How Immunoscience is Transforming Treatment for Type 1 Diabetes

Although presymptomatic T1D (Stages 1 and 2) can be detected months or years before symptoms appear, most people are not diagnosed until they feel unwel. ^{10 11}

Over the past 50 years, scientists around the world have worked to unravel the processes underlying T1D and how they can be targeted with new medicines. Today, we know that T1D is an autoimmune disease that causes patients to produce little or no insulin because their immune system mistakenly attacks the insulin-producing cells in the pancreas.¹¹ We also know that this attack begins long before symptoms appear.

“We’ve built up an understanding of what the immune system is doing before, during and after the development of clinical T1D,” said Mark Peakman, Cluster Head, Immunology & Inflammation Research at Sanofi. “This enables us to think about a series of stages, or gates, that patients go through as the disease progresses and how we can control or potentially close those gates.”

Understanding those gates is the foundation of Sanofi’s immunoscience strategy in T1D, Peakman said. “Immunoscience is our way of looking at the role the immune system plays not only in how diseases develop, but also how we can change their course.”

The first disease-modifying therapy for T1D builds on a new understanding of the natural history of the disease which shows that it develops through distinct stages. It is used at stage 2, where insulin-producing cells are under attack, but symptoms have not yet appeared. To delay a patient’s progression from stage 2 to stage 3, the therapy targets a protein called CD3 on the attacking T cells.

One such gate is the infiltration of cytotoxic, or cell-killing T cells in the pancreas, peaking in patients whose disease has reached stage 3, where the number of functioning insulin-producing cells declines to the point that the body cannot regulate blood sugar levels. ^{12 13}

The therapy builds on a breakthrough in immunoscience made in the last decade showing that T cells can exist in a less unresponsive state known as “exhaustion”. In the intervening time, scientists started searching for medicines that can induce T cell exhaustion and discovered potent effects of monoclonal antibodies directed against CD3.

“Rather than eradicate those cell-killing T cells, which leaves us with no way to fight off viruses and other pathogens, the anti-CD3 can switch them to another state where they are exhausted and no longer able to cause cell damage,” Peakman said. “It’s the first medicine of its kind to work in this way in T1D, where it stimulates the immune cells just enough to push them into a state where they are less active.”

Sanofi is identifying additional gates that we can target through new medicines. These include the CD40/CD40L costimulatory pathway – a set of molecules used by immune cells to communicate with each other. Our scientists are developing a monoclonal antibody that blocks this pathway and stops the immune assault on insulin-producing cells in the pancreas.

“We are thinking about the disease from its very early stages all the way through to clinical diabetes, when people have symptoms,” Peakman said. “In addition to exploring where along that spectrum our drugs work best, we understand that the immune response evolves as the disease progresses. And we’re using immunoscience to figure out that evolution.”

“With our immunoscience portfolio, our innovation in vaccines and our diabetes heritage, we have the knowledge and experience at Sanofi to develop new medicines to help patients with T1D and maybe even help prevent disease onset altogether,” Niemöller said.

Sanofi’s work in T1D could represent a paradigm shift that can be applicable across therapeutic areas.

“Here, instead of reacting to a patient’s disease, we are using immunotherapy to delay the disease, to put off the day the disease appears by as many years as possible,” Peakman said.

Making T cells less responsive could possibly be applied in other autoimmune diseases. And our approach in T1D could pave the way for the identification of biomarkers that can potentially predict the onset or progression of other autoimmune conditions and possibly contribute to the research in the novel immunomodulatory treatment approaches.

At Sanofi, we are studying the pathways, cell types and interactions that make up these components to identify the broader immune mechanisms that might help us combat disease, and then matching them to potential therapeutic areas.

As with T1D, we are working on new treatments designed to harness the immune system, either by changing the balance of the immune responses that go awry in systemic, chronic diseases or by applying immune-mediated mechanisms to fight diseases.

Through our immunoscience approach, we are applying deep biological pathway knowledge and expertise across different, sometimes seemingly unrelated therapeutic areas, with the goal of bringing forward transformative new options for people around the world.