CNK-UT009 Cell Therapy Starts A Phase-I Clinical Trial

CNK-UT009, as tested here, is a one-time infusion of living cells designed to modify the immune system’s behavior.  The idea behind it is that by reprogramming T cells, it may be possible to suppress the misdirected immune response that causes type 1 diabetes while potentially allowing remaining beta cells to function better.  Animal studies suggest that this method could reduce autoimmunity and improve C-peptide levels.

The company developing this is ST Phi Therapeutics Co., Ltd. (in China) and should not be mixed up with STɸ "ST phi" (in Washington state USA).  They are both biotech companies, but otherwise completely different.  ST Phi Therapeutics has developed infrastructure (or "a platform", in biotech terminology) called CNK-UT.  It is variant of CAR-T genetic engineering, but (they claim) better than CAR-T.  See the discussion section for more on CAR-T.  They have used their CNK-UT platform to create at least four different specific treatments, of which CNK-UT009 is one.  All of these are in early research phases.

The Study

The goals of the study are to evaluate the safety and tolerability of the CNK-UT009 cell injection and to determine the maximum tolerated dose. This will be assessed by monitoring adverse events and the severity of any treatment-emergent adverse events. The primary efficacy endpoint is C-peptide levels.  Secondary endpoints include changes in HbA1c levels, continuous glucose monitoring data, average daily insulin dosage, and the level of islet autoantibodies. 

The trial is single-arm, open-label study, meaning 12 participants (all adults with T1D) will receive the CNK-UT009 cell injection, and there will be no placebo or control group.  This trial is open to both people with established T1D and T1D honeymooners.

 

The study will also examine how long the modified cells stay in the body (pharmacokinetics) and whether participants develop antibodies against the treatment (immunogenicity).

The trial is currently recruiting at Zibo Central Hospital (Zibo, Shandong, China)

For more information, interested participants should contact: 

Dr. Xiaoming Pang   Email: pxm@sdu.edu.cn  Phone: +86-5332361126

Results are not expected until end of 2026. 

Discussion

CAR-T is a general term for genetically engineered T-cells (part of the immune system).  Since T-cells are part of the immune system which leads to T1D, changing them is a promising method to treat T1D.  The US FDA and EU regulators have approved several different CAR-T therapies for cancer, but none yet for autoimmune diseases.

More Information

For those interested in learning more, here are key links:

• Clinical Trial Registration: https://clinicaltrials.gov/study/NCT07051564
• Zibo Central Hospital (trial sponsor): http://www.zbzxyy.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 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! 

IMMUNOSTEM starts a Phase-I Clinical Trial in Honeymooners

IMMUNOSTEM technology refers to using a virus (specifically a lentivirus) to deliver a new gene into cells, which will then produce a specific protein PD-L1 (Programmed Death-Ligand 1).  This protein plays a key role in the immune system by telling T-cells not to attack a specific other cell (in this case, beta cells).  This is done to the patient's own blood.  It is removed, treated in this way, and then put back, thereby treating the T-cells in the blood so they will not attack beta cells.

Digression: this whole area of research was motivated by cancer.  The PD-L1 protein is hijacked by cancer cells to help them hide from the immune system.  By genetically engineering cells to produce human PD-L1, scientists can research this process.  But the researchers for this study hope to use this mechanism to protect beta cells from the autoimmune attack that starts T1D.

The PD-L1 overexpression technology licensed by Altheia Science was developed by researchers who later co-founded the company. Alessandra Biffi and Paolo Fiorina did this work at Boston Children's Hospital.  

To create the IMMUNOSTEM treatment, specific blood cells from a patient are collected through a procedure called leukapheresis. These collected cells are then genetically engineered using a modified virus, the PD-L1 lentiviral vector, to carry new genetic instructions. These instructions enable the cells to produce the PD-L1 protein.  After modification, the cells are frozen and later re-infused into the patient's bloodstream as a single injection.

