A1-01

Identification of novel immune suppressive cells in tumors

Identification of novel cell types that should be depleted to enhance antitumor immunity

Particular focus:

• Research using human samples
• Research using preclinical model to confirm antitumor activity
• Research in which cell markers for those cells can be identified

Out of scope: pancreatic cancer-related research, regulatory T (Treg) cell-related research

A1-02

Technologies that induce host immune responses against solid tumors to enhance therapeutic effects

Techniques to overcome cancer heterogeneity:

• Techniques for modulating the innate immune system to induce T cell responses against neoantigens
• Techniques for modifying the tumor microenvironment (e.g., relieving immune suppression)

Requirements: These techniques should be applicable to adoptive cell therapy, multispecific antibody-based therapy, etc.

A1-03

Technologies for optimizing CAR molecules and obtaining binders suitable for CAR

Technologies to optimize CAR molecules for sufficient functionality in vivo

Particular focus:

• Platform to obtain antigen-binding moieties suitable for CAR and optimize them
• Techniques for optimizing each domain of CAR molecules

A1-04

Technologies and evaluation systems for the avoidance of on-target, off-tumor toxicity of adoptive cell therapy

Research that contributes to avoiding on-target, off-tumor toxicity of adoptive cell therapy:

• Technologies to activate CAR-T cells in tumor environment-specific manner and hence reduce or avoid off-target toxicity to normal tissues
• Evaluation systems to assess on-target toxicity of adoptive cell therapy in vitro and in vivo

A1-05

Technologies that provide off-the-shelf immune cell therapy for cancer treatment

Technologies for off-the-shelf immune cell therapy, such as allogeneic cell therapies and in vivo gene transduction techniques. Manufacturing and analytical methods for clinical use of allogeneic cell therapy are also included (e.g., large-scale production of homogeneous cells, large-scale cryopreservation).
Requirements: Efficacy comparable to that of autologous CAR-T therapy
Out of scope: NK cell

A1-15

NK cell engager

Novel NK cell engager with the potential to show anti-tumor efficacy against solid tumors. The concept that enables superior efficacy to DF1001 (Dragonfly therapeutics) would be preferable.

A1-06

Tumor-specific binders for cancer therapy and their discovery methods

Antibodies or antibody-like binding molecules (antibody mimetics, Fab, scFv, sdAb, etc.) against tumor tissue (tumor cells/tissues, immune cells, stromal cells, etc.)-specific targets and their discovery methods
Note:

• Tumor tissue-specific targets refers to those characterized by tumor tissue-specific conformational changes (to an active conformation) or modifications (phosphorylation, glycosylation, etc.), rather than their elevated expression levels in tumor tissues.
• Binder discovery methods preferably include methods for identifying tumor tissue-specific targets.

A1-07

Research on bi-/multi-specific antibodies for cancer therapy

• Identification of bi-/multi-specific antibodies (Bs/MsAbs) or antibody-like binding molecules (e.g., antibody fragments, mimetics, single domain antibodies (sdAbs)) with unique MoA
• Design of Bs/MsAb using Artificial Intelligence (AI) or Machine Learning (ML) technologies

A1-08

Targeting two molecules in close proximity on the cell membrane

Research on induced proximity of two molecules on the cell membrane. This includes 1) methods for detection and evaluation of proximity molecules, 2) search, identification, analysis of the physiological effects of the proximity molecules that can lead to drug discovery research, and 3) binders that recognize the two molecules.

A1-16

Small molecule binders to cancer related proteins applicable to heterobifunctional degraders

Small molecule binders (e.g., inhibitors) that became out of focus in the external research organizations (e.g., academia, biotech, pharma) due to lack of in vivo efficacy or other issues.
Particular focus:

• Unpublished binders
• Cellular active (GI50 <100 nM) and cancer cell selective (>10-fold) binders
• Binders to protein that is related to cancer cell proliferation

A1-09

Cancer-specific neoantigens and their discovery technologies

Cancer-specific neoantigen candidates and novel technologies to systematically identify them
Requirements:

• Not classical approach like WES/RNA-seq/NetMHC prediction flow
• Neoantigen candidates are validated at protein level.
• Clinical samples/real world data can be analyzed.

