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Knopp Biosciences Presents New Phase 2 Data at ERS 2021 Demonstrating that Reduction in Eosinophil Count by Dexpramipexole Significantly Correlates with Improvement in Lung Function

Knopp Biosciences LLC today reported further clinical and biomarker data demonstrating that reduction in eosinophil count by oral dexpramipexole significantly correlated with improved lung function in the positive Phase 2 EXHALE trial of dexpramipexole in patients with moderate-to-severe eosinophilic asthma. The data were presented in a late-breaking abstract session at the European Respiratory Society International Congress 2021.

Eosinophils, a type of white-blood cell, are validated as a therapeutic target in asthma by the regulatory approval of multiple eosinophil-lowering biologics. Treatments approved to date for eosinophilic asthma are monoclonal antibodies requiring injection or infusion; dexpramipexole is administered orally.

The EXHALE trial was a randomized, double-blind, placebo-controlled trial of dexpramipexole in patients with moderate-to-severe asthma and blood absolute eosinophil count (AEC) ≥300/µL. Dexpramipexole study drug at oral doses of 75 mg/day, 150 mg/day, or 300 mg/day was added to standard of care. The primary endpoint was change in AEC from Baseline to Week 12 compared to placebo.

As previously reported, EXHALE met its primary endpoint, demonstrating dose-dependent lowering of eosinophils, with significant reductions in AEC from Baseline to Week 12 at all doses tested (75 mg/day: ratio to Baseline 0.40, p=0.019; 150 mg/day: ratio to Baseline 0.31, p=0.001, and 300 mg/day: ratio to Baseline 0.21, p<0.0001). Dexpramipexole demonstrated a significant, dose-dependent effect on eosinophil lowering by log-linear testing (p<0.001), and a significant increase from baseline in lung function as measured by prebronchodilator FEV1 change (ΔFEV1 +172 mL vs placebo, p=0.015), pooling data across study arms (75 mg/day, 150 mg/day, and 300 mg/day) and visits (Weeks 4, 8, 12, and 16/18).

Today’s presentation to ERS 2021 reported that eosinophil reduction by dexpramipexole significantly correlated with improvement in prebronchodilator FEV1 (combined 300 mg/day and 150 mg/day dexpramipexole, Spearman correlation coefficient -0.58, p<0.0001). FEV1, the amount of air a patient can forcibly exhale in one second, is a fundamental measure of asthma control.

The newly reported results also included the dose-dependent effects of dexpramipexole on nasal eosinophil peroxidase (EPX), a marker of airway eosinophilia associated with mucus plugging and airway trapping in severe asthma .1 In a prespecified analysis, nasal EPX at Week 12 was reduced by 89.0% (p=0.020), 82.6% (p=0.021), 35.5% (p=0.540), and 16.7% for the 300 mg/day, 150 mg/day, 75 mg/day, and placebo arms, respectively (p-values relative to placebo). These results reinforced previous reports showing effective tissue eosinophil lowering by dexpramipexole in chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome .2,3

“These results add to the body of evidence that dexpramipexole reduces eosinophil burden in affected tissues as well as in blood, and strengthen the hypothesis that reductions in blood and tissue eosinophils by dexpramipexole is associated with improved lung health,” said Michael Bozik, M.D., CEO of Knopp. “As we prepare for entry into Phase 3 clinical trials, the results also reinforce our confidence in the potential of dexpramipexole as the first oral agent that can significantly reduce the risk of exacerbations in eosinophilic asthma.”

As previously reported, dexpramipexole was well tolerated in the EXHALE trial, with no serious adverse events and no adverse events leading to discontinuation. Seventy-four of the 76 dexpramipexole-treated patients completed the primary assessment phase.

ABOUT KNOPP BIOSCIENCES LLC

Knopp Biosciences is a privately held drug discovery and development company focused on delivering breakthrough treatments for immunological and neurological diseases with high unmet need. Knopp’s clinical-stage oral small molecule, dexpramipexole, is in development for moderate-to-severe eosinophilic asthma. Knopp’s preclinical Kv7 platform is directed to small-molecule treatments for developmental and epileptic encephalopathies, other epilepsies, neuropathic pain, and smooth-muscle disorders. Please visit www.knoppbio.com.

ABOUT DEXPRAMIPEXOLE

Dexpramipexole, a selective inhibitor of eosinophil maturation, is an oral small molecule drug in development by Knopp for asthma and other eosinophil-associated diseases. In hypereosinophilic syndrome, dexpramipexole has previously been shown in a Phase 2 trial to significantly reduce requirements for oral corticosteroids and in a subset of patients to produce durable disease remission. In its earlier development in amyotrophic lateral sclerosis, dexpramipexole was shown to be well tolerated in Phase 1, Phase 2, and Phase 3 trials comprising approximately 1,200 patients.

This press release contains "forward-looking statements," including statements relating to planned regulatory filings and clinical development programs. 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 any investigational drug product will be successfully developed or manufactured or that final results of clinical studies will be supportive of regulatory approvals required to market a product. Knopp undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events, or otherwise.

Knopp's pipeline consists of investigational drug products that have not been approved by the U.S. Food and Drug Administration. These investigational drug products are still undergoing pre-clinical or clinical study to verify their safety and effectiveness.


1 Dunican EM et al. J Clin Invest. 2018 Mar 1; 128(3): 997–1009.

2 Laidlaw TM et al. Laryngoscope. 2019 Feb;129(2):E61-E66.

3 Panch SR et al. Blood. 2018 Aug 2; 132(5): 501–509.

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