Past Calls for Proposals

Call For Proposal - A Series (Archive)

Call for Proposals A01 (Hit2Lead)

Call Opens: 20 September 2024
Submission Deadline: 29 October 2024, 1200 hrs (SGT)

Maximum Duration: 12 months
Maximum Quantum: S$2.5 million (including 30% indirect costs)

Scope

Hit2Lead will support RNA drug development from hit generation to lead compound(s) identification.
(This Call is only open to all indications except Infectious Diseases.)

Entry Criteria

Projects applying for Hit2Lead must have a validated target. The application must demonstrate using in vitro and in vivo preclinical models that the target is convincingly implicated in the disease. The application must demonstrate that a tool compound can modulate the target in vitro and in vivo and show improvements in surrogate markers.

Desired Outcomes

At the end of Hit2Lead, projects should identify 3-5 lead compounds that demonstrate efficacy, stability and toxicity in vitro, as well as efficacy in vivo, based on specifications listed in the target product profile.

Call For Proposal - N Series (Archive)

Call for Proposals N07

Call Opens: 20 September 2024
Submission Deadline: 29 October 2024, 1200 hrs (SGT)

Maximum Duration: 36 months
Maximum Quantum: S$5 million (including 30% indirect costs)

Call for Proposals N07 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Expanding the therapeutic utility of mRNA modalities beyond prophylactic vaccines requires frequent parenteral administration (e.g. intravenous, intramuscular, subcutaneous, intradermal) which leads to non-selective uptake by the liver and results in poor efficacy coupled with dose-limiting toxicities.

  • Identify novel delivery systems that support parenteral administration of mRNA once every 1-4 weeks for non-vaccine applications
  • A well-defined mRNA delivery system that features the following:
    • Compatible with clinically viable route(s) of administration
    • Reduced biodistribution (<10% of administered dose) of mRNA and the carrier system to hepatocytes
    • Selective delivery to and expression in at least one organ/cell type from the list below with the ability to discriminate between different cell types in vivo:
      • Organs: liver, heart, eye, brain, skin, lung and spleen
      • Cell types: non-hepatocyte cells (e.g. hepatic stellate cells, Kupffer cells); cardiomyocytes; photoreceptor cells, retinal pigment epithelium, microglial cells; neurons, astrocytes, glial cells, Schwann cells; keratinocytes, melanocytes; alveolar epithelial cells, lung resident macrophages, fibroblasts, mast cells; T lymphocytes, B lymphocytes, antigen-presenting cells (e.g. dendritic cells), natural killer cells; T lymphocytes, tumour-infiltrating lymphocytes, stromal cells
    • High potency and/or expression efficiency in vivo in the target tissue with a robust characterisation of expression profiles across different cell types after a single dose
    • Durable expression for at least 1 week post-administration with a Peak/Trough ratio of <2 in a small animal model
    • Linear dose-response relationship across a 3-log dose range with an acceptable tolerability profile after a single dose
    • Consistent and durable expression upon repeated dosing at least once a week for 8 weeks with an acceptable tolerability profile in a small animal model
    • Due diligence process to maximise patentability and freedom to operate
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development
  • Use of automation to increase throughput, streamline workflows and/or reduce costs

Optional

  • Collaboration with suppliers (e.g. industry) to increase access to raw materials

RNA: ribonucleic acid; mRNA: messenger RNA

Call for Proposals N06

Call Opens: 20 September 2024
Submission Deadline: 29 October 2024, 1200 hrs (SGT)

Maximum Duration: 36 months
Maximum Quantum: S$5 million (including 30% indirect costs)

Call for Proposals N06 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Active targeting strategies are needed to achieve organ-/cell-specific, extrahepatic delivery of synthetic RNA, especially ASO and siRNA.

