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Bing505z
04-27-2015, 07:22 AM
Kineta, University of Groningen Present New, Positive Data for Dalazatide in ANCA Vasculitis, an Orphan Disease

Press Release: Kineta, Inc. – Tue, Apr 21, 2015 10:00 BST

LONDON--(BUSINESSWIRE)--
Dalazatide demonstrates targeted activity in multi-organ autoimmune disease that spares general immune response
Kineta, Inc., a biotechnology company focused on the development of immune modulating drugs for critical diseases, and researchers from the University of Groningen, Netherlands, announced new data from a study that showed dalazatide (formerly ShK-186) is effective in immunomodulating the cells causing inflammation and damage of small blood vessels in various organs in samples from patients with Granulomatosis with Polyangiitis (GPA). ANCA-associated vasculitis illnesses such as GPA are rare autoimmune diseases but can be severe, affect multiple organ systems and lead to kidney failure and lung hemorrhage. In the US, vasculitis diseases account for 300,000 hospitalizations each year and are associated with significant morbidity and mortality. The data were presented at the 17th International ANCA and Vasculitis Workshop in London by Kineta collaborators Lucas L. Lintermans and Dr. Wayel H. Abdulahad.
The collaboration between Kineta and the University of Groningen was based on earlier published research by Dr. Abdulahad showing that during flares of disease, GPA patients had elevated numbers of effector memory T cells in their urine. “A key question was whether these effector memory T cells expressed high levels of Kv1.3 and could be functionally blocked by dalazatide,” stated Dr. Ernesto J. Muñoz, Associate Director of Translational Immunology at Kineta.
In today’s study data, funded by the Dutch Arthritis Foundation, circulating mononuclear cells were isolated from the blood of GPA patients and from healthy volunteers. The cells were treated in culture with dalazatide which is a selective Kv1.3 channel blocker. Results showed that the T cells from GPA patients made higher levels of inflammatory cytokines upon in vitro stimulation, and these inflammatory cytokines were lowered in the presence of dalazatide. Cytokines are the “communicators” and activators in the body’s immune system.
“Treatment with dalazatide caused the patient T cells to reduce their production of inflammatory cytokines including IL-7A, IFN gamma and TNF alpha to the levels observed in the healthy volunteer’s cells. Importantly, the cells that showed this reduction were only the effector memory T cells while naïve and central memory T cells were not affected,” said Lintermans, the PhD candidate performing the studies. This suggests that dalazatide may suppress the cells causing vascular inflammation in GPA patients without impairing the ability of patients to fight infections.
“Validation of Kv1.3 as a target for ANCA* vasculitis lends a rationale for exploring the therapeutic scope of dalazatide in other autoimmune diseases that affect the kidney, including most notably, lupus nephritis,” concluded Dr. Abdulahad, principal investigator of the study.
Previous research has also shown that systemic administration of dalazatide is effective in preventing disease in models of psoriasis, multiple sclerosis, rheumatoid arthritis and autoimmune kidney diseases, among others. Dalazatide is also currently being tested in a proof of concept Phase 1B clinical trial in psoriasis patients. Data is expected in the second quarter of 2015.
About dalazatide
Dalazatide (formerly ShK-186) has a novel mechanism of action (MOA). Preclinical data have shown that dalazatide is a selective and potent blocker of the voltage-gated Kv1.3 potassium channel, which is a key channel in the activation of effector-memory T cells. Effector memory T cells are implicated in the pathology of many autoimmune diseases. Dalazatide was the first Kv1.3 specific inhibitor advanced into human clinical trials. Dalazatide is also being studied as a potential therapy in other autoimmune diseases, including multiple sclerosis, lupus, type 1 diabetes, inflammatory bowel diseases and autoimmune eye diseases. The lupus, multiple sclerosis, and inflammatory bowel disease research is being conducted in conjunction with the Alliance for Children’s Therapeutics, a drug development and funding collaboration between Kineta and Seattle Children’s Research Institute. *(ANCA) anti-neutrophil cytoplasmic antibodies
Kineta, Inc. is a Seattle-based privately held biotechnology company specializing in clinical advancement of novel drug candidates derived from leading edge scientific research. Our world-class scientists are pioneers in developing life-changing classes of new drugs designed to be more effective and safer than current medicines. Kineta seeks to improve the lives of millions of people suffering from autoimmune and viral diseases and from severe pain. Our progressive business model focuses on targeting unmet medical needs and rapid achievement of important clinical milestones. For more information on Kineta, Inc. visit our website, www.Kinetabio.com (http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.Kinetabio.com&esheet=51083541&newsitemid=20150421005107&lan=en-US&anchor=www.Kinetabio.com&index=1&md5=56fc87f78a2a76f5f7786355d7d8fa60)
NOTICE: This document contains certain forward-looking statements, including without limitation statements regarding Kineta’s plans for clinical studies and regulatory filings. You are cautioned that such forward-looking statements are not guarantees of future performance and involve risks and uncertainties inherent in Kineta’s business which could significantly affect expected results, including without limitation progress of drug development, ability to raise capital to fund drug development, clinical testing and regulatory approval, developments in raw material and personnel costs, and legislative, fiscal, and other regulatory measures. All forward-looking statements are qualified in their entirety by this cautionary statement, and Kineta undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.
ContactKineta, Inc.
Dan Eramian, 206-518-5566
[email protected]



