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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
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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
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Immunology
Dexpramipexole Moderate-to-severe eosinophilic asthma
Dexpramipexole Severe eosinophilic asthma (1)
(1) UK government funded Phase 2 trial to commence in 1H2020
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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
S
N
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
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Corticosteroids
Dexpramipexole
Biologics
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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
Blood
Tissue
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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
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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
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V7
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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.”
BEAT SEVERE ASTHMA CONSORTIUM: Prof Salman Siddiqui,
Chief Investigator (Leicester)
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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
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€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
(7/100,000)
Xeljanz
Moderate-severe ulcerative colitis 600,000
Active psoriatic arthritis 2-3MM
Tecfidera Relapsing multiple sclerosis
Gilenya
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
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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
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2013: FDA links ezogabine to retinal abnormalities and blue skin discoloration
2017: GSK voluntarily withdraws ezogabine from market for poor commercial performance
Ezogabine
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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
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Untreated control
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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
mutation
9/2019
9/2019
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.
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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
Disclaimer
This preliminary information has been prepared by the Company solely for information purposes to assist the recipient in deciding whether to proceed with further analysis of the transaction contemplated herein. This document does not constitute an offer or invitation for the sale or purchase of securities. The information set out herein is preliminary and should not be relied upon for any purpose. The investment opportunity described herein is speculative and entails a high degree of risk. Due to the illiquidity of this investment, if you invest you must expect to bear the economic risk of the investment for an indefinite period. There is no assurance that any market will develop for the securities described herein. Certain statements in this document that are not historical fact constitute "forward-looking statements." You are cautioned not to place undue reliance on these for ward-looking statements. The Company generally identifies forward-looking statements by using words like "believe," "intend," "target," "expect,'' "estimate," "may," "should," "plan," "project," "contemplate," "anticipate," "predict" or similar expressions. You can also identify forward-looking statements by discussions of strategies, plans or intentions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause the actual results of the Company to be materially different from historical results or from any results expressed or implied by such forward-looking statements. All forward-looking statements herein are qualified in their entirety by this cautionary statement. The Company made the statements in these materials as of the date hereof unless it is stated otherwise. Neither the delivery of these materials, nor any sale of securities by the Company after the date of these materials, shall create any implication that the information contained herein or the affairs of the Company have not changed since the date hereof or that such information is correct as of any time subsequent to its date. The Company management based all estimates and projections as to events that may occur in the future (including projections of revenue, expense and net income) upon their best judgment as of the date of these materials and upon assumptions and circumstances and events that have not yet taken place, may not have an empirical basis, are subject to variation and are inherently unpredictable. Whether or not such estimates or projections may be achieved will depend upon the Company achieving its overall business objectives and the availability of funds, including funds from the sale of the securities described herein. There can be no assurance that any estimates or assumptions will prove accurate or that any of the projections will be realized. The Company does not guarantee that any of these projections will be attained. Actual results will vary from the projections, and such variations may be material. You should not construe the contents of these materials as legal, tax or investment advice. You should consult your own counsel, accountant or business advisor as to legal and other matters concerning your investing in these securities. These materials are not all-inclusive, nor do they contain all the information which you may require. Consult your own legal, tax or investment counsel regarding the legality or suitability of your investment in these securities under applicable legal, investment or similar laws, regulations or fiduciary standards. The Company makes no representation regarding your investment herein under any legal, investment or similar law, regulations or fiduciary standards. The information in this document is not targeted at the residents of any particular country and is not intended for distribution to, or use by, any person in any jurisdiction or country where such distribution or use would be contrary to local law or regulation. Furthermore, the securities referred to in this document are not available to persons resident in any jurisdiction or country where such distribution would be contrary to local law or regulation. The Company is offering certain securities pursuant to exemptions from registration provided by Section 4(2) of the Securities Act of 1933,as amended (the "33 Act") and regulations thereunder, certain state securities laws and certain rules and regulations promulgated pursuant thereto. The offering of the securities is not registered under the 33 Act and are subject to certain transfer restrictions. In making an investment decision with respect to the securities, you must conduct and rely on your own evaluation and investigation of the Company and the terms of the offering, including the merits and risks involved, and not the contents of this confidential, preliminary information. The securities have not been registered with or approved by the United States Securities and Exchange Commission ("SEC") or any state securities or other jurisdiction's securities commission or other regulatory authority. Neither the SEC nor any state or other jurisdiction's securities commission or other regulatory authority has passed upon the accuracy or adequacy of this confidential preliminary information. Any representation to the contrary is unlawful. The Company will only make offers and sales of common stock to persons who: (a) are "accredited investors" within the meaning of Regulation D under the 33 Act; (b) are sophisticated in business and financial matters; (c) the Company believes have the knowledge and experience to evaluate the merits and risks of the investment; (d) have sufficient financial means to bear the risk of total loss of their investment; (e) have substantial income; and (f) can afford the illiquidity of these securities. The Company reserves the right to approve or disapprove each prospective purchaser and accept or reject any offers to purchase securities in whole or in part in its sole discretion. The securities will bear a restrictive legend that any purchaser of the securities may not resell, transfer or otherwise dispose of the securities unless the transaction effecting such disposition is registered under the 33 Act, or an exemption therefrom is available.
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