On October 27, 2021 DiaCarta Inc., a precision molecular diagnostics company and leading developer of novel oncology tests using liquid biopsy, reported the publication of a study in PLOS ONE that demonstrates that DiaCarta’s ColoScape Xenonucleic Acid (XNA)-mediated quantitative real-time polymerase chain reactions (qPCR) clamping assay detects mutant cell-free DNA (cfDNA) from precancerous colorectal cancer (CRC) lesions and colorectal cancer (Press release, DiaCarta, OCT 27, 2021, View Source [SID1234592074]).

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The paper entitled, "A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening," evaluated the performance of XNA-mediated qPCR clamping technology for the simultaneous and qualitative detection of somatic mutations in CRC patients.1 Nineteen mutations in a panel of genes associated with early events in CRC pathogenesis are targeted in the ColoScape assay.

The ColoScape XNA-mediated qPCR clamping assay is a novel multi-gene mutation diagnostic assay for the qualitative detection of colorectal cancer-associated gene mutations in liquid biopsy and FFPE tissue samples. ColoScape utilizes XNA technology, innovative synthetic Xenonucleic acid molecular oligomers that hybridize with target wild-type DNA sequences. The XNA oligomers act as molecular clamps to enable the accurate amplification of mutant sequences only, using qPCR.

In this study, a total of 380 clinical samples, including plasma cfDNA and FFPE samples from patients with precancerous and different stages of CRC, were analyzed with the ColoScape assay.1 With liquid biopsy the preliminary assay clinical specificity for CRC was 100% and the clinical sensitivity was 92.2%; for precancerous lesions clinical specificity was 95% and clinical sensitivity was 62.5%.1 With FFPE samples the preliminary assay clinical specificity for CRC was 96% and the clinical sensitivity was 92%, making this assay robust, specific and highly sensitive. Currently, DiaCarta has large clinical trials ongoing in Europe, Asia, and US.

"This study validates the diagnostic application of the ColoScape assay in the early detection of precancerous lesions and colorectal cancer based on the amplification and detection of cfDNA mutants from one tube of blood," said Aiguo (Adam) Zhang, Ph.D., CEO, DiaCarta, Inc. "Our technology has the potential to disrupt the standard method of FFPE or stool samples used for the diagnosis of colorectal cancer. ColoScape’s sensitivity and specificity may yield detection of colorectal cancer before the disease progresses to more acute stages. In addition, our new generation of ColoScape test includes a panel of methylation genes powered by XNA, which generates even higher sensitivity, especially for the precancerous lesions."

On October 27, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and NeoCura Bio-Medical Technology Co., Ltd. ("NeoCura"), a leading AI-enabled RNA precision medicine biotech company committed to building a global top RNA innovative drug platform, reported that they have entered into a strategic collaboration agreement to carry out a clinical study in China on the combination therapy of sintilimab from Innovent and individualized neoantigen vaccine NEO_PLIN2101 from NeoCura (Press release, Innovent Biologics, OCT 27, 2021, View Source [SID1234592071]).

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Innovent will collaborate with NeoCura in China to assess the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the combination therapy using sintilimab from Innovent and NEO_PLIN2101 from NeoCura in cancer patients, to advance the clinical development of combination immunotherapy for multiple solid tumors, and prepare to submit the Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) in the near future.

Dr. Liu Yongjun, President of Innovent, stated: "We are impressed by NeoCura’s differentiated R&D pipeline and international research team, and we are pleased to enter into this strategic collaboration to explore the clinical value of sintilimab in combination with neoantigen vaccines for solid tumors. Innovent has a robust pipeline with strong capabilities in immunology and cancer biology. Currently, we have five innovative drugs approved and launched in China and will have more than 10 innovative drugs to be launched in the next 2-3 years. Our fully integrated platform has accumulated strong R&D, clinical development and commercialization capabilities and is ideal for partners at home and abroad. We also hope to further explore the new opportunities in expanding indications and enhancing therapeutic efficacy of sintilimab in combination with novel therapies. We look forward to wider and in-depth collaboration between the two parties in the future. "

