American Noble Gas is an oil and gas exploration, development, and production company with a history of operations in Texas, Kansas, Oklahoma, and the Rocky Mountain region of the US. The Company is currently exploring and developing natural gas, helium, and other noble gases and brine minerals contained in the Hugoton Gas Field, a prolific natural gas and helium gas field spanning the states of Kansas, Oklahoma, and Texas, through a 40% participation in a farmout agreement that covers drilling and completion of up to 50 wells. American Noble Gas also owns 60.7143% of GMDOC, LLC, LLC which acquired certain oil and gas leases covering approximately 10,000 acres located in Southern Kansas near the Oklahoma border. The GMDOC leases currently produce approximately 100 barrels of oil and 1.2 million cubic feet of natural gas per day on a gross basis. The Company also owns mineral rights to approximately 11,000 acres in the Otis/Albert Field located on the Kansas Central Uplift.
2. 2
Forward Looking Statements
This presentation contains certain “forward-looking” statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All
statements, other than statements of historical or present facts, are forward-looking statements, including statements regarding our future financial condition, future revenues,
projected costs, prospects, business strategy, and plans and objectives of management for future operations, including our plans to submit for regulatory filings. In some cases,
you can identify forward-looking statements by terminology such as “believe,” “will,” “may,” “might,” “estimate,” “continue,” “anticipate,” “intend,” “target,” “project,” “model,”
“should,” “would,” “plan,” “expect,” “predict,” “could,” “seek,” “goal,” “potential,” or the negative of these terms or other similar terms or expressions that concern our expectations,
strategy, plans, or intentions. These statements are based on our intentions, beliefs, projections, outlook, analyses, or current expectations using currently available information,
and are not guarantees of future performance, and involve certain risks and uncertainties. Although we believe that the expectations reflected in these forward-looking
statements are reasonable, we cannot assure you that our expectations will prove to be correct. Therefore, actual outcomes and results could materially differ from what is
expressed, implied, or forecasted in these statements. Any differences could be caused by a number of factors including but not limited to: our expectations regarding the
timing, costs, conduct, and outcome of our clinical trials, including statements regarding the timing of the initiation and availability of data from such trials; the timing and
likelihood of regulatory filings and approvals for our product candidates; whether regulatory authorities determine that additional trials or data are necessary in order to obtain
approval; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; our
plans to research, develop, and commercialize our product candidates; the commercialization of our product candidates, if approved; the rate and degree of market acceptance
of our product candidates; our expectations regarding the potential market size and the size of the patient populations for our product candidates, if approved for commercial
use, and the potential market opportunities for commercializing our product candidates; the success of competing therapies that are or may become available; our expectations
regarding our ability to obtain and maintain intellectual property protection for our product candidates; the ability to license additional intellectual property relating to our product
candidates and to comply with our existing license agreements; our ability to maintain and establish relationships with third parties, such as contract research organizations,
suppliers, and distributors; our ability to maintain and establish collaborators with development, regulatory, and commercialization expertise; our ability to attract and retain key
scientific or management personnel; our ability to grow our organization and increase the size of our facilities to meet our anticipated growth; the accuracy of our estimates
regarding expenses, future revenue, capital requirements, and needs for additional financing; our expectations related to the use of our available cash; our ability to develop,
acquire, and advance product candidates into, and successfully complete, clinical trials; the initiation, timing, progress, and results of future preclinical studies and
developments and projections relating to our competitors and our industry.
Additional factors that could cause actual results to differ materially from our expectations can be found in our Securities and Exchange Commission filings. Moreover, we
operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors,
nor can we assess the effects of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those
contained in, or implied by, any forward-looking statements. All forward-looking statements included in this presentation are expressly qualified in their entirety by these
cautionary statements. The forward-looking statements speak only as of the date made and, other than as required by law, we undertake no obligation to publicly update or
revise any forward-looking statements, whether as a result of new information, future events, or otherwise.
