March 2022 - Restore Vision & Clarity - cloudfront.net
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Restore Vision & Clarity March 2022
Disclosures and Forward-Looking Statements
• This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation
Reform Act of 1995. Such statements include, but are not limited to, statements concerning the regulatory
timelines, commercial timelines, cash runway, scalability, and future clinical trials in RM, presbyopia, NVD and
DR/DME, including the potential for Nyxol to be a “best in class” presbyopia drop. These forward-looking
statements are based upon the Company’s current expectations and involve assumptions that may never
materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from
those anticipated in such forward-looking statements as a result of various risks and uncertainties, including,
without limitation: (i) the success, costs, and timing of regulatory submissions and pre-clinical and clinical trials,
including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical
trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the
inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its
preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market
opportunities, (viii) the effects of COVID-19 on clinical programs and business operations, (ix) the success and
timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s
product candidates and (x) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of
important factors that could cause actual events to differ from expectations should not be construed as
exhaustive and should be read in conjunction with statements that are included herein and elsewhere,
including the risk factors detailed in documents that have been and may be filed by the Company from time to
time with the SEC. All forward-looking statements contained in this presentation speak only as of the date on
which they were made. The Company undertakes no obligation to update such statements to reflect events
that occur or circumstances that exist after the date on which they were made.
• The Company makes no representation or warranty, express or implied, as to the accuracy or completeness
of the information contained in or incorporated by reference into this presentation. Nothing contained in or
incorporated by reference into this presentation is, or shall be relied upon as, a promise or representation by
the Company as to the past or future. The Company assumes no responsibility for the accuracy or
completeness of any such information. This presentation also contains estimates and other statistical data
made by independent parties and by us relating to market shares and other data about our industry. This data
involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such
estimates. The trademarks included herein are the property of the owners thereof and are used for reference
purposes only. Such use should not be construed as an endorsement of such products.
2
§ Differentiated, Late-Stage Pipeline for Front and Back of the Eye
ü Nyxol with > 330 patients treated across 9 trials (505(b)(2) regulatory pathway)
ü APX3330 with > 340 patients treated across 11 trials (NCE development pathway)
ü Nyxol and APX3330 achieved promising clinical data and favorable safety profile
across multiple Phase 1, 2, and 3 trials
¡ Near-term Commercialization Opportunities in Multiple Large Unmet Markets
NASDAQ: OCUP ü Addressing 4 large markets with unmet needs: RM, Presbyopia, NVD, and DR/DME
ü Successful trial execution with 2 recent positive Phase 3 & Phase 2 data read-outs for Nyxol in
RM and Nyxol + LDP in Presbyopia, respectively
Multiple Catalysts in 2022:
ü Stable, small-molecule drugs with commercial scalability
ü Nyxol alone VEGA-1 P2 trial for P JAN 2022
ü Robust and growing IP portfolio: US and global patents issued thru 2034 for both assets as
• Nyxol MIRA-3 P3 trial for RM EARLY 2022 well as new 2039 Nyxol patent issued for presbyopia
• Nyxol Pediatric trial for RM EARLY 2022
¡ Multiple data readouts in 2022 with Track Record of Execution
• Nyxol LYNX-1 P3 trial for NVD EARLY 2022
ü $24.5 million cash reported at 12-31-21 sufficient for operations into 2Q 2023
• APX3330 ZETA-1 P2b trial for DR/DME 2H22
ü Highly experienced management, Board and KOLs with broad ophthalmic and biotech drug
• NDA Filing for Nyxol for RM LATE 2022 development and commercialization success
ü Low-cost, fast-enrolling, short-duration clinical trials
P= Presbyopia
RM = Reversal of Mydriasis ü Favorable precedent regulatory environment for ophthalmic drug approval
NVD = Night Vision Disturbances
DR/DME = Diabetic Retinopathy/Diabetic Macular Edema ü Analyst coverage by Cantor, Canaccord, Jones Trading, Alliance Global, and HCW
3
Ophthalmology – An Attractive Biotech Sector
Demographics, M&A, Regulatory Approvals and Efficient Trials Favor Ophthalmic Drugs
Deal Activity New Product Approvals
September 2021
7 of 60 FDA Drug Approvals in 2021 Were
April 2021
Ophthalmic Drugs1 and 1 in 2022
Aging
$1.75B Population
*sNDA
Active Favorable
October 2021
December 2021
Partnering in Regulatory
2021 Environment
~$2B Lower Cost,
Quick Enrolling,
Short Duration
Clinical Trials
December 2021 December 2021
~$1.5B $670M Ranibizumab biosimilar
Source:
1. Endpoint Dec 29, 2021- Hitting a new record on drug approvals, the FDA offers a thumbs-up to another atopic dermatitis contender;
2. OIS Year in Review 2021;
4 3. Company press releases
Nyxol® & APX3330: Development History and Patents
Significant Preclinical & Clinical Data Supporting Safety, MOA, Efficacy, and PK Profile
Nyxol® APX3330
Novel α1/ α2 Blocker Oral REF-1 Inhibitor
505(b)(2) New Chemical Entity
9 Exposure in
11
Exposure in
Completed >330 Humans Patent
Coverage >340 Humans Patents to
Phase 1,
Phase 2, and
Subjects
Dosed
28 2034+
Completed
Phase 1 and
Subjects
Dosed
365 2034+
Days Phase 2 Trials Days
Phase 3 Trials
US Market Opportunity
Reversal of US Market Opportunity
RM ~$500 M DR Diabetic
Mydriasis
Retinopathy
Presbyopia
$10+B
P $10B - $20B Oral Rx Revenues*
DME
Diabetic
Macular Edema
Night Vision
NVD
Disturbances
$2B - $4B
5 Source: Eisai and Apexian Data; GlobalData Market Research Report, 2020; Company Estimates for US Market Size; *Ocuphire internal estimates
Ocuphire Pipeline & Clinical Milestones
Multiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated this Year
Product Regulatory
Indication Candidate Pre-clinical Phase 1 Phase 2 Phase 3 Approval Anticipated Milestones
q MIRA-3 Phase 3 data expected in
early 2022 (n=330)
ü ★
Reversal of Nyxol®
Mydriasis (RM) Eye Drop MIRA-2
★ q MIRA-4 Pediatric safety study data
expected in early 2022 (n=20)
Nyxol®
Eye Drop
q VEGA Phase 3 program planned to
Presbyopia (P)
Nyxol® +
VEGA-1 ü initiate in mid 2022
Low-Dose (0.4%)
Pilocarpine
Eye Drops
Dim Light or Night
Vision Nyxol® q LYNX-1 Phase 3 data expected in
Disturbances Eye Drop ★ early 2022 (n=140)
(NVD)
Diabetic
Retinopathy (DR)/ APX3330 q ZETA-1 Phase 2b data expected in
Macular Edema Oral Pill ★ 2H22 (n=90-100)
(DME)
DME or Wet Age-
APX2009 q Seeking partner funding for IND
Related Macular
Degeneration
(Intravitreal or ü Positive data readout enabling studies and further
Local Delivery) development
(wAMD) ★ Ongoing trial
6 Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution)
NYXOL®
EYE DROPS
RM Reversal of Mydriasis
Nyxol as a Single Nyxol with LDP
1 2
P Presbyopia Drop for Presbyopia
0.4%
Adjunctive Therapy
NVD Night Vision Disturbance
7
Nyxol’s Differentiated MOA as an α1 Blocker
Phentolamine Mesylate Reformulated as a Proprietary Topical Eye Drop è Nyxol
Phentolamine Mesylate is the Active Ingredient in Nyxol: a Non-selective α1 & α2 Antagonist
Blocking α1 Blocking α1
Reduces Pupil Size Dilates Blood Vessels
Iris Dilator Nyxol blocks α1
Muscle receptors only found on
the Iris Dilator Muscle Phentolamine mesylate is approved
for 2 indications:
• Regitine® (Pheochromocytoma)
– intravenous injection approved
Decreases Pupil Size in 1952
(Moderate Miosis)
Iris Sphincter • OraVerse® (Reversal of oral
Muscle anesthesia) – intramuscular
injection approved in 2008
Nyxol® is the only eye drop in clinical development for
505(b)(2) Regulatory Approval Pathway
multiple indications that does not affect the ciliary muscle
Note: α2 MOA contributes to IOP lowering, not pupil size reduction
8
Nyxol Product Candidate Profile
Novel, Differentiated Alpha 1/2 Blocker Eye Drop for Refractive Indications
Nyxol: 0.75% Phentolamine Ophthalmic Solution
Preservative Free, EDTA Free, and Stable
Efficacy Data Favorable Safety Profile Durable
Nyxol Improves Vision by No Systemic Effects Effects Last ≥ 24 Hours
Decreasing Pupil (~1-1.5mm) No Changes in Blood Pressure Chronic daily dosing of Nyxol
No Changes in Heart Rate at bedtime reduces pupil size
↑ Near
for up to 24 to 36 hours
Well-Tolerated Topical Effects
↑ Distance
Mild, Transient, Reversible Eye
↑ Contrast Sensitivity (night) Redness
IOP Unchanged or Decreased
No Headaches
9 Nyxol Clinical Trials
RM
I had a premium cataract
I have to visit my retina MD for my
procedure by my MD, and I was
monthly injections, where I am
unable to see clearly for two
dilated. Being dilated every month is
days. My doctor said it was due
a huge burden on my day.
