NEW YORK, Sept. 12, 2022 /PRNewswire/ — DarwinHealth, Inc., (www.DarwinHealth.com) a New York-based biotechnology and most cancers drug discovery firm pronounces the September 9, 2022 on-line publication in Current Protocols (Wiley Science) of their proprietary most cancers drug discovery and validation pipeline, “A Patient-to-Model-to-Patient (PMP) cancer drug and biomarker discovery protocol for identifying and validating therapeutic agents targeting tumor regulatory architecture.”
Link to the article supplied herein: https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpz1.544
As the scientists be aware of their publication, the Patient-to-Model-to-Patient (PMP) protocol, which represents DarwinHealth’s foundational drug, biomarker, and novel most cancers goal discovery pipeline/expertise, addresses immediately the present Achilles heel of most cancers drug growth, i.e., the shortcoming to forge exact and predictive connections amongst three important parts required for profitable drug discovery and validation in human trials, together with: (a) figuring out the mechanistic -biological drivers and determinants of the most cancers cell state; (b) characterizing and concentrating on therapeutically vital molecular targets governing the transcriptional state of most cancers cells; and (c) producing validated biomarkers which might be correct predictors of medical response in trial settings.
These boundaries to precision-based most cancers therapy and drug discovery are made much more complicated by the heterogeneous nature of most cancers, a problem that the DarwinHealth group addresses by using single cell evaluation together with proprietary algorithmic instruments, thereby making it attainable to taxonomize tumor subtypes primarily based on their transcriptional identification state.
Leveraging an oncotecture-based framework for most cancers biology, the PMP method reported by DarwinHealth employs computational algorithms and experimental methodologies to reconstruct and interrogate the regulatory logic of human most cancers cells for figuring out and therapeutically concentrating on a “tumor checkpoint” with novel, in addition to current pharmacological brokers. Importantly, the PMP protocol systematically identifies, from particular affected person tumor samples, the Master Regulator (MR) proteins that comprise the tumor checkpoint. Then, utilizing gene expression profiles (RNA sequencing), it identifies in vitro and in vivo fashions that, by recapitulating the affected person’s tumor checkpoint, represent acceptable cell line and animal fashions to additional elucidate tissue context-specific drug mechanism of motion.
Use of these matched fashions permits exact, biomarker-based pre-clinical validations of drug efficacy, the outcomes of which may then be translated for use in additional superior PDX validations and human trials, that are presently in progress utilizing this expertise. Specifically, the mixture of drug context-specific mechanism of motion and the exact identification of sufferers’ tumor checkpoints gives a personalised, mechanism-based biomarker for enrichment of potential medical trials with sufferers probably to answer the pharmacologic remedy underneath investigation.
Explaining the scientific and business implications of DarwinHealth’s PMP drug and biomarker discovery platform, science journalist Forest Ray, PhD, reviews on the paper and its expertise in an article printed on-line for genomeweb. Link is supplied herein:
https://www.genomeweb.com/biomarker-discovery-validation/darwinhealth-applies-systems-bio-workflow-improve-clinical-trial#.Yx2tXi8RpB0
“PMP is a patient-centered, systems biology-driven, protocol that integrates highly sophisticated computational methods and experimental approaches—incorporating the precision of single-cell analysis—to optimize and accelerate drug discovery,” famous lead writer, Dr. Pasquale Laise, Senior Director of Computational Biology at DarwinHealth. “While the protocol is fully generalizable and can be applied to any cancer type or subtype, each step of the PMP discovery pipeline is tailored to the molecular profiles of tumors from individual patient samples and, therefore, is also able to identify large cohorts of patients representing distinct pharmacotypes linked to mechanistic biomarkers, an alignment that maximizes the chances of success in biomarker-directed clinical trials.”
The identification and drug-based concentrating on of tumor checkpoints is a hallmark of DarwinHealth’s proprietary methodology targeted on most cancers drug growth. “The PMP protocol constitutes a systematic approach for identifying and targeting the core set of regulatory proteins (or master regulators) controlling the transcriptional identity [phenotypic state] of cancer cells, which distinguishes this Compound-2-Clinic (C2C) developmental roadmap from all other available strategies,” defined DarwinHealth CSO, Dr. Mariano Alvarez. “Importantly, it expands the concept of oncogene addiction to the transcriptional regulators of the cancer cell state, which are universally present and, therefore, can be dissected for every tumor. The protocol closes the circle by dissecting such Master Regulators directly from the patient’s tumor tissue, and then by using a drug’s context-specific mechanism of action—empirically elucidated in cognate in vitro models—the pipeline predicts the therapeutic response of drugs under evaluation in the setting that matters most: clinical trials.”