link:

https://uk.finance.yahoo.com/news/kineta-university-groningen-present-positive-090000461.html

Pete
04-27-2015, 09:25 AM
If I understand this correctly and put it in simple terms, this drug is a combination replacing prednisone and immunosuppressants.

Debbie C
04-27-2015, 11:26 AM
I didn't read the whole article but the side effects sounds worse than the drugs we take now

Debbie C
04-27-2015, 11:37 AM
I read it wrong at first,so after re-reading it sounds promising but it will probably be years till its on the market

vdub
04-27-2015, 11:51 AM
HA! I was reading down through the messages and I saw Deb's first message, so I went back up to re-read and see what I missed... :-) I should have kept reading to her 2nd message....

I went to the manufacturer's website (Kineta® :: Autoimmune Disease (http://www.kinetabio.com/autoimmunediseases.html)) where they discuss the drug. It appears to be a pretty broad drug to be used against a lot of auto-immune diseases. Maybe AnneKat can run up to Seattle and talk to them. :-)

JeanMarie
04-28-2015, 12:30 AM
Probably a long time coming but no harm done in keeping my fingers & toes crossed!! Thanks for posting this.

morningsunshine
04-28-2015, 12:55 AM
Interesting!! Thank you for the post. I'll add "dalazatide" to my news alerts.

annekat
04-28-2015, 01:17 AM
HA! I was reading down through the messages and I saw Deb's first message, so I went back up to re-read and see what I missed... :-) I should have kept reading to her 2nd message....

I went to the manufacturer's website (Kineta® :: Autoimmune Disease (http://www.kinetabio.com/autoimmunediseases.html)) where they discuss the drug. It appears to be a pretty broad drug to be used against a lot of auto-immune diseases. Maybe AnneKat can run up to Seattle and talk to them. :-) Nope, vdub, I'm not one for running up to Seattle, or anywhere. Maybe Kirk (me2) can hobnob with his docs at UW about it... there is a link on the site about an "alliance" between UW and Kineta, to collaborate on and further the research and development of this kind of stuff. If this turns out to be a breakthrough, it would sure be exciting for it to be happening in our own backyard, let alone that it could help so many. It's a shame that if these things are valuable, they take so long to get approved and put into use.

kaysee
04-28-2015, 01:44 AM
Interesting article. Some of my ancestors are from Groninger, Netherlands which made if even more interesting for me. This drug could put a lot of other drugs that we use now out of the market. I would like to know if there are side effects.

drz
04-28-2015, 10:33 AM
I like the concept of a drug that might help a variety of autoimmune diseases. This should fit nicely into Marta's idea of finding the common thread. And this might be part of the "cure".

me2
04-28-2015, 11:03 AM
My scientist/doc at the University of Washington told me about ten years ago that things were headed in this direction.
I hadn't seen any progress until now. I only see him about once a year now but when I do I'll ask him about this.

