SSI Qu Biologics trial for Crohn's disease RESULTS

[Lady Organic]

High Response and remission Rates in Anti-TNFα Naïve Patients Treated with Qu Biologics’ Novel Immune Therapy for Crohn’s Disease.

http://www.quibd.com/status-update/...iologics-novel-immune-therapy-crohns-disease/

Posted on August 31, 2017

Vancouver, British Columbia – April 19th, 2017 – Qu Biologics Inc., a biopharmaceutical company developing Site Specific Immunomodulators (SSIs), a unique platform of immunotherapies designed to restore the body’s innate immune system, reports high response and remission rates in anti-TNFα naïve patients in its recently completed randomized, placebo controlled trial in moderate to severe Crohn’s disease (CD). In the study, treatment with QBECO SSI for 8 weeks resulted in a statistically significant response rate of 64% compared to 27% in the placebo control (p=0.041). Clinical remission rates after 8 weeks of treatment were also impressive at 50%, more than double the placebo rate of 23% (p=0.16). Clinical response and remission rates were assessed using the standard Crohn’s Disease Activity Index (CDAI), defined as a decrease in CDAI of ≥70 points (response) and CDAI score ≤150 points (remission).

Dr. Brian Bressler, UBC Clinical Assistant Professor of Medicine, Division of Gastroenterology, and Principal Investigator of the trial, explained, “remission rates in similarly designed randomized placebo controlled trials with current ‘gold-standard’ treatments for CD, Remicade® and Humira®, are approximately 35% in anti-TNFα naïve patients at similar time-points, so the 50% remission rate in this important patient group in this trial is promising.” Dr. Hal Gunn, CEO of Qu Biologics, added, “We are pleased with the high response and remission rates in the QBECO-treated anti-TNFα naïve CD patients at the early Week 8 time-point, particularly as data from the trial suggests that many patients continue to improve on SSI treatment after this time-point. Future studies will assess response and remission rates with longer treatment periods.”

Anti-TNFα naïve patients (i.e., patients who have not been treated with the immunosuppressive drugs Remicade®, Humira®, Cimzia® and Simponi®) represent approximately two-thirds of Crohn’s disease patients in Europe and North America and a higher percentage of patients elsewhere. Patients who have previously been treated with and failed anti-TNFα agents are known to be a more difficult to treat patient group. Data from the trial’s cytokine analysis suggests that patients previously treated with anti-TNFα agents may have greater baseline innate immune suppression/dysregulation. SSI treatment is designed to restore innate immune function and therefore, a longer period of SSI treatment may be required in this latter patient group. As Jim Pankovich, Qu Biologics’ VP Clinical Operations and Drug Development noted, “In patients previously been treated with TNFα inhibitors who completed 16 weeks of SSI treatment, 40% were in remission, suggesting that this more challenging patient group may respond to QBECO SSI with longer treatment.”

Dr. Hal Gunn added, “When this data is combined with the genetic and cytokine biomarker data from the trial, it suggests that we may be able to select patient groups with an even higher probability of response and remission with QBECO SSI treatment. These results are very encouraging and will guide us in the design of our next study and in future Phase 3 studies.” Qu Biologics plans to initiate a larger follow-on clinical trial in Crohn’s disease in late 2017/early 2018 with a 52-week QBECO SSI treatment period.

For more information about Qu Biologics and the science behind SSIs, please visit www.qubiologics.com.

 

[SauceySciencey]

Arthur Hurst, 1921, Guys Hospital Reports.

Crohn, Burril, 1935, 1952.

Hurst was doing this almost 100 years ago. They theorised so long as a systemic response was induced (the worse the better), the patient would respond. They tried everything they could. Anti-dysentery serum (from patients who'd had dysentery) would work. Different vaccines commonly used at the time (typhoid etc) but titrated so a "protein" shock was induced (Hurst would inject almost 100 mL IV into a patient) were injected.

Fever, chills, joint pain, and then sudden remission. Of course, this is greater volume than the "SSI"..

One GI Crohn cites in his paper tried horse serum. That worked too. The only time it didn't work was when a patient didn't have the "febrile" shock. Numerous GIs reported the same thing. The odds of that being random are very low.



Another GI Hurst and Crohn cite used Mercurochrome (which is known to be immunogenic and cause a protein shock like state..it's why mercury was added to vaccines in the past) with great success in a patient.

Bargen tried his typhoid vaccine. Didn't get a response UNLESS they had a febrile shock. Crohn's summary in his paper later on (1952) showed better response rates than humira, too, 45 odd years before Humira came out. Fancy that.

I'm hopeful for this trial, but at the same time, it bugs me that they'll charge us all a bucketload if it passes. Just to get a patent he called it "SSI", when he's never shown it has to be a "bug" specific to the GI tract.

And there's plenty of papers in the past 20 years that have done similar things in mice.

