Three Clinical Trial Terminations: Two for Siplizumab, One for TOL-3021

Sometimes clinical trials are terminated while on going.   This is always sad for me, but it is important to keep track of the failures and also the reasons for those failures.  This blog describes three such cases.  Two are relatively recent, one fairly old, but I had not blogged on the termination before.

Phase 1b Clinical Trial of Siplizumab for T1D, Started in 2023, Terminated Due to White Blood Cell Depletion

The clinical trial, registered as NCT05574335, was an open-label, Phase 1b study designed to enroll a small group of eight participants. The trial started enrolling in 2023 and was open to individuals between 8 and 45 years of age who had been diagnosed with T1D within the previous 18 months. Participants were assigned to one of four dosing groups. The goal of the study was to identify a safe dosing regimen and to assess the effects of the treatment on residual beta cell function, with follow-up evaluations extending up to one year.

The biological being tested was Siplizumab, an investigational monoclonal antibody designed to target and selectively suppress specific immune cells, including T cells and natural killer cells. In this trial, Siplizumab was administered to participants in weekly doses for a total of 12 weeks. Prior to being evaluated in T1D, Siplizumab had undergone clinical testing as a potential treatment for psoriasis and for the prevention of acute graft-versus-host disease.

The study was initially placed on an enrollment hold and was ultimately terminated in Nov 2025 because participants experienced a greater than anticipated decrease in their white blood cell counts, a condition known as lymphodepletion.  

Clinical Trial Record: https://clinicaltrials.gov/study/NCT05574335

Phase 2 Clinical Trial of Siplizumab for New-Onset T1D, Started in 2023, Terminated for Business Reasons

The clinical trial, registered as NCT06025110, was a Phase 2, randomized, single-blind, placebo-controlled study that started in 2023. It was open to adults between 18 and 45 years of age who were recently diagnosed with T1D. The study expected to enroll 143 participants, but actually enrolled only 9.   It was designed to measure whether the treatment could preserve or improve beta-cell function. The primary endpoint evaluated the change in C-peptide levels at week 52 for patients treated with the medication compared to those receiving a placebo.

The biological being tested was TCD601, also known as Siplizumab. It is an investigational monoclonal antibody designed to selectively target and suppress the function of specific immune cells (specific T cells and natural killer cells). In this trial, the biological was administered to participants over a 12-week treatment period. Prior to this study, Siplizumab had been tested as a possible treatment for psoriasis and for the prevention of acute graft-versus-host disease, and it has also been evaluated in clinical trials for kidney and liver transplant recipients.

The trial was terminated in August 2025 due to "business reasons".  This is a few months before the study above was terminated for safety reasons.  The trial sponsor, ITB-MED, stated that the decision to halt the study was not related to any safety, efficacy, or regulatory concerns. Moving forward, ITB-MED and its strategic clinical partner, Nefro Avillion Clinical Development, will focus their resources on advancing transplant medicine, including kidney transplant induction. 

Clinical Trial Record: https://clinicaltrials.gov/study/NCT06025110

Phase 2 Clinical Trial of TOL-3021 for T1D, Initiated in 2019, Withdrawn Prior to Enrollment

The clinical trial, registered as NCT03895437 and known as the SUNRISE study, was designed as a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial. The study planned to enroll approximately 99 individuals between the ages of 12 and 41 years who had been diagnosed with T1D within the past five years.  The primary endpoint of the study was to evaluate the preservation of the body's own insulin production, measured by C-peptide levels during a four-hour mixed meal tolerance test, over a 52-week period. The trial was formally registered and initiated in March 2019 but did not proceed to the enrollment phase.

The biological treatment being evaluated was TOL-3021. It was designed to induce immune tolerance and stop the immune system from attacking insulin-producing beta cells. In this trial, TOL-3021 was intended to be administered as a weekly intramuscular injection for 52 weeks. 

The clinical trial was officially withdrawn before it enrolled its first participant, so no one was enrolled in the study. The exact reasons for the withdrawal were not published on the clinical trial registry.  Tolerion has not been active recently, so I don't expect and future work on TOL-3021.

