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Topical SADBE likely to treat ALL HHVs. Available in US & EU.

Hipsman

Senior Member
Messages
543
Location
Ukraine
SQX770 is a topical immunotherapy that has completed a Phase 1/2, larger Phase 2, and Mechanism of Action clinical trial for HSV-1 and HSV-2 (oral and genital). Phase 2b and Phase 3 trials are planned for the coming year. The company conducting the clinical trials is Squarex Pharmaceuticals.

This immunotherapy is applied to the inner bicep (arm) to induce a systemic (i.e. throughout the body) immune response to HSV-1 and HSV-2. Specifically, SQX770 is a contact immunotherapy that works by introducing an allergen (SADBE) to the body via the skin. This allergen tricks the body into thinking that a foreign pathogen is invading (which is how allergies work), and as a result, the immune system begins to mass produce T-cells to fight this foreign invader. This immune response by SQX770 is very similar to the one induced by poison ivy. In particular, SQX770 upregulates interferon gamma, a cytokine produced by T-cells that is essential in suppressing HSV. Those are naturally asymptomatic with HSV (about 87% of the infected population) have very highly upregulated interferon gamma levels.

Results of the clinical trials:

(1) Phase 1/2: An initial application of SQX770 resulted in a 67% reduction in OB frequency over the 4-month period afterwards, with over half of participants experiencing a 100% reduction in OB frequency.

(2) Larger Phase 2: An initial application of SQX770 resulted in a 62% reduction in OB frequency over the 4-month period afterwards.

(3) Mechanism of Action: An initial application of SQX770 showed that the immunotherapy boosted T-cell immunity, upregulated interferon gamma gene expression, and enhanced viral antigen recognition (which is why SQX770 is effective for different viruses, such as HSV-1, HSV-2, and HPV).

A more detailed summary of the trials can be found by reading Squarex's White Paper.

Some common questions and associated answers:

(1) Why does Squarex advertise SQX770 as an immunotherapy for oral herpes (cold sores)? Will it work for other types of herpes?

Yes, it will work for all types of herpes, because the immune response induced by the immunotherapy is systemic. It functions like a therapeutic vaccine. The reason Squarex is marketing this therapy for oral herpes is because Valtrex (valacyclovir) is already marketed for genital herpes. In other words, legally, Squarex can state that SQX770 is the first treatment on the market that can prevent cold sores. The company cannot say the same for genital herpes since Valtrex (valacyclovir) is already marketed as a preventative for genital herpes outbreaks when used suppressively. This is nuanced bullshit, but I get it, since the company needs to maximize potential sales. I'd like to note that their White Paper states how their clinical trials enrolled individuals with HSV-1 and HSV-2 of all types.

(2) Why does Squarex want to run trials on SQX770 when it is already made at compounding pharmacies (in the US) to treat HPV (warts)?

Because 2% SADBE (SQX770) is not currently commercialized for any illness at the moment. In the United States, we have compounding pharmacies that will specially make a drug or treatment that is not commercialized or mass produced, because the demand for that drug is so low. For example, let's saw you were allergic to a particular compound used in making Valtrex. Well, GSK (who makes Valtrex) isn't going to find a substitute compound to help you out. But a compounding pharmacy will do so. As a result, you'll pick up your Valtrex prescription at this compounding pharmacy with the substituted ingredient. Over the decades, 2% SADBE has been used as an immunotherapy to treat warts, but there hasn't been any company to run trials on it for HPV (or HSV for that matter). Squarex is trying to commercialize this for HSV, so that they can mass produce it. So instead of picking it up at a compounding pharmacy, you instead pick it up at CVS, Rite Aid, or Walgreens as a mass-produced drug.

(3) Is SQX770 applied to the outbreak?

NO. It is only applied to the arm, because the immune response induced by it is systemic. You could put it on the outbreak, but the reaction rash caused by the immunotherapy may be a bit uncomfortable around your lesions.

(4) How long does one application of SQX770 boost the immune system for?

It begins to exert itself on the immune system 14-21 days after application, with the maximum immune response occurring after 43 days and lasting until 121 days after application.

(5) Will I have to take SQX770 forever?

Theoretically, no. Over time, the immunotherapy slowly builds up memory T-cells that will better control HSV reactivations over time. So, after years of use, it is expected to no longer need to take the immunotherapy.

(6) Can I take this with antivirals or supplements?

Sure, but it is unknown how they may interact with each other. I recommend taking the immunotherapy alone.

(7) How can people access this immunotherapy if it hasn't completed clinical trials yet?