Bing505z
04-28-2015, 11:25 AM
My scientist/doc at the University of Washington told me about ten years ago that things were headed in this direction.
I hadn't seen any progress until now. I only see him about once a year now but when I do I'll ask him about this.


Definitely in the right direction, from another thread: " Don't stop researching (http://www.wegeners-granulomatosis.com/forum/general-wg-chat/4796-don-t-stop-researching-2.html) " posted by member BookNut -

Member pwc51 posted the following on 4-20-2015:

"I went to the Vasculitis UK Patient Symposium in London yesterday. A full on day with 18 world experts presenting. One of the presenters was Dr Peter Merkel from the US who gave an overview of the research going on. He listed many many items and stressed that there has never been more Vasculitis research going on than today!! It seems there are potentially some interesting new drugs in the pipeline. When the slide decks are published I will see if I can get some of the relevant data to this site. What surprised me was the fact that in some cases the drug companies are now 'sponsoring' some of the research - exciting times! "



I would love to see the material from that Symposium!

me2
04-28-2015, 08:56 PM
I wrote an email to the UK Vasculitis people about this great symposium they had to see if there were videos available from it like there are from symposiums here in the US. I got a very nice and prompt response. Here is what it was in part:
Hello Kirk


Yes, I believe the Patient Symposium was a great success. The whole event was video's under the auspicious of the Vasculitis Foundation in the US. Therefore, I am sure that once the editing has been done it will be available through the VF on some media, or will be available from Vasculitis UK - although the exact mechanisms have yet to be agreed.


So watch this space. I will copy this to John Mills and I'm sure that when it is available it will be advertised widely on the various vasculitis social media group sites.


I also believe that there will be a special Symposium V-UK Newsletter later in the year and, if so, this will be available to read on the V-UK website.

(Me2 again- so, it looks like we will be able watch this some time in the not too distant future. I know it takes a little while after symposiums for the VF to get a video ready. As soon as any of us hear about it being available lets start a thread on it. I have been to a few of these symposiums and they are extremely well done and full of valuable cutting edge information for us weggies.

Thanks Bing505z for pushing some interest in this)

kaysee
04-29-2015, 08:11 AM
I wrote an email to the UK Vasculitis people about this great symposium they had to see if there were videos available from it like there are from symposiums here in the US. I got a very nice and prompt response. Here is what it was in part:
Hello Kirk


Yes, I believe the Patient Symposium was a great success. The whole event was video's under the auspicious of the Vasculitis Foundation in the US. Therefore, I am sure that once the editing has been done it will be available through the VF on some media, or will be available from Vasculitis UK - although the exact mechanisms have yet to be agreed.


So watch this space. I will copy this to John Mills and I'm sure that when it is available it will be advertised widely on the various vasculitis social media group sites.


I also believe that there will be a special Symposium V-UK Newsletter later in the year and, if so, this will be available to read on the V-UK website.

(Me2 again- so, it looks like we will be able watch this some time in the not too distant future. I know it takes a little while after symposiums for the VF to get a video ready. As soon as any of us hear about it being available lets start a thread on it. I have been to a few of these symposiums and they are extremely well done and full of valuable cutting edge information for us weggies.

Thanks Bing505z for pushing some interest in this)

So please let the rest of us know when anyone notices these videos are posted. Thanks everyone.

Rini
04-29-2015, 04:05 PM
Science! I am very excited about the idea of medications in the future. It would be very nice to have a one thing helps all. This just screams payday for someone. My bets are still on the genetic nano technology guys but this is good evidence that chemistry could really be the answer :D

Debbie C
04-30-2015, 01:15 PM
HA! I was reading down through the messages and I saw Deb's first message, so I went back up to re-read and see what I missed... :-) I should have kept reading to her 2nd message....
LOL,,,Sorry vdub to make you reread that again,that will teach you to listen to everything I say !!!!!!!!!!!!!!

morningsunshine
05-01-2015, 01:25 AM
If anyone wants to read more about Dalazatide, I found this great overview:

