On April 11, 2023 Beactica Therapeutics AB, the Swedish precision oncology company, reported that its LSD1 programme has been selected for a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting 2023 (Press release, Beactica, APR 11, 2023, View Source [SID1234629971]). The conference will take place on April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida.

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Dr Konrad Koehler, Head of Discovery, will present a poster entitled Potentiation of Immunotherapy by LSD1 Modulation on Sunday April 16, 2023, at 1:30 PM – 5:00 PM. The location is at the Orange County Convention Center, Section 24, Abstract Presentation Number: 705. The session category is Immunology.

Beactica Therapeutics’ poster presentation will include new positive results with BEA-17 from in vitro and in vivo studies, including potentiation of anti-PD1 checkpoint inhibitors in a syngeneic animal model of colon cancer (CT26) and potentiation of standard of care (radiation + temozolomide) in a syngeneic animal model of glioblastoma (GL261).

BEA-17 was recently granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of glioblastoma (GBM).

Organised by the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the AACR (Free AACR Whitepaper) Annual Meeting is the largest and most important cancer drug discovery event in the world. It has an anticipated attendance of more than 20 000 scientists, clinicians, advocates, and other attendees. The event spans integrative cancer science, global impact, individualised patient care and showcases the best and most up-to-date cancer science available.

About BEA-17

BEA-17 is a first-in-class small molecule targeted degrader (non-PROTAC) of the epigenetic enzyme LSD1 and its co-factor CoREST. The compound has shown promising preclinical in vivo potentiation of immune-modulating treatments in several cancer forms, including anti-PD1 checkpoint inhibitors in syngeneic models of colon cancer (CT26) and standard of care (temozolomide and radiation) in syngeneic models of glioblastoma (GL261). Pharmacokinetic studies of BEA-17 show good blood-brain-barrier penetration and oral availability. BEA-17 is investigational and not approved anywhere globally. Its efficacy and safety in humans have not been established. BEA-17 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of glioblastoma (GBM).

On April 11, 2023 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, reported the recent initiation of dosing of HST-1011 in its Phase 1/2 clinical trial in patients with advanced solid tumors (Press release, HotSpot Therapeutics, APR 11, 2023, View Source [SID1234629970]). HST-1011 is an orally bioavailable, potent, selective small molecule allosteric inhibitor of casitas B-lineage lymphoma-B (CBL-B).

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"Dosing of the first patient with HST-1011 is an important milestone for HotSpot signifying our evolution into a clinical-stage company with the first-in-human dosing of a product candidate derived from our proprietary Smart Allosterydrug discovery platform," said Tim Reilly, Ph.D., Chief Development Officer of HotSpot. "Importantly, we believe that HST-1011, as a highly potent and selective inhibitor of the long sought after target CBL-B, may represent an important new immunotherapy treatment option for cancer patients."

The Phase 1/2 study of HST-1011 is an open-label clinical study designed to evaluate HST-1011 alone and subsequently in combination with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), in patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. Additional information on this clinical trial can be found on www.clinicaltrials.gov (NCT05662397). The combination therapy component of the study is enabled by a clinical supply agreement with Regeneron for provision of Libtayo.

"Despite tremendous progress in the field of immuno-oncology (I-O), significant unmet need persists for patients with advanced solid tumors, as many cancers are found to be unresponsive to or lack durable responses following treatment with currently available therapies," said Jason Luke, M.D., F.A.C.P., Director of the Immunotherapy and Drug Development Center at the University of Pittsburgh Medical Center’s Hillman Cancer Center and the lead Principle Investigator on HotSpot’s ongoing Phase 1/2 clinical study. "We believe CBL-B’s role as a master regulator of immune cell activation presents a differentiated therapeutic opportunity. We are excited to explore this novel mechanism and new I-O treatment in collaboration with HotSpot and the other investigators and sites participating in this trial."

HotSpot will be presenting the HST-1011 first-in-human Phase 1/2 clinical trial design at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, Florida, during the Clinical Trials in Progress poster session. The details for the presentation are as follows:

Title: Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD-1 in patients with advanced solid tumors
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Session Date and Time: Tue., Apr. 18, 1:30-5:00 PM ET
Location: Poster Section 46
Poster Board Number: 14
Abstract Number: CT251

About HST-1011
HST-1011 is an investigational orally bioavailable, selective, small molecule allosteric inhibitor of CBL-B, an E3 ubiquitin protein ligase critically involved in immune cell response. Because CBL-B functions as a master regulator of effector cell (T cell and natural killer cell) immunity, its inactivation removes its endogenous negative regulatory functions to substantially enhance anti-tumor immunity. Preclinical data has demonstrated HST-1011’s ability to bind to and inhibit a natural hotspot on CBL-B, yielding the activation and propagation of a targeted anti-tumor immune response. Enabled by HotSpot’s proprietary Smart Allostery platform, HST-1011 is designed with tight binding, low nanomolar potency, a slow dissociation rate from the target to enable sustained pharmacology, and greater selectivity for CBL-B relative to C-CBL.

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