Issuer Free Writing Prospectus
Filed Pursuant to Rule 433
Registration No.
333-193204
March 21, 2014
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A Pharmaceutical Platform Focused on Trapping Aldehydes
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Forward-Looking Statements
This presentation includes statements contains forward-looking statements that involve risks and uncertainties. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “target,” “design,” “estimate,” “predict,” “potential,” “plan” or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Forward-looking statements include, but are not limited to, statements about: our expectations regarding our expenses and revenue, the sufficiency of our cash resources and needs for additional financing; our anticipated growth strategies; our expectations regarding competition; the anticipated trends and challenges in our business and the market in which we operate; the timing and success of preclinical studies and clinical trials conducted by us and our development partners; the ability to obtain and maintain regulatory approval of our product candidates, and the labeling for any approved products; the scope, progress, expansion, and costs of developing and commercializing our product candidates; the size and growth of the potential markets for our product candidates and the ability to serve those markets; the rate and degree of market acceptance of any of our product candidates; our ability to establish and maintain development partnerships; our ability to attract or retain key personnel; our expectations regarding federal, state and foreign regulatory requirements; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates; and our use of proceeds from this offering.
Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. Any forward-looking statement made by us in this presentation speaks only as of the date on which it is made. Except as required by law, we assume no obligation to update these statements publicly, or to update the reasons actual results could differ materially from those anticipated in these statements, even if new information becomes available in the future.
Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, we caution you that forward-looking statements are not guarantees of future performance and that our actual results of operation, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this presentation as a result of, among other factors, the factors referenced in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the prospectus contained in our Registration Statement on Form S-1 filed with the Securities and Exchange Commission for our proposed initial public offering, as amended (the “Registration Statement”). In addition, even if our results of operation, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-looking statements contained in this presentation, they may not be predictive of results or developments in future periods.
You should read carefully Registration Statement, including the factors described in the “Risk Factors” section of the prospectus contained in the Registration Statement, to better understand the risks and uncertainties inherent in our business and underlying any forward-looking statements.
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Free Writing Prospectus Statement
This presentation highlights basic information about us and the offering. Because it is a summary, it does not contain all of the information that you should consider before investing in our common stock.
We have filed a registration statement (including a prospectus) with the United States Securities and Exchange Commission (SEC) for the offering to which this presentation relates. The registration statement has not yet become effective. Before you invest, you should read the prospectus in the registration statement (including the risk factors described therein) and other documents we have filed with the SEC for more complete information about us and the offering. You may get these documents for free by visiting EDGAR on the SEC Web site at http://www.sec.gov. The preliminary prospectus, dated March 21, 2014, is available on SEC website at http://www.sec.gov.
Alternatively, we or any underwriter participating in the offering will arrange to send you the prospectus if you contact Aegis Capital Corp., Prospectus Department, 810 Seventh Avenue, 18th Floor, New York, NY 10019, telephone: 212-813-1010, e-mail: prospectus@aegiscap.com.
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Offering Summary
Issuer Aldeyra Therapeutics, Inc. Exchange/Ticker NASDAQ Capital Market / ALDX Shares Offered 2,275,000 (100% primary) Over-Allotment 15% or 341,250 (100% primary) Price Range $10.00—$12.00
Clinical development of NS2, working capital,
Use of Proceeds and other general corporate purposes
Sole Book-Runner Aegis Capital Corp.