to my dilation. I did not expect
my dilation to last that long.
I have to stay indoors. They say it only lasts a few hours,
but it lasts all day, and it is very annoying.
10RM Reversal of Mydriasis Unmet Need & Landscape
With No Commercially Available Treatment, Nyxol is Uniquely Positioned as a New Reversal Drop
The Problem No Currently Available Treatments
• At many annual eye exams and specialty
visits, pupils are pharmacologically Current Landscape:
dilated, impairing vision for 6-24 hours
• Rare off-label use of cholinergic
• Dilated eyes experience: agonists (e.g., pilocarpine) given
– Heightened sensitivity to light ciliary muscle safety issues
– Inability to focus, headaches
• Optomap® is offered by
– Difficulty reading, working & driving optometrists to avoid dilations for
– Halos and glare ~$50 cash-pay, however images
may provide limited view of
– Cycloplegia (loss of accommodation)
retina and disease pathology
Nyxol’s MOA Uniquely Suited As A Reversal Drop For Dilations
11 Source – Optos plc PricingRM MIRA-2 and MIRA-3 Phase 3 Registration Trial Design
Randomized, Double-Masked, Placebo-Controlled, Parallel, One-Day Trial
Endpoints
0.75% Nyxol Mydriatic Nyxol drop(s)
Agent (2 drops study eye, Primary: % of subjects (study eye)
A, B, or C 1 drop fellow eye)
returning to baseline (within 0.2 mm)
Primary photopic pupil diameter (PD) at 90
12 to 16 Endpoint
Follow
Treatment Up Visit min
US sites Mydriasis
1:1 -1 Hour
(Max Dilation)
Secondary:
1:1
2:1
0 min 1 Hr 2 Hr 3 Hr 4 Hr 6 Hr 24 Hr
185 to 330 • % of subjects returning to baseline
subjects 30min 90min at 0min, 30min, 1h, 90min 2h, 3h,
Mydriatic 4h, 6h, 24h (overall, by mydriatic
Placebo drop(s)
Placebo Agent (2 drops study eye, agent, by iris color)
A, B, or C 1 drop fellow eye)
• Mean change in pupil diameter at
Eligibility all timepoints
Randomization
Screening
• Accommodation
(Tropicamide/Paremyd)
MIRA-3 Started in Nov 2021; Enrolled 368 in Feb 2022 • Visual Acuity with Glare (new)
• Pupillary Light Reflex (new)
Topline Results MIRA-3 Expected in Early 2022 • Safety and tolerability (redness)
MIRA-2 Topline Results Presented March 2021
12 Mydriatic Agents 3:1:1 – 2.5% phenylephrine (alpha-1 agonist), 1% tropicamide (cholinergic blocker), Paremyd® (combination)RM MIRA-2 RM Phase 3 Trial Met Primary & Secondary Endpoints
49% of Patients Returned to < 0.2mm of Baseline at 90 Minutes vs. 7% Placebo
MIRA-2 Phase 3 Trial
Nyxol Returned More Subjects to Baseline Pupil Diameter (PD) Nyxol Reduced PD Faster Across All Mydriatic Agents*
% of Subjects Returning to ≤ 0.2 mm of Baseline PD Mean Pupil Diameter
100% pRM Summary of Positive MIRA-2 Phase 3 Results for Nyxol Eye Drops
Rapid Efficacy with a Favorable Safety Profile in Reversing Mydriasis with Nyxol
• Met primary endpoint at 90 minutes with high
statistical significance with Nyxol 2 drops (49% vs
7%; pRM NDA Submission Targeted in Late 2022
Ongoing Activities Set Ocuphire on Path to a Potential Regulatory Approval in 2023
Target Label Indication
The treatment of pharmacologically
induced mydriasis produced by Topline Results
adrenergic (e.g., phenylephrine) or
parasympatholytic (e.g., tropicamide)
Expected in Early 2022
agents, or a combination thereof.
