Bayhill Therapeutics Announces Presentation of MS Drug Candidate BHT-3009 at American Academy of Neurology 60th Annual Meeting

PALO ALTO, Calif., Apr 10, 2008 (BUSINESS WIRE) -- Bayhill Therapeutics, Inc., a clinical-stage biopharmaceutical company leveraging its proprietary therapeutic BHT-DNA(TM: 98.28, +0.30, +0.30%) platform to develop novel and targeted autoimmune disease treatment candidates, today announced that the Company's co-founder and Vice President of Research, Hideki Garren, M.D., Ph.D., will present at the American Academy of Neurology 60th Annual Meeting (AAN) in Chicago. Dr. Garren's podium presentation will discuss Bayhill's lead product candidate BHT-3009 in relation to an abstract (#857) entitled "Results from a Phase 2 Trial of a Myelin Basic Protein Encoding DNA Vaccine for Relapsing Multiple Sclerosis" at session S22: "Multiple Sclerosis: Clinical Trials III" on Wednesday, April 16 at 2:30 PM central time at McCormick Place West Convention Center, Chicago, IL.

Please note, the details of the abstract remain under embargo until the commencement of Dr. Garren's presentation at the conference. Bayhill Therapeutics will provide additional details at that time.

About BHT-3009 an Investigational Product

BHT-3009 is an antigen-specific plasmid encoding myelin basic protein (MBP: 24.40, +0.30, +1.24%) that has the potential to gain a significant share of the multi-billion dollar MS market as an effective treatment with limited side effects and a superior administration profile. Early clinical data suggests that BHT-3009 reprograms the immune system to tolerize to, rather than attack, the MBP in the myelin sheath of the central nervous system of MS patients. In particular, data from two completed placebo-controlled clinical trials signaled BHT-3009's potential to treat Relapsing Remitting Multiple Sclerosis (RR-MS) patients with high levels of immune activity, with a safety profile similar to placebo.

About Multiple Sclerosis (MS: 45.89, +0.47, +1.03%)

MS is a chronic autoimmune disease characterized by the immune system's attack on specific self-antigens, such as myelin basic protein (MBP: 24.40, +0.30, +1.24%) present in the myelin sheath of the central nervous system. This attack on self-antigens leads to the onset of MS, which is characterized by symptoms of numbness, lack of coordination, blindness and paralysis.

According to an article published in The New England Journal of Medicine in 2006, MS is the most common non-traumatic cause of disability in young adults in the United States and Europe. According to the National Multiple Sclerosis Society (NMSS: 1.31, +0.06, +4.80%) an estimated 400,000 people in the United States have MS, while more than two million people are afflicted worldwide.

About Bayhill Therapeutics

Bayhill Therapeutics is a clinical-stage biopharmaceutical company leveraging its proprietary therapeutic BHT-DNA(TM: 98.28, +0.30, +0.30%) platform to develop a pipeline of novel and targeted treatment candidates for autoimmune diseases. The Company's product candidates are designed to restore the immune system to its normal state known as "tolerance," by selectively eliminating specific, harmful immune responses while leaving the rest of the immune system intact. The Company has two lead products in the clinic based on BHT-DNA(TM: 98.28, +0.30, +0.30%) that have demonstrated positive safety and tolerability, in addition to preliminary efficacy. The first product candidate, BHT-3009, was the subject of a completed Phase II trial for multiple sclerosis (MS: 45.89, +0.47, +1.03%). The second product candidate, BHT-3021, is currently in a Phase I/II trial for type 1 diabetes (T1D). More information about Bayhill Therapeutics is available at www.bayhilltx.com.

SOURCE: Bayhill Therapeutics, Inc.