Well, because it is already available for HPV at compounding pharmacies, anyone in the United States can get it prescribed off-label. The benefits of Squarex commercializing the therapy is that it will allow for better quality control and provide necessary information on dosing and safety for HSV.

(8) Will it reduce transmission?

In theory, yes. But Squarex is purely focused on marketing this therapy to those with chronic outbreaks. So the trials will only focus on efficacy regarding OB reduction.

(9) Is a reaction rash necessary for the immunotherapy to work?

Yes and No. For an initial application, a reaction rash usually does not occur, BUT the immunotherapy still triggers an immune response to HSV. Further applications however should cause a reaction rash. This is because the immunotherapy functions via a contact allergen, and like any allergen, the more exposure to it, the more severe and pronounced the immune response to it. If you are applying it the second or third time and still do not have a reaction rash, chances are your prescription was made incorrectly. On a personal level, I did not get a reaction rash the first time, but the therapy still worked and stopped my weekly outbreaks. The second time however I DID get a rash. The clinical trials from Squarex also show that a reaction rash for an initial application is not necessary.

More information:
 

Hipsman

Senior Member
Messages
543
Location
Ukraine
I can't read it all right now but you said in the title "all HHVs" but I don't think it's mentioning HHV6, is it?
The anwser is in the quoted post and I fully agree with it, here it is again:
(1) Why does Squarex advertise SQX770 as an immunotherapy for oral herpes (cold sores)? Will it work for other types of herpes?
Yes, it will work for all types of herpes, because the immune response induced by the immunotherapy is systemic. It functions like a therapeutic vaccine. The reason Squarex is marketing this therapy for oral herpes is because Valtrex (valacyclovir) is already marketed for genital herpes. In other words, legally, Squarex can state that SQX770 is the first treatment on the market that can prevent cold sores. The company cannot say the same for genital herpes since Valtrex (valacyclovir) is already marketed as a preventative for genital herpes outbreaks when used suppressively. This is nuanced bullshit, but I get it, since the company needs to maximize potential sales. I'd like to note that their White Paper states how their clinical trials enrolled individuals with HSV-1 and HSV-2 of all types.
 

Osaca

Senior Member
Messages
344
The anwser is in the quoted post and I fully agree with it, here it is again:
Are we sure about this? I mean of course the immunemodulatory effect is always the same one, but how many T-cells do we need to produce for this to be sufficient? Or why is Atara Bio's approach for EBV & MS which introduces T-cells not this simple and far more specific (https://onlinelibrary.wiley.com/doi/full/10.1002/cti2.1444, https://onlinelibrary.wiley.com/doi/full/10.1002/cti2.1444)? EBV and some of the other viruses can be very good at hiding and masking itself, is this drug sufficient to suppress our EBV B-cell problems?

With only having read the white paper linked above https://img1.wsimg.com/blobby/go/3e0683c9-3b12-4984-9169-a0811b6955c1/downloads/Disease and drugs white paper v5.pdf?ver=1619415420616, they seemed to be more focused to measure outbreaks instead of viral load, the mechanism could be slightly different for us, right? Like the difference between mono, chronic EBV or tissue reactivations. The only measurments I see are in-vitro responses to HSV-1 and are
  • Lower anti-HSV-1 antibody levels (significant)
  • Higher interferon gamma gene expression when exposed to HSV-1 (significant)
  • Lower interleukin-5 gene expression when exposed to HSV-1 (significant)
What this means for other viruses might still have to be seen. But it sure sounds good! Together with the BCG vaccine and possibly some other things still to come we might be able to boost ourselves out of this disease some day. Thanks for posting this!
 
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Osaca

Senior Member
Messages
344
That's funny I was just thinking about this yesterday and searched the forums and was surprised no one had tried this. I might try it. I still think that upcoming Pritelivir and Im-250, which are new drugs for HSV are not talked about enough.
I think Pritelivir isn't talked about enough, because it's been in trials for over a decade (seems to be related to some initial problems in the eye of animals and not efficiency) so maybe some don't have the biggest hope in it coming to us in the near future.

Lovely, keep us updated!
 

Osaca

Senior Member
Messages
344
So do you think this works similar to something like say the BCG vaccine only externally? Also do you know if anyone has been able to get it prescribed for HHV6?
There's very limited data, but one fundamental difference between the vaccine protocol and SADBE seems to be that in the case of SADBE for HSV-1 & HSV-2 less if definitely more. If you go for more than an application every 3 months it basically looses it effectivity as there seems to be a critical ratio of CD8+ T cells that is important to hit. Whether that would be similary for us or for EBV/HHV-6 is something we don't know.