A1-10

Tumor environment-dependent functional peptides and their discovery technologies

• Peptides that become functional by activation (increased binding to antigens, payload dissociation, etc.) only in tumor microenvironment, which exhibits characteristics such as high ATP concentration, low oxygen levels, low pH, and abundant proteases compared to normal tissues.
• Discovery technologies of above peptides

A1-11

Antibodies, peptides and small molecules with high penetration and retention in tumor stroma

Antibodies (including smaller formats such as VHH antibodies and scFvs), medium-sized molecules and small molecules that possess high penetration and retention in stroma-rich cancers (e.g., pancreatic cancer)
Preferences:

• Molecular targets are well defined.
• Antibodies have stable physicochemical properties.

A1-12

Drug discovery for cancer theranostics

Drug discovery for cancer theranostics based on protein engineering
Particular focus: Cancer targeting peptides/proteins conjugated to the payload of small molecules, near‐infrared fluorescent dyes, or radioisotope (RI). Proteins include antibody fragments, modified proteins, etc.
Note: Although any research topic is acceptable (targets, technologies, ideas, approaches, etc.), the research is limited to those with ideas for its clinical application.

A1-18

Radioisotope payloads for the application to solid cancer therapy

Technologies for cancer radiotheranostics based on antibodies or peptides:

• Stable supply of radioisotopes (RIs)
• Chelation techniques that allow stable labeling of the RI to antibodies or peptides

Note: Radiotheranostics combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy.

A1-13

Human tumor microenvironment models

1. Models that faithfully reflect the characteristics of human pancreatic cancer:
   • In vivo models that contain more than 70% stromal regions, show high expression of digestive enzymes, and have tissue structures such as lumens that closely resemble the clinical features of human pancreatic cancer
   • Ex vivo models such as pancreatic cancer slice cultures that allow high-throughput evaluations of cytotoxicity and penetration
2. In vivo/in vitro/ex vivo models that reflect human tumor microenvironments, especially the infiltration of immune cells and stromal cells, and can evaluate host immune responses in lung cancer, pancreatic cancer and colorectal cancer

A1-17

Next-generation near-infrared light irradiation devices

Next-generation near-infrared light irradiation methods and devices that are simpler, deeper reaching, and less invasive than existing methods. Attachable devices such as luminescent sheets are also included.

A1-14

Research to improve radiotherapy

Studies/ideas that may reform current radiotherapy:

• Studies to enhance the efficacy or improve the safety of existing radiotherapies (including combination therapies).
• Ideas that can be applied to systemic therapy to target systemic metastatic tumors

Particular interest: novel concepts/approaches based on the pharmacological mechanisms of action of radiation
Out of scope: combinations of existing drugs, targeted alpha therapy (TAT)

A2-01

Novel therapeutic targets/pathways leading to drug discovery for psychiatric disorders

Research to identify novel therapeutic targets/pathways for psychiatric disorders
Focused diseases: treatment resistant depression, refractory epilepsy, obsessive compulsive disorder Requirements:

• Target/pathway is shown to be related to disease states in humans.
• Evaluation methods that can predict clinical efficacy are available.

Out of focus:

• Target/pathway is devoid of human disease information.
• Target/pathway cannot be evaluated in rodents.

A2-02

Novel therapeutic targets/pathways targeting glial cell functions involved in the pathogenesis of psychiatric disorders

Research on novel therapeutic targets/pathways that focus on dysfunction of glial cells involved in the pathogenesis of psychiatric disorders
Focused diseases: treatment resistant depression, schizophrenia, refractory epilepsy
Requirements:

• Target/pathway is shown to be related to disease states in humans.
• Evaluation methods that can predict clinical efficacy are available.
• Pathological hypothesis based on CNS inflammation in primary diseases is available.

Out of focus:

• Target/pathway is devoid of human disease information.
• Research on inflammation during fetal or neonatal period leading to developmental disorders
• Research on secondary CNS inflammation caused by peripheral inflammation

A2-03

Animal models of neurodegenerative diseases

Research on animal models of neurodegenerative diseases:

• Disease models showing prodromal symptoms
• In vivo brain imaging analysis of organelle dynamics and neurophysiological activity in health and disease
• Disease models focusing on the resilience and metabolism of neural cells (including, but not limited to, lipid metabolism, lipid droplet and neurodegenerative lysosomal disorders). This also aims to explore new therapeutic targets.

