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Calidi is at the forefront of the genetic medicine revolution in cancer and other indications

RedTail: A Decade in Development

The RedTail platform is genetically engineered to avoid immune clearance, thereby allowing for systemic administration. Because replication only occurs in tumor cells, the delivery of genetic medicines is precisely targeted to the tumor.

Stepwise creation of the platform:
A decade of engineering to create RedTail

Vaccinia virus is engineered for selective tumor targeting, making it a powerful tool for gene medicine delivery.

The manufacturing process is optimized to create a highly protective secondary envelope, enabling efficient systemic delivery.

Genetic engineering to express CD55 on surface of envelope to further reduce immune recognition

Selection of CLD-401: Immune protected for systemic delivery, replication only in tumor cells, and delivering genetic medicine to transform tumor site into IL-15 superagonist producers for precise activation of anti-tumor immunity

Selection of CLD-501: Immune protected for systemic delivery, replication only in tumor cells, and high in situ expression of both a TROP-2 T-cell engager and IL-15 superagonist for T-cell activation

Programmability of extracellular membrane for enhanced targeting and option to delivery multiple genetic payloads

CLD-401

Upon systemic administration, CLD-401 homes to metastatic sites, induces tumor cell lysis and immune priming, and activate immune cells in the tumor microenvironment through the in situ production of high levels of IL-15 superagonist.

CLD-401 is administered via IV infusion

The manufacturing process is optimized to create a highly protective secondary envelope, enabling efficient systemic delivery.

IL-15 superagonist production, along with immune priming, alters the TME and allows for a potent immune response

Innate (NK cell) and adaptive (CD8 T-cell) activation can drive a memory response to the tumor.

In Situ T-Cell Engagers

RedTail viruses enable T-cell engagers in solid tumors by simultaneously expressing high concentrations of a functional T-cell engager and an inducer of T-cell activation (e.g., IL-15 SA) restricted to the tumor microenvironment (in situ) allowing for potent T-cell meditated tumor cell destruction

Going Forward

We continue to enhance the utility of the RedTail platform by expanding what genetic medicine payloads can be delivered and by enabling the precise targeting of the platform

Envelope and CD55 expression facilitate survival in the complement-rich bloodstream, enabling systemic dissemination.

Viral replication depends on cell proliferation, active mitogenic signaling and enhanced nucleotide biosynthesis E.g: Tumor cells.

Payload(s) expressed as virus replicates Immune-stimulating payloads used in oncology

Envelope and CD55 expression facilitate survival in the complement-rich bloodstream, enabling systemic dissemination.

Viral replication depends on cell proliferation, active mitogenic signaling and enhanced nucleotide biosynthesis E.g: Tumor cells.

Trop-2 TCE and IL-15 Superagonist payloads expressed in situ at the tumor as virus replicates.

Additional Add-ons:

Envelope can be used to target other cell types
Envelope engineering for “programmable” targeting

Viral replication in proliferative cells like activated B- cells

Other Payload(s)

  • Immune-suppressive payloads to be used in autoimmunity
  • Alternative cancer therapeutic payloads
Publication
RedTail
SITC Poster – In Situ Tumor Delivery of IL-15 Superagonist via RedTail Gene Therapy Achieves Durable Tumor Clearance
 
Event
RedTail
Transforming all Tumor Sites: The Power of Systemic Enveloped Virotherapy
SITC 2024
 
Event
RedTail
Transforming Tumor Immune Microenvironments with a Novel Systemic Enveloped Oncolytic Virotherapy Targeting All Tumor Sites
ASCO Annual Meeting 2024
 

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