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type1.science

SIG-002 (Lilly/Sigilon Afibromer-encapsulated islets)

Eli Lilly and Company (acquired Sigilon Therapeutics, 2023)

A cautionary tale, not a contender — bought, then buried in silence.

Stem-cell-derived islets sealed inside Sigilon's "Afibromer" spheres, meant to hide them from the immune system so no anti-rejection drugs are needed. Eli Lilly bought the whole company in 2023 to own it — and then went quiet. A clinical trial application was expected in 2024; as of July 2026 there is no registered SIG-002 trial anywhere in the world, no human has ever received it, and Lilly has said nothing. The only time the same Afibromer shield was put into people — in Sigilon's haemophilia programme — the spheres came back coated in scar tissue and the patient mounted an immune response anyway.

Not in trialsPreclinicalstem-cellisletencapsulationimmunoprotectionimmunosuppression-freeallogeneicipscpreclinicalcure-candidatebig-pharmaOfficial site ↗

The scorecard

Immunosuppression-free30

Designed to need zero anti-rejection drugs — but that is an intention, not a result. No human has ever received SIG-002, so it has no immunosuppression-free evidence of any kind, and it scores far below the one therapy with human drug-free data (Sana's UP421, n=1). Worse, the one time this exact Afibromer shield was tested in humans (SIG-001, haemophilia A) it did not shield: retrieved spheres were coated in fibrotic overgrowth and a patient developed antibodies against the encapsulated cells' product. Scored above lifelong-immunosuppression therapies only because it does not ask for chronic drugs — not because it has shown it can go without them.[3]

Insulin independence3

Zero human data. No C-peptide, no insulin-dose, no glycaemic result in any person has ever been reported for SIG-002.[6]

Durability3

No durability data. The platform's only human read-out is a warning: the SIG-001 spheres explanted from a haemophilia patient were covered in pericapsular fibrotic overgrowth — the exact foreign-body response the Afibromer material was built to prevent — and the mechanism was never identified.[3]

Low invasiveness40

SIG-002's own delivery route has not been disclosed. The same sphere platform was placed in humans (SIG-001) via a laparoscopic procedure under general anaesthesia — more invasive than an infusion, though the spheres are in principle retrievable, which is a genuine safety advantage.[5]

Eligibility breadth30

Nobody is eligible: there is no trial to join. The design — lab-grown iPSC-derived islets, no donor needed, no immunosuppression — would in principle be broadly eligible, but that is a promise on paper, and it is scored as such.[6]

Maturity5

Preclinical and, on the public record, dormant. A clinical trial application was anticipated in 2024; two years later there is still no IND, no CTA, and no registered trial under Lilly or Sigilon. Not scored as dead — Lilly stopped disclosing Phase 1 projects, so silence is not proof of cancellation — but nothing has been shown.[2]

Editor’s take

We list SIG-002 not because it is promising but because it is instructive. It is what a well-funded, technically credible, immunosuppression-free cure candidate looks like when the science does not cooperate: an $8bn-a-quarter pharma company paid to own the platform outright, said a trial was coming, and then went silent for two years. Nothing here has been refuted — and nothing here has been shown either. If you are looking for a cure that frees you from anti-rejection drugs, this is not it yet, and there is no honest way to say when it might be.

The full picture

SIG-002 is an encapsulated islet cell therapy that has never been given to a human being. That sentence is the whole record, and it is worth sitting with, because SIG-002 is otherwise exactly the sort of programme the field gets excited about: lab-grown insulin-producing cells, sealed inside a protective sphere, designed to work with no immunosuppression at all.1 It is owned outright by Eli Lilly. It has been in development, in one form or another, since 2018.2 And as of July 2026 it has produced no human data, no registered trial, and no public word on whether it is still alive.

The idea. Sigilon Therapeutics built a platform it called Shielded Living Therapeutics: engineered cells packed into tiny spheres coated with a proprietary biomaterial, Afibromer, whose job is to stop the immune system from noticing them.1 In 2018 Lilly licensed that technology specifically for islet-cell encapsulation, paying $63 million up front against up to $410 million in milestones.2 The product of that collaboration is SIG-002: islet cells derived from induced pluripotent stem cells — so no organ donors, and in principle an unlimited supply — encapsulated in Afibromer spheres and implanted, where they would sense glucose and release insulin for years.13 If the shield held, recipients would need no anti-rejection drugs. That is the prize the entire encapsulation category is chasing.

