Autoimmune Disease

A New Frontier for Cell Therapy

Our Opportunity

As the third most common cause of chronic illness in the U.S., autoimmune diseases affect as many as 23.5 million people1. More than 80 known autoimmune diseases exist with suboptimal treatment and no cures, representing a leading cause of death and disability.

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Current therapeutic modalities include injectable monoclonal antibodies and small molecule oral medicines that do not always achieve optimal and long-lasting disease control. For example, the introduction of monoclonal antibodies targeting the TNF-alpha cytokine (also known as “anti-TNF agents”) has brought progress to the care of patients with many autoimmune diseases, yet patients often need to be switched to either another anti-TNF agent or to a new modality as disease control diminishes and symptoms return.

Autoimmune diseases may also require extreme, broadly immunosuppressive approaches (for example, corticosteroids or calcineurin inhibitors) which can leave patients with dampened immune responses, rendering them susceptible to infections and malignancies. Looking at the most recent approaches for the spectrum of immune-mediated disorders categorized as inflammatory bowel disease (IBD), up to one third of patients demonstrate primary nonresponse and another 30% of patients become refractory due to secondary loss of response.2

Kyverna aims to successfully apply cell therapy to autoimmunity. We believe that Kyverna’s engineered cells have the potential to address the underlying mechanisms of autoimmune disease with the additional benefits of improving safety and tolerability by minimizing toxicity associated with current treatments.

Potential Disease Targets

In its simplest form, autoimmune disease emerges when the complex network of the normally protective human immune system is unable to discern between self and non-self. Abnormal immunity against self-antigens may be evidenced by a rise in antibodies (called “autoantibodies”) against a variety of molecules. A cell population responsible for the production of antibodies, the B cells, has been identified as playing a key role in so-called humoral auto-immunity. Other immune cells have been identified at the root of autoimmune diseases and in particular an imbalance between T cells that dampen inflammation (regulatory T cells, or Tregs) and T cells that cause inflammation (effector T cells, or Teff). For these reasons, autoimmune diseases lend themselves to cell therapy treatment approaches.

Our goal is to demonstrate the clinical potential of Kyverna’s engineered T cell therapies as safe, effective, and potentially curative treatments for autoimmune diseases. Our initial disease targets are diseases for which there are no approved treatments, or for which the results of existing treatments could be further improved. In the absence of an approved treatment, physicians will often try out other medicines, exposing patients to the side-effects of these medicines with no demonstrated efficacy for the patients’ disease. This reality underscores the pressing need to come up with better solutions for patients. While other autoimmune diseases already have approved treatments (e.g. Inflammatory bowel disease or IBD), a significant portion of patients do not experience adequate disease control with such treatments and would benefit from new approaches.

Lupus Nephritis

What it is

An autoimmune disease in which chronic kidney inflammation can ultimately lead to complete kidney failure and the need for renal replacement.

Where it strikes

Systemic lupus erythematosus is among the top 15 most prevalent autoimmune diseases in the U.S.1, affecting approximately 330,000 patients3 Lupus nephritis affects up to 60% of patients with systemic lupus erythematosus (SLE).

Current treatments

Two conventional approaches; one small molecule, and one biologic agent were recently approved by the FDA for the treatment of patients with active lupus nephritis in combination with a background immunosuppressive regimen. Despite these approvals there is still an unmet medical need for truly transformative approaches that will eliminate the use or need for potent immunosuppressants, dialysis, or kidney transplantation.

Systemic Sclerosis

What it is

A multisystem autoimmune disease that is characterized by widespread vascular dysfunction and progressive fibrosis (scarring) of the skin and internal organs.

Where it strikes

The prevalence of systemic sclerosis is estimated to span from 50 to 300 cases per 1 million people.4

Current treatments

While some treatments may alleviate symptoms, there are currently no effective or approved therapies for the underlying disease process.

Inflammatory Bowel Disease

What it is

Inflammatory bowel disease (IBD), namely ulcerative colitis and Crohn’s disease, are two distinct autoimmune diseases that involve inflammation of the gastrointestinal tract.

Where it strikes

Approximately 1.3% or 3 million U.S. adults reported being diagnosed with IBD.5

Current treatments

Several classes of agents are available in oral, injectable or local formulations. Both small and large molecules (biologics) are available. Mechanisms of action range from broad anti-inflammatory agents (e.g. corticosteroids, aminosalicylates, and JAK inhibitors) to biologic agents targeting select cytokines or addressins. Despite this plethora of approaches, few patients experience sustained disease remission.

  1. Hayter et al., Autoimmune Rev., 2012 Aug;11(10):754-65.
  2. E. Carter et al., Nature Reviews Rheumatology, 12, Oct. 2016, 605-620.
  3. Global Data

  4. https://www.uofmhealth.org/conditions-treatments/rheumatology/what-scleroderma
  5. Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of inflammatory bowel disease among adults aged ≥18 years—United States, 2015.