Our Research Interests

Pain/Sensory Neuron

Oncology

  • Small Molecule Programmes

Epigenetics

Novel targets for epigenetic factors* that cause tumour regression in vivo
  • *· writers, erasers, readers of histone/DNA modification
  • · chromatin remodeling factors
Novel targets for RNA functions** (directly or indirectly) that cause tumour regression in vivo
  • **· RNA maturation/modification (splicing factors, RNA modifying enzymes, etc.)
  • · miRNA, lncRNA

Cancer metabolism

Small molecule modulators (inhibitors or activators) of cancer-specific metabolism (need to show a clear rationale that explains tumour selectivity)
Inter-disciplinary research targets in this area, such as IDO, IDH inhibitors

Cancer microenvironment

Small molecule modulators (inhibitors or activators) or novel targets of tumour immuno-suppression

Others

Novel therapeutic approaches against steroid-dependent cancers such as castration-resistant prostate cancer

General drug profiles of interest: novelty and competitiveness

Drug discovery programmes targeting cancer vulnerabilities, genetic/epigenetic aberrations, driver mutations, or drug resistance
Novel anti-cancer targets or drug discovery programmes with the following potentials for both
  • Sensitive patient stratification or predictive markers based on genetic/epigenetic aberrations etc.
  • High cancer selectivity based on biological rationale or experimental data

Less prioritized concepts and areas:

Molecules targeting “best-in-class” with no evidence (potential) to switch from the current standard of care, that is “me-too-drug”
Opportunities without in vivo validation data available
Opportunities whose mechanism is only dependent on metastasis process (e.g. cell motility inhibition)
Differentiation/growth signals essential for homeostasis
General cancer hormonal therapy
  • Biologics Programmes

Molecular targets/mechanisms or methods for cancer therapy by “biologics”

For tumour rejection by inducing non-apoptotic/highly-immunogenic cell death or by interrupting tumour (or virus)-evoked immune evasion pathways
To augment immunogenicity of low-antigenic neoantigens
Associated with cancer immune suppression, immune escape or immune checkpoints
Associated with chemo-resistant cells
For cancer-associated fibroblast or cancer-associated mesenchymal stem cells
From autoimmune disease research
Novel immune adjuvants that activate intracellular molecule(s)

Research should provide prospects to create drugs with superiority such as novelty and/or potency fulfilling unmet medical needs in oncology.

At Daiichi Sankyo, we have developed a proprietary antibody-drug conjugate technology that has recently been validated in the clinic. Our novel linker and payload offer advantages over current ADC technologies. We are interested in acquiring novel monoclonal antibodies that would be good candidates for our ADC platform  for oncology indications. Target characteristics such as tumour-specific and sufficient expression levels and internalization are critical factors for good mAb candidates.

No interest in targets already in clinical development

Biologics” mean antigen-binding proteins such as antibodies, antibody-like formats etc., and have to demonstrate in vitro and/or in vivo proof of influence of the target (validated status)

Pain/Sensory Neuron Programmes

  • Pain

Innovative targets/pathways for refractory pain (chronic/mixed pain)

Targets involved in descending inhibition pathway
Targets/compounds cross-talking with opioid signalling

Novel targets, pain pathway modifying targets and innovative idea to improve existing analgesics are preferable

Mechanisms related to chronic pain formation/transition

Brain function/network reinforcing chronic pain
Molecular targets, compounds, and pathways

Methods and Technologies

Objective and quantitative methods translating from pain animal models to clinical (e.g. blood biomarker, fMRI)
Novel animal models of refractory pain/addiction (e.g. highly recapitulate human chronic pain) and opioid addiction/reward models with relatively high throughput

Mid-size molecules penetrating into the CNS

No interest in the clinical indications of acute inflammatory pain and acute migraine

No interest in the targets of opioid with simple formulation change, Trp antagonists (Trp V1, M8), and MoA targeting for end injury/inflammation

  • Sensory neuronal systems

〈Target disease condition〉

Vision loss from retinal degeneration

Sensorineural hearing loss

Endolymphatic hydrops (Ménière's disease)

〈Pathways/mechanisms of interest〉

Regeneration of neuronal and sensory cells

Protein degradation/trafficking in neurons

Volume and composition control of endolymph

We have particular interest in modulators of autophagy or ER stress that work specifically in nervous systems. We also have an interest in novel genes and mechanisms related to congenital retinal or cochlear neuropathy.

No interest in neuroprotectants with unknown mechanism of action or angiogenesis/inflammatory targets

End-Organ Disease Programmes

Novel drug targets for diseases with pathways/mechanisms described below

  • Heart Disease

Acute & chronic heart failure (AHF/CHF)

Improvement of CV morbidity (prevention of decompensation/re-hospitalization/renal failure) and mortality
Symptomatic improvements (dyspnoea/walking distance) coupled with morbidity or mortality benefits

Arrhythmia (Persistent/permanent atrial fibrillation (AF))

Terminate persistent/permanent AF and/or maintain sinus rhythm in patients with AF with little risk of ventricular adverse effects

〈Pathways/mechanisms of interest〉

Improvement of cardiac performance without affecting heart rate/O2 consumption
Direct inhibition of primary cardiac hypertrophy
Congenital heart disorder (e.g. Dilated/hypertrophic cardiomyopathy)
Prolongation of action potential duration specifically in atrium or unique mechanisms to terminate atrial fibrillation
  • Stroke

Novel approaches for the treatment of stroke/transient ischemic attack (TIA)

We are focusing on novel and innovative therapies for not only acute stroke but late sequela of stroke.

