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PowerPoint PresentationKnopp Biosciences Creating new treatments to change the course of human health
Investment highlights
U.S. Phase 2 trial in moderate-to-severe asthma underway, results 3Q2020
UK Phase 2 trial in severe asthma to commence in 1H2020
Preclinical Kv7 platform delivering small molecule treatments for KCNQ2 epileptic encephalopathy and other CNS hyperexcitability disorders
Plan to file IND for KB-3061 in rare pediatric epilepsy by YE2020
Experienced management team with successful development and commercialization track record in immunology and neuroscience
Management team with track record of blockbuster approvals and launches
Michael Bozik, M.D. President and CEO
Steven Dworetzky, Ph.D. CSO, SVP Discovery
Mark Kreston Chief Commercial Officer
Calman Prussin, M.D. VP, Clinical
Dexpramipexole Moderate-to-severe eosinophilic asthma
Dexpramipexole Severe eosinophilic asthma (1)
(1) UK government funded Phase 2 trial to commence in 1H2020
Portfolio focus: Novel approaches to high unmet needs in immunological and neurological diseases
Dexpramipexole in immunology Kv7 platform in neurology
Only oral eosinophil-depleting drug
Significantly de-risked, regulatory clarity
Phase 2 trial initiated in moderate-to- severe eosinophilic asthma – projected to become a $9B market segment
Patent protection to at least 2034
Highly differentiated target product profile with unique MOA
Pipeline-in-product potential
Lead compound KB-3061 initiating IND- enabling studies
Genetically defined KCNQ2 epileptic encephalopathy initial indication
Patent protection to at least 2035
Significant inbound strategic partnering interest
Platform delivering novel activators for new indications
Eliminated by the kidneys, not metabolized by the liver
Easy to synthesize and manufacture, low COGS
Differentiated product profile
Shown to induce disease remission and reduce steroid dependency in hypereosinophilic syndrome
Well tolerated for chronic use
Dexpramipexole: First-in-class oral drug delivering targeted eosinophil depletion in blood and tissue
97% lowering, BL to Month 6, p= 0.001
Laidlaw T et al. Laryngoscope. 2019 Feb;129(2):E61-E66. Panch et al. Blood. 2018 Aug ;132(5):501-509.
Oral dexpramipexole delivered highly significant blood and tissue eosinophil depletion in two Phase 2 trials
Sinusitis with nasal polyps Hypereosinophilic syndrome
Pre-treatment Post-treatment
Panch et al. Blood. 2018 Aug ;132(5):501-509.
Regulatory approvals validate the eosinophil as a biomarker for asthma clinical outcomes
Ortega 2015
“The panel endorsed the concept that
higher eosinophil counts were predictive of greater benefits in reduction of exacerbation and
corticosteroid use.”
Higher blood eosinophil levels associated with greater exacerbation risk
Phase 2 dose-ranging biomarker trial in moderate-to-severe asthma is enrolling and on track for 3Q 2020 topline result
Primary endpoint:
Key inclusion criteria: Asthma requiring ICS/LABA (GINA steps 3-5) Blood eosinophil count ≥ 300 Variable expiratory airflow limitation
Eosinophil Recovery
Placebo (n = 25)
n -i
Oral dexpramipexole 150 mg/day (n = 25)
Primary Assessment Phase
UK government funding trial of oral dexpramipexole as “pre-biologic” for severe asthma starting 1H 2020
Investigator proposal: “Dexpramipexole has been selected in T2-HIGH asthma as it is a novel, orally active, and highly potent anti-eosinophil agent.”
Chief Investigator (Leicester)
15 studies, 1200 patients Exclusivity in place to at least 2034
Oral dexpramipexole benefits from extensive safety database and extended commercial exclusivity opportunity
Bozik M et al. J Clin Pharmacol. 2011;51(8):1177-85; Cudkowicz M et al. Nat Med. 2011;17(12):1652-6. Cudkowicz M et al. Lancet Neurol. 2013;12(11):1059-67; Laidlaw T et al. Laryngoscope. 2019;129(2):E61-66; Panch et al. Blood. 2018;132(5):501-09.
Significant new market segment being created in eosinophilic asthma, with all approved drugs requiring injection
Sales performance: Company earnings reports Market forecast: Bank of America Merrill Lynch. GlaxoSmithKline: Up to Neutral. Sept. 7, 2015.
