On May 06, 2024 ArteraAI, the developer of multimodal artificial intelligence-based prognostic and predictive cancer tests, reported the validation of its first multimodal artificial intelligence (MMAI) digital pathology-based post-radical prostatectomy biomarker for stratifying risk of metastasis and identifying differential absolute benefit for the addition of hormone therapy to salvage radiation therapy in radical prostatectomy patients with biochemical recurrence (BCR) (Press release, Artera, MAY 6, 2024, View Source [SID1234642708]).

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Researchers successfully trained and validated the model for patients who experience BCR after radical prostatectomy surgery, which is strongly associated with the risk of the disease spreading. The data was presented by Dr. Todd Morgan from Michigan Medicine as an oral presentation at the 2024 AUA Annual Meeting, on Sunday, May 5, 2024.

A radical prostatectomy is the removal of the prostate in a patient with prostate cancer and has served as a primary treatment for this disease for many years. However, about 20-40% of patients who undergo the procedure eventually develop BCR, which is an indicator of the cancer returning. In this event, salvage radiotherapy is usually recommended and clinicians are also faced with the decision of whether to further intensify the treatment by combining the salvage radiotherapy with hormone therapy.

"There is a continued need to optimize treatment for men with BCR post-radical prostatectomy to avoid both over- and under-treatment," said Morgan, urological surgeon and Chief of Urologic Oncology at Michigan Medicine. "In the near future, clinicians and patients may be able to use this digital pathology-based biomarker to better understand the risk of further disease progression and inform the treatment plan for these patients in particular."

For the study, researchers aimed to develop a novel biomarker for patients with BCR post-radical prostatectomy using multimodal deep learning on digital histopathology to stratify the risk of distant metastasis. Data from two Phase 3 randomized trials, NRG/RTOG 9601 and 0534, were used for development and validation. Clinical and histopathological data were available for 1,855 of the 2,573 eligible patients (72.1%). The training cohort included 1,322 men and the validation cohort included 533 men. Digitized images of prostatectomy tumor samples were utilized to develop an MMAI model to estimate the risk of distant metastasis and identify benefits from adding hormone therapy to salvage radiation therapy.

"We’re thrilled to have had the opportunity for our data to be presented at AUA," said Andre Esteva, Co-founder and CEO of ArteraAI. "These data exemplify how ArteraAI plans to extend its platform in the future for patients who have undergone a radical prostatectomy."

Prior to this research, no AI-based models had been developed in cohorts of radical prostatectomy patients. This is the first MMAI digital pathology-based post-radical prostatectomy biomarker that has successfully been trained and validated using data from Phase 3 clinical trials of men post-prostatectomy to show prognostic capability for all tested endpoints as well as differential absolute benefit for the addition of hormone therapy to salvage radiation therapy.

For more information on ArteraAI, visit Artera.ai.

On May 06, 2024 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315), a global biotechnology company focused on the discovery of novel antibody-based therapeutics, reported a TCR-mimic antibody evaluation and potential licensing agreement with BioCopy AG ("BioCopy"), a research-based biotechnology company headquartered in Basel, Switzerland (Press release, Biocytogen, MAY 6, 2024, View Source [SID1234642707]).

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The agreement grants BioCopy access to fully human TCR-mimic antibodies targeting an intracellular antigen generated by Biocytogen’s proprietary RenTCR-mimicTM mice. BioCopy will conduct an evaluation and retain the option to license these antibodies for the development of novel cancer therapies.

"We are glad to provide BioCopy with our TCR-mimic antibodies," said Dr. Yuelei Shen, President and CEO of Biocytogen. "Our in vivo matured TCR-mimic antibodies demonstrated favorable affinity and excellent specificity. Combined with BioCopy’s expertise in TCR-mimic antibody screening and engager development, we are optimistic that our collaboration will generate novel drugs that benefit cancer patients."

BioCopy will use Biocytogen’s TCR-mimic antibodies and test them against promising intracellular tumor associated antigens. Here, BioCopy will use its automated end-to-end platform for the optimization of multispecific biotherapeutics to further develop these TCR-mimic antibodies into next-generation oncological drugs.

