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Forest

Phylogica Crispr based peptide vaccine scores top marks on Herpes

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Forest

Thanks Goran123 for your positive feedback. Hopefully Year 2019 will be a positive turning point for all of us. I hope everybody will Be able to keep up with the positive vibe and positive energy. 

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ManagingIllness

CRISPR is not mentioned in any of the articles I am reading. I think the important news is on this page: https://phylogica.com/technologies/intracellular-delivery/

Delivering drugs to infected ganglia neurons is difficult, if not impossible, given current methods. They, along with a few competitors, are developing novel ways to get drugs into cells, and that's big when it comes to "curing" chronic viral infections.

Also, "Phylogica’s tests showed that 75 per cent of mice that received the vaccination had no detectable virus after being infected with the Herpes Simplex Virus (HSV)."https://phylogica.com/wp-content/uploads/2018/12/181206_In-vivo-success-peptide-vaccine_1880059.pdf


 

Quote

The concept is that the CPP delivers the HSV antigen into dendritic cells. The dendritic cells trigger an immune response (production of T-cells) directed specifically towards the antigen expressed on the virus (the same antigen that the CPP delivers to the dendritic cell). The more effective the CPP is in delivering the antigen to the inside of the dendritic cell, the greater the magnitude of immune response through production of a type of T-cell known as a cytotoxic (‘killer’) CD8+ T cell. These T-cells then seek out and kill the virus.

Edited by ManagingIllness

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Forest

Hi ManagingIlleness,

Your insight is very valuable. I totally agree that one of the end goal is to be able to eradicate the latent virus at the root ganglia nodes. That is one crucial dimension of the problem. What is exciting from this company is the multi-dimensional nature of their approach. Not just one dimension. If you look closely on their approach you will notice that they have successfully help eradicate some type of cancer scenarios as per the following article. You will also appreciate the fact that their multidimensional approach may lead to the eradication of shedding by the immune system itself while they partner with other companies to address the latent viruses at the ganglia node level.. This will be a very good achievement for lot of people in the community. It is interesting to see some early success for  some scientists who take a more holistic approach to herpes and cancer. Here is additional insights on their success with cancer.

 Phylogica’s peptide technology effective in development of cancer vaccine

https://smallcaps.com.au/phylogica-peptide-technology-development-cancer-vaccine/

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Forest

I also forget to mention the quality of their investors. Having one of the richest IKEA executive as chairman and shifing the strategic focus of the company from research and development towards effective products with clinical trials, are great news as well. 

Can you imagine if their successful deliver methodology is combined with Excision Therapeutics effective cleaving of latent viruses. Wow...

Not only it will be Elegant science but it will be real, tangible and concrete achievement for all humanity.

This is definitely a positive and impressive news that can help us start to think in terms of “What Ifs”...

Again, thanks for your valuable feedbacks. I am sure some in the community may call them directly to get more insights. This looks like a very open, transparent and communicative company. Let us keep the positive vibe going.

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mcmich

Hi

Not sure if this can cure people already infected. From what I have read your body will not destroy nerve cells that are infected with viruses, rather the body tries to keep the virus dormant or to have the immune system primed to kill virus copies that come out of the cell. Your body will not make new nerve cells, so this is why the body does not destroy nerve cells. 

Anyway, going to e-mail the company to see if they can explain things a bit better.......

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Forest

Hi mcmich,

Your understanding and conclusions are right on target. I also admire the next steps you are initiating to establish direct connection with the company in order to enrich all of us with additional facts. Very well done... I may also look and see if they have a real-time twitter feed.

 

 

 

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ManagingIllness

From what I read, this actually is for irradiation from the cells where HSV resides, hence my early quote about 75% of mice being treated having no HSV detectable.