Marine Drugs | Free Full-Text | Development of Highly Selective Kv1.3-Blocking Peptides Based on the Sea Anemone Peptide ShK | HTML (http://www.mdpi.com/1660-3397/13/1/529/htm)

Some tidbits I found interesting:

-The phylum Cnidaria includes some of the most venomous animals on our planet. Within this phylum, the Anthozoa class are found in both fresh water (hydroids) and salt water (sea anemones, jellyfish and corals) environments [1,2]. Most of these animals possess unique stinging cells known as cnidoblasts, which function like hypodermic needles, delivering a potent venom cocktail that helps to both immobilize prey and deter predation. As chromatographic separation methods have improved over the past several decades, the venom components from many of these species have been isolated and studied. The venom of the Caribbean sun anemone, Stichodactyla helianthus, contains, among other components, large cytolytic proteins and numerous ion channel blocking peptides

-medical reports of people with autoimmune diseases documented amelioration of their symptoms following scorpion envenomation, prompting interest in understanding the cause of this effect


Rituximab is made from Chinese hamster ovaries...now on to Dalazatide from Caribbean Sun Anenomes! It's amazing that there are researchers out there looking into such specific things. And of course, I'm grateful for the animals that are being studied!

What's interesting to me is that it seems this works more on the T cells, wheras Rituxan works on the B cells. My nephrologist mentioned that there are multiple pathways in the immune system through which Wegener's works, not just the B cells, which is why sometimes people can flare even when their B cells are depleted after a course of RTX. I wonder if T cells are another pathway that is being studied?

I always have more questions about this diesease and am interested in continuing to follow the research. @me2, please let us know when the videos from the UK symposium are posted!

me2
05-06-2015, 01:01 PM
From today: http://www.kinetabio.com/press_releases/PressRelease20150505_dalazatide.pdf

I see my Rheumy tomorrow. I will ask him about this. It doesn't sound like it is being studied specifically for WG but in my experience it could be applied relatively soon. I remember when Rituxan was just experimental.

While I am in Seattle I will stop by Kineta and see if there is anything good in their dumpster. That's my level of science

annekat
05-06-2015, 01:27 PM
Awesome, Kirk. They did mention ANCA Vasculitis although it wasn't in the specific studies discussed. Will be interested to see what your doc has to say.

me2
05-06-2015, 02:03 PM
My neighbor with MS sent me the local TV story link--
Targeted therapy has the potential for fewer side-effects (http://www.king5.com/story/news/health/2015/05/05/kineta-autoimmune-dalazatide-psoriasis-lupus/26941989/)

vdub
05-06-2015, 02:49 PM
It would be really neat to run by the company and be able to talk to someone about it. A single broad-based product with fewer side-effects would be real nice. I also notice that juvenile diabetes melitus was on the list. My son has that.

Geoff
05-06-2015, 09:03 PM
THese articles are very uplifting and give me huge confidence that a possible cure/treatment is going to be announced before too long. Great thread and many thanks to all the contributers! :thumbup:

annekat
05-07-2015, 01:29 AM
I love this! If they do a clinical trial on WG patients, sign me up! Too bad these things take so long to come into general use. Meanwhile, maybe we should all move to the Caribbean and start harvesting sea anemones! :wink1:

me2
05-08-2015, 04:25 AM
Will be interested to see what your doc has to say.

I saw my Rheumatologist yesterday.
At the end of my appointment I asked my doc if he had heard of dalazatide. He said no. I said it was a new drug being developed. I asked if he knew
Dr Anne Stevens. He looked a little surprised and said "yes".

I said she was involved with the company developing the drug. (I found this on the Kineta web site before going to my appointment)

He said "Well, it can't be the same one because I just saw her yesterday here in Seattle"

I said "Well, I think it IS the same one because she is connected to University of Washington Pediatric Rheumatology and I thought you might know her. Its a Seattle company"

He then took the print out I had brought with me and we looked it over briefly and he helped me to understand some of it. He thanked me for bringing the info.
(with sincerity)
He joked that he should think about buying stock in the company. I replied that the thought had occurred to me too.

