BHT-3009

An abstract titled “One Year Follow-up Results from a Phase II Trial of the BHT-3009 DNA Vaccine for Multiple Sclerosis,” has been accepted for presentation at the 61st Annual American Academy of Neurology (AAN) meeting, to be held in Seattle, Washington from April 25 through May 2, 2009.

Data in the abstract indicates that BHT-3009 has a durable effect and continues to have a favourable safety profile for up to 12 months following the completion of dosing. BHT-3009 is an antigen-specific plasmid encoding myelin basic protein (MBP) that aims to reprogram the immune system to tolerize to, rather than attack, myelin antigens in the central nervous systems of multiple sclerosis (MS) patients.

In August 2008, Bayhill completed the 12-month follow-up phase (Survey Protocol) of a Phase II clinical trial of BHT-3009 in relapsing-remitting MS (RR-MS) patients. The Survey Protocol data demonstrated a decrease in relapse rates and a corresponding continued reduction in magnetic resonance imaging (MRI) gadolinium enhancing (Gd+) lesion activity. The Survey Protocol data builds on results previously published in Annals of Neurology (63(5):611-20, 2008), which demonstrated a reduction in MRI Gd+ lesions during the 44-week treatment period. Key updated results for the Survey Protocol are as follows:

Relapse data: The annualized relapse rate (ARR) decreased during the first six months of the Survey Protocol (0.16 and 0.37 relapses per year in the 0.5 mg and the 1.5 mg dose cohorts, respectively). The ARR and the proportion of relapse-free patients over the full 12-month Survey Protocol was comparable to recently published studies from both approved MS therapies and compounds in late stage clinical development.
MRI parameters: Consistent with ARR reduction, a decrease in total brain Gd+ lesions was maintained seven months after the last dose of BHT-3009, with an improvement in the number Gd+ lesion-free patients and a reduction in the mean number of Gd+ lesions for all patients.

Safety: BHT-3009 continued to demonstrate an excellent safety profile 13 months after the last dose of BHT-3009, with reported safety data similar to the safety data reported during the 44-week treatment phase. There were no treatment related serious adverse events, and greater than 95% of all adverse events were mild to moderate.

Mark W. Schwartz, PhD, CEO and President of Bayhill Therapeutics, commented, “We are pleased to report that Survey Protocol data on BHT-3009 demonstrate continued improvement in both MRI and relapse rates in patients with RR-MS. These data support the design and execution of a Phase IIb clinical trial of BHT-3009 targeting the overall RR-MS patient population, in preparation for Phase III studies. We are currently in discussions with potential partners to support the next stage of development for BHT-3009, and we are confident that our completed data in RR-MS patients makes BHT-3009 an attractive opportunity for pharmaceutical and biotechnology companies looking for a groundbreaking first-line approach towards the treatment of MS.”

ABOUT THE TRIAL

Two hundred and eighty nine patients with relapsing-remitting MS (RR-MS) were initially randomized to receive intramuscular (IM) injections of either BHT-3009 (0.5 mg or 1.5 mg) or placebo for 44 weeks (treatment period). Of these patients, 95 out of 96 patients originally treated with 0.5 mg and 83 out of 84 patients originally treated with 1.5 mg of BHT-3009 participated in the 12-month follow-up phase (Survey Protocol). The primary objective of the Survey Protocol was to evaluate safety after 44 weeks of treatment with BHT-3009, and secondary objectives included examination of gadolinium (Gd+) enhancing lesions by brain magnetic resonance imaging (MRI) as well as clinical relapse activity.

Source: Bayhill Therapeutics Inc (09/03/09)

Typically, DNA vaccines are composed of a bacterial plasmid that encodes a protein of specific interest behind a strong promoter (a DNA nucleotide sequence that forms a recognition site for the enzyme required for gene expression). The use of a DNA vaccine is considered the most simple or minimal way to induce an immune response.

Multiple sclerosis is an autoimmune inflammatory neurodegenerative disease of the central nervous system of unknown cause. The prevalence of the disease is known to be 1.1-2.5 million cases worldwide, and the disease is diagnosed in women twice as frequently as in men. Emerging evidence from recent studies suggests that aberrant immune-regulation is an important component in the pathogenesis of MS.