About Biocytogen’s TCR-mimic Antibody Discovery Platform

Biocytogen’s TCR-mimic platform focuses on the discovery of fully human antibodies to intracellular targets that are presented on the cell surface by MHC class I molecules. Leveraging proprietary RenTCR-mimicTM (HLA/RenMab) mice and specialized immunization protocols, Biocytogen’s platform is designed to generate TCR-mimic antibodies that are highly specific for peptide/HLA complexes and not HLA itself. Using a high-throughput antibody screening platform, Biocytogen swiftly identifies TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients to overcome tumor immune escape. Currently, antibody hits for multiple intracellular targets, including TAAs, cancer-testis antigens, mutated protein antigens, and viral protein antigens, are being evaluated in vivo and in vitro. Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies.

On May 06, 2024 Arsenal Biosciences, Inc. (ArsenalBio), a clinical stage programmable cell therapy company focused on engineering advanced CAR T-cell therapies for solid tumors, reported the presentation of four abstracts at the American Society of Gene + Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting in Baltimore, Md., May 7-11, 2024 (Press release, ArsenalBio, MAY 6, 2024, View Source [SID1234642706]). These data highlight the portfolio of solutions ArsenalBio is developing to address unmet need in solid tumor cancers, including those currently being studied as potential treatments for ovarian cancer (NCT05617755) and kidney cancer (NCT06245915).

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"We continue to advance the science of CAR T-cell therapy and to develop new tools to improve the potency and persistence of our fundamental integrated circuit T cell technology"

"We continue to advance the science of CAR T-cell therapy and to develop new tools to improve the potency and persistence of our fundamental integrated circuit T cell technology," said Nick Haining, B.M., B.Ch., ArsenalBio’s Co-Founder and Chief Scientific Officer. "The entry into the clinic with our second T cell medicine just five years into our company’s journey is a testament to the rigorous nature of our approach, the robustness of our data, and the urgency of our purpose – to address the unmet need for safe and effective treatments for solid tumor cancers."

The following abstracts will be presented as poster presentations during the ASGCT (Free ASGCT Whitepaper) annual meeting.

Abstract 811: Development of AB-2100, a PSMA-inducible anti-CA9 CAR T cell therapy intended for the treatment of ccRCC
Date and Time: May 8, 2024 at 12:00 p.m.
Presenter: Mark Landon, M.S.

AB-2100 is designed to treat relapsed/refractory clear cell renal cell carcinoma (ccRCC). It is an autologous integrated circuit T (ICT) cell product, generated by inserting a DNA cassette into a safe harbor locus within the T cell. It is designed to use three mechanisms to attack tumors while sparing healthy tissues: a logic gate requiring the presence of two antigens in the tumor microenvironment; a synthetic pathway activator (SPA) that enhances antitumor activity; and shRNAs that armor it against immunosuppression. These T cell functions were tested in xenograft models to study the specificity of the logic gate in addressing tumors expressing CA9 as well as both PSMA and CA9 (as the CAR T cells are designed to do). This approach was shown to be successful in overcoming the suppressive mechanisms of the tumor microenvironment and addressing ccRCC expressing both PSMA and CA9 in xenograft models.

Abstract 782: Development of a microscopy-based IF/ISH assay for detection of ICT cells in patients treated with AB-1015
Date and Time: May 8, 2024 at 12:00 p.m.
Presenter: Nickolas Attanasio

AB-1015 is an autologous, genetically modified integrated circuit T (ICT) cell product in clinical development for the treatment of ovarian cancer. It integrates an "AND" logic gate designed to limit off-tumor toxicity through a requirement for dual tumor antigen recognition. To better understand the performance characteristics of AB-1015 ICT cells in human tissue, a custom multiplex immunofluorescence (mIF) assay was developed using the RNAScope platform to detect CD3 protein and mRNA transcripts of both the PrimeR and CAR portion of the circuit by in situ hybridization (ISH). After validation in xenograft models, the assay was used to detect ICTs in one on-trial tumor biopsy sample of an AB-1015 patient.

Abstract 839: Single-cell, pooled CRISPR screening reveals T cell intrinsic regulators of exhaustion in context of chronic antigen stimulation
Date and Time: May 8, 2024 at 12:00 p.m.
Presenter: Glenn Wozniak, Ph.D.

T cell exhaustion from chronic antigen stimulation and an immunosuppressive tumor microenvironment limits the efficacy of T cell therapies used to treat solid tumors. This research used CRISPR/Cas9-based screening, paired with deep sequencing, to identify intrinsic genetic perturbations that can prevent T cell exhaustion. By developing pools of genetically engineered CAR T cells each designed to achieve up- or down-regulation of a single target gene and subjecting the pools to chronic antigen stimulation to replicate hallmarks of T cell exhaustion, we can understand the function of individual genetic changes on T cell function. Our results demonstrated the potential for pooled CRISPR screening to measure complex phenotypes and provided data to direct the development of future advanced CAR T cell therapies.