Regulatory Approval
Submit NDA by
late 2022
Preservative-Free
Single Unit Vial (5-pack)
Manufacturing
Completed 3 registration
batches; 1-year CMC
stability needed for NDA
Pediatric Safety
Complete RM trial with
20 subjects ages 3 to
11 per agreed FDA
P3 Clinical Trial initial pediatric plan
Complete a 2nd Phase
Nyxol® 3 trial in RM (enrolled
~368 subjects) which
also meets 24-hour
safety population
exposure requirement
15RM Reversal of Mydriasis (RM) Market Opportunity
With No Commercially Available Treatment, Nyxol May Achieve Significant Revenue Potential
GlobalData Market Research Findings
MIRA Trials
100M
Annual Eye
Dilations
Represent
95% of
Dilation
65% Report
Moderate to
58% 0
Drops Used Severe physicians would start
Impact to prescribing Nyxol Current Commercially
in Practice Daily
within 1st year Available Treatments
80% of Function
Patients
Likely to
Request Patient
Drop Willingness
to Pay $10 -
$20+ 81% 68%
patients would be more physicians would be
willing to use Nyxol even
likely to schedule yearly
if patients had to still wear
eye exams with a
sunglasses within 1st hour
reversal drop
~$500+M
Estimated US RM Market Opportunity
Source: GlobalData Market Research Survey
16 Calculation: 100M Annual Eye Dilations X 65% X 80% X $10 per patient = $500+M OpportunityRM Pre-Commercial 2022 & Go-To-Market Strategy 2023
Activities Underway to Support Capital-Efficient Nyxol RM Commercial Launch
Pre-Commercial Activity Go-To-Market Strategy Landscape
No approved
drug/competition;
Market data-mining for high
Development volume practices
(KOLs) Retina
Potential Options for 3,000 Retinal Specialists
Commercialization
Easy Adoption
Physician
Targeting Work with strategic or
channel partner with Components
existing commercial
ophthalmic products of an Efficient Ophthalmology
Launch 20,000 Ophthalmologists
Patient Dilations are a routine part
Hire contract
Journey of practice;
commercial
adoption requires no staff
organization or patient training
Build own salesforce
Direct to Physicians Optometry
Brand 46,000 Optometrists
Awareness No need for pharmacy;
no reimbursement,
private pay
17 Sources: ASRS; AMA; AAO; Women in Optometry (WO); AOA Excel and Jobson Medical Information; Physician Interviews Conducted by Ocuphire; GlobalData market researchRM
Summary of Nyxol Reversal of Mydriasis Program
Nyxol, the first ophthalmic formulation of phentolamine mesylate, has a differentiated MOA uniquely
suited for reversal of pharmacologically-induced mydriasis
In MIRA-1 and MIRA-2, Nyxol met its primary endpoint of rapidly returning subjects as well as
many key secondary endpoints
Consistent with prior trials, Nyxol has demonstrated favorable safety and tolerability with a MOA
uniquely suited to avoid safety issues associated with cholinergic drug (e.g., pilocarpine) reversal of
dilations
MIRA-3 completed enrollment of 368 patients at 15 sites in the US with data expected in early 2022;
MIRA-4 Pediatric Safety trial is currently ongoing
We anticipate the results of these trials will support an NDA submission for Nyxol in late 2022
Nyxol has the potential to be the ONLY commercially-available, FDA-approved Rx treatment to
reverse pupil dilation in a growing $500+M US Market
18P
NYXOL®
for
PRESBYOPIA
“By age 45, 80% of Americans will Effectively everyone over 40 will
struggle with Presbyopia, and by have the problems with reading.
age 50, nearly everyone will.”
NY Times Physician KOL
19P
2021: The Time for Presbyopia Drops
Headlines from Academia and Industry Articles with an Early First Approval for VuityTM
10/29/2021
“The correction of presbyopia remains
ophthalmology’s ‘Holy Grail’…”
-OIS
20 Sources: Academic review articles, journals, and publications between July 2021 to December 2021Nyxol® with Low-Dose Pilocarpine (LDP) as an Adjunctive Drop
P
Moderate Action on Iris Dilator and Iris Sphincter Muscles for Functional Near Vision Improvement
0.75% Nyxol 0.4% LDP
Iris Dilator Iris Sphincter
Muscle Muscle
Inhibition Activation
0.4%
• Phentolamine (alpha1/2 antagonist) • Pilocarpine (cholinergic agonist)
• Novel MOA (iris dilator) • Known MOA on sphincter (and ciliary) muscle
• 24+ hour PD durability • Potent miotic at approved doses (1%, 2%, 4%)
• Moderate pupil reduction • Low concentration avoids known safety issues:
• Well-tolerated with no systemic effects Ø Headache, brow ache, and redness
• Stable, preservative-free, single-use vial Ø Accommodative spasm causing loss of
distance vision especially at night
Evening drop Daytime drop
Potential One Drop Solution Potential Two Drop Solution
Nyxol with Durable Optimal Pupil Target is 2-3 mm Nyxol + LDP for Presbyopes
Functional Near Vision Who Need More Power
21 Source: Nyxol® data from 9 completed trials; Pilocarpine product label and literaturePresbyopia VEGA-1 Phase 2 Trial
P
Completed Randomized, Double-Masked, Placebo-Controlled, Multi-Center One-Week Trial
VEGA-1 Visit 1
Evening Dosing
(3-4 doses)
Visit 2
(3 – 6 Days Later)
Treatment
Arms Endpoints
Baseline Nyxol LDP Drop Nyxol + LDP Primary: % of subjects with ≥ 3
0.75% Nyxol lines of improvement in distance-
17 US sites corrected near visual acuity
Baseline Nyxol No Treatment Nyxol Alone
comparing Nyxol + LDP vs
150 placebo alone at 1 hour
4 arms
presbyopic Baseline Placebo LDP Drop LDP Alone Secondary:
patients
• % of subjects with ≥ 2 and ≥ 3
Placebo
lines gained at time points from
Baseline Placebo No Treatment Placebo Alone 30 min to 6 hours in photopic
lighting comparing Nyxol +
Randomization Screening
LDP vs placebo, Nyxol alone,
and LDP alone
Eligibility Criteria
• No loss of distance vision
• Males or females ≥ 40 and ≤ 64 years of age
• BCDVA of 0.0 LogMAR(20/20 Snellen equivalent) or better in each eye under photopic conditions
• Pupil diameter at time points
• DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse in photopic conditions in each eye & binocularly • Safety and tolerability
(redness)
Phase 2 Enrollment Completed Feb to May 2021 – 150 Subjects
Reported Topline Results in June 2021 and Jan 2022
22 Clinical trial NCT#04675151. DCNVA = distance-corrected near visual acuity . BCDVA = best corrected distance visual acuityP
VEGA-1: Nyxol+LDP Met Primary & Secondary Endpoints
60% Patients with Nyxol+LDP had ≥ 15 Letter Near Gain with Fast Onset & Durable Responses
VEGA-1 Phase 2 Trial
Percent of Subjects with ≥ 15 Letters Binocular Photopic DCNVA Improvement from Baseline
Phase 2
Primary Endpoint
70%
p≤0.0001 Durable benefit
p≤0.0001 p=0.004
63% over 6 hours
60% 60%
60%
p=0.02 p=0.02
Percent of Subjects (%)
50% 47% 47%
p=0.09 p=0.06
40% 37%
33%
30% 28%
21% 21%
19%
20% 16% 16%
14%
10%
0%
0 0.5 1 2 3 4 6
Rapid onset Time (Hours) 0.4%
of efficacy Placebo (n=43) Nyxol+LDP (n=43)
Note: PP population differs from mITT by only one subject; results were essentially identical.
