Counterpoint Biomedica
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Counterpoint Biomedica
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Executive Summary

  • Counterpoint Biomedica LLC has adapted a proven Tumor-Targeting Platform to enable the major FDA-approved chemotherapies and biologic therapies to work more efficiently by providing an “Active” mode of drug delivery without altering the drug itself.  This gain-of-targeting-function is accomplished by the tumor-targeted adaptor proteins (called  onco-aptamers). When added to the final drug formulation, onco-aptamers  bind tightly to the respective cancer drug and then guide the  drug-aptamer complexes through the general circulation to primary and  metastatic lesions by seeking out abnormal (abaplastic) XC-protein signatures that are exposed  in all cancerous tissues. Through this mechanism, onco-aptamers increase  the effective local concentration of the drug within the tumors,  thereby enhancing the cancer drug’s Safety and Efficacy while lessening unwanted side effects—enabling lower drug doses to be more effective.​
     

  

The Counterpoint Approach: Tumor-Targeting Onco-Aptamers are Designed to Improve Drug Delivery.  The "two-handed" structure of a representive Onco-Aptamer is shown schematically in the following figure:

 

The Core Design Elements of the Tumor-Targeting Platform (A):

(i) A Drug-Binding Domain is designed to bind with high affinity to a specific class of therapeutic agents (i.e., Cargos). (ii) A proven XC-Binding Domain for active and selective tumor targeting is common to all Onco-Aptamers.
The Therapeutic Agents:  Small Molecules (B), Monoclonal Antibodies (C).
N- and C-Terminal Modifications (A) enhance stability, function in vivo.
Note:  the targeted anticancer agent is essentially unmodified and is bound by  non-covalent interactions to the bifunctional tumor-targeting  Onco-aptamer.

Tumor Targeting, An Enabling Platform

    

The Clinical Problem: Systemic Biodistribution and Dose-Limiting Toxicities 

The inherent toxicities of approved chemotherapeutic and biologic agents are a result of ungoverned / non-specific drug biodistribution, which damages normal tissues and organs.

This inefficiency requires larger doses to ensure sufficient uptake of the drugs. 


Passive Drug Delivery is very inefficient, requiring high plasma levels to be effective, which also kills normal cells resulting in systemic toxicities. 


The Majority (>95%) of passively administered cancer agents are known to accumulate in non-target organs—liver, spleen, lungs. 


Monoclonal antibodies (mAbs) are considered to be safer than small molecules, but this is not the case with Immune Checkpoint Inhibitors, linked to serious adverse events (AEs). 

 The Clinical Solution:  “Active” and Efficient Tumor Targeting. “Active”  Tumor Targeting delivers pharmaceutical agents more efficiently to  diseased tissues—specifically to invasive cancers—effectively raising  the local concentration of the anti-cancer agent within tumors, and  improving the Therapeutic Index. Targeting the exposed collagenous  proteins (XC-proteins) of the abnormal tumor microenvironment—a  pathologic characteristic of all invasive cancers—represents an active  means of targeting therapeutic agents selectively to tumors. Targeting  anticancer agents to the tumor XC-proteins present in all invasive  cancers has many clinical advantages:  Higher effective local  concentrations at lower drug doses. 

 

A Tumor-Targeted Vaccine:  This enabling platform is also aimed at targeting GM-CSF,  a potent immunostimulatory cytokine, to cancerous lesions—in order to  enhance humoral and cell-mediated immune responses by means of a  personalized vaccination strategy. Unlike cumbersome Transduced  Cancer-Cell Vaccines, whereby cancers cells are genetically modified by  viral vectors to secrete GM-CSF, in an effort to generate anti-tumor  effects, the  endowment of tumor targeting directly to the cytokine, as a  gain-of-function, now enables delivery to lesions upon simple  intravenous infusion.

Targeted Diagnostics Pipeline: Most recently, the enabling platform biotechnology focused on improving Cancer Diagnostics and Liquid Biopsies  with the engineering of specific antibodies and polypeptide targeting  aptamers: synthetic polypeptide constructs designed to recognize  abnormal pericellular collagens and/or vimentin proteins arrayed on the  surfaces of circulating tumor cells (CTCs) of mesodermal origin (e.g.,  sarcomas), as well as epithelioid CTCs that have undergone the classical  Epithelial-to-Mesenchymal Transition (EMT). These Targeted Diagnostic  Reagents may be used clinically for differential diagnosis, patient  monitoring, or targeted cancer therapy.


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