The authors, Drs Olaf Stüve, Petra Cravens and Todd Eager, draw attention to recent clinical studies involving BHT-3009, a DNA vaccine encoding full-length human myelin basic protein. MS is a demyelinating disease i.e. it involves degeneration of the myelin sheath surrounding axons - components of the neurons that make up nerve tissue. The authors highlight a recent safety trial with BHT-2009 - the first trial with a DNA vaccine for an autoimmune disease in human patients - which showed it to be safe and well tolerated, although clinical efficacy is, as yet, difficult to assess. However, a forthcoming Phase IIb clinical trial comparing two doses of BHT-3009 with placebo in 289 patients with relapsing-remitting multiple sclerosis (RRMS) promises to reveal more about the potential clinical benefits of this approach.

DNA vaccination has advantages over existing treatments - DNA vaccines are non-infectious, easily manufactured and inexpensive to produce. Subject to the outcome of the Phase IIb study, we may see the initiation of a Phase III study. Depending on the duration of that potential study, and provided that the use of BHT-3009 in a larger patient cohort can demonstrate safety and efficacy, the authors suggest that approval for its use in patients with RRMS could be possible within 5 years.

*DNA-based vaccines: the future of multiple sclerosis therapy. Stüve O, Cravens PA and Eager TN. Expert Review of Neurotherapeutics 8(3) 351-360 (2008)

Source: PharmaLive ©2008 Canon Communications Pharmaceutical Media Group (25/04/08)

Bayhill Therapeutics, Inc's co-founder and Vice President of Research, Hideki Garren, M.D., Ph.D., gave a podium presentation at the American Academy of Neurology 60th Annual Meeting (AAN) in Chicago. Dr. Garren's presentation, "Results from a Phase II Trial of a Myelin Basic Protein Encoding DNA Vaccine for Relapsing Multiple Sclerosis," provided further analysis of data from a Phase II study evaluating BHT-3009, a tolerizing DNA vaccine for multiple sclerosis (MS).

Dr. Garren's presentation focused on findings from all patients enrolled in two of the study's sites, a total of 80 patients from whom cerebral spinal fluid (CSF) was collected at week 0 to define a responder population based on baseline CSF levels of total immunoglobulin (IgG).

Patients whose baseline CSF IgG levels were greater than or equal to 2.5 mg/dl, representing 73% of the 80 patients in the cohort who provided CSF, demonstrated a statistically significant response to 0.5 mg BHT-3009. In this population, the number of new gadolinium (Gd)-enhancing lesions shown on brain magnetic resonance imaging studies (MRIs) from weeks 28 to 48 was reduced by 44% (p=.04) versus placebo. Annualized relapse rates for this group were reduced by 36%.

Patients in the 0.5 mg dose group of BHT-3009 also demonstrated the induction of immune system tolerance. The group dosed with 0.5 mg of BHT-3009 showed statistically significant reductions in autoantibodies targeting six different myelin proteins. These autoantibodies were measured by Bayhill's proprietary microarray technology at weeks 0 and 44. The reduction in autoantibodies targeting multiple myelin proteins indicates that BHT-3009 may produce a broad response in a heterogeneous population of MS patients. The placebo group did not demonstrate significant changes in any autoantibodies.

Commenting on the data from the Phase II study, Dr. Lawrence Steinman, Professor of Neurology and Neurological Sciences at Stanford University School of Medicine and co-founder of Bayhill said, "We are pleased with the results of this study in which we saw not only a strong response to BHT-3009 but also the induction of tolerance. We look forward to confirming both the dose of BHT-3009 and the patient selection criteria we have identified in a Phase IIb study scheduled to commence later this year."

The study enrolled 289 relapsing-remitting MS patients aged 18 to 55 who had suffered at least one relapse in the previous year and whose screening MRI was consistent with MS and showed 0-5 Gd-enhancing lesions. For inclusion, the subjects also needed an Expanded Disability Status Scale rating of less than or equal to 3.5. Patients were randomized 1:1:1 into placebo, 0.5 mg of BHT-3009, or 1.5 mg of BHT-3009, injected intramuscularly at weeks 0, 2, 4, and every 4 weeks thereafter until week 44. The primary endpoint was the 4-week rate of occurrence of new Gd-enhancing lesions on brain MRIs from weeks 28 to 48.

