On April 11, 2023 OnCusp Therapeutics, a global biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported that the preclinical data on its lead program CUSP06 will be presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida (Press release, OnCusp Therapeutics, APR 11, 2023, View Source [SID1234629969]).

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The poster presentation will showcase data demonstrating that CUSP06, a high affinity anti-CDH6 Antibody Drug-Conjugate (ADC) with an exatecan payload (DAR8), shows potent anti-tumor activity in multiple preclinical models, demonstrates significant differentiation from a DXd-payload competitor, and is well tolerated in mice, rats and cynomolgus monkeys.

POSTER PRESENTATION DETAILS

Title: CUSP06/AMT-707, a new CDH6-targeting antibody-drug conjugate, demonstrates potent antitumor activity in preclinical models

Session Category: Experimental and Molecular Therapeutics
Session Date and Time: Wednesday Apr 19, 2023, 9:00 AM – 12:30 PM
Location: Poster Section 21
Poster Board Number: 27
Published Abstract Number: 6320

The abstract is available here and the Poster will be available on the OnCusp website shortly after the presentation.

"We are very excited to present data highlighting the exciting preclinical profile of CUSP06, a differentiated, potential global second-in-class CDH6 ADC, as we pivot to become a clinical stage company this year" stated Eric Slosberg, PhD, Chief Development Officer and co-founder of OnCusp Therapeutics.

About CUSP06:

CUSP06, a preclinical-stage CDH6 ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is specially designed to complement the exatecan payload, generating a highly stable and homogenous ADC. The payload is a weak substrate for BCRP/Pgp. In preclinical data, this linker/payload has been shown to enable a stronger "bystander effect" than competitor ADCs. CUSP06 has a drug-to-antibody ratio of 8. OnCusp obtained the exclusive global rights (ex-China) to lead the development and commercialization of CUSP06, from Multitude Therapeutics.

On April 11, 2023 Quadriga BioSciences, a clinical-stage oncology company developing QBS10072S (QBS72S) for the targeted treatment of cancer, reported the dosing of the first subject in a Phase 2 study evaluating QBS72S for the treatment of brain metastases of breast cancers (Press release, Quadriga BioSciences, APR 11, 2023, View Source [SID1234629968]).

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"The treatment of brain metastases is a significant unmet need in oncology, as no approved therapies exist," said Gordon Ringold, Ph.D., Chief Executive Officer of Quadriga BioSciences. "With its ability to cross the blood brain barrier and target cancer cells, QBS72S has the potential to improve outcomes in these patients. We look forward to investigating this more closely with our colleagues at Stanford Medicine."

Most therapies for breast cancer have limited efficacy when metastasized to the brain, due in part to the inability for current chemotherapeutics to cross the blood brain barrier (BBB) in sufficient concentrations.

"Breast cancer is one of the most common tumors to metastasize to the brain. Breast cancer brain metastases worsen prognosis, negatively affect quality of life, and currently available treatments are limited," said Melanie Hayden Gephart, M.D., Professor of Neurosurgery at Stanford Medicine, co-director of the Stanford Brain Tumor Center, and Principal Investigator of the Phase 2 clinical study. "QBS72S has shown promise in preclinical studies due to its targeted mechanism of action. I look forward to the opportunity to investigate this compound for patients in need."

QBS72S is also being investigated as a potential glioblastoma treatment in the Phase 2 INSIGhT study at the Dana-Farber Cancer Institute (find more information here). The two Phase 2 studies are each funded by Small Business Innovation Grants (SBIR). The breast cancer study received initial support from the California Breast Cancer Research Program.

About QBS72S

QBS72S is a novel, first-in-class chemotherapeutic agent that mimics an aromatic amino acid for cellular uptake by the amino acid transporter LAT1 (L-type amino acid transporter 1) thereby enabling the drug to cross the blood brain barrier (BBB) as well as to selectively target numerous types of rapidly growing cancer cells. Once inside the cell QBS72S causes double-stranded DNA breaks resulting in cell death. Most aggressive cancers express high LAT1, which is commonly associated with poor prognoses.1

About the Study

The Phase 2 open-label clinical trial is designed to assess the safety, tolerability and efficacy of QBS72S in patients with brain metastases from breast cancer. The study will recruit up to 35 patients with the primary objective of determining preliminary efficacy through overall response rate. Secondary endpoints include measurement of progression free survival, overall survival, duration of response, and adverse events.

