as a frontline treatment for several solid tumors, including melanoma, renal cell carcinoma, and non-small cell lung cancer. However, the high toxicity associated with anti-CTLA-4 antibodies has limited their broader use. Porustobart, a next-generation fully human anti-CTLA-4 antibody developed using the HCAb Harbour Mice platform, is the first of its kind to enter clinical development globally. Its unique properties offer the potential to overcome the efficacy and toxicity challenges of conventional anti-CTLA-4 therapies, making it a promising candidate in the field of cancer immunotherapy.

The phase I trial was conducted in two stages: a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). A total of 40 patients received treatment aimed at evaluating the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of the combination therapy for the treatment of solid tumors, with a particular focus on melanoma.

Safety Results

Among the 40 patients who received study treatment, 10 (25.0%) patients reported grade ≥3 treatment-related adverse events (TRAEs). The commonly reported TRAEs were rash (30.0%), abnormal liver function (30.0%), leukopenia (25.0%), and fever (20.0%). Additionally, 5 (12.5%) patients experienced immune-related adverse events (irAEs) with maximum severity of Grade 3. No Grade 4 or 5 irAEs occurred.

Efficacy Results

Efficacy was evaluated in 32 melanoma patients treated with the recommended phase II dose (RP2D) of porustobart 0.3 mg/kg combined with toripalimab 240 mg every three weeks (Q3W), and who had available post-baseline imaging data. The objective response rate (ORR) was 33.3% in the anti-PD-1/PD-L1 treatment-naïve subgroup. For patients with mucosal melanoma, the ORR in this anti-PD-1/PD-L1 treatment-naïve subgroup was 40.0%. A high baseline Treg/CD4+ ratio in the tumor was identified as an independent predictive factor for immunotherapy efficacy.

In summary, the combination of porustobart 0.3 mg/kg with toripalimab 240 mg Q3W demonstrated promising antitumor activity and manageable safety in patients with advanced melanoma, including the difficult-to-treat mucosal subtypes. Further studies are needed to confirm these findings, particularly in patients with mucosal melanoma.

"We are encouraged by the positive results from our phase I study of porustobart in combination with an anti-PD-1 antibody, which has shown a favorable safety profile and early signs of clinical activity," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "Porustobart is the first internally developed molecule generated from our HCAb Harbour Mice platform. We look forward to moving forward with further studies to fully explore the potential of this combination in addressing unmet medical needs and ultimately making a meaningful difference in patients’ lives."

About Porustobart

Porustobart (HBM4003) is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. It is the first fully human heavy-chain-only monoclonal antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 expressing Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect present a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combination therapy.

On October 9, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that the company will present a poster at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics to be held October 23-25, 2024, in Barcelona, Spain (Press release, ORIC Pharmaceuticals, OCT 9, 2024, View Source [SID1234647110]).

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!

Poster presentation details:

Title: ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, demonstrates best-in-class properties against exon 20 insertions and other atypical EGFR mutations
Poster #: PB050
Poster Session: Molecular Targeted Agents
Date & Time: Wednesday, October 23, 2024, 9:00 – 11:00 a.m. CEST
Location: Exhibition Hall

Abstract highlights:
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR and HER2 with high potency against exon 20 insertion mutations and other atypical EGFR mutations. It has previously demonstrated systemic and intracranial clinical responses in patients with EGFR and HER2 exon 20 insertion mutations. In an expanded preclinical comparative analysis, ORIC-114 demonstrated best-in-class properties including brain penetrance, superior kinome selectivity, potent activity across EGFR PACC mutations and exon 20 insertion mutations, relative to firmonertinib, zipalertinib, and BDTX-1535. Additionally, evidence of molecular response in ctDNA from patients whose tumors harbored PACC mutations and exon 20 insertion mutations was observed with ORIC-114 treatment. ORIC-114 is a promising potential therapy for patients with non-small cell lung cancer harboring atypical mutations in EGFR, including those presenting with active CNS metastases, and is being evaluated in a global clinical trial (NCT05315700).

Full abstracts are available for viewing on the symposium website here.

On October 9, 2024 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, reported that it will present the first preclinical data on its novel Werner syndrome helicase (WRN) inhibitor in a poster presentation at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain (Press release, Nimbus Therapeutics, OCT 9, 2024, View Source [SID1234647109]).

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!

WRN is a helicase required for DNA replication and DNA repair and is a validated target for tumors with microsatellite instability (MSI). Nimbus will present preclinical data on NTX-452, a novel WRN inhibitor developed using the company’s computational drug discovery platform.

Details of the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium presentation are as follows:

Abstract Title: Preclinical Characterization of NTX-452, a Potent, Selective and Highly Efficacious WRN Inhibitor for the Treatment of MSI-H Tumors

Date: Friday, October 25, 2024

Time: 9:00 a.m. – 3:00 p.m. CEST

Session Title: DNA Repair Modulation (e.g. PARP, CHK, ATR, ATM)

Abstract Number: 356