Phase I/II therapeutic

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Phase I/II therapeutic

Postby dignan » Mon Nov 08, 2004 11:50 am

This article talks about an early phase MS therapeutic I haven't heard of before, Tovaxin...


PharmaFrontiers Completes Acquisition of Multiple Sclerosis Cell Therapy Developer Opexa Pharmaceuticals Inc.

HOUSTON--(BUSINESS WIRE)--Nov. 8, 2004--Cell therapy developer PharmaFrontiers Corporation (OTCBB:PFTR) has closed its previously announced acquisition of Opexa Pharmaceuticals Inc., a Houston-based developer of cell-based therapeutics for autoimmune diseases, initially targeting multiple sclerosis (MS).

In the all-stock transaction, Opexa shareholders received 2.5 million shares, or approximately 25 percent of PharmaFrontiers' 9,866,838 outstanding shares. PharmaFrontiers was advised in the transaction by Sanders Morris Harris Group Inc.

Opexa's Tovaxin(TM) T-cell therapy is in FDA Phase I/II human dose ranging clinical trials to evaluate its safety and effectiveness in treating MS. Its novel approach to MS therapy is expected to receive "fast track" status from the U.S. Food and Drug Administration.

"As a wholly owned subsidiary of PharmaFrontiers, Opexa will expand our cell therapy technology base and bring in key scientific personnel and existing research that is strongly complementary with PharmaFrontiers' adult stem cell tissue regeneration development program," said PharmaFrontiers CEO David McWilliams. "We believe that stem cell-initiated regeneration of the tissue sheath around nerve fibers bears serious investigation as a logical and potentially effective follow-on to a therapy that stops the nervous system destruction of MS," he added.

Opexa's patented and proprietary technologies are the result of research conducted at Baylor College of Medicine. The approach enables the development of individualized cell therapies that produce an immune response against myelin reactive "pathogenic" T-cells. These T-cells are involved in the cause of MS, facilitating attacks on the myelin insulation that protects nerve fibers in the body's central nervous system. Tovaxin(TM) targets the specific self-reactive T-cell receptor with the goal of avoiding the deleterious side effects of current MS therapies. As a subcutaneously delivered cell therapy, Tovaxin(TM) also potentially offers a competitive therapeutic advantage over the currently available protein-based palliative therapeutics to MS. Opexa is also developing applications of its technology in the diagnosis of MS.

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Postby bromley » Mon Nov 08, 2004 12:12 pm

Dignan,

Good spot. It must be good news for us ms sufferers that there are a number of drugs currently being developed, which hopefully offer better treatments than are currently available.

Today's news on Antegren looks promising - the 66% appears to be much better than the CRABs. Lets hope the results are replicated when it is used outside the trial arrangements. Whatever, it must be good for competition - to stay in this market, the drugs companies now have a new benchmark - the CRAB manufacturers all seemed happy with c.25%. It will be interesting to see how the combined Antegren and Avonex trial does - one of the attractions of Antegren is the once a month infusion - but if the combination works will Avonex have to be self-injected on the current frequency?

Is anyone looking at Antegren plus minocycline? What we really need is a neuro-protector to go with the drugs which reduce attacks.

Aimspro results are due in mid 2005 and Campath results in 2006. Lets hope there's some more good news.

Re-myelination is an area which is currently being examined. But I'm still not clear how this would help if the myelin destructive process is continuing. Anyone have any thoughts on this?

Also - what is being done for PP and SP sufferers?

Bromley
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Postby OddDuck » Mon Nov 08, 2004 12:32 pm

dignan,

From a cursory look, this research these guys are doing sounds more like it!!! I mean, it appears to be a smarter approach (to me anyway). That's what I said earlier somewhere. Isn't it much safer and maybe even better to see about targetting how to increase IL10 (for example). Selective immunotherapy. THAT'S more in line with my thoughts and provides a comfortable "feeling" for me anyway! I'm going to watch these guys! Thanks!! This was a bright spot for me - especially lately!

bromley: Well, that's my personal chagrine about MS research. How little is being done or found yet that might be helpful for progressive MS types. But.....I know they are trying. :(

Deb

EDIT: You know. I looked at these folks a little closer. So far, I really like them! VERY interesting. Notice, also, that on their website, they didn't try to BS you about their clinical trial test results so far. Honest people. They are just starting out, but it looks like their initial approach is one with integrity. (Let's hope it holds up under economic and competitive pressure, of course.) But......so far. I like these guys (and gals)! Level headed approach.
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Sorry to be a spoilsport....