3. 3
Investment Highlights
Addressing important patient needs and large markets within kidney disease
• Hyperphosphatemia patients live with extreme treatment burden
• No medicines approved for acute kidney injury (AKI) and limited treatment options for patients with chronic kidney disease (CKD)
Product candidates utilizing proven mechanisms of action
• Renazorb: Phosphate binder for the treatment of hyperphosphatemia in patients with CKD
• UNI-494: an innovative patented drug in late preclinical development with a novel mechanism of action that targets mitochondria.
Mitochondrial dysfunction is implicated in acute and chronic disease pathologies in organ systems with high energy demands like the
kidney, liver, heart and eye
Significantly De-risked Regulatory Pathway for Renazorb
• Pursuing a 505(b)(2) regulatory pathway for U.S. approval as per guidance and alignment with the FDA
• Ongoing healthy volunteer bio-equivalence study expected to complete this clinical study before the year end
• Ongoing bioequivalence study in healthy volunteers expected to complete by YE22
Cash runway to file Renazorb NDA and to initiate clinical trials for UNI-494 until early 2023
• Closed out-licensing deal in China with Lee’s Pharma for Renazorb
• Ongoing out-licensing discussions for Renazorb with other biopharma partners outside the US for other geographies
5. 5
Chronic Kidney Disease (CKD)
and Hyperphosphatemia
• Gradual loss of kidney function that can
worsen over time leading to lasting damage
• CKD stages range from 1 to 5
• Stage 5 is End Stage Renal Disease (ESRD)
• In CKD, hyperphosphatemia is caused by a
chronic dysregulation of mineral metabolism
as a result of progressive kidney damage
Chronic Kidney Disease (CKD) Hyperphosphatemia
Resorption
Absorption
P
• Electrolyte disorder in which untreated
elevated phosphate levels in the blood
lead to cardiovascular complications and
vascular calcification
• Occurs in at least 80% of patients with
Stage 5 CKD on dialysis* (>500,000
patients in the US)
6. 6
Hyperphosphatemia is Strongly Associated
with Mortality and Hospitalization
Uncontrolled phosphorus confers a 7% - 102%
increase in relative risk of mortality
Death
Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis
Geoffrey A. Block, Preston S. Klassen, J. Michael Lazarus, Norma Ofsthun, Edmund G. Lowrie and Glenn M. Chertow
JASN August 2004, 15 (8) 2208-2218; DOI: https://doi.org/10.1097/01.ASN.0000133041.27682.A2
0.75
1.00
1.25
1.50
1.75
2.00
2.25
< 3 3 - 4 4 - 5 5 - 6 6 - 7 7 - 8 8 - 9 > 9
0.90
1.00
1.10
1.20
1.30
1.40
1.50
4 - 5 5 - 6 6 -7 7 - 8.0 8 - 9 > 9
All-Cause
Cardiovascular
Relative
Risk
of
Death
Relative
Risk
of
Hospitalization
Hospitalization
Serum Phosphorus Concentration
(mg/dl)
Serum Phosphorus Concentration
(mg/dl)
Reference
range
Reference
range
7%
↑
25%
↑
43%
↑
67%
↑
2x
↑
10%
↑
15%
↑
29%
↑ 28%
↑
38%
↑
Uncontrolled phosphorus confers a 10% - 38%
increase in relative risk of hospitalization due
to cardiovascular causes
8. 8
Renazorb Product Profile
§ Renazorb (lanthanum dioxycarbonate nanoparticles) is a novel phosphate
binder treatment for hyperphosphatemia in patients with chronic kidney
disease (CKD)
§ MOA: Renazorb binds to dietary phosphate in the GI tract which is then
excreted via the feces resulting in reduction of serum phosphate levels
§ Proprietary nanotechnology
§ Enhanced surface area
§ Lower molecular weight
§ Immediate release tablets
§ Smaller pills
§ Swallowed (Not Chewed)
Reduced pill burden = potential for improved patient adherence
9. 9
Renazorb Global Intellectual Property
1
2
3
1 Renazorb is protected by a family of U.S. patents and a
related family of patents outside the U.S.
