TransCode has decoded the major challenge of RNA delivery
"....clinical success has been out of reach due to three delivery related challenges: protecting the therapeutic oligonucleotide from dismantling by the immune system; maintaining stability so the molecule can do its job; and penetrating the target organs and cells. "
Our TTX platform leverages an iron oxide nanoparticle that has been extensively used for imaging, has been repurposed as a delivery mechanism for RNA oncology therapeutics. This proprietary image-guided delivery system is the backbone of our pipeline of targeted therapeutics, which is designed to safely and efficiently deliver therapeutics to their intended RNA target. Review pre-clinical and clinical evidence supporting TTX delivery
Optimized TTX Platform advantages:
RNA has long been viewed as an attractive therapeutic modality because it can be used to target a wide array of diseases; it involves rational and straightforward drug design, the drugs are highly selective for their target, and nominal amounts of drug are required to achieve powerful therapeutic effect. In addition, such drugs have the ability to engage targets that are otherwise ‘undruggable’ by small molecules and proteins, thus opening up whole new avenues for treating intractable diseases. Turning this concept into a clinical reality, however, is no small feat. ASOs and siRNAs have been in clinical development for decades, and for much of this time, clinical success has been out of reach due to three delivery related challenges: protecting the therapeutic oligonucleotide from dismantling by the immune system; maintaining stability so the molecule can do its job; and penetrating the target organs and cells. We believe that demonstrating our ability to overcome the challenge of RNA delivery to genetic targets outside the liver would represent a major step forward in unlocking therapeutic access to genetic targets involved in a range of cancers.
We employ a modular drug design approach to develop product candidates that we believe canefficiently deliver therapeutics to genetic targets. This approach is based on four complementary design elements that together address the challenges of RNA drug development in oncology:
- Modular Design for Therapeutic Development— Our discovery platform consists of a modular ‘toolbox’ for developing therapeutics designed to attack specific disease-causing RNA targets based on the phenomenon of genetic complementarity. These therapeutics incorporate modular RNA/DNA components, such as antagomirs, mimics, miRNA sponges, siRNA duplexes, ribozymes, and others.In addition to these oligonucleotide chemistries, we can synthesize nanocarriers for the therapeutic oligonucleotides, using rational modular approaches. Combined, the modularity of these oligonucleotide and nanocarrier components allows us to synthesize libraries of potential therapeutic agents designed for a given indication.
- Genetic Code — The genetic code provides a coded blueprint for drug design. We can take advantage of the coded nature of the genome to computationally design oligonucleotides that target dysregulated genes. Our modular toolbox takes advantage of our rapidly expanding knowledge about the human genome and the annotation of the genome and about which genes contribute to cancer, and how. Armed with this knowledge, we can take advantage of the coded nature of the genome to design synthetic RNA or DNA molecules called oligonucleotides or Oligos, that correspond to genetic targets of interest. Once we determine the code of the cancer target, we can apply oligos that are harmonized to that genetic target and rewrite the story on cancer. This is what TransCode means – to change the code. What gives us an advantage over others is a key component of our modular tool box - our delivery system.
- Nanocarrier Delivery Mechanism — Our strategy seeks to leverage a nanoparticle that has been extensively used in humans for imaging purposes by repurposing it to deliver oligonucleotides to cancer cells. The nanocarrier is tunable to pre-designed specifications to deliver therapeutic oligonucleotides to an RNA target in tumors and metastases without compromising its integrity.These nanocarriers differentiate us from competitive delivery approaches which rely on lipid particles or chemical structures, such as GalNAc. Competitive delivery approaches effectively target sites in the liver but not sites in tumors and metastases. Our nanocarrier is derived from and is chemically similar to nanoparticles extensively used in imaging or for treating iron deficiency anemia.
- Image Guided — Because our product candidates are innately detectable using non-invasive imaging, we can monitor their delivery to the tissue of interest and measure their bioavailability. The ability to monitor delivery using Magnetic Resonance Imaging, or MRI, can be instrumental to assessing and controlling the amount of oligonucleotide that reaches the targeted tissues. MRI use during the design phase of the product candidate could guide drug design, delivery schedule, route, and dose and could suggest alternatives should treatment with the therapeutic candidate fail in a given patient.This is critical during drug development because it should allow us to optimize drug design to maximize therapeutic effect.