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Tolimidone (MTX228) Starts A Phase-IIΔ Clinical Trial on Honeymooners

These researchers are testing Tolimidone (also known as MTX228), which has a long history.  It was developed by Pfizer as a treatment for gastric ulcers, but it failed to show enough benefit in a phase-II clinical trial. Years later, Melior Pharmaceuticals repurposed Tolimidone for type 2 diabetes, and ran a phase II clinical trial for that.  However, the company has not issued press releases since 2021, and there has been no new news on Tolimidone for T2D since 2019.

Later researchers found the enzyme which Tolimidone activates, called Lyn kinase, helps determine whether beta cells survive or die. In their experiments, turning Lyn kinase off caused beta cells to die and led to diabetes in mice, while activating it protected beta cells and encouraged them to multiply (including human beta cells). Those findings led to this study.

Tolimidone is administered as a capsule or tablet.

The Study

This is an open-label study where everyone gets the treatment (no placebo group). There is no blinding.  The different groups get different doses: 100 milligrams once a day, 100 milligrams twice a day, or 200 milligrams once a day, for three months. Adults between 18 and 65 who have had type 1 diabetes for at least a year can join.

The trial's main measurement is the change in C-peptide over 3 months, which reflects how much insulin the body is producing on its own.  Other measurements collected through the trial's optional longer follow-up include changes in daily insulin dose, HbA1c, fasting blood sugar, the amount of time spent in a healthy blood sugar range as tracked by a wearable glucose sensor, and the number of low blood sugar episodes, and more C-peptide data.

Recruitment began in mid-2025.  They hope for main results by October 2026 and publication by end of 2027.

The trial is currently taking place at a single site: University of Alberta, Edmonton, Alberta, Canada.

People interested in learning more about participating can contact Dominique Forrest at the University of Alberta by phone at 780-248-1770 or by email at dforres1@ualberta.ca.

Discussion

There is an obvious contradiction in how this study is structured.  The drug is expected to work by saving beta cells, by preventing them from dying.  However, the study is recruiting people who have had type-1 for more than a year, so are not in their honeymoon, and (presumably) have few to no beta cells left.  You would think a study aimed at a drug to save beta cells would recruit people who still had beta cells, or more of them.  I can't explain this.

I consider this a "phase-IIΔ" study, rather than a regular "Phase-II" study, because there has never been a phase-I study in type 1 diabetes.  There has been for other diseases, so this is like a phase-I study with respect to effectiveness, but a phase-II study with respect to safety.  The size (24 people) is closer to phase-I than phase-II.

The researchers are testing multiple doses in this clinical trial, so that they can run a follow on trial (probably another phase-II study) using the dose which shows the best results here.

More Information

• ClinicalTrials.gov listing: https://clinicaltrials.gov/study/NCT06474598
• Biodexa Pharmaceuticals: https://biodexapharma.com/
• Press release announcing the first patient enrolled: https://biodexapharma.com/biodexa-announces-recruitment-of-first-patient-in-phase-2-study-of-tolimidone-in-type-1-diabetes/
• Press release announcing Health Canada's approval of the study: https://biodexapharma.com/biodexa-announces-phase-2a-study-of-tolimidone-in-type-1-diabetes-approved-by-health-canada/
• Wikipedia page for Tolimidone: https://en.wikipedia.org/wiki/Tolimidone
• BioSpace coverage of the trial's first patient enrollment: https://www.biospace.com/press-releases/biodexa-hits-key-milestone-for-its-type-1-diabetes-candidate-tolimidone-enrolls-first-patient-in-phase-2a-study
• University of Alberta feature on the preclinical research behind the trial: https://www.ualberta.ca/en/folio/2023/11/could-a-pill-cure-diabetes.html
• Biodexa's interim financial results discussing the trial's progress: https://biodexapharma.com/interim-results-for-the-six-months-ended-june-30-2025/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

OPT101 Starts a Phase-II Clinical Trial

OPT101 is a small peptide (a type of protein) designed to target CD40, which plays a central role in the inflammatory autoimmune response that damages the insulin-producing beta cells in people with T1D.  The drug is given by subcutaneous injection, meaning it is injected just under the skin, like insulin.

The researchers hypothesize that by regulating inflammation related to CD40 immune cells (called Th40 cells), they can protect or restore the function of pancreatic beta cells, which would improve a person’s ability to produce their own insulin. 