Out of scope: Mouse models with mutations in genes related to lysosomal diseases

A2-04

In vitro models of neuronal dysfunction for the discovery of novel therapeutic targets

Innovative and robust bioassay systems that recapitulate neuronal dysfunction in neurodegenerative diseases Particular interest: Culture/assay methods that reflect the disease-related phenotype and/or gene expression profile of the cell types that contribute to the development and progression of neurodegenerative diseases (e.g., neurons (cortical, motor, dopaminergic cells), reactive astrocytes in ALS, multiple subtypes of microglia observed in AD)
Out of scope: Conventional patient-derived iPS cells or genetic models (e.g., a-Syn A53T)

A2-05

Research for finding novel therapeutic targets with clinical relevance to neurodegenerative diseases

Research for finding novel therapeutic targets utilizing clinical information regarding prognosis of neurodegenerative diseases and/or data from clinical trials
Example: Based on the clinical information that thin people progress faster in ALS and that calorie intake is the standard of care in the early stages of the disease, enhancing energy metabolism in motor neuron can be a therapeutic target for ALS.

A2-06

Novel biomarkers in central nervous system disorders

Novel biomarkers and their measurement techniques in the area of psychiatric disorders and neurodegenerative diseases. We are interested in biomarkers that can be effectively utilized in non-clinical settings with high translational potential for clinical use. Additionally, we are seeking highly specific biomarkers that can aid in patient stratification and serve as predictive biomarkers for treatment outcomes.
Particular focus:

• Techniques related to neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Lewy body dementia, amyotrophic lateral sclerosis, multiple system atrophy)
• Evaluation systems that can specifically detect microglia (separate from macrophages)
• Non-invasive methods for assessing CNS pathologies such as neuroinflammation (e.g., imaging)

A2-07

Novel DDS technology to penetrate BBB

Novel DDS technology that enables systemic delivery of the CNS drugs using modalities that are considered difficult to penetrate BBB

A2-08

Nose-to-brain delivery of peptides

• Technologies for delivering short peptides to brain via nasal administration
  Particular focus: Technologies that have a clear advantage over existing technologies in terms of delivery efficiency
• Methods for predicting nose-to-brain transport in humans based on species differences in nasal anatomy and physiology

A3-01

Novel therapeutic targets of macrophages in fibrosis

1. Novel therapeutic targets of macrophages in fibrosis such as MASH or IPF. The target is limited to those that have not been tested in clinical trials.
   Particular focus:
   • Relationship among disease, pathogenic cells and therapeutic target molecules is shown.
   • Targets with genetic evidence or targets that were identified from omics data analysis using human clinical samples
2. An exploratory study of novel therapeutic targets of macrophages in fibrosis
   Particular focus:
   • Study utilizing omics data analysis
   • Study utilizing transcriptome analysis, GWAS analysis or whole exome analysis from human samples
   • Study that can evaluate the relationship between target cell and target molecule utilizing single-cell analysis

A3-02

Drug validation tools that mimic pathological condition of fibrosis

Technologies to validate drug candidates using tissues/cells from clinical specimens of fibrosis such as MASH or IPF:

• Drug validation tools using tissue slices
• Drug validation tools using human immunocompetent cells in fibrosis
• Validation of drug targets using above tools

A3-03

Novel therapeutic targets for heart failure

Research to explore novel therapeutic targets for heart failure (HFrEF, HFpEF, cardiomyopathy, etc.) using human myocardial samples, iPS cell-derived cardiomyocytes from heart failure patients, etc.
Note: We aim at drug discovery for knockdown/replacement therapy using siRNA or AAV based on the newly identified target.