  • Accelerate discovery of novel targeting ligands
  • Diversify chemical moieties used as targeting ligands
  • An integrated system that interrogates a broad chemical library of at least one class of ligands against multiple biological targets, featuring the following:
    • Broad range of natural/unnatural chemical motifs that can be chemically conjugated to synthetic RNA, including but not limited to peptides, sugars, aptamers and small molecules
    • Effective integration of artificial intelligence and/or machine learning to interrogate large combinations of building blocks, scaffold compositions, and other molecular designs
    • Due diligence process to maximise patentability and freedom to operate
    • Rapid “hit” identification of novel ligands that selectively bind to, and be internalized by, at least 2 of the following organs and/or cell types:
      • Organs: liver, heart, eye, brain, skin, lung and spleen
      • Cell types: non-hepatocyte cells (e.g. hepatic stellate cells, Kupffer cells); cardiomyocytes; photoreceptor cells, retinal pigment epithelium, microglial cells; neurons, astrocytes, glial cells, Schwann cells; keratinocytes, melanocytes; alveolar epithelial cells, lung resident macrophages, fibroblasts, mast cells; T lymphocytes, B lymphocytes, antigen-presenting cells (e.g. dendritic cells), natural killer cells; T lymphocytes, tumour-infiltrating lymphocytes, stromal cells
    • Ability to optimise the “hits” to generate “lead shuttles” with validated selectivity and cytoplasmic shuttling capacity
    • Ability to stably conjugate candidate ligands to a model synthetic RNA and achieve >90% and selective gene modulation/knockdown in target cell types in vitro at an IC50 that is >20 times lower than untargeted controls
    • Demonstration of selective target gene modulation/knockdown in vivo at an ED50 that is >10 times lower than untargeted controls with an acceptable tolerability profile, using a clinically accepted route of administration
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development
  • Use of automation to increase throughput, streamline workflows and/or reduce costs

Optional

  • Collaboration with suppliers (e.g. industry) to increase access to raw materials

RNA: ribonucleic acid; siRNA: small interfering RNA; ASO: antisense oligonucleotide; IC50: half maximal inhibitory concentration; ED50: median effective dose



 

Call for Proposals N05

Call Opens: 8 April 2024
Submission Deadline: 31 May 2024, 1200 hrs (SGT)

Maximum Duration: 36 months
Maximum Quantum: S$5 million (including 30% indirect costs)

Call for Proposals N05 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Current development of safe and effective carriers to encapsulate nucleic acid drugs for various clinical applications is not sufficiently efficient.

  • Accelerate development of safe and effective carriers
  • Diversify raw materials for nucleic acid encapsulation
  • An integrated system to develop carriers for encapsulating nucleic acids, that features the following:
    • Ability to investigate a broad range of lipids, polymers, and other raw materials for formulating carriers;
    • Ability to simultaneously evaluate a series of standard quality attributes minimally including particle size, polydispersity, translation efficiency, and cytotoxicity in vitro 
    • At least two viable applications based on the route of administration, for example:
      • One novel formulation for intramuscular administration to achieve in vivo efficacy, safety and stability comparable to or better than a benchmark drug (e.g. COVID-19 vaccine)
      • One viable formulation for intravitreal administration, transdermal administration, or other routes of administration, achieving acceptable in vivo efficacy, safety and stability using a reference standard
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

  • Collaboration with suppliers (e.g. industry) to increase access to raw materials
  • Use of automation to increase throughput, streamline workflows, and/or reduce costs
  • Use of artificial intelligence and/or machine learning

 

Call for Proposals N02

Call Opens: 8 April 2024
Submission Deadline: 31 May 2024, 1200 hrs (SGT)

Maximum Duration: 18 months
Maximum Quantum: S$4 million (including 30% indirect costs)

Call for Proposals N02 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Current design processes for siRNA and/or ASO drug candidates are not sufficiently holistic to predict downstream effects.

  • Accelerate drug development through smart design
  • Improve drug profile early in development
  • Tighten iterative loop between design and testing
  • A disease-agnostic algorithm (or a set of algorithms) for ASO and/or siRNA that demonstrates the following:
    • Hit rate of >20% with picomolar IC50 (potency), acceptable efficacy, stability, specificity (off-target value), and cytotoxicity profile with validated in vitro assays
    • New and broadly applicable combinations of known chemical modifications, leading to better performance than benchmark sequences (approved drugs or clinical trial candidates), measured using in vitro and in vivo assays
  • An integrated, preferably automated system of robust, validated in vitro assays to evaluate at least 96 siRNA and/or ASO drug candidates simultaneously for characteristics including but limited to the following:
    • Efficacy/potency
    • Stability
    • Specificity (off-target value)
    • Cytotoxicity
    • Mechanistic functions (e.g. RNase H cleavage, Ago2 loading, ribosomal loading)
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

  • Collaboration with data partners (e.g. industry) to test and validate new algorithm(s)
  • Use of artificial intelligence and/or machine learning

RNA: ribonucleic acid; siRNA: small interfering RNA; ASO: antisense oligonucleotide; IC50: half maximal inhibitory concentration

Call for Proposals N04

Call Opens: 8 April 2024
Submission Deadline: 17 May 2024, 1200 hrs (SGT)

Maximum Duration: 24 months
Maximum Quantum: S$3 million (including 30% indirect costs)

Call for Proposals N04 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Current designs for mRNA drug candidates are not sufficiently effective.