Postby ElanMike » Tue Nov 09, 2004 12:06 pm

PharmaFrontiers Corp. looks like a pump-and-dump scheme. At 12/31/03, the company had no assets. On 9/30/04 they did an unregistered private placement (warning Will Robinson! warning!) that netted them all of $1.5 million. You can look up all of their SEC filings here:

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I know business not science. But even I can tell that these guys have no hope (look at summary of previous results). A lot of these unsavory types in the penny stock world are focusing on biotech these days in the hopes of attracting foolish investors who don't bother to read the full regulatory filings.

The stock is barely traded. But it is up 533% in the last year!! The promoters of this stock will try and get suckers to buy into the stock before selling out their holdings.

Sorry but the only thing to do is ignore this piece of crap.

PS As stated previously, I am an investor in Elan, therefore I am biased. Please confirm all of my information with the links provided to you.

From the website:
http://www.opexapharmaceuticals.com/technologies.htm
Between 1996 and 1998, a T cell vaccination study was conducted at Baylor/Methodist International Multiple Sclerosis Center. In this study, a group of 114 patients with MS were treated with injections of irradiated autologous Myelin Basic Protein (MBP)-reactive T cells. Fifty-four patients completed the study and the results on changes in rate of relapse, Expanded Disability Status Scale (EDSS) and MRI lesion activity over a period of 24 months were analyzed. The study revealed that depletion of MBP-reactive T cells correlated with a prolonged time to progression in both patient groups and a reduction (40%) in rate of relapse in the relapsing-remitting (RR)-MS cohort as compared to the pre-vaccination rate and natural history of MS. However, the reduction in EDSS was minimal in RR-MS patients while the EDSS was slightly increased in secondary progressive (SP)-MS patients over a period of 24 months. Serial semi-quantitative MRI examinations showed no significant change in mean MRI lesion score as compared to baseline MRI. Further investigations to evaluate the treatment efficacy of T cell vaccination in controlled trials are continuing.

Click here to read more about MS research being conducted at the BCM Department of Neurology.

Clinical Trials
TovaxinTM is currently being evaluated at the Baylor/Methodist, Multiple Sclerosis Center in two Phase I/II clinical trials under a sponsor-investigator IND. One trial is a 9 patient dose escalation study designed to further evaluate toxicity, tolerability and clinical efficacy of the vaccine. Patient enrollment for this study began in July 2002.

The second trial is a Phase II open-label, booster-dose study of up to 25 patients who received clinical benefit from TovaxinTM in the previous Phase I/II study of this product, and who are now failing standard treatment for MS. Each patient will receive two treatments with TovaxinTM. This study is designed to further study the safety and tolerability of TovaxinTM in MS patients, to perform preliminary evaluation of the timing of booster doses for subsequent studies, and to evaluate efficacy.
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Postby OddDuck » Tue Nov 09, 2004 12:32 pm

ElanMike,

I'll agree they are small and just now starting out. BUT...........Opexa Pharmaceuticals were formed and provided initial funding by Baylor. Baylor has set up a venture capitalist organization that helps fledgling companies start up.

Yea, it could be that the acquisition of them now is unsavory. That would be a bummer. I did "speculate" whether Opexa could hold up under economic and competitive pressure. I'll have to look further into PharmaFrontiers Corp. As I mentioned, I just did a cursory overview.

The initial research itself, though, was initiated by Baylor and their neurologists. The research itself looks pretty sound. Now, what a company DOES with it from here on out is another thing altogether. And what you posted is exactly what I was referring to. At least they didn't try to BS a person by publishing "glowing" clinical trial results that you know darn well is probably a bunch of crap.

Well.........it'll be interesting to watch, huh?