2
3
Both the U.S. patent family and the foreign patent family were
filed in 2011, and the U.S. coverage has statutory expiry in
2031
Corresponding patents granted in Canada, Europe, Japan,
China, Australia, and other countries also have statutory
expiration dates in 2031
10. 10
Mean Urine Phosphate (±SE) Excretion
per Day – In Vivo Rat Study
Renazorb Demonstrates Equivalency to Fosrenol and
Superiority to Sevelamer in Phosphate Binding
1 Urine tests that reflect treatment of medication
SOURCE:Data on File [m4-2-1-1-rat-mpi-1071-001]; Updated as of 11/10/21
At equivalent doses of
elemental lanthanum, the MW
of Renazorb is 30% less than
that of Fosrenol, yet binds a
comparable amount of
phosphate
When compared to an
equivalent dose of Sevelamer,
Renazorb binds a significantly
greater amount of phosphate
11. 11
Phase 1 Clinical Trial: RENAZORBTM was Well-Tolerated
with Dose-Dependent Phosphate Lowering Effect
1
Study Design:
Open label, dose ranging study (evaluated 4
doses : 1500, 3000, 4500 and 6000 mg/day),
in N=32 healthy volunteers
Primary endpoint: Phosphorus binding
capacity
Renazorb showed statistically significant
phosphate reduction with:
ü 3000 mg/day (-159.59 mg/L)
ü 4500 mg/day (-249.61 mg/L)
ü 6000 mg/day (-301.57 mg/L)
Secondary endpoint: Drug Safety
All treatment-related adverse events (AEs) were
mild in severity. No severe or life-threatening
AEs were reported
2
3
-400
-300
-200
-100
0
100
200
300
Baseline 8 9 10 11 12
Treatment Day
Off Treatment
On Treatment
Placebo
1500 mg/day
3000 mg/day
4500 mg/day
6000 mg/day
1 Baseline is the mean of phosphate concentrations from study day 2 to day 6
Note:Urine phosphate concentrations for each day is recorded on the morning of the following
day at a 24-hour interval
SOURCE: Data on File [rzb-11-101-synoptic-csr.pdf]; Updated as of 3/8/22
Urine Phosphate Concentration Change from Baseline1
(n=32 Healthy Volunteers)
mg/L, Urine Phosphate
13. 13
1.12
0.43
0.29
0.23
0.22
0.12
0.03
United States EU+UK Japan China ROW LATAM Canada
Source: Fortune Business InsightsTM, Hyperphosphatemia Treatment Market, 2021-2028
2.46
Billions of USD
(2021)
5.3% CAGR
in the forecast period
2021-2028
Unicycive owns worldwide rights to Renazorb
Renazorb Commercial Opportunity
Global Hyperphosphatemia Market Size
14. 14
Available Hyperphosphatemia Treatments
are Inadequate
1Phosphate binders in chronic kidney disease: an updated narrative review of recent data, J Nephrol. 2020 Jun;33(3):497-508
2Chiu YW, et al. Clin J Am Soc Nephrol. 2009
Juergen Floege, MD, Nephrologist
Executive Committee Member,
KDIGO CKD-MBD Guidelines
June 2020
“Ideally, we would have phosphate binders with high phosphate-binding
capacity (translating into low pill burden and good patient adherence)…
…we still do not have such a phosphate binder.”1
The daily pill burden of maintenance dialysis
patients is among the highest across various
chronic disease states including HIV/AIDS,
diabetes mellitus, and congestive heart failure2
• 19 pills per day (median)
• 49% of pill burden from phosphate binders
• Higher pill burden was independently associated
with lower quality of life scores (HR-QOL)
• 62% of patients are non-adherent (self-reported)
15. 15
Unmet Needs in Treatment of Hyperphosphatemia with Phosphate Binders (Unaided)
Lower Pill Burden/Better Patient Compliance Stated as the
Greatest Unmet Need in Hyperphosphatemia Treatment
Base: n=100 Nephrologists • Q1. What is the greatest unmet need in the treatment of hyperphosphatemia with phosphate binders?
