Centers for Therapeutic Innovation Call for Proposals

Funding Agency:
Pfizer Inc.

The 2021 CTI Call for Proposals is seeking partnering opportunities for novel targets in the areas described below with applications across Pfizer’s core therapeutic areas. Submission Deadline: June 28th 2021

Agency Website

Areas of Interest

Inflammation & Immunology:

- Cellular senescence and inflammation resolution mechanisms: directly targeting the interactions between pathogenic fibroblast and macrophage subsets in autoimmunity and fibrosis.  Novel targets to modulate cellular senescence mechanisms would be prioritized, including senolytic and senomorphic approaches to modulate fibroblasts/myofibroblasts function and tissue remodeling. Additionally, targets on tissue progenitor cells that induce tissue regeneration without carcinogenic risk would be considered.  

- Tolerance induction mechanisms in autoimmunity: novel targets that modulate the activity of regulatory macrophages (Mregs), regulatory B cells (Bregs), and tolerogenic dendritic cells (tolDCs).  Small molecule approaches to modulate intracellular signaling pathways are preferred although novel cell surface targets will be considered.

- Modulating the activity of pathogenic immune cells: targeting novel extracellular/cell surface molecules or intracellular signaling pathways on pathogenic B cells, inflammatory monocytes, neutrophils, mast cells or other granulocytes to ameliorate autoimmune disease.

- Promotion of epithelial barrier repair by directly targeting the epithelial barrier in IBD.  Modulation of such targets should induce repair functions with measurable effects on tight junction function and/or goblet cells and mucus layer at the genetic and cellular level.   

Out-of-scope:  Targets in replicative senescence e.g. telomerase; direct induction/modulation of regulatory T cells (Tregs); known targets (such as JAKs, BAFF, BLyS/APRIL, BTK, TNFα, IL1β) modulation of immune cell functions that indirectly affect epithelial barrier function

Internal Medicine:

- Novel mechanisms and/or human genetic approaches to target heart failure with preserved ejection fraction (HFpEF). Including, but not limited to, novel targets and pathways regulating skeletal muscle vascular growth and function.

- Mechanisms addressing cachexia associated with chronic disease and aging 

                  - Pathways targeting muscle growth and function   including metabolism and mitochondrial energetics 

                  - Inflammatory pathways underlying cachexia of chronic disease 

- Gut-brain signaling in regulation of energy balance (obesity/cachexia) - Targeting vagal sensory pathways in the gut or nodose ganglion to regulate feeding.    

- Novel approaches for the treatment of diabetic nephropathy or chronic kidney disease, founded on evidence from human pathophysiology and/or genetics 

Out-of-scope: nutraceutical approaches to muscle growth and function; approaches that cause browning of white fat/thermogenesis 

Oncology:

- Induction or targeting of senescent-like arrest of tumor cells to overcome drug resistance and/or improve immune response to solid tumors  

- Enhancing immune-mediated tumor cell killing: activation of repeat elements, antigen presentation, prevention or reversal of immune-senescence & -exhaustion mechanisms 

- Splicing stress R-loops and restoration of RNA processing - selective targeting of splicing via RNA binding proteins and RNA helicases 

- Targets driving the DNA damage response and replicative stress, including nucleases, deubiquitinases, and helicases; synthetic lethal relationships outside of BRCA1/2. 

- Exploiting vulnerabilities of cancer cells due to endoplasmatic reticulum (ER) stress and activation of the Unfolded Protein Response (UPR) 

- Exploiting defects in the ubiquitin proteasome system (UPS) system

- Novel oncogenic transcription factors and their complexes, as well as new mechanisms for their modulation

- Cellular repolarization/reprogramming to induce immune-mediated killing of cold tumors

- Novel and broadly shared cancer neo-epitopes that could be leveraged in cancer vaccines, T-cell receptor (TCR) mimetics, and TCRxCD3 bispecific antibodies 

- Novel approaches to oncolytic viruses permitting IV delivery and reduced immunogenicity 

Out-of-scope: cytotoxic antibody-drug conjugates, rare tumor indications

Rare Disease:

Approaches for the cause or treatment of Repeat Expansion Diseases 

- Targets directly impacting the pathogenic repeats at the level of DNA/RNA 

- Molecular mechanisms that modulate or regulate the pathogenic repeat  

- Assays for DNA mismatch repair and biomarkers of somatic repeat instability 

Novel concepts for the cause (mutant or modifier genes, causal signaling pathways) or treatment (reverse existing pathology) of Rare Cardiac Diseases 

- Rare inherited, Dilated, & Arrhythmogenic Hypertrophic Cardiomyopathy

- Amyloid light-chain amyloidosis (AL-Amyloidosis) 

- Rare heart rhythm disorders

Opportunities addressing the pathogenesis or progression of Rare Renal Disorders; Focal Segmental Glomerulosclerosis, IgA Nephropathy, Alport Syndrome, or Autosomal Dominant Polycystic Kidney Disease:

- Novel targets/pathways to improve glomerular filtration

- Mechanisms to reduce IgA deposition or slow renal decline post deposition

- Mechanisms to reduce cyst size, growth, formation and downstream effects on renal function

Out-of-scope: ultra-rare diseases, ex vivo gene therapy, broad hemodynamic modifiers and fibrotic mechanism

Funding Type

Grant

Eligibility

Faculty

Category

Medical
Medical - Basic Science
Medical - Clinical Science
Medical - Translational

External Deadline

June 28, 2021