Deb

EDIT:
A lot of these unsavory types in the penny stock world are focusing on biotech these days in the hopes of attracting foolish investors who don't bother to read the full regulatory filings.


Oh, that reminds me.....did you have the chance to peruse Biogen Idec's SEC's (that I made reference to in another thread?)

SECOND EDIT: Also, (unfortunately?), my opinions that are expressed come from an unbiased position, as I own no stock in anything.
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Tovaxin data shows a 92% reduction in attacks

Postby IHaveMS-com » Fri Oct 14, 2005 7:22 am

Hi to all,

PharmaFrontiers has survived and is entering phase IIb/III trials on Tovaxin. I will paste in below the press release about a 92% reductions in attacks. This data was presented at the International MS conference in Greece in September 2005.

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PharmaFrontiers Presents Positive Tovaxin(TM) Research at International Multiple Sclerosis Meeting
Monday October 3, 5:00 am ET


THE WOODLANDS, Texas--(BUSINESS WIRE)--Oct. 3, 2005--PharmaFrontiers Corp. (OTCBB:PFTR - News), a company involved in the development and commercialization of cell therapies, presented positive interim research findings of its Phase I/II clinical trials of Tovaxin(TM), a novel T cell therapeutic vaccine for Multiple Sclerosis on Friday, September 30, 2005, at the 21st European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the 10th Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) congress held in Thessaloniki, Greece. The trial results not only indicated that the treatment appeared safe and well tolerated with no dose-limiting toxicities, but that Tovaxin depletes the myelin-peptide reactive T cells that may contribute to the Multiple Sclerosis (MS) disease processes.
Tovaxin is a trivalent formulation of attenuated myelin-peptide reactive T cells (MRTCs), which are derived from peripheral blood and produced ex vivo as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) reactive T cells.

The Tovaxin treatment depleted MRTCs in patients with MS. The patients in the trial also had improvements in the Multiple Sclerosis Impact Scale (MSIS), which measures subjective physical and psychological parameters, and the Kurtzke Expanded Disability Status Scale (EDSS), which is an objective measure of the patient's physical disability.

"Seeing safety, tolerance and early effectiveness data at this stage of development is gratifying. More important is seeing the lowering of the MRTCs and the improvement in the clinical measures that reaffirms our belief that Tovaxin may be the key to treating patients who are in the earlier stages of MS," said David B. McWilliams, chief executive officer of PharmaFrontiers. "Based on mounting evidence from our research and others, we believe that autoimmune mechanisms directed at myelin tissue of the central nervous system may play a major role in causing MS.

"With our clinical development partner, INC Research, Raleigh, NC, we plan to initiate a follow-on Phase IIb clinical study of clinically isolated syndrome and early relapsing-remitting MS patients by the first quarter of 2006 to advance our understanding of this novel T cell therapeutic vaccine for MS," said McWilliams.

MRTCs play a critical role in the pathogenesis of MS. Previous T cell therapy pilot studies used a monovalent formulation of attenuated MRTCs to deplete MBP reactive T cells. Because several myelin antigens are described as potential autoantigens for MS, depletion of MRTCs using a trivalent formulation may have enhanced therapeutic effects.

The dose escalation study was designed for patients with relapsing-remitting or secondary-progressive MS, intolerant of, or having failed, current therapy. Blood was obtained from each patient from which T cells reactive to two peptides each of three proteins (MBP, PLP, and MOG) were expanded ex vivo and prepared as a trivalent formulation of MRTCs. The MRTCs were attenuated by Cesium137 irradiation prior to patients receiving subcutaneous injections of either 6-9 million cells (Dose 1) or 30-45 million cells (Dose 2) at weeks 0, 4, 12 and 20. MRTC frequencies were performed at baseline and weeks 5, 13, 21, 28 and 52. Patients were evaluated for changes in EDSS, MSIS and exacerbations.

"Tovaxin is a patient-specific therapeutic vaccination strategy for MS patients. To formulate Tovaxin T cell vaccine, the patient's own myelin peptide-specific activated T cell lines are harvested and attenuated on the day of vaccine administration," said Jim C. Williams, Ph.D., PharmaFrontiers chief operating officer and co-author of the study who presented at the meeting. "The shelf-life of the final product is approximately three days."