Dr. Wang Yi, founder of NeoCura, stated: "At present, neoantigen vaccines are a revolutionary emerging therapeutic approach worldwide. NeoCura has been focusing on the R&D of tumor neoantigen vaccines since its establishment, hoping to overcome the challenges of existing immunotherapy in the treatment of solid tumors through the application of new technologies. The collaboration with Innovent will play a synergistic role of personalized neoantigen vaccines and monoclonal antibody drugs and jointly explore the clinical effect of the combination therapy in the treatment of solid tumors, which is expected to improve the objective response rate of cancer immunotherapy and bring new opportunities for cancer combination regimens."

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of non-squamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has one regulatory submission under review in China for sintilimab, for the first line treatment of esophageal squamous cell carcinoma.

Additionally, four clinical studies of sintilimab have met their primary endpoints:

Phase 3 study in combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma
Phase 2 study as second-line treatment of esophageal squamous cell carcinoma
Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy
Phase 3 study in combination with BYVASDA (bevacizumab biosimilar injection) and chemotherapy (pemetrexed and cisplatin) for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of non-squamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

About NEO_PLIN2101

NEO_PLIN2101 is a personalized neoantigen vaccine developed by NeoCura, which can be custom made according to the unique tumor gene mutation of each patient. Through high-throughput sample sequencing and AI algorithm epitope prediction, high-quality neoantigen fragments that can be efficiently presented by tumor cells and elicit a potent immune response are selected from patient’s tumor sample. The mRNA vaccine encoded corresponding neoantigen is synthesized in vitro, vaccinated into patients to activate tumor-specific T cells to control tumor growth and reduce tumor burden. Compared to conventional approach, NEO_PLIN2101 has stronger specificity and immunogenicity that can induce anti-tumor immune response in cancer patients.

On October 27, 2021 Aston Sci., a portfolio model biopharmaceutical company, reported that the study results of its therapeutic cancer vaccine pipelines, AST-301 and AST-021p, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)(SITC) in November (Press release, Aston Sci, OCT 27, 2021, View Source [SID1234592070]). The respective abstract for AST-301 and AST-021p were accepted by the SITC (Free SITC Whitepaper).

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The data from the study of AST-301, a pDNA-based cancer vaccine, using mice models with HER2-expressing gastric cancer shows the efficacy of monotherapy and combination therapy of the vaccine. At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June, Aston Sci. demonstrated the medical efficacy and long-term safety of AST-301 through the results from phase 1 clinical trials on 66 patients with HER2-positive advanced breast cancer. AST-301 is currently under IND review by the Ministry of Food and Drug Safety for subsequent clinical trials.

Aston Sci. also presents the efficacy of combination therapy of AST-021p using a breast cancer mouse model. AST-021p is an investigational therapeutic cancer vaccine composed of two different peptides which are derived from HLA class II binding epitopes of human HSP90 protein. The results of comparative evaluation on tumor growth inhibition and immunogenicity when used in combination with several immune adjuvants, including "L-pampo" (TLR-2/3 ligand-based immune adjuvant) in-licensed from the CHA Vaccine Institute, will be presented. Currently, AST-021p is in phase 1 clinical trial for recurrent or advanced solid tumors for which there is no standard treatment.

"As cancer has become a disease requiring more prevention and management due to technological advances in early diagnosis, the need for adjuvant therapy for early cancer treatment and prevention of recurrence after surgery has increased. Aston Sci. shifted our focus to meet such demand." said The CEO of Aston Sci., Hunwoo Shin, "We strive to increase the clinical value of cancer vaccines through subsequent clinical trials and research, and also focus our capabilities on future business development."

In addition, Aston Sci. has 10 pipelines in various preclinical and clinical stages including AST-301 and AST-021p. By 2030, the company plans to expand its pipeline to 15 drugs in 4 clinical fields, focusing on efficient development of new drugs with high unmet medical needs and high demand in clinical fields.

Aston Sci. decided to list on the KOSDAQ in order to facilitate its clinical and business development, and as part of that, NH Investment & Securities was selected as the listing manager in May. It is in the works, with the goal to list in early 2023 upon receiving technology evaluation within the next year.

