NIBR Scientific Needs List for the NIBR Global Scholars ... · Scientific Needs List is designed to guide you in aligning your proposal with the NIBR portfolio. Please note that the

Academic Partnerships & External Innovation Public

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NIBR Scientific Needs List for the NIBR Global Scholars Program 2020 The Novartis Institutes for BioMedical Research (NIBR) is seeking to advance science through the NIBR Global Scholars Program (NGSP). For NGSP, NIBR is requesting proposals exploring breakthrough science that is a strategic fit with the NIBR portfolio. The NIBR Scientific Needs List is designed to guide you in aligning your proposal with the NIBR portfolio. Please note that the development of novel technologies, tools, and animal or cellular models in this list would only qualify for NGSP within the context of a broader project and not as standalone proposals. These specific topics are marked by an (*). NIBR also welcomes transformative ideas that could be game changers for patients, even if they do not directly fit the NIBR Scientific Needs List.


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Topics of NIBR Scientific Needs List for NIBR Global Scholars Program 2020 Disease Areas

Autoimmunity, Transplantation & Inflammation Cardiovascular and Metabolic Immuno-Oncology Musculoskeletal Diseases Neurosciences Oncology Ophthalmology Respiratory Diseases Tropical Diseases Additional Disease Areas

Platform technologies

Analytical Sciences & Imaging Biologics Cell and Gene Therapy Chemical and Biological Therapies Discovery Chemistry Engineering Technologies and Innovation


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DISEASE AREAS Autoimmunity, Transplantation & Inflammation Diseases, Indications Rheumatoid and/or spondylo-arthritis New therapeutic concepts to treat rheumatoid and/or spondylo-arthritis, positively differentiated from standard of care in terms of efficacy. Increase understanding of molecular disease pathology and patient endotypes.

• Unexplored new molecular pathways/mechanisms to achieve remission or overcome unresponsiveness to standard of care

• Molecular pathology in relevant disease tissue • Markers/possibilities for patient stratification for existing and emerging therapies • New translational animal and cellular models, which enable to discover/validate novel

pathomechanisms and to characterize patient subpopulations at the molecular level * Scientific Concepts Inflammasome biology in disease Identify indications with high unmet medical which are driven by activation of NLRP3 and other inflammasomes.

• Identify new markers of inflammasome activation • Demonstrate inflammasome activation in relevant disease tissue • Demonstrate impact of inflammasome pathway in translational animal model • Identify new activating signals for NLRP3 and other inflammasomes • Identify disease links for inflammasomes other than NLRP3

Novel delivery technologies for tolerogenic principles Looking for different forms of nanoparticles (not cell therapies) which may include tissue/cell targeting and/or special distribution properties.

• Research tools for exploring potential utility in T1D * Metabolic pathways for tolerance inducing approaches Immune cells adopt a metabolic state (signature) that is linked to their effector function. Interfering with this signature may provide means to modulate immune cells towards a tolerizing phenotype (e.g. Tr1 or iTreg cells). Looking for ways to modulate the immune metabolism and identify novel targets.

• Tools and platforms to investigate immune metabolism (carbohydrates, lipids, proteins and transcriptomics). Critical is the comparison of different immune cell subsets and pathways involved in activation, suppression and differentiation also in the context of a relevant microenvironment, e.g. organ specific tissue and under inflammatory vs steady state conditions

* NGSP proposals must have broader context; see note on second page


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Cardiovascular and Metabolic Diseases/ Indications/ Targets Heart Failure

• Novel HFpEF and HFrEF agents or targets • Post-MI heart failure prevention agents or targets • Cardiomyocyte regenerative agents or targets • Safe inotrope and lusitrope agents or targets • Novel agents or targets that promote favorable cardiomyocyte energetics

Arrhythmia (only oral LMW, atrial fibrillation, not ventricular tachycardia)

• New atrial fibrillation (AF) targets and agents for rhythm control or prevention, particularly in AF with structural heart disease or heart failure. Ion channel and non-channel targets.