Primary Market Research: Renazorb Conjoint Study, March 2022
60%
33%
15% 15%
8% 7% 5%
1%
0%
Lower pill burden/
Better patient
compliance
Greater
efficacy
Fewer side
effects
Once daily
dosing / Not
taken with meal
Other New MOA Lower Cost /
Better Coverage
None
In Q1, 2022, Unicycive commissioned a market
research study of 100 US-based nephrologists
16. 16
Renazorb is a novel form of Lanthanum
— the most potent known phosphate binder
2.0
1.9
1.7
1.5
1.3
1.0 1.0
0.75
0.0
0.5
1.0
1.5
2.0
2.5
Lanthanum
1
Alum
inum
1
M
agnesium
1
Alum
inum
2
M
agnesium
3
Calcium
4
Calcium
1
Sevelam
er
1,2
Renal failure rat model (5/6 nephrectomy). All binders dosed at 1,000 mg/kg/day.
Renal Failure, 33(2): 217–224, (2011)
Index
Value
1 carbonate, 2 hydroxide, 3 hydrate, 4 acetate
Seminars in Dialysis—Vol 24, No 1 (January–February) 2011 pp. 41–49
RPBC=relative phosphate-binding coefficient per gram
of binder (calcium carbonate with an index value of 1.0)
17. 17
Source: Average daily dose: dailymed.nlm.nih.gov, Pill volumes and weights: Data on file, Unicycive Therapeutics, Product images are proportionally sized
Renvela® is a registered trademark of Sanofi, Calphron® is a registered trademark of NEPHRO-TECH, INC., Auryxia® is a registered trademark of Akebia Therapeutics. Fosrenol™ is a trademark of
Takeda Pharmaceutical Company Limited, Velphoro® is a registered trademark of Vifor Fresenius
Renazorb Offers a Substantially Reduced Pill Burden
Compared to Available Phosphate Binders
Renazorb™
lanthanum dioxycarbonate 1,000mg
3 tablets per day, swallowed
Weight – 4.8 g; Volume – 2.3 cm3
Renvela®
sevelamer carbonate 800mg
9 tablets per day, swallowed
Weight – 10.1 g; Volume – 9.7 cm3
Calphron®
calcium acetate 667mg
9-12 tablets per day, swallowed
Weight – 10.7 g; Volume – 9.0 cm3
Auryxia®
ferric citrate 210mg
8-9 tablets per day, swallowed
Weight – 9.5 g; Volume – 7.4cm3
Velphoro®
sucroferric oxyhydroxide 500mg
3-4 tablets per day, chewed
Weight – 10.1 g; Volume – 7.3 cm3
Fosrenol®
lanthanum carbonate 1,000mg
3 tablets per day, chewed
Weight – 12.6 g; Volume – 8.0 cm3
19. 19
Renazorb Regulatory Strategy
and Key Milestones
FDA Regulatory Strategy - based on Type C interaction and written response from FDA (Q4, 2021)
• 505(b)(2) regulatory pathway for the potential U.S. approval of Renazorb
• Leverage pre-clinical and clinical data from existing lanthanum-based product (Fosrenol)
Strategy involves the following studies for potential approval of Renazorb:
• Bioequivalence study in healthy volunteers comparing urinary phosphorus changes between Renazorb and Fosrenol
• 6-month oral toxicity study in mice
• Standard information on manufacturability and commercial supply readiness of product
Commercial strategy underway to leverage large market opportunity
• Product positioning, market access, and market shaping activities ongoing to optimize value proposition
• Pursuing parallel commercial model pathways to address highly-concentrated nephrology market opportunity
• Outsourced contract sales organization
• Partnership with pharma company already selling into the nephrology call point
20. 20
Mitochondria are
concentrated in high energy
consuming organ systems
Eye
Heart
Kidney
Liver
Mitochondrial Dysfunction is Linked
to Acute and Chronic Diseases
Mitochondrial dysfunction is
implicated in diseases of
these organs
21. 21
Mitochondrion
Inner
membrane
Outer
membrane
mitoKATP channel
MPT pore
Mitochondrial
permeability
transition pore
UNI-494 Restores Mitochondrial Function
Mechanism of Action
Source: Hazel H Szeto J Am Soc Nephrol 28: 2865, 2017; Shiraishi et al., 2014
Ca+
↑ROS
↓ATP
CLOSED
OPEN
SUR
Kir1
Mitochondrial Dysfunction
• A hallmark feature of
mitochondrial dysfunction is
chronic opening of MPT Pores
• Chronic opening of MPT Pore
leads to water and solute influx,
injury and subsequent death
↓ SIRT 3
↓ MnSOD
↓ROS
CLOSED
OPEN
NC
↑ATP
Restored Function
↑SIRT 3
↑MnSOD
• UNI-494 is an ATP-sensitive K+
channel (KATP) activator
• Binds to SUR2 subunit of KATP
channel that in turn leads to
closing of MPT pores
• Nicorandil binding to SUR results
in blockade of production of
Reactive Oxygen Species (ROS)
22. 22
UNI-494 Profile
Known
MOA(s)
Demonstrated
Safety & Efficacy
Approved
indication
(EU/Asia)
Controlled
release
Pharmacokinetics
Linker
(chemical modifier)
Enhanced
Pharmaceutical
Properties
Established
Legacy
UNI-494
Nicorandil
(parent compound)
New
Opportunities
New
Chemical
Entity
Fresh IP
Reduced
Toxicities?