The Study

This is a Phase 2, randomized, placebo-controlled trial testing the safety and early efficacy of OPT101. The study is not a single, uniform experiment, but is divided into three parts (A, B, and C).

Part A is an open-label phase where 18 adults will receive escalating doses of OPT101 (1.0, 1.5, or 2.0 mg/kg) three times a week for two weeks to evaluate tolerance and how the drug is processed by the body.   Parts B and C will be the core, placebo-controlled portions. In these parts, participants will be randomized to receive either the highest tolerated dose from Part A or a placebo for 48 weeks . The study plans to enroll a total of 72 participants across all parts.  In each group, twice as many people will get the treatment as get the placebo.

Everyone enrolled will be between 18 and 50 years old, but the time since diagnosis varies by part.  Part A allows diagnosis within the last 20 years, Part B is for people diagnosed between 1 and 10 years prior, and Part C is for those diagnosed within the last year.  So parts A and B include both honeymooners and people with established T1D, while part C only includes honeymooners.

The primary objective of the study is to measure the "Change in C-peptide" from baseline to the end of the 48-week treatment period. C-peptide is a direct and reliable indicator of a person's own insulin production. The secondary endpoints are designed to gather more detailed information and include measuring various pharmacokinetic parameters (i.e. to understand how the drug behaves in the body). 

The clinical trial officially began recruiting patients in April 2026, with a primary completion date estimated for May 2026 and a final study completion date in August 2028.

For people interested in learning more or potentially participating, the global contact for the study is Lisa Boswell, who can be reached by phone at 303-503-9954 or via email at lb@op-t.com.

The study is being conducted at several locations across the United States. The recruiting sites include the University of Alabama at Birmingham, the Diablo Clinical Research Center in California, the Barbara Davis Center at the University of Colorado Anschutz Medical Campus, the University of Chicago Medical Center, and the Rainier Clinical Research Center in Washington.

The trial is sponsored by Op-T LLC, the company developing OPT101.  Support for the research into OPT101's mechanism of action has also been provided by a grant from the National Institutes of Health (NIH).

Discussion

The previous Phase 1 trial, presented at the ENDO 2025 meeting of the Endocrine Society, reported an increase in C-peptide in T1D subjects who had undetectable levels of it at the start of the study. This is a good result, and motivated this phase-II study.  The results also indicated that the drug was effective in reducing inflammatory biomarkers like Th40, IFNγ, and TNFα.

The current trial introduces several changes based on the Phase 1 study. The most significant change is the route of administration, moving from an intravenous infusion to a subcutaneous injection. Intravenous infusions requires medical supervision (often by a nurse), while subcutaneous injection is the way insulin is injected (so anyone can do it).  

Phase 1 studies are more focused on testing safety, and while this one generated preliminary data on  efficacy, the current Phase 2 trial is designed to provide a more definitive answer on whether the drug works. This larger, longer, and placebo-controlled study will be critical to understanding the true potential of OPT101.

More Information

- ClinicalTrials.gov listing: https://clinicaltrials.gov/study/NCT06964087

- Previous Phase 1b study on ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05428943

- Sponsor Company: Op-T LLC

- NIH Grant Information: https://taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01DK131196&arg_ProgOfficeCode=119

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Allogeneic CD7-Targeted CAR-T Cell (RD13-02) Starts Second Phase-I Clinical Trial

RD13-02 uses specially engineered immune cells designed to remove certain immune cells believed to drive the autoimmune attack that damages insulin-producing beta cells. Researchers hope that by removing these harmful immune cells, the immune system may stop attacking the pancreas and allow remaining beta cells to continue working.  This is a CAR-T therapy.  CAR-T is a genetic engineering technique which has been generating a lot of excitement recently.  A specific type of immune cell (called T cells) are taken from a healthy donor and then genetically engineered in the laboratory to attack a specific target.  They are then grown in large quantities and used for treatment.