23 VEGA-1 TLR Table 14.2.1.2VEGA-1: Planned P3 Efficacy Endpoint Met by Nyxol and Nyxol+LDP
P
Nyxol Single Drop and LDP Combination Provide Statistically Significant 3-line Near Vision Gain
Nyxol as a Single Nyxol with LDP
1 Drop for Presbyopia
2 Adjunctive Therapy
0.4%
Percent of Subjects with ≥ 15 Letter Gain In Near & < 5 Letters Percent of Subjects with ≥ 15 Letter Gain In Near & < 5 Letters Loss
Loss In Distance Vision in Photopic Binocular DCNVA In Distance Vision in Photopic Binocular DCNVA
100% Time 0=12 Hours Post-Nyxol Dose Time 30 Minutes
100%
Percent of Subjects (%)
80% Nyxol+LDP is
Percent of Subjects (%)
80% statistically
superior to
60% p=0.02
60% Nyxol alone and
60% LDP alone
p=0.03
40% p=0.008
29% 40% 33%
p=0.02 26%
20% 12% 20% 14%
0%
0%
Placebo (n=74) Nyxol (n=73) Placebo (n=43) Nyxol+LDP (n=43) Nyxol (n=30) LDP (n=31)
53% of subjects achieved ≥ 10 letter improvement in DCNVA at 12 hours 79% of subjects achieved
DCNVA ≥10 letter improvement in DCNVA at 1 Hour
Letters Gained
(p=0.005 vs placebo) and a similar trend at other time points (p=0.005 vs placebo) and a similar trend at other time points
24 VEGA-1 TLR Table 14.2.2.1.1; Table 14.2.2.2; Table 14.2.1.7; Table 14.2.1.2P
VEGA-1: Improvement in Functional Near Vision
Nyxol and Nyxol with LDP Both Provide Durable Improvement in Functional Near Vision
VEGA-1 Phase 2 Trial
50%
Percent of Subjects (%)
Baseline 56% achieved 20/40 or
40% 36% 34%
12 Hours better at 12 hours
Nyxol as a Single 30%
22% 23%
1 Drop for Presbyopia 19%
20% 16% 15%
12% 11%
10% 5%
3% 3%
0% 0% 0% 0% 0% 0%
0%
20/15 20/20 20/25 20/32 20/40 20/50 20/63 20/80 20/100
Improvement in Snellen Equivalent
50%
84% achieved 20/40 or
Percent of Subjects (%)
40%
40% Baseline better at 1 hour 33%
30% 1-Hour 26%
23% 23%
20% 16%
2 Nyxol with LDP 12%
Adjunctive Therapy 7% 9% 7%
10%
0.4%
0% 0% 0% 0% 0% 0% 2% 0%
0%
20/15 20/20 20/25 20/32 20/40 20/50 20/63 20/80 20/100
Snellen Acuity
(Binocular DCNVA)
Similar trend was seen at all timepoints
Baseline Inclusion: Photopic DCNVA of 20/50 or worse
25 Source: VEGA-1 TLR Table 14.2.24.1 Percent of Subjects with Photopic DCNVA by Time Point (PP Population)P
What is the Optimal Pupil Size?
Literature Highlights New Drops to Treat Presbyopia Achieve Optimal Pupil Diameter of 2-3 mm
Photopic Lighting (100 -1000 lux)
Natural Pupil Size ~ 4 mm
“A fixed 2- to 3-mm small pupil or a 30% pupil miosis can
both produce near visual acuity gains without significant
losses to distance acuity or image quality, and therefore
can be considered as optimal for a presbyope experiencing
100 a wide range of light levels.”
Optimum
NEAR 2.0-3.0 mm - Optometry and Vision Science, November 2016
Vision
VSTOF (Constricted/natural)
10
Natural
Pupil
1
“The impact of pupillary modulation on the functional
DISTANCE depth of field differs among patients with refractive error
Vision versus those who are truly emmetropic.”
0.1
0% 20% 40% 60% 80% 100% - Cataract & Refractive Surgery Today (CRST), January 2022
% Constricted Pupil Size of Natural Pupil
26 Source: Xu et al, OVS 2016; Pepose & Xu CRST article 2022, Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic EyesP
VEGA-1: Mean Pupil Diameter Over Time
Achieved Optimal Pupil Size in Nyxol+LDP and Nyxol Alone Consistent with Near Vision Gains
VEGA-1 Phase 2 Trial
Best Eye (PP Population)
**pP
Summary Of Positive VEGA-1 Phase 2 Results
Nyxol and Nyxol + LDP has Demonstrated Efficacy Response & Well Tolerated Safety Profile
Well-Controlled, Multi-Center Phase 2 Trial Evaluating Nyxol & Nyxol+LDP
1 2
Nyxol as a
Nyxol with LDP
Single Drop
Adjunctive Therapy
Single Durable 0.4%
Two Drops Tunable
Drop Option
Met planned P3 endpoint at Met primary endpoint at Nyxol and Nyxol+LDP
12 hours (29%; p=0.02) Efficacy 1 hour (60%; p=0.004)
Pooled Safety Findings
Efficacy
Durable near vision gain at Durable near vision gain
12 and 18 hours Durability through at least 6 hours
• No serious AEs, most AEs were mild
56% Functional Vision 84% • No headaches, no brow aches, and
(12 hours post-dose) (20/40 or better) (1-hour post-dose)
Safety no blurry vision AEs were reported
Sustained PD reduction at
Reduction in PD
Sustained PD reduction at • No loss in distance vision under
least 18 hours least 6 hours
photopic and mesopic lighting
•
•
Ages 40-64
20/50 or worse DCNVA
Breadth of Patients •
•
Ages 40-64
20/50 or worse DCNVA
• ~5% mild, transient redness
• Light and dark irides Showed Efficacy • Light and dark irides
• No change in IOP
PP Population, VEGA-1 Trial
28 *Trend toward statistical significance even in smaller Nyxol arm from time 0 to time 6 hours (n=30); larger sample size for all arms planned in Phase 3 programTwo Treatment Options for Spectrum of Presbyopic Patients
P
Two NDA Submissions Targeted in 2023: Nyxol Alone and Nyxol+LDP
Pursuing Product Labels for 1 Drop
and 2 Drop Options for the Treatment
of Presbyopia
Nyxol as a Single Agent for Nyxol with LDP as Adjunctive
Presbyopia Therapy for Presbyopia
0
Single Durable Drop
.
Two Drops Tunable Option
4
%
Initiating VEGA Phase 3 Program in
Mid-2022 for Both Labels
29P
Potential ‘Best in Class’ Presbyopia Drop(s)
Nyxol and Nyxol+LDP Combination Data Differentiate on Efficacy, Safety, and Durability
Ocuphire
Product Attributes* VUITYTM Nyxol Nyxol+LDP
1) Efficacy (> 3-Line Gain w/o loss Caveats of cross- 29% 60%
26-31%
of 1 line in DCNVA - Primary trial comparisons (12 hours) (1 hour)
(3 hours)
Endpoint Responders)* for VUITY TM and
Nyxol/LDP. No Significant No Significant
2) Safety: Loss of Distance in No Significant Loss Loss
Mesopic Loss Differences include
age, severity of No Headaches No Headaches
3) Tolerability: Headaches and >5% Headaches near vision loss, 5% redness lighting conditions,
doses, timing, and #
4) Durability (% responders at the of patients 37% at 18 hours 37% at 6 hours
18% at 6 hours
longest timepoint)
Nyxol’s Potential Differentiated Solution
Placebo Adjusted Values for Vuity ™ were 15-23% in Gemini 1 & 2; Placebo Adjusted Nyxol was 16% and Nyxol+LDP was 33% (all stat significant)
30 Source: Nyxol Data: ASCRS (July 2021) Abstract# 76645 (Phase 2) and VEGA-1; Abstract 74336 (Phase 3). VUITY™ Data FDA Label and AAO 2021 Presentation.P
Presbyopia Eye Drops Competitive Landscape
Nyxol Creates a New, Differentiated MOA Class; Nyxol+LDP Offers Tunability Option
Other Cholinergic Agonists*
Pupil modulation MOA
Lenz
Soften lens MOA Visus (aceclidine;
(Brimochol®; aceclidine+
brim) Novartis
Combination drugs carbachol+brim)
(EV-06)
*act on sphincter and
ciliary muscles in dose-
Eyenovia
dependent manner
(MicroLine; Alpha
2% pilo) Ocuphire Antagonist
NDA (Nyxol)
Allergan
(VUITY TM;
1.25% pilo)
Ocuphire
Orasis (Nyxol + 0.4% pilo)
(CSF-1;
Phase 3
Low dose pilo)
Alpha Antagonist
Cholinergic Phase 2 & pilocarpine*
Agonist*
(pilocarpine)
Phase 1
31 Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020P
Presbyopia is a Burgeoning Market Opportunity
Large Disease Category with Global Spend on Reading Glasses; Tens of Millions of Likely Early Users in US
~128M Presbyopes in the US
The Problem
• Lens loses ability to
100%
change shape when of adults over the PSUEDOPHAKIA
viewing objects up close age of 40 years are
as we age at risk of developing
presbyopia
Emmetropes Hyperopes Pseudophakes Myopes
• Dependence on reading • Naturally • Poor near vision • Cataract surgery • Poor distance
glasses for intermittent occurring clear (starting at age for artificial lens vision
vision
and prolonged use, but • No refractive
40) (monofocal,
multifocal IOLs)
unable to see near and far error/post-LASIK
at same time $56 B
66 M 14 M 9M 39 M
$36 B
• Aesthetics and
inconvenience
Assume 50% use eye drops*
~44 M Patients
Likely To Be Early Users of Presbyopia Eyedrops
Source:
1. Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data.
2. Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday.
32 3. NEI/NIH https://www.nei.nih.gov/sites/default/files/health-pdfs/Presbyopia.pdfKey Findings from GlobalData Market Research on Presbyopia
P
Insights Very Consistent with Presbyopia Eye Drop Market Research Surveys
120+ Million 90% 70% 40%
presbyopia patients wear patients would consider patients have asked their
Presbyopia patients an eye drop as an physicians about
reading glasses ≥ once
in the US alternative to reading alternatives to reading
per day
glasses glasses
70% > $50/mo
51% 67% patients considered the
Patient Willing to Pay
physicians would offer eye
physicians indicated 2 drops/bottle dosing to
drops as a first-line Vuity™ is priced at $79
interest in Nyxol+LDP be moderately-to-very
presbyopia treatment for a 30-day supply
convenient
Physician Perspective Patient Perspective
N=120 n=134
33 GlobalData Market Research Survey; Jasper 2021 poster presentation at AAOptometry 2021P
VuityTM is the First FDA-Approved Eyedrop for Presbyopia
Approval Sets the Stage for Market Development by Large Pharma to Build a Large Market
~44 M Patients
~$10B - $20B
Likely To Be Early Users Estimated US Presbyopia
of Presbyopia Eyedrops Market Opportunity
FDA Approval of Vuity™ positive 3-6 refills per
year assumed
for the presbyopia space
~2 Billion Presbyopes
Opportunities for new entrants with
differentiated product attributes in a newly Private Cash Pay Globally for Even
established segment with physicians and
(Vuity™ fill List Larger Market Potential
Price)
patients/consumers
Source:
1. Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data.
34 2. Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday.P Summary of Nyxol and Nyxol + LDP Presbyopia Program
Nyxol as a single drop is differentiated as a new MOA class working on the iris dilator
muscles; Nyxol with LDP as adjunct therapy uniquely offers pupil ‘tunability’ depending on
patient lifestyle
In VEGA-1 trial:
• Nyxol+LDP met its primary efficacy endpoint ≥ 15 letter near visual acuity gain.
• Nyxol as a single drop met efficacy endpoints at 12 hours and 18 hours
Consistent with prior trials across other indications, Nyxol, dosed alone or with LDP, has
demonstrated favorable safety and tolerability
VEGA Phase 3 program planned for Nyxol and Nyxol+LDP for the treatment of presbyopia to
initiate mid-2022
Potential NDA submissions for presbyopia in 2023
• Nyxol as a single drop
• Nyxol with LDP as adjunct therapy
Presbyopia drops projected to be one of the largest $10+B new segments in Ophthalmology
35NVD
NYXOL®
for
DIM LIGHT OR I’m no longer comfortable driving at night, especially with
NIGHT VISION my son in the car. I have a hard time playing beach
volleyball in the evenings due to the bright lights at the
DISTURBANCES courts. Post-LASIK, Age 42
36NVD
Market Opportunity in Dim Light or Night Vision Disturbances
No Approved Treatments with Ripe Opportunity for Growth
The Problem No Approved Treatments
• Peripheral imperfections scatter light when
pupils enlarge in dim light, causing halos, Moderate-Severe NVD
starbursts, and glare that impair vision ~16 M
• The imperfections may be caused by LASIK
surgery, IOL implants, certain types of cataracts
(cortical), and natural reasons (especially with Night Myopia Cortical Cataracts Post-Lasik Post-IOL Implant
age) 11 M 4M 0.5 M 0.3 M
• Symptoms cannot be properly corrected by any
type of lens (reading glasses, contact lenses) or
surgical procedures Seeking Treatment Findings
Patients willing to try a new eye drop treatment 67%
Before $2B - $4B
Estimated US NVD Market Opportunity
Pupil reduction with Nyxol may offer a potential solution
After to peripheral optical imperfections
37 GlobalData Market Research Report, 2020; Photos are illustrativeNVD
NVD LYNX-1 Phase 3 Registration Design
Ongoing Randomized, Double-Masked, Placebo-Controlled Two-Week Trial
0.75% Nyxol
daily evening dose Endpoints
LYNX-1 (14 days)
Primary: % of subjects with
≥ 3 lines of improvement in
20 US sites mesopic low contrast best-
Day 8 Day 15
Day 0 Assessments Assessments corrected distance visual
140 - 160 1:1 acuity (Day 8)
patients with
NVD Secondary (Days 8 & 15):
Primary
Placebo Endpoint
• Pupil diameter
Eligibility daily evening dose • Visual acuity measures
Randomization (distance and near)
Screening (14 days)
• Safety and tolerability
Phase 3 Initiated in Dec 2020; Enrolled 145 Patients Jan 2022 (redness)
Top Line Expected Early 2022
38NVD
Nyxol Demonstrated Clinical Effect in NVD
Key Endpoints Observed in Multiple Phase 2 Trials; 24 to 36 Hour Durable Pupil Modulation
NYX-SNV Phase 2 Trial ORION-1 Phase 2 Trial
Improved Low Contrast Distance Visual Acuity* Durable > 24-hour Pupil Modulation Effect
% of Eyes with Mesopic Low Contrast Pupil Diameter Change from Baseline in
Visual Acuity Improvement Mesopic Conditions (Study Eye)
Baseline Pupil Diameter: Placebo 4.6mm, Nyxol 4.7mm
80% p=0.029 0.2
Placebo (n = 20) 1% Nyxol (n = 19)
69% Placebo n=16 p = 0.0002 p = 0.0001 p = 0.0004
Pupil Diameter Change from Baseline
0
Nyxol n=32
Percent of Subject Eyes
60%
-0.2
ANCOVA (mm and %)
-0.07 -0.05
-0.5% -0.11
p=0.04 -0.4 -2%
-1%
40% 34%
31% p=0.16 -0.6
19% -0.8 14-day
20%
Daily
6% -1 Evening
Dosing,
0%
0% Last Dose -0.88
-1.2 on Day 14
-0.99 -1.00 -19%
≥ 1 line ≥ 2 lines ≥ 3 lines
-20% -21%
-1.4
Source NYX-SNV Source: NYXG-201 Day 8 Day 15 Day 16
39 *NYX-SNV trial was small and not designed for a statistical 3-line improvement in low-contrast visual acuity; the ~20% effect was used for powering and sizing of Phase 3 trialAPX3330
ORAL TABLET
DR Diabetic Retinopathy
DME Diabetic Macular Edema
40DR
Clinical Unmet Need in Diabetic Retinal Diseases
DME
Increasing Prevalence of DR with No Early Intervention Options
The Problem Growing Incidence of Diabetes
and DR
• DR/DME are major causes of vision loss in working
34 M US
aged adults Diabetes
>450 M WW
• Diabetic population expected to increase dramatically
7 M US
worldwide DR
>150 M WW
