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Cellworks CBM Clinical Study Identifies Novel Biomarkers for ATRA Benefit and Failure in AML Patients

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SOUTH SAN FRANCISCO, Calif., June 04, 2021 (GLOBE NEWSWIRE) — Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, today announced results from a Cellworks Clinical Trial, in which the Cellworks Computational Omics Biology Model (CBM) accurately predicted that All-Trans Retinoic Acid (ATRA) combined with cytarabine, etoposide, idarubicin (ATRA-CEI) benefits a subset of non-APL (Acute Promyelocytic Leukemia) Acute Myeloid Leukemia (AML) patients. The study also revealed novel biomarkers and key mechanisms of resistance to ATRA-CEI benefit and failure in adults with AML.

The results from this Cellworks clinical trial will be featured in a poster session with comments from Dr. Scott Howard, MD, MSc, University of Tennessee, Health Science Center, as part of the 2021 ASCO Annual Meeting June 4-8th during the Hematologic Malignancies-Leukemia, Myelodysplastic Syndromes, Allotransplant Track and available online as abstract 7027.

ATRA has revolutionized the treatment of APL, and subsequent in vitro data studies showed that some non-APL AML patients may benefit from addition of ATRA to standard therapy. This study aimed to predict ATRA response a priori to determine the optimal treatment for each patient. Cellworks CBM was used to predict and evaluate the impact of initial therapy with ATRA combined with cytarabine, etoposide, idarubicin (ATRA-CEI) to access the biomarkers responsible in adults with AML. The Cellworks CBM biosimulated the downstream molecular effects of cell signaling, drugs and combination therapies on patient-specific in silico cancer cells.

“ATRA plus arsenic trioxide is the standard of care for APL. ATRA also has activity against a subset of non-APL AMLs, so identifying sensitive patients ahead of time allows addition of an additional effective agent whose toxicities are non-overlapping with cytarabine, anthracyclines, and etoposide. Furthermore, understanding the biologic basis of ATRA sensitivity paves the way for even more progress in AML in future studies,” said Dr. Scott Howard, MD, MSc, University of Tennessee, Health Science Center and Co-Principal Investigator for the Cellworks CBM ATRA AML study. “In this study, we aimed to more deeply understand the response to ATRA-CEI in individual non-APL AML patients at the molecular level. Cellworks results were impressive– particularly in uncovering novel biomarkers for ATRA failure/benefit and identifying patient responders who have monosomy 7, where non-response is the norm.”

“Cellworks CBM provides oncologists with an artificial intelligence tool in the clinic capable of revealing oncogenic and transcriptional mechanisms underlying unsuspected drug vulnerabilities and sources of drug resistance,” said Dr. Michael Castro, MD, neuro-oncologist and medical oncologist specializing in molecular oncology, precision medicine, and immunotherapy of cancer at Beverly Hills Cancer Center; Chief Medical Officer for Cellworks Group, Inc.; and Co-Principal Investigator for the Cellworks CBM ATRA AML study. “Cellworks CBM can identify non-APL patients who derive benefit ATRA and avoid its unnecessary use in patients unlikely to respond, thus improving efficacy while reducing toxicity and cost.”

Clinical Study Methods and Results

AML patients in clinical trial NCT00151242 had their leukemia sequenced as part of the trial. Their genomic profiles were used for computational modeling by the Cellworks CBM, which uses curated data about genomic aberrations from PubMed as input to generate disease-specific protein network maps and predict drug responses. Disease biomarkers unique to each patient were identified using the Cellworks therapy biosimulation platform. Digital drug simulations were conducted by measuring the effect of ATRA-CEI on a composite cell growth score of cell proliferation, apoptosis and other hallmarks for cancer. ATRA-CEI was mapped to the patient genome along with a mechanism of action and validated based on the genomic profile and its biological consequences.

Of 171 patients treated with ATRA-CEI, 107 responded (R) and 64 did not respond (NR). Of the 64 NRs, there was a subset of 18 patients with favorable genomic features who did not respond and their non-response was correctly predicted by Cellworks CBM in all 18 cases. Mutations of DNMT3A, EZH2, ASXL, FLT-3 and GART amplification emerged as novel biomarkers of ATRA-CEI failure.

In general, monosomy 7 is expected to confer ATRA resistance due to the presence of EZH2 and KMT2E gene deletions. In this study, 18 of the 32 patients with monosomy 7 did not respond. However, 14 patients with monosomy 7 did respond, and Cellworks identified these patients had co-occurrence of deletions involving IGFBP3, PMS2, HUS1, CDK5, XRCC2/4, AKR1B10 and others that overcame ATRA resistance associated with monosomy 7.

“In this study Cellworks CBM was able to identify non-responders among patients considered likely to respond, and responders among patients considered unlikely to respond,” said Khush F. Mehta, CEO of Cellworks Group, Inc. “By using computational modeling of all genetic biomarkers, we are able to take a holistic view of a patient’s response to drugs, which explains this study’s success versus traditional one-mutation, one drug approaches.”