Atherosclerosis

• Pharmacological revascularization / atherosclerosis regression targets or agents Metabolism/obesity

• Agent/combination for safe and durable weight loss comparable to bariatric surgery • Appetite suppressants / satiety enhancers or targets for same • Calorie wasting / futile cycle strategies • New genetically validated targets for obesity or improved adipose function • Targets/pathways/agents that improve cardiac metabolism

Valvular Heart Disease

• Understanding the pathophysiology of aortic stenosis and its progression Enabling concepts/ technologies

• Targeted delivery technologies: o Cell-type specific drug delivery to cardiomyocytes, macrophages, endothelial

cells or adipocytes. LMW, antibodies, siRNAs. Modality agnostic. o AAV or non-viral gene delivery that provides durable gene expression in

cardiomyocytes, hepatocytes, adipocytes or macrophages without inflammation o Efficient delivery of siRNAs beyond the hepatocyte

• Cellular models *: o Atrial and ventricular cardiomyocytes for in-vitro studies that are demonstrably

more mature than existing iPSC or ES-derived cells o 3D cultures that would enable studying tissue/nerve interactions (intestinal

organoids with neuronal cells, adipocytes with neuronal cells) • Animal models *:

o Rodent model with durable atrial fibrillation o Animal model of atrial fibrillation with heart failure o Animal model of aortic stenosis

• Understanding pathophysiology of: o HFpEF. Patient subsetting by risk and mechanism o Atrial fibrillation. Patient subsetting by risk of progression and mechanism

• Technologies to measure cardiac energetics in rodent models * • Improved longitudinal imaging of atherosclerotic plaques in humans and animals • Plasma biomarkers of atherosclerotic plaque burden or activity • High throughput technologies to validate large numbers of SNPs


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Exclusions/Out of Scope

• LDL or triglyceride lowering agents • Glucose-lowering agents for diabetes w/o disease modification • NASH agents



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Immuno-Oncology

Disease/Indications

• Pancreatic cancer • Colorectal cancer • Breast cancer • AML • B-cell malignancies

Within the context of these diseases, 1. Elucidate the role of immune metabolism, by identifying novel metabolic pathways that modulate adaptive and innate immunity.

• Determine and understand signatures of metabolic states that drive regulatory and effector immune cell responses

• Interrogate the immune-metabolome to identify novel immune-modulatory targets • Access novel tools and platforms to investigate immune metabolism

o carbohydrates, lipids, proteins and transcriptomics • Analysis of immune cell subsets and pathways involved in activation, suppression and

differentiation. Include impact of microenvironment, e.g. cancer, organ specific tissue, inflammatory vs steady state conditions

2. Novel approaches to activate innate immunity to elicit an integrated immune response against cancer.

Novel tumoricidal targets or therapies for reprograming the tumor microenvironment via innate immune cells. • New translational animal and cellular models to discover/validate novel mechanisms and

characterize patient subtypes at a molecular level 3. Molecular mechanisms mediating interactions between the neural and the immune systems.

• Mechanistic insights into neuro-immune communication and neural circuits regulating immunity in cancer setting

• Novel targets, pathways or therapies capable of reprogramming the tumor microenvironment via Immune-Sensory- Neuron Interface

• New translational animal and cellular models to discover/validate novel mechanisms and to characterize patient subpopulations at the molecular level

4. Novel CAR-T components.

• Novel surface T cell antigens target and their cognate T cell receptors (TCR) • Novel and specific tumor surface protein (and their cognate TCR) to enable next

generation of CART cells therapy • Novel markers and pathways of resistance to CART therapy


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Musculoskeletal Diseases Diseases, Indications Osteoarthritis Regenerative approaches for osteoarthritis.

