Code Biotherapeutics
Revolutionizing Genetic Medicine Delivery

Gene therapy holds the promise to cure a wide range of diseases and strengthen a body's capacity to fight illnesses by replacing a faulty gene or adding a new one. However, with the existing delivery vehicles used for introducing specific DNA sequences in gene therapy, accomplishing this feat with precision is a herculean task.

The frequently used adeno-associated virus (AAV) vectors in gene therapies can only deliver the genes once in full capability, as the human immune system generates natural immunity, preventing it from re-entering. Despite dramatic developments in genetic medicine, the efficacy and durability of some of these therapies wanes, and since AAV vectors can’t be used to re-dose the patients, the effects of debilitating genetic disorders may return over time. The AAV vectors also lack real targeting capabilities, making it necessary to inject large doses of the medication while expecting some of it will hit the target. Consequently, the safety profile of these AAV delivered gene therapies put patients at a higher risk of experiencing side effects.

“We are pioneering an era of change in the delivery of genetic medicines. We are revolutionizing the prevailing ways of genetic medicine payload delivery through our transformative technology to treat debilitating genetic disorders,” says Brian McVeigh, Chairman & CEO of Code Biotherapeutics. “Our one-of-a-kind platform uses non-viral DNA-based vectors to deliver safer, redosable, and titratable treatments for genetic diseases.”

Code Bio is pioneering the targeted delivery of genetic medicines using its proprietary, novel, multivalent, synthetic DNA delivery platform, dubbed 3DNA. Steered toward treating debilitating genetic disorders, the platform is engineered to eliminate many

inherent challenges in genetic medicine delivery and offers unparalleled tissue and cell targeting specificity, improved bioavailability, the capability to deliver large genetic payloads, the ability to re-dose, and can be manufactured via a scalable, modular, reproducible process.

Code Bio’s non-viral vectors use synthetic DNA strands for delivering genes or RNAi based medications. It attaches a targeting agent to the DNA strands, which are linked together to form a scaffold, helping the mechanism achieve real-time targeting. Consequently, doctors can send small doses to the actual cell, gaining efficacy and reducing safety risks. Code Bio has taken this to animal tests, where its delivery mechanism has shown success in redosing.

Through its targeting capabilities, Code Bio can also improve the efficiency of delivery of siRNA and enable delivery of siRNA to tissues and cells not typically accessible when using the current industry standard delivery vehicle of lipid nanoparticles (LNP’s).

Since LNP’s are lipid-based particles, they are drawn to the liver instead of hitting the right target cell. With 3DNA, siRNA can target specific cells and quickly treat the ailment. To that end, Code Bio is also conducting discovery research programs for formulations to treat diseases through turning off or knocking down a gene in cells located in tissues outside of the liver.

Presently, the company is advancing its internal pipeline of genetic medicines focusing on Duchenne’s Muscular Dystrophy (DMD), a debilitating genetic disorder. DMD is currently treated using AAV, which can carry up to 5 kilobase pairs of a genetic sequence. Alternatively, the dystrophin gene is greater than 10 kilobase pairs in sequence, making it difficult for AAV to treat DMD. To improve the efficacy, researchers are using a micro-dystrophin or mini-dystrophin approach where they are trying to treat a truncated section of that dystrophin gene with AAV. However, the result is unsatisfactory because of AAV’s inability to be redosed.

Code Bio is working on the first stage of its discovery program, looking at delivering its version of the micro-dystrophin or mini-dystrophin to treat DMD. If successful, it could be used as a redosable therapy for new patients and those who have already been administered AAV. Code Bio is generating data to derive efficacious results from the therapy. Its next step is designing a formulation incorporating the Beckers’ Gene sequence which is two-thirds the length of a full-length dystrophin gene. It is simultaneously researching to develop an entire 14-kilobase pair sequence to treat DMD.

Code Bio’s discovery research program starts by analyzing the diseases that have affected the tissue or cell to find the possible payloads to treat the ailment. Depending on the payload, it can send any medication— antibody, peptide, gene construct, or siRNA—to treat the disease. This shows potential for treating multiple conditions, even rare ones, in the future.

A testament to the potential of Code Biotherapeutics' 3DNA genetic medicine delivery platform is its strategic collaboration with Takeda Pharmaceuticals’. They are working together to explore utilizing 3DNA for treating liver-mediated diseases and central nervous system (CNS) diseases. To treat CNS diseases, Code Bio has already shown data that demonstrates its capability to cross the blood-brain barrier and target specific brain cells.

“Our chemistry, translational research, and technology development teams comprise industry leaders whose experience and expertise are enabling us to make progress towards our mission of treating diseases that have to this point been untreatable,” adds McVeigh.

Code Bio’s research and achievements are fuelled by various investors, including institutional investors like NEA, Northpond, 4BIO Capital and Hatteras; strategic investors like Amgen Ventures, Takeda Ventures, UCB Ventures, and UPMC Enterprises; and investors from disease venture philanthropy groups. It has collaborations with many pharmaceutical companies that enable it to advance multiple avenues with the 3DNA platform through financial and strategic assistance.

Code Biotherapeutics’ top-notch platform, expertise, and dedication to going above and beyond to develop treatments for difficult to treat conditions, while ensuring higher efficacy and accuracy, is a ray of hope for a world tormented by complex and deadly diseases.