On June 6, 2022 Thermo Fisher Scientific Inc., the world leader in serving science, and TransMIT GmbH Center for Mass Spectrometric Developments reported that spatial multi-omics applications in pharma and clinical labs (Press release, Lifescience Newswire, JUN 6, 2022, View Source [SID1234615684]).

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As part of the relationship, TransMIT will combine its proprietary scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) MSI and 3D-surface MSI technology with the exceptional high resolution accurate mass (HRAM) power of Thermo Scientific Orbitrap MS instrumentation. TransMIT’s AP-SMALDI⁵ AF ion source coupled with Orbitrap MS technology enables spatial distribution mapping of a variety of molecules such as biomarkers, metabolites, peptides or enzymatically-digested proteins by their molecular masses. This approach can be applied to omics applications such as metabolomics, lipidomics, proteomics, glycomics and to pharmaco-kinetic studies in a variety of tissues.

"This co-marketing agreement will provide integrated solutions for mass spectrometry imaging, offering a label-free approach to map the distribution of a wide range of both known and unknown compounds directly sampled from biological tissue," said Jim Yano, senior director, life sciences mass spectrometry portfolio management, chromatography and mass spectrometry, Thermo Fisher Scientific. "Due to its high performance in spatial resolution, TransMIT’s AP-SMALDI⁵ AF ion source is the perfect match for the high mass resolution and accurate mass capabilities of the Orbitrap MS instrumentation."

Professor Bernhard Spengler, director, TransMIT Center for Mass Spectrometric Developments, said, "Our AP-SMALDI⁵ AF ion source coupled with Thermo Fisher’s Orbitrap technology create an MSI platform for high spatial resolution along with high mass resolution and mass accuracy. The AP-SMALDI-Orbitrap setup enables scanning of tissue samples or 3D objects with the pulsed laser beam of 5 μm spot size routinely without oversampling, providing a powerful solution for drug development and spatial multi-omics applications."

Announcement of the new co-marketing agreement coincides with the 70th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics, being held June 5-9, 2022 where Thermo Fisher is showcasing its latest innovations in Booth 400 at the Minneapolis Convention Center, Minneapolis, Minnesota and at the Hilton Minneapolis Grand Ballrooms E, F, G.

On June 6, 2022 JSR Corporation (Head Office: Minato-ku, Tokyo, Representative Director and CEO: Eric Johnson, JSR Corporation) reported that it has entered into a facility usage agreement with AuB Co., Ltd. (AuB), a company engaged in the study of intestinal microbiota in athletes, for the Collaborative Lab, a collaborative research facility with startups, which is located in a new research laboratory "JSR Bioscience and Informatics R & D center (JSR BiRD)" in Kawasaki City, Kanagawa Prefecture, which opened last July (Press release, JSR, JUN 6, 2022, View Source [SID1234615601]).

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AuB, founded in Oct 2015, is a company that conducts food-tech business based on research into the intestinal bacteria of athletes. Representative director Keita Suzuki is a former top athlete who was a professional player for the Urawa Red Diamonds, a J.League soccer team, and also played for Japan’s national team. Since its foundation, the company has analyzed the intestinal environment of more than 750 athletes (1,700 samples), developed proprietary materials based on this knowledge, and developed a business to sell them externally. In the future, the company is also considering entering the pharmaceutical field.

JSR is developing its life science business as a core business, focusing on diagnostic reagent materials, bioprocess materials, and drug discovery support businesses. At the same time, JSR is engaged in research on the microbiome, etc. as next-generation technology research, and is pursuing the realization of innovation that leads to new products and services required for a healthy and long-lasting society. Through joint research with AuB in collaboration labs, we aim to further accelerate next generation research and commercialize it.

On June 6, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported it will host an investor webcast on Friday, June 10, 2022 at 8:00am ET (2:00pm CEST) to discuss initial clinical data from its on-going Phase 2 APEX trial evaluating bezuclastinib in patients with Advanced Systemic Mastocytosis being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Press release, Cogent Biosciences, JUN 6, 2022, View Source [SID1234615619]).