This is a link to a clear and concise PDF they made describing the therapy: https://phylogica.com/wp-content/uploads/2018/12/181206_In-vivo-success-peptide-vaccine_1880059.pdf

Quote

The concept is that the CPP delivers the HSV antigen into dendritic cells. The dendritic cells trigger an immune response (production of T-cells) directed specifically towards the antigen expressed on the virus (the same antigen that the CPP delivers to the dendritic cell). The more effective the CPP is in delivering the antigen to the inside of the dendritic cell, the greater the magnitude of immune response through production of a type of T-cell known as a cytotoxic (‘killer’) CD8+ T cell. These T-cells then seek out and kill the virus.

 

Edited by ManagingIllness

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Forest

Hi ManagingIlleness

You stated earlier the following “Delivering drugs to infected ganglia neurons is difficult, if not impossible, given current methods. ” 

I have checked to see if this company has been able to build an arsenal to go after the neurons. I am glad to say that they have been one of the first to secure a remarquable patent to enter brain cells and potentially deliver a cargo ie Crispr cargo. This is a clear evidence and I remain confident that through effective partnerships, they can bridge the gap and go after the infected ganglia. 

Phylogica was granted this US patent (US 2014/0141452 A1) for peptides entering brain cells

Delivering cargoes into the brain endothelial cells is a first step towards developing better medicines for neurological conditions of the central nervous system”

https://phylogica.com/wp-content/uploads/2017/10/171004_PYC-Granted-US-Patent-for-Peptides-Entering-Brain-Cells_1722426.pdf

”Discovering and developing medicines that target the brain is significantly impeded by the blood brain barrier, and more specifically, by brain endothelial cells which are resistant to foreign molecules. We have now shown that brain endothelial cells are accessible to Phylogica’s Phylomers and that these peptides could be candidates for delivering drug cargoes into the brain. The brain represents a large market with wide unmet need, which is expected to increase with an ageing population.”

I also checked their tweets and found this video presentation from their CEO articulating their strategic approach to help companies accelerate their clinic trials and FDA approvals.

http://www.finnewsnetwork.com.au/Presentations/Phylogica/PYC_2017_AGM/index.html

 

Edited by Forest

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Cas9

As I understand it;

1. An antigen is a part of a virus that generates an immune response (i.e. antibodies).
2. Dendritic cells are the cells that produce antibodies.

This company is using cell penetrating peptides to insert the hsv antigen/s into the dendritic cells, not the neurons. This causes the dendritic cells to produce a powerful set of antibodies against the hsv virus. Specifically, it produces killer T-Cells.

So it looks like this process is to block the virus from infecting those who have not been infected by killing the virus before it's able to infect the neurons. It doesn't cure those that have already been infected, however, it may be effective in reducing OBs and shedding.

This technology may also have the ability to enter neurons, but for their hsv peptide vaccine, that's not how it's being used.

That's my take. Maybe someone else has a different understanding.

Edited by Cas9

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Gunthersunshine
11 hours ago, Forest said:

I also forget to mention the quality of their investors. Having one of the richest IKEA executive as chairman and shifing the strategic focus of the company from research and development towards effective products with clinical trials, are great news as well. 

Can you imagine if their successful deliver methodology is combined with Excision Therapeutics effective cleaving of latent viruses. Wow...

Not only it will be Elegant science but it will be real, tangible and concrete achievement for all humanity.

This is definitely a positive and impressive news that can help us start to think in terms of “What Ifs”...

Again, thanks for your valuable feedbacks. I am sure some in the community may call them directly to get more insights. This looks like a very open, transparent and communicative company. Let us keep the positive vibe going.

Far out! If an IKEA executive is invested in this hopefully he’ll put it all together very quickly and doesn’t lose the Allen key in the process!

Sorry ... that will be one of my last dad jokes for the year.

Science on all fronts looks promising for 2019!

Hopefully we can all be sitting back this time next year ringing in the new year  either cured ( that’s a very big hope) or very close to one.

