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type1.science

iTolerance iTOL-102 (SA-FasL microgel + islets)

iTolerance, Inc. (Miami, FL) — iTOL-100 microgel platform; islet cells from NewcelX (formerly Kadimastem) IsletRx. Technology licensed from Georgia Tech (Andrés García) and the University of Missouri / Louisville (Haval Shirwan, Esma Yolcu).

Kill the attackers, don't hide from them — a good idea that has never met a human.

Instead of walling islets off behind a membrane, this approach kills the immune cells that come to attack them. Tiny PEG microgels coated with SA-FasL — a protein that triggers suicide in activated T cells — are simply mixed in with the islets and laid on the omentum, aiming to build a pocket of local tolerance rather than suppress the whole immune system. In monkeys it worked: grafts survived past six months while controls rejected in about four weeks. But the monkeys got three months of rapamycin, they never came off insulin, and their diabetes was chemically induced — so nothing in that experiment tested autoimmunity, which is the thing that actually causes T1D. Pre-IND, no IND filed, no trial, no human has ever received it.

Years awayPreclinicalencapsulationimmunomodulationmicrogelfaslisletpre-indlocal-tolerancestem-cellOfficial site ↗

The scorecard

Immunosuppression-free45

The most interesting local-immunomodulation result in a large animal — and still short of the claim on the tin. The monkeys received a 3-month course of systemic rapamycin monotherapy, tapering to nothing at month 3; grafts then survived drug-free for the rest of the study. That is genuinely "no *chronic* immunosuppression", and the control arm proves the SA-FasL is doing the work, since identical rapamycin without SA-FasL rejected in ~28 days. Three things hold the score down hard. The induction course is real systemic immunosuppression, not zero. The model was streptozotocin-induced diabetes, which the authors themselves note "does not involve autoimmunity" — so the mechanism was never tested against the disease it is meant to treat. And no human has received this. It must sit well below Sana's 75, which is backed by the only human drug-free evidence that exists.[1]

Insulin independence12

The result the press releases do not mention: the monkeys "did not achieve insulin independence". They got an 80–90% cut in daily insulin and restored C-peptide, and one of four nearly reached independence late — a real metabolic signal, and removing the graft promptly returned them to hyperglycemia, proving the islets were doing the work. But the headline endpoint was missed. The authors attribute this to marginal single-donor islet mass rather than a mechanism failure, which is plausible and untested. No human data at all.[1]

Durability25

Four monkeys held glycemic control for >134, >170, >177 and >188 days, versus 21–35 days for controls. The upper bound is unknown in the useful direction: the animals were euthanized with grafts still functioning because of COVID-era facility constraints, so the grafts did not fail — the study stopped. Encouraging, but it is ~6 months in four animals, nothing longer, and nothing in a human.[1]

Low invasiveness50

A genuine design advantage: there is no capsule, no device and no chemical modification of the islets. The microgels are simply admixed with the cells and immobilized on the omentum in a fibrin matrix, which means the product can be assembled at the point of transplant. Against that, it is still intra-abdominal surgery to reach the omentum, and the human omentum differs substantially from the thin primate one — the authors flag this as an open question about the site itself. The graft was surgically retrievable in the study, which is a meaningful safety property.[1]

Eligibility breadth20

Entirely hypothetical — there is no trial, so no eligibility criteria exist. The theoretical case is good: pairing with NewcelX's stem-cell-derived IsletRx would remove the deceased-donor bottleneck, and dropping chronic immunosuppression would remove the "fit enough to take the drugs" gate that keeps islet transplant a last-resort therapy. Both of those are promises, neither is a result.[3]

Maturity8

Pre-IND and no further. A Type B pre-IND meeting was completed with the FDA in February 2025; the companies' own release says they came away "updating their plans for a safety toxicology study" — i.e. the agency sent them back to do more preclinical work. As of July 2026 no IND has been filed, no trial is registered anywhere, and no human has been dosed. The corporate ground has also shifted under the program: partner Kadimastem merged into NewcelX, and the most recent public update is a $166k milestone tranche from the BIRD Foundation.[2]