– Losing vision is one of diabetic patients' top
concerns US Projected Market in DR*
• Approved therapies for DR are effective but require
IVT injection
• DR patients are not routinely treated with approved
DR/DME affects about 1 in 4 people
with type 1 and type 2 diabetes
$10+B
Oral Rx Revenues
injectable anti-VEGF drugs until they develop
center-involved DME or PDR
– DR progresses resulting in vision loss
Oral Alternatives To Injectable Therapies Are
• Early, noninvasive intervention targeting DR
represents a therapeutic unmet need Needed For Earlier Stages Of Disease
Source:
1. American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions;
2. Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918
41 3. Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000DR APX3330 History and Ref-1 Inhibition Mechanism
DME Ref-1 Involved in Multiple Key Pathways that Contribute to Diabetic Retinopathy and DME
Mechanism of Action – Ref-1 Inhibition
• Ref-1 (reduction-oxidation effector factor-1) is a
Hypoxia Inflammation
novel target discovered by Dr. Mark R. Kelley at
Indiana University School of Medicine
Ref-1 APX3330 Ref-1 • APX3330 is a small molecule oral drug candidate
and a first-in-class inhibitor of Ref-1
NF-κB
• APX3330 previously developed by Eisai for
HIF-1α TNF-α multiple hepatic inflammatory indications and later
Chemokines by Apexian for advanced solid tumors in 11 Phase
1 and 2 trials
Other Growth
Factors – Similar oncology origin as approved anti-VEGFs
VEGF
(Signaling
(Signaling
Cascade) Cascade) • MOA uniquely decreases both abnormal
angiogenesis and inflammation by blocking
pathways downstream of Ref-1
Anti-VEGF Neovascularization Steroids • Extensively studied in over 20 in-vitro and animal
studies with favorable efficacy and safety
Lucentis®
EYLEA®
42 Logsdon et al (2018), Li et al (2014).DR In vitro Validation of APX3330 Mechanism of Action
DME APX3330 Reduces VEGF Levels and Inflammatory Cytokines; Provides Neuronal Protection
APX3330 reduces VEGF protein APX3330 reduces pro-inflammatory APX3330 increases DNA oxidative
expression cytokines in LPS stimulated macrophages repair and neuronal protection
in preclinical stroke model
Control APX3330
VEGF
APX3330 enhances Ref-1
endonuclease activity in dorsal
root ganglion neurons
Increasing APX3330 dose
Source:
1. Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018
2. Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages.
3. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315
4. Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the
43 DNA repair function of APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017).DR Preclinical Data: Oral APX3330 Blocks Neovascularization
DME Lesion Volume Decrease with Oral APX3330 in Murine Laser CNV Model Similar to EYLEA® Data
L-CNV Mouse Retina Model L-CNV Mouse Retina Model
Lesion Size and Corresponding Fluorescent Stains in L-CNV Models EYLEA*
Treated with APX3330 at 25 mg/kg oral gavage
APX3330 APX3330 Gavage OCT
Vehicle 25 mg/kg 50 mg/kg Lesion Volume
-44%
-55%
Silva et al, 2021
ü Efficacy was also seen after single intravitreal injection of 20µM APX3330 in mouse L-CNV model**
ü Efficacy was also seen after dosing intraperitoneal injection of 50 mg/kg twice daily, 5 days on/2 days off, for 2
weeks in mouse L-CNV model***
ü Efficacy was also seen after single intravitreal injection of 20µM APX3330 in Vldlr -/- mice model****
Source:
1. Silva et al. ARVO 2021 Annual Meeting
2. *Published data on EYLEA. This study was performed independently from APX3330 study and is a cross-study comparison.
44 3. **Li 2014; *** Pasha 2018; ****Jiang 2011 (Vldlr -/- : Very Low-Density Lipoprotein receptor knock-out mice)DR
Phase 1/2 Clinical Trials: PK Data Supporting the ZETA-1 Trial
DME
APX3330 is Bioavailable and Reaches the Retina via Oral Administration
Plasma levels with 120 and 240 mg/day APX3330 dosing is Oral administration of APX3330
multiple times higher than plasma concentrations for mouse reaches the retina
efficacyè planned clinical dose is 600 mg/day
25 mg/kg APX3330 oral gavage
Mouse measured in mouse retina1
~40 µg/ml (240 mg/day) in
human plasma 10 mg/kg APX3330 oral gavage
Rat measured in rat eye2
~20 µg/ml (120 mg/day) in
human plasma
2 µg/ml in mouse plasma at 2hrs;
300 mg BID (600 mg/day total)
25 mg/kg oral single dose
Established PBPK model predicts
APX3330 reaches sufficient human
Human retinal concentrations3
Source:
Eisai PK clinical data APX_CLN_0002 (left panel)
1. Apexian preclinical data
2. Eisai preclinical data
45 3. Silva et al. Presented at the ARVO 2021 Annual MeetingDR DR/DME ZETA-1 Phase 2b Design
DME Ongoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial)
Endpoints
ZETA-1
25 US sites
APX3330 600mg/day (BID) Primary: % of subjects with a ≥
2 step improvement
on the DRSS (Diabetic
90-100 participants Retinopathy Severity Scale)
with moderately score at week 24
Week 0 Week 4 Week 12 Week 24
severe-to-severe 1:1 Secondary:
NPDR or mild PDR
Primary • Central subfield thickness
Endpoint (CST)
Noncentral DME is
permitted • BCDVA (ETDRS)
Placebo BID • DRSS change at week 12
Eligibility Screening Randomization
• Rescue subjects
• Safety and tolerability
Phase 2b Initiated in Apr 2021; ~70% Enrolled Subjects (as of Jan 2022)
Exploratory:
Top Line Expected in 2H22 • Labs / PK
NPDR = non-proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema)
PDR = proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema)
46 ZETA-1 Clinical Trial is Sponsored by Ocuphire Pharma https://clinicaltrials.gov/ct2/show/NCT04692688?term=ZETA-1&draw=2&rank=1DR Why DRSS is an Important Endpoint?
DME FDA Accepted Endpoint for EYLEA® in PANORAMA Pivotal DR Trial - 2 Step Improvement on the DRSS Score at Week 24
Diabetic Retinopathy Severity Scale (DRSS) PANORAMA: Reduction of DRSS Significantly reduces the incidence
of Vision Threatening DR
Non-proliferative disease Proliferative disease
ETDRS Severity
Level
Steps
Very Mild Mild Mod Sev. Very Mild Mod High Risk
. Sev. .
