Therapeutics-oriented Proposals

Neuroscience

REF#1

Novel drug discovery proposals for neurodegenerative disorders, genetic neurological diseases, other rare diseases with neurodegeneration and innovative research related to healthy aging, such as novel therapeutic approaches to prevent or stop progression of neurodegeneration

Neurodegenerative disorders of particular interest:

Amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), Down syndrome with Alzheimer’s disease, cerebral amyloid angiopathy (CAA)

Genetic neurological diseases of particular interest:

Huntington’s disease (HD), ataxias, spinal bulbar muscular atrophy (SBMA), muscular dystrophies (DM1, FSHD, DMD), Charcot-Marie-Tooth disease (CMT)

Topics of high priority include:

• Novel therapeutic approaches in the indications above including those targeting aberrant glial cells, key autonomous and non-autonomous disease-relevant pathways
• Research on cellular senescence with relevance to neurodegenerative disease
• Proposals on innovative therapeutic approaches (e.g. small molecule, nucleic acid, antibody) targeting key pathobiological features including abnormal RNA/DNA structures, RNA splicing and protein production widely observed in rare/intractable neurological disease
• Novel therapeutic approaches addressing irregularities in sleep/circadian rhythm, waste clearance, BBB integrity, age-associated chronic inflammation, organelle homeostasis, DNA damage and sensory system
• Research aiming to faithfully recapitulate clinical symptoms and pathology, driven by clinical sample use and/or reverse translation approach

REF#2

Small molecule-based approaches to address neurodegenerative disorders, genetic neurological diseases

Chemistry-driven drug discovery programs based on innovative mechanism of action addressing the following aspects will be prioritized:

• Protein degraders targeting ubiquitin-proteasome or autophagy-lysosome systems
• DNA/RNA targeting molecules (e.g. RNA-binding proteins and/or their complex)
• Molecular chaperones

Neurodegenerative disorders of particular interest:

Amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple system atrophy (MSA), Down syndrome with Alzheimer’s disease, cerebral amyloid angiopathy (CAA)

Genetic neurological diseases of particular interest:

Huntington’s disease (HD), ataxias, spinal bulbar muscular atrophy (SBMA), muscular dystrophies (DM1, FSHD, DMD), Charcot-Marie-Tooth disease (CMT)

Oncology

REF#3

Induction of antitumor effects in “cold” tumors insensitive to immune checkpoint inhibitors

• Clinically relevant models that faithfully recapitulate the microenvironment of “cold” tumors
• Proposals addressing tumor-promoting inflammation and tumor evasion of immune destruction
• Proposals addressing novel mechanisms of genome instability and mutations in tumor (classical DNA damage response will be out of focus)

REF#4

Innovative and differentiated technologies/concepts feeding into the immuno-oncology drug discovery for solid tumors

• Novel technologies enabling a selective drug delivery to the TME or tumor-draining lymph nodes (TDLN) via systemic administration – excluding conventional antibody-drug conjugate (ADC) approaches
• Novel approaches/models for target identification/validation focusing on the modulation of antitumor immune responses by (1) cancer-associated fibroblasts or (2) B cells/tertiary lymphoid structures (TLS) in the TME
• Multidimensional single-cell studies aiming for the discovery of novel disease mechanisms/drug resistance mechanisms (such as immune checkpoint blockade) in cancer patients

Rare Diseases (Genetic and Hematology)

REF#5

Novel therapeutic approaches for lysosomal storage disorders, inborn errors of metabolism (liver metabolic & neurometabolic) and rare non-malignant hematologic diseases, especially sickle-cell disease and hemophilia

The following topics will be prioritized:

• Next-generation gene therapy/gene editing technologies, prioritizing in vivo approaches
• Non-viral gene therapy delivery technologies that allow re-dosing, addressing current challenges such as nuclear translocation of transgenes
• Targeting technologies for CNS and liver for use in viral and non-viral gene therapies
• Small molecules with potential for transformative treatment, as well as novel targets for small-molecule intervention in above disease areas