  • Accelerate drug development through smart design
  • Improve drug profile early in development
  • A disease-agnostic algorithm (or a set of algorithms) to design linear and/or non-linear mRNA drugs, that achieves the following:
    • >6-fold increase of in vitro protein expression compared to benchmark sequences (i.e. approved drugs or clinical trial candidates)
    • >3-fold increase of in vivo expression, along with similar efficacy, durability, and safety compared to benchmark sequences, via intramuscular administration and separately via intravenous administration, using established delivery methods and validated assays
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

  • Collaboration with data partners (e.g. industry) to test and validate new algorithm(s)
  • Use of artificial intelligence and/or machine learning

RNA: ribonucleic acid; mRNA: messenger RNA

Call for Proposals N03

Call Opens: 8 April 2024
Submission Deadline: 17 May 2024, 1200 hrs (SGT)

Maximum Duration: 18 months
Maximum Quantum: S$3 million (including 30% indirect costs)

Call for Proposals N03 aims to address the following problem statement:
# Problem Statement Objectives Deliverables

1.

Limited access to bespoke chemistries and modifications impedes synthesis of hit compound libraries for siRNA/ASO drug development.

  • Support hit compound synthesis
  • Develop novel chemical modifications for siRNA and/or ASO drugs
  • A robust, high-throughput workflow for oligonucleotide synthesis that achieves the following:
    • Ability to synthesise siRNA and ASO with a mixture of standard chemical modifications
    • Quality control demonstrating >80% purity and other standard quality attributes required for hit screening
    • Turnaround time of <2 weeks to generate a library of at least 96 distinct candidates each for siRNA and ASO
  • At least 1 novel chemical modification to demonstrate at least one of the following improvements, using relevant in vitro and in vivo functional assays:
    • Increase potency
    • Extend duration of drug effect
    • Improve release into the cytosol
    • Reduce toxicity
  • Use of electronic laboratory notebooks to digitise and centralise management of experimental data, to facilitate downstream drug development

Optional

  • Collaboration with knowledge partners (e.g. industry) to test new chemistries
  • Use of automation to increase throughput, streamline workflows, and/or reduce costs

RNA: ribonucleic acid; siRNA: small interfering RNA; ASO: antisense oligonucleotide

Call for Proposals N01

Call Opens: 19 December 2023
Submission Deadline: 24 January 2024, 1200 hrs (SGT)

Maximum Duration: 3 years
Maximum Quantum: S$3 million (excluding 30% indirect costs)

Call for Proposals N01 aims to address the following problem statements:
#Problem Statement Objectives Deliverables

1.

Lack of local production capacities and automation capabilities to accelerate the development of mRNA assets to clinical readiness

  • Develop mRNA manufacturing and quality control capabilities to be routinely operated in compliance with GLP, with ability to adopt GMP-like operations on demand
  • Develop automation strategies to improve consistency, reduce waste and increase turnaround time
  • Demonstrate GLP production at sufficient yield and quality for preclinical studies
  • Develop analytical workflows and control strategies to enable adoption of QbD framework
  • Integrate unit operations to support end-to-end manufacturing
  • Demonstrate quantified improvements over conventional processes

2.

Lack of local production capacities and automation capabilities to accelerate the development of siRNA/ ASO assets to clinical readiness

  • Develop siRNA/ ASO manufacturing and quality control capabilities to be routinely operated in compliance with GLP, with ability to adopt GMP-like operations on demand
  • Develop automation strategies to improve consistency, reduce waste and increase turnaround time
  • Demonstrate GLP production at sufficient yield and quality for preclinical studies
  • Develop analytical workflows and control strategies to enable adoption of QbD framework
  • Integrate unit operations to support end-to-end manufacturing
  • Demonstrate quantified improvements over conventional processes

RNA: ribonucleic acid; mRNA: messenger RNA; siRNA: small interfering RNA; ASO: antisense oligonucleotide; GLP: Good Laboratory Practice; GMP: Good Manufacturing Practice; QbD: Quality by Design