Why we file this as a cautionary entry. The shield has been tested in humans once, and it did not hold. Not in diabetes — in haemophilia A. Sigilon's SIG-001 used the same Afibromer sphere platform, loaded with cells engineered to make clotting Factor VIII, placed laparoscopically into the abdomen.4 In July 2021 the FDA put the trial on clinical hold: the third and highest-dosed patient had developed inhibitors to Factor VIII — an immune response against the very protein the hidden cells were producing.5 When the spheres were retrieved, they were found covered in pericapsular fibrotic overgrowth — scar tissue laid down by the foreign-body reaction, forming a physical barrier that rendered the spheres unviable.3 The mechanism was never identified.3 Sigilon closed the haemophilia programme; the trial is registered as terminated after just three participants.4

This is the central problem of encapsulation, stated as plainly as the field ever states it: a barrier tight enough to hide cells from the immune system is also a barrier to oxygen and nutrients, and the body scars over anything you implant.6 Sigilon said it had reworked the sphere chemistry to strengthen their integrity and stability, and that those changes went into SIG-002.3 Whether that fix works is unknown, because it has never been tested in a person.

What Lilly actually bought. In June 2023 Lilly acquired Sigilon outright: $14.92 per share in cash — about $34.6 million up front, a bargain-bin price for a public biotech — plus contingent value rights worth up to $309.6 million if milestones are hit.1 Those milestones are telling: they are tied to a future "first human clinical trial" and a "first human clinical trial for registration purposes," which confirms in the acquisition's own contract language that SIG-002 had not reached the clinic.1 At the time of the deal, SIG-002 was reported to be finishing IND-enabling studies, with a clinical trial application anticipated in 2024.7

Then, silence. That 2024 date has come and gone. As of our search on 15 July 2026: there is no registered SIG-002 trial in Lilly's type 1 diabetes portfolio on ClinicalTrials.gov, and a sponsor search for Sigilon returns exactly two records — the terminated haemophilia trial, and an MPS-1 study that was withdrawn with zero participants enrolled.8 Lilly has issued no update on the programme.

We are careful about what we conclude from this. Lilly's public pipeline page explicitly states that "Phase 1 projects are no longer disclosed" — so SIG-002's absence from the pipeline is not evidence that it has been killed.9 It may be quietly progressing. It may be shelved. We cannot tell, and neither can you, and that is precisely the point: a programme with no filing, no trial, and no disclosure has shown nothing, and cannot be ranked as though it has. We score it research rather than discontinued because we have no source stating it was cancelled, and we will not assert a death we cannot document.

How it scores, and why the immunosuppression score is low. SIG-002 is designed to be immunosuppression-free. It has not demonstrated being immunosuppression-free, because it has not been demonstrated at all. As of July 2026 exactly one human on earth has carried transplanted insulin-producing cells with zero immunosuppression — the single participant in Sana's UP421 study, at a deliberately sub-therapeutic dose, still on injected insulin.6 SIG-002 has nothing comparable, and its only human-tested shielding material failed. A design intention does not outrank a human result, and on this site it never will.

References

  1. Eli Lilly and Company / Sigilon Therapeutics. Lilly to Acquire Sigilon Therapeutics. PR Newswire (29 June 2023). https://www.prnewswire.com/news-releases/lilly-to-acquire-sigilon-therapeutics-301866460.html ↩ ↩2 ↩3 ↩4 ↩5

  2. Lilly and Sigilon Therapeutics Announce Strategic Collaboration to Develop Encapsulated Cell Therapies for the Treatment of Type 1 Diabetes. Eli Lilly Investor News (5 April 2018). https://investor.lilly.com/news-releases/news-release-details/lilly-and-sigilon-therapeutics-announce-strategic-collaboration ↩ ↩2

  3. Weintraub A. Eli Lilly to Buy Sigilon, Betting the Biotech Can Overcome a Cell Therapy Limitation. MedCity News (June 2023). https://medcitynews.com/2023/06/el-lilly-acquisition-cell-therapy-type-1-diabetes/ ↩ ↩2 ↩3 ↩4

  4. A Phase 1/2 Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of SIG-001 in Adult Patients With Severe or Moderately-Severe Haemophilia A Without Inhibitors. ClinicalTrials.gov NCT04541628 (status: terminated). https://clinicaltrials.gov/study/NCT04541628 ↩ ↩2

  5. Sigilon Therapeutics Announces Clinical Hold on SIG-001 Phase 1/2 Study in Hemophilia A. Hemophilia Federation of America (9 July 2021). https://www.hemophiliafed.org/sigilon-therapeutics-announces-clinical-hold-on-sig-001-phase-1-2-study-in-hemophilia-a/ ↩