De-risked
Development Less Frequent
Dosing?
New
Indications
23. 23
UNI-494 Animal Studies Increased Drug Exposure 4X
vs Nicorandil
Source: Nicorandil dog PK data from Kim et al., Asian J Pharm Sci, 2014
*Abbreviation: AUC- Area Under the Curve
• PK data normalized by dose of
nicorandil and compared to historical
data
• Dosing of UNI-494 resulted in a 4X
greater exposure (*AUC) of nicorandil
than dosing nicorandil alone
0
50
100
150
200
250
300
0 1 2 3 4 5 6 7 8
Dose-Normalized
Nicorandil
Concentration
Nicorandil Concentrations (ng/mL) Following Oral
Administration of UNI-494 or Nicorandil to Dogs
UNI-494 Nicorandil
Nicorandil concentrations (ng/mL) following oral
administration of UNI-494 or nicorandil to dogs
24. 24
UNI-494: Potential to Improve on an
Established Legacy
Efficacy
• Evidence of pre-clinical and clinical efficacy in
acute and chronic kidney diseases
Safety/Tolerability
• Overall safe and well-tolerated
• Most common adverse events (AEs) are related
to vasodilation (headache, flushing, dizziness)
• Associated with gastro-intestinal (GI) tolerability
and rare GI ulcerations and perforations
Pharmacokinetics
• Short half-life (~1 hour), necessitating TID/BID
dosing
Source: https://apps.medicines.org.au/files/swpikore.pdf;
• Utilizes a known, safe, chemical linker to
create pro-drug
• Pro-drug addresses gut safety concerns
present with nicorandil
• Controlled release of active drug in
plasma from pro-drug may enable QD
dosing
• Greater drug exposure (AUC) may allow
for lower dosing
NICORANDIL UNI-494
25. 25
UNI-494 Global Intellectual Property
1
2
1 UNI-494 is protected by a broad issued patent
• Patent granted in the U.S. and Europe with expiry 2032
• Patent pending in Japan and China
• Exclusively licensed to Unicycive
2
Additional patents filed for UNI-494 in the U.S. and globally
• If granted, would expire 2040
• International patent applications planned from this patent family
• Additional multiple patent applications being filed
27. 27
Acute Kidney Injury (AKI) and
Current Treatment
Acute Kidney Injury (AKI)
Background
• Characterized by a sudden loss of kidney function
• Persistent AKI is characterized by the continued
decreased in urine output or increases in serum
creatinine (as defined by KDIGO) beyond 48 hour
from AKI onset up to day 7
• AKI and CKD can form a continuum whereby initial
kidney injury can lead to persistent renal injury,
eventually leading to CKD
• In most cases the damage to the kidney is
irreversible, and the patient needs to have a renal
transplant or be on dialysis for life
• Treatment options include:
There are no approved medicines to
treat AKI
• Renal replacement therapy
• Renal transplant
• Radical surgery and dialysis
AKI Acute Kidney Injury
CKD Chronic Kidney Disease
First 90days
28. 28
AKI Incidence & Mortality
1 in 5 adults and 1 in 3 children worldwide experience
AKI during a hospital episode of care
21.6% in adults
33.7% in children
23.9% in adults
13.8% in children
Source: Susantitaphong et al: Clin J Am Soc Nephrol 2013
AKI-Associated Mortality Rates
AKI-Associated Incidence Rates
Among the 154 studies (n=3,585,911) that
adopted a KDIGO-equivalent AKI definition
29. 29
1 Length Of Hospital Stay (≤7 Days) = reference; 2 Duration of AKI (1-2 Days) = reference; 3 Stage of AKI (Stage 1) = reference; 4 Age (18-30 Years) = reference; 5 Sepsis (No) = reference;
6 Anemia (No) = reference;
1012_Abebe A, et al. Sci Rep. 2021.; Updated as of 4/12/22