• Drug modalities with pre-clinical efficacy • Biomarkers (local and/or systemic) with pre-clinical validation

Peripheral neuropathy Understanding of therapeutic intervention nodes in peripheral neuropathy.

• New potential therapeutic targets to treat peripheral neuropathy (validated in animal models, clinical biomarkers or GWAS)


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Neuroscience Indications & Concepts Targets with validated data in humans (genetic –large databases/ pharmacological/ clinical/ medical records). First-in-class/best-in-class programs. Neurodegeneration Late-stage clinical programs.

• Parkinson’s Disease e.g. LRKK2, Pink1/Parkin, GCAS and USP30

• Alzheimer’s Disease e.g. APOE4 –targeting lipid metabolism

• Multiple Sclerosis Primary progression. Interest in re-myelination (large effect). Exclusions: relapse or remitting MS, approaches w/ CD20, SP-1, thyroid hormone.

• Frontotemporal Degeneration, Progressive Supranuclear Palsy, Amyotrophic Lateral Sclerosis, Huntington's disease

Neuropsychiatric disorders Transformative programs with genetically validated targets or new MoA, proof-of-concept, differentiated from existing serotonin, dopamine, acetylcholine approaches.

• Schizophrenia e.g. NMDA receptor-PAMs to target hypofunction of glutamate/serine receptors –synapse and ion channel biology

• Depression, Addiction Schizophrenia, aggression regulation (e.g. antagonism of lateral hypoth./ amygdala)

Pediatric neurology

• Autism • Monogenic diseases (w/pop > 2-10k; GTx) • Syndromic intellectual disability (e.g. Syngap1) • Early-onset epilepsy • Neuromuscular diseases • Mitochondrial disorders, Lysosomal Storage Disorders (late-stage assets)

Neuroinflammation

• In neurodegeneration and psychiatric disorders • Neuroinflammation and microbiome (Novel mechanisms of action)

Enabling Technologies

• CNS delivery o Transformative, e.g. >10-fold improvement over current exposure

• siRNA o NS delivery, intrathecal, t1/2 ~6mo >10-fold improvement

• Novel gene editing platforms targeted to the CNS o Novel AAV capsids with improved transduction, gene activation, payload (>4kb) o Gene editing (e.g. capable of AAV or other viral vector delivery to CNS) o Gene regulation (e.g. genetic switches)

• Digital therapies o Digital diagnostics


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Exclusions/Out of Scope

• Pain (unless neuropathic pain) • Symptom treatments are of lower priority • Addictions • Stroke • Spinal cord injury • Traumatic brain injury • Stress disorders (e.g. PTSD) • Anxiety (high bar) • Devices (e.g. electro stimulators. Interest if device for CNS delivery) • Enabling technologies: Exosomes


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Oncology Targeting RAS

• Novel approaches to targeting RAS driven tumors • Novel targets in RAS driven tumors

Novel Target Identification Approaches • Novel approaches and systems to target identification for tumor and immune cell targets • New model systems differentiated from internal ones, computational methods, screening

concepts • Novel approaches to identify and/or predict efficacious combinations

Radio Ligand Therapy

• Identifying new targets for Radio Ligand Therapy (RLT) • Developing new models for predicting RLT response • Advancing the understanding and application of RLT against different tumor types • Identifying new combinations of RLT and other cancer therapies that generate improved

responses in tumors


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Ophthalmology

Disease/Indication; Scientific concept New therapeutic concepts to treat intermediate macular degeneration (iAMD), positively differentiated from complement therapy

• Increased understanding of iAMD pathology and patient endotypes • Molecular pathology of AMD donor human eyes • Analysis of sub-retinal drusen or soft drusen composition • Models of AMD lipid dysfunction * • Models of choroidal dysfunction *

Enabling technologies Non-invasive means of serially measuring label free drug levels, LMW or biologics in ocular tissues (in particular posterior tissues, but anterior segment tissue, e.g. Trabecular Meshwork, too)