The study's results demonstrated that MRTCs in the peripheral blood were depleted in a dose dependent manner and analyses showed reductions in all three types of MRTCs at all follow-up visits. All patients in the Dose 2 group had a 100% reduction in MRTC counts at the week five follow-up visit. Percentage reductions were greater in the Dose 2 group than in the Dose 1 group at every follow-up visit. Correlation between the reduction in overall MRTC frequencies and the physical component of the MSIS (p=0.0086) was strong. There was a trend to improved EDSS (p=0.0561). The annual relapse rate (ARR) for the patients prior two years before therapy was 1.28 and following therapy the ARR was 0.10 (92 percent reduction) adjusted for the number of months in the study. The treatment appears to be safe and well tolerated with minimal adverse events and no dose-limiting toxicities.

"If myelin autoreactive T cells are the basis for MS, then we now appear to have a precision guided treatment to seek out and selectively suppress these T cells," said Brian D. Loftus, M.D., director of Neurology Research at the Diagnostic Clinic of Houston, principal investigator for PharmaFrontiers' two current Phase I/II clinical trials of Tovaxin, and co-author of the study who also presented at the meeting.

The presentation, "Autologous T Cell Therapy in Multiple Sclerosis: An Open Label Safety and Dose Range Study," is authored by Dr. Loftus, Mitzi Montgomery, DVM, Ph.D., PharmaFrontiers vice president of Preclinical Development, and Dr. Williams.

Previous studies of T cell vaccination conducted by Jingwu Zhang, M.D., Ph.D., director of Research, Baylor Multiple Sclerosis Center at The Methodist Hospital, and colleagues have shown that a monovalent (MBP selected MRTCs) formulation was safe and potentially beneficial in relapsing-remitting and secondary-progressive patients.

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21st Congress of the European Committee for the Treatment and Research in Multiple Sclerosis
10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis
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Therapy - immunomodulation - Part II
Friday, September 30, 2005, 15:30 - 17:00
Autologous T cell therapy in multiple sclerosis: an open-label safety and dose-range study
B. Loftus, M. Montgomery, J. Williams (The Woodlands, USA)

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Objective: To evaluate the safety of a trivalent autologous T cell therapy (TCT) (Tovaxin™) and the effective dose to deplete myelin peptide-reactive T cells (MRTCs) in Multiple Sclerosis. Background: MRTCs play a critical role in the pathogenesis of MS. Previous TCT pilot studies used a monovalent formulation of attenuated MRTCs to deplete myelin basic protein (MBP) reactive T cells. Because several myelin antigens are described as potential autoantigens for MS, depletion of MRTCs using a trivalent formulation (TF) may have enhanced therapeutic effects.
Design/Methods: Patients with relapsing remitting- or secondary progressive-MS intolerant of or having failed current therapy donated blood from which T cells reactive to two peptides each of three proteins [MBP, proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG)] were expanded ex vivo and prepared as a TF of CD4+ and CD8+ MRTCs. The MRTCs were attenuated by Cesium137 irradiation prior to patients receiving subcutaneous injections of either 6-9 million cells (dose 1) or 30-45 million cells (dose 2) at weeks 0, 4, 12 and 20. MRTC frequencies were performed at baseline and weeks 5, 13, 21, 28 and 52. Patients were evaluated for changes in Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS) and exacerbations.
Results: MRTCs in the peripheral blood were depleted in a dose dependent manner and analyses showed reductions in all 3 types of MRTCs at all follow-up visits. All patients in the dose 2 group had a 100% reduction in MRTC counts at the week 5 follow-up visit. Percentage reductions were greater in the dose 2 group than in the dose 1 group at every follow-up visit. Correlation between the reduction in overall MRTC frequencies and the physical component of the MSIS (p=0.0086) was strong. There was a trend to improved EDSS (p=0.0561). One exacerbation was observed in the dose 1 group. The treatment appears to be safe and well tolerated with minimal adverse events and no dose-limiting toxicities.
Conclusion: MRTCs in patients with MS can be depleted by Tovaxin treatment. MSIS and EDSS clinical measures are improved and the treatment appears safe and well tolerated. A Phase IIb double-blind placebo-controlled trial to study the effects of Tovaxin in treatment of early relapsing MS patients is being planned.
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Some information about me and the current study.
I am in the FDA trial for Tovaxin, an MS vaccine. The vaccine appears to have arrested my disease and has done the same for the other people in the study. I have two small websites that show a timeline of events. The first one is http://www.ihavems.com It starts with the first injection and goes for 18 months. My websites are little 10-page boilerplate sites, so my timeline continues on a second website http://www.timswellness.com from June 2004 to the present.

