Friday, February 6, 2026

Open Letter: Focus On Hidden Transplanted Beta Cells

An open letter to everyone who cares about research aimed at type 1 diabetes cures.

I've been blogging on research aimed at curing type 1 diabetes for almost 20 years, but I've never sent out a message like this before.  However, for me, the results from a single person clinical trial of Sana Biotechnology's UP421 treatment should motivate a change in how we all think about research to cure T1D.

Until now, I've taken a "diversification of research" point of view.  At any time, there are 20 or 30 
active research projects aimed at curing T1D, and I supported all of them, based on their results to date.  I did not favor one over another based on what I thought would happen in the future.  My policy was that we don't know which one will succeed, so we need to support all of them and see which one actually does succeed.

But now, I'm starting to change my point of view.  I'm starting to see that one approach is working better; is moving to the front of the competitive pack, and deserves more support and more optimism, than the others.

Sana's UP421 study gave one person a small dose of genetically engineered beta cells.  The genetic engineering (using the CRISPR-Cas9 gene editing technology) is designed to render the cells invisible to the immune system in order to avoid the need for any immune suppression, both to prevent foreign organ rejection and to prevent autoimmune attacks.  C-peptides were generated and immune suppression was not needed.  Six month results were published in the New England Journal of Medicine, and they have released one year results at an investor's conference.  Sana is planning on a follow up product, SC451 to start clinical trials in 2026.

Obviously, this result has important limitations: one person, less than one year, a small dose, and a small effect.  It used cadaver beta cells and Sana is switching to a different cell source for the future.  However, what it did show was invisibility to the immune system, and steady generation of insulin for the first 6 months of data.  It did generate less insulin for the next six months, dropping to about half of its initial high point, and that will need to be investigated.

The reason I am excited about this result is that the required scientific breakthrough(s) have already happened.  The genetic engineering required to hide the transplanted beta cells appears to be successful in this one person study.  Much of the study's results were aimed at confirming this invisibility.  The remaining work is much more engineering development than scientific breakthrough.  Sana needs to 
transplant more cells, they need to be tested for longer, and (especially) in more, different people. 

I think that all organizations working to cure type 1 diabetes, should do the following for the next few years, and I think that we, as a community that cares about T1D research should be encouraging them to:
  1. Establish a focus on genetically engineering beta cells which evade the immune system, as a potential cure for type 1 diabetes.
  2. Put 5% of their research funds into helping Sana's SC451 product (or successors) progress down the path towards general availability.
  3. Start advocating with the FDA now to smooth the approval process for this treatment when it is available, and to ensure insurance coverage for this treatment.
  4. Put an additional 5% (or a little more) into adjacent research, non-Sana projects to use genetic engineering to hide beta cells.
Research is about the unknown, and I'm not saying that Sana is going to cure T1D, but I think they are close enough so that we should focus more on them and their research area (generically engineering beta cells to avoid the immune system).  I don't think spending 10% of our research money on this one area is extreme right now. 

BreakthroughT1D's Project ACT (Accelerate Cell Therapies), which they started in 2024, is already a step in this direction.  It's focus is wider than beta cells genetically engineered to hide from the immune system, but it certainly covers them.  In addition, the T1D Fund (BreakthroughT1D's venture capital business fund) is already funding Sana .  There is also a Swedish foundation which is focused on funding this research in a university setting.  These are all great steps, but the entire T1D community needs to "put a brick on the accelerator" for this.  

My thinking here is similar to BreakthroughT1D's (then JDRF's) policy on the Artificial Pancreas.  I believe that JDRF's actions there sped up availability of an Artificial Pancreas by several years, and I think we can do the same now, but this time with a cure.  

I have often said that the first signal we will get that a cure for type 1 diabetes will occur
is that one person will be cured in a clinical trial.  Sana's 2025 result is not quite that, but it is on the path.  

None of this means that I'm going to stop following (or even slow down following) other research areas.  I continue to believe that limiting ourselves to one one path to a cure is a dangerous form of scientific extremism.  So while I am calling on more focus and more support for genetic engineering to hide transplanted beta cells from the body's immune system, I'm not going to exclude other research paths from my blog.  I will continue to report on all cure focused research.

Note: There is also another company called Sana which does AI work.  This research is being done by Sana Biotechnology.