Bayhill Therapeutics, Inc.
Mark W. Schwartz, Ph.D, President/CEO, 650-320-2800
mwschwartz@bayhilltx.com
Fred Kurland, Chief Financial Officer, 650-320-2800
fkurland@bayhilltx.com
or
The Ruth Group
Sara Ephraim, 646-536-7002 (Investors)
sephraim@theruthgroup.com
Janine McCargo, 646-536-7033 (Media)
jmccargo@theruthgroup.comCopyright Business Wire 2008

Tolerogenic DNA Plasmid Vaccine Decreases Brain Lesions in MS Patients: Presented at ECTRIMS

By Chris Berrie PRAGUE, CZECH REPUBLIC -- October 13, 2007 -- Intramuscular injection of the tolerogenic DNA plasmid vaccine BHT-3009 that encodes full-length human myelin basic protein (MBP) is safe and well tolerated, and provides significant favourable benefit on several measures of brain lesion activity in patients with relapsing-remitting multiple sclerosis. This multicentre, randomised, double-blind, placebo-controlled phase 2b trial was presented here by coinvestigator Hideki Garren, MD, PhD, Vice President of Research, Bayhill Therapeutics, Palo Alto, United States, at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). During his presentation on October 12, Dr. Garren stressed the two important aspects of construction of BHT-3009 as a DNA plasmid. "We include the antigen, MBP, as the entire molecule, rather than specific epitopes, and we include some specific changes in the DNA background to try to drive the [T-cell] tolerance." In a previous 30-patient phase 1/2 trial, BHT-3009 was shown to be safe and well tolerated (Bar-Or et al., [Arch. Neurol. 2007, 64, 1407-1415).

The current study enrolled 289 patients who were aged 18 to 55 years and had a confirmed diagnosis of MS according to McDonald criteria, at least one relapse in the previous year, and not received any treatment with disease-modifying agents in the previous 6 months. Study subjects also had screening magnetic resonance imaging (MRI) scans that were consistent with MS, with 0-5 Gd-enhancing lesions and an expanded disability status scale (EDSS) of 3.5 or greater.

The aim of the study was to evaluate the efficacy and safety of BHT-3009 in patients with relapsing-remitting MS, and to confirm that BHT-3009 causes immune tolerance.

The primary endpoint was the rate of occurrence of new Gd-enhancing lesions on cranial MRIs performed every 4 weeks from weeks 28 to 48 of treatment. Secondary endpoints were cranial MRI measures of Gd lesion volume, T2 lesion volume/number, and T1 black hole volume. The researchers monitored for relapses and disability scores. Finally, the immune response to MBP was also determined, to confirm previous results and to prospectively identify patients who respond to BHT-3009.

Patients were randomised to one of three treatment arms: 96 received placebo; 104 patients received BHT-3009 0.5 mg (low dose); 89 patients received BHT-3009 1.5 mg (high dose). Treatment was administered by intramuscular injection on weeks 0, 2 and 4, and then every 4 weeks until week 44.

Patients' baseline disease characteristics, number of relapses in the previous year, mean EDSS and MS functional composite (MSFC) overall z scores. The three treatment groups also had similar baseline MRI parameters.

In the 267 patients in per protocol cohort evaluation from weeks 28 to 48, results show that low-dose BHT-3009 achieved a near-significant 50% decrease versus placebo in median 4-week rate of new Gd+ lesions per patient (P =.07). No high-dose BHT-3009 effects seen.

However, Dr. Garren stressed that while this primary endpoint was not satisfied, when the MRI results were taken over the full treatment period (weeks 8 to 48), the 61% reduction versus placebo at low-dose BHT-3009 was significant (P =.05).

At week 48, low-dose BHT-3009 achieved a significant 51% decrease in mean Gd+ lesion volume (P =.02), although there was only a trend for decrease in T2 lesion volume.

The immunology assessment was on the 80 patients in the subgroup with cerebrospinal fluid (CSF) samples at screening and at week 44. In the screening for CSF anti-MBP reactivity, the low-dose BHT-3009 patients with the higher antibody titers (with a 1:1 low:high cut-off) showed a significant decrease versus placebo in new Gd+ lesions per MRI at week 28 (P =.02). Similarly, for CSF auto-antibody changes from screening to week 48, there were 23 fewer myelin-specific auto-antibodies in the 0.5 mg BHT-3009 group, while the placebo group had no change in auto-antibodies.

In the safety analysis on the 286 patients who received at least one dose of BHT-3009, common adverse events were mostly mild to moderate, and relatively well balanced across treatment groups. Dr. Garren indicated that psychiatric adverse events were slightly higher in the placebo group (14.7% vs 8.7% vs 9.2%), and renal and urinary events were slightly higher in the 1.5 mg BHT-3009 group (5.3% vs 8.7% vs 11.5%). Adverse events that were severe or worse were also more common in the placebo group (11 vs 7 vs 8). However, these all differences were not statistically significant.