On October 27, 2021 Prevencio, Inc. reported the presentation of data demonstrating that its Artificial Intelligence (AI) driven HART CVE blood test scores strongly correlate with subsequent adverse cardiac events in lung cancer patients undergoing radiation treatment (Press release, Memorial Sloan-Kettering Cancer Center, OCT 27, 2021, View Source [SID1234592069]). Researchers and clinicians from Memorial Sloan Kettering Cancer Center collaborated to test their lung cancer population.

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"With cancer patients living longer, understanding the adverse cardiac effects due to cancer treatments, such as radiation therapy, is of utmost importance," said Annemarie Shepherd, M.D., Assistant Member in Radiation Oncology Cancer Center. "We analyzed serial patient blood samples before, during and after radiation treatment and interestingly found a significant correlation between an increase in the HART CVE scores during radiation and the development of cardiac events in follow up after radiation."

Charles B. Simone, M.D., Chief Medical Officer of the New York Proton Center and Member in Radiation Oncology at Memorial Sloan Kettering Cancer Center, added, "It is critical that we identify more sensitive means of predicting which patients will have adverse cardiac events from radiation therapy, and we are pleased to collaborate with Prevencio to use their novel machine learning-based HART CVE test to do so."

In the general cardiac population, HART CVE had previously been reported to be more accurate (86% AUC accuracy) at predicting risk of heart attack, stroke or cardiac death as compared to single protein blood tests, such as high sensitivity troponin (~65% accuracy), and clinical risk scores (~57% AUC accuracy).

"It is gratifying to work with Dr. Shepherd and Dr. Simone and their team at Memorial Sloan Kettering Cancer Center to demonstrate HART CVE’s usefulness in their lung cancer patients," said Rhonda Rhyne, President and Chief Executive Officer of Prevencio. "We believe our tests will also prove helpful for breast and esophageal cancer patients undergoing radiation therapy."

In the U.S., lung cancer is the second most common cancer in both men and women, with approximately 235,760 new cases annually. Currently, there are more than 550,000 lung cancer patients in the U.S.

Prevencio recently launched for patient use its two lead tests, HART CVE (for one-year risk of heart attack, stroke, or cardiac death) and HART CADhs (for obstructive heart disease diagnosis). For additional information, visit Prevencio, Inc.

About Prevencio HART Tests: Powered by AI, Prevencio is revolutionizing blood tests for cardiovascular disease and custom diagnostics. Employing this novel approach, the Company has developed seven blood tests that significantly improve diagnosis and risk assessment for a variety of heart and blood vessel-related complications.

Our three lead tests include:

HART CVE – 1-year risk of heart attack, stroke, or cardiac death
HART CADhs – obstructive coronary artery disease diagnosis
HART KD – Kawasaki disease diagnosis
HART test results have been peer-reviewed published 25 times, including at leading cardiovascular meetings—(European Society of Cardiology Congress – 2016, 2018, 2021; American College of Cardiology Scientific Sessions – 2017, 2018, 2019 (2), 2020, 2021; American Heart Association Scientific Sessions – 2017, 2018, 2019; American Diabetes Association Scientific Sessions – 2018, 2019; Pediatric Academic Societies International Sessions – 2021; International Spinal Cord Society Scientific Sessions –2021; ASTRO Scientific Sessions – 2021) and in top-tier journals—(Journal of American College of Cardiology – Mar 2017; American Journal of Cardiology – July 2017; Clinical Cardiology – June 2018; Open Heart – November 2018, May 2019, Jan 2019; Biomarkers in Medicine – June 2020; Journal of American Heart Association – Aug 2020).

On October 27, 2021 Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory disease, reported a research collaboration with the French non-profit research organization CRYOSTEM (Press release, Rheos Medicines, OCT 27, 2021, View Source [SID1234592068]). The goal of the research collaboration is to provide biological resources from HSCT (Hematopoietic Stem Cell Transplantation) patients in order to evaluate MALT1-targeted therapeutics, including Rheos’s lead product candidate, RHX-317, for Graft-versus-Host Disease (GvHD), based on functional immunologic profiling of patients and identification of molecular signatures for MALT1 activity. This collaboration supports a precision medicine approach to enable the treatment of GvHD, by defining the predominant metabolic pathways in the anabolic hub that drive key pathogenic pathways in GvHD patient subsets.