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Management and Directors
Todd Brady, M.D., Ph.D. – President, Board of Directors CEO, and Director
– over 15 years of pharmaceutical Boyd Clarke – former CEO Aviron
business and clinical development (acquired by MedImmune)
Domain Associates, Phenome Gary Phillips, M.D. Chief Strategy Sciences, (acquired by Officer Mallinckrodt Pharmaceuticals
Xanthus/Antisoma), Aderis
Pharmaceuticals (acquired by Ben Bronstein, M.D. – former CEO Schwarz/UCB) Peptimmune (acquired by Genzyme) Neal Walker, D.O. – CEO Aclaris
Scott Young – Chief Operating Therapeutics Officer North American
– over 25 years of pharmaceutical clinical Marty Joyce – former CFO of Serono Inc. development
– Genetics Institute, Genzyme, Jesse Treu, Ph.D. – Domain Associates
Oxigene, Repligen
Todd Brady – CEO Aldeyra Therapeutics
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Investment Highlights
Unique, Innovative Platform Technology to Trap Aldehydes
Rare and mass-market diseases in which toxic aldehydes are implicated
Modest Funding Required for Multiple Clinical Events
$10M for currently planned clinical development of aldehyde traps: Phase II/III results for most advanced program and Phase II results from three other indications in 2015
Initiate four Phase II and one Phase I trials in 2014
Lead compound in 4 topical indications: two dermal and two ocular
Large Markets with Significant Unmet Medical Need
Markets for orphan indications alone are substantial, and positive data may suggest efficacy in a broad array of mass-market diseases
Strong Patent Portfolio of Compositions, Uses, and Formulations
Extend to late 2020s worldwide and to 2033 in US, assuming Hatch-Waxman extension
Marquee Investors Validate Science
Johnson & Johnson Development Corporation and Domain Associates – one of the oldest and largest healthcare venture capital funds worldwide
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NS2 Product Portfolio
Sjögren- Acute
Discoid Ocular Larsson Anterior (1) Lupus Rosacea Syndrome Uveitis
Rare Disease Rare Disease Rare Disease
No FDA-Market with No FDA- with Need for with Need for Approved Opportunity Approved Effective Therapy Effective Therapy Therapy Therapy without Toxicity without Toxicity
Topical
Topical
Formulation Dermatologic Topical Eye Drop Topical Eye Drop Dermatologic and Oral
Issued Issued Issued Issued Patents Composition of Composition of Composition of Composition of Matter Matter Matter Matter
DATA EXPECTED IN SECOND HALF OF 2015: Phase I Phase II Phase III
Sjögren-Larsson Syndrome (Dermatologic) Sjögren-Larsson Syndrome (Oral) Discoid Lupus Acute Anterior Uveitis
Ocular Rosacea (1)
(1) Ocular Rosacea with Meibomian Gland Dysfunction
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Aldehydes Are Mediators of Disease
Toxic mediators of numerous diseases
Modify cellular constituents, Free Aldehydes lead to indigestible aggregates, and are pro-inflammatory Lipid, DNA, Protein, Oxidation, Carbohydrate
Dehydrogenases attempt to Metabolism
Modification eliminate free aldehydes
High levels are implicated in autoimmune, inflammatory, neurological, cardiovascular and endocrinologic diseases
Cytokine Release NF-KB Activation
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Aldehyde Traps: A Novel Therapeutic Approach
Aldehyde • Aldeyra’s compounds rapidly trap Binding free aldehydes
Adduct • Trapped aldehydes are Transport transported to the lysosome
Cellular • Drug and aldehydes are Disposal metabolized within hours
Aldeyra’s lead aldehyde trap, NS2, appears to have minimal pharmacology; it does not seem to affect receptors or proteins. No similar technology believed to be available.
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Trapping Aldehydes Generates a Broad Anti-Inflammatory Response
Mice treated with NS2 or vehicle 30 minutes prior to
0%
endotoxin exposure; TNF-a IL-1b IL-5 IL-17 cytokines measured two
Levels -20%
hours after endotoxin exposure -40%
Cytokine ** Vehicle in -60% ** vs.
*** -80% Reduction ** -100% ** p<0.01 *** p<0.001
In an endotoxin model of cytokine generation in mice, NS2 administration significantly reduced levels of a broad array of pro-inflammatory cytokines.