Market on track to reach $2B+ in 2019 Market forecast to reach $9B annually
Sales performance: £563 MM FY 2018
£550 MM YTD Sept 2019
Product level sales not reported
Sales performance: $295 MM FY 2018
$498 MM YTD Sept 2019
€1,377MM YTD Sept 2019 (all indications) Asthma sales not reported separately
Oral blockbuster brands command significant share in highly competitive biologic/injectable markets
References: Disease associations, Cleveland Clinic, company reports 14
Brand Sponsor Disease area(s) U.S.
population estimates
Active psoriatic arthritis 2-3MM
Moderate-severe ulcerative colitis 600,000
Active psoriatic arthritis 2-3MM
Tecfidera Relapsing multiple sclerosis
Secondary progressive MS
Secondary progressive MS
20+ novel chemotypes designed and tested, over 3000 compounds synthesized
Library contains molecules with a broad range of selective Kv7.2/7.3 activities
Patents issued covering Series A-1 (USP 9,650,376) and Series A-2 (USP 9,481,653)
Rare pediatric epilepsy IND candidate KB-3061 selected with backups in place
Program focus is on Series A:
– A-1 (> 800 compounds)
550 compounds
600 compounds
other series
Series B
Series A
Knopp has synthesized the world’s most advanced library of Kv7.2/7.3 activators
Goals of the Knopp Kv7.2/7.3 activator program
Discover and develop best-in-class Kv7.2/7.3 activators with superior potency
Capitalize on opportunities for significant improvement over ezogabine and ezogabine analogs
− Eliminate chemical instability hypothesized to have resulted in ezogabine black box warning
− Improve selectivity and tolerability by eliminating GABAA activity
− Reduce ezogabine (TID) dosing frequency
Restore current to mutated KCNQ2 channels
2013: FDA links ezogabine to retinal abnormalities and blue skin discoloration
2017: GSK voluntarily withdraws ezogabine from market for poor commercial performance
IND candidate KB-3061 more potent, more selective, more stable, and better tolerated than ezogabine
ED50=0.5 mg/kg TI>40x
ED50=20 mg/kg TI<3x
B a
s e
li n

Data presented at American Epilepsy Society Annual Meeting, Baltimore, MD. Dec. 9, 2019.
T0 T8
Untreated control
Data developed in collaboration with Coooper Lab, Baylor College of Medicine. Data presented at American Epilepsy Society Annual Meeting, Baltimore, MD. Dec. 9, 2019.
Gene mutations severely reduce ion channel current, causing KCNQ2 epileptic encephalopathy
Seizures from first few days of life
Abnormal brain development, with severe to profound intellectual and motor disability
− Potent Kv7.2/7.3 activation with GABAA attenuation achieved (α1β32)
− Transporter screening, cardiac screening, CYP profiling, and mini-Ames complete
− Potent with wide therapeutic index in rat MES model
− Restores current for three highly recurrent KCNQ2 missense variants at or above baseline wt/wt currents
− Non-GLP rat toxicology and toxicokinetics complete with robust safety margin
− KB-3061 backups in place
DMFP initiated
− Synthetic route in place with good potential for development into a scalable process suitable for NCSS and cGMP materials
− Analytical and process development studies initiated
Clinical development plan to be reviewed with FDA at pre-IND meeting
− Guidance on Phase 1 studies and initial efficacy study in infants with KCNQ-EE to be secured
− Potential for single pivotal study approval
KB-3061 development status
References: NIH, NORD, disease associations, company reports 21
Brand Sponsor Launch Disease area(s) U.S. population
estimates Annual U.S. WAC price
Global revenue
Epidiolex 2018
Dravet syndrome
Kalydeco 2012 Cystic fibrosis with CFTR mutation
1,000 annual cases 30K total ~%5 with CFTR
Year 1: $750,000 Year 2+: $375,000
$1.7B 2018 $1.5B YTD
300 annual cases 1K-3K total
$2.1MM (one-time treatment)
$1.6 billion market cap in eosinophilic asthma
Government funding awarded to Knopp Pre-revenue public market comparables
$10 million for epilepsy program*
$8 million for neuropathic pain program**
$2.1 million for dexpramipexole Phase 2 exacerbation trial
23 • * NIH Blueprint Award U44NS093160.
• ** NIH HEAL Award U44NS115732.
Potential to drive liquidity through IPO or M&A with 2020 milestones
2019 3Q 4Q
KB-3061: KCNQ2-EE*
Phase 2 POC in atopic dermatitis
$25 mm Series C funds studies with near-term valuation catalysts
Sustainable value-creation driven through pivotal studies, life-cycle, and platform development
Kv7 Platform
Novel clinical candidates – Neuropathic pain** – ALS – Tinnitus
Phase 1 IND
2021 1Q 2Q
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