Top-line data for the same study, which demonstrated strong evidence of antigen-specific tolerance produced by BHT-3009, was announced in a separate press release dated October 4, 2007.

About BHT-3009

BHT-3009, an investigational product, is an antigen-specific plasmid encoding myelin basic protein (MBP). Early clinical data suggest that BHT-3009 reprograms the immune system to tolerize to, rather than attack, MBP and other myelin proteins in the myelin sheath of the central nervous system of MS patients. In particular, data from two completed placebo-controlled clinical trials demonstrated BHT-3009's potential to treat relapsing remitting (RR)-MS patients with high levels of immune activity, with a safety profile similar to placebo.

Source: Bayhill Therapeutics, Inc. (18/04/08)

New investigation results, 'Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial,' are detailed in a study published in Archives of Neurology. In this recent report, researchers in Montreal, Canada conducted a study "To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS) The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding The trial was conducted at 4 academic institutions within North America."

"Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg) The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-gamma-producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays," wrote A. Bar-Or and colleagues, Montreal Neurological Institute.

The researchers concluded: "We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI."

Bar-Or and colleagues published their study in Archives of Neurology (Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial.

Source: Archives of Neurology, 2007;64(10):1407-15).(12/11/07)

Bayhill Therapeutics Inc., announced today top line data from a phase IIb study of its lead investigational drug candidate, BHT-3009, for the treatment of multiple sclerosis (MS). Patients in a prospectively defined group with high anti-myelin basic protein (MBP) antibodies in their cerebral spinal fluid (CSF) showed statistically significantly fewer gadolinium-enhancing lesions in their brain after treatment with 0.5 mg of BHT-3009 compared with placebo.

Reductions in T2 volumes and T1 black holes were also observed in this same population. In addition, there were strong trends in these same measures when applied to the trial’s intent-to-treat patient population. BHT-3009 was found to be well tolerated in this study. Furthermore, using the company’s proprietary protein microarray technology, statistically significant reductions in several CSF myelin-specific autoantibodies were achieved in all patients treated with 0.5 mg of BHT-3009, compared with placebo. These findings thus demonstrate strong evidence of antigen-specific tolerance produced by BHT-3009.

The Company announced that it intends to schedule an end of Phase II meeting with the FDA to discuss designs for registration trials.

Hideki Garren, M.D., Ph.D., Bayhill’s co-founder and Vice President of Research will present data from this trial at the American Neurological Association meeting in Washington D.C. on October 9 and at a podium presentation at the annual conference of the 23^rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic on October 12. Mark Schwartz, Ph.D., Bayhill’s CEO and President will also present data from this trial at the BIO Investor Forum 2007 in San Francisco on October 10.

The phase IIb trial is a multi-center, randomised, double-blind placebo-controlled trial of 289 relapsing remitting MS patients. Patients were dosed monthly for one year with intramuscular injections of the investigational product BHT-3009. The trial’s endpoints are brain magnetic resonance imaging (MRI) measures of disease activity including gadolinium-enhancing lesions, T2 lesions and T1 black holes. These endpoints are uniformly used in Phase II trials for multiple sclerosis.

Commenting on the data from the Phase IIb trial, Dr. Lawrence Steinman, Professor of Neurology and Neurological Sciences at Stanford Medical School and co-founder of Bayhill said, "A long sought after goal in immunology has been to obtain tissue specific tolerance, without globally suppressing the immune system. We are delighted with the demonstration of tolerization of the immune system to myelin proteins in individuals with multiple sclerosis.”

“We are pleased with the top line results of our Phase IIb trial. BHT-3009 is the first of several programs arising from our BHT-DNA technology platform,” said Dr. Schwartz. “This platform is capable of rapidly producing new molecular entities targeting major unmet medical needs in large autoimmune disease markets. Our second program from this platform is BHT-3021, currently in the clinic for autoimmune Type 1 diabetes. We are very excited about expanding our efforts in these programs.”