It was a productive visit. My doctor is a great guy and a great doctor. I am lucky to have him helping me.

But I think the lesson is to not listen to those who tell you to look only to doctors for advice and direction. Under the best of circumstances they may simply not be informed even if it is with a company in their own town and involving people they see on a daily basis. Don't let anyone accuse you of 'doctoring' simply because you are finding your own information, educating yourself and taking action on your own behalf.

A good doctor , a real doctor, a real friend, will tell you what another doctor at the UW told me many years ago when I was using the internet to bring in information to him. He was for a period of time the Dean of the University of Washington Medical School. He has incredible credentials as a real doctor David Chandler Dale M.D. | UW Medicine (http://www.uwmedicine.org/bios/david-dale)

He told me that no will care about my health as much as I do. He was trying to encourage me to keep doing what I was doing. His point was , as stated in his bio, that he encouraged me to be responsible for my own health and to see him as an advisor. This is not the old school, antiquated model of medicine where people are discouraged and even attacked by other ill-qualified lay people when they take responsibility for their health.

Don't let doctors or anyone else discourage you from seeking your own answers.

annekat
05-08-2015, 05:34 AM
Thanks, Kirk. There is just too much going on in the daily life of even a very good doctor to always be on top of the newest studies and developments. Obviously, Kineta is not directly contacting docs who treat diseases such as ours, because they are a long ways from being able to provide this treatment to everyday patients, if it turns out to be a winner. It is interesting, though, that it was on the mainstream local network news, and I guess your doc was just not watching at the time. I really enjoyed reading about the exchange between you and your doc, and I think he sounds like a really great guy. I like that he won't just shut down a new idea or new info coming from a patient. And the other doc you mention... it sounds like UW in general has some really great ones. I'm impressed.

I agree that we need to keep researching and gathering info on our own behalf, because docs just don't have time, or are too stubborn in some cases, to do it. We still need to be careful out there, as I'm sure there is a lot of misinformation and what some might call 'quackery' that we will run across. It becomes an art to wade through the stuff on the internet, for example, and to learn what sources we can trust the most. Occasionally we will run across sources we are unfamiliar with that may actually be presenting valid information. In those cases, I look for repetition of the same info from other sources, and in the case of studies, look for names of vasculitis experts I've learned about here on the forum. It all can get tricky and we may be misled sometimes, but what else can we do? I think it is just as likely that we will find good information that we haven't seen shared yet.

renidrag
05-09-2015, 10:34 AM
My sister, who has had many many more medical problems than I, gave me the best advice. HMO actually means Maintain your own Health. I have followed that advice. Tonight she is in Mass General recovering from a hernia operation along with many other problems.
Dale

annekat
05-09-2015, 11:29 AM
My sister, who has had many many more medical problems than I, gave me the best advice. HMO actually means Maintain your own Health. I have followed that advice. Tonight she is in Mass General recovering from a hernia operation along with many other problems.
Dale That is good advice, and we can't do it without having access to medical information that relates to our particular cases. Some docs I've had seem reluctant to explain things to me, as if it is something I don't need to know or understand, as long as I'm in their care. I don't buy that one bit. So, thanks to places like this forum and the more reputable internet sites, as well as Facebook groups, we have a fighting chance at being able to understand and articulate what is going on with us and can take steps to care for ourselves when the doc isn't around, which is most of the time.

Dale, I hope for a quick recovery for your sister from her surgery, and that she'll successfully be able to manage her other health issues.

Pete
05-09-2015, 11:48 AM
My sister, who has had many many more medical problems than I, gave me the best advice. HMO actually means Maintain your own Health. I have followed that advice. Tonight she is in Mass General recovering from a hernia operation along with many other problems.
Dale

Hoping she recovers quickly and overcomes the other issues.

me2
05-09-2015, 01:50 PM
Dale,
I hope your sister does well. I had hernia surgery a few years ago and it was a little more painful and longer recovery than I was lead to believe. Plus, no one told me about the horrible side effects of the pain medications. They cause terrible constipation. And since it is muscles around the stomach it becomes a nightmare without proper preperation.