  6. Aghazadeh Y, et al. Islet Cell Replacement and Regeneration for Type 1 Diabetes: Current Developments and Future Prospects. BioDrugs / PMC (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC11906537/ ↩ ↩2

  7. Kansteiner F. Lilly to Buy Diabetes Cell Therapy Partner Sigilon for Just Over $300M. BioSpace (29 June 2023). https://www.biospace.com/article/lilly-to-buy-diabetes-cell-therapy-partner-sigilon-for-300m-/ ↩

  8. ClinicalTrials.gov registry search, Eli Lilly and Company / Sigilon Therapeutics, type 1 diabetes (searched 15 July 2026). https://clinicaltrials.gov/search?cond=Type%201%20Diabetes&spons=Eli%20Lilly%20and%20Company ↩

  9. Lilly Clinical Development Pipeline (accessed 15 July 2026) — "Phase 1 projects are no longer disclosed." https://www.lilly.com/discovery/clinical-development-pipeline ↩

Coming soon

ETA · Unknown — no filing, no announced timeline

  • →Any regulatory filing at all — the IND/CTA that was anticipated in 2024 has still not appeared on any registry as of July 2026
  • →Any Lilly statement on whether SIG-002 is alive, paused, or dead; the company no longer discloses Phase 1 projects, so the programme is invisible either way

Sources

  1. [1]Lilly to Acquire Sigilon Therapeutics · manufacturer · 2023-06-29 — Announces the acquisition — $14.92/share (~$34.6M) up front plus contingent value rights worth up to $111.64/share (~$309.6M total). Describes SIG-002 and the Afibromer matrix "designed to shield them from immune rejection". The CVR milestones are tied to a future "first human clinical trial", confirming SIG-002 had not entered the clinic.
  2. [2]Lilly to Buy Diabetes Cell Therapy Partner Sigilon for Just Over $300M · news · 2023-06-29 — "SIG-002 … is expected to complete IND-enabling studies this year, with a clinical trial application anticipated in 2024." The source of the 2024 date that has now come and gone.
  3. [3]Eli Lilly to Buy Sigilon, Betting the Biotech Can Overcome a Cell Therapy Limitation · news · 2023-06-29 — Reports that SIG-002 remained in preclinical development, and that the SIG-001 spheres retrieved from a haemophilia patient were "covered with pericapsular fibrotic overgrowth … rendering Sigilon's spheres unviable".
  4. [4]Sigilon Therapeutics Announces Clinical Hold on SIG-001 Phase 1/2 Study in Hemophilia A · news · 2021-07-09 — The FDA clinical hold: the third and highest-dosed patient developed inhibitors to Factor VIII — an immune response against the product of cells the Afibromer shield was supposed to hide.
  5. [5]A Phase 1/2 Study of SIG-001 in Adult Patients With Severe or Moderately-Severe Haemophilia A Without Inhibitors · registry · 2020-09-28 — Registry record for the only human trial of the Afibromer sphere platform. Status TERMINATED; 3 participants enrolled; sponsor Eli Lilly and Company with Sigilon as collaborator. Exclusion criteria reference contraindication to "general anaesthesia or laparoscopic procedure", indicating laparoscopic placement of the spheres.
  6. [6]ClinicalTrials.gov — Eli Lilly and Company, type 1 diabetes trials · registry · 2026-07-14 — Searched 15 July 2026. Across Lilly's registered type 1 diabetes studies there is no SIG-002 trial, and no Lilly-sponsored encapsulated islet or cell therapy study of any kind. A sponsor search for "Sigilon" returns only two records — SIG-001 (terminated) and SIG-005 in MPS-1 (withdrawn, zero enrolment).
  7. [7]Lilly and Sigilon Therapeutics Announce Strategic Collaboration to Develop Encapsulated Cell Therapies for the Treatment of Type 1 Diabetes · manufacturer · 2018-04-05 — The original 2018 deal — $63M up front, up to $410M in milestones, exclusive worldwide licence to Afibromer for islet-cell encapsulation.
  8. [8]Lilly Clinical Development Pipeline · manufacturer · 2026-07-14 — Checked 15 July 2026. The page states that "Phase 1 projects are no longer disclosed", so SIG-002's absence from the public pipeline is not by itself evidence that it has been cancelled. This is why we score it `research`, not `discontinued`.
  9. [9]Islet Cell Replacement and Regeneration for Type 1 Diabetes - Current Developments and Future Prospects · peer-reviewed · 2025-03-01 — Review of the central encapsulation problem: a membrane tight enough to block immune cells also blocks oxygen, and the foreign-body reaction lays down fibrotic scar that chokes off diffusion.