A3-04

Animal models of microcirculation disorders

Animal disease models that reflect clinical pathologies of microcirculation disorders and are used to evaluate compounds that improve microcirculation. An animal model with diabetes in the background is more preferable.
Examples: type II myocardial infarction, INOCA, ANOCA, coronary artery disease, cerebral small vessel disease, atrial fibrillation, HFrEF, HFpEF

A3-05

Novel and unique disease models of macular degeneration

Drug discovery research using disease models of macular degeneration (e.g., atrophic age-related macular degeneration, Stargardt disease) that have high translational potential for clinical use:

• In vitro and in vivo disease models that are close to human disease states in terms of disease state inducers, gene expression, and pathology
• Research to evaluate the efficacy of drugs using above models

A3-06

Drug discovery research for gene-independent therapy of retinitis pigmentosa

Research for the treatment of retinitis pigmentosa (RP). Given the wide range of genetic mutations that cause RP, we are interested in therapy that is effective across a broad spectrum of genotypes.

• Drug target molecules/mechanism and/or drug candidates that may enable gene-independent therapy. The target molecules are limited to those with proven efficacy in animal models or those supported by analysis of patient samples.
• An exploratory study of genes that may exhibit therapeutic effects upon overexpression or knockdown in gene-independent manner

A3-07

Drug discovery research for dry age-related macular degeneration

Research for the treatment of dry age-related macular degeneration:

• Drug target molecules/mechanism and/or drug candidates with promising therapeutic benefits. The target molecules are limited to those with proven efficacy in animal models or those supported by analysis of patient samples.
• An exploratory study of genes that may exhibit therapeutic effects upon overexpression or knockdown

A4-01

Novel targets for gene therapy

>Novel targets for gene therapy that are expected to have therapeutic effects through gene supplementation, knockdown, or a combination of both.
For gene supplementation, modified sequences that lead to differentiation from natural protein sequences in terms of efficacy and chimera sequences with non-human species are also included.
Requirements:

• The target is limited to those that exhibit therapeutic effects in tissues and cell types to which the gene can be delivered by AAV (including cases where the drug's efficacy is exerted through secretion into systemic circulation).
• For a novel target of single gene knockdown, the target is limited to those that can be differentiated by gene therapy from existing therapies against the same target.

Particular focus:

• A research that can evaluate the effects of target in in vitro/in vivo systems
• An exploratory study of novel targets using patient cells and tissues that allow omics data analysis or genomic analysis

Out of scope: Diseases with a prevalence of less than 1 in 100,000 individuals in Japan and the US

A4-02

Novel therapeutic approaches for chromosomal abnormalities

Technologies to validate target candidates for the treatment of refractory chromosomal abnormalities such as translocations, deletions and trisomies, using tissues/cells from clinical specimens and model animals. The target candidate is limited to those suitable for gene therapy.
Examples:

• Pathological mechanism studies using disease-specific iPS cells or human-derived organoids
• Target validation tools using organ-on-a-chip systems that mimic clinical pathologies
• Target validation tools using novel animal models that mimic clinical pathologies
• Validation of drug targets using above tools

A4-03

Gene therapy to normalize repeat sequences in trinucleotide repeat disorders

Novel gene therapy technologies to normalize repeat sequences for treatment of diseases such as Huntington's disease, spinocerebellar ataxia, and myotonic dystrophy type 1. This includes genome editing technologies, but we prioritize methods with higher selectivity to repeat sequences that demonstrate high efficacy and safety.
Out of scope: small molecules

A4-05

Techniques for evaluating in vivo delivery of gene therapy agents

Techniques that can quantitatively assess in vivo delivery of AAV capsids in gene therapy, and have high translational potential for clinical use
Examples:

• Establishment of a human liver perfusion model
• Establishment of human tissue organ-on-a-chip systems

Out of scope: commercially available humanized mice/primates

A4-04

Diseases that can be treated by protease inhibition

Diseases in which proteases are involved in disease states
Particular focus: diseases with following characteristics

• Can expect dramatic improvement by single protease inhibition
• No toxicity or little toxicity is expected by systemic inhibition of the protease
• Target validation has been completed using animal model or at cellular level
• Preferably an animal model of the disease is available

Out of scope:

• Need to inhibit three or more proteases to treat diseases
• Proteases without extracellular secretion
• Diseases treated well by existing drugs
• Cancer
• Infectious disease