Abstract 814: Development of logic-gated "Payload" module in CAR T cells aimed at increasing local concentration of a secreted pro-inflammatory module in an antigen-dependent manner
Date and Time: May 8, 2024 at 12:00 p.m.
Presenter: Gavin Shavey, M.S.

This experiment aimed to study whether the logic-gated secretion of a pro-inflammatory module (Payload) could provide an ICT-extrinsic enhancement to the success of these therapies by supporting activation of the endogenous immune system to aid in the anti-tumor response. The study evaluated the ability of a variety of supplemented cytokines to enhance both the ICT and the bystander immune cells anti-tumor function in vitro by engineering and testing 30+ cytokine variants to be secreted as Payloads. Incorporation of such Payloads into ICT cells resulted in significant augmentation of anti-tumor activity. We showed Payloads can enhance the function of both ICT and bystander immune cells without signs of increased transformation risk and can increase capacity for tumor clearance in vivo at significantly lower dosage.

For more information about ArsenalBio, visit www.arsenalbio.com.

On May 6, 2024 Geneoscopy, Inc., a life sciences company focused on developing diagnostic tests for the advancement of gastrointestinal health, reported that the U.S. Food and Drug Administration (FDA) approved its noninvasive colorectal cancer screening test, ColoSense (Press release, Geneoscopy, MAY 6, 2024, View Source [SID1234642705]). ColoSense is indicated as a screening test for adults, 45 years of age or older, who are at typical average risk for developing CRC.

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Designated as a Breakthrough Device by the FDA, ColoSense is the first noninvasive colorectal cancer screening test to provide a dynamic view of disease activity by using RNA biomarkers. RNA biomarkers are not subject to age-related methylation patterns that can lead to variability in test performance across different age groups.1-2

"Securing FDA approval for ColoSense marks a significant milestone for Geneoscopy and demonstrates that our patented RNA technology can provide millions of eligible adults with a safe and effective option for detecting CRC and advanced adenomas," said Andrew Barnell, CEO and co-founder of Geneoscopy. "This achievement is a testament to our deep dedication and commitment to bringing innovative technology to market that will improve outcomes for this deadly, yet preventable, disease."

Geneoscopy’s CRC-PREVENT trial evaluated participants aged 45 and older from various racial, ethnic, and socioeconomic backgrounds. Using a novel decentralized enrollment approach, 64% of participants had never been screened for colorectal cancer, and 68% of participants had not scheduled a colonoscopy at the time of enrollment. This is unlike traditional centralized trials, in which patients are typically already engaged in healthcare screening programs. In average-risk individuals, ColoSense successfully demonstrated 93% sensitivity for CRC and importantly identified 100% of CRC in Stage I, when the disease is most curable. Additionally, ColoSense detected 45% of advanced adenomas, when the disease is most preventable. Notably, the study reported 100% CRC sensitivity and 44% AA sensitivity in patients aged 45-49, a critically important screening demographic.

Colorectal cancer is the second deadliest cancer in the United States. However, millions of eligible Americans do not get screened due to a lack of access to or avoidance of invasive options like colonoscopies. CRC incidence rates are also rising among younger populations under 50 years old, prompting a recent shift in the United States Preventive Services Task Force’s guidelines to recommend initiation of CRC screening at age 45.3 Underscoring the critical nature of this issue, the American Cancer Society recently reported that colorectal cancer is now the leading cause of cancer death for males and the second leading cause of death for females under 50.4 Further compounding this challenge, approximately 40% of unscreened and eligible Americans are ages 45-49.5,6

"The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients," said Anjee Davis, president of Fight CRC. "We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses."

FDA approval of ColoSense is a significant step in making this important screening tool available to patients. Geneoscopy is working with payors, professional societies, and advocacy partners to support a commercial launch later this year or early in 2025 to ensure patients have timely access to ColoSense to support CRC screening. Geneoscopy will launch ColoSense in collaboration with Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services.

