our programs

Our protein editing platform offers unique possibilities for pipeline development, including basket trials across diseases caused by the same mutations.

HC Bio is dedicated to shepherding therapeutic tRNAs through the clinic and establishing them as a new class of medicine across a broad spectrum of genetically driven diseases.

Hemophilia A

Our lead program in severe hemophilia A aims to establish anticodon engineered (ACE) tRNAs as a breakthrough treatment option for the 20 percent of patients with PTC-driven factor VIII deficiency.

Patients with severe hemophilia A have low levels of FVIII activity (<1% of normal physiological levels) that cause spontaneous bleeding. Our ACE-tRNAs aim to improve on current therapies by enabling liver endothelial cells to produce full-length, functional FVIII under endogenous gene and protein regulation. The resulting FVIII proteins would not exceed physiological levels and have normal binding affinity with other proteins in the coagulation cascade.

Preclinical Data

Our lead program in severe hemophilia A is supported by preclinical data that includes in vitro assays demonstrating tRNA-mediated restoration of full-length clotting protein FVIII and that specifically shows activity in cells containing a PTC in the protein’s open reading frame.

We are building on these data through IND-enabling studies with the goal of enrolling a phase 1 clinical trial. Because of the versatility of tRNA-based therapies, approval in severe hemophilia A can act as a proof of concept and unlock treatments for a range of bleeding disorders.

Globally, there is a tremendous unmet need to provide treatment for those living with inheritable bleeding disorders such as hemophilia A. As a community, over the past 50 years, we’ve experienced an expansion of treatment options to include injected synthetic protein-based medicines as well as gene therapies. We welcome and encourage continuing innovation in this disease area, such as the work being done by HC Bioscience.
Mark Skinner
Living with hemophilia
President/CEO of the Institute for Policy Advancement Ltd, specializing in patient-centered outcomes research; Former president of World Federation of Hemophilia

Duchenne Muscular Dystrophy

Our research program in Duchenne muscular dystrophy (DMD) aims to treat 26% of cases caused by mutations that lead to a shortened/nonfunctional dystrophin protein—a critical component of muscle cells. Without dystrophin, people with DMD experience progressive and fatal neuromuscular degeneration.

Genetic-based approaches to treating DMD are uniquely challenging because dystrophin is one of the largest human genes. This size precludes viral delivery of a full-sized gene; current DNA and RNA-based therapies generate smaller versions of the protein that lack full function.

By overwriting PTCs during translation and adding the intended amino acid to the growing dystrophin protein, our anticodon engineered (ACE) tRNAs have the potential to be the first treatment option that restores full length, functional dystrophin.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and occurs in approximately 1 in every 5,000 male births.

Individuals with DMD face significant challenges including decreased heart function, weakened bones, and overall loss of muscle mass. Throughout adolescence, they may become reliant on wheelchairs and may lose the ability to feed themselves or breathe independently.

The symptoms of DMD can be lessened by physical therapy and steroids. Recent breakthroughs in genomic-based medicines are providing new approaches for addressing the muscular dystrophy caused by Duchenne.

Oncology

Our oncology program targets protein dysfunction at the root of uncontrolled cell proliferation. We are exploring approaches to restore the function of cancer-suppressing proteins disabled by nonsense mutations, as well as ways to fatally destabilize the proteome in cancer cells by systemically inserting missense amino acid substitutions.

Restoring tumor suppressors with the PTCX ("Patch") platform

Our PTCX platform, which enables production of full-length proteins that would otherwise be truncated due to a PTC, can rescue protein function that regulates cell division.

We are exploring this approach with, among others, APC, a suppressor of the Wnt signaling pathway which, when overactive, is a key driver of colorectal cancer. APC-mediated restoration of normal cell proliferation addresses an urgent unmet medical need as there are currently no true Wnt signaling targeting drugs available and up to 70% of colorectal patients carry a PTC in their APC gene.

OUR PTCX PLATFORM
Wnt signaling is difficult to target because it is very complex and involved in many processes. tRNA-based approaches are ingenious because they work with the regulatory machinery of the cell to restore normal Wnt signaling as opposed to externally drugging the pathway. I am hopeful and excited by the impact that this technology can have for patients.
Oladapo Yeku, M.D., Ph.D.
Medical Oncologist
Massachusetts General Hospital

Proteome destabilization with the
 SWTX ("Switch") platform

HC Bioscience is developing a variation on our PTCX platform that drives cancer cells to self-destruct.

Instead of overwriting genetic errors to add the intended amino acid, our SWTX tRNAs deliberately misread codons and deliver the incorrect amino acid into all proteins being produced by the cancer cell. This creates disruptive amino acid substitutions throughout the proteome analogous to a systemic missense mutation, leading to nonfunctional proteins and cell death.

Cancer-specific delivery

To specifically target cancer cells, we are engineering SWTX tRNAs as a first-and best-in-class programmable payload for antibody drug conjugates (ADCs). ADCs delivering cytotoxic tRNAs would have multi-targeted mechanism of action with unprecedented drug-to-antibody ratio and long durability.

Stay informed on our latest strides in protein editing and building a new class of genomic medicine.

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