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Knopp Biosciences

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Knopp Neurosciences Presents Further Encouraging Trends in its Phase 2 Study of KNS-760704 (Dexpramipexole) in ALS

April 16, 2010

TORONTO, April 16, 2010--In an invited presentation today before the annual meeting of the American Academy of Neurology, Knopp Neurosciences Inc. ("Knopp") described further encouraging trends observed in a previously reported Phase 2 study of KNS-760704 (dexpramipexole) in ALS.

Knopp reported that post hoc analyses showed a significant, dose-dependent trend of reduced treatment failure, as measured by both the ALS Functional Rating Scale-Revised ("ALSFRS-R") and forced vital capacity, over the 12-week, placebo-controlled portion of the study.

• In the case of ALSFRS-R, the number of treatment failures, defined as the loss of 6 points or greater in ALSFRS-R scores from baseline, totaled 9 subjects (or 33%), in the placebo group; 8 subjects (35%), in the 50 mg/day group, 4 subjects (15%) in the 150 mg/day group, and 2 subjects (8%) in the 300 mg/day group (p=0.014).

• In the case of pulmonary function, the number of treatment failures, defined as a reduction in forced vital capacity of 20% or greater from baseline, totaled 8 subjects (30%) in the placebo group, 3 subjects (13%) in the 50 mg group, 3 subjects (12%) in the 150 mg group, and 1 subject (4%) in the 300 mg group (p=0.028).

Knopp emphasized that these encouraging trends require confirmation in the large, long-term, controlled Phase 3 study setting necessary to establish that the drug is both safe and effective for ALS patients. Nevertheless, the additional analyses reported today were concordant with trends previously reported from Knopp's Phase 2 study, which suggested the potential for dexpramipexole to improve outcomes in both function and survival.

"Despite the limited sample size and treatment periods, ongoing review of the Phase 2 data shows consistently encouraging trends in both pre-specified and post hoc analyses," said Merit Cudkowicz, M.D., Professor of Neurology at the Massachusetts General Hospital of Harvard Medical School, who served as the principal investigator in the trial and who presented the Knopp study results by invitation at the Academy's 2010 Clinical Trials Plenary Session. "We are eager to initiate Phase 3 studies as soon as protocol development and other arrangements are completed."

As previously reported, the two-part Phase 2 study found that dexpramipexole met its primary objective in assessing its safety and tolerability in ALS patients for up to nine months. Secondary objectives included measuring the clinical effects of dexpramipexole on functional decline and mortality. The two-part design of the study provided the opportunity to assess the effects of the drug in the same sample of ALS subjects in two randomized, double-blind treatment periods separated by a one-month placebo washout.

In Part 1 of the study, 102 subjects received daily doses of 50 mg, 150 mg, or 300 mg of dexpramipexole or placebo for 12 weeks. As previously reported, dexpramipexole showed a dose-dependent trend in slowing the rate of disease progression as measured by the difference in slopes of the ALSFRS-R across treatment groups, with the greatest benefit observed in the 300 mg dose group.

In Part 2 of the study, 92 subjects were re-randomized to receive daily doses of 50 mg or 300 mg of dexpramipexole for 24 weeks.  In addition to results again suggesting a dose-dependent trend in slowing the rate of disease progression as measured by the ALSFRS-R, there was also a trend toward a survival benefit in the 300 mg group compared with the 50 mg group. In an exploratory test comparing subject rankings on the basis of mortality and functional outcomes, subjects in the 300 mg group had a significantly improved outcome compared with the 50 mg group.

Knopp expects to initiate Phase 3 studies of dexpramipexole in ALS before the end of 2010.

About KNS 760704 (dexpramipexole)

KNS 760704 is a low molecular weight benzothiazole shown to improve mitochondrial function and to confer significant cellular protection in neurons under stress. The chirally pure form of the synthetic benzothiazole (6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino) benzothiazole, KNS-760704 is highly orally bioavailable, water soluble, renally excreted, and only moderately protein bound. The compound has received orphan drug designation from the U.S. Food and Drug Administration and the European Commission for the treatment of patients with ALS, as well as Fast Track designation from the FDA.

About ALS

Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease and Charcot's sclerosis, is a rapid, universally fatal neurodegenerative disorder characterized by progressive muscle weakness and wasting. ALS affects adults in the prime of life and creates a substantial burden for caregivers. U.S. prevalence is approximately 20,000 and the global incidence is approximately two per 100,000. Only one drug has been approved for the treatment of ALS. Life expectancy after symptom onset is usually three to five years.

About Knopp Neurosciences Inc.

Knopp Neurosciences, based in Pittsburgh, PA, USA, is a drug discovery and development company focused on delivering breakthrough treatments for neurological disorders through innovation, experience, and partnership. The company's lead product candidate is KNS 760704, an orally bioavailable small molecule in development for the treatment of ALS. Knopp's leadership includes experienced neuroscience drug development and discovery executives formerly associated with major pharmaceutical companies. Knopp's financing has been led by Saturn Capital Inc. of Boston as placement agent and Saturn Partners II as lead funder.

This press release contains "forward-looking statements," including statements relating to Knopp's planned regulatory filings and clinical development programs for KNS 760704. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including the uncertainties inherent in clinical trials and product development programs, the availability of funding to support continued research and studies, the availability or potential availability of alternative therapies or treatments, the availability of patent protection for the discoveries, and strategic alliances, as well as additional factors that may cause Knopp's actual results to differ from our expectations. There can be no assurance that KNS-760704 will be successfully developed or manufactured or that final results of clinical studies will be supportive of regulatory approvals required to market the products. Knopp undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events, or otherwise.

Media Contact:
Thomas Petzinger Jr.