This Clinical Trial

This trial is a Phase I study where everyone gets the treatment, meaning there is no placebo group and no randomization.  All 15 people will receive treatment.  They will all be honeymoon adults (aged 18 to 40), within 180 days of diagnosis.

Patients will get one infusion and have follow-up for 24 months.  The primary endpoint of this Phase I study is safety, but secondary endpoints will evaluate the early efficacy of the treatment, especially c-peptide levels, as well as management issues like blood glucose levels, insulin requirements, A1c numbers, etc.

This study is being done at one site in Italy.  Contact info is:

Name: Paolo Rizzardi, MD

Phone Number: +39 335 1935042

Email: paolo.rizzardi@altheiascience.com

Location: Padua, Italia, Italy, Azienda Ospedale-Università Padova

Discussion

Since this is a new type of gene therapy (for T1D), there are two new risks involved.  One is infusing the new cells, and the other is using the virus to genetically modify them ahead of time.  However, the cell infusion has been done for decades for treating cancer, and is considered safe in that context.  

The other new (to T1D) risk is the use of a lentivirus to directly modify a cell's DNA to produce PD-L1. It is not currently in use as an FDA approved treatment for any disease.  Both gene therapy and lentiviral vectors have approved uses for other conditions, but not to produce PD-L1 as used here. 

Altheia Science is focused on applying PD-L1 technology to type 1 diabetes, but is also working on using it to treat Multiple Sclerosis, another autoimmune disease.

A study published in November 2024 by these researchers showed that a PD-L1 based treatment resulted in NOD mice stabilizing with a BG level of 150-300, while those untreated did not stabilize below 600 (when it could no longer be measured).
Previous Research Publication: https://pubmed.ncbi.nlm.nih.gov/29141886

As far as I know, this is the only research attacking T1D using this PD-L1 approach, but there has been several successes in using lentivirus to inject DNA in the past for a variety of rare genetic diseases: β-thalassemia, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, and Wiskott-Aldrich Syndrome.

For More Information

• Company: https://www.altheiascience.com
• Clinical Trial Registery: https://clinicaltrials.gov/study/NCT06938334
• Researchers' Study Explanation: https://www.altheiascience.com/immunostem

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!

Results from a Phase-II Clinical Trial of Baricitinib

Baricitinib works by interfering with signaling pathways inside immune cells, to reduce inflammation and lower the immune system.  It is part of a class of drugs called Janus kinase (JAK) inhibitors.  JAK comes in two forms, JAK1 and JAK2, and Baricitinib targets both of them.

Baricitinib is not a new drug; it was first approved by the US Food and Drug Administration (FDA) in 2018.  It is taken as a once-daily oral pill and used to treat other autoimmune diseases, such as rheumatoid arthritis and alopecia areata (an autoimmune form of hair loss).  Because it has been in use for several years for other autoimmune conditions, its safety profile is well-understood.

Since the drug works on other autoimmune diseases, it seems reasonable to try it on type-1 diabetes.  Also, there has been the usual success with nonobese diabetic mice, which are commonly used to test potential type-1 diabetes cures.

This Study

This study is a phase 2, double-blind, randomized, placebo-controlled trial. A total of 91 patients were enrolled, with 60 individuals assigned to receive Baricitinib and 31 to the placebo group. Participants were honeymooners, having been diagnosed within 100 days before the start of the treatment.  They took one Baricitinib pill daily for almost a year.

The primary end point was the C-peptide level after a year. C-peptide is a substance released when the body produces insulin, serving as a reliable indicator of remaining beta-cell function. 

Secondary endpoints included several practical measures of diabetes management, average daily insulin dose,  A1c levels, and various metrics of glycemic control gathered from continuous glucose monitors. Tertiary end points included measuring things inside the immune system to see how Baricitinib affected them, especially what are called "effector memory CD8+ T cells".

