Biologics Today and in the Future
Many chronic and debilitating illnesses are treated with biologic therapies today. These diseases include genetic disorders that require protein replacement as well as disorders that require dynamic protein delivery such as Type 1 Diabetes, blood factor disorders and lysosomal storage diseases. While protein-based therapeutics have transformed patient care, built tremendous value and fueled the growth of the biotech industry, significant unmet needs remain:
- Dosing of protein based therapies leads to sub-optimal delivery and compromised efficacy due to inability to provide consistent pharmacokinetics
- Often administered by frequent injection or infusion, leading to a significant burden for patients and caregivers
- New modalities to address protein delivery, e.g. gene therapy, face considerable technical, regulatory, and safety challenges when administered systemically
- Some proteins, e.g. those with short half-lives, are not viable as therapeutics leaving patients with no treatment options
- There is a significant opportunity for next generation protein therapeutics administered in a natural way to advance patient care
Components of the Sigilon Therapeutics Platform
In a world first, Sigilon Therapeutics is pioneering technologies that will harness the full power of cell therapeutics. Our proprietary Afibromer™ (afibrotic polymers which do not trigger a fibrotic response) technology allows a new category of therapeutic with extremely broad potential: encapsulated cell therapeutics that do not require immunosuppression. Sigilon Therapeutics’ cell-driven therapeutics are designed to have advantages over traditional biologic therapies, including:
- Improved outcomes over current standard of care
- Restore protein levels at a constant rate
- Provide years of therapy without need for redosing
- Safe and reversible therapeutic modality
- Replace frequent injection or infusion
- Deliver proteins for previously untreatable and serious diseases
- Broadly applicable to a variety of biologics and treatment modalities
- Offer a rapid preclinical timeline and favorable regulatory pathway
These advantages should provide significant clinical outcome benefits and free patients from therapies that are disruptive to quality of life. Imagine a therapy that both improves outcomes and only requires intervention measured in years rather than days.
Cell therapies have significant potential and have been delivered to the body for many diseases over the last 25 years. Cell therapies have been tested in the treatment of diabetes, cancer, Fabry disease, mucopolysaccharidosis type VII, myocardial infarct, polycythemic disease, congestive heart failure, hemophilia B, retinal diseases, glaucoma and Parkinson’s disease. While implanted cells have shown the ability to produce desired therapeutic proteins, genetically dissimilar cells are attacked and destroyed by the immune system. This has occurred even if the cells are encapsulated within biomaterials. The biomaterials used in the past evoke a foreign body response which results in a fibrotic covering rendering encapsulated cells useless as therapeutics. This is demonstrated in the below picture which shows polystyrene beads coated with our Afibromer™ technology vs uncoated beads. You can clearly see that when these beads are implanted into an animal, you have rapid fibrosis of the uncoated beads, while the Afibromer™ coated beads remain pristine.
As mentioned above, Sigilon Therapeutics was founded based on the discovery of novel biomaterials called Afibromers™. Cells that are encapsulated in Afibromer™ coated capsules are invisible to the immune system and do not trigger fibrosis – the scarring response that the body uses to isolate foreign bodies and which is responsible for nutrient deprivation and cell necrosis.Our proprietary cells are engineered to secrete therapeutic proteins and, in combination with our Afibromer™ technology, these implanted cells are hidden from the immune system, and levels of the missing protein in the body can be restored for long periods of time following a single intervention.
The proper characteristics of our proprietary cell lines are critical to the success of our therapeutics and optimization for particular indications. Our cell lines are designed to:
- Express high levels of desired protein
- Be easily transfected
- Display contact inhibition
- Possess high viability on encapsulation
- Scale up for product manufacturing
- Have a record of prior use in humans
In addition, our proprietary cell lines provide the ability to “plug and play” different expression cassettes (depending on the targeted therapeutic protein) to decrease both the time and money spent in preclinical discovery and development.
Our novel Afibromer™ polymer chemistry is used to encapsulate our cells and prevent the foreign body response which has proven to be a significant hurdle for previous therapies. The discovery of multiple different chemistries that provide the protection from immune attack allow us to have flexibility to optimize the encapsulation for the specific cell line and disease. This series of novel small molecules can be covalently attached to biomaterial surfaces and polymers. Utilizing this technology, we have demonstrated a solution to the fibrosis challenge in multiple animal species for up to 12 months. Our therapeutic products are comprised of engineered proprietary cells protected by our novel polymer chemistry to create a “living therapeutic” that is placed into a living patient. Among other advantages, this therapy is designed to be stable for more than a year providing both benefits in efficacy as well as in quality of life given the greatly reduced frequency of treatment required.
Afibromer™ Chemistry Prevents Macrophage Detection
Macrophage Attacking Conventional Material