About BHT-3009

The investigational product BHT-3009 is an autoimmune DNA vaccine that encodes MBP. It is designed to reprogram the immune system to tolerate rather than attack the brain’s myelin sheath. After administration of BHT-3009, immunological studies indicated that MS patients demonstrated decreased MBP-specific T cells in their blood and decreased anti-MBP antibodies in their spinal fluid. Normal T cells were not affected.

Source: Bayhill Therapeutics, Inc. (05/10/07)

In patients with multiple sclerosis (MS), the immune system attacks the myelin sheaths that protect nerve cells in the brain and spinal cord, according to background information in the article. The nerve cells axon, which transmits messages to other neurons, is eventually destroyed. The cause of MS is unknown, but evidence points to the involvement of immune cells and antibodies that recognise and attack specific substances in the myelin, such as myelin basic protein. Certain cytokines, small proteins produced by cells that trigger inflammation, also may play a role.

Amit Bar-Or, M.D., of the Montreal Neurological Institute and colleagues tested a DNA vaccine, BHT-3009, that encodes a full-length human myelin basic protein. Between 2004 and 2006, the researchers administered the vaccine to 30 patients with relapsing-remitting MS [characterised by symptomatic periods and periods of remission] or secondary progressive MS [when symptoms progressively worsen, but there still may be periods of remission]. After one, three, five and nine weeks, participants received intramuscular injections of placebo or BHT-3009 (in doses of .5 milligrams, 1.5 milligrams or 3 milligrams), with or without 80-milligram pills of atorvastatin calcium, a lipid-lowering drug previously shown to be effective in autoimmune conditions. After 13 weeks, participants who initially received placebo received four injections of BHT-3009.

Magnetic resonance imaging (MRI) and other safety evaluations were performed at the beginning of the study, and again after five, nine, 13, 26, 38 and 50 weeks. BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI and produced beneficial antigen-specific immune changes, the authors write. These changes included a reduction in the number of cytokine-producing CD4+ T cells (a type of white blood cell) specifically targeting myelin proteins. This reduction was found in the blood as well as in the cerebrospinal fluid of three patients who voluntarily underwent lumbar puncture after completing the course of BHT-3009. Atorvastatin did not appear to provide additional benefit.

There were no increases in clinical relapses, disability, drug-associated laboratory abnormalities, adverse events or the number and volume of contrast-enhancing [visible on MRI] lesions on brain MRI with BHT-3009 treatment compared with placebo, the authors write. In fact, there was a trend toward a decrease in the number and volume of contrast-enhancing lesions in the brain in patients treated with BHT-3009 compared with placebo.

Based on these results, a phase 2b trial a randomised clinical trial in approximately 290 patients of BHT-3009 is already under way. If successful in MS, antigen-specific DNA vaccines can be developed for prevention or treatment of related diseases, such as type 1 diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis, the authors conclude. (14/08/07)

Design
The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding.

Setting
The trial was conducted at 4 academic institutions within North America.

Patients
Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years.

Interventions
 BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg).

Main Outcome Measures
The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses.

Results
BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-–producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays. We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone.

Conclusion
In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI.

Trial Registration clinicaltrials.gov Identifier: NCT00103974.

Amit Bar-Or, MD; Timothy Vollmer, MD; Jack Antel, MD; Douglas L. Arnold, MD; Caroline Anita Bodner, MSc; Denise Campagnolo, MD; Jill Gianettoni, BS; Farzaneh Jalili, BSc; Norman Kachuck, MD; Yves Lapierre, MD; Masaaki Niino, MD, PhD; Joel Oger, MD; Mary Price, BS; Susan Rhodes, MS; William H. Robinson, MD, PhD; Fu-Dong Shi, MD, PhD; Paul J. Utz, MD; Frank Valone, MD; Leslie Weiner, MD; Lawrence Steinman, MD; Hideki Garren, MD, PhD

Author Affiliations: Montreal Neurological Institute (Drs Bar-Or, Antel, Lapierre, and Niino and Mss Bodner and Jalili) and NeuroRx Research (Dr Arnold), Montreal, Quebec, Canada; Barrow Neurological Institute, Phoenix, Arizona (Drs Vollmer, Campagnolo, and Shi and Mss Price and Rhodes); Bayhill Therapeutics, Inc, Palo Alto, California (Ms Gianettoni and Drs Valone and Garren); University of Southern California, Los Angeles (Drs Kachuck and Weiner); University of British Columbia, Vancouver, British Columbia, Canada (Dr Oger); and Stanford University, Stanford, California (Drs Robinson, Utz, Steinman, and Garren).