What I should have done was take large doses of senna (a laxative) and dulcolax (a stool softener) right off the bat before things got bad. I have tried this since then before taking pain killers and it makes all the difference. Being loose is NO big deal compared to being sore from surgery and constipated on top of that.

CT01
11-25-2016, 07:05 AM
Hi, I have joined the forum to help a friend suffering from Wegener's. I see that the posts are from April 2015. I am hoping that there has been progress on the mentioned alternate Drug- Dalazatide by now. If anyone has any more information on the drug then please share the same...it will be very big help...Chetna

Bing505z
12-01-2016, 02:40 PM
Hi, I have joined the forum to help a friend suffering from Wegener's. I see that the posts are from April 2015. I am hoping that there has been progress on the mentioned alternate Drug- Dalazatide by now. If anyone has any more information on the drug then please share the same...it will be very big help...Chetna


From what I have seen for 2016, I believe the drug is still in trial. Recent articles list success treating Lupus and Multiple Sclerosis. I have not seen clinical trial results for GPA by Kineta. Here is a link to Kineta:

"Dalazatide is being studied as a potential treatment for multiple autoimmune diseases including lupus, psoriasis, psoriatic arthritis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, type 1 diabetes mellitus, atopic dermatitis, asthma, ANCA vasculitis and autoimmune uveitis."

http://www.kinetabio.com/autoimmunediseases.html

Bing505z
12-01-2016, 03:08 PM
Hi, I have joined the forum to help a friend suffering from Wegener's. I see that the posts are from April 2015. I am hoping that there has been progress on the mentioned alternate Drug- Dalazatide by now. If anyone has any more information on the drug then please share the same...it will be very big help...Chetna

Check this out:

"ChemoCentryx Announces Presentations of Positive Results from Phase II ANCA-Associated Vasculitis Trials (‘CLEAR’ and ‘CLASSIC’) of Orally Administered Complement 5a Receptor Inhibitor CCX168 (‘Avacopan’)"
-- Oral presentation at the American Society of Nephrology (ASN) Kidney Week 2016 to highlight Phase II AAV CLEAR trial results --
-- Oral presentation at the American College of Rheumatology (ACR) 2016 Annual Meeting to highlight Phase II AAV CLASSIC trial results --
MOUNTAIN VIEW, CA, USA I November 07, 2016 I ChemoCentryx, Inc., (CCXI (http://finance.yahoo.com/q?s=ccxi)), today announced oral presentations at two upcoming medical meetings discussing the positive results obtained from the Phase II CLEAR and CLASSIC trials of CCX168 (newly designated ‘avacopan’) in patients with anti-neutrophil cytoplasmic auto-antibody (ANCA) -associated vasculitis (AAV). Avacopan is a potent orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR, and is the lead drug candidate in the Company's orphan and rare disease program.
The current standard of care in AAV uses high doses of chronic glucocorticoids (steroids such as prednisone or prednisolone), which can cause significant safety issues, including premature death. The Phase II CLEAR trial was designed to assess whether avacopan could provide highly effective control of AAV disease while also eliminating the need for steroids. Separately, the Phase II study known as CLASSIC was designed primarily as a safety study to inform eventual labeling requirements for avacopan. As previously reported, the CLEAR and CLASSIC trials both successfully met their objectives.
“The positive results from the CLEAR and CLASSIC trials mark the successful culmination of our Phase II development program with avacopan in AAV. We believe the data show strongly that avacopan, via a novel mechanism for the treatment of AAV, provides rapid and effective control of the disease. Importantly, the data also show that avacopan eliminates the need for chronic high doses of steroids currently used in the standard of care,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “It follows that the robust datasets to be presented at these two upcoming medical meetings support our advancing avacopan into Phase III development, which we are now preparing to do.”


Link: http://pipelinereview.com/index.php/2016111662997/Small-Molecules/ChemoCentryx-Announces-Presentations-of-Positive-Results-from-Phase-II-ANCA-Associated-Vasculitis-Trials-CLEAR-and-CLASSIC-of-Orally-Administered-Complement-5a-Receptor-I.html