More Information on Sana Biotechnology's results:

Foundation created to support the university side of this research:

About Project ACT:


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! 
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Friday, January 30, 2026

SAR442970/Brivekimig Starts a Phase IIΔ Trial In Honeymooners (T1D OBTAIN)

The treatment being tested is called Brivekimig (previously SAR442970). It is a type of biologic drug known as a bispecific nanobody. It is a small, engineered protein designed to bind to and block two specific molecules in the immune system simultaneously: Tumor Necrosis Factor-alpha (TNF-alpha) and OX40 Ligand (OX40L). 

TNF-alpha and OX40L are two of the chemical messengers that help coordinate and sustain the autoimmune attack which starts off T1D. By blocking both of these messengers at the same time, the drug aims to interfere with the autoimmune process, potentially protecting the remaining beta cells from further destruction and preserving the body's ability to produce some of its own insulin.  TNF-α is a well-known driver of inflammation, while OX40L plays a role in activating immune cells that attack beta cells. By targeting both, researchers hope to protect beta cells from destruction while avoiding the broad immune suppression seen with some other treatments.

SAR442970 is given as a subcutaneous injection, similar to how insulin is administered.

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 wase like phase II (in size).

The Trial

This is a randomized, double-blind, placebo-controlled trial, meaning participants are randomly assigned to receive either SAR442970 or a placebo, and neither they nor the researchers know who is getting which treatment. The study includes 84 participants aged 12 to 35 who were diagnosed with T1D within the last 90 days.

The trial is divided into two parts: Part A includes adults (18–35 years old), and Part B includes adolescents (12–21 years old). Participants will be treated for 52 weeks, followed by a 26-week follow-up. The primary goal is to measure changes in C-peptide levels at 26 weeks. Secondary outcomes include changes in insulin requirements, A1c levels, and other measures of diabetes management.

Participants will be randomly assigned, in a 3-to-1 ratio, to receive either SAR442970 or a placebo. This means for every four people who join, three will receive the active drug and one will receive the placebo. 

The primary goal, or primary endpoint, of the study is to measure the change in C-peptide levels after 26 weeks of treatment. C-peptide is released along with insulin and serves as a reliable marker of how much insulin a person's body is still making. Preserving C-peptide is the main objective of therapies like this one. Secondary endpoints include looking at C-peptide levels after a full year, as well as changes in A1c, daily insulin requirements, and time spent in the target glucose range. The study will also carefully monitor the safety and tolerability of the drug over the entire treatment and follow-up period.

For more information about participating in this trial, you may contact Sanofi by phone at 800-633-1610 (extension 6) or by email at contact-us@sanofi.com.

The trial is being conducted at multiple locations across several countries, including the US, Argentina, Australia, Brazil, Canada, Chile, Israel, and Saudi Arabia.

Discussion

A noteworthy aspect of the T1D OBTAIN trial is its use of a bispecific nanobody. Unlike traditional antibodies, nanobodies are smaller and can be engineered to hit multiple targets at once. This dual-target strategy, aiming at both TNF-alpha and OX40L, represents a more complex approach than simply blocking a single immune pathway, which has been the focus of most past research in this area.

This treatment was developed by Sansofi, and they are running several different clinical trials to test it on different diseases: Crohn’s disease (Colitis ulcerative), Hidradenitis Suppurativa, Focal Segmental Glomerulosclerosis, and Minimal Change Disease.  I'm not sure why they chose those diseases.  The first is an autoimmune disease, similar in some ways to T1D, the second is an immune disease (but not autoimmune), while the causes of the third and fourth are not really known, and might be a lot of things.

The summary of the running trials is this: The Hidradenitis Suppurativa phase-II trial ended successfully, and they started a larger phase-II trial.  The other trials are still ongoing.  These are all roughly 90 person, phase-II trials and are expected to end in the next year or two.  Because Hidradenitis Suppurativa is an immune disease, but not an autoimmune disease (like T1D), I don't think we should read much into the good results seen in that study. 

More Information







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!
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Wednesday, January 7, 2026

Rituximab and Treg Cells Starts a Phase IIΔ Trial In Youth At Risk Of Diabetes

A new clinical trial is exploring whether two different immune therapies, used alone or in combination, can delay or prevent the onset of  T1D in people who are at high risk, but have not yet been diagnosed with T1D. The study will test a cell-based therapy using a patient's own cells (regulatory T cells) and and a drug called rituximab.