One paper used the active ingredient in whooping cough vaccine (filamentous hemagglutinin) in DSS treated mice. It abrogated the colitis.

https://www.ncbi.nlm.nih.gov/pubmed/16952913

Another paper did something similar.

https://www.ncbi.nlm.nih.gov/pubmed/21881971

They used normal, happy, non-pathogenic fecal organisms - smashed them up and injected them into mice with colitis. Same result.

Another paper
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907795/

It wasn't live VSL 3 that did anything. It was dead VSL 3. Specifically the DNA, apparently. The body picks up the bacterial DNA, thinks it's infected, starts a systemic response. Following this, a systemic anti-inflammatory response occurs, which presumably inhibits the colitis, or reduces it.

In another paper, they didn't inject the smashed up VSL #3. They broke it up and fed it to mice. So they don't just have to inject it (the upper GI tract absorbs most of it, apparently).

And another paper using E coli nissle 1917, although this was in a cell line, not an animal study.


On a related side note, I'd like to thank Burril Crohn himself, and Arthur Hurst. If I hadn't read those papers I would've gone through with the surgery, instead of almost 2 months pain free and off prednisone. It seems I won the lottery, considering when I told them to discharge me they all said I'd be back in a week. I should've bought a lottery ticket...

 

[Anonymous77]

How exactly did you manage to implement Crohn and Hurst's therapy on yourself?

 

[SauceySciencey]

I used VSL # 3 and mutaflor. I didn't ingest them. I cultured them for 3 days.

In one of the papers, it was something the E coli nissle 1917 was spitting out as it grew that was responsible. So, grew mutaflor. Spun down in a centrifuge (I have access to one). The medium was then autoclaved (effectively pressure cooked at 130 degrees celcius) and put aside.

For the VSL # 3 paper, I cultured for three days, spun down and took the pellet of microbes, used a particular method using ethanol to inactivate/lyse. In the VSL #3 papers, it was bacterial DNA that the immune system of mice.

I combined the VSL # 3 DNA (which is a few different microbes mind you) and the mutaflor conditioned medium.

Then I waited 2 weeks. I gave aliquots to a colleague who plated it out and incubated in her lab. This was to check nothing was still alive (I decided paranoia was best). Plates were clean. I think I overdid the culturing , though, I was told the protein concentration was about 1.2 mg/mL (that's an awful lot!)

I then halved the serum with bacteriostatic water to make it somewhat more isotonic (I ended up with 0.6% sodium chloride (0.9 is normal)). The serum is passed to another colleague, where it's sterilised and aliquoted under aseptic conditions.

On the right leg, I started with 10 uL (1:100 of a mL) subcut injection of serum.

On the left, 10 uL of sodium chloride.

24 hours later, nothing.

Increased to 20. Repeat.

Then 40.

I got to 300 uL. Right leg had a response (meaning, I had a light pink skin reaction, somewhat raised), but left leg did not. So, body was picking up something in the serum and responding.

When the redness is gone, I re-inject. Sometimes it's within 48 hours I need to re-inject. Other days it's 72, but never more than that.

About 30 injections in, the pattern is

-low grade feverish/flushed.
-my arthritis sometimes plays up the day after injection. I have Ankylosing Spondylitis. I haven't had any back problems for 2 years. It will be "twingey" 24 hours after injection, but go away after a few hours. Not pain, but I can feel it, if you understand me.
-no flare ups. not one.

I have an MRI scheduled in October, we'll see what we'll see, I suppose.


Of course, I'm one person, and I'm a damn good scientist, although retired due to crohn's (for now). I won't say it worked, or didn't work. But I will say looking at my clinical history that the odds of my sudden improvement coinciding with the beginning of injections is very low that this was random. I went from needing to go to hospital 2-3 times a month for about 3 months prior to deciding to do this. I was on methotrexate, humira, prednisone for a year. Didn't seem to have an effect on the crohn's. I vomited every day (retched, actually). I lost 40 kgs (mostly muscle, pah!). In the past 2 months, I've put on about 10 kgs (half fat, half muscle...oops). My daily white cell count hasn't gone above 12. Average was 19 the prior 6 months (I do it myself).

There's also the random fact that I stopped the methotrexate prior to starting, and pulled back on weekly humira to just fortnight (for the Ankylosing Spondylitis). One would suspect I'd get worse, not better. Again, that could be random. But the odds are low. I'm kicking myself for not setting up the ability to measure TGF-B, IL-10 (would be costly). It wouldn't be proof positive but there'd be evidence of systemic anti-inflammatory mechanisms correlating to injection. Whilst not definitive, it would edge the odds of this being random even lower.



I'd also like to say I didn't do this half-heartedly. It's been at the back of my mind since diagnosis. I had alot of help. It would be possible to do this in a "kitchen" lab (I did for some things) but ultimately I was relying on access to a clinical grade laboratory and equipment/people. I wouldn't have tried if I didn't, and I kept putting it off for that very reason.