Stage 3 Acute Kidney Injury (AKI) Significantly Associated
with Increased Risk of Mortality
Hazard Ratio (95% CI) of Mortality in AKI Patients by Risk Factors (n=203)
0 10 20 30
*p<0.05
Hazard Ratio (95% CI)
0.32 (0.04, 2.30)
0.05 (0.02, 0.13)
1.30 (0.08, 20.88)
7.93 (1.05, 59.95)
8.10 (3.69, 17.79)
4.28 (1.05, 18.30)
2.35 (0.29, 18.62)
9.47 (3.14, 28.89)
12.27 (2.74, 49.80)
P-Value
0.251
<0.001*
0.851
0.045*
<0.001*
0.049*
0.416
<0.001*
0.003*
1
50
60
Risk Factors
LOHS1 (Days): >7
Duration of AKI2 (Days): 3-6
Age4 (Years): ≥60
Stage of AKI3 (Stage): 2
Sepsis5
Duration of AKI2 (Days): ≥7
Age4 (Years): 30-60
Anemia6
Stage of AKI3 (Stage): 3
31. 31
UNI-494: Development Strategy
Pursuing AKI as initial indication with CKD as a follow-on program
Nicorandil has compelling published scientific data which supports
development of UNI-494 for Acute Kidney Disease (AKI) and Chronic
Kidney Disease (CKD)
UNI-494 is a novel pro-drug of a marketed agent, nicorandil, with
improved properties and long patent life
2
1
3
32. 32
Nicorandil – Renoprotection in Animal Models
Model Regimen Outcome Reference
STZ-induced diabetic
nephropathy in eNOS
ko mice
Therapeutic – treatment initiated 4
weeks after STZ induction
30 mg/kg/day for 8 weeks
No decrease in BP but significant reduction in
proteinuria, glomerular injury, collagen
deposition, and podocyte loss
Tanabe et al., 2012
5/6th nephrectomy in
rats
Therapeutic – treatment initiated at
time of nephrectomy – 15 mg/kg for
12 weeks
No decrease in BP but significant reduction in
proteinuria, sCr and BUN, glomerular injury, and
tubulointerstitial injury
Shiraishi et al., 2014
Anti-Thy1 nephritis in
rats
Prophylactic – treatment initiated 3
days before anti-Thy1 injury
10 and 30 mg/kg/day for 12 days
No decrease in BP but significant reduction in
proteinuria, renal hypertrophy, collagen
deposition, and TGFb expression
Sudo et al., 2009
Acute ischemia-
reperfusion injury in
rats
Therapeutic– treatment initiated 10
min prior to ischemic injury-10 mg/kg
Significant protection against I-R-induced injury
including proteinuria and histological damage
Shimizu 2011
Dahl salt-sensitive
hypertensive rats
Prophylactic – treatment initiated at
time of switch to high salt diet
No decrease in BP but significant reduction in
proteinuria, NAG excretion, and oxidative stress
Tashiro et al., 2015
Spontaneously
hypertensive WHY rat
Therapeutic – treatment initiated at
11 weeks of age
No decrease in BP but significant reduction in
proteinuria, kidney size, and tubular damage
Serizawa et al., 2013
• Nicorandil shown effective in numerous well-established animal models of kidney disease
at doses that do not reduce blood pressure
33. 33
Nicorandil: Clinical Evidence for Renoprotection
Acute Kidney Injury
Clinical Setting Outcome Reference
Acute Kidney Injury
Patients with poor kidney
function scheduled for PCI
(n=213) randomized to saline
or nicorandil
• Dose: 0.096 mg/mL cont. infusion; 4 hours before and 24
hours after PCI
• Significant reduction in contrast-induced nephropathy (2.0%
vs 10.7%, p <0.02)
• Reduction in contrast-induced increase in sCr and cystatin C
• Reduction in contrast-induced decline in eGFR
Nawa et al.,
2015
At-risk patients scheduled for
PCI (n=128) randomized to
placebo or nicorandil
• Dose: 10 mg/day; 30 mins before to 3 days after PCI
• Significant reduction in contrast-induced nephropathy (4.7%
vs 21.9%, p <0.008)