The Results

The grey, placebo line shows the normal progression of T1D during the honeymoon phase.  C-peptide generation falls steadily until it hits some small residual levels, where it stays constant.  The amber, treatment line shows pretty much the opposite.  C-peptide generation goes up, but then plateaus out.  There is no doubt in my mind that this is a good outcome.  Generating more C-peptide is good, and this is not just holding constant; at the beginning it is going up.

But there are two big questions here.  First, is the difference important.  Untreated people leveled out at a level around 0.43, but treated people leveled out at about 0.65 and that is still way below healthy.  Second, this plateau was constant for the last 6 months of the study. and while the people were continuing to get Baricitinib.  This tells me that at this dose, it is not just a matter of time to get more improvement.

Discussion

To me, the obvious next question is: will a higher dose show more improvement?  This study shows improvement, but not enough to cure anyone, or even make much difference in treatment.   Would a higher dose of Baricitinib have a bigger impact?

Another follow on question is: will earlier treatment prevent T1D?  This is harder to study, and we will need to wait longer for the results.  However, any treatment which preserves beta cells might prevent T1D, if given in the pre-honeymoon phase.  And it is important to remember, this treatment did more than just preserve C-peptide production, it increased it.

The findings also support the concept that JAK inhibitors, as a class of drugs, may hold promise for treating type 1 diabetes. This could lead to further exploration of other JAK inhibitors in future clinical trials for this condition. 

One other clinical trial testing JAK inhibitors is being run now.  It is testing both abrocitnib and ritlecitinib.  It started in 2023 and they hope to finish in 2026.  It is recruiting in several sites in California, Other USA locations, Australia, and one in Canada.  You can see details here:

https://www.clinicaltrials.gov/study/NCT05743244

(click on the grey space to see a map of study locations)

For More Information

• US Clinical Trials Registry (ClinicalTrials.gov): https://clinicaltrials.gov/study/NCT04774224
• Australian New Zealand Clinical Trials Registry for BANDIT study: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380252
• Study Web Site: https://www.trialnet.org/events-news/blog/study-finds-jak-inhibitor-baricitinib-slows-t1d

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!

Avotres Announces Results from a Phase-I Trial of AVT001

This blog posting reports on the results of Avotres recent phase-I clinical trial into AVT001 and the company's future plans for testing.  I reported on the start of this trial here:

https://cureresearch4type1diabetes.blogspot.com/2019/12/avotress-avt001-starts-phase-i-trial.html

AVT001 is an "autologous dendritic cell therapy" meaning that a person's own dendritic immune cells are taken out, processed in some way, and then put back.  Dendritic cells can be thought of as the immune systems "sensors".  They detect foreign invaders and then communicate that knowledge to other types of immune cells (especially T cells).

This trial flows out of some work done at Columbia University.  Researchers there found a defect in a specific type of immune cell called a HLA-E–restricted CD8+ T cells.  They believe that this defect leads to the immune system attacking the beta cells in the pancreas and causing type-1 diabetes.   The basic technique being tested here is to take out dendritic cells from the patient and treat those cells so that when they are put back into the patient, they (in turn) fix the defect in the HLA-E–restricted CD8+ T cells which leads to type-1 diabetes.

This Study and Its Results

This study involved 25 people, 16 were in the treatment group and 9 in a control group.  They were 16 years old or older, and in their honeymoon phase after diagnosis of T1D.  There were primary end points for safety and a secondary end point for C-peptides.  For me, the key results are below.  

The table below covers a year, from left to right on the bottom, and the amount of C-peptides a person generated, from zero up, on the left side.   A flat line shows success.   The body continues generating C-peptides. For the first 150 days for the treated group, C-peptide numbers do not drop at all.  This is the flat purple line. After that they did drop at about the same rate as untreated people.  This is the purple line dropping down. You can notice that the purple line and the dotted orange line (the untreated group) drop at about the same rate. The difference is that the untreated group started immeadiately, but the treated group stayed constant for at least 150 days. Since the treatment group was given three infusions, 30 days apart, the treatment last 90 days (infusions were on days 1, 30 and 60).  The treatment prevented beta cell loss for at least 90 additional days.  Safety and side effect data showed that there were no safety issues.

