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Opexa Provides Additional Promising Data Including Statistically Significant Reduction in Disability With Tovaxin® for the Treatment of Multiple Sclerosis

Tovaxin Also Demonstrates Reduction in Relapse Risk and Myelin T-cell Reactivity in Patients With More Active Disease

THE WOODLANDS, Texas--(BUSINESS WIRE)--Opexa Therapeutics, Inc. (NASDAQ:OPXA), a company dedicated to the development of patient-specific cellular therapies for the treatment of autoimmune diseases such as multiple sclerosis (MS) and diabetes, today announced additional positive data from the company’s Phase IIb TERMS clinical trial (Tovaxin® for Early Relapsing Multiple Sclerosis). The latest analysis focused on a prospective group of patients (n=50) with an annualized relapse rate (ARR) of greater than 1 at study entry which is comparable to ARR baselines of patients in previous Tovaxin studies. These findings demonstrate a statistically significant improvement in disability as measured by the Expanded Disability Status Scale (EDSS) (p=0.045) for patients treated with Tovaxin as compared to those receiving placebo. In this group, 28.1 percent of patients treated with Tovaxin showed an improvement in EDSS as compared to only 5.6 percent in the placebo group. Additionally, there was an 88 percent reduction in the level of brain atrophy and a more than 20 percent reduction in the number of gadolinium (Gd) lesions progressing to black holes in the Tovaxin group, which may suggest a beneficial neuroprotective effect. Overall, the analysis shows that patients treated with Tovaxin demonstrated a benefit across all clinical and magnetic resonance imaging (MRI) endpoints (primary, secondary and tertiary) in this patient population. Immunology data also appears to support Tovaxin’s mechanism of action, indicating that patients with less myelin T-cell reactivity have a lower risk of relapse. Additional quality of life measurements, such as the Timed 25 foot Walk, also showed a benefit for Tovaxin over placebo (0.14 vs. -0.02, as measured by respective Z scores).

The data shows that these patients when treated with Tovaxin demonstrate an ARR of 0.28 which represents a 55 percent reduction compared to those patients on placebo. This relapse rate is on par with the lowest relapse rates observed with currently available MS treatments which range from 0.2 to 0.9. Study findings also show Tovaxin possesses an impressive safety and tolerability profile. Opexa expects to conduct a Phase II close-out meeting with the United States Food and Drug Administration during the first half of 2009 to discuss next steps for the further clinical development of Tovaxin. Opexa is actively engaged in discussions with potential strategic partners for the Tovaxin program.

The TERMS study provided Opexa the opportunity to create a comprehensive database of clinical immunology and epitope data in MS patients that may significantly advance the understanding and treatment of the disease. This type of information is particularly important for Opexa as Tovaxin’s dual mechanism of action involves the depletion of myelin-reactive T-cells in the peripheral blood and the regulation of anti-inflammatory T-cells to rebalance an MS patient’s immune system. Previous studies show that if the myelin-peptide reactivity in a patient’s peripheral blood is reduced, the clinical symptoms associated with MS will also be reduced. The initial analysis of the study’s immunology and epitope database has shown that patients treated with Tovaxin appeared to have less myelin-peptide reactivity over the course of the study than those on placebo. This was measured using Opexa’s proprietary Epitope Analysis Assay (EAA) which assessed reactivity across all three key myelin proteins at several time points throughout the 52-week study. Additionally, over the full course of treatment, more patients on Tovaxin remained in the lower quartile of peptide reactivity (56 percent) than those on placebo (39 percent). This epitope data appears to correlate with the study’s MRI and clinical endpoints which, among other findings, showed that following the full course of treatment (weeks 28-52), the ARR in the Tovaxin group dropped to 0.065 (0.749 for placebo).

The pattern emerging from the analysis of the immunology and epitope database suggests that those patients exhibiting a higher T-cell reactivity often demonstrated a worsening of at least one MRI endpoint (Gd lesion, Gd volume, new T2 count or progression to black holes) and one clinical endpoint (either relapse or EDSS). The converse also appears true with less T-cell reactivity implying less or no worsening of certain MRI and clinical endpoints.

Additionally, the immunology data shows that reactivity to all three of the key myelin proteins (MOG, PLP and MBP) was broadly present in study patients, which may be an important finding for the future treatment of MS. Opexa is also assessing which specific peptides from each of the proteins may provide the most relevant targets for the company to enhance its manufacturing process and further strengthen its intellectual property portfolio.

“Tovaxin seems to be demonstrating a benefit to these patients as indicated by immunology, MRI and clinical parameters,” stated Dr. Clyde Markowitz, associate professor of neurology and director of the MS center at the University of Pennsylvania School of Medicine. “This is interesting data and additional trials are certainly warranted to further explore the potential of this novel treatment.”

Previously reported top-line results from the TERMS study demonstrated that Tovaxin was safe and well tolerated with no serious adverse events related to treatment. The most common adverse event related to Tovaxin was mild injection site reaction. Continued analysis of safety and tolerability data has confirmed these top-line results with no serious adverse events observed in any Tovaxin-treated patients during the entire study.

