Human Genetics: A new paradigm in drug discovery
“Human genetics provides definitive evidence of which biological pathways drive disease. We strive to comprehensively learn everything we can from genetics about how and why a gene or pathway leads to disease so that we can stop or reverse those processes to bring benefit to patients.”
Head, Data Science & Scientific Infrastructure
Increase our chance to succeed using human biology data
Despite many successes in treating animal models of Alzheimer’s disease, this has not translated to humans. We believe that by guiding our drug discovery and development efforts using human biology data, we will increase our chance to succeed in developing novel therapies for patients.
Genetics of AD: immune genes, pathways, and cells
Over the last decade, the genetic architecture of late-onset AD has been extensively characterized, revealing immune genes, pathways, and cell types (including microglia) that were not previously thought to play a major role in disease. We are focusing our drug discovery efforts on understanding how to optimally target these pathways.
Collaboration with external academic labs and consortia
Our group analyzes high-dimensional genetic and other human data, both internally and in collaboration with external academic labs and consortia. We then work closely with G2D2 biologists and chemists to incorporate those insights into experiments.
Bridging Concepts to Compounds
“Human genetics reveals novel and unconventional AD targets with loss or diminished biological functions. We strive to discover novel agents to modulate the disease states including by restoration or enhancing the target functions. Utilizing internal and external collaboration, we seek to build cutting-edge discovery technologies and capabilities.“
Head, Discovery Sciences
Innovative drug discovery through cutting edge technology platforms
AD human genetics reveal unconventional targets, frequently with minimal biological understanding or research history. Such targets frequently require the need to reactivate or enhance diminishing function in a disease state.
Novel therapeutics require a high level understanding of targets at a molecular level, and exploration of new therapeutic approaches.
To address these challenges, we build cutting-edge technology platforms combining structural biology, chemical biology, computational chemistry, novel assay development and compound screening automation.
Advancing science through collaboration
To deliver an innovative immunodementia* drug to patients in an accelerated timeframe requires all talented minds to work together.
We have established collaborations with many cutting-edge laboratories around the world to accelerate the discovery process.
Targeting AD Through Chemistry, Data Science and Human Genetics
“Direct interrogation of genetic targets with stereochemically defined and topologically novel nucleic acids has already yielded a novel oncology immunotherapy and provides an example of our precision chemistry platform”
Deputy President & Head, Precision Chemistry
We seek to apply the full power of organic chemistry to solve the challenge of drugging Alzheimer’s targets informed by human biology. Eisai’s rich history in natural products-based research has demonstrated that the areas of chemical space practically accessible to drug discovery are far greater than previously thought possible.
For example, the fully synthetic marine natural product-inspired therapeutic agent eribulin consists of a polycyclic ketal embedded in a 22-membered macro-cyclic ketone containing 19 stereogenic centers.
Direct interrogation of genetic targets with stereodefined and topologically novel nucleic acids in our labs has already yielded an immunotherapeutic clinical candidate (E7766) and provides an example of our precision chemistry platform.
Our platform applies targeted solutions — across a range of modalities — that are specific to genetically defined drug targets.
The combined power of precision chemistry, data sciences and human genetics will be essential to develop breakthrough immunodementia therapeutics.
The Next Horizon
“There’s a real sense of excitement in the field with genetic insights into the pathology of age-related dementias. At G2D2 we take a focused, team-based approach to drug discovery. There’s always something new to learn from your colleagues, and a sense that immense human health care impact is within reach.”
Sally T. Ishizaka
Choosing the right target
Finding a disease risk-associated gene is just the first step in the drug development journey. We begin by understanding the connection between a risk or a protection-associated genetic variant and the underlying biology of disease.
The Immunodementia biology group works closely with colleagues in genetics to dissect risk variant effects on protein and cell functions, and to establish disease-relevant assays that reflect target activity. Working internally and with collaborators, we are always trying to expand the biology around our targets.
From mechanism to therapy
G2D2 possesses an array of technologies that we apply to find and optimize molecules that will turn disease processes towards a more healthy function.
Following through, we analyze the effects of our candidate drugs in disease models, and explore molecular markers that will help us choose appropriate patient populations and assess drug effects in clinic. Unbiased ‘omics approaches give us a comprehensive view of disease mechanisms and compound effects, while cutting-edge optical imaging provides critical mechanistic insights.
*Immunodementia is a novel genetically validated target modulating immune mechanism that treats dementia.