Source: Arch Neurol. 2007;64:(doi:10.1001/archneur.64.10.nct70002). © 2007 American Medical Association. All Rights Reserved. (14/08/07)

Co-founder and Vice President of Research, Hideki Garren, MD, PhD, will present clinical data for Bayhill's Phase I/II trial of BHT-3009, and details on the Phase IIb trial of BHT-3009, which is currently being enrolled in Europe.

ENS ABSTRACT AVAILABLE AT: http://bayhilltx.com/bayhill_ens_2006_abstract.pdf

RESEARCH/PROGRAM HIGHLIGHTS:

1. Bayhill's Phase I/II clinical investigation of BHT-3009 is believed to be the first human trial of an antigen-specific DNA plasmid for multiple sclerosis (MS), an autoimmune disease.

2. BHT-3009 is an antigen-specific treatment for MS. The MS therapeutic has been designed to NOT cause broad-based immunosuppression.

3. Bayhill's experimental MS therapeutic, BHT-3009, has been designed to down-regulate rogue T cells specific for MBP. Left unchecked, these rogue T cells shred the myelin sheath that insulates the nerve cells of the brain and spinal cord, resulting in MS. BHT-3009 down regulates, or tolerizes, these MBP specific T cells and only these T cells. The remainder of the immune system remains intact to fight infections and cancer.

4. Researchers and clinicians believe that BHT-3009 is distinguished from other antigen-specific approaches attempted in the clinic in several ways:

• (1) the DNA allows low-level persistence of the antigen for 2-4 weeks, thus allowing for less frequent dosing.
• (2) BHT-3009 expresses full-length MBP, thereby encompassing all possible target auto-antigens rather than a single auto-antigen, and allowing for a broader possible population of responders to the drug.

5. Bayhill's Phase I/II clinical trial of BHT-3009 is complete. In the Phase I/II trial, clinicians observed that BHT-3009 is safe and reported that "adverse events" were higher in the placebo arm compared to the treated arms.

a. Clinicians observed brain MRI trending toward improvement in Gad + lesion count with BHT-3009 versus placebo.

b. All patients are clinically stable, or improved with treatment.

c. Peripheral T cell assays showing decrease in activity of MBP specific T cells were observed in a number of patients.

d. Thus, safety and proof-of-concept were demonstrated in this phase I/II 30-patient trial.

Phase IIb trial

Enrollment in this double-blind, placebo-controlled, multi-center trial has begun. A total of 252 patients are being recruited in the following countries: Bulgaria, Czech Republic, Finland, Poland, Romania, Russia, Serbia, Slovakia, Turkey, Ukraine, UK, and in the US.

Over 120 patients have been enrolled and randomize to the study as of 30 May 2006.

Dosing will be for one-year with MRI Gad + lesion formation as the primary endpoint.

Source: Bayhill Therapeutics Inc. (30/05/06)

"In a Phase I/II trial evaluating BHT-3009 in patients with multiple sclerosis, we observed a good safety profile, and, in a small number of patients, evidence of a long-lasting antigen-specific immuno-suppression effect," said Mark W. Schwartz, PhD, President and CEO, Bayhill Therapeutics.

BHT-3009 research and clinical data was presented last week at the American Academy of Neurology in San Diego. One of two presentations was selected as one of the meeting's "scientific program highlights," and was among the top five percent of the research presented at this year's meeting: Abstract: http://www.bayhilltherapeutics.com/AAN_2006_abstract_S02_004.pdf.