• Significant reduction in contrast-induced decline in eGFR
Iranirad et al.,
2017
Nicorandil is associated with improved clinical outcomes in several randomized
clinical trials in patients with kidney disease
34. 34
Nicorandil Reduces Incidence of CIN in Patients
Undergoing CAG/PCI: Meta-Analysis of 7 RCTs
Pranata et al Cardiovascular Revascularization Medicine 21 (2020) 1121-1127
Nicorandil Dose 10 mg TID for oral administration (6 studies) or 12 mg by IV over 30 mins in one study)
Efficacy of nicorandil in patients with renal dysfunction
Efficacy of nicorandil (Oral vs IV). Efficacy in oral appears better
35. 35
Nicorandil: Clinical Evidence for Renoprotection:
Chronic Kidney Disease
Clinical Setting Outcome Reference
Chronic Kidney Disease
Proteinuric patients (n=136)
randomized to placebo, ISDN
or nicorandil for 6 months
• Dose 15 mg/day for 6 months
• Significant (44%) reduction in proteinuria (p < 0.0001);
• Significant reduction in urinary endothelin-1 excretion
Lee & Chang,
2009
Hemodialysis patients (n=129)
who underwent PCI and were
randomized to chronic placebo
or nicorandil
• Dose 15 mg/day
• Significant improvement in 3-year all-cause survival (79% vs
61%) (p= 0.01)
• Significant improvement in 3-year cardiac death-free
survival (87% vs 71%) (p=0.009)
Nishimura et al.,
2009
Nicorandil is associated with improved clinical outcomes in several randomized clinical
trials in patients with chronic kidney disease
36. 36
Patients Treated with Nicorandil Had Significantly Lower Urine
Protein Excretion1 at Follow-Up2 Compared to Baseline
1 Proteinuric (300– 3000 mg/day), valsartan-treated hypertensive patients with blood pressure less than 140/90 mmHg
2 Post 6-month intervention therapy
SOURCE: 936_Lee TM, et al. J of Hypertension.2008.; Updated as of 3/3/22
37. 37
Nicorandil Reduces the Risk of Fatal Cardiac Events1
Compared to Control2 (87% vs 71%)
1 In hemodialysis patients who had obtained complete coronary revascularization (absence of both restenosis and de novo coronary lesions) by means of 1 or more PCI procedure
2 Lack of nicorandil
SOURCE: 940_Nishimura M, et al. Am J Kidney Dis. 2009.; Updated as of 3/3/22
50
60
70
80
90
100
0 1 2 3 4 5
64 57 46 28 13 2
65 53 39 23 16 5
Nicorandil
Control2
# at Risk
Nicorandil
Control2
Years
Log-rank test
p=0.009
KM Graph for Fatal Cardiac Events in Nicorandil (n=64) and Control2 Groups (n=65)
Cardiac Death-Free Survival Rate
38. 38
Nicorandil Reduces the Risk of Death Compared to Control
(79% vs 61%)
KM Graph for All-Cause Death1 in Nicorandil (n=64) and Control2 Groups (n=65)
Cumulative Survival Rate
1 In hemodialysis patients who had obtained complete coronary revascularization (absence of both restenosis and de novo coronary lesions) by means of 1 or more PCI procedure
2 Lack of nicorandil
SOURCE: 940_Nishimura M, et al. Am J Kidney Dis. 2009.; Updated as of 3/3/22
64 57 46 28 13 2
65 53 39 23 16 5
50
60
70
80
90
100
0 1 2 3 4 5
Years
# at Risk
Nicorandil
Control2
Nicorandil
Control2
Log-rank test
p=0.01
39. 39
UNI-494 FDA Strategy and Key Milestones
FDA Regulatory Strategy:
• Confirm pro-drug has acceptable tolerability in animal studies at
desired doses
• Identify pro-drug dose(s) for initial human study, Demonstrate
conversion of UNI-494 to nicorandil in humans
• Seek FDA clearance to initiate Phase 1 study (IND approval)
Unique attributes for regulatory approval of UNI-494:
• Leverage pre-clinical and clinical data from nicorandil outside