• Advanced imaging/spectroscopy technologies that would require no or very minimal modifications to the target molecule of interest

Non-surgical, next generation refillable reservoir type of implant for ocular drug delivery to the vitreous for controlled release of a biologic

• plug-n-play long acting drug delivery system with an equivalent needle gage of ≥ 22G, as opposed to a surgical procedure

Preclinical system for continuous ocular infusion in small animals

• Next generation ocular mini drug pump



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Respiratory Diseases New concepts for pre-clinical models of COPD & IPF Novel translational in vivo animal models that capture mechanistic changes in disease and correlate with clinical findings, enabling:

• Discovery/validation of novel disease mechanisms • Characterization of patient subpopulations at the molecular level • Efficacy testing of new inhaled modalities/technologies • Generation of PK/PD data for lead compounds

New in vitro models for complex lung disease, including COPD and IPF

• In vitro models reflecting disease cellular and structural features • New human in vitro models that address aspects of structural, functional, and biological

features of complex lung disease; includes o New models of alveolar structure and cell-cell interactions o In vitro models of rare stem cell populations (e.g. distal airway stem cells) o Co-culture models with multiple disease-relevant cell types o Approaches for organoid culture that facilitate high-throughput screening

These approaches do not necessarily need to be lung-specific; for example, an in vitro model of epithelial-innate immune interactions in the gut would be of potential interest. Single cell RNA seq analysis for specific lung disease patient populations

• scRNA seq datasets for defined patient populations (e.g. COPD, interstitial lung diseases) • Novel data analysis approaches to these datasets will enable us to develop novel

therapeutic hypotheses Genetic associations for COPD or IPF

• Approaches to dissecting specific genetic determinants of risk or protection for COPD and IPF that address the challenges of the heterogeneity of the diseases and the environmental factor complications

• Genetic studies which show clear correlation with respiratory disease phenotypes and/or progression

• Data that suggests certain genetic loci increase risk for patients or are protective for patients

New Biomarkers for Respiratory Diseases • Clinical trials endpoints that correlate with changes in disease/outcomes, especially ones

that provide significant information in shorter time periods • New biomarkers and/or validated endpoints to enable more efficient clinical studies of

therapies in COPD, IPF, or Asthma Novel regenerative therapies to treat COPD

• Novel regenerative pharmacology approaches that enable the reversal the destruction of alveolar spaces in COPD patients

• Unexplored pathways or mechanisms to regenerate alveolar air spaces without fibrosis • Novel translational in vitro and in vivo model systems * • Novel markers to characterize appropriate patient populations



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Tropical Diseases (Novartis Institute for Tropical Diseases) Diseases, Indications Kinetoplastid diseases

• Chagas Disease o Sterile cure o Biomarkers for disease progression o In vivo models for disease progression * o Novel therapies (new targets to treat Chagas) o Adjunct therapy

• Leishmaniasis o Relapse free cure o Safe, short, broad-spectrum treatments

• Human African Trypanosomiasis o Safe, single dose cure

Cryptosporidiosis

• Promising anti-cryptosporidium compound with limited systemic exposure Malaria

• Radical cure • Fast-Killing blood stage anti-malarial targets

Scientific Concepts

• Novel screening platforms or assays for anti-parasitics • Novel therapeutics and disease management "kits" for diarrheal syndromes • Innovative therapies for major causes of maternal and child harm in developing countries

Enabling Technologies & Models Cryptosporidiosis *

• Cryptosporidium GI organoid model • Clinically relevant in vivo model (neonatal calf model) • Controlled human infection model for cryptosporidiosis

Malaria

• Sustained delivery technologies (malaria prophylaxis) • Biomarkers for hypnozoite liver infection • Long-term hepatocyte cultures *

Dengue

• Rapid field diagnostic for dengue



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Additional Disease Areas Liver, renal, hematopoietic stem cell transplant, benign hematology Insights into patient segmentation in NASH or diabetic kidney disease Identify information related to the etiology or epidemiology of NASH or diabetic kidney disease, including but not limited to patient sample profiling or biomarkers.