SADBE is currently opening itself up for investors and are planning an IPO this year to fund Phase 3 trials for HSV-1 and HSV-2. Prescription for HHV6 is not needed as you can purchase this drug fairly easily.
 

vision blue

Senior Member
Messages
1,884
@Judee thanks for bringing this thread to my attention. When im
Less dizzy looks like a must read! Sure hope i don’t decide its perfect only to find i cant get any.

Update: questions for anyone who might now. I have not read the white paper yet

When its used for warts (hpv)), is it also applied on the arm or is it applied right the wart?

So would using poison ivy work?

I need to read the white paper. I thought t cells were specific to the type of invader.

Maybe the reason it stops working is that the initial t cell response to an unknown pathofen is a GENEAL t cell response whereas after its learned to recognizw the invader it becomes a SPECIFIC t cell reponse. So thats why initially, it works on all viruses but then later will onlybwork for the agebt actually applied.

Bummer. Hope thats wrong and will read the white paper in hopes i change my mind. based on this initial reasoninh i wont invest money in in the ipo. Im watching shark tank right bow so inguess id sayb”Im out”’

One also wonders if this will only work for viruses with skin manifestations. So the t cells might have sone signal- invasion vis skin, ramps up all skin defenses until we figure out what this thing is.

Id probablybtry it once. But the whole idea behind it seems important. Perhaps each time apply a different novel invader to get that general t cell response before it learns. Nice at least to have one get out of jail card

More thinking out lous- need to see if works multiple times on warts (and again if applied on thecwart
Warts by the way fascinating. They trick immune system to remain undetected - so perhaps the methodoly generally is a good one for viruses that hide, tho nobe other hides in plsin sight like warts. Visual imagery works a lot better at getting rid of warts than it does for other skin conditions and viruses.

I wobder if overdoing it can lead to autoimmune illness, some of which ate t cell mediated.

I guess I’m way behind on the new treatments and I didn’t know about the other things in the pipeline that people in this thread of mentioned
 
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Hip

Senior Member
Messages
17,905
Quoting the Reddit post:
Why does Squarex advertise SQX770 as an immunotherapy for oral herpes (cold sores)? Will it work for other types of herpes?

Yes, it will work for all types of herpes, because the immune response induced by the immunotherapy is systemic.

That Reddit poster has made a statement that SADBE will work for all the herpesviruses, but I see no evidence for that at all when I Google searched, and the Reddit poster provides no references to support that statement.



SADBE (squaric acid dibutyl ester) is classed as a topical immunosensitiser (aka: topical contact sensitiser, or topical immunotherapy). Topical immunosensitisers have been used since the 1960s.

SADBE seems to work for cutaneous viruses: SADBE is placed topically on the arm, and then has a systemic immune boosting action against viruses like herpes simplex and the skin wart virus (papillomavirus). It is also used to treat alopecia areata (autoimmune hair loss).



But when I performed this Google search on ME/CFS viruses:

coxsackie-virus | echovirus | enterovirus | Epstein-Barr | cytomegalovirus | HHV-6 topical-immunosensitiser | topical-contact-sensitiser | topical-immunotherapy | squaric-acid-dibutyl-ester | SADBE | SQX770

nothing at all came up for ME/CFS viruses such as enterovirus or EBV.


Note however that Dr Pridgen believes fibromyalgia is due to herpes simplex, so possibly SADBE might have some benefits for fibro.
 
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Hipsman

Senior Member
Messages
543
Location
Ukraine
@Hip thank you for pointing that out, yes I'm well aware there is 0 data to show it would work for other viruses. But don't you think there is a good chance SADBE will work for other viruses?
 

Osaca

Senior Member
Messages
344
@Hip thank you for pointing that out, yes I'm well aware there is 0 data to show it would work for other viruses. But don't you think there is a good chance SADBE will work for other viruses?
I don’t know if there’s a good chance, but there’s a non-zero chance. It would be nice if more data was available. As always it isn’t. Currently we only know that T-cells increasing IFN-gamma seems to be the mechanism by which it works against HSV-1 & HSV-2. Whether there’s more going on, or how relevant this is to us, is something we can’t guess. Perhaps we do not need this at all and instead need a different T-cell response, or a B-cell or antibody response? For HSV-1 & HSV-2 higher levels of IFN-gamma seem crucial, for us the situation seems more complicated, our illness is also far more severe.