That's hopeful news in terms of prevention.  It suggests that giving this drug before the honeymoon phase might prevent T1D or at least delay it.   Of course, a study giving this treatment to pre-honeymooners would be needed to see if this actually happened.  Such a test would compare pre-honeymooners who got the treatment to pre-honeymooners who did not, and see how many of each group progressed to the honeymoon phase of type-1 diabetes.  If enough people are enrolled, and they are followed for long enough, such as trial could be run.   My memory is that such trials have been run lasting 2 and 5 years, and enrolling from 1 to 3 hundred people, so it is reasonable to do.

Also, it is important to remember that this treatment involves removing white blood cells from a  person's blood, treating the cells in a lab, and then intravenously infusing them back into the person with T1D.  So this is two clinic visits per treatment.

Poster: https://www.avotres.com/_files/ugd/1b81f5_edb8f657a28440638f8e32d2ec98ec4f.pdf

Journal Article: https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2300238

Clinical Trial Registry: https://clinicaltrials.gov/study/NCT03895996

What Next?

From the point of view of Avotres, this was a clearly successfully phase-I/II and so are in discussions with the FDA to set up a phase-III clinical trial as the next step.  There is no advantage in speculating as to what the FDA will do.  The only thing that makes sense to do is wait a few months (or a year) and see what actually happens. 

From my point of view, this was a successful phase-I study, which showed that AVT001 might work as a T1D prevention.  If given to people before the honeymoon, it might delay or even prevent the onset of T1D.  Therefore, Avotres could turn this into a prevention/delay treatment (like Tzield®) by running three more studies (one one phase-II study and two phase-III studies as a minimum) to get approval.

In addition Avotres could try to apply AVT001 to treatment of established T1D in a different set of clinical trials, and see where that led.  

For background, the FDA generally requires one phase-I study, one phase-II study, and two phase-III studies as a minimum for approval, although there are occasional exceptions.

Company website: https://www.avotres.com/ and https://www.avotres.com/companyoverview

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!

No Blog Postings Until August

I have not posted anything in this blog for the last 5 weeks, and I don't expect to for the next few weeks.  That is because my father has passed away.  It was not sudden or unexpected, but it is still very shocking.  He was diagnosed with terminal pancreatic cancer about six months ago, and was slowly declining.  However, in mid-May, he started quickly declining, and died on 10 June 2025.  His cancer had nothing to do with diabetes, although it did cause him to have high blood glucose for the last few months of his life.

My plan is to take a break from blogging for the rest of June and July, but then start blogging again in August.

My dad taught me several things which have directly shaped this blog, including:

• Optimism, which is why I blog on cures, even as we are so far away from a cure, but also allows me to do something (blogging) that I had never done before, and in an area (medicine) that I have no special skills or training.   
• As a small kid and repeatedly throughout my life, he told me: when talking to someone else (anyone else), to always be willing to talk about what they were interested in.  Learn why they liked it, why they found it exciting, and the complexities they found in whatever was important to them.  Reading other's research is similar to talking to them about something they are very, very interested in.
• As a young adult, he reminded me that "your children will take you in directions you would not have gone yourself".  This blog is a testament to an unexpected place that my child has taken me.
• My dad understood that facts were just web searches.  But the important thing was understanding why something was true, how it was true, what it meant, how changes in the world would change the fact, and how changes in the fact would change the world.  These were the questions that interested him, and you can see how those questions fuel this blog.

Joshua

Diamyd’s GABA-Based Remygen® Unsuccessful in Phase 1 Clinical Trial

This clinical trial tested whether long-term daily treatment with Remygen®, an oral drug developed by Diamyd Medical, could help restore insulin production in adults with longstanding type 1 diabetes (T1D). The active component of Remygen® is GABA (gamma-aminobutyric acid), a compound that in earlier experimental studies appeared to support the regeneration of insulin-producing beta cells, improve insulin release, and reduce inflammation.