RD13-02 targets a protein called CD7, which is found on the surface of most T cells and natural killer cells (both of these cells are parts of the immune system). In T1D, some T cells mistakenly attack insulin-producing beta cells in the pancreas.  The hope is that RD13-02 will attack these bad T-cells, and have a good impact on T1D.  Since these are foreign cells, RD13-02 also carries two engineered inhibitory receptors that help it evade rejection by the host's immune system, as well as other modifications designed to prevent the donor cells from attacking the patient's tissues.

RD13-02 was developed by Nanjing Bioheng Biotech Co., Ltd., a Chinese biotechnology company that operates internationally under the name Imviva Biotechnologies.  

This Study

There is a single treatment group of nine people, and no control group, so everyone enrolled receives the RD13-02 infusion. Participants must be between 18 and 40 years old and either be at-risk of T1D  (with two measured autoantibodies) or in their honeymoon phase.  RD13-02 is given as a single intravenous infusion.

The primary outcomes of the trial focus on safety and preservation of beta cell function via C-peptide levels during a mixed meal tolerance test. C-peptide levels are used to evaluate how well the pancreas continues to produce insulin.

Secondary outcomes examine several aspects of glucose control and disease progression. These include changes in insulin dose requirements, changes in HbA1c, fasting blood glucose levels, and time in range measured by continuous glucose monitoring. Another goal is to measure how long the infused RD13-02 cells persist and multiply inside the body after treatment.

Recruitment started in April 2026, with primary data collection expected to be complete by December 2027 and the study finishing by April 2028.

For those interested in participating or learning more, the study contact is:

Jingjing Jiang, MD, PhD  

Zhongshan Hospital, Fudan University, Shanghai, China  

Phone: 86-021-64041990  

Email: jiang.jingjing@zs-hospital.sh.cn

The trial is being conducted at a single site: Zhongshan Hospital, Fudan University, Shanghai, China.

Discussion

The key issues for all treatments aimed at removing the "bad" T-cells is how selective they are.  Do they remove the bad T-cells but leave the good ones.  Either extreme, getting rid of too many good T-cells or too few bad ones, will fail.  That is why treatments like this one need to be tested.

This is not the first human trial of RD13-02 in T1D. A separate, smaller pilot study (NCT07142161) run directly by Nanjing Bioheng Biotech enrolled three participants with autoimmune T1D.  That study has not yet finished, and results have not been published.  Also it was very strictly a safety study, with no data gathered on efficiency.  However, I assume it informed the design of the current, larger Shanghai trial.

RD13-02 has been tested in blood cancers including these studies:

• NCT06732492: A Phase 1 study of RD13-02 in patients with relapsed or refractory CD7-positive natural killer/T-cell malignancies, planned enrollment of 10 patients, currently recruiting.
• NCT06622694: A Phase 1 study in hematologic malignancies, 15 patients, currently recruiting.
• NCT05716113: Completed Phase 1 study in T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma, 20 patients, results presented at ASH 2024.  

More Information

• ClinicalTrials.gov listing (this study): https://clinicaltrials.gov/study/NCT07528105
• ClinicalTrials.gov listing (previous study): https://clinicaltrials.gov/study/NCT07142161
• Imviva Biotechnologies (Nanjing Bioheng Biotech international site): https://www.bioheng.com/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

SAB-142 From SAb Biotherapeutics Starts a Phase II Trial (SAFEGUARD)

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

• ClinicalTrials.gov listing (NCT07187531): https://clinicaltrials.gov/study/NCT07187531
• Phase-I SAB-142 Results: https://ir.sab.bio/static-files/d6f0e78d-2429-4f5f-97e1-0b3b930f8c3c
• SAFEGUARD study website for participants: https://safeguardstudy.com/
• SAB BIO company website: https://www.sab.bio
• Press release: First patient dosed: https://ir.sab.bio/news-releases/news-release-details/first-patient-dosed-sab-bios-safeguard-clinical-trial-sab-142
• Press release: Phase 1 data:  https://www.globenewswire.com/news-release/2026/04/22/
• Breakthrough T1D Australia article on SAFEGUARD opening in Australia:  https://www.breakthrought1d.org.au/research/clinical-trials/
• T1D Fund (Breakthrough T1D venture arm) on SAB-142 IND clearance:  https://t1dfund.org/news/fda-provides-clearance-to-ind-application-for-type-1-diabetes-therapy-sab-142-by-sab-biotherapeutics/
• NCT04509791 publication: https://pubmed.ncbi.nlm.nih.gov/40976248/
• NCT04291703 publication: https://pmc.ncbi.nlm.nih.gov/articles/PMC8173803/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Rezpegaldesleukin (or NKTR-358) Starts A Phase-IIΔ Clinical Trial on Honeymooners (RESET T1D)