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"CRYOSTEM chose to establish this collaborative research program with Rheos because it aligns with our mission to promote our collection of biological resources to help scientists accelerate innovation and extract new knowledge to allow better prevention, diagnosis and treatment of GvHD as one of the HSCT major complications that is a barrier to effective stem cell transplants for patients," said Professor Régis PEFFAULT de LATOUR, co-founder and scientific coordinator of CRYOSTEM.

The research program brings together the collaborators’ two domains of expertise to address the challenge of treating GvHD, a major cause of post-transplant morbidity and mortality in patients who undergo allogeneic HSCT. With its proprietary technology platform, Rheos brings insights from studies showing that MALT1 activity underpins the activation of multiple cell types and signaling pathways within a metabolic hub that is dysregulated in GvHD, as well as approaches to predict and stratify patient response to treatment. CRYOSTEM operates through a national biobanking network bringing together transplant units and Biological Resources Centers to accelerate research in the area of complications of HSCT, housing the first and unique collection in Europe dedicated to HSCT complications. This collection of approximately 200,000 biological samples, taken from patients before and after transplant, support research projects that meet rigorous selection criteria by a world-renowned scientific committee.

"This research collaboration with the world-class experts at CRYOSTEM will enable us to significantly build on our existing work in immune cells from healthy donors, and now study GvHD patient samples to evaluate the effect of inhibiting a key drug target on the activation state of multiple immune cells and the specific pathways that are dysregulated in GvHD," said Dania Rabah, Ph.D., Chief Scientific Officer of Rheos Medicines. "We believe the data generated under this collaboration can validate our precision medicine approach to identify novel patient subsets in autoimmune and inflammatory diseases, while also informing the clinical development plan for RHX-317, our novel MALT1 inhibitor drug candidate to treat GvHD."

Under the terms of the research collaboration, CRYOSTEM will provide Rheos with biological resources for post-transplant patients in three categories: those who developed acute GvHD, those who developed chronic GVHD, and those who did not develop GvHD. Rheos will evaluate therapeutic targets for GvHD through these study methods:

Measure the effectiveness of MALT1 inhibition against disease-relevant functions of immune cells, comparing results across the three different categories of patient samples to determine sensitivity of MALT1 inhibitor drug response and target validation in chronic GvHD.
Perform multi-omic analyses of patient samples to define signatures reflecting MALT1 therapeutic activity.
Upon successful completion of these initial studies, both parties may agree to expand the research to include larger GvHD patient cohorts and additional evaluation of patient subsets to predict therapeutic response for a potential precision medicine approach to GvHD.

"As with many diseases that have an aberrant immune response, today’s treatments for GvHD involve broad immunosuppression, and we lack molecularly-targeted medicines that target disease pathways," said Robert Zeiser, M.D., Head of Tumor Immunology and Immune Modulation and professor at the University of Freiburg Medical Center in Germany. "Rheos’s therapeutic approach to target MALT1 for the treatment of GvHD is built on compelling findings that MALT1 activates cellular activity and signaling pathways that are dysregulated in GvHD. I look forward to continued progress with this MALT1 inhibitor that offers a promising new approach for patients with GvHD."

About MALT1

MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a dual-function scaffolding molecule and paracaspase that is expressed preferentially in immune cells. In addition to its role in NF-κB mediated lymphocyte activation and proliferation, Rheos has shown that MALT1 activity is central to the anabolic shift that fuels pathogenic functions of immune cells. Inhibiting MALT1 attenuates the activity of multiple immune cell types simultaneously to dampen the inflammatory response in the activated immune system. Because of its role in cellular metabolism, the effects of MALT1 inhibition can be monitored by metabolite signatures, opening an opportunity to monitor disease and evaluate activity of therapeutics in patients and patient subsets.