New Interferon Formulations Promise to Eliminate Injections in Multiple Sclerosis Treatment

SAN DIEGO, CA January 12, 2009/MarketWire/-- Nerveda Inc. and Aegis Therapeutics
LLC today announced preclinical results from their joint collaboration aimed at
developing non-injectable formulations of the beta-interferons. The beta interferons,
beta-1a (tradename Rebif®), and beta 1b (tradenames Betaseron® and Betaferon®) are
closely related injectable protein drugs in the interferon family that are used to treat both the relapsing-remitting and secondary-progressive forms of multiple sclerosis (MS). The beta interferons are currently administered by subcutaneous injection and have been proven clinically to slow the advance of multiple sclerosis and reduce the frequency of attacks. Current worldwide combined annual sales of Rebif®, Betaseron® and Betaferon® are approximately $4 Billion.

Because proteins are large and fragile molecules, they cannot be administered orally
and are typically administered by injection. They are often subject to instability due to aggregation of the protein molecules – particularly upon storage and handling at nonrefrigerated temperatures. The resulting protein aggregates are more poorly absorbed
into the blood stream upon injection due to their increased size, and induce development of circulating antibodies to interferon in patients that reduce the effectiveness of the drug over time.

Leading medical scientists at Johns Hopkins University, expert in the treatment of
neurological diseases, in collaboration with Nerveda and Aegis have applied Aegis’
Intravail® transmucosal absorption enhancement, and ProTek® protein stabilization
technologies to address these problems and have demonstrated for the first time that the beta interferons can be administered intranasally to prevent nerve damage in preclinical animal models of multiple sclerosis. In addition, the new formulations were shown to reduce or eliminate the immunogenicity of Betaseron® and Rebif®, administered either by injection or intranasally, while substantially increasing stability in a stress test involving constant agitation at elevated temperatures for extended periods of time.

Dr. Edward Maggio, Ph.D., CEO of Aegis Therapeutics, who participated in the
research, said, “since interferons will continue to be the foundation of MS therapy, it is critical that non-invasive delivery options for patients be developed.” Maggio also indicated, “the reduction in immunogenicity and the increase in stability also address a significant unmet need of the currently available beta-interferon therapies.”
Nerveda plans to begin testing the new formulation in clinical trials in early 2009 in
collaboration with clinicians and scientists at John Hopkins University Medical Center
and other sites.

* Rebif® is a registered trademark of Pfizer, Inc.
* Betaseron® is a registered trademark of Bayer Healthcare Pharmaceuticals
* Betaferon® is a registered trademark of Bayer Schering Pharma AG
* Intravail® and ProTek® are registered trademarks of Aegis Therapeutics, LLC

About Nerveda Inc.

Nerveda is a privately funded specialty pharmaceutical and diagnostic company focused
on improving the quality of life for patients suffering from neurodegenerative diseases
and their caregivers. Nerveda supports the clinical development of products licensed
from Johns Hopkins University, including neuroprotective compounds and stem cell
therapeutics that show promise in treating auto-immune disorders.

About Aegis Therapeutics

Aegis Therapeutics LLC is a drug delivery technology company commercializing its
patented or proprietary drug delivery and drug formulation technologies through productspecific licenses. Our patented Intravail® drug delivery technology enables the noninvasive delivery of a broad range of protein, peptide and non-peptide macromolecular therapeutics that can currently only be administered by injection. Aegis’ Intravail® absorption enhancement agents provide exceptionally high and unmatched bioavailability performance, comparable in efficiency to subcutaneous injection, via the intranasal administration route. Intravail® has also been successfully applied to buccal, oral, and rectal administration of small molecule, peptide, and nucleotide-analog type drugs. Our patented ProTek® technology allows creation of proprietary, easily manufacturable, and stable aqueous or lyophilized dosage forms that maintain the integrity and physiological activity of many protein and peptide therapeutics. ProTek® technology is applicable to injectable, intranasal, and other dosage forms of peptide or protein therapeutics.

For more information about Aegis, please visit the Aegis website at: htpp://www.aegisthera.com.

Contact:
Aegis Therapeutics LLC
Ralph Barry, Chief Business Officer
1-858-618-1400 Ext. 102
Email: rbarry@aegisthera.com

Contact:
Nerveda Inc.
Cam Gallagher, CEO
1-(858) 705-2365
Email: CGallagher@NervedaBio.com

MS Relapse-Rate Higher in Adolescent-Onset Patients

By Michael Smith, North American Correspondent, MedPage Today
Published: January 12, 2009

Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

BOSTON, Jan. 12 -- When multiple sclerosis symptoms start in adolescence, the later annual relapse rate is nearly three times as great as it is for adult-onset disease, researchers here said.

The finding suggests that adolescent-onset MS has a more inflammatory disease course, according to Tanuja Chitnis, M.D., of Massachusetts General Hospital, and colleagues.

But the biological basis of the difference remains unclear and requires more study, Dr. Chitnis and colleagues said in the January issue of Archives of Neurology.

Several studies have shown that initial disease progression is slower in patients whose disease begins before the age of 18, the researchers said, but have differed on rates of relapse.

To clarify the issue -- and see whether the slower progression is related to relapse rates -- Dr. Chitnis and colleagues studied patients treated in the pediatric and adult MS centers at Massachusetts General and Brigham and Women's after July 2001.

Patients were eligible if treatment started within 12 months of the first symptom and were followed for at least a year. All told, the researchers identified 110 adult-onset patients and 21 whose disease started before they were 18.

The main outcome measure was annualized relapse rate, defined as the number of relapses divided by the number of person-years at risk. Rates for the adult and younger groups were compared using a proportional means model, as well as a negative binomial regression that excluded the first attack.

In both models, the researchers found that the annualized relapse rate was significantly higher in the younger cohort. Specifically:

* When the first attack was included, adolescent patients had an annualized rate of 1.4, compared with 0.65 for adult-onset patients. The difference was significant at P0.001 and yielded an adjusted rate ratio of 2.81 (with a 95% confidence interval from 2.07 to 3.81.

* Excluding the first attack yielded a pediatric rate of 1.13 and an adult rate of 0.4, also significantly different at P0.001.The adjusted rate ratio was 2.93 (with a 95% confidence interval from 1.93 to 4.46).

When the researchers controlled for the effects of disease-modifying treatment -- such as interferons, glatiramer acetate (Copaxone) or oral immunosuppressants -- the difference remained significant, with rate ratios of 2.82 and 3.02, depending on the model.

And when age was treated as a continuous variable, the age at onset was significantly associated with relapse rate at P0.001, Dr. Chitnis and colleagues found.

While several studies have shown that disease progression is slower in adolescent-onset cases, the researchers said they were unable to show that in this case because of the relatively short disease duration.

But if that is so, Dr. Chitnis and colleagues argued, the finding that younger patients have more relapses implies "greater plasticity, less neurodegeneration, and potentially more repair and remyelination in the younger nervous system."

The authors pointed out that "it remains possible that patients with more severe pediatric-onset MS were selectively evaluated at our centers. However, distance from the center, a proxy measure for referral bias, which has been shown to influence clinical characteristics in prior articles in the neurology and oncology literature, was not different between our pediatric-onset and adult-onset groups."

The study was supported by the National Multiple Sclerosis Society. The researchers did not report any conflicts.

Primary source: Archives of Neurology
Source reference:
Gorman MP, et al "Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis" Arch Neurol 2009; 66(1): 54-59.