Technology

DISCOVERING OUR LEAD COMPOUNDS

Comprehensive screening identified two lead compounds with ATLX–0199 and ATLX–0190 being selected as leads

  • Observed to be safe
  • Prevent or reverse morphine and fentanyl induced depression of breathing
  • Prevent or reverse negative effects on ventilation-perfusion in lungs (alveolar-arterial gradient)
  • Prevent or reverse the disturbances in blood gas chemistry (e.g., pH, pCO2, pO2 and sO2)
  • Do not reduce the analgesic (pain relief) effect
  • Potential in modulating other negative opioid-induced side effects (addiction/ tolerance/withdrawal/GI motility)

PIPELINE

Atelerix’s lead molecules are ready for clinical development, with additional NIH-funded follow-ons, targeted at reversal of weaponized opioids, in the pipeline

HOW IT WORKS

ATBCs interact with the signaling pathways of activated opioid receptors, reversing opioid-induced side effects without diminishing pain relief

Opioids Trigger 2 Basic Pathways:

G Protein and ERK/Barr

Activated opioid receptors trigger multiple molecular signaling pathways, including the G Protein Pathway which causes pain relief/euphoria and the ERK/Barr Pathway which prompts side effects

HOW IT WORKS

ATBCs interact with the signaling pathways of activated opioid receptors, reversing opioid-induced side effects without diminishing pain relief

Naloxone Blocks Both Pathways, Displacing the Opioid

Naloxone displaces the opioid on the receptor, shutting down the signaling pathways that regulate both the side effects and the pain relief

HOW IT WORKS

ATBCs interact with the signaling pathways of activated opioid receptors, reversing opioid-induced side effects without diminishing pain relief

ATBC Compounds Selectively Interact with the ERK/Barr Path

ATBC compounds interact with a specific portion of the activated ERK/Barr signaling pathway, inhibiting side effects while preserving pain relief

AVAILABLE DATA

In-vitro & in-vivo data show compelling pre-clinical proof of concept

ATLX-0199 (D-Cystine diME)

  • ATLX-0199 increases minute ventilation and overcomes opioid-induced respiratory depression.
  • ATLX-0199 (D-Cystine diME) reverses the respiratory depression and V/Q mismatch after 10 mg/kg IV morphine in conscious rats.
  • ATLX-0199 (D-Cystine diME) does not negatively impact the analgesic actions of morphine in freely-moving rats.

ATLX-0190 (D-CYSee)

  • ATLX-0190 is active on ventilatory control systems.
  • ATLX-0190 reverses the ventilatory-depressant effects of morphine in freely-moving rats.
  • ATLX-0190 reverses the negative effects of morphine on arterial blood-gas chemistry in freely-moving rats.
  • ATLX-0190 does not negatively impact the analgesic actions of morphine in freely-moving rats.

Additional data on opioid withdrawal response, tolerance, motility, modulation of addiction and co-administration with naloxone is available under CDA

PRE-CLINICAL PROOF OF CONCEPT

ATLX-0199 increases minute ventilation and overcomes opioid-induced respiratory depression

Minute ventilation (VE) is the total volume of gas entering (or leaving) the lung per/min

It is equal to the tidal volume (TV) multiplied by the respiratory frequency rate (f).

VE = TV x f

No toxicity observed to date at maximal effective doses

PRE-CLINICAL PROOF OF CONCEPT

ATLX-0199 reverses the respiratory depression and V/Q mismatch after 10 mg/kg IV morphine in conscious rats

Studied blood gas parameters include:

Blood pH

Increases in CO2

Hemoglobin saturation

Oxygen imbalance between lungs and arteries

PRE-CLINICAL PROOF OF CONCEPT

ATLX-0199 does not negatively impact the analgesic actions of morphine in freely-moving rats