About Cellworks Group

Cellworks Group, Inc. is a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology. Using innovative multi-omics modeling, computational biosimulation and Artificial Intelligence heuristics, Cellworks predicts the most efficacious therapies for patients. The Cellworks unique biosimulation platform is a unified representation of biological knowledge curated from heterogeneous datasets and applied to finding cures. Backed by UnitedHealth Group, Sequoia Capital, Agilent and Artiman, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers and software technologists working toward a common goal – attacking serious diseases to improve the lives of patients. The company is based in South San Francisco, California and has a research and development facility in Bangalore, India. For more information, visit www.cellworks.life and follow us on Twitter @cellworkslife.

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Artificial Intelligence

XtalPi Unveils XtalGazer: A Comprehensive AI-Driven Polymorph Selection Platform

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CAMBRIDGE, Mass., March 28, 2024 /PRNewswire/ — XtalPi Inc., a leading global technology company in integrating artificial intelligence (AI) and robotics to advance the discovery of groundbreaking medicine and innovative materials, announced today the launch of its proprietary comprehensive solid form discovery and selection platform, XtalGazer. This advanced platform aims to significantly improve the polymorph selection process for the pharmaceutical industry by integrating AI- and automation-powered experimental and computational approaches.

XtalGazer provides a total solution for delivering high-quality polymorph screening and selection methods to expedite drug development and mitigate risks. It represents a paradigm shift in solid-state research, moving from the traditional trial-and-error approach to a data-driven, design-led methodology. The platform provides an expansive suite of foundational tools to accelerate polymorph discovery, characterization, and selection process, empowering pharmaceutical companies to conduct thorough research with less active pharmaceutical ingredient (API) in shorter development cycles.
A key component of XtalGazer is XtalCSP, a crystal structure prediction platform to perform global searches of crystal structures for target molecules and the other optional components in the corresponding searching space, offering a deep insight into possible stable forms. Furthermore, crystallization strategy recommendations will provide AI-backed experimental design to help avoid human bias. XtalGazer also utilizes MicroED to rapidly elucidate crystal structures from powder samples, reducing the need for growing single crystals.
XtalPi’s launch of XtalGazer marks another significant step in the company’s ongoing exploration of solid-state research. From crystal structure prediction platforms being one of the first products to launch at XtalPi, to today’s comprehensive polymorph selection platform, XtalPi will keep fulfilling its promise to solving challenging problems in this space. XtalPi will continue to deliver faster, more accurate, and more comprehensive approaches to building an ecosystem for the R&D process in solid-state, pre-formulation and crystallization.
For more information about XtalPi, please visit www.xtalpi.com.
About XtalPi:
XtalPi is an innovative technology company powered by artificial intelligence (AI) and robotics. Founded in 2015 on the MIT campus, XtalPi is dedicated to driving intelligent and digital transformation in the life science and new materials industries. With tightly interwoven quantum physics, AI, cloud computing, and large-scale clusters of robotic workstations, XtalPi offers a range of technology solutions, services, and products to accelerate and empower innovation for biopharmaceutical and new materials companies worldwide.
Media Contact: Vivienne [email protected]
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ICIS and Base Oil News Announce Partnership to Enhance Market Insights

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LONDON, March 28, 2024 /PRNewswire/ — ICIS, a global source of commodity intelligence, is pleased to announce a strategic partnership with Base Oil News, a premier news outlet founded by industry expert Iain Pocock that provides in-depth coverage of the base oils and lubricants market. This collaboration marks a significant milestone in the dissemination and exchange of critical market data and insights.

With more than two decades of journalism experience at Bloomberg, Reuters, and Argus Media, Iain Pocock brings unparalleled expertise to this partnership. His deep understanding of illiquid energy markets makes him a credible and influential figure in the industry. Since November 2023, Iain has been working closely with ICIS to share and exchange valuable data and insights, enhancing the services both platforms offer to the base oils and lubricants market.
Through the collaboration, Iain integrates ICIS’ extensive content and data resources in Base Oil News market coverage. In return, he contributes market insights to ICIS News, including expert and exclusive analysis of supply and demand dynamics, price margins, and other critical market drivers. This exchange ensures that subscribers of both ICIS and Base Oil News have access to the most comprehensive, timely, and accurate market information, empowering them to make informed decisions.
“It’s a very exciting partnership – where we leverage each other’s strengths and provide actionable insights to our customers,” said Iain Pocock, Founder of Base Oil News. “The market is the winner.”
“As ICIS is already the world’s most trusted pricing benchmark for base oils, this collaboration with Iain Pocock and Base Oil News provides an even stronger and deeper service to our customers,” said Stephen Burns, Editorial Director at ICIS. “Iain’s expertise and extensive industry connections are invaluable, and we have established a fruitful partnership that benefits the market at large.”
For the latest insights from Iain Pocock on ICIS News, visit ICIS News.  
About ICIS
ICIS – Independent Commodity Intelligence Services – helps businesses through seamlessly delivering data and analytics, across the chemical, fertilizer and energy markets. A trusted source and benchmark for price information and insight across key commodities markets worldwide. Our independent, transparent market intelligence informs thousands of quality decisions every day, taking the pressure out of negotiations and giving customers space for more innovative thinking, through published datasets including price assessments, price forecasts, supply and demand fundamentals and more.
Over 150 years of shaping the world by connecting markets to optimise the world’s valuable resources. With a global team of more than 600 experts, ICIS has employees based in London, New York, Houston, Karlsruhe, Milan, Mumbai, Singapore, Guangzhou, Beijing, Shanghai, Dubai, Sao Paulo, Seoul, Tokyo and Perth.
ICIS is part of RELX, a FTSE15 company with a market cap of £64bn and an employee base of over 30,000 experts across 40 countries.
About RELX
RELX is a global provider of information and analytics for professional and business customers across industries. The Group serves customers in more than 180 countries and has offices in about 40 countries. It employs approximately 30,000 people of whom almost half are in North America. RELX PLC is a London listed holding company which owns 52.9% of RELX Group. RELX NV is an Amsterdam listed holding company which owns 47.1% of RELX Group. The shares are traded on the London, Amsterdam and New York Stock Exchanges using the following ticker symbols: London: REL; Amsterdam: REN; New York: RELX and RENX. Total market capitalisation is approximately £64bn | €75bn | $81bn.
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Trianz Welcomes Israel Abraham as Vice President of Services for Extrica.ai – The Data to AI Platform