• Biomarkers of disease progression or likelihood of therapy response • Patient samples that could be profiled in collaboration with Novartis

Novel insights into alcoholic liver disease Scientific or medical insight into alcoholic liver diseases.

• Research tools * and new biology to enable pharmacological intervention in alcoholic liver diseases

• Insights into clinical trials in patients with alcoholic liver diseases that could enable more efficient study execution or greater likelihood of success

Mechanistic insights into kidney diseases Mechanistic insight into kidney disease, with a preference for biological concepts for treatment of proteinuric kidney disease, causes of kidney fibrosis, or polycystic kidney disease.

• Research tools * and new biology enable pharmacological intervention in diseases originating from defects in, or insults to, the renal tubules or glomeruli

New biology to enable reduced intensity hematopoietic stem cell transplant Identify new approaches to avoid the need for fully myeloablative conditioning before hematopoietic stem cell transplant (HSCT).

• New targets or technologies to create sufficient space in the bone marrow niche to enable engraftment of transplanted HSCs

Benign hematology: beyond sickle cell disease Therapeutic concepts in non-malignant hematology that are amenable to either pharmacological intervention or gene therapy, excluding sickle cell disease (SCD) or indications for which there is an adequate standard of care.

• New targets or biology to treat non-malignant diseases of the blood

Lipid droplet biology in the context of NASH or liver fibrosis Elucidation of the mechanism of action that genetic variants have on the development of NASH and liver fibrosis.

• Understand reported genetic interaction of both genes at molecular level • Identify novel genetic interactors/sensitizers using GWAS data

Hepatology: Translatable assays to predict efficacy of compounds in disease animal models and patients Animal models that:

• Increase the correlation between the efficacy of LMW compounds in cellular 2D assays and in disease animal models.

• Better reflect human disease Models that can be used to benchmark LMW compounds (either publicly available or provided by Novartis) with proven efficacy in animals and humans, and serve as validation regimen in mouse/human organs.

• Complex cellular in vitro assays that predict efficacy by incorporating the key cell types and disease stimuli

• Human primary cells and iPSC-derived cells * NGSP proposals must have broader context; see note on second page


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Platform Technologies

Analytical Sciences & Imaging Enabling Technologies & Models Machine learning for analyses of omics data Advanced methods for analysis of large and diverse sets of omics data for biomarker or compound mode of action information.

• Clustering data to disease endotypes or according to compound mode of actions. • Biomarker or mechanism of action information.


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Biologics Tissue-specific drug delivery Novel approaches to targeting therapeutics to tissues with high specificity and safety.

• Modular system that can be loaded with therapeutic drug and tissue-specific tag, allowing for tailored targeting of multiple tissues

o Example: nanoparticles that can be loaded with drugs and tagged with targeting moiety

• ‘Tissue tags’ that could be used in such a system to provide tissue specificity and safety o Examples: extracellular matrices biomacromolecules like collagen or hyaluronic

acid Intracellular delivery of biologics Novel approaches to overcoming extracellular and intracellular biological barriers that can inhibit drug delivery by nanocarriers. Compartment-targeted delivery can be pathway specific or have a more general mechanism.

