Ann: OmniCAR technical issues resolved and program to progress, page-28

Yeah shell i agree a lot of the finer detail was left out. Omnicar reconstruction should merit a presentation on it alone. But I'm sure company had its reason and in due time we will be briefed. but as shareholders we must take a breath and acknowledge the complex works that took place this wasn't a small accomplishment it was thanks to our scientific leaders who deserve some recognition I'm not sure if any other small cap biotech on the ASX could of pulled it of also at a low financial cost. if i had to guess they stated they took part in protein engineering, usually proteins are engineered for on and off switch for cell therapies.. i asked ChatGpt for more details to explain. but I'm only guessing here

Switchable Systems in Cell Therapy

Switchable systems are an advanced application in cell therapy that allow for precise control of therapeutic cells, enhancing their safety, specificity, and efficacy. These systems involve engineered proteins that act as "switches," enabling the activation, deactivation, or modulation of cell functions in response to external signals, such as small molecules, light, or specific environmental cues.

Key Types of Switchable Systems:

1. Drug-Inducible Switches:

   • These systems use engineered proteins that respond to specific drugs or molecules to control cell behavior.
   • Example:
     • Inducible CAR-T Cells: CARs are designed to be active only in the presence of a small molecule (e.g., rimiducid). This approach limits off-target activity and prevents excessive immune responses.
   • Applications:
     • Managing cytokine release syndrome (CRS), a common side effect of CAR-T therapy.
     • Temporarily activating therapeutic cells at the tumor site for localized treatment.

2. Light-Inducible Systems:

   • Proteins are engineered to respond to specific wavelengths of light, allowing for spatial and temporal control over cell functions.
   • Example:
     • Light-sensitive receptors can control T-cell activation or migration when exposed to near-infrared or visible light.
   • Applications:
     • Precise targeting of cancer cells without affecting healthy tissues.
     • Research settings to study cellular behavior in real-time.

3. Environment-Sensitive Switches:

   • Proteins designed to activate or deactivate based on environmental conditions like pH, temperature, or oxygen levels.
   • Example:
     • Hypoxia-sensitive CARs activate only in low-oxygen environments, common in tumor microenvironments, reducing damage to normal tissues.
   • Applications:
     • Targeting hypoxic tumors or inflamed tissues in autoimmune diseases.

4. Dual-Signal Systems:

   • Require two signals to activate, improving specificity by reducing activation in unintended environments.
   • Example:
     • SynNotch receptors: A customizable system where one receptor recognizes a primary signal (e.g., tumor antigen), activating a second receptor that triggers therapeutic action.
   • Applications:
     • Ensuring therapeutic cells are activated only in the presence of two tumor-specific antigens.

5. Suicide Switches:

   • Designed to terminate therapeutic cells if severe side effects or adverse reactions occur.
   • Example:
     • Incorporating a caspase-based self-destruction pathway activated by an external drug like ganciclovir.
   • Applications:
     • Enhancing patient safety by providing a fail-safe mechanism in CAR-T or stem cell therapies.

Advantages of Switchable Systems in Cell Therapy:

• Safety: Minimize risks like off-target effects or overactivation of therapeutic cells.
• Flexibility: Enable dynamic control of cell functions throughout treatment.
• Efficacy: Allow precise targeting of diseased tissues, improving therapeutic outcomes.
• Adaptability: Can be tailored for different diseases and patient needs.

Challenges and Future Directions:

• Complexity: Designing reliable switchable systems requires extensive testing and optimization.
• Delivery: Ensuring therapeutic cells receive the external signal effectively, especially in deep tissues.
• Scalability: Producing engineered cells with switchable systems on a large scale for clinical use.

Switchable systems represent a groundbreaking innovation in cell therapy, making treatments safer, more controlled, and adaptable for diverse medical challenges. They are increasingly pivotal in creating the next generation of personalized, precise therapies.