PRECIGEN TRIPLE-GENE

Advancing targeted, controllable, multigenic therapies for cardiovascular diseases

MULTIGENIC THERAPY

Triple-Gene is a clinical stage gene therapy company focused on developing advanced therapies for complex cardiovascular diseases.

The Challenge

  • 25 million patients globally suffer from heart failure
  • ~6.5M patients in the US affected
  • About every 90 seconds a person in the US dies from heart disease

Developing a holistic treatment for heart failure requires improvements in angiogenesis, calcium homeostasis-associated cellular energetics, reductions in inflammatory signals, and the activation/recruitment of stem cells to support heart remodeling. We are focused on advancing targeted, controllable, and multigenic gene therapies for the treatment of cardiovascular diseases.

Our lead clinical candidate is a Phase 1 non-viral investigational gene therapy that drives expression of three candidate effector genes involved in heart failure.

Triple-Gene is a majority-owned subsidiary of Precigen.

Heart failure is a complex clinical syndrome. Frequently initiated by injury to the heart, only rarely is heart failure caused by a single genetic lesion. Precigen Triple-Gene’s unique therapeutic approach combines a multigenic therapy with delivery directly to cardiac tissue to address underlying disease mechanisms. We believe targeting multiple points in the disease progression pathway is necessary to effectively treat heart failure pathologies and bring relief to patients suffering from this devastating disease.

Our Approach

Our unique approach implements technologies that are targeted, controllable and multigenic.

  • Targeted: We employ genome delivery systems designed to match disease and/or injury-related specifications.
  • Controllable: We create modulated gene systems in concert with DNA/RNA/protein-based regulatory motifs, to enable spatiotemporal controls over one or more therapeutic effector molecules.
  • Multigenic: We optimize multi-effector therapies to advance treatment or cure underlying disease etiologies and also to ameliorate effects of chronic comorbid tissue damage.

Triple-Gene’s lead Phase 1 stage investigational therapy INXN-4001 for heart failure uses non-viral delivery of a constitutively expressed multigenic plasmid designed to express human SDF-1α, VEGF165, and S100A1 gene products which affect progenitor cell recruitment, angiogenesis, and calcium handling, respectively. The investigational plasmid therapy is designed to target the underlying molecular mechanisms of pathological myocardial remodeling. It is delivered via Retrograde Coronary Sinus Infusion (RCSI) which allows for cardiac-specific delivery to the ventricle.

RCSI is a procedure used to deliver biological molecules to the heart. In RCSI, a balloon-catheter is inserted into the coronary sinus and left inflated for a time to occlude the coronary sinus and facilitate circulation of the therapeutic in the heart. Therapeutic molecules are infused through the catheter. Once infusion is complete, the balloon-catheter is deflated and removed.

Our Platform Advantages

Triple-Gene’s multigenic therapies are designed to drive expression of three or more potent gene products targeted at reprogramming cells and organs toward a positive health state. Our genetic architecture is built upon a suite of integrated platform technologies. We employ non-viral delivery of DNA to develop therapeutics that address the underlying causes of cardiovascular disease.

  • Non-viral delivery eliminates issues of immunogenicity seen with viral-based methods
  • Multigenic therapies can target multiple aspects of disease
  • Our approach has enabled proof-of-concept to clinical IND in under 24 months.

Administration of our plasmid DNA therapy through the RCSI approach allows for delivery via capillary filtration increased by hydrostatic and osmotic pressures. The efficiency of transduction is dependent on the volume and time of infusion.

We are building a developmental pipeline targeting cardiovascular disease using three or more cardiac effector genes and employing several therapeutic delivery modalities. Our team is focused on completing the current Phase I study for our lead clinical candidate INXN-4001 for heart failure in adult patients with implanted Left Ventricular Assist Device (LVAD) while moving additional candidates through discovery.

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