It involves drawing a person’s blood, isolating a specific type of immune cell, multiplying these cells in a laboratory, and then infusing them back into the same person. These regulatory T cells are the body’s natural “peacekeepers,” responsible for preventing the immune system from attacking its own tissues.  Rituximab is a well-established prescription medication that works by targeting and removing a different type of immune cell, known as a B cell. B cells play a role in the autoimmune attack that causes T1D.

The regulatory T cells will be administered through an infusion, while rituximab will be given as an injection. The trial will involve multiple infusions and injections over a period of time. This is not a new treatment; both regulatory T cells and rituximab have been used in other diseases. However, combining them to prevent type 1 diabetes is novel.

Rituximab has been approved by the FDA for many years to treat other autoimmune conditions, such as rheumatoid arthritis, as well as certain types of cancer.  Its safety profile is well understood from its use in these other conditions. Treg therapy is still experimental and not approved for general use. However, it has been studied in human clinical trials for more than a decade for T1D and other autoimmune diseases. To date, these studies have generally shown it to be safe.

The Study

This study is a randomized, controlled trial, participants will be randomly assigned to different treatment groups. The trial will include approximately 150 children aged 6 to 16 who already have two autoantibodies associated with type 1 diabetes and therefore are at very high risk of developing type 1 diabetes. They will be followed for five years.

There will be four groups in the trial, which cover all the combinations of treatment and  placebo:
1. Group I will receive both regulatory T cells and Rituximab.
2. Group II will receive regulatory T cells and a placebo.
3. Group III will receive Rituximab and a placebo.
4. Group IV will receive two placebos, one simulating Rituximab, the other the cell infusion.

The primary endpoints of the study are the number of days from the start of the treatment to the first signs of high blood sugar levels and the number of adverse events reported. 

The secondary endpoints include C-peptide levels, daily insulin dose, and the number of participants in remission. 

Families interested in the trial can contact the study team for more information:

Marta Druch, Clinical Trial Director  Email: m.druch@poltreg.com  Phone: +48 731 471 845
Grzegorz Orlik, Medical Director  Email: g.orlik@poltreg.com  Phone: +48 790 680 020

The trial is being conducted at eight locations across Poland:
  • Bialystok, Poland (Recruiting)
  • Gdansk, Poland (Not yet recruiting)
  • Katowice, Poland (Not yet recruiting)
  • Lodz, Poland (Not yet recruiting)
  • Lublin, Poland (Not yet recruiting)
  • Opole, Poland (Not yet recruiting)
  • Rzeszów, Poland (Not yet recruiting)
  • Wroclaw, Poland (Not yet recruiting)
More details, including full eligibility criteria, are available on the clinical trial registry: https://clinicaltrials.gov/study/NCT06688331  

This trial is funded by PolTREG S.A., a company specializing in cellular therapies.

Discussion

One thing that I like about this study is that they are testing two different treatments, but all the possibilities (both treatments, one treatment, the other treatment, and no treatments).  This means it should be easy to see if either treatment is helpful and if the treatments help each other be more effective than either alone.  

Running a clinical trial on children ages 6 to 16 is also good, since that is the age that most people with T1D are diagnosed. 

The long duration of the trial, five years, means we will be waiting a long time for results.  This is unfortunate, but if the goal is prevention, I do not see any other way to run the clinical trial. 

Related Trials

Study NCT00279305, a Phase 2 study which completed in 2009 with 87 honeymooner T1D participants aged 8-45, investigated Rituximab. The study found that rituximab preserved C-peptide generation as compared to placebo.

Study NCT01280682, completed in 2018 in China.  It enrolled 120 honeymooner T1D patients aged 8-70.  This trial showed that rituximab treatment slowed the decline in C-peptide compared to insulin-only treatment and resulted in lower HbA1c levels at six months.

Study NCT03929601 is an ongoing Phase 2 study with 74 honeymooner T1D participants aged 8-45. This study compares sequential Rituximab and Abatacept therapy to Rituximab alone, aiming to improve C-peptide response at 24 months. Secondary endpoints include safety, insulin use, and HbA1c. It is expected to finish in March 2029.

Study NCT07041268, an ongoing Phase 2 trial recruiting an estimated 116 honeymooner T1D adolescents (12-17 years old) in Russia, is examining repeated Rituximab. The primary endpoint is the change in mean C-peptide levels, with secondary goals including insulin dose and HbA1c. This study anticipates completion by March 2028.

More Information

For more information about this clinical trial, you can visit the following links:

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! 
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