I also told my GP (local doctor) what I was doing.

Frankly, if I was diagnosed right now, I wouldn't do this. I'd wait for the SSI to come out (assuming it passes, which I think it will). I did this , however well controlled, in desperation.

That being said, I did promise my partner that I'd find a way to fund a clinical trial for a generalized protocol for this treatment. Which can't be patented by anyone, but anyone can derive (a hospital lab could do this on a small scale so cheaply it's not funny). She's about the only person who believes me that I'll find a way, mind you (which is why I love her!). Once a problem gets in my head, I don't stop (which is either a good thing or a bad thing)

I'm slowly getting back into my previous work (nothing to do with crohn's), although I'd love to see Qu's data on their cytokine and immune biomarkers. That is actually my specialty - developing predictive techniques with high dimensional data (in cancer, mainly). If that works out I'll be waving goodbye to academia and going private. I don't care if I spend every penny of the money on this, I'll damn well do it. And if it doesn't work, I'll rob a bank to fund it. I'm really gunning to find out what this would do in a wider population of patients, and whether it works, and whether it really matters what you are using, so long as it induces that systemic response mediate via TLR signalling, which appears to be the mechanism (although it could be something else, or a combination).

 

[Crohn2357]

Deleted.

 

[Mommabear]

SauceySciencey - so basically are you saying that it seems from your reading and experience any kind of "vaccine" stimulates the immune system enough to clear whatever infection is lurking? So, in your opinion the MAP vaccine will have a good chance of working?

 

[SauceySciencey]

No I wouldn't say it's a vaccine. A vaccine is something specifically spurring the adaptive immune system to respond by developing antibodies to a foreign/invasive antigen. This is more evoking a systemic response with respect to the innate immune system, where following the systemic response is a stark anti-inflammatory regimen. It's the same reaction some people get to some drugs, like antibiotics. It's just something foreign the body picks up and invokes the first line of response/defence. The same happens with some chemicals, such as mercury (not that you'd want to inject that!). Some vaccines can do this to people (it's one of the major side effects - the body just picks up that somethings foreign and assumes an infection).

What happens after no one can be certain of, but we do know following sepsis/serum shock a very sharp and stark anti-inflammatory response happens. Whether that specific mechanism happens with the Qu treatment, or any treatment similar to this, is open to debate. All we can say is that there appears to be a statistically significant trend in positive results with these clinical trials.

I really don't have an opinion on MAP that's worth sharing. I haven't read everything that's been done on it, so I can't comment.

 

[RocketMan]

Hi Saucey,

I find your experiment really interesting -- bravo to you for going through with that and for sharing your experience. I was hoping that you could provide a quick update. How are you doing a couple of months later? Are you still taking the injections?

 

[David]

VERY interesting that they combined a genetic biomarker with this. Very exciting!

 

[SauceySciencey]

VERY interesting that they combined a genetic biomarker with this. Very exciting!

Not sure if it's a genetic signature, as in gene expression, or immune signature, and where they tested this in the biological hierarchy. I suspect they did a cytokine-chemokine profile (they really must believe in what they are doing, the last one of those I did in some cancer patients cost 5000 dollars a test, unless it's come down some), which would be the protein-level expression.

I suspect looking at the whole network of systemic cytokine/chemokine expression would be somewhat more revealing instead of stand-alone gene expression studies. Looking at the cytokine-chemokine network entirely would be like overlapping hundreds of different spider-webs, and attempting to see which patterns are the same in relation to the clinical history. Alot of cancer bioinformaticians are slapping their heads and ignoring alot of gene expression itself and looking directly at the top level stuff and seeing greater correlation to the clinical history of the sample (relapse, whether a drug worked etc).

 

[SauceySciencey]

Hi Saucey,

I find your experiment really interesting -- bravo to you for going through with that and for sharing your experience. I was hoping that you could provide a quick update. How are you doing a couple of months later? Are you still taking the injections?

Update is...no more prednisone - still on Humira and methotrexate oral (GI said to, although i didn't really want to go back on this stuff, although I didn't want to say why...ha...imagine her face) weekly.

I still can't say whether it is directly doing anything - it may be doing nothing. What I can update is this

I had three incidents requiring some codeine. All in the same week that I decided not to have the injections to see what would happen.

That's still not proof. Just makes it more interesting.

Give me a plate reader (can even be an old one from the 90s!), some blood, and a cytokine profiling kit from bio-rad http://www.bio-rad.com/en-au/product/bio-plex-pro-human-cytokine-chemokine-growth-factor-assays ...which costs about 3000 dollars...and we can do an experiment to prove, at least in my case, that something is happen. Otherwise, nothing is happening.

I'm still doing the injections, though :ybiggrin:

The only change is I've told them to increase the incubation time from 12 hours to 36, just so I could get the volume I inject (where I get the a red skin immune response) from roughly 650 uL (0.65 mL) to about 75 uL.