No interest in antithrombotic therapies and so-called “neuroprotectants” for acute stroke treatment

  • Vascular Dysfunction
Peripheral arterial disease (CLI/IC)
Microvascular dysfunction mediated by diabetes (diabetic macular edema, wound healing)

〈Pathways/mechanisms of interest〉

Oxygen delivery to muscle
Endothelial integrity (vascular leak)
Granulation tissue formation (angiogenesis)
Vascular maturation (pericyte-EC interaction)
Vascular malformation
  • Kidney Diseases

Kidney disease and complications

Target validation for treatment of ADPKD
Mechanism of intestinal IgA production in IgA nephropathy
Removal of uremic toxin and its specific clinical indication around AKI/CKD
Protection against nephrotoxic agent
Animal disease models with ectopic calcification
  • Liver Dysfunction
Improvement of abnormal hepatobiliary metabolism (urea cycle disorder, organic acidemia, cholestasis, etc.)
Improvement of symptom associated with cirrhosis (hyperammonemia, etc.)

〈Pathways/mechanisms of interest〉

Direct modulation of causal metabolic pathway
  • Gastrointestinal Disorder
Improvement of immune dysfunction and inflammation (IBD, etc.)
Recovery of gastrointestinal motor function (FD, etc.)
Amelioration of GI symptoms (IBS, constipation, diarrhea, etc.)

〈Pathways/mechanisms of interest〉

Direct suppression of intestinal tract stricture caused by fibrotic change
Novel immune regulation mechanism
Structural and functional recovery of intestinal mucosa
  • Fibrotic Diseases

Prevent or delay the progress of organ fibrotic change

Interstitial pneumonia (IPF, etc.)
Sarcoidosis
Hepatic fibrosis (NASH, cirrhosis, PBC, PSC, etc.)
Cystic fibrosis

〈Pathways/mechanisms of interest〉

Regulation of macrophage activation/proliferation

Other Disease Programmes

  • Rare Diseases

Monogenic / Rare Diseases

Innovative therapeutics for genetically-defined diseases with high unmet medical needs (severe/progressive/high lethality)
  • Direct approaches toward pathogenic mutations (e.g. functional improvement of the pathogenic protein, correction of aberrant splicing, or modulation of the protein level)
  • Any therapeutic areas if the disease is caused by single gene mutation
  • Particular interest in congenital metabolic diseases and neuromuscular diseases

No interest in rare cancers

Basic Research

Identification and/or functional analysis of causative genes or novel molecular targets
Pathological mechanisms of genetic diseases that could be common with sporadic diseases
Novel knock-in animal models generated by inserting mutant human genes
  • Anaemia

Novel Approaches for the treatment of anaemia

Novel therapies for haematological diseases, especially for anaemic disorders with erythropoietin resistance (sickle cell anaemia, cancer-related anaemia etc.)

No interest in erythropoiesis-stimulating agents and iron supplementation

  • Gut Microbiome-Related Diseases

Novel approaches for gut microbiome-related diseases

Novel therapeutic targets and approaches for the gut microbiome that can modulate disease outcome

Particular interest in the relationship between the gut microbiome and diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), non-alcoholic steatohepatitis (NASH), Celiac disease, etc.

Basic research

Unique animal disease models which prove to be useful tools to advance understanding of gut microbiome-related diseases

No interest in cancer and “Microbiota-based" therapeutics, such as fecal microbiota transplantation or therapy using genetically engineered bacteria; infectious disease

Cell Therapy

  • SSCs/PCs or PSC-DCs

Novel somatic stem/progenitor cells (SSCs/PCs) or pluripotent stem cell-derived cells (PSC-DCs) that have therapeutic potential for serious diseases with very limited treatment options

〈Requirements〉

Patentablility
Definite characteristics that can be distinguished from the other known SSCs/PCs/PSC-DCs (and from which benefits in clinical use could be inferred)

〈Preferences〉

Supposed candidate target diseases/therapeutic areas to be applied
Data suggesting clinical efficacy
Versatility of the technology that is used for making the cells and/or defining the cell characteristics
In the case of PSC-DC, consideration about the purification process, safety, and formulation

We are particularly interested in technologies concerning cell/gene modifications that improve cell therapeutic effects remarkably and/or reduce immunogenicity in recipients drastically.