“This landmark first-in-class study has yielded impressive results for Tovaxin in MS patients with high disease burden, including a marked reduction in disability, relapse risk and levels of T-cell reactivity. These findings are very encouraging and we are eager to continue the clinical development of this novel therapeutic,” commented Neil K. Warma, president and chief executive officer of Opexa Therapeutics. “There remains a tremendous unmet medical need for MS patients, and we believe a safe and effective patient-specific treatment may generate considerable interest among regulatory authorities, patients, physicians and potential strategic partners. With this in mind, we remain committed to aggressively pursuing our two primary objectives: the continued development of Tovaxin towards a pivotal Phase III trial and a high-value partnership for the Tovaxin program. With the MS market exceeding $6 billion and growing, we believe Tovaxin is very competitively positioned from a safety, efficacy and patient compliance perspective.”

Webcast [link] of their Third Quarter Results conference call. 

My summary, so take it for what it's worth.

Highlights from their further analysis of Phase IIb Data
• Number of enhancing lesions in Tovaxin arm was more than twice that of the placebo group at study initiation. 
• Made it difficult to achieve statistical significance on primary and secondary endpoints
• Annualized Relapse Rate (ARR) shown is 0.21, which is on the lowest end of all available drugs which range from 0.2 to 0.9, and consistent with prior Tovaxin results.
• Designed study to include many patients with >1 ARR to match earlier Tovaxin studies, where they appeared to have a better response to treatment. Wanted to be able to compare data.
• Focus on sub-group of 50 patients who have an ARR greater than 1.0. Cannot show statistical significance with this group but there are encouraging, non-random results.

◦ Topline data from IIb showed this group to have the largest reduction in relapse rate at .55 reduction in relapses per year across the whole study.
◦ Analyzed clinical, MRI and immunology data to see if there is correlation in this data.
◦ Clinical: 

▪ Most significant new data-Patients demonstrated a statistically significant improvement in disability on EDSS scores. P-value of 0.045. 28.1% of patients on Tovaxin showed improvement in EDSS vs. 5.6% in placebo group.
▪ Combined with an ARR of 0.28 in this patient population shows a strong clinical benefit.
▪ On timed 25' walk quality of life measurement, Tovaxin showed 0.14 vs. -0.02 for placebo. Reflective of fatigue benefitting Tovaxin.
▪ Because it is a small sub-group, they do not believe they will be able to show statistical significance with this sub-group, but because all measurements appear to favor Tovaxin, it suggests the results are not random and favor a strong and positive trend.

◦ Radiological: 

▪ Analysis showed that patients on Tovaxin showed improvement on all primary, secondary, and tertiary endpoints.
▪ Primary endpoint of cumulative number of enhancing lesions-24% improvement over placebo
▪ Secondary endpoint of cumulative number of new enhancing lesions-22% improvement.
▪ Tertiary endpoint of brain reduction. Tovaxin showed 88% reduction (improvement) in brain atrophy vs. placebo (-0.04 Tovaxin vs. -0.32 placebo), which could indicate a further neuro-protective effect of Tovaxin. Being investigated and will work with Myelin Research Foundation to assess.
▪ Looked at number of Gad enhancing lesions that progressed to black holes. >20% reduction in number that progressed.
▪ 60% greater improvement in absolute change in T2 lesions volume.

◦ Superb safety profile. No serious adverse events associated with Tovaxin treatment, which includes all 150 patients in IIb. Patient compliance will be better addressed with Tovaxin than any currently available therapy.

◦ Immunological:

▪ Currently monitoring reactivity of 109 peptides across 3 proteins. All three proteins are broadly present in MS patients.
▪ They have been able to map Myelin t-cell reactivity over time vs. these peptides over 150 patients to map and are starting to compare these changes with their clinical and radiological data for correlation. First time that any study has been able to accomplish this. 
▪ Initial analysis shows that patients on Tovaxin appear to have less myelin peptide reactivity vs placebo.
▪ Following the full course of treatment in "efficacy period of weeks 28-52", ARR dropped to 0.065 Tovaxin vs. 0.749 placebo. 
▪ Pattern suggests that patients with higher t-cell reactivity showed worsening of MRI and clinical outcomes. With higher peptide reactivity there seems to be an increase across at least one MRI endpoint and clinical endpoint and converse appears to be true as well.
◦ Much information to be analyzed.

• Looking for potential partner and are keen to acquire an experienced partner to assist in design and execution of Phase III clinical trial.
• Cash position takes them into early 2009.
• Looking at strategic partnership, possible financing, or possible merger and acquisition activity to go forward.

Isn't that an amazing result? ARR dropped from >1 to almost 0...

Cheers
Hansjoerg

..

Well, as Dr. Wynn told me, the top line data isn't all the data. It was just unfortunate.

As they further analyze, it seems that there is cause for hope. They just need more data, more money, and hopefully ultimately a Phase III with a bigger sample to prove that the trends are real and not just hopeful interpretations.

Given all of the downsides to the other meds, and the lack of side effects from this one, along with my stability, I'm staying for the long haul unless something changes for the worse or they kick me out.

..

thanks Patrick...good analysis.

_________________
“When everything seems to be going against you, remember that the airplane takes off against the wind, not with it.” - Henry Ford

Well, it may be that they don't yet know what a full course of treatment outside of the trial would be. I'm thinking that's part of the reason they're doing the study.

for the purposes of the study, the full course of treatment is the 5 shots. For Tim's maintenance, and this is from a horribly imperfect memory, he wasn't getting 5 a year I don't think.

And as usual, I have no idea what I'm talking about.