Please refer to www.clinicaltrials.gov [NCT05305365] for additional clinical trial details.

On April 11, 2023 Lunit reported that New findings demonstrate important progress in the development of novel diagnostics for immunotherapy among other important cancer therapies (Press release, Lunit, APR 11, 2023, View Source [SID1234629967]). Lunit will deliver five poster presentations featuring its AI-biomarker platform, Lunit SCOPE IO, at the annual meeting to be held in Orlando, Florida, on April 14-19.

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One of the studies to be presented evaluates a deep learning-based ensemble model to predict the KRAS G12C mutation, most common among KRAS gene mutations, which accounts for 25% of non-small cell lung cancer patients. Employing the AI model developed using samples from The Cancer Genome Atlas LUAD and LUSC (TCGA-Lung), researchers conducted a novel approach to improve the performance of KRAS G12C prediction.

According to the research, the prediction model showed improved accuracy compared to previously reported KRAS mutation prediction studies. The Lunit SCOPE based KRAS G12C mutation prediction model showed a high predictive power with an AUC (Area Under the Curve) of 0.787, indicating the accuracy of the AI algorithm. It also showed AUC of 0.745 in validation with independent external data.

"As the KRAS G12C mutation has become targetable in NSCLC, tissue-based KRAS mutation tests are now an essential practice for treatment decisions," explained Chan-Young Ock, Chief Medical Officer at Lunit. "By combining simple H&E analysis model with Lunit SCOPE IO’s in-depth predictive features, our novel approach showed significant improvement in prediction. In the future, we believe that such a model will be able to provide predictive results before applying molecular testing, which is relatively time-consuming and expensive, and may help enable rapid treatment decisions."

Another study demonstrates the effectiveness of Universal immunohistochemistry (UIHC), an AI-powered image analyzer, in detecting and quantifying untrained new targets of interest expressed in multiple cancer types. The AI model was trained on the dataset of PD-L1 and HER2 stained lung, bladder, and breast cancer slides, and evaluated on its performance on the hold-out IHC dataset of untrained target and cancer types. Compared to the AI models trained with a single IHC and cancer type, UIHC showed superior performance for new IHC and cancer types. Researchers concluded that UIHC model will be a useful tool for the future clinical research targeting novel tumor-associated antigens.

Other studies to be presented further demonstrate the effectiveness of Lunit SCOPE IO as a diagnostic aid in the treatment of various cancer types.

Lunit SCOPE IO analyzes a patient’s cancer tissue slide image by observing the distribution of tumor-infiltrating lymphocytes (TIL)—one of the immunocytes that fight cancer cells. Based on the spatial distribution pattern of TILs and cancer cells in the tumor microenvironment, Lunit SCOPE IO identifies the tissue sample as one of three immune phenotypes (IP): inflamed, immune-excluded, or immune-desert.

In one study assessing Lunit SCOPE IO as a predictive biomarker for anti-PD-1 therapy in advanced biliary tract cancer (BTC), researchers conducted a retrospective analysis of the relationship between the clinical outcomes and TIL using the AI solution. After analysis of pre-treatment whole slide images and clinical outcomes, patients with the inflamed IP had favorable clinical outcomes after anti-PD-1 therapy than other phenotype groups, showing that immune phenotypes as classified by Lunit SCOPE IO could be an effective biomarker to predict the clinical outcomes of patients with advanced BTC.

Other studies include an analysis of the distribution of TILs and associated genomic signatures based on proximity to the tumor-stromal border (TSB) in the TCGA pan-carcinoma dataset, as well as an application of Lunit SCOPE IO in the TCGA ovarian cancer dataset demonstrating the enrichment of inflammatory immune and transcriptomic traits in the Inflamed IP classified by the AI solution.

"We are excited to bring new research using Lunit SCOPE in more cancer types and treatment settings," said Brandon Suh, CEO of Lunit. "Lunit will continue to enable novel academic research and innovative product development to provide the most appropriate treatment for cancer patients."

Visit the Lunit team at Booth 2671. Reach out to schedule a meeting at ([email protected]).

