Untapped Potential of Protein Phosphatases

​Disruption of Protein Tyrosine Phosphatase (PTP) function underlies​ cancer, inflammatory diseases, diabetes, ​neurological diseases including Alzheimer’s, and various rare diseases. ​

• Protein phosphatase enzymes partner and complement protein kinase enzymes in the ​regulation of signaling
  
  
• Global protein kinase signal transduction-based drug market >$100 billion
  
  
• Protein phosphatases, e.g. PTP1B, have similar therapeutic ​potential to kinases 
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• Never been successfully “drugged”​

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• Developing novel therapeutics targeting the role of protein tyrosine phosphatases in signaling pathways involved in the pathology of multiple diseases
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• Advancing two orally bioavailable small molecules into clinical trials by Q3 2022 for:
  • Rett Syndrome
  • Cancer
  • Wilson Disease

• Building a library of novel selective PTP1B (phosphatase) inhibitors with therapeutic potential for other major metabolic, inflammatory and neurodegenerative diseases
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• Active collaboration with Prof. N. K. Tonks at Cold Spring Harbor Laboratory to build a new class of protein phosphatase-targeted drugs

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The Challenge: Poor or No Oral Bioavailability in First
Generation PTP1B Inhibitors

• PTP1B is a phosphatase enzyme that was first validated as a therapeutic target for diabetes and ​obesity
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• Developing successful PTP1B-inhibitor drugs proved to be challenging

• The PTP1B catalytic site is highly charged and first generation PTP1B inhibitors were not orally bioavailable
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• The active site is highly conserved between members of the PTP family – potential to inhibit enzymes other than PTP1B

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The Solution: DepYmed Has Overcome the Challenges of ​Developing PTP1B-Targeted Inhibitors as Drugs​

DepYmed Has Successfully Developed a PTP1B-Targeted Inhibitor Drug Platform

• DepYmed uses allosteric inhibitors to “drug” this important class of enzymes and advance a pipeline of promising therapeutic candidates
  
  
• These inhibitors are potent, specific and orally bioavailable

• ​Nicholas Tonks, Ph.D. of Cold Spring Harbor Laboratory, who discovered the protein tyrosine phosphatase family, is the scientific founder of DepYmed and works closely with the company in optimizing therapeutic candidates

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Key Features of Molecules From DepYmed’s Innovative PTP1B Inhibitor Platform

DepYmed’s proprietary portfolio of allosteric PTP1B inhibitors ​include molecules that:​

• Are orally bioavailable​
• Are efficacious in animal models of disease
• Are commercially manufacturable and scalable​

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DepYmed Platform - Two Types of PTP1B Inhibitors

A Novel Mechanism for Allosteric Regulation of PTP1B

Krishnan et al (2014) Nature Chemical Biology 10: 558-566

Single-Action Inhibitors
(MoA: Exclusively Inhibit PTP1B Enzyme)

​Application: Rett Syndrome, Oncology

Dual-Action PTP1B Inhibitors
(MoA: Inhibit PTP1B + Chelate Copper)

​Application: Oncology, Wilson Disease

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DepYmed continues to develop the next generation of more potent PTP1B inhibitors and copper chelators. These are currently in preclinical development in collaboration with Cold Spring Harbor Laboratory.

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