The full picture

Most encapsulation puts a wall between the islets and the immune system. iTolerance's iTOL-100 platform does something more aggressive and more elegant: it recruits the immune system's own self-destruct switch. Tiny PEG microgels are decorated with SA-FasL, an engineered form of Fas ligand — the protein that healthy tissue uses to tell an activated T cell to die. The microgels are mixed straight in with the islets and laid on the omentum. T cells that arrive to attack the graft encounter FasL and undergo apoptosis; regulatory T cells accumulate; and the graft becomes, in the authors' phrase, locally tolerated.1

No capsule. No membrane. No oxygen-diffusion problem. No chemical modification of the islets. That is a genuinely attractive design — and it is why this record exists.

The product being developed for T1D, iTOL-102, pairs iTOL-100 with IsletRx, the stem-cell-derived islet product from NewcelX (formerly Kadimastem) — covered separately on this site. This record is about the immunomodulation half.

What the monkey study actually showed

This is the study everything else rests on, so it is worth reading carefully.1 Four diabetic macaques received allogeneic islets co-transplanted with SA-FasL microgels on the omentum. Three controls received identical islets with plain microgels lacking SA-FasL. The results were clean:

  • Grafts survived >134, >170, >177 and >188 days in the SA-FasL group. Controls rejected at 21, 27 and 35 days — mean survival under a month.
  • The animals were euthanized with functioning grafts, for pandemic-related facility reasons. The grafts did not fail; the study stopped. What happens at a year is simply unknown.
  • Surgically removing the graft caused prompt hyperglycemia, which is the proof that the transplanted islets, not residual native ones, were doing the work.
  • The effect was local: FoxP3+ regulatory T cells accumulated at the graft site, with no change in systemic T-cell frequencies or responses to donor and third-party antigens. Liver and kidney function stayed normal, with none of the toxicity that has historically dogged FasL.

That is a real, well-controlled, peer-reviewed large-animal result, and the control arm is what makes it persuasive: the SA-FasL is unambiguously doing something.

Three things the press releases leave out

1. There was rapamycin. Every animal — treated and control — received a three-month course of systemic rapamycin monotherapy, starting three days before transplant, targeting a trough of 40 ng/mL for two weeks and 20 ng/mL thereafter, then stopped abruptly at month 3.1 Now, the honest reading cuts both ways here. Rapamycin was withdrawn, and the grafts survived months afterward drug-free — so this is a legitimate demonstration of no chronic immunosuppression, which is a real and meaningful thing. And rapamycin alone plainly isn't sufficient: the controls got the same regimen and rejected anyway, and the authors note that rapamycin monotherapy fails to prevent islet rejection in NHPs even at troughs above 50 ng/mL. But a three-month systemic induction course is not nothing, and "immunosuppression-free" is not a phrase that survives contact with it. The accurate claim is transient immunosuppression, not no immunosuppression.

2. The monkeys never got off insulin. The paper says it in as many words: the animals "did not achieve insulin independence."1 What they got was an 80–90% reduction in daily insulin, restored C-peptide, and normal fasting glucose, with postprandial excursions still occasionally above 300 mg/dL (16.7 mmol/L). One of the four nearly reached independence toward the end. The authors attribute the shortfall to marginal islet mass from a single donor — a fair point, since single-donor grafts are typically insufficient in humans too, and a dosing problem is more fixable than a mechanism problem. But the endpoint was missed, and no press release about this program says so.

3. There was no autoimmunity. This is the deepest limitation, and to their credit the authors state it themselves: the streptozotocin-induced diabetes model "does not involve autoimmunity, an important consideration when transplanting in the setting of human T1D."1 Streptozotocin is a chemical that poisons beta cells. The monkeys had destroyed beta cells; they did not have type 1 diabetes. So what the experiment tested was allorejection — the immune response to foreign tissue — and nothing else. Type 1 diabetes is an autoimmune disease, and the memory T cells that destroyed a person's own beta cells decades ago are still there, waiting for new ones. Whether SA-FasL microgels can blunt that is a plausible hypothesis and an untested one. Every cell-replacement therapy for T1D has to answer two questions — rejection and autoimmunity — and this study answers one.