Risk of vision-threatening events increases with worsening step progression
47 Eylea® Panorama studyDR Masked Safety Findings from Ongoing ZETA-1 Trial
DME Favorable Safety Profile (as of 1/12/2022) Observed with 600 mg Oral Daily Doses in DR Subjects
68 >3700 28 6
Randomized Subject-Days of Subjects with AEs SAEs, all unrelated
APX3330
Masked Safety Data Subjects Exposure (52 total events) to study medication
ZETA-1 Trial (50% on APX3330)
• 52 TEAEs in 28 subjects
– 6/52 AEs were considered probably or possibly related to study medication
• 4 Mild (vertigo, rash, pruritus, frequent bowel movements); 2 moderate (diarrhea*, DME**) Review of masked
– 46/52 AEs were ‘not’ or ‘unlikely’ related (32 mild, 14 moderate) safety data for 600
• 6 SAEs in 6 subjects mg/day daily dose
– None of these treatment emergent events were related to study medication is consistent with
• Cellulitis , dyskinesia, transient ischemic event, COVID-19, progression of multivessel coronary artery the favorable safety
disease, cholecystitis profile seen in
• Only 2 subjects have withdrawn from study due to AEs*/** previous studies
• No major organ toxicities (liver, heart, kidney, brain, lung) or vital sign abnormalities (blood pressure or heart rate) with APX3330
were observed
• Incidence of mild rash and diarrhea in the diabetic patient population is even lower than previously observed in
hepatitis patients
*vasovagalnear syncope same subject considered unrelated to study medication and **DME same subject possibly study medication related (APX3330 or placebo)
48 Note: ZETA-1 Interim Data as of database 1/12/22. Complete monitoring will be performed before final database lockDR
APX3330 Product Candidate Profile for Multiple Retinal Indications
DME Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data
APX3330: Well-tolerated Oral Dose up to 600mg/day
Twice Daily Dosing
Expected Efficacy Data Favorable Safety Profile
Improving Eye Health in Diabetics >5800 Subject-exposure days* at ≥600 mg/day dose
↓ Inflammation
↓ Abnormal Angiogenesis Few Systemic Adverse Effects
• < 5% Mild Gastrointestinal (diarrhea)
• < 5% Mild Skin Rash (reversible)
Enhance Compliance & Exposure
Oral pill may reduce the burden of frequent No Organ Toxicity (Liver, Cardiovascular {BP, HR},
anti-VEGF injections Kidney, Neurologic, Pulmonary)
No Ocular Effects
• No observed ocular AEs
49 *Phase 1 and Phase 2 clinical trials by Eisai, Apexian and Ocuphire (*includes ~34 subjects from ongoing ZETA-1 study)DR Broad Opportunities to Treat Retinal Diseases with APX Platform
DME APX3330 May Treat Patients Across Retinal Diseases as Single Agent or Adjunctive Therapy
Potential Differentiated Solution
• Potential First Oral Rx for Retina Diseases DR
– First-line earlier intervention for the diabetic eye APX3330
– Add-on therapy to current anti-VEGF treatments to reduce DME
intravitreal injection burden
Current anti-VEGF
• Proven Novel Mechanism Wet AMD treatments
– May decrease both inflammation and angiogenesis
Dry AMD
• Convenient Daily Regimen APX2009
APX2014
• Favorable Oral Safety Profile APX3330
RVO
– As seen in 11 completed Phase 1 and Phase 2 clinical trials (Local Delivery)
• Improve Patient Compliance GA
– Potentially alleviate the frequent burden of injections
Inflammatory component is common across
these retina indications and potentially
addressable by the MOA of Ref-1
50DR Large Global Market Opportunity in Retinal Disease
DME Retinal Global Markets Served by Anti-VEGF Injections Alone are Greater than $10B+ Today
Global Disease Prevalence (Patients) Anti-VEGF Injectable Global Revenue6
$5+B
28 M GA Revenues3
5M
$20 B
RVO2
93 M GA3
DR and Projected Global Revenue
DME
combined1 $10+B 2030
Oral Rx Revenues5
196 M 4% CAGR
AMD4 ↑ Aging
(wet/dry)
↑ Access
↑ Diabetes
↑ New Rx
Products
$13 B
Global Revenues
Source: 2020
1. Nancy M. Holekamp, Overview of Diabetic Macular Edema, 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513508/pdf/jogh-09-010427.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513508/pdf/jogh-09-010427.pdf;
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513508/pdf/jogh-09-010427.pdf
3. Boyer DS et al., Retina 2017 2 2. Wong WL, et al. Lancet Glob Health. 2014;2:e106-16; Global Data AMD Global Drug Forecast and Market Analysis, JAMA Ophthalmology, Gibson 2012
4. https://www.brightfocus.org/macular/article/age-related-macular-facts-figures
5. Ocuphire internal analysis and assumptions
51 6. Market Scope 2020Summary of APX3330 Program
DR
DME
APX3330 is a novel orally administered drug initially being developed for DR/DME
APX3330 targets Ref-1 which plays a role in signaling under both ischemic and
inflammatory conditions, both of which are relevant to diabetic eye disease; resulting
in inhibiting clinically validated pathways downstream of Ref-1(e.g., VEGF and
inflammation)
ZETA-1’s masked safety findings as of 01/12/2022 support favorable safety profile
of APX3330 as an oral treatment option for DR consistent with 11 prior Phase 1 and
2 clinical trials
APX3330 randomized, double-masked, placebo-controlled, multi-center ZETA-1 Phase
2b trial enrollment on track at 68 subjects (of 90-100 subjects) with results
expected in second half of 2022
Oral APX3330 has potential utility as adjunctive treatment with anti-VEGF
injections for other retinal vascular/inflammatory diseases such as DME, GA, RVO
and AMDs; future opportunities with APX2009/2014 pipeline locally or orally delivered
52Team/Boards, Milestones,
and Financial Data
53Ocuphire Management Team
Decades of Biotech and Drug Development Experience
Mina Sooch, MBA
President & CEO
Charlie Hoffmann, MBA Amy Rabourn, CPA
and Founder
VP Corporate Development VP, Finance
and Operations
Ronil Patel, MS Daniela Oniciu, PhD Mitch Brigell, PhD Barbara Withers, PhD
Senior Director BD and Global Head, R&D, Chemistry Head, Clinical Development VP, Clinical and
Market Strategy and Product Development and Strategy Regulatory Strategy
Bindu Manne Chris Ernst Laura Gambino Drey Coleman
Head, Market Development Global Head, QA Director, Project Management VP, Clinical Operations
and Commercialization and Manufacturing
54Ocuphire's World-Class Medical Advisory Board
Fortunate for the Insights of Leading KOLs & Drug Candidate Co-Founders
elCON Medical Retinal Specialist
Refractive Specialist Refractive Specialist
Refractive Specialist Peter Kaiser, MD
Jay Pepose, MD, PhD Ed Holland, MD
Eliot Lazar, MD Harvard Medical
UCLA School of Medicine Loyola University Chicago
Georgetown University School
Refractive Specialist Mark Kelley, PhD
Refractive Specialist Retinal Specialist
Marguerite McDonald, MD Indiana University
James Katz, MD David Boyer, MD
Columbia University Co-Founder Apexian/APX3330
University of Illinois Chicago Medical School
Retinal Specialist Retinal Specialist
Refractive Specialist Refractive Specialist
David Lally, MD David Brown, MD
Mitch Jackson, MD Y. Ralph Chu, MD
Vanderbilt University Baylor University
University of Chicago Northwestern University
Refractive Specialist Refractive Specialist
Jack Holladay, MD
Retinal Specialist Retinal Specialist
Thomas Samuelson, MD
University of Texas Michael Allingham, MD, PhD Jeffrey Heier, MD
University of Minnesota
University of North Carolina Boston University
Optometry Optometry
Paul Karpecki, OD Douglas Devries, OD
Indiana University University of Nevada
55Ocuphire Board of Directors
Seasoned Directors with Decades of Drug Development, M&A/Financings, and Ophthalmology
Mina Sooch, MBA Sean Ainsworth, MBA Jay Pepose, MD, PhD
Vice-Chair, Board Director Lead Independent Director, Board Director
President & CEO Board Director
Cam Gallagher, MBA
Chair, Board Director
James Manuso, PhD/MBA Richard Rodgers, MBA Susan Benton, MBA
Board Director Board Director Board Director
Talfinium Investments, Inc.