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NS2 Decreases Dermal Inflammation in Animal Models
150 150
) ) * p<0.05 (mm (mm ** p<0.01 * Thickness 100 ** Thickness 100 Ear Ear Mouse 50 Mouse 50
0 0
Vehicle NS2 Vehicle NS2
Murine Model of Contact Dermatitis (PMA) Murine Model of Allergic Dermatitis (Oxazolone) 6.5 hours after NS2 Administration 24.5 hours after NS2 Administration
Single dose of NS2 has early and potent anti-inflammatory effect that reduces swelling in two different models of skin inflammation
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NS2 Speeds Healing and Reduces Scarring of Lesions in Animal Models
Hamster cheek pouch radiation-induced oral mucositis
Severe
3
Vehicle Moderate p=0.1 Score 2 Score Marked mucositis p=0.01 Fibrosis 1 Mild Vehicle
NS2 Minimal
NS
0
2
6 21 36
Day None
NS2 speeds lesion healing and reduces scarring in a model of skin and eye disease
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NS2 Protects a Key Lipid Relevant to Skin and Eye Disease in Cell Systems
p<0.01
p<0.01
Aldehyde- Aldehyde Damaged Aldehyde- Lipid Damaged Control Lipid NS2+Aldehyde
Normal SLS SLS Mutants + Human Skin Cells Cells Mutants NS2
NS2 prevents aldehyde-mediated damage of lipid that is critical to dermal moisture barrier and ocular tear integrity
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NS2 Traps Aldehydes Generated by Dry Conditions in Human Tissue
Malondialdehyde concentration in human tissues after 72 hours of NS2
Human Skin Tissue Human Ocular Tissue p < 0.05 30 12 M) p < 0.01
25 )M 10
Levels 20
Aldehyde Levels (Malondialdehyde mM)
Normal Tissue Dry Tissue Dry Tissue + NS2 Normal Tissue Dry Tissue Dry Tissue + NS2 Eye Drop Dermatologic
Potential to reduce aldehyde-mediated damage in diseases characterized by dry tissue
(Including Sjögren-Larsson Syndrome and Ocular Rosacea with Meibomian Gland Dysfunction)
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NS2 Summary of Efficacy: Multiple Mechanisms of Action
NS2
Decreased Aldehyde
Anti-inflammatory Load Lipid Protection
Lesion Healing Anti-fibrotic
The same biological mechanisms may apply to many rare and prevalent diseases.
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Positive NS2 Eye Drop Phase I Results
o 48 healthy volunteers
o Double masked and placebo controlled
o Two treatment stages for two drug concentrations:
- Single day 0.25% & 0.5% bid & qid
- Seven day 0.25% & 0.5% qid o Eye drops were well tolerated in all treatment groups o No plasma exposure detected by LC-MS/MS (<5 ng/ml) NS2 is Phase II-ready as an eye drop
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Acute Anterior Uveitis and Ocular Rosacea with Meibomian Gland Dysfunction
Ocular
Uveitis
Rosacea
Acute anterior Ocular ocular inflammation inflammation with dry eye
Pain, Burning/itching, photophobia, eyelid swelling, loss of vision corneal damage
Estimated
May exceed 25,000 US
10M patients patients/year
Aldehydes are inflammatory mediators of both ocular diseases, and can lead to degradation of tear quality
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Anticipated Clinical Trial Designs for Ocular Disease
Acute Anterior
Uveitis Ocular Rosacea (1)
Formulation Eye Drop Eye Drop Control Active 1:1 Placebo 1:1 Total Patients 40-45 Patients 40 Patients
Treatment Time 8 weeks 12 weeks
Endpoints Cell Counts, Symptoms Ocular Signs, Symptoms
(1) Ocular Rosacea with Meibomian Gland Dysfunction
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Sjögren-Larsson Syndrome (SLS): A Rare Disease with No Approved Therapy
Rare disease caused
Symptoms include by mutation in Fatty severe skin thickening Aldehyde (ichthyosis), retinal Dehydrogenase, leading disease, and to high levels of toxic neurological disorders aldehydes
Diagnosed at birth, but Estimated no approved therapy 1/250,000 people = about that addresses disease; 1000 patients in US and Therapeutic aldehyde trap patients survive into a greater number in
50s Europe (1) would be analogous to an enzyme replacement therapy
(1) Extrapolating from a Swedish estimate, it is generally assumed that there are approximately 1,000 SLS patients in the United States and a greater number of SLS patients in Europe.