United States with comparability package
• Design of more homogenous AKI patient population including
patients with CIN where nicorandil has been shown to be
efficacious
Milestones
ü Completed chemical synthesis for animal
studies - 3Q, 2021
ü Initiated animal safety studies - 3Q, 2021
• Complete preclinical studies – 1H, 2022
• File IND – mid-2022
• Initiate Phase 1 clinical trial – 2H, 2022
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Unicycive Leadership
Sandeep “Steve” Laumas, MD
Goldman Sachs,
North Sound Capital
Shalabh Gupta, MD
UBS, Genentech
John Ryan, MD, PhD
Wyeth, Merck,
Kadmon
Board of Directors
Brigitte Schiller, MD
CMO at Satellite
Healthcare
Shalabh Gupta, MD
Chief Executive Officer
UBS, Genentech
Pramod Gupta, PhD
EVP, Pharmaceutical &
Business Operations
Spectrum, B&L, Abbott
Management
John Townsend, CPA
Chief Financial Officer
Guardion Health Sciences,
Cytori Therapeutics
Doug Jermasek, MBA
EVP, Corporate Strategy
Genzyme-Sanofi, Akebia,
Keryx, Pfizer, Abbott
Guru Reddy, PhD
VP, Preclinical R&D
Spectrum, Ciphergen,
Pangene, Yale
41. 41
Unicycive Advisors
Ravi Mehta, MD
Prof Emeritus of
Medicine, UCSD
Scientific Board
Pablo Pergola, MD, PhD
Director, Clinical Advancement
Center, PLLC, a wholly-owned
subsidiary of Renal Associates
Glenn Chertow, MD, MPH
Chief, Division of Nephrology at
Stanford University School of
Medicine
Myles Wolf, MD
Charles Johnson, Prof
of Medicine and Chief,
Division of Nephrology
at Duke University
School of Medicine
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Catalyst Rich 2022 and Beyond
üFDA meeting
üPresent clinical and preclinical data at
NKF Conf
üInitiate BE study in healthy volunteers
• Data readout from BE study
• Complete 6-month mouse study
• Near-term NDA filing
Renazorb
üEarly animal PK studies completed
üMulti-kilo scale chemical supplies for
animal safety studies completed
üAnimal safety studies initiated
üPhase 1 human studies planning
initiated
• Start of Phase 1 human studies
• Global patent progress ongoing
UNI-494
32
43. 43
Investment Highlights
Addressing important patient needs and large markets within kidney disease
• Hyperphosphatemia patients live with extreme treatment burden
• No medicines approved for acute kidney injury (AKI) and limited treatment options for patients with chronic kidney disease (CKD)
Product candidates utilizing proven mechanisms of action
• Renazorb: Phosphate binder for the treatment of hyperphosphatemia in patients with CKD
• UNI-494: an innovative patented drug in late preclinical development with a novel mechanism of action that targets mitochondria.
Mitochondrial dysfunction is implicated in acute and chronic disease pathologies in organ systems with high energy demands like the
kidney, liver, heart and eye
Significantly De-risked Regulatory Pathway for Renazorb
• Pursuing a 505(b)(2) regulatory pathway for U.S. approval as per guidance and alignment with the FDA
• Ongoing healthy volunteer bio-equivalence study expected to complete this clinical study before the year end
• Ongoing bioequivalence study in healthy volunteers expected to complete by YE22
Cash runway to file Renazorb NDA and to initiate clinical trials for UNI-494 until early 2023
• Closed out-licensing deal in China with Lee’s Pharma for Renazorb
• Ongoing out-licensing discussions for Renazorb with other biopharma partners outside the US for other geographies