The PMP protocol is designed to deal with shortfalls and limitations in present approaches to most cancers remedy and biomarker growth. “Much like a building stands on multiple pillars—with the caveat that compromising any single pillar would not cause the entire structure to collapse—optimal, enduring approaches to cancer therapy require targeting multiple tumor dependencies simultaneously,” explains Dr. Andrea Califano, Professor and Chair, Department of Systems Biology, Columbia University (https://news.columbia.edu/news/deciphering-cancer-messy-and-complex-were-here-it), and Co-Founder of DarwinHealth. “The technology and approach to cancer drug discovery highlighted in this manuscript provides significant complementarity to oncogene therapy by targeting an entire repertoire of tumor vulnerabilities, as represented by Master Regulator proteins that are responsible for maintaining the aberrant state and regulatory programs of the tumor cell.”
DarwinHealth’s PMP platform and drug discovery pipeline undergird the foundational expertise the corporate has deployed for many scientific collaborations and partnerships targeted on identification of novel most cancers targets, technology of novel biomarkers, and drug growth. “The Patient-to-Model-to-Patient protocol (PMP) we report is a patient tumor sample-centered, systems biology-based pipeline for cancer drug discovery with broad applications in the precision oncology and immuno-oncology space,” defined Dr. Gideon Bosker, DarwinHealth Co-Founder and CEO. “Each step of the compound-to-clinic drug development and validation pipeline reported in Current Protocols is leveraged by the integration of computational algorithms and experimental data to ensure the targeted regulatory architecture—the ‘tumor checkpoint’—and the mechanism-of action (MOA) of drugs being evaluated are consistently and actionably linked as the protocol progresses from cell lines to animal models and finally, into patients for clinical translation. Its universality in the context of cancer biology permits the PMP model to be applied across a broad spectrum of hematological and solid tumors, where numerous clinical trials based on this drug discovery technology are currently in progress. Moreover, the application of PMP technology to optimize immune response and diminish immunosuppressive effects among cell subtypes—including Tregs, fibroblasts, and macrophages—in the tumor microenvironment represents one of the most promising trajectories for developing drugs that can rescue response of immune checkpoint inhibitors by reprogramming phenotypic states of immunosuppressing cells.”
When deployed in a systematic trend, as it’s at DarwinHealth the place the business functions of the PMP protocol are underneath continuous refinement and growth, the PMP-based most cancers goal, biomarker, and drug discovery pipeline gives a roadmap for precision- and MOA-based identification of investigational, proprietary, and FDA-approved therapeutic brokers concentrating on each tumor regulatory structure, in addition to the regulatory structure of immune-centric cells.
About DarwinHealth
DarwinHealth: Precision Therapeutics for Cancer Medicine is a “frontiers of cancer,” biotechnology-focused firm, co-founded by CEO Gideon Bosker, MD, and Professor Andrea Califano, Clyde and Helen Wu Professor of Chemical Systems Biology and Chair, Department of Systems Biology at Columbia University. The firm’s expertise was developed by the Califano lab over the previous 15 years and is solely licensed from Columbia University.
DarwinHealth makes use of proprietary, techniques biology algorithms to match nearly each most cancers affected person with the medication and drug combos which might be probably to provide a profitable therapy consequence. “Conversely, these same algorithms also can prioritize investigational drugs and compound combinations of unknown potential against a full spectrum of human malignancies, as well as novel cancer targets,” defined Dr. Bosker, “which make them invaluable for pharmaceutical companies seeking to both optimize their compound pipelines and discover mechanistically actionable, novel cancer targets and compound-tumor alignments.”
DarwinHealth’s mission assertion is to deploy novel applied sciences rooted in techniques biology to enhance medical outcomes of most cancers therapy. Its core expertise, the VIPER algorithm, can establish tightly knit modules of grasp regulator proteins that symbolize a new class of actionable therapeutic targets in most cancers. The methodology is utilized alongside two complementary axes: First, DarwinHealth’s applied sciences help the systematic identification and validation of druggable targets at a extra foundational, deep state of the most cancers cell’s regulatory logic so we and our scientific companions can exploit subsequent technology actionability primarily based on basic and extra common tumor dependencies and mechanisms. Second, from a drug growth and discovery perspective, the identical applied sciences are succesful of figuring out doubtlessly druggable novel targets primarily based on grasp regulators, and upstream modulators of these targets. This is the place the DarwinHealth oncotecture-based method, with its emphasis on elucidating and concentrating on tumor checkpoints, gives its most necessary options and repositioning roadmaps for advancing precision-focused most cancers drug discovery and therapeutics.
The proprietary, precision medicine-based strategies employed by DarwinHealth are supported by a deep physique of scientific literature authored by its scientific management, together with DarwinHealth CSO, Mariano Alvarez, PhD, who co-developed the corporate’s important computational infrastructure. These proprietary methods leverage the flexibility to reverse-engineer and analyze the genome-wide regulatory and signaling logic of the most cancers cell, by integrating information from in silico, in vitro, and in vivo assays. This gives a absolutely built-in drug characterization and discovery platform designed to elucidate, speed up, and validate exact developmental trajectories for pharmaceutical property, so their full medical and business potential could be realized. For extra info, please go to: www.DarwinHealth.com.
Logo – https://mma.prnewswire.com/media/966600/DarwinHealth_Logo.jpg