What Was the Clinical Trial Testing?

The trial enrolled 35 adult men with T1D for at least five years and divided them into three treatment groups. One group received a lower daily dose of GABA, a second received a higher dose, and a third group received the higher GABA dose plus a short-term course of alprazolam (an anti-anxiety, benzodiazepine drug). The treatment lasted six months.

Researchers monitored insulin production using fasting and post-meal C-peptide levels, tracked blood glucose control, and recorded any side effects or adverse events. The goal was to assess both the safety of long-term GABA use and whether it had any regenerative effect on the pancreas.

What Were the Results of the Clinical Trial?

The trial found that Remygen® did not restore insulin production or improve any markers of beta-cell function.

C-peptide levels, which reflect the body’s natural insulin production, remained unchanged in all treatment groups throughout the six-month period. This included individuals who had some detectable C-peptide at baseline, as well as those with undetectable levels. No meaningful changes were observed for insulin production either.

Measures of blood sugar control—including continuous glucose monitoring data and HbA1c—also remained stable, with no significant improvements seen in any group.

Additionally, the trial found no change in the body’s hormonal response to low blood sugar. This was in contrast to some earlier short-term studies that had hinted at possible effects of GABA in this area.

In terms of safety, the treatment was generally well tolerated, but side effects were common.  One participant had a serious liver reaction, likely related to the drug, though liver function returned to normal after stopping the medication.

Discussion

My memory is that, at its height, there were 4 or so GABA related clinical trials running.  But this was the last GABA clinical trial that I knew of, so I think this line of research is dead for now.

Diamyd has also been developing a DNA-based immunotherapy (also called Diamyd®) aimed at slowing or stopping the immune system’s attack on beta cells, a different strategy from GABA. That program remains in clinical development. 

Clinical Trial Registry: https://www.clinicaltrials.gov/study/NCT03635437

EU Clinical Trial Registry: 2018-001115-73

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 boarder 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!

Changes to My Blogging: AI

I'm going to start using generative AI (what people call "chatbot" technology) to help me create draft blog postings.    In all cases, I will review and edit every word to ensure three things:

• Every posting has the right tone.
• Every piece of information in the posting is accurate.
• Every posting conveys the truth, as I understand it, in terms of importance, future directions, risks, unknowns, and so on.  I check that the things implied the posting implies are true, are in fact, true.

This blog has never accepted as sufficient mere facts-and-figures accuracy (what the media often calls "fact checking").  In addition to checking facts, I have always spent a lot of time checking that the tone, implications and views conveyed in this blog are also the truth, as far as I know it.  That will continue, even as I use AI to help write initial drafts of the blog.

I'm starting to use AI for three related reasons:  First, blogs take a lot of time and I hope that using generative AI will allow me to create blogs of the same quality in less time.  I'm not going to save time in the editing or reviewing part of writing blogs, but crafting the English takes me a lot of time and I hope AI can speed the process. Second, I hope that I can use this newly available time to either create more blogs or create more complex blogs.   I want to do more analysis and historical perspective type blogs, rather than just writing all the time to keep up with the clinical trial results.  I feel that is sort of the news equivalent of "treading water", and what I want is to get ahead of the news and use the news to write more inciteful posts.  Third, it would be nice to get news about clinical trials out quicker so you can read about it sooner after the results are announced.

In terms of "how will I use AI", I'm not going to use it in a simple minded or unthinking way! I am going to experiment with several different methods and expect to end up using a combination of these techniques, and incrementally improving them over time.  

• For example, one simple technique would be to have many different chatbots respond to the same question, and then I, as a human, merge the best parts (or the best language) from each of their responses together to create a posting.   
• Another technique I will try is asking very specific, very focused questions of AI in order to generate parts of the blog posting.  Then (as a human) merging those parts together into a posting.
• I will also experiment with creating very complex detailed questions for the AI in order to generate blog postings all at once.  (This is called "prompt engineering".)

The future is the undiscovered territory, and I am going exploring.

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 boarder 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!