A new clinical trial is testing Rezpegaldesleukin, also known as NKTR-358, or REZPEG, as a potential treatment to slow or stop T1D in honeymooners.  Rezpegaldesleukin is a modified form of interleukin-2 (IL-2), which plays a key role in regulating the immune system. 

The drug is given by subcutaneous injection, similar to an insulin injection, once every two weeks. It has been studied across nine completed Phase 1 and Phase 2 trials in a total of approximately 746 participants for conditions including lupus, atopic dermatitis, psoriasis, and ulcerative colitis. It is not yet approved for any disease, anywhere in the world. 

Reminder: "Phase IIΔ" is my name for a trial that is the size of a phase II trial, but there has been no phase I trial of the treatment being tested, so in some ways it is like phase I (first in humans) but in other ways more like phase II (in size).

The Study

This is a randomized, double-blind, placebo-controlled Phase 2 trial enrolling 66 participants at three sites.  Participants are assigned in a 2:1 ratio — approximately 44 to Rezpegaldesleukin and 22 to a placebo.  Eligible participants must be between 8 and 45 years old, and diagnosed with T1D within the previous 100 days. Treatment consists of biweekly subcutaneous injections for 26 weeks, followed by a 6-month observation period, for a total follow-up of 12 months.

The primary goal of the study is to measure the change in C-peptide levels from the start of the study to the 1 year mark. C-peptide is used as a reliable indicator of how much insulin the body is naturally producing, which is essential for determining if the treatment is successfully protecting beta cells. Secondary goals include monitoring changes in A1c levels and the total amount of daily insulin required by participants. These endpoints provide a measure of whether the treatment is improving the long-term management of the disease and preserving the body's natural metabolic function.

Contact: Jessica Conaty — 813-396-9234 — Jessica.Conaty@epi.usf.edu

Locations:

• University of Pittsburgh, Pittsburgh, Pennsylvania (recruiting)
• Vanderbilt University, Nashville, Tennessee (not yet recruiting)
• University of British Columbia, Vancouver, British Columbia, Canada (not yet recruiting)

Primary completion is estimated for May 2028.

The trial is sponsored by the NIH and conducted by TrialNet. TrialNet is supported by  BreakthroughT1D (formerly known as JDRF). Nektar Therapeutics, the company developing Rezpegaldesleukin, is supplying the drug and providing support for pharmacokinetic analyses.

Discussion

The central idea behind Rezpegaldesleukin is that type 1 diabetes results in part from a failure of immune regulatory cells.  Researchers have known for many years that low doses of interleukin-2 can increase these cells and sometimes improve autoimmune diseases.  If you go to my blog and search for "IL-2" you will find a lot of previous clinical trials.  

In particular, a series of dose-finding trials carried out by researchers at Assistance Publique – Hôpitaux de Paris, including the DF-IL2 trial (NCT01353833) and the DFIL2-Child trial (NCT01862120), demonstrated that low-dose interleukin-2 could selectively expand regulatory T cells in both adults and children with T1D without triggering significant side effects, and this trial is built on that research. 

However, standard interleukin-2 has a short lifetime in the body and can also stimulate other immune cells that may worsen inflammation. Rezpegaldesleukin was engineered to overcome those problems by selectively activating regulatory T cells and remaining active longer after injection.

Rezpegaldesleukin is being developed by Nektar Therapeutics, a clinical-stage biotechnology company based in San Francisco. From 2017 until 2023, Nektar shared development rights with Eli Lilly and Company, which co-sponsored a large Phase 2 trial in lupus (the ISLAND trial, NCT04433585). That 291-patient trial was unsuccessful. Therefore, Eli Lilly chose not to continue development of the drug for lupus, and Nektar reacquired full rights to the program and continued the research in other diseases. 