  • Adoptive T cell therapy

Technologies for high quality iPSC-derived T cells

Comparable to native T cells in terms of cell killing, tumour infiltration, and cytokine production
TIL (tumour infiltrating lymphocyte) research which enables the identification of differences between TILs and non-TILs

Technologies which potentiate T cells:

to overcome the immunosuppressive tumour microenvironment and elicit intrinsic immunity
to have high infiltrating activity into tumour tissues
to have a strong killing ability
to elucidate effective suicide mechanism

Relevant animal models and/or in vitro assays:

for measurement of T cell efficacy and potency
to predict risks of cytokine release syndrome and/or neurotoxicity

Technology

  • Oncology

Unique research platforms utilizing clinical specimens, cutting-edge technology, computational biology, or “big data”

In vitro and/or in vivo unique analytical methods for epigenetics, cancer metabolism, cancer stemness, immuno-modulation, microenvironment (e.g. in vivo/clinical flux analysis of metabolites; single cell gene expression analysis to evaluate intra-tumour heterogeneity)

Novel cancer models (in vitro and/or in vivo)

Reflecting clinical disease conditions and having better predictability of drug efficacy (e.g., tumour types with high unmet medical needs such as glioblastoma)
Reflecting cancer stemness properties or heterogeneity relating to resistance or refractoriness
Reflecting immunosuppressive tumour microenvironment in cancer patients (to forecast efficacy and toxicity in human)
Using efficient/conditional genome editing in cancer cell-lines

New technologies enhancing cancer-specific targeting or cancer immunity

New protein/peptide/small-molecule scaffolds that are applicable for drug conjugation
  • High internalization into the cancer cell
  • High tumour penetration
  • High selectivity for tumour sites
  • Pro-drug technology activated only in tumour sites

No interest in liposomes and exosomes as a delivery modality

  • Nucleic Acid Therapeutics (NATs) and Gene Vaccines
Novel mRNA modification methods suitable for nucleic acid therapeutics
Novel molecular targets in genetic disorders suitable for nucleic acid therapeutics
Novel molecular antigens in genetic disorders, rare cancers and pediatric cancers suitable for gene vaccines but not for peptide vaccines
Novel delivery platforms for systemic or local administration of antisense oligonucleotides, siRNA or modified mRNA

Daiichi Sankyo owns chemically modified ENA® oligonucleotides technology*. ENA® is currently being applied as a treatment for Duchenne Muscular Dystrophy in a clinical trial. In order to enhance our capability of ENA technology, we are interested in innovative delivery systems for antisense oligonucleotides, especially targeting muscle, CNS and bone marrow.

No interest in viral vectors, delivery systems specific for plasmid DNA therapy, peptide vaccines

  • Engineering for Protein Therapeutics
Novel affinity purification tags which can be removed during DSP of protein therapeutics
Novel bio-conjugation methods to fuse two or more molecules by enzymatic reaction

We have protein therapeutics other than antibody format (IgG). We welcome innovative and versatile technologies that improve DSP of protein therapeutics.

No interest in removal of an affinity tag with protease and chemical conjugation

  • Gene Therapy

Novel technologies for gene therapy which can overcome the problems of current technologies

Existing gene therapy technologies have some limitation or problems such as gene size, immunogenicity, risk related to gene insertion, administration route. Therefore, our interest is technological innovation relevant to gene therapy, such as novel vector (e.g. no insertion, bigger gene size, longer expression, on/off system) or delivery system (e.g. minimum immunogenicity).

No interest in gene therapy associated with gene insertion into host genome

  • Drug Metabolism and Pharmacokinetics

Analytical studies of drug response using quantitative systems biology model based on experimental data

Quantitative research using mathematical models which mimic the physiological response in humans

This research will be applied to understanding the physiological conditions and pharmacological effects, estimating unknown mechanisms of drug effects, and to selecting novel drug targets and predictive biomarkers.

In vitro cellular systems precisely mimicking in vivo conditions of drug metabolism and transport

Novel ideas/methods improving IVIVE, including cell-preparation procedures from fresh tissues, long-term cell culturing, and organ-on-a-chip technologies which mimic metabolism and uptake/efflux in liver, kidney and small-intestine

Existing in vitro technologies (microsomes, cryo/fresh cells) have limitations in extrapolating in vivo phenomena, due to in vitro insufficient activity of the metabolic enzymes and transporters. Thus, we are looking for proposals that overcome these limitations.

Analytical platforms which detect biomarkers in body fluid (e.g. blood, urine etc.) in the oncology field

Novel analytical methods of biomarkers in exosomes and circulating tumour cells
Novel liquid-biopsy platforms, other than circulating cell-free DNA, exosomes, and circulating tumour cells

Proposals should include the information on character of samples to be collected and detection methods to be used, such as NGS (next generation sequencing), MS (mass spectrometry) and Imaging.

Delivery systems/platforms

Novel tumour-specific drug delivery systems/platforms for compounds, antisense oligonucleotides and biologics superior to conventional passive and active targeting techniques
  • No interest in molecular modification and conjugation with antibodies and synthetic polymers
Novel cell/tissue-specific delivery platforms for vaccine antigens and adjuvants to target antigen presenting cells, such as dendritic cells and Langerhans cells, etc.

High-throughput in vitro systems predicting human blood-brain barrier and/or blood-retinal barrier permeability with high accuracy

We are looking for methods that quantitatively estimate permeability and which overcome species differences between rodents and human models.