Knopp Biosciences Creating new treatments to change the course of human health

Investment highlights

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Focused on developing and delivering breakthrough treatments for immunological and neurological diseases

Lead program oral dexpramipexole in clinical trials for eosinophil-associated diseases

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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PEOPLE EXPERIENCE PRODUCTS

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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Robust pipeline of differentiated assets with blockbuster potential

Immunology

COMPOUND INDICATION

COMPOUND

KB-3061 KCNQ2 epileptic encephalopathy

Kv7 modulator

Kv7 modulator

Neuropathic pain

Hearing disorders

Neurology (Kv7 platform)

PRECLINICAL PHASE 1 PHASE 3 PHASE 2

Dexpramipexole Moderate-to-severe eosinophilic asthma

Dexpramipexole Hypereosinophilic syndrome

DISCOVERY

INDICATION

Kv7 modulator ALS

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

Profound eosinophil lowering in four clinical trials

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

World’s most advanced library of Kv7 activators

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

H 2 N

N H

Dexpramipexole in eosinophil-associated diseases

Novel mechanism: Eosinophil maturation inhibitor

Exceptional pharmacological and pharmaceutical properties

Greater than 98% orally bioavailable

No high-affinity pharmacological interactions identified

Eliminated by the kidneys, not metabolized by the liver

Easy to synthesize and manufacture, low COGS

Differentiated product profile

Equal-to-better eosinophil lowering than biologics in asthma

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

94% lowering, BL to Month 6, p< 0.001

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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

78% lowering, BL to Month 3, p=0.01

Blood

Tissue

Eosinophil lowering effectiveness driven by unique mechanism of action: eosinophil maturation inhibition (EMI)

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Eosinophilic myeloblast

Eosinophilic promyelocyte

Eosinophilic myelocyte

Eosinophilic metamyelocyte

Eosinophilic band cell

Mature eosinophil

Point of maturation inhibition

X

Eosinophilic promyelocyte

Mature eosinophil

On treatment Pre-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.”

-June 11, 2015 Pulmonary-Allergy Drugs Advisory Committee Meeting

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:

Change in blood eosinophils

Secondary endpoints:

FEV1, ACQ

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Key inclusion criteria: Asthma requiring ICS/LABA (GINA steps 3-5) Blood eosinophil count ≥ 300 Variable expiratory airflow limitation

Eosinophil Recovery

Phase

Study Week 0 4 8 12

Placebo (n = 25)

Oral dexpramipexole 75 mg/day (n = 25) Ru

n-i

n

-2 24 16

Study Visits

V1 V2 V3 V4 V5 V6 V8 V9

Oral dexpramipexole 150 mg/day (n = 25)

Primary Assessment Phase

Oral dexpramipexole 300 mg/day (n = 25)

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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)

Prof Andrew Wardlaw (Leicester)

Prof Ian Pavord (Oxford)

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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

Annual U.S. WAC

price Global revenue

Otezla

Moderate-severe psoriasis 2MM

>$41,000 $1,608MM 2018 $1,429MM YTD 9/2019

Active psoriatic arthritis 2-3MM

Bechet’s disease oral ulcers 25,000

(7/100,000)

Xeljanz

Moderate-severe rheumatoid arthritis 1.5MM

>$44,000 $1,774MM 2018 $1,634MM YTD 9/2019

Moderate-severe ulcerative colitis 600,000

Active psoriatic arthritis 2-3MM

Tecfidera Relapsing multiple sclerosis

850,000

>$83,000

$4,274MM 2018 $3,271MM YTD 9/2019

Gilenya

Relapsing multiple sclerosis

1MM >$82,000 $3,341MM 2018 $2,420MM YTD 9/2019

Secondary progressive MS

Clinically isolated syndrome (MS)

Aubagio

Relapsing multiple sclerosis

1MM >$76,000 €1,647MM 2018 €1,397MM YTD 9/2019

Secondary progressive MS

Clinically isolated syndrome (MS)

Kv7 activator platform

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)

– A-2 (> 1000 compounds) 2000 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

2011: Ezogabine (GSK) approval for adjunctive treatment of partial-onset seizures validates Kv7.2/7.3 as epilepsy drug target

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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

Ba

se

lin

e

10

µM

30

61

10

µM

EZ

O

0

50

100

150

GABAA PAM Assay

% C

on

tro

l

✱✱

Data presented at American Epilepsy Society Annual Meeting, Baltimore, MD. Dec. 9, 2019.

T0 T8

0

50

100

Stability to Photo-oxidation

Time pt.

%C

om

po

un

d r

em

ain

ing KB-3061

EZO

* * <1% ezogabine

KB-3061 restores function in mutated ion channels, suggesting disease-modifying potential in rare infant brain disorder

0

1

2

3

4

5

6

7

8

9

10

wt/T274M Poren=4

wt/R581L CTDn=6

wt/A294V Poren=7

Cu

rren

t D

ensi

ty (

pA

/pF)

wt/wtwt/mutwt/mut + 0.3 µM KB-3061

Untreated control

*

* indicates p < 0.001

*

*

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

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Target potency, favorable ADMET profile, and preclinical efficacy established

− Potent Kv7.2/7.3 activation with GABAA attenuation achieved (α1β3ɣ2)

− 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

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Rare, genetic diseases create blockbuster opportunities

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

250 annual births (1/16,000)

15K-20K total $25,0000-$75,000

Weight-based

$1.9B (projected 2025)

$102MM 1H 2019

Lenox-Gastaut syndrome

350 annual births 30K-50K total

Kalydeco 2012 Cystic fibrosis with CFTR mutation

1,000 annual cases 30K total ~%5 with CFTR

mutation

$311,000 $1B 2018 $755MM YTD

9/2019

Myozyme/ Lumizyme

2010 Pompe disease

100 annual births 5K-10K total

$298,000 €840MM 2018 €680MM YTD

9/2019

Spinraza 2016 Spinal muscular atrophy

500 annual cases 10K-25K total

Year 1: $750,000 Year 2+: $375,000

$1.7B 2018 $1.5B YTD

9/2019

Zolgensma 2019 Type 1 spinal muscular atrophy

300 annual cases 1K-3K total

$2.1MM (one-time treatment)

$2B projected at peak

$160MM 1Q 2019

Soliris/ Ultomiris

2007

Paroxysmal nocturnal hemoglobinuria

500 annual cases

$536,000 Soliris $3.6B 2018

$3.1B YTD 9/2019

Atypical hemolytic uremic syndrome

1/500,000

$458,000 Ultomiris

Summary

$2.1 billion market cap in rare pediatric epilepsy

Knopp science validated by significant government funding, commercial opportunity validated by public markets

$6.1 billion market cap in rare eosinophil-associated diseases

$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.

Phase 2

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Potential to drive liquidity through IPO or M&A with 2020 milestones

2019 3Q 4Q

2020 1Q 2Q 3Q 4Q

Dexpramipexole: moderate-to-severe eosinophilic asthma

KB-3061: KCNQ2-EE*

Dexpramipexole

Phase 3 in HES

Phase 3 in asthma

Phase 2 POC in EGID

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

Phase 2/3 in KCNQ2 EE (KB-3061)

Phase 2 in pediatric epilepsies (KB-3061)

Novel clinical candidates – Neuropathic pain** – ALS – Tinnitus

Phase 1 IND

2021 1Q 2Q

• * NIH Blueprint Award U44NS093160. • ** NIH HEAL Award U44NS115732.

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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