Sigilon Therapeutics is a Cambridge, MA-based biotech company developing innovative therapeutics by encapsulating cells in a novel coating that renders them invisible to the immune system. The engineered cells contained in the company’s particles can provide long-term continuous therapy for a range of chronic disorders, including hemophilia and diabetes, and eliminate the need for intermittent injection or infusion. With this technological breakthrough Sigilon hopes to “fundamentally change the trajectory of disease treatment.”
Medgadget editor Tom Peach recently spoke with Devyn Smith PhD, Chief Strategy Officer of Sigilon Therapeutics, to learn more about the company’s technology.
Tom Peach, Medgadget: Devyn, what is your role at Sigilon Therapeutics and what was your background prior to joining the team?
Devyn Smith, Sigilon Therapeutics: I joined Sigilon a year ago as the Chief Strategy Officer and Head of Operations—I joined as I was excited to work on novel cell therapies, after a background working in this area in both consulting and in a large Pharmaceutical company. I think our technology offers a real opportunity to providing durable, meaningful treatments for paitients. By way of background, I began my career with a PhD in Developmental Biology at Harvard Medical School. I then spent some time in strategy consulting before moving into the biotech sector; I went to Pfizer and became COO of the Neusentis Research Unit in the UK, focusing on regenerative medicine and pain and sensory disorders, and also served as Head of Strategy for the Medical Sciences Division of Pfizer R&D.
Medgadget: What is the story behind Sigilon as a company? Where did you start and how did you get to where you are today?
Devyn Smith: We began about 10 years ago at MIT, where the labs of Robert Langer and Daniel Anderson were working on a project focused on creating a novel biomaterial that could encapsulate and protect cells from the body’s immune system. Over the course of that research, a library of compounds was discovered that can be used to coat a biomaterial, prevent the body’s immune system from recognizing the implant, and, thus, remain in the body for years. This work formed the basis of Sigilon Therapeutics, which was founded about 18-months ago. We are currently 30 employees and have taken that coating technology and coupled it with proprietary cell technology to build what we call “living therapeutics.”
Medgadget: What are some of the problems with conventional biologic therapies?
Devyn Smith: Current biologic therapies are effective, but the big challenge is that they must be re-dosed frequently. The initial dose of a drug leads to a very high concentration of the therapeutic in the blood. Then, over time the proteins are degraded, and this concentration drops before re-dosing, which results in a series of peaks and troughs of therapeutic levels. It’s often at these peaks and troughs that you see side effects and adverse events due to either too much or too little therapeutic in the body. In the case of treating something like hemophilia, this could mean patients have to be infused and keep receiving those infusions two or three times a week. Additionally, there are also some proteins that are currently just not amenable to becoming effective therapies because they degrade too fast and would need continuous infusions.
Medgadget: What is the structure of one of Sigilon’s therapeutic particles?
Devyn Smith: So let’s start with the inside. The center of the particle contains a population of cells, between a few hundred and many thousands. These cells have been created with some very specific properties: they must live a long time, they must divide very slowly, if a neighboring cells dies, they should replace it, and they must produce consistently high-levels of the desired protein for a very long time. The cells are then embedded in a modified alginate capsule, 1.5mm in diameter. The third component of the technology is the small molecule (Afibromer™) that then coats the outside of these capsules and prevents the body from recognizing the capsule as a foreign body. The cells are protected from the immune system by the capsule, and the capsule is protected from the body by the coating that prevents local fibrosis.
Medgadget: So what advantages does this system have when compared to current biologic therapies?
Devyn Smith: Firstly we’ve eliminated those peaks and troughs of traditional dosing of biologics with a constant source of the therapeutic. For example, in a hemophilia patient, that could mean eliminating bleeds in their joints, which are common when the therapeutic levels hit a trough. Secondly a patient only needs to receive our therapy once and they will receive adequate treatment for many years because of the steady release of the therapeutic. This means that a patient can basically live a normal life—and not have to even think about their condition for years on end. All of these benefits come with additional security compared to something like gene therapy, which also offers a long-duration treatment option, as our therapy can both be re-dosed and is stoppable/removable if needed.
Medgadget: How are these therapeutic particles actually delivered to the body?
Devyn Smith: The particles are placed in the lesser sac (omental bursa), which is like a little tote bag between the liver and stomach with a convenient window to introduce material through. This is a great space for the particles, as it’s a highly vascularized zone and drains right into the portal system, so a therapeutic can be rapidly delivered to the rest of the body. The capsules are also well protected in this location—it would be possible to implant the particles subcutaneously, but you would probably risk crushing them with trauma. We are also exploring other areas in the body to place our therapy.
Medgadget: What are the main target diseases for Sigilon’s technology? Can the particles only dose passively or is there a possibility of a controlled delivery?
Devyn Smith: Our primary targets include hemophilia, where patients experience some of the side effects we’ve already talked about along with requiring multiple infusions a week. We’re also looking at lysosomol storage disorders, which is another area where constant dosing of proteins can really benefit patients significantly. The third area we are currently exploring is diabetes, where treatment is currently very invasive with patients needing insulin shots or a pump system. In this case, the fact that we can deliver a particular cell line to the body that could sense the glucose level in the environment and respond with an appropriate dosing of insulin is really very exciting.
Medgadget: What is the path to seeing Sigilon’s particles in clinical usage?
Devyn Smith: We are currently in regulatory discussions and are moving rapidly towards clinical studies with a goal of the first in-human use the end of next year (2019). We have also just received our first Advanced Therapy Medicinal Product classification by the European Medicines Agency for our hemophilia B candidate. One of the beauties of the platform is that we’ve eliminated a lot of the traditional target risk in pharmaceutical development because we are pursuing known targets and disorders with a clear clinical and regulatory path. What is novel is our modality of delivery, which should really revolutionize treatment—and do so quite rapidly.
Medgadget: What do you think is the future of cell-based therapeutics? Are we going to see a complete end to conventional biologic therapies?
Devyn Smith: The goal is that with diseases like hemophilia or diabetes, a patient receives hopefully one treatment and they are good for three, five or ten years. This is fantastic as we’ve eliminated the need for the short-term injectable therapeutics, and the patient is effectively disease-free. This would clearly have significant implications for current therapies in these diseases. We believe that the safety record of our therapy will really be a differentiator. We think in time there will be a migration towards the majority of treatment being delivered via cell therapy, and patients will be able to live completely disease-free lives.
Link: Sigilon website…