Which product has the data?

A detail worth being precise about, because the companies are not. The primate study used cadaveric donor islets, and iTolerance's own site files that work under iTOL-101.2 iTOL-102 — the stem-cell-islet version, the one actually headed for the clinic — has no published large-animal result of its own. The platform is shared; the data is not transferable for free. Stem-cell-derived islets are immunologically not the same thing as primary donor islets, and the microgel dose, the graft mass and the engraftment kinetics all change with them.

Where it stands, July 2026

A Type B pre-IND meeting with the FDA was completed on 24–25 February 2025.3 The companies' own release describes receiving "critical feedback" and says they are "updating their plans for a safety toxicology study and the preparation of a First-in-Human clinical trial" — which, read plainly, means the agency sent them back for more preclinical work before an IND. That is a normal outcome, not a bad one, but it is the opposite of a green light.

Since then: no IND has been filed. No trial is registered — ClinicalTrials.gov returns nothing for iTOL-102, iTOL-100 or IsletRx, and a sponsor search across iTolerance, Kadimastem and NewcelX turns up only an unrelated completed ALS study.4 No human has received this. Meanwhile partner Kadimastem has merged into NewcelX, and the most recent substantive public news is a $166,000 milestone tranche from the BIRD Foundation, bringing that program's total to roughly $882,000.5 Those are seed-scale numbers for a company that would need to fund a cell-therapy IND.

The bottom line

The science is real, the control arm is convincing, and the concept — induce tolerance in one square inch of tissue instead of suppressing the immune system of an entire person — is one of the better ideas in this field. If it works in humans it would matter enormously.

But as of July 2026 the ledger reads: no IND, no trial, no human, no insulin independence even in monkeys, three months of rapamycin in the study that made the reputation, and no autoimmune model anywhere in the package. Exactly one person on earth is currently living with transplanted insulin-producing cells and no immunosuppression at all — Sana's UP421 patient — and it is not this technology.

A good idea is not a result. This is a good idea.

References

  1. Lei J, Coronel MM, Yolcu ES, et al. FasL microgels induce immune acceptance of islet allografts in nonhuman primates. Science Advances 8:19, eabm9881 (13 May 2022), via PubMed (PMID 35559682). Design: SA-FasL microgels n=4 vs control microgels n=3, MHC-mismatched allogeneic islets on the omentum. Rapamycin monotherapy 0.2 mg/kg IM daily for 3 months from day −3, trough 40 ng/mL for 2 weeks then 20 ng/mL, discontinued without weaning at month 3. Graft survival >134/170/177/188 days vs 21/27/35 days in controls (mean 27.7). Animals terminated with functioning grafts due to COVID-19 facility constraints. Insulin independence not achieved; 80–90% reduction in exogenous insulin requirement. Limitations section states the STZ model "does not involve autoimmunity". https://doi.org/10.1126/sciadv.abm9881 ↩ ↩2 ↩3 ↩4 ↩5

  2. iTolerance, Inc. Company site — iTOL-100 platform and pipeline. Describes an early-stage preclinical company; the non-human-primate study is attributed to iTOL-101 (cadaveric islets), with iTOL-102 (stem-cell-derived islets) listed separately. No IND, trial or human data claimed. https://itolerance.com/ ↩

  3. Kadimastem and iTolerance Successfully Complete Pre-IND Meeting with the FDA for its Type 1 Diabetes Treatment (Type B meeting held 24–25 February 2025; "critical feedback"; "updating their plans for a safety toxicology study and the preparation of a First-in-Human clinical trial"). PR Newswire press release (26 February 2025). https://www.prnewswire.com/news-releases/kadimastem-and-itolerance-successfully-complete-pre-ind-meeting-with-the-fda-for-its-type-1-diabetes-treatment-302384761.html ↩

