Genewity is pioneering advanced technologies aimed at revolutionising immune reconstitution for patients with severe immune deficiencies. In close collaboration with world-leading institutions and industry partners, we focus on rigorous preclinical and clinical research to deliver transformative therapies that restore immune function. Our innovative solutions leverage gene-modified cell therapies to address complex immune disorders, ultimately enhancing patient well-being and healthcare outcomes. With a commitment to scientific excellence and patient-centric care, Genewity is at the forefront of transforming the future of immunotherapy.

Revolutionising immune reconstitution with a gene therapy for RAG1-SCID

For a simplified version of this explanation, click here.

Severe Combined Immunodeficiency (SCID) is a rare and life-threatening immune disorder caused by mutations that inhibit the full development of the immune system. One of the most frequent causes of SCID are mutations in the RAG1 gene (RAG1-SCID). This gene is essential for V(D)J recombination, a process that generates diverse immune receptors in T-cells and B-cells. In RAG1-SCID, this process is disrupted, severely weakening the adaptive immune system.

People with RAG1-SCID are highly vulnerable to infections, where even mild ones can become life-threatening. The condition became widely known in the 1970s with the case of the "bubble boy," who had to live in a sterile environment for survival due to SCID.

Currently, allogeneic haematopoietic stem cell transplantation (HSCT) is the only available treatment for most forms of SCID. Patients without a matched donor have significant risk of mortality, and the recovery process from allogeneic transplantation is complicated by the risk of graft-versus-host disease (GVHD), in which the immune cells derived from donor stem cells attack the recipient's body. Additionally, HSCT often requires patients to travel long distances to specialised centres for extended periods, which is an added challenge for individuals with compromised immunity.

Genewity is now able to offer an innovative potential cure for RAG1-SCID (i-RAG) that involves inserting a functional RAG1 gene into the patient’s haematopoietic stem cells. In the RECOMB open-label trial, five patients have been recruited thus far, demonstrating impressive early clinical evidence for long-term efficacy and safety. Notably, the first two patients enrolled in the trial are now attending school, respond normal to vaccinations, are independent of prophylactic intravenous immunoglobulins and are living normal lives, cured of what was once a fatal disease.

Of note, with i-RAG, the cells travel, not the patient. The patient’s blood is sent to a central lab, where selected cells are modified with the functional RAG1 gene. After extensive quality control, the processed stem cells are sent back to the patient’s local hospital for transplantation, avoiding the need for the patient to travel.

Genewity is currently planning to expand the trial to the U.S. alongside the marketing approval from the European Medicines Agency (EMA). The goal is to make the therapy accessible to as many patients as soon as possible.

Revolutionising immune reconstitution with autologous thymus tissue

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The thymus is a small organ located above the heart that plays a key role in developing a balanced immune system, especially in the development of functional T-cells. Similar to SCID, for children born without a functioning thymus, even common illnesses like the flu can become life-threatening, since T-cells do not develop without the thymus. On the other hand, if the thymus promotes excessive immune activity, it can lead to autoimmune disorders, where the immune system mistakenly attacks the body's own tissues.

Unfortunately, no thymic stem cells exist to regenerate the thymus, and thymic cells cannot be cultured ex vivo. This presents a significant challenge for patients with immune dysfunctions where traditional therapeutic options are limited. At Genewity, we have developed a proprietary technology that addresses this unmet need: i-Thymus. By introducing a master transcription factor into patient-derived induced pluripotent stem cells (iPSCs), we can differentiate autologous cells into functional thymic organoids for the replacement of thymic function without the limitations of donor tissue.

The ability to generate thymic organoids from a patient’s own cells positions Genewity as a leader in the field of immune reconstitution. The i-Thymus platform offers a patient-specific solution to address immune dysfunction, targeting severeconditions (e.g. congenital athymia) where T-cell immunity needs to be switched ON, but also autoimmune diseases, where T-cell immunity needs to be switched OFF.

In autoimmune disease, we are striving to restore immune tolerance by harnessing the thymus' natural ability to induce apoptosis in auto-reactive T-cells and promote the development of regulatory T-cells. Based on the i-Thymus platform, we are creating specialised thymus tissue (i-TOL) to reprogram the patient’s immune system toward a tolerogenic state, offering a promising new avenue for treating autoimmune diseases.