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Corporate UpdateAugust 2017
Legal Disclaimer
This presentation contains forward looking statements which reflect the Company’s plans, goals
and expectations as of this date. All statements other than statements of historical facts which
address the Company’s expectations on such matters as sources of capital, the Company’s plans
for the future with respect to financial performance or operating strategies, can be identified as
forward-looking statements. The Private Securities Litigation Reform Act of 1995 provides a safe
harbor for forward looking information made on the Company’s behalf. Actual results may differ
materially from the expectations expressed in the forward-looking statements. There can be no
assurance that those plans, goals or expectations will be realized. Additional information
concerning these and other risk factors affecting Tenax Therapeutics, Inc.'s business can be
found in the Company's public periodic filings with the Securities and Exchange Commission,
which are available via www.tenaxthera.com. Tenax Therapeutics, Inc. disclaims any intent or
obligation to update these forward-looking statements beyond the date of this presentation. This
caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of
1995. This presentation is not an offer or a solicitation of an offer to buy any securities in the
Company.
2
Tenax- Late-Stage Specialty Pharma Company
▪ Capital-efficient strategy with low R&D spend
- Search, Develop and Commercialize
- Executed by experienced management
▪ Late stage product with commercial rights In