I have a thread "Tovaxin new MS vaccine" going on Montel's Corner. http://www.spotlighthealth.com/common/f ... ?m=2&sb=12 In it, I discuss being in an FDA trial for Tovaxin, which is a vaccine that targets and eliminates the myelin reactive T-cell that cause MS.

I am actually out doing things again. I just returned from a solo trip to see some friends in San Francisco. This is amazing, since two years ago, my parents were taking me from our home in Michigan to Houston in a wheelchair.

Tovaxin is an autologous vaccine. That means they take some of my blood, cull out the T-cells and introduce them to human myelin. Those that react to the myelin are culled out and replicated. Once there are enough for the vaccine, about 45 million cells, the T-cells are irradiated so that they are still alive, but cannot reproduce. That is the vaccine.

The vaccine is injected just under my skin, you can see some pictures at http://www.timswellness.com , and the body treats these T-cells as a foreign invader and makes antibodies to eliminate only these specific T-cells. These antibodies not only take out the T-cells from the vaccine, but also eliminate all of that same type of T-cell throughout my body.

The body produces 2 to 3 trillion red blood cells per day. I am not sure how many T-cells are produced per day, but if 1 or 2 per million are troublemakers, that means there are hundreds of millions of myelin reactive T-cells floating around in the blood stream of someone with MS. A flare is when the body produces too many of these bad T-cells. No one is sure why this happens, but it may be caused by an upper respiratory infection, or a cold sore, or some other immune response that triggers the body to produce T-cells that mistake myelin as something bad.

By eliminating these 1 or 2 per 1 million T-cells does not compromise the immune system, but it does eliminate all of the T-cells that destroy the myelin. No bad T-cells means no more attacks. Anyone on Tovaxin will need to get a booster twice a year to keep the antibodies at a level sufficient to continue to eliminate all of the myelin reactive T-cells as they are produced. This is just like a flu shot. The company has a nice animation of how Tovaxin works at http://www.pharmafrontierscorp.com/toxavin.php

I think about 30 to 40% of the damage that was done by the attacks has been reversed. The body will repair itself, as long as the attacks stop. I am helping myself by doing a lot of exercising and activities that improve my small motor skills.

I am doing many things that I was no longer able to do. When I started the vaccine, my parent's were cutting my food and feeding it to me. I am able to cut my own food, and today, I peeled some shrimp. Realizing that I can again do something as insignificant as peel a shrimp really makes me feel good. I used to wonder why people got so excited to see a disabled family member regain some little ability, now I understand, and I understand why my family is trilled at even my smallest improvement.


PharmaFrontiers was asked to be a presenter at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Thessaloniki Greece. I will paste in the press release and the poster session from Greece. It showed a 92% decrease in attacks compared to the CRAB drugs 33% and a decrease in disability where the CRAB drugs have none. The company hopes to start phase IIb/III trials at the end of this year. Enrollment will start in Texas and at the other sites (I don't know where) after the first of the year.

The company is PharmaFrontiers and the company website is http://www.pharmafrontierscorp.com/ The principal investigator for the current studies is Dr. Brian Loftus BLoftus@diagnosticclinic.com The study is posted on his website http://www.loftusmd.com/Articles/MS/Tce ... eRRMS.html

To get on the list for the next trial of Tovaxin, the best person to email is Shannon Inman sinman@pharmafrontierscorp.com . She works for the company and is keeping a file of interested people. There will be sites throughout the US and some in Canada. There may be some outside of North America.

Best regards, Tim
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