Source: Bayhill Therapeutics Inc.(30/05/06)

Scientists at Bayhill Therapeutics report promising findings for an investigational multiple sclerosis (MS) drug, BHT-3009, which represents a novel DNA plasmid-based approach for the treatment of the life-threatening disease.

In a number of patients with myelin basic protein (MBP) specific active T cells, BHT-3009 was shown to down-regulate these T cells, the primary cause of MS, an autoimmune disease. Left unchecked, the MBP-specific T cells shred the protective myelin sheath that encases the neurons responsible for nerve transmission. The absence of the myelin sheath results in unpredictable and increasingly destructive short circuits in the body's central nervous system, critical to life function. While scientists don't yet know what causes this pathology in MBP-specific T cells, when these T cells become pathogenic, they cause MS. Bayhill's drug development specifically centers on shutting down the disease causing activity of these MBP-specific T cells. From pre-clinical concept to clinical demonstration, the specifically of Bayhill's DNA plasmid therapy has resulted in a strong safety profile.

The Bayhill research is one of the first hints that scientists engaged in multiple sclerosis drug discovery can directly and specifically affect MBP-specific T cells in humans. In an ongoing placebo-controlled 30-patient Phase I/II investigation in relapsing MS patients, a team of Bayhill scientists and clinicians at four medical centers in North America have demonstrated antigen-specific reduction and desired effect, specifically affecting MBP T cells.

These data and findings were presented in a poster session at the 21st Congress of the European Committee for Treatment and Research of Multiple Sclerosis in Thessaloniki, Greece by Bayhill co-founder and Vice President of Research, Hideki Garren, MD, PhD: Antigen-specific immunomodulation in multiple sclerosis patients treated with MBP encoding DNA plasmid (BHT-3009) alone or combined with atorvastatin. The poster was one of five selected by peers to receive a prize for scientific novelty and clinical promise. 

In order to assess whether the underlying autoimmune mechanism of pathogenesis is affected by the DNA vaccine, Bayhill scientists performed immune assays on peripheral blood, including T cell proliferation, using a CFSE-based antigen-specific, intracellular cytokine assay (CFSE/IC). The assay has shown potential correlation with MRI, the standard of care in measuring inflammation in the brain and progress of the disease. For this reason Bayhill believes the CFSE/IC assay to be clinically relevant.

Using the assay, the team observed:

• MBP specific T cells can be detected in peripheral blood (as contrasted to the more invasive evaluation of the central nervous system) of MS patients using the CFSE/IC assay, and that there is some degree of correlation between brain MRI activity and MBP specific T cell reactivity. Bayhill scientists believe this is a breakthrough.
• BHT-3009 reduces MBP specific T cell reactivity in a number of cases. In these patients, the team observed antigen-specific reduction in MBP reactive T cells by week 9 of treatment.
• There is no indication of induction of immunity against MBP with BHT-3009. The significance of this finding is indicative of the safety of the BHT-3009 in that it does not activate the disease causing cells.

"This is the first clinical trial of a DNA plasmid for antigen-specific immunotherapy of any autoimmune disease," said Dr. Garren. "The preliminary data suggest that BHT-3009 can specifically decrease the activity of MBP reactive T cells. Additional clinical testing of BHT-3009 is warranted and needed, but we hope to eventually provide patients with a safe and disease specific option to fill the current void in MS treatments."

About Bayhill Therapeutics

Bayhill Therapeutics Inc., founded with technology developed in Professor Lawrence Steinman's laboratory at Stanford University, is focused on the translation of research into therapeutics by developing novel drugs for the treatment of autoimmune diseases. The company has established a therapeutic platform of BHT-DNA(TM) antigen-specific therapeutics, with broad potential applications in treating autoimmune diseases, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Bayhill's lead product in this platform, BHT-3009, is an antigen-specific DNA plasmid and is currently in early-stage clinical testing in multiple sclerosis patients. Bayhill is preparing for a phase II trial to begin in early 2006. In addition, Bayhill is developing a second therapeutic program, BHT-Oligo(TM) oligonucleotide based drugs, for treating autoimmune diseases.

Source: Bayhill Therapeutics Inc.(19/12/05)

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