  4. ClinicalTrials.gov. Intervention search for iTOL-102 / iTOL-100 / IsletRx — zero registered studies as of 15 July 2026. Sponsor search across iTolerance, Kadimastem and NewcelX returns only NCT03482050 (AstroRx for ALS, completed, unrelated). https://clinicaltrials.gov/search?intr=iTOL-102 ↩

  5. NLS Pharmaceutics and Kadimastem Highlight Continued BIRD Foundation Support for ITOL-102 Diabetes Program Following Merger (merged entity NewcelX continues the iTolerance collaboration; fifth BIRD disbursement of $166,000, total approximately $882,000; no IND or trial-start date given). PR Newswire press release (29 October 2025). https://www.prnewswire.com/news-releases/nls-pharmaceutics-and-kadimastem-highlight-continued-bird-foundation-support-for-itol-102-diabetes-program-following-merger-302598239.html ↩

Coming soon

ETA · Pre-IND since February 2025. IND-enabling toxicology still under way; no IND filed, no trial registered, no first-in-human date announced. Realistically years from a human result, and the program has no published primate data for the stem-cell version it intends to take into the clinic.

  • →IND-enabling safety toxicology study — the work the FDA asked for at the February 2025 pre-IND meeting. Must complete before an IND can be filed.
  • →A first-in-human trial of iTOL-102. No IND filed, no protocol registered and no start date announced as of July 2026.
  • →Large-animal data for iTOL-102 itself. The published primate study used cadaveric donor islets (iTOL-101); the stem-cell-islet combination that is actually going to the clinic has no published primate result of its own.

Sources

  1. [1]FasL microgels induce immune acceptance of islet allografts in nonhuman primates · peer-reviewed · 2022-05-13 — The pivotal preclinical study, via PubMed (PMID 35559682). Key details: SA-FasL microgels n=4, control microgels n=3; 3-month rapamycin monotherapy (trough 40 ng/mL for 2 weeks, then 20 ng/mL, stopped at month 3 without weaning); graft survival >134–188 days vs 21–35 days in controls; animals terminated with functioning grafts for COVID-related reasons. The paper states plainly that the animals "did not achieve insulin independence" (80–90% reduction in exogenous insulin), and that the streptozotocin model "does not involve autoimmunity, an important consideration when transplanting in the setting of human T1D."
  2. [2]Kadimastem and iTolerance Successfully Complete Pre-IND Meeting with the FDA for its Type 1 Diabetes Treatment · manufacturer · 2025-02-26 — Company press release. Type B pre-IND meeting held 24–25 February 2025; the companies report receiving "critical feedback" and are "updating their plans for a safety toxicology study and the preparation of a First-in-Human clinical trial". The FDA does not publish pre-IND outcomes, so the framing is the companies'.
  3. [3]iTolerance — iTOL-100 platform and pipeline (iTOL-101, iTOL-102) · manufacturer — Company describes itself as an early-stage preclinical company. Notably, the non-human primate study is attributed to iTOL-101 (cadaveric donor islets + iTOL-100), not to iTOL-102 (stem-cell-derived islets + iTOL-100). No IND, trial or human data is claimed anywhere on the site.
  4. [4]NLS Pharmaceutics and Kadimastem Highlight Continued BIRD Foundation Support for ITOL-102 Diabetes Program Following Merger · manufacturer · 2025-10-29 — Most recent substantive public update located. Confirms the merged entity NewcelX carries the iTOL-102 collaboration forward; BIRD Foundation milestone payments total roughly $882k. No IND date, no trial-start date.
  5. [5]ClinicalTrials.gov — search for iTOL-102 / iTOL-100 interventions · registry — Checked 15 July 2026: zero registered studies for iTOL-102, iTOL-100 or IsletRx. A sponsor search across iTolerance / Kadimastem / NewcelX returns only NCT03482050, an unrelated completed ALS trial.