DarwinHealth Publication Reports Step-by-Step Protocol for its Tumor Checkpoint-Based, Compound-to-Clinic (C2C) Cancer Drug Discovery Pipeline: Elucidates a Patient-to-Model-to-Patient (PMP) Roadmap for Precision- and Mechanism-Based Identification and Clinical Validation of Novel, Investigational and FDA-Approved Therapeutic Agents Targeting Tumor Regulatory Architecture

NEW YORK, Sept. 12, 2022 /PRNewswire-AsiaNet/ --

DarwinHealth, Inc., (www.DarwinHealth.com) a New York-based biotechnology and

cancer drug discovery company announces the September 9, 2022 online

publication in Current Protocols (Wiley Science) of their proprietary cancer

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."

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Link to the article provided herein:

https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpz1.544

As the scientists note in their publication, the Patient-to-Model-to-Patient

(PMP) protocol, which represents DarwinHealth's foundational drug, biomarker,

and novel cancer target discovery pipeline/technology, addresses directly the

current Achilles heel of cancer drug development, i.e., the inability to forge

precise and predictive connections among three critical elements required for

successful drug discovery and validation in human trials, including: (a)

identifying the mechanistic -biological drivers and determinants of the cancer

cell state; (b) characterizing and targeting therapeutically significant

molecular targets governing the transcriptional state of cancer cells; and (c)

generating validated biomarkers that are accurate predictors of clinical

response in trial settings.

These barriers to precision-based cancer treatment and drug discovery are made

even more complex by the heterogeneous nature of cancer, a challenge that the

DarwinHealth group addresses by employing single cell analysis in combination

with proprietary algorithmic tools, thereby making it possible to taxonomize

tumor subtypes based on their transcriptional identity state.

Leveraging an oncotecture-based framework for cancer biology, the PMP approach

reported by DarwinHealth employs computational algorithms and experimental

methodologies to reconstruct and interrogate the regulatory logic of human

cancer cells for identifying and therapeutically targeting a "tumor checkpoint"

with novel, as well as existing pharmacological agents. Importantly, the PMP

protocol systematically identifies, from specific patient tumor samples, the

Master Regulator (MR) proteins that comprise the tumor checkpoint. Then, using

gene expression profiles (RNA sequencing), it identifies in vitro and in vivo

models that, by recapitulating the patient's tumor checkpoint, constitute

appropriate cell line and animal models to further elucidate tissue

context-specific drug mechanism of action.

Use of these matched models permits precise, biomarker-based pre-clinical

validations of drug efficacy, the results of which can then be translated for

use in more advanced PDX validations and human trials, which are currently in

progress using this technology. Specifically, the combination of drug

context-specific mechanism of action and the precise identification of

patients' tumor checkpoints provides a personalized, mechanism-based biomarker

for enrichment of prospective clinical trials with patients most likely to

respond to the pharmacologic therapy under investigation.

Explaining the scientific and commercial implications of DarwinHealth's PMP

drug and biomarker discovery platform, science journalist Forest Ray, PhD,

reports on the paper and its technology in an article published online for

genomeweb. Link is provided 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," noted lead author, 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 targeting of tumor checkpoints is a hallmark

of DarwinHealth's proprietary methodology focused on cancer drug development.

"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," explained 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 address shortfalls and limitations in current

approaches to cancer therapy and biomarker development. "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 technology the company has deployed for many scientific

collaborations and partnerships focused on identification of novel cancer

targets, generation of novel biomarkers, and drug development. "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,"

explained 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 fashion, as it is at DarwinHealth where the

commercial applications of the PMP protocol are under continual refinement and

expansion, the PMP-based cancer target, biomarker, and drug discovery pipeline

provides a roadmap for precision- and MOA-based identification of

investigational, proprietary, and FDA-approved therapeutic agents targeting

both tumor regulatory architecture, as well as the regulatory architecture of

immune-centric cells.

About DarwinHealth

DarwinHealth: Precision Therapeutics for Cancer Medicine is a "frontiers of

cancer," biotechnology-focused company, 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

company's technology was developed by the Califano lab over the past 15 years

and is exclusively licensed from Columbia University.

DarwinHealth utilizes proprietary, systems biology algorithms to match

virtually every cancer patient with the drugs and drug combinations that are

most likely to produce a successful treatment outcome. "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," explained 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 statement is to deploy novel technologies rooted in

systems biology to improve clinical outcomes of cancer treatment. Its core

technology, the VIPER algorithm, can identify tightly knit modules of master

regulator proteins that represent a new class of actionable therapeutic targets

in cancer. The methodology is applied along two complementary axes: First,

DarwinHealth's technologies support the systematic identification and

validation of druggable targets at a more foundational, deep state of the

cancer cell's regulatory logic so we and our scientific partners can exploit

next generation actionability based on fundamental and more universal tumor

dependencies and mechanisms. Second, from a drug development and discovery

perspective, the same technologies are capable of identifying potentially

druggable novel targets based on master regulators, and upstream modulators of

those targets. This is where the DarwinHealth oncotecture-based approach, with

its emphasis on elucidating and targeting tumor checkpoints, provides its most

important solutions and repositioning roadmaps for advancing precision-focused

cancer drug discovery and therapeutics.

The proprietary, precision medicine-based methods employed by DarwinHealth are

supported by a deep body of scientific literature authored by its scientific

leadership, including DarwinHealth CSO, Mariano Alvarez, PhD, who co-developed

the company's critical computational infrastructure. These proprietary

strategies leverage the ability to reverse-engineer and analyze the genome-wide

regulatory and signaling logic of the cancer cell, by integrating data from in

silico, in vitro, and in vivo assays. This provides a fully integrated drug

characterization and discovery platform designed to elucidate, accelerate, and

validate precise developmental trajectories for pharmaceutical assets, so their

full clinical and commercial potential can be realized. For more information,

please visit: www.DarwinHealth.com.

CONTACT: Gideon Bosker, MD, CEO, DarwinHealth, Inc., Email:

GBosker@DarwinHealth.com, Phone: (+1) 503-880-2207

SOURCE  DarwinHealth