Pipeline

Chronic granulomatous disease (CGD) is a rare and severe genetic disorder which significantly impairs the immune system. It leaves patients vulnerable to recurrent and severe bacterial and fungal infections, often leading to dysregulated inflammation and serious complications. CGD affects approximately 1 in 200,000 live births, and the median life expectancy for individuals with the condition is around 45 years.

Patients with CGD experience recurrent infections that can severely impact their quality of life and increase the risk of life-threatening complications. Current treatment options include antibiotics, antifungals, interferon gamma, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ex vivo HSC-targeted gene therapies have shown benefit in clinical trials, but this approach carries significant burdens for the few patients that can access it.

Our lead program, EN-374, aims to address these challenges by restoring critical immune function through the delivery of a corrected gene directly to HSCs in vivo, followed by enrichment. This is designed to free patients from their symptoms, replicating the transformative outcomes of ex vivo approaches without the associated treatment burdens and risks.

Sickle cell disease (SCD) is a debilitating genetic disorder characterized by a mutation in hemoglobin resulting in abnormal red blood cells. Patients with SCD endure a difficult and often agonizing journey, facing severe complications, including debilitating pain crises, anemia, infertility, increased risk of infections, stroke, and organ damage. This condition affects approximately 100,000 individuals in the U.S. and millions globally.

The small proportion of patients that can access treatment with today’s ex vivo gene therapies for SCD face an intricate and lengthy treatment process, involving multiple complex steps such as blood transfusions, stem cell mobilization and collection, long manufacturing timelines, myeloablative conditioning, and extensive hospital stays to manage severe side effects. This journey is risky, emotionally and physically draining for both patients and their families and caregivers. These burdens highlight the urgent need for more streamlined and effective solutions. Patients face similar or greater challenges with allogeneic stem cell transplantation which also carries a higher risk of mortality.

Our approach includes a transformation of the patient journey through a simpler, outpatient process through which we will reactivate an alternative form of hemoglobin directly in vivo through engineered HSC delivery followed by enrichment. We aim to significantly reduce the patient burden while providing a transformative, long-term solution for managing the complications of SCD that can be scaled to patients throughout the world.

Solid tumors represent a major challenge in oncology, accounting for approximately 90% of all cancer diagnoses. The complexity of solid tumor microenvironments can hinder effective therapy delivery and immune response, making treatment particularly difficult. Despite major breakthroughs with CAR T-cell therapies in treating blood cancers, many patients with solid tumors face poor prognosis, with survival rates varying widely depending on the tumor type and stage.

Our goal is to give patients new hope in their fight against cancer with gene therapies that provide lasting anti-tumor responses. By engineering multiple types of immune cells for enhanced tumor infiltration and persistence, we aim to create off-the-shelf therapies that can treat more cancers in more patients. Following proof-of-concept in solid tumors, we intend to expand our work into blood cancers.