Enable Biosciences – Advancing Early T1D Detection

This article has been updated to reflect current testing methods and costs since the original 2023 interview with Enable Biosciences CEO Peter Robinson.

The Evolution of Diabetes Testing

Throughout history, brilliant minds have tried to understand the nature of diabetes and its course of treatment. From the early fifth century, physicians only knew how to test an individual’s urine for sweetness using tasters or ants.

In 1841, researcher Karl Trommer developed the first clinical diabetes test by adding acid hydrolysis to the individual’s urine sample. In 1922, developers introduced an oral glucose tolerance test (OGTT), where the patient ingests sugar, and blood glucose levels are checked two hours later.

The 1950s advent of urine test strips and 1970s blood glucose monitors blazed the way for the A1C or HbA1c test, which measures blood sugar over several months. Other current testing includes the standard capillary glucose test and fasting plasma glucose (FPG). And now, the prominent developers Enable Biosciences have created an antibody test for early detection of type 1 diabetes (T1D).

Type 1 Strong had the opportunity to speak with one of Enable Biosciences’ Co-Founders and Chief Operating Officer, Peter Robinson, Ph.D., about the development, process and what the future holds for testing.

“The test we produce is one of the best in the world at predicting who will get type 1 diabetes, and it is extremely important because, as of November 2022, there is a drug therapy that can delay the onset of type 1 diabetes,” said Robinson. “But it must be administered before clinical symptoms and before there is any metabolic indication of type 1.”  

After completing his chemistry doctorate for graduate work at UC Berkeley and Stanford, Robinson explained they had developed a sensitive technique for detecting modification to proteins. “It was a basic science project. We weren’t really eyeing any applied methodologies, but then, when the lab was moving from Berkeley to Stanford, we had two to three months on our hands, so we participated in a startup accelerated program through UCSF (UC San Francisco). During that process, we interviewed a lot of endocrinologists who painted a picture of a field and a disease that was on the cusp of changing the way it’s detected and the tools that might be available to prevent or delay the onset of type 1.”

Enter Enable Biosciences

Seven years later, Robinson and his colleagues re-tooled the technology to detect the biomarkers to predict whether someone is at risk for developing T1D. “We and many others are trying to advance accessibility and the knowledge that these tests exist, and if you are at risk, there is something you can do about it—to delay the onset.”

In addition to type 1 diabetes, the San Francisco-based biotechnology company develops ultrasensitive tests for HIV, Lyme disease, Celiac, COVID and many food allergies.

Enable Biosciences’ lab and office space resides in the birthplace of biotech, south San Francisco, and consists of around 15 employees, primarily engineers and scientists. Robinson founded the diagnostics company with three others: David Seftel, MD, MBA, is the chief executive officer, Jason Tsai, chief technology officer and gold medalist at the 2008 International Chemistry Olympiad; and Carolyn Bertozzi, a Standford professor who was awarded the 2022 Nobel Prize in chemistry.

Enable Biosciences develops analytical tools for precision medicine and has been awarded $4.5 million in grants to develop assays for early detection and treatment of diseases.

“We have been thankful to be on the end of generous support from the National Institutes for Diabetes and Digestive and Kidney Diseases (NIDDK). This division of the National Institutes of Health has really fueled our research and development cycles for the now clinically available test,” Robinson said. “It has been a collaborative effort from the beginning, and we’ve had quite an extensive list of collaborators. We also work closely with groups at Stanford University, the Joslin Diabetes Center, and the University of Florida, among many others.”

Antibody Detection by Agglutination-PCR

Enable Biosciences developed ADAP, or Antibody Detection by Agglutination-PCR, an immunoassay technology designed to detect very low levels of disease-associated autoantibodies.

The company's T1D test currently screens for three major type 1 diabetes-associated autoantibodies:

• GAD65 (GAD) autoantibodies
• IA-2 autoantibodies
• Insulin autoantibodies (IAA)‍

The company's clinical reference laboratory is CLIA-certified and CAP-accredited. Its T1D test is a laboratory-developed test and has not been cleared or approved by the U.S. Food and Drug Administration (FDA).

Why Early Detection Matters

Type 1 diabetes does not necessarily begin when blood glucose becomes elevated or symptoms develop. The autoimmune process can begin much earlier.

The presence of one T1D-associated autoantibody indicates increased risk, while the presence of two or more persistent autoantibodies is a marker of early-stage T1D.

This distinction is important because early detection creates an opportunity for monitoring before a person becomes seriously ill.

DKA remains a potentially life-threatening complication of T1D and can be the first indication that someone has the disease. Screening and monitoring can give families and health-care providers an opportunity to recognize the progression toward symptomatic disease before an emergency occurs.