Examples: • Cell penetrating peptides • Receptor mediated uptake • Endosomal escape • Viral (AAV or Lenti) gene delivery • Bacteria mediated gene delivery (type 3 secretion system or similar approaches)

Microfluidics high-throughput antibody screening with high sensitivity detection Novel approaches for single cell microfluidic or nanowell high-throughput antibody screening with advantages over current commercially available options. Improvements include highly sensitive detection capabilities that enable multiple options such as luminescence. Mass Photometry for improved molecule characterization Approaches to determine molecular weight using mass photometry that are improvements over conventional Mass Spec that would permit identification of:

• Clippings in therapeutic proteins in complex matrices, e.g. serum or cell culture supernatant

• Identifying protein clippings/Neo-N & C-termini • Molecular mass determination of large molecules, macromolecules and complexes (100-

1000 Kda such as therapeutic proteins, AAV, Lentiviruses) under native conditions Understanding the immune-pathogenesis mechanisms of different diseases Using cutting-edge technologies, we are interrogating the human immune repertoire to understand the role of the immune system in a variety of diseases, and to discover novel therapeutic modalities. For this, we are interested in projects that examine the molecular patterns in:

• Human tissues from patients who have recovered from otherwise chronic diseases or have a strong familial history of certain disorders such as idiopathic juvenile arthritis and heart failure

• Human auto-antibodies repertoires of individuals who have recovered from a known, specific disease in order to better understand the targets (auto-gens) and molecules (including antibodies)

Our interest covers data sets as well as access to human tissues in order to perform novel molecular interrogations.


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Cell and Gene Therapy

Scientific Concepts Cell Therapy

• CAR-T for hematology • Novel cellular approaches to solid tumors, focusing on native and engineered T Cell

Receptors (TCRs) • Innovative technical advances in switches, gene editing, and non-viral expression

systems Gene Therapy All therapeutic areas, particularly in ophthalmology, neurosciences, non-malignant hematology, metabolic disorders (Lysosomal Storage Disorders), hepatology, nephrology. In vivo delivery systems Viral (e.g., AAV, lentivirus) and non-viral (e.g., liposomes, lipid nanoparticles), that offer improvement in any of the following:

• Cargo size (>4.7kb of gene size) • Minimizing immunogenic response • Specificity for target tissues, in particular hematopoietic stem cells (e.g., capsid

engineering) • Adequate and durable gene expression (e.g., specific promoters) • Delivery of alternative cargos (e.g., biologics) to address chronic disorders beyond

monogenic disease Innovative genome editing technologies (e.g., multiplex editing, smaller editing components)

• Innovative gene expression vectors and controllable switches


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Chemical and Biological Therapies Create novel paths to transformative medicines through data and technology in areas of indicated interest to NIBR Tools to improve characterization of novel targets

• Assays for recording/measuring target engagement in cells Examples: Novel –omics, –seq and other related assays that are adaptable to cells of various origin (ideally including primary cells and at the single cell level), especially assays that can be multiplexed

• Complex cellular assays that are physiologically relevant and reflect the disease biology o Complex multicellular models that have the potential to bridge gaps between

mechanistic models and in vivo approaches. Must capture biology with higher relevance than classical 2D models, be scalable (in comparison with in vivo), have faster turnaround (in comparison with in vivo), and reduce use of animal models (3R).

Examples: spheroids, organoids or 3D organized structures, that can contain extra cellular matrixes and/or be submitted to different physical/chemical cues (i.e. shear forces)

Novel modalities to address targets that are currently ‘undruggable’

• Novel approaches and technologies that enable rapid (de-)validation or acceleration of the prototype

Examples of areas of interest: o Myc biology o Myc PPI o Ribosomal & protein translation expert for STI o Autophagy targeting chimera o RNA decay pathways other than NMD Examples of technology features of interest: o Cost effective proteome-wide profiling technology for targeted protein stabilization

(TPS) or targeted protein degradation (TPD) o Novel methods for cost effective & high throughput RNA-protein and RNA-

compound interaction detection o Better ligands / starting point for autophagy targeting chimera

Novel approaches to drugging transcription

• Novel readouts & assays for drugging transcription Sophisticated cellular and in vitro readouts of transcription, genomic location and genomic status in response to small molecules aimed at transcription factors (TFs) and epigenetic targets