Here’s to a good new year. X

Edited by Gunthersunshine

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mcmich

Hi

The CEO already responded to my e-mail. This vaccine has not been tested as a therapeutic vaccine. So CAS9 is correct that this vaccine protects uninfected individuals (or mice in this case). Whether or not it helps people already infected will require further testing and study. Again, just my understanding of the human body (not my field) is that your body never kills neurons,. You need them to talk, move, tell your heart to beat, etc. So once infected, this vaccine will not cure you. It may be helpful to reduce OB's and shedding. It will be at least 2 years before they start any human testing. So, again, 10-15 years if all go well.

Going to do a follow up e-mail to have ask if someone can explain how this peptide vaccine can help intracellularly. Since the viral DNA is integrated into the cell DNA, the only way to remove it is through CAS9/sgRNA. It needs to be cut out of the DNA sequence in the cell.

Edited by mcmich

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mcmich

Response from CEO

"Hi Mark,

 
It's a very complicated area and I don't profess to understand the details even of our own program (fortunately we have team members who do). The short answer to your question in relation to a therapeutic vaccine (ie. vaccine after viral exposure) is that we don't know because we haven't yet tried it - the models we have published to date relate solely to the prophylactic setting (ie. vaccine before viral exposure). The theory of viral clearance, however, remains the same if we can stimulate a sufficiently large immune response. We will assess whether we can achieve this therapeutic objective in 2019.
 
We have additional questions to answer before we can put forward our best shot at developing a cure. For example:
- which adjuvant should we be using;
- which antigens elicit the most effective immune response;
- do we need to a use a targeting moiety for the antigen presenting cells we are seeking to deliver to;
- how frequently do we need to dose etc.
 
With respect to what's going on at the cellular level - again, very complex from my understanding but the immune response captures the virus in two stages (both extracellular movement around the body and intracellularly once it has infected a host cell - see the article below for a good overview):
 
 
On the type of HSV we are modelling, we are using HSV-1 at the minute. Really, though, we are just looking at the ability of our CPPs to elicit the CD4+/CD8+ T-cells (agnostic of indication). The cancer and viral models are both being used for this purpose - the next one we are trialling will be in melanoma but is directed towards a competitive evaluation of the Cell Penetrating Peptide (CPP). 
 
We are about 24 months away from phase I at best but will know more about our strategic direction, lead indication and timelines after we present our data at the Keystone Conference in Vancouver in January.
 
I hope that is helpful and feel free to share with your forum.
 
Kind regards,
 
Rohan

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MikeHerp
9 hours ago, Gunthersunshine said:

Far out! If an IKEA executive is invested in this hopefully he’ll put it all together very quickly and doesn’t lose the Allen key in the process!

Sorry ... that will be one of my last dad jokes for the year.

Science on all fronts looks promising for 2019!

Hopefully we can all be sitting back this time next year ringing in the new year  either cured ( that’s a very big hope) or very close to one.

Here’s to a good new year. X

I kind of doubt we'll be cured by next year.  Their vaccine isn't actually a cure, and it isn't even in clinical trials.  From the sounds of it, they aren't sure if it ever will be.  But if it is, it will be 2 years before they start the process.  Add another 5 top 6 years for phases 1-3.  So best case scenario is 7 to 8 years from now.

Frankly, I doubt this will ever go anywhere.  This is just another obscure company with limited funding.  It's shares are trading on the Australian stock exchange, for 3 cents per share--meaning there's little investor excitement about it.  

It's good that another company is fiddling with the concept.  But, I doubt this will ever get anywhere.  Like RedBioTec which was supposed to have begun trials in early 2018, but instead hasn't even updated its website regarding HSV since 2017.  I'd keep expectations low.  

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MikeHerp

That said, I believe there will be more advances and break throughs in the next few years.  

Pritelivir may have a chance to be approved within 2 to 3 years, which could help.

CRISPR will start to make its way into the clinic, raising the possibility that it will be tried in the not too distant future in the clinic against HSV as well.

There might also be some news about the 2 or 3 vaccines that are still stuck in development.

So stuff is in the works.  I didn't mean to sound discouraging.  

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