Unfortunately, things like viral shedding are left unstudied for SADBE. Their trials, even the mechanism of action trial, focuses on studying outbreaks, how that translates to us, local tissue reactivations or similar is something we can’t guess.

Unfortunately, I have hardly come across case reports of people using SADBE that had so much immunomodulatory effects that continuous use was not necessary (that’s mainly because they continue using it because it’s easy, cheap and risk free). IMO that would be a decent observation which would speak for quite a strong immunomodulatory effect, something we might need (but then again things like BCG are also not “strong enough” and require continuous use). It would be interesting to compare how exactly BCG’s immunomodulatory effects compare, unfortunately we can’t get studies there either. BCG shows promise, but it alone doesn’t seem to be enough to conquer MS, unfortunately it also hasn’t received further investigations. One of BCG’s main mechanisms is thought to be based on CD4+ T-cell modulation, whilst SADBE and HSV-1 & HSV-2 seem to be more CD8+ T-cell controlled, but at least it doesn’t seem compeletely different.

Finally there’s even more drugs often prescribed for the same problems with very similar methods of action and possibly even more effective like Imiquimod (Aldara) and Resiquimod (and probably even other ones).

We have probably no option but to experiment with all of these to find out more.
 

Hip

Senior Member
Messages
17,905
@Hip thank you for pointing that out, yes I'm well aware there is 0 data to show it would work for other viruses. But don't you think there is a good chance SADBE will work for other viruses?

I think one would have to read up about the mechanism of action of SADBE to try to figure out if it would work for other viruses. But apparently the mechanism of action is not well understood, so there may only be limited information.

The viruses and conditions that SADBE is known to work for are all cutaneous conditions: cold sores on the skin, warts on the skin, and autoimmune hair loss on the scalp. And of course SADBE itself is applied topically on the skin, although it has a systemic effect.

So I wonder if SADBE only works for skin-based conditions?
 

Forummember9922

Senior Member
Messages
170
Mine is shipping to me now, will update how it goes. Feel like it could go either way. Lets see if my body likes more T cells. Got prescription via instructions on a pinned post in the sadbe subreddit.
Seems like it ups Interferon gamma?
Theres a good bit of reading on the MePedia RE Interferons

When Asking GPT to compose a list of immunomodulatory effects of squaric acid and cross referencing each of those items with how they are altered in CFS, There is nothing really jumping out at me that would make Squaric acid the holy grail. That being said, The results of people with HSV taking squaric acid can be remarkable symptom reduction. And for me, I deal with lingering daily pain from GHSV1 which only began after my cfs onset so yolo.

I tried to get into the current Pritelivir trial but they are extremely picky for their criteria of immunocompromised. If anyone has hsv and is immunocompromised maybe it's worth trying to get into the Pritelivir trial, especially if Valtrex doesn't help.
 
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Osaca

Senior Member
Messages
344
Some new SADBE research: https://www.sciencedirect.com/science/article/pii/S009286742200472X?via=ihub.

This is once again a dermatological result. SADBE is used for the treatment in a mouse model of giant congenital nevi that can progress into invasive melanoma, aka very easily said: SADBE clears lesions causes a major regression of these moles and prevents the development of such melanoma. They showed that the activity of SADBE was mediated by macrophages.

Different to usual they also looked at the effects of applying SADBE directly to the affected area and also went for more frequent dosages (3 times a week vs. once every 2 months for HSV-1/2). They noticed if SADBE was directly applies to the area a depigmentation of those areas took place which was confirmed by measurements of melanocytes and melanin.

When studiying how SADBE could be working in this situation they depleted certain cell types and looked at whether SADBE was still effective. Depletion of CD4+ T cells, NK1.1+ NK cells, CD8+ T cells, and CD19+ B cells didn't have an effect on the efficacy of SADBE, however depletion of macrophages via anti-F4/80 significantly inhibited the ability of SADBE to clear melan-A-positive cells. This led them to conclude that macrophages (CCL2, CCL7) play a role in this process. Furthermore they saw that SADBE attracts both inflammatory and anti-inflammatory macrophages.

Doing a further analysis showed something which has also been seen to be somehow related to ME/CFS and LC in some studies. SADBE increased TNFα signaling via NF-κB.

This is just what I gathered by first glimpsing over this paper, but there seems to be different pathways in different situations for SADBE. Here the removal of moles with direct application on the areas seems to be a very different mechanism to preventing outbreaks of HSV-1/2 via T-cell modulation.

hmwqplb9llab1.jpg