▎WuXi AppTec Content Team Editor
Editor’s note: In addition to traditional small molecule drugs and antibody drugs, cell and gene therapy, RNAi and other oligonucleotide therapy, CRISPR gene editing therapy and more new types of molecules In recent years, it has gradually moved to the foreground and has become the focus of the biomedical industry, which is expected to rewrite the future treatment pattern of patients. As biopharmaceuticals enter a new era, WuXi AppTec’s content department has also launched a series of “Fast New Molecules”, inviting the surging wave of new molecular therapies to conduct interviews – these interviews are led by companies that focus on creating new types of new molecules. therapy, and has recently completed a large amount of early financing, which can be described as a rising future star in the industry. In a series of interviews with WuXi AppTec’s content department, they will also introduce to the industry how to use new molecular types to break through the limitations of existing therapies and bring new breakthroughs!
Guest profile: The guest of this interview, Dr. Andrea van Elsas, is an investment partner of Third Rock Ventures, a well-known venture capital firm, and the chief scientific officer of Abata Therapeutics, which completed 95 million yuan last year. US$ Series A financing to engineer T cells through cell engineering to address autoimmune diseases such as multiple sclerosis (MS). He is also Chairman of the Scientific Advisory Board of Lava Therapeutics.
WuXi AppTec Content: Andrea, thank you for taking the time to interview us. We learned that Abata is developing targeted autologous Treg cell therapy for severe autoimmune diseases such as multiple sclerosis. Could you please introduce your company’s innovative therapy to readers?
Dr. Andrea van Elsas: Over the past 25 years, regulatory T cells (Tregs) have been well studied, and Tregs function to suppress/control inflammation and support It has a wide range of functions in tissue repair and so on. One of Abata’s co-founders, Dr. Diane Mathis, is a pioneer in this field and has published numerous high-impact work revealing the role of Tregs in limiting overactive immune responses and promoting repair in a variety of organs and tissues. key role. Tregs inhibit inflammation through multiple mechanisms, such as cell-cell interactions and secretion of soluble immunosuppressive factors into the inflammatory environment. These highly potent Tregs function to dominate the activity of effector T cells, such as those in the meningeal lymph nodes, which are activated once T cell receptors (TCRs) detect myelin-associated antigens produced by tissue damage . By studying the transport of lymphocytes into the brain, Abata co-founder and chief medical officer Richard Ransohoff, MD, discovered that T cells require activation of T cell receptors (TCRs) via cognate antigens presented by meningeal macrophages to remain in the brain.
In the past few years, a handful of teams have clinically tested Treg cell therapy, but they have not tested it in patients with progressive forms of multiple sclerosis. Tregs therapy proved to be safe, however its efficacy was not ideal, we think this may be because most Tregs cells do not carry the appropriate T cell receptors to help them enter inflamed tissue. By inserting specific T cell receptors into Tregs cells by means of cell engineering, we have greatly increased the number of specific T cells that can be transported to diseased organs and exploited their multiple pharmacological effects to treat progressive diseases . In addition to this, Tregs cells are thought to persist and differentiate into tissue-resident Tregs, the persistence of T cells is important in autoimmune diseases, and even a single administration of Tregs may provide very durable clinical benefits. Not only that, but in preclinical models, Tregs have been found to secrete factors that stimulate myelin repair, increasing their potential long-lasting benefits. In addition to progressive multiple sclerosis, Abata’s research team is currently working on TCR-modified Tregs cells for the treatment of type 1 diabetes and inclusion body myositis.
WuXi AppTec Content: How does Treg therapy affect people with multiple sclerosis?
Dr. Andrea van Elsas: With our first drug product candidate, ABA-101, Abata is targeting patients with progressive MS. ABA-101 is an autologous Treg product that we engineered to express a specific T cell receptor to guide Tregs to the site of disease, an R&D project in collaboration with Abata founder Dr. Roland Martin. Several drugs are currently approved for the treatment of patients with relapsing-remitting MS with considerable success. However, we do not have effective therapeutic options to treat progressive forms of multiple sclerosis after the outbreak of the disease. This can be attributed, at least in part, to: 1) relapsing-remitting MS is driven by immune cells that enter the meningeal region from the peripheral blood; 2) drugs used to treat relapsing-remitting MS can effectively target peripheral blood 3) In contrast, progressive MS is driven by lymphocyte aggregates that form in the meninges, and cytokines secreted by these lymphocytes activate myeloid cells as well as other cell types, destroying local myelin structures; 4) The currently approved drugs for MS do not appear to affect the inflammatory activity associated with these meningeal lymphocytic infiltration. Drawing on experience in oncology—using TCR-engineered Tregs to treat disease—Abata is taking the first steps toward harnessing the amazing potential of cell therapy to treat patients with autoimmune diseases with high unmet medical needs.
WuXi AppTec Content: What do you see as key challenges in realizing the full potential of your company’s innovative therapies, Abatawhat is the solution?
Dr. Andrea van Elsas: First, TCR is a key element of this innovative therapy, however autoantigen-specific TCRs are very rare and HLA class II restricted The principles and technical methods of sexual TCR are currently under development. Second, as a therapeutic approach, autologous cell therapy requires effective investment in manufacturing processes, facilities, and teams. Third, trial endpoints that assess the clinical activity of any one drug in patients with progressive MS vary widely among patients.
Building on the TCR expertise of Abata founder Dr. Michael Birnbaum, Abata has recruited a distinguished team of scientists to create and operate an effective TCR R&D platform covering Data science optimizations and tools needed for Treg functional studies and cell engineering. To maximize learning from the initial few cohorts of ABA-101 patients, Abata will use imaging techniques developed by Danny Reich, MD, a senior NIH investigator and a key consultant to the company, to assess the status of MS lesions before and after treatment. Quantitative determination was performed. In addition to using various clinical biomarkers to determine the number of Treg cells and their activity in the meningeal compartment, we aim to complete the proof-of-concept of Abata’s TCR-modified Treg platform. Following ABA-101, Abata aims to have three Treg products in clinical development by 2026.
WuXi AppTec Content: How will Abata harness the potential of new data technologies, artificial intelligence or machine learning?
Dr. Andrea van Elsas: Abata recognized the potential high potential of artificial intelligence and machine learning by working with existing experts at Third Rock Ventures during the company’s incubation process. Influence. Following the company’s official launch in 2021, Abata has recruited a very strong data science team and is now applying world-class machine learning expertise to all aspects of the discovery, manufacturing and development of Treg therapies. I think we’ve only scratched the surface of the potential of AI/ML in drug development at a time when Abata is exploring new applications.
WuXi AppTec Content:Thanks for your insight, is there anything you want to share with us before the interview is over?
Dr. Andrea van Elsas: With regard to Abata’s autologous cell therapy product candidates, our goal is to explore state-of-the-art scientific and technological solutions to enable Treg therapy Production and application reach a scale that is much larger than the patient population the industry has undertaken to date. Simply put, the key question is how do we make Treg therapy accessible, not just to 100 or 1,000 patients, but to 100,000 patients per year.
WuXi AppTec Content: Thank you so much for sharing!