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The event will be led by Andrew Robbins, Cogent’s President and CEO, and will include a presentation by Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute. The speakers and additional members of Cogent leadership will be available during the Question and Answer session.

The webcast will be accessible through the Investors and Media section of Cogent’s website at www.cogentbio.com. Following the live webcast, an archived replay will also be available.

On June 6, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages in patients with sepsis and solid tumors, reported that the Israeli Ministry of Health (MOH) authorized the initiation of a company-sponsored Phase I/II clinical trial evaluating Allocetra combined with chemotherapy in patients with peritoneal metastases arising from solid cancer (Press release, Enlivex Therapeutics, JUN 6, 2022, View Source [SID1234615635]).

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Peritoneal cancer, whether originating from a primary tumor within the peritoneum or from a metastatic tumor elsewhere in the body, is a terminal disease with a poor prognosis. Patients with peritoneal metastases are in urgent need of novel treatment options, as standard-of-care (SOC) chemotherapy provides only modest survival benefits. The median survival of patients with peritoneal metastases differs based on the location of the primary tumor but is frequently poor, with survival rates of 2.9 months, 6.5 months, and 6.9 months reported for cancers of pancreatic, gastric, and colorectal origins, respectively.

The planned Phase I/II trial is an open-label dose escalation and expansion trial that is expected to enroll a total of approximately 12 patients across four cohorts. It is designed to evaluate the safety and potential preliminary efficacy of Allocetra combined with SOC chemotherapy in patients with peritoneal metastases arising from solid cancer. The study will begin with two cohorts of intra-patient and intra-cohort dose escalation to determine the maximum feasible dose (MFD) of Allocetra in this population, followed by two additional cohorts comparing administration of Allocetra at the selected dose either before or after administration of SOC via a pressurized intraperitoneal aerosol chemotherapy procedure (PIPAC; a technique applied when patients are not eligible to receive the standard treatment due to a considerable tumor load, or large quantities of persistent ascites and other circumstances).

Intraperitoneally delivered Allocetra and SOC chemotherapy administered via PIPAC will be given to patients every six weeks. Systemic chemotherapy will also be administered per the treating oncologist’s plan. The primary endpoint is the number and severity of Allocetra-related adverse events and serious adverse events during the 16-week period, starting from the first administration of study treatment. Secondary endpoints include efficacy assessments, such as best overall response rate (ORR), progression-free survival, and overall survival. Changes from baseline in macrophage and immune cell characteristics in peritoneal fluid and tissues will also be assessed as an exploratory endpoint.

Currently, the efficacy of many anti-cancer agents is hampered by the body’s tumor defense mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. The TAMs typically form a physical layer on top of the solid tumor and induce immunosuppression in the solid tumor microenvironment. This in-turn promotes tumor growth and metastasis and contributes to poor clinical outcomes and response to therapy. Previously reported preclinical data from solid tumor models suggest that Allocetra has the potential to reprogram pro-tumor macrophages back to their homeostatic state and may thereby promote disease resolution and provide patients that do not respond well to existing FDA-approved therapies with an effective treatment option.

Einat Galamidi, M.D., Vice President, Medical of Enlivex, stated: "Receiving this authorization from the MOH is an important step toward expanding Allocetra’s potential therapeutic impact into oncology. Our preclinical studies suggest Allocetra may enhance the efficacy of a broad range of therapeutic agents by weakening tumor defense mechanisms through a novel mechanism of action that drives macrophage populations towards a more anti-cancer state. We look forward to beginning the clinical evaluation of this hypothesis through both this chemotherapy combination study and an additional planned solid tumor study that will evaluate Allocetra combined with a checkpoint inhibitor."

Enlivex plans to initiate the Phase I/II trial evaluating Allocetra in combination with chemotherapy in patients with peritoneal metastases arising from solid cancer in Q3 2022. The Company also expects to initiate a Phase I/II trial evaluating Allocetra in combination with an immune checkpoint inhibitor in late 2022.