Early detection has become even more important since the FDA approved Tzield (teplizumab), the first disease-modifying therapy shown to delay the onset of stage 3 type 1 diabetes. Tzield is approved for adults and children ages 8 and older with stage 2 T1D.

“We are a clinical testing lab in addition to a test manufacturer, and that is what we contribute to the partnership,” Robinson said. “We offer testing services to people recommended by their physician, and a physician must do the Tzield eligibility.”

Robinson added that Enable Biosciences provides a biochemical measurement to a clinician, who then determines if it’s a good match for treatment. “Doctors will often have these tests taken over time to increase the confidence of the predictions since this is definitely something you want to get right. The therapy is fairly costly as well as being a week-long IV infusion that can be challenging to administer.”

Early Detection is Key

Early detection is paramount for managing and reducing the impact of T1D by providing new drug therapies to delay type 1 symptoms and onset. Studies have shown the Tzield drug has starved off the disease for up to two years in patients. Considering the hefty cost of insulin, pump and CGM therapy, and the emotional toll the condition takes, two years means a great deal. 

The autoimmune disorder now affects over 1.6 million people in the United States, with 40,000 new cases annually. The disease causes glucose levels to rise, which may lead to various health complications, including diabetic ketoacidosis (DKA), a potentially life-threatening condition. “Screening is really, really important to reduce the risks of DKA,” said Robinson. “Far too many families face serious, long-lasting implications if type 1 goes undiagnosed. DKA is very dangerous and deadly. One observation showed if you can identify individuals, coupled with education, DKA rates decreased from 60 to three percent.”

Testing for diabetes has come a long way, from the water tasters, using ants, urine test strips, and fasting to the A1C. Robinson explains that the A1C is critical to get a full picture of the disease’s progression, the immune system’s state, and the individual’s metabolism. “The markers that our tests indicate, the autoantibodies, are the earliest indicators that an autoimmune process is happening at all.”

How Enable's Testing Works Today

Enable's testing process has evolved since the company's original consumer-focused launch.

Today, Enable's T1D autoantibody test is provider-ordered clinical testing rather than a direct-to-consumer test that an individual independently orders without a health-care provider.

A health-care provider orders the laboratory test through Enable. The company supplies blood-spot collection kits to participating clinics. A dried blood spot sample is collected using a small blood sample and then sent to Enable's clinical reference laboratory in South San Francisco for analysis.

The company's current materials describe the process as:

1. A health-care provider orders the T1D autoantibody test.
2. Enable provides the sample-collection materials to the clinic.
3. A blood-spot sample is collected.
4. The sample is mailed to Enable's CLIA-certified, CAP-accredited laboratory.
5. Enable analyzes the sample for T1D-associated autoantibodies.
6. Results are provided to the ordering health-care provider.

What Does Enable Testing Cost?

The company’s current testing terms state that the maximum amount a patient will pay is $189. For uninsured patients or those who choose not to use insurance, $189 is also the company’s Good Faith Estimate.

What the Future Holds

Thanks to advances in screening and a better understanding of the human immune system, we now know that type 1 diabetes is not sudden and usually starts long before insulin is required. 

“The need for better testing methodologies was much more profound in the type 1 diabetes space, so we felt we could have a more substantial impact on this field because the need was so much greater,” said Robinson.

Enable Biosciences’ team of scientists, engineers and clinicians have created tools for predictive medicine that help users determine their eligibility for preventative therapy.

“With attempts to make disease-modifying therapies for type 1 for certainly over 50 years, if not more, for the first time ever, we have something that works – Tzield can delay the onset,” said Robinson. “That not only is an incredible success story and good news for patients, but it also allows our healthcare system to understand the significance and draw attention to the fact that something has changed. In a big country like the United States with a very complex and fragmented healthcare system, it’s not going to be something that one company or organization does, but it certainly feels worth it to get through this 1,000-mile journey.”

When asked what Robinson is most enthusiastic about in the biotechnology testing field, he said, “I’m very excited about the next five years as we see this unfold. There’s also a universe of new therapies coming through the pipeline with different mechanisms throughout the different stages of the disease. We have this first really good tool, and it will only get better from here, which I think is a really fantastic thing to consider.”

Robinson added, “I’m watching, and obviously, this is much further down the road, but a lot of these islet cell replacement therapies, an interesting science, have a really high promise if they can get through the very big existential hurdles and complicated technologies – but it would be really fantastic as well to have tools that help individuals with type 1. So hopefully, we’ll see some progress there in the near future.”