56Track Record of Achieving Milestones è Exciting 2022 News Cadence
Multiple Late-Stage Data Catalysts Expected in 2022 for Potential First NDA Approval in 2023
2021 2022
Report Positive Phase 3 Data for RM (MIRA-2) Report Positive Nyxol Alone Phase 2 Data for Presbyopia
Report Positive Nyxol+LDP Phase 2 Data for Presbyopia Report 2nd Phase 3 Data for RM (MIRA-3)
(VEGA-1)
Report Pediatric Data for RM (MIRA-4) Early
New Patent Claims for Presbyopia 2022
Report Phase 3 Data for NVD (LYNX-1)
ASCRS 2021 Presentation for MIRA-2 & VEGA-1
Submit Nyxol NDA for RM
Manufacture 3xRegistration Batches for Nyxol Blow-Fill-
Seal (BFS) Eye Drops Report Phase 2 Data for DR/DME (ZETA-1)
Initiate 2nd Phase 3 RM AND Pediatric RM trial Initiate VEGA Phase 3 Presbyopia Progam
Ongoing Partnering Discussions with Leading Ophthalmic Companies (including European and Asian Players)
57OCUP – Market Snapshot
Active Trading Volume and Sufficient Cash Runway Through 2Q 2023
Ticker OCUP
Price $3.40 As of 2-15-22
Market Cap $64.2 M As of 2-15-22
Shares 18.8 M As of 12-31-21
Research Analyst Coverage on OCUP
Outstanding John Newman Canaccord Genuity
Kristen Kluska Cantor Fitzgerald
Cash $24.5 M As of 12-31-21 (unaudited)
James Molloy Alliance Global Partners
Cash Runway Sufficient into 2Q Guidance as of 2-15-22 Prakhar Agrawal Jones Trading
2023 Matthew Caufield H. C. Wainwright
Average Daily 204 K As of 2-15-22 (YTD Avg)
Volume
Short Interest 176 K; 1.0% of Float As of 1-31-22
58 Source: FactSetRestore Vision & Clarity
www.ocuphire.com
ir@ocuphire.com
Ocuphire Pharma
Click here to view Ocuphire Pharma’s
Investor R&D Day RecordingOverall Highlights - Ocuphire Investor R&D Day January 31st, 2022
Key Topics Presented by KOLs Drs. Boyer, Kaiser, Karpecki, Jackson, Pepose, and Katz
Nyxol®
Nyxol® eye drops, as a platform, are uniquely APX3330
positioned to address growing markets in
refractive disorders The well-controlled, multi-center Phase 2b
ZETA-1 for APX3330 is ~70% enrolled
Nyxol, if approved in 2023, would be the only Rx
drop for reversing dilations and improving the
APX3330 new interim masked safety data
patient experience in an eye care practice
support favorable safety profile as a potential
oral treatment for diabetics with DR/DME
Nyxol represents a novel class with a
differentiated MOA and potential as a convenient
single evening drop with efficacy at 12 hours (and APX3330 oral with dual MOA targeting VEGF
18 hours) in the large presbyopia market and inflammation may be well-suited to
reduce treatment burden and/or improve
Ocuphire plans to pursue Nyxol both as a single outcomes adjunctive to traditional anti-VEGF
agent and with low dose pilocarpine as intravitreal injections across retinal diseases
adjunctive therapy to treat a breadth of
presbyopia patient types è more details to follow
60P
R&D Day - What’s Important?
Nyxol+LDP has the Potential to be “Best in Class” Presbyopia Eyedrop
Efficacy Signal Efficacy Signal
Percent of subjects with >3-line improvement in • Achieve “functional near vision” and
near vision with less than 5 letters of distance intermediate vision
loss in Nyxol+LDP combo compared to Nyxol • Achieve optimal pupil size
alone and LDP alone as demonstrated in 2 • Durability
well-controlled, multi-center clinical trials • Dynamic/responsive pupil
Safety
FDA Safety
No loss of distance (included in efficacy) Guidance • No loss of distance vision
Maintain night distance vision • No headaches or brow aches
Well-tolerated • Reliable night distance vision
Physician/ • No stinging or burning
Broad Label Opportunity Patients • Minimal redness
For Vuity™, FDA did not limit the use of the
product to clinical trial parameters such as: Patient Experience
• age • Tunability - ability to customize treatment
• lighting conditions (photopic or mesopic) based on patient’s lifestyle needs
• monocular or binocular • Favorable tolerability for continued use and
• phakic status Rx refills
61 Vuity Label 2021RM
R&D Day - What’s Important?
Nyxol Has the Potential to be the Only FDA-Approved Treatment Option to Reverse Dilation
Efficacy Signal Efficacy Signal
• Statistically significant percent of subjects on • Compelling magnitude of response compared to
Nyxol compared to placebo returning to baseline placebo with statistical significance
(within 0.2 mm) photopic pupil diameter (PD) at • More rapid response with Nyxol vs. placebo
90 min demonstrated in 2 well-controlled, multi- • Works in all iris colors
center clinical trials • Works across all commonly used mydriatic agents
• Precedent set with RevEyes Approval
FDA
Safety Safety
Guidance • No systemic side-effects such BP, HR, headache
• Well-tolerated drop
• No ocular or systemic AEs or SAEs • Mild, transient hyperemia is acceptable and common
Physician/ in RX drops
Patients
Label Expansion Patient Experience
• Opportunity to expand label with ongoing pediatric trial • Patients desire more rapid return to normal activities
in patients 3 years and up given safety shown in • Patients actively asking for ‘reversal’ drops
dental reversal approval for phentolamine • Patients want a comfortable experience post-dilation
• Patients more likely to maintain their annual exams if
option to reverse dilation is presented
62DR R&D Day - What’s Important?
DME APX3330 Has the Potential to be 1st Line of Therapy for DR Patients
Efficacy Signal Efficacy Signal
Percent of patients on APX3330 with a ≥ 2 step • Clinically meaningful decrease in diabetic
improvement on the DRSS score at week 24 retinopathy severity with APX3330
compared to placebo in 2 well-controlled, multi- • Early intervention with oral may reduce
center clinical trials progression to vision threatening DR into DME
FDA
Safety Guidance Safety
Approval depends on a product's benefit outweighing • No major organ toxicities
its risks in the intended population as demonstrated in • Well-tolerated (e.g., AEs acceptable if mild and
multi-center, 2 years clinical trial Physician/ infrequent for oral)
Patients
Non-Invasive Treatment Option Non-Invasive Treatment Option
FDA does not require comparative arm of approved • Eylea®, although approved, is currently not used as
anti-VEGF injections such as Eylea for DR standard of care because of the treatment burden
for asymptomatic DR patients
• Ability to be prescribed by all eye care doctors
• Oral option increases global access, especially in
underserved regions
63 Eylea® label; APX3330 Investigator Brochure, ZETA-1 clinical trialYou can also read