ABOUT ALLOCETRATM

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On June 6, 2022 Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, reported results from the myCare-004 study, which demonstrate that the Cellworks Singula Therapy Response Index (TRI) is highly predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) for gastroesophageal adenocarcinoma (GEA) patients (Press release, Cellworks, JUN 6, 2022, View Source [SID1234615652]). In this retrospective study, Singula TRI provided additional predictive information for OS and DFS beyond patient age, patient gender and physician-prescribed treatment.

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The results from the myCare-004 clinical study were featured in a poster session as part of the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting during the Gastrointestinal Cancer – Gastroesophageal Pancreatic and Hepatobiliary Track and available online as Abstract 4064.

"This study confirmed that there are many dysregulated signaling pathways responsible for hallmark behaviors of cancer and variable drug response in gastroesophageal adenocarcinoma patients," said Dr. Elizabeth Smyth, Cambridge University Hospitals NHS Foundation Trust and Co-Principal Investigator of the myCare-004 clinical study. "Cellworks personalized therapy biosimulation enables us to utilize a patient’s comprehensive next generation sequencing (NGS) results and understand the downstream molecular effects of specific drugs on cell signaling to predict how each patient will respond to therapies prior to treatment. The next step is to evaluate whether biosimulation-informed therapy selection can be used prospectively to improve the survival of GEA patients."

"Gaining a better understanding of the molecular determinants of gastroesophageal adenocarcinoma is key to improving therapy response rates for GEA patients," said Dr. Rebecca Fitzgerald, MD, Professor of Cancer Prevention at the University of Cambridge; Director of the CRUK Cambridge Centre Early Detection Institute; and Co-Principal Investigator of the myCare-004 clinical study. "There are limited treatment options for this cancer type and we look forward to testing the Cellworks personalized therapy predictions in a prospective trial."

The Cellworks Biosimulation Platform simulates how a patient’s personalized genomic disease model will respond to therapies prior to treatment and identifies novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks Computational Omics Biology Model (CBM), a network of 7,000+ human genes, 30,000+ molecular species and 100+ signaling pathways. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks platform analyzes the impact of specific therapies on the patient’s personalized disease model and generates a Singula biosimulation report with Therapy Response Index (TRI) scores from 0 to 100 that predict the efficacy of specific chemotherapies.

myCare-004 Clinical Study

Background

In this study, the Cellworks Singula Therapy Response Index (TRI) was used to prospectively predict the Overall Survival (OS), Disease Free Survival (DFS) and Mandard-tumor regression grade (TRG) in a retrospective cohort of gastroesophageal adenocarcinoma patients from the UK OCCAMS consortium. 271 GEA patients were selected who had pre-chemo treated biopsies with 50x whole genome sequencing. 234 patients were male and 30 female with a median age of 65.6 years. Within the study population, there were 35 T2, 215 T3, 70 N0, 126 N1, 62 N2 and 266 M0. Patients were prescribed chemotherapy treatments according to UK clinical guidelines.

Methods

A mechanistic model created for each patient using comprehensive genomic inputs biosimulated downstream molecular effects of cell signaling and drugs for a patient’s personalized in silico disease model. Random sampling stratified by clinical factors was used to split the data into independent training (N=140) and validation (N=131) subsets. Multivariant Cox Proportional Hazard (PH) and Proportional Odds models were used to predict survival and pathological response as a function of the pre-defined Therapy Response Index (TRI) and clinical thresholds compared with standard clinical factors.

Results

Cellworks Personalized Therapy Biosimulation found that 99% of the patients’ tumors had deficiency in DNA repair genes. Other pathways included amplification of multi-drug resistance pumps, TP53 mutations and aberrations of the PI3K/AKT pathway genes. Cellworks Singula Therapy Response Index (TRI) provided additional predictive information for OS and DFS beyond physician prescribed treatment and standard clinical factors. TRI was also predictive of TRG in univariate analysis. TRI scores were generated for 82 alternate therapies for each patient, enabling selection of optimal therapies with estimates of improvements in median OS and DFS compared to standard care (SC).

Conclusions

The study found that Cellworks Singula TRI was predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) beyond clinical factors in this cohort of gastroesophageal adenocarcinoma (GEA) patients. These positive results suggest the utility of biosimulation-informed therapy selection to improve survival of GEA patients.