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Discoid Lupus: A Rare Disease of Skin
Rare disease Symptoms associated with high characterized by lesions aldehyde levels and that are inflamed, non-antibodies to aldehyde- healing, and fibrotic modified proteins (scarring)
Steroids commonly Estimated prevalence is prescribed but toxicity 100,000 patients in the Therapeutic aldehyde trap could limits use United States
reduce inflammation, promote healing, and diminish scarring
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Anticipated Clinical Trial Designs For Dermatologic Disease
Sjögren-Larsson
Discoid Lupus
Syndrome
Formulation Dermal Topical Dermal Topical Control Placebo 1:1 Placebo 1:1 Total Patients 12 Patients 20 Patients
Treatment Time 8 weeks 12 weeks
Endpoints Visual Rating CLASI
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Unmet Medical Need for Our Clinical Indications
We believe market demand is substantial for a novel therapy that is safe and effective in the indications that we intend to develop
There is no FDA-approved therapy for Sjögren-Larsson Syndrome
There is no FDA-approved therapy for Ocular Rosacea with Meibomian Gland Dysfunction
Therapies for discoid lupus and acute anterior uveitis are associated with significant side effects
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Orphan Topical Drug: Attractive Pricing, Large Market
Orphan Topical Pricing for Cutaneous Lymphoma 25% of body
Twice per day surface area treatment treated
Payer research Estimated confirms similar or
>$200,000 per year higher pricing for a topical SLS therapy
Total US SLS market: ~$200M
* NS2 has not received orphan designation
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Intellectual Property Portfolio: Composition of Matter into the 2030s
Formulation Topical dosing
Method Uses for aldehyde traps in diseases
NS2 to 2033 in US, assuming Hatch-Composition Waxman extension; Issued or allowed worldwide*
*Pending in Brazil, India
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Rare Disease Company Valuation Comparables
Diseases in
Company Stage Phase II or III Valuation Clinical Trials
(1) $77M
Aldeyra Therapeutics (ALDX) Phase II 4(1)
(midpoint post-money)
Bluebird Bio (BLUE) Phase II 2 $648M
Sarepta Therapeutics (SRPT) Phase II 1 $1.1B Ultragenyx (RARE) Phase II 2 $1.8B Synageva BioPharma (GEVA) Phase III 1 $3.1B
Intercept Pharmaceuticals (ICPT) Phase III 4 $8.2B
Rare disease-focused biotechnology companies are highly valued, but Aldeyra has potential to expand to prevalent diseases as well.
(1) Anticipated by end of 2014, pending FDA review, among other contingencies. Data as of 3/20/14
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Pre-IPO Capital Structure
Capitalization Shares Outstanding % Outstanding
Common Stock (1) 3,970,164 85% Stock Options (2) 609,842 13% Warrants (3)110,647 2% Fully-Diluted Shares Outstanding 4,690,653 100%
(1) Includes Preferred Stock to be converted to Common Stock at IPO (2) Does not include 155,148 options to be granted at IPO
(3) Common Stock to be issued upon net exercise of outstanding warrants at IPO (assuming an $11.00 offering price); does not include underwriter warrants
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Use of Proceeds and News Flow
Research and Development: $10M
– Orphan designations, IND filings, and additional pre-clinical data and publications
– Phase II/III for Sjögren-Larsson Syndrome (SLS)
– Phase II for discoid lupus
– Phase II for acute anterior uveitis
– Phase II for ocular rosacea
– Phase I for NS2 oral administration (for SLS)
Working capital and other general corporate purposes
Data from all trials expected in 2015
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Investment Highlights
Rare, Innovative Platform Technology to Trap Aldehydes
Orphan and mass-market diseases in which toxic aldehydes are implicated
Modest Funding Required for Multiple Clinical Events
$10M for currently planned clinical development of aldehyde traps: Phase II/III results for most advanced program and Phase II results from three other indications in 2015
Initiate four Phase II and one Phase I trials in 2014
Lead compound in 4 topical indications: two dermal and two ocular
Large Markets with Significant Unmet Medical Need
Markets for orphan indications alone are substantial, and positive data may suggest efficacy in a broad array of mass-market diseases
Strong Patent Portfolio of Compositions, Uses, and Formulations
Extend to late 2020s worldwide and to 2033 in US, assuming Hatch-Waxman extension
Marquee Investors Validate Science
Johnson & Johnson Development Corporation and Domain Associates – one of the oldest and largest healthcare venture capital funds worldwide
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