Back in April, I blogged about a Phase-II study called "Anti-Thymocyte Globulin and Verapamil Start A Phase-2 Clinical Trial" (NCT06455319). I should have included this trial at the same time, since they are closely related, but I didn't so I'm publishing this blog, now.
Both studies are testing ATG in honeymooners. The previous study was testing either just ATG or ATG and Verapamil. This study is testing a specific form of ATG produced by a specific company, SAb Biotherapeutics. See the discussion section for details of how SAB-142 and ATG differ. The first study is sponsored by a University, the second by a company, however I would not read too much into that, since the University was were many of the people involved in the company worked or continue to work.
About the SAFEGUARD Trial
SAFEGUARD (NCT07187531) is a randomized, double-blind, placebo-controlled Phase 2b study. It has two parts. Part A is an open-label, parallel-arm dose-ranging portion to confirm the dosing approach in adults; Part B, which is the main double-blind portion, will randomize participants to one of three groups — high-dose SAB-142, low-dose SAB-142, or placebo. The trial is enrolling approximately 159 participants total. All participants receive two treatment courses six months apart, and all are eligible for a 12-month long-term extension study after the main study ends.
To be eligible, participants must be between 5 and 40 years old (Part A is adults 15–40; Part B includes children from age 5), must weigh at least 16 kg, and must have been diagnosed with T1D within the prior 100 days according to American Diabetes Association criteria. They must have residual beta cell function (a random C-peptide of at least 0.2 nmol/L) and at least one T1D-related autoantibody (GAD65, IA-2, ZnT8, or insulin autoantibodies). People who have previously received teplizumab or any anti-CD3 treatment, or who have significant uncontrolled medical conditions, are excluded.
The primary endpoint for Part A is safety: specifically, the incidence of treatment-emergent adverse events, adverse events of special interest, and serious adverse events through four weeks after dosing. The primary endpoint for Part B is the change from baseline in C-peptide measured after a two-hour mixed meal tolerance test at 12 months — the same gold-standard measure of beta cell function used in all prior T1D immunotherapy trials. Secondary endpoints include continuous glucose monitoring measures (time in tight range, time in range, time above and below range), HbA1c levels, daily exogenous insulin use, hypoglycemia rates, and several composite measures of beta cell function and partial remission. SAB-142 drug levels and immunogenicity will also be tracked throughout.
SAB-142 is given by intravenous infusion — a drip into a vein, lasting roughly four to six hours, on two consecutive days. In the SAFEGUARD trial, participants receive two such treatment courses, six months apart.
The trial is supported in part through the Type 1 Diabetes Clinical Research Network (T1DCRN) and the Australasian Type 1 Diabetes Immunotherapy Collaborative (ATIC), both of which are supported by Breakthrough T1D (formerly JDRF). SAB BIO raised $175 million in a private placement in 2025 to fund the SAFEGUARD trial through completion.
To contact the SAFEGUARD study team:
Phone: 1-844-763-1890
Email: SAFEGUARD@sab.bio
Trial sites are located in:
United States:
San Francisco, CA; Aurora, CO; Gainesville, FL; Miami, FL; Atlanta, GA; Indianapolis, IN; Boston, MA; Kansas City, MO; Buffalo, NY; Chapel Hill, NC; Fargo, ND; Philadelphia, PA; Fort Worth, TX; Houston, TX; Charlottesville, VA; Seattle, WA; Tacoma, WA
Elsewhere:
Australia: Brisbane, Nedlands (Perth), Parkville (Melbourne) ×2, St Leonards (Sydney), Westmead (Sydney), Austria: Graz ×2, Innsbruck, Vienna ×2, Belgium: Jette (Brussels), Leuven, Liège, Denmark: Herlev, Finland: Helsinki, Turku, France: Paris ×2, Germany: Augsburg, Hanover, Oberschleißheim (Munich), Italy: Milan, Turin, Verona, Lithuania: Kaunas, New Zealand: Auckland ×2, Christchurch, Dunedin, Hamilton, Wellington, Poland: Opole, Poznań, Warsaw ×3, Slovenia: Ljubljana, Spain: Barakaldo, Málaga, Seville, United Kingdom: Cambridge, Cardiff, Edinburgh, Liverpool, London ×2, Nottingham, Oxford
Discussion
What makes SAB-142 different from previous forms of ATG is how it is made. Most ATG currently used in medicine is derived from rabbits (called rabbit ATG or rATG): rabbits are immunized with human immune cells, and their resulting antibodies are collected and purified. SAB-142, by contrast, is produced using genetically engineered cattle — specifically cows that have been given a human artificial chromosome so that their immune systems generate fully human antibodies rather than rabbit antibodies. The drug is made by SAb Biotherapeutics, Inc. (also known as SAB BIO), a clinical-stage pharmaceutical company based in Miami.
There was a Phase-I clinical trial of SAB-142 done in 2025 in Australia. I have not found a scientific journal article for these results, but SAb has published them at conferences. It tested single ascending doses up to 4.5 mg/kg in healthy volunteers, and a 2.5 mg/kg dose in a small cohort of six adults with established T1D. These showed that all four T1D participants who received SAB-142 at 2.5 mg/kg demonstrated preservation of C-peptide relative to baseline at Day 120, with three of the four showing C-peptide actually stayed at or above the baseline level. Those three participants also showed increases in average blood glucose time in range (from 73% to 85%) without any increase in injected insulin use. The placebo-treated participant with T1D showed the expected decline in C-peptide over the same period. I consider these results to be good, but not great. Certainly good enough to motivate a Phase-II trial, and that is where we are now.
Follow-up work from the same group, confirmed sustained immunomodulation and better metabolic control in a subset of participants. More recently, the MELD-ATG trial (NCT04509791), run by Universitaire Ziekenhuizen KU Leuven as part of the INNODIA network in Europe, enrolled 114 participants aged 5 to 25 to explore the minimum effective dose of rATG — that study completed in December 2024 and results are being analyzed.
There are several clinical trials (both past and present) testing ATG in various forms and in various ways:
- NCT01106157 was a 25 person, phase-I clinical trial of a combination or ATG and G-CSF. Showed a small improvement in C-peptide
- NCT04291703 was a smaller, longer term follow on study to NCT01106157. No strong results.
- NCT02215200 was a 89 person, phase-II, follow on to NCT01106157. It found that GCSF did not improve results, but that ATG did improve C-peptide production.
- NCT07216391 is an in-progress, 60 person clinical trial directly comparing ATG to Teplizumab in delaying the onset of T1D in people who are at risk (preventing people who already have two or more autoantibodies from progressing to T1D symptoms).
- The WAVE T1D trial (NCT07061574), is an in-progress, 120 person phase-II study at the City of Hope Medical Center. I've blogged on it previously. It is testing whether low-dose rATG followed by either adalimumab or verapamil preserves insulin secretion over two years in people aged 9 to 20 with new-onset T1D. They hope to have results in 2030.
- The MELD-ATG trial (NCT04509791) completed enrollment of 114 participants in Europe in December 2024. It found a small improvement in C-peptide results.
Breakthrough T1D has provided support for the SAFEGUARD trial through its funding of the ATIC clinical trials network in Australia and the T1DCRN network.
More Information