Examples: o A LMW molecule that modulates transcription of a new target or pathway o An assay for transcription factor biology or a combination of cellular assays and

sequencing tech. In-vitro validation is sufficient. o Novel readouts of activity and target engagement other than reporter gene

assays and gene signature profiling (broad RNAseq) • Novel approaches to evaluating transcription factors as potential drug targets


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Discovery Chemistry Enabling Technologies & Models Phenotypic screening of large libraries in cellular assays

• Enabling screening of DNA encoded libraries in cellular assays • Synthesis of large libraries by the use of mix and split solid support synthesis without

tags, using diverse chemical reactions and biasing the libraries for a particular task • Compounds anchored by photo-cleavable, traceless linkers • Screening in microfluidic devices or fiber-arrays, beads co-localized with cells • Hit rates should be low; deconvolution by combination of synthetic pathway, choice of

building blocks, mass spectrometry; followed by re-synthesis for further validation PET tracer candidates for receptor occupancy or pharmacodynamics studies

• PET tracer candidates to either image a target for a drug discovery project, or a biomarker of disease (e.g. neuroinflammation, tumor, fibrosis)

• Preferably with basic validation as imaging agent to allow quantification of a target or disease for which there is no clinical tracer available

Technologies to vectorize radiotherapeutics and targeted payloads

• New complexing ligands for Ga3+ and Lu3+, or 18F-Al and 177Lu, preferably with a handle for coupling to targeting agent

• New molecules able to complex both radioisotopes at room temperature, leading to highly stable chelates for in vivo use

New methodologies to quantify in-vivo target engagement non-radioactively

• For preclinical and clinical studies • With priority for indications that do not have a validated translational animal model

Small molecule regulated transgene expression in gene therapy

• Low molecular weight system to control transgenes at the transcription, translational or post-translation step

• Applicable in vivo, with the potential to be translated to humans Liposomal permeability assays that are advantageous over traditional assays

• Simplification over existing systems based on Caco2 or MDCK cells • Enabling higher throughput and ideally time dependence of small molecule permeation

hERG assays differentiating blocker trapping versus non-trapping

• Assays which measures frequency dependence of blockade with good throughput • Assay results to be used to validate a Novartis in-house computational model

In vitro technologies to predict and quantify the ecological impact of drug candidates

• Prediction of resilience in waste waters and ecological systems • Quantification of long-term ecotoxicity • “Green” replacements for ecologically damaging chemical groups


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Drug delivery In vitro blood-retina barrier assay and model

• Assess retinal disposition and measure blood-retina disposition of oral compounds Biasing drug distribution with small molecules as targeting entities

• Overcomes the complexity of assembling antibody-drug conjugates and the biological implications of using whole antibodies

• Lung cell specific targeting moiety conjugated to systemically administered drug • Liver specific targeting moiety conjugated to drug

Viral capsid modification to alter distribution in gene therapy Capsids with different cell specificity to allow transduction of non-permissive cell types. Capsids with improved transduction efficiencies to allow lowering systemic viral load >10-fold.

• High yielding and site-specific capsid conjugation chemistry, not based on recombinant AAV modification

• Modifications to capsids that reduce effects of neutralizing antibodies but maintain transduction efficiency


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Engineering Technologies and Innovation Enabling Technologies & Models

• Compound sequestration in droplets • Measurement of gel stiffness, structural changes • Implementation and instrumentation of interdigitated electrodes / arrays • Electrical instrumentation of microplates • Biomarker sensing devices and bio-sensor development • Microfluidic valves • Silicon based compound tagging (as an alternative to DNA tagging) • Impedance based droplet/cell counting • Bead based (or other solid substrate) compound sequestration methods amenable to

droplet microfluidics • Minimally invasive, reoccurring murine blood sampling • Lung model tech, e.g. quantification of gas exchange across a membrane in a multi-well

format

Documents

NIBR Scientific Needs List for the NIBR Global Scholars ... · Scientific Needs List is designed to guide you in aligning your proposal with the NIBR portfolio. Please note that the