Tell us about LogicBio. What kind of treatments are you pursuing?
We’re developing a new form of genome editing based on a technology called GeneRide. It uses a viral vector to carry into the patient’s cells a corrective transgene that’s capable of taking over the duties of the mutated gene causing the patient’s disease. That part is nothing new – it’s a common and well-validated technique used in many gene therapies. What comes next is what makes GeneRide different.

Unlike other gene editing approaches, we don’t bring “molecular scissors” into the cell’s
nucleus to cut the patient’s DNA. Nor do we bring in an external promoter to “turn on” the new gene we’ve just delivered. Those techniques have demonstrated risks, so we avoid them. Instead, we harness the cell’s natural repair mechanism, known as homologous recombination. That allows us to insert our transgene in precisely the right spot – next to a powerful promoter that can activate the new gene even as it continues to perform its normal functions.

When the new gene turns on, it begins expressing the proteins that the patient has been lacking. What’s more, the new transgene remains integrated in the patient’s genome even as his or her cells divide, so the therapy should be durable. That’s very important, especially in treating children as you want the therapy to continue to work as they grow.

Our goal with these therapies is to reduce symptoms and forestall progression of the disease. We hope to make a significant difference in patients’ lives by treating them early before their disease advances.

Have you tested this yet in patients?
We’re moving very methodically through the R&D process. We have demonstrated proof of concept that GeneRide works in multiple animal models. We are now conducting additional studies in preparation for submitting a request to the U.S. Food and Drug Administration to launch clinical trials in patients.

Why are you focusing on MMA?
As readers of this newsletter know all too well, there’s a huge unmet need for therapies to help individuals with MMA and other organic acidemias. We have spent time with these families and have been truly moved by their strength in the face of a disease that has few treatments. (Here, we share the story of one remarkable family living with MMA on our website.)

We also firmly believe that MMA is a disorder that is well-suited to be treated by our GeneRide approach. Early intervention is critical to combat the devastating effects of the disease. Our preclinical research demonstrates that we can safely and precisely deliver corrective transgenes to the liver of newborn mice. By editing the patients’ genomes so they begin producing the key enzymes they lack, we hope to be able to prevent or minimize the devastating damage caused during the metabolic crises that are characteristic of MMA.

Will all patients with MMA be eligible for your clinical trial, or only certain mutations?
Each of our therapies will deliver a different corrective transgene. Our first program will target MUT MMA and will insert a functional copy of the MUT gene into the patient’s genome.

Therefore, we will only be able to enroll patients with MUT mutations in our first trial. If
successful, we will be looking at other mutations in future programs.

What ages will be eligible for the clinical trial?
We are still working with the FDA on the specifics of our first trial. In general, our approach is aimed at pediatric patients.

What other diseases do you hope to treat?
We are working now on other diseases that target the liver, including Crigler-Najjar syndrome, alpha-1 antitrypsin deficiency, and hemophilia B. Down the road, we hope to expand into rare genetic diseases that target muscles and the central nervous system.

What’s your message for patients with organic acidemias?
We have enormous admiration for the strength and determination of individuals living with organic acidemias and their families – and we have enormous admiration, too, for all the work that OAA does to educate the public and advocate for the community.

We want everyone to know that this an exciting time in the biotech field, with great strides being made in addressing rare genetic diseases. We believe the new therapeutic approaches being explored by LogicBio and other companies hold real promise. We all feel a great urgency to bring novel treatments to patients, and we’re working hard to do just that.