More Information

• ClinicalTrials.gov listing: https://clinicaltrials.gov/study/NCT07142252
• Nektar Therapeutics company website: https://www.nektar.com
• Nektar Therapeutics pipeline page: https://www.nektar.com/our-pipeline/
• Wikipedia page for Rezpegaldesleukin: https://en.wikipedia.org/wiki/Rezpegaldesleukin
• Scientific paper describing earlier Rezpegaldesleukin trials: https://doi.org/10.1038/s41467-024-53384-1
• Earlier Trial: https://clinicaltrials.gov/study/NCT01353833
• Results: https://pubmed.ncbi.nlm.nih.gov/24622415/
• Another Earlier Trial: https://clinicaltrials.gov/study/NCT01862120
• Results: https://pubmed.ncbi.nlm.nih.gov/32607749/

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!

Phase-I Clinical Trial of Islet Transplantation Into Eye

Pancreatic islet transplantation is an approach designed to restore the body’s ability to produce insulin by transplanting beta cells (insulin-producing cells) from a donor pancreas.  I don't consider most of these to be cures, because they require taking immune suppression drugs for the rest of the person's life.  For me, that is just trading one disease for another.

However, part of the eye (the anterior chamber) is what immunologists call an "immune-privileged" site — meaning the immune system is naturally less aggressive there than elsewhere in the body.  This trial is testing transplanting beta cells into the eye, rather than into the abdomen.  Instead of taking systemic anti-rejection drugs that affect the entire body, participants receive localized immune-suppressing treatment in the form of eye drops applied directly to the eye.  Because the immune suppression is localized rather than systematic (whole body), the risks are far less.  For me, that is a big advantage and means this might really be a cure.

The transplantation procedure is expected to take about twenty to thirty minutes. 

The Study

This is an old study that I have not previously blogged on.  It started in 2019, just before COVID and they hope to finish at the end of 2026 (but see below).

This is a small (2 person) Phase 1 trial where everyone gets the treatment.  There is no control group. To be eligible, participants must be between 18 and 75 years old and have T1D or type 2 diabetes (with or without insulin dependence). Most importantly, they must be legally blind in at least one eye — meaning the transplant goes into an eye that has already lost most or all useful vision, so the participant's sight is not put at additional risk.

The trial's three primary endpoints are all assessed at 24 months after transplantation. The first two focus on safety, but the third is effectiveness related: C-peptide in the fluid of the transplanted eye and direct visualization of the islet graft using standard eye examination tools and imaging. 

To learn more or inquire about participation, contact:

Midhat H. Abdulreda, Ph.D.

Diabetes Research Institute, University of Miami

Phone: 305-243-9871

Email: mabdulreda@miami.edu

Trial locations:

• Bascom Palmer Eye Institute, Miami, Florida, USA
• Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USA

Discussion

The clinical trial registry claims they will finish collecting data from patients at the end of 2026 and publish results in 2027.  However, that is obviously not correct, because they are still recruiting, and need to follow patients for 2 years.  So obviously the clinical trial registry has not been updated.  I don't know if they have stopped recruiting and the completion dates are correct or if they are still recruiting and the completion dates are wrong.

No matter what is published, however, this study only includes 2 people, so even if the results are very positive, several more studies will be required.

Because the transplantation is in the eye, doctors can observe the transplanted cells directly using imaging tools that are already widely used in by eye doctors. In theory, this could allow researchers to monitor graft health and immune reactions in ways that are not possible when islets are transplanted elsewhere.

The scientific foundation for this trial was laid over many years in baboons. Animal studies were published in 2011, 2019, and 2020, by the same researchers involved in this trial.  These studies showed C-peptide creation, successful immune tolerance without whole body immune suppression, and general safety.

More Information

• ClinicalTrials.gov (US FDA registry): https://clinicaltrials.gov/study/NCT02846571
• Diabetes Research Institute — study page for participants: https://diabetesresearch.org/intraocular-islet-transplant/
• University of Miami Miller School of Medicine — announcement of the trial:  https://news.med.miami.edu/miller-school-diabetes-trial-eye-pancreatic-islet-transplant
• CellR4 publication on intraocular islet transplantation: http://www.cellr4.org/article/2120

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com 

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!