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SANTA CLARA, Calif., March 28, 2024 /PRNewswire/ — Digital transformation technology & services company Trianz is pleased to announce the appointment of Israel Abraham as Vice President of Extrica Platform Services.

Trianz has embarked on a transformative journey, redefining its value proposition with an ‘IP Led’ model, with a commitment to deliver the fastest time to value, lowest human dependence, and highest ROI. Central to this approach are our hyper-automated platforms, Concierto.Cloud, Extrica.AI, and Pulse, driving industry-leading transformations in cloud, data and analytics, AI, and the digital workplace.
Israel Abraham is a very well-known pioneer and industry leader in AI, data management, and analytics systems, with over three decades of experience. He joins as the services leader for Extrica- the Trianz Data to AI platform, which productizes data, provides data a face and purpose, and accelerates time to insights and AI by 50% or more. In the role of Extrica Services leader, Israel will lead the shaping, visioning, and delivery of Extrica.ai based enterprise wide datamesh, BI, and AI solutions for customers worldwide.
“We are thrilled to welcome Israel Abraham to the Trianz family,” said Sri Manchala, CEO of Trianz and author of Crossing the Digital Faultline. “He is a leader in modernization as well as conceptualization of data platforms anew. Israel’s prior background in the industry with financial services and insurance giants underscores our commitment to securing top-tier talent that brings real-world experiences and needs to our technology platforms. As we continue to broaden our footprint in the digital transformation space, Israel’s visionary leadership and practical experience will serve as the cornerstone in accelerating insights and AI to deliver transformative value to our clients.”
Having played pivotal roles in highly reputed and large organizations such as Liberty Mutual Insurance, MassMutual, Safeco, and CNA Insurance, Israel has garnered recognition as a seasoned leader in big data and AI cloud implementations. His accolades include the prestigious 2014 Ventana Research IT Innovation Award, the 2009 Informatica MDM Innovation Award, and three filed Data Engineering patents in the last four years.
“Trianz has been at the forefront of digital innovation, and Extrica.ai is a paradigm shifting data to AI platform that completely changes how analytics and AI are delivered- much faster, taking business ahead of change. I am excited to scale the adoption of the Extrica platform, which has attracted attention from giants across the industry and hyperscalers,” said Israel Abraham. “I look forward to engaging with customers, bringing my own experiences, and collaborating with the talented team at Trianz to further enhance the capabilities of the Extrica Platform Services to transform data & AI strategies, execution, and outcomes for customers.”
About Trianz
Trianz is a leading-edge technology platforms and services company that accelerates digital transformations at Fortune 100 and emerging companies worldwide in data & analytics, digital experiences, cloud infrastructure, and security. Our ‘IP Led Transformations’ approach, informed by insights from a recent global study spanning 20+ industries and 5000+ companies, addresses challenges posed by the rapid pace of AI-driven transformation, digital talent scarcity, and economic uncertainty. Our IP and platforms, including Concierto, Extrica, and Pulse, revolutionize cloud adoption, data analytics, and AI insights, empowering organizations to navigate the complexities of digital transformation seamlessly.
Founded in California and with an organization of over 2,000 associates across the United States and India, Trianz is a Premier Partner of AWS, consistently rated #1 by clients for value delivery over the past five years. Trianz has been ranked as one of the best Consulting Firms by Forbes and has been certified as a Great Place to Work for three years in a row. To learn more about Trianz, email [email protected] or visit www.trianz.com.
Watch Trianz CEO Sri Manchala’s insightful interview with Bloomberg on Partner | Crossing The Digital Faultline & Leading Towards Transformative Success – YouTube and delve deeper into his book Crossing the Digital Faultline at Crossing the Digital Faultline | Trianz.
Trianz Media [email protected] +1-408-387-5800
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