About ColoSense

ColoSense is intended for the qualitative detection of colorectal neoplasia-associated RNA markers and for the presence of occult hemoglobin in human stool. ColoSense is for use with the ColoSense Collection Kit, the ColoSense Test Kit, the ColoSense Software, and the following instruments: Polymedco iFOBT Analyzer; bioMérieux EMAG Nucleic Acid Extraction System; and Bio-Rad QXDx ddPCR System. ColoSense is a single-site test performed at Geneoscopy, Inc.

A positive ColoSense result may indicate the presence of colorectal cancer (CRC), advanced adenomas (AA), or serrated precancerous lesions (SPL) and should be followed by a colonoscopy. ColoSense is indicated as a screening test for adults, 45 years of age or older, who are at typical average risk for developing CRC. ColoSense is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-risk individuals.

Results from Geneoscopy’s pivotal CRC-PREVENT trial were published in The Journal of the American Medical Association (JAMA) in October 2023. For more information, visit www.colosense.com.

On May 6, 2024 Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ("Calliditas") reported data from the proof-of-concept Phase 2 trial evaluating setanaxib, its lead NOX enzyme inhibitor, in combination with pembrolizumab, in patients with squamous cell carcinoma of the head and neck (SCCHN) (Press release, Calliditas Therapeutics, MAY 6, 2024, View Source [SID1234642704]). The analysis showed statistically significant improvements in progression-free survival (PFS), as well as in overall survival (OS), with statistically significant changes in tumor biology consistent with the mechanism of action of setanaxib.

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The trial is a randomized, placebo-controlled, double-blind Phase 2 study investigating the effect of setanaxib 800mg twice daily in conjunction with pembrolizumab 200mg IV, administered every 3 weeks (a standard treatment regimen for SCCHN) with the full dataset reflecting all patients having had the opportunity to complete at least 15 weeks of treatment. The basis for the analysis consisted of a dataset of 55 patients with recurrent or metastatic SCCHN and moderate or high CAF-density tumors (Cancer Associated Fibroblasts). A tumor biopsy was taken prior to randomization and then again after at least 9 weeks of treatment.

The treatment groups were well-balanced with no clinically relevant differences between the groups observed at baseline. Patients treated with pembrolizumab and setanaxib showed statistically significant improvements in key secondary endpoints, such as progression-free survival, (PFS median 5 months versus 2.9 months; Hazard ratio= 0.58) and statistically significant improvement in overall survival (OS at 6 months 92% vs 68%; OS at 9 months 88% vs 58%; Hazard ratio=0.45) compared to patients treated with pembrolizumab and placebo. There was also an improvement in disease-control rate in setanaxib-treated patients, with 70% in the setanaxib arm showing a best response of at least stable disease compared to 52% in the placebo arm. No significant difference in the primary endpoint of best percentage change from baseline in tumor size was observed. Transcriptomic analysis of tumor biopsy samples showed a statistically significant increase in CD8+ T-cells in tumor tissue from patients treated with setanaxib, indicating an increase in tumor immunological activity consistent with the mechanism of action of setanaxib. The tolerability of setanaxib when given with pembrolizumab was generally good, with no new safety signals identified.

"It is very encouraging to see statistical significance on important clinical outcomes in this relatively small study, which provides an excellent basis for advancing setanaxib in this hard-to-treat population," said Kevin Harrington, Professor in Biological Cancer Therapies at The Institute of Cancer Research (ICR) London, Consultant Clinical Oncologist at The Royal Marsden NHS Foundation, London, and Investigator on the trial.

"This is a very exciting result which provides clinical evidence of the mode of action of setanaxib in line with our thesis of its anti-fibrotic effects, and with results beyond our expectations for a study of this size. It is exciting that we now have positive clinical evidence in support of our first in class NOX platform," said CEO Renée Aguiar-Lucander.

"I am delighted that we have seen statistical significance and clinically meaningful improvements in longer term outcomes of PFS and OS in this indication. I’d like to extend my thanks to investigators, clinical trial site staff, and most importantly patients, who have all contributed to this important study," said CMO Richard Philipson.

The company is conducting additional clinical trials with setanaxib and will read out its Phase 2 trial in PBC (primary biliary cholangitis) in Q3 of 2024 and is expecting the investigator led Phase 2 trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in Q4 of 2024, subject to recruitment. There is also an ongoing Phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 1H, 2025.

The company plans to arrange an R&D day in Stockholm later this month to provide additional details regarding the Phase 2 trial and other data supporting the mechanism of action of setanaxib. Further details will be provided by way of a press release.