In terms of relapse and disability, there was an overall very low rate of MS relapse, with 0.4 relapses in the placebo group, with no significant differences across the groups for relapse rates, time to relapse, or in mean EDSS and MSFC in this trial, added Dr. Garren.

The higher 1.5 mg dose of BHT-3009 had no patient benefits, potentially due to induction of four proteolipid protein peptide (PLP) antibodies, he said. However, the 0.5 mg dose did provide significantly favourable benefit for several measures of brain lesion activity, he added.

At the same time, this latter treatment showed high levels of CSF auto-antibodies as predictive for best responders for this patient subgroup analysis, with BHT-3009 causing antigen-specific tolerance, as seen by the reduction in CSF auto-antibody levels.

Funding for this study was provided by Bayhill Therapeutics.


[Presentation title: Phase 2b Trial of a MBP-Encoding DNA Plasmid (BHT-3009) for the Treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). Abstract 48]



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Bayhill Therapeutics to Present Positive Data From a Phase IIb Trial of BHT-3009 in Multiple Sclerosis

October 04, 2007 06:00 PM Eastern Daylight Time

Preparations for a Phase III Trial Underway

BIO Investor Forum 2007
PALO ALTO, Calif.--(BUSINESS WIRE)--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 23rd 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, randomized, 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.

About Multiple Sclerosis

MS is characterized by an errant autoimmune reaction that causes damage to the myelin sheath and axon. MBP is a component of the myelin sheath, and in MS this protein is targeted by MBP-specific active T cells. These T cells consequently damage the protective myelin sheath that encases the neurons responsible for nerve transmission, resulting in destructive short circuits in the body’s central nervous system.

MS is the most common non-traumatic cause of disability in young adults. Approximately 400,000 in the United States today suffer from the disease, at a national cost of nearly $10 billion. Symptoms of this chronic, progressive disease can include muscle, sensory and visual impairments, fatigue, bladder, bowel and sexual dysfunction.

About Bayhill Therapeutics

Bayhill Therapeutics Inc. is a clinical-stage biotechnology company focused on developing and commercializing therapeutics that fundamentally alter the way autoimmune diseases are treated. The company has developed two therapeutic platforms with broad applicability to a range of autoimmune diseases. Bayhill’s BHT-DNA autoimmune vaccine is designed to eliminate disease-causing cells without affecting normal protective immune system cells. BHT-DNA is being studied in a recently completed Phase II trial for multiple sclerosis and a Phase I/II trial for autoimmune diabetes. Bayhill’s second therapeutic platform is an oligonucleotide; the first product candidate is in preclinical development for systemic lupus erythematosus. More information about Bayhill Therapeutics is available at www.bayhilltx.com.


Contacts
Bayhill Therapeutics, Inc.
Mark W. Schwartz, Ph.D., 650-320-2801
President, CEO, Director
mschwartz@bayhilltx.com
Fred Kurland, 650-320-2808
Chief Financial Officer
fkurland@bayhilltx.com

DNA Vaccine Against Multiple Sclerosis Appears Safe, Potentially Beneficial

CHICAGO, IL -- August 13, 2007 -- A newly developed DNA vaccine appears safe and may produce beneficial changes in the brains and immune systems of individuals with multiple sclerosis, according to an article posted online today that will appear in the October 2007 print issue of Archives of Neurology, one of the JAMA/Archives journals.

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 cell's 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 recognize 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, MD, 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 [characterized by symptomatic periods and periods of remission] or secondary progressive MS [when symptoms progressively worsen, but there still may be periods of remission].

After 1, 3, 5 and 9 weeks, participants received intramuscular injections of placebo or BHT-3009 (in doses of.5 mg, 1.5 mg or 3 mg), with or without 80-mg 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 5, 9, 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 randomized 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.

The work described in this article was funded by Bayhill Therapeutics, Inc.


ArchNeurol. 2007;64(10):(doi:10.1001/archneur.64.10.nct70002).


SOURCE: American Medical Association