Lunit’s Abstracts at AACR (Free AACR Whitepaper) 2023

1. 5399 / 15 – Deep learning-based ensemble model using H&E images for the prediction of KRAS G12C mutations in non-small cell lung cancer

2. 5392 / 8 – Universal immunohistochemistry positivity classification of cancer cells across multiple cancer types and antibodies using artificial intelligence

3. 4333 / 8 – Spatial analysis of tumor-infiltrating lymphocytes in tumor microenvironment as biomarker for immune checkpoint inhibition in biliary tract cancer

4. 5389 / 5 – Micron-resolution spatial analysis near the tumor-stromal border reveals a distinct density distribution of tumor-infiltrating lymphocytes and related genomic features

5. 5446 / 29 – Immune phenotypes classified by deep learning-based H&E tissue analyzer demonstrate distinct immune landscape and transcriptomic features in ovarian cancer

On April 11, 2023 Virtuoso Therapeutics, Inc., a private oncology-focused company developing novel bispecific antibodies reported that it will present three posters highlighting the preclinical data from leading bispecific antibody and ADC programs at the American Associate for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting (Press release, Virtuoso Therapeutics, APR 11, 2023, View Source [SID1234629966]).

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The details of the Company’s presentations at the AACR (Free AACR Whitepaper) are as follows:

Poster Presentation #1870:

Title: VBI–003, a CD47xEpCAM bispecific antibody as a potential treatment for colorectal and small cell lung cancers
Session Category: Immunology
Session Title: Therapeutic Antibodies 1
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 17th 9:00AM-12:30PM
Location: Section 25

Poster Presentation #6334:

Title: VBI-002, a CD47xICAM-1 bispecific antibody for the treatment of hepatocellular carcinoma, melanoma and non-small cell lung cancers
Session Category: Immunology
Session Title: Anticancer Immunotherapeutics
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 19th 9:00AM-12:30PM
Location: Section 22

Poster Presentation #6298:

Title: A novel topoisomerase I inhibitor based anti-ICAM–1 antibody drug conjugate for the treatment of hematologic malignancies and solid tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Growth Factor Receptors as Therapeutic Targets
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 19th 9:00AM-12:30PM
Location: Section 21

"We believe that our best-in-class CD47 bispecific antibodies confer greater tumor selectivity without sacrificing potency and efficacy. They have been optimized and are ready to begin IND enabling studies," said Sofie Qiao, PhD, President and CEO of Virtuoso Therapeutics. Posters will be available at www.virtuosotherapuetics.com after the meeting.

On April 11, 2023 Strata Oncology, Inc. ("Strata"), a next-generation precision oncology company enabling smarter and earlier cancer treatment, reported that it will present new data in four scientific posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place April 14-19, 2023 in Orlando, Florida (Press release, Strata Oncology, APR 11, 2023, View Source [SID1234629965]).

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The data to be presented includes results for innovative, proprietary predictive biomarkers for fam-trastuzumab-deruxtecan-nxki, sacituzumab govitecan and pembrolizumab. Strata has developed these biomarkers and others using data collected through an observational clinical trial protocol called the Strata Trial (NCT03061305). All of these biomarkers take advantage of the company’s unique molecular profiling platform that combines DNA and quantitative RNA sequencing on a single small tumor tissue sample.

Strata Oncology to present new data in four scientific posters at the AACR (Free AACR Whitepaper) Annual Meeting, taking place April 14 – 19.

"Strata Oncology is leading the way in bringing expression-based therapies, such as antibody-drug conjugates and immunotherapies, into the precision era with highly quantitative RNA and multivariate predictive treatment selection algorithms," said Scott Tomlins, M.D., Ph.D., Strata Oncology co-founder and chief medical officer. "Data from the Strata Trial is allowing us to identify new biomarker-guided patient populations for therapies already on the market, thus opening up treatment pathways that can drive better outcomes for more people. We look forward to sharing our latest advances at the AACR (Free AACR Whitepaper) meeting."

Poster presentation details:

Poster Title: 968/19 – Evaluation of Her2 RNA expression as a potential predictive biomarker for anti-Her2 therapy
Track: Biomarkers of Therapeutic Benefit 1
Session Date and Time: Sunday Apr 16, 2023, 1:30 PM – 5:00 PM EDT
Overview: Trastuzumab-deruxtecan is effective in "HER2 Low" (1+ or 2+ expression by immunohistochemistry (IHC)) breast cancer. There is increasing interest in defining a sub-population of IHC 0+ tumors that may have HER2 expression below the limit of IHC detection/quantification and may thus also be responsive. Using data from its high dynamic range assay for HER2 expression and clinical outcome data from the Strata Trial, Strata defined a HER2 RNA low threshold based on IHC from breast cancer patients. At this threshold, nearly half of 0+ breast cancers were classified as HER2 RNA Low, as were more than a quarter of non-breast solid tumors, representing tumors that may be responsive to anti-HER2 therapies. HER2 RNA Low has the potential to be an alternative biomarker to Her2 IHC Low, with the opportunity to further expand trastuzumab-deruxtecan use.

Poster Title: 2171 /13 – A multivariate biomarker predicts sacituzumab govitecan response in solid tumors
Track: Biomarkers of Therapeutic Benefit 3
Session Date and Time: Monday Apr 17, 2023, 9:00 AM – 12:30 PM EDT
Overview: Despite the recent clinical success of antibody drug conjugates (ADCs), such as the TROP2-targeted ADC sacituzumab govitecan (SG), predictive biomarkers for these therapies are lacking. Leveraging DNA and RNA sequencing data and clinical outcomes data from the Strata Trial, Strata developed a multivariate biomarker algorithm, which combines TROP2 and proliferation by gene expression with tumor cellularity, that produced biomarker positive rates correlating with the objective response rates observed for SG in the IMMU-12-01 basket trial. The multivariate biomarker accounts for 67% of the variability observed in SG response rates and may thus identify patients likely to benefit from SG. Interestingly, most tumor types had biomarker positive rates >5%, suggesting the potential for a tumor type-agnostic approach to patient selection. The biomarker has the potential to improve the selection of patients who are more likely to benefit from SG and may be generalizable to other ADCs.

Poster Title: CT059 / 17 – StrataPATH: a multicohort, non-randomized, open-label phase 2 trial to explore efficacy and safety of FDA-approved cancer therapies in novel biomarker-guided patient population
Track: Phase II and Phase III Clinical Trials in Progress
Session Date and Time: Monday Apr 17, 2023, 9:00 AM – 12:30 PM EDT
Overview: The Strata Precision Indications for Approved Therapies (Strata PATH; NCT05097599) trial is a non-randomized open-label, prospective pan-tumor therapeutic trial designed to evaluate the efficacy and safety of multiple FDA-approved cancer therapies in new, biomarker-guided patient populations. Enrollment into a cohort of this basket trial is based on novel biomarkers including DNA, quantitative RNA expression and novel multivariate algorithms that account for both tumor and tumor microenvironment variables hypothesized to predict improved therapeutic response. The therapeutic classes evaluated in Strata PATH include targeted therapies, antibody-drug conjugates, immunotherapies, and angiogenesis inhibitors. Strata PATH provides the next important step forward in precision medicine, guiding clinical trial and therapy selection by expanding biomarker testing to quantifiable RNA expression and multivariant algorithm based molecular testing.

Poster Title: 4348 / 23 – Validation of an integrative pan-solid tumor predictor of pembrolizumab monotherapy benefit
Track: Biomarkers of Therapeutic Benefit 4
Session Date and Time: Tuesday Apr 18, 2023, 9:00 AM – 12:30 PM EDT
Overview: Strata previously reported the development and validation of an integrative Immunotherapy Response Score (IRS) algorithm, which integrates tumor mutation burden (TMB) and quantitative gene expression of tumor and tumor microenvironment biomarkers to predict anti-PD-1 or PD-L1 (together anti-PD-[L]1) monotherapy benefit across solid tumors from routine formalin fixed paraffin embedded samples. Strata has now evaluated IRS performance for predicting immunotherapy benefit in a second, independent validation cohort of patients treated with pembrolizumab monotherapy. As seen before, pembrolizumab monotherapy real-world progression-free survival (rwPFS) was significantly longer in IRS-high vs. IRS-low patients. In a case cross-over analysis of patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS was significantly longer than preceding therapy in IRS-high patients but not IRS-low patients. These results confirm the pan-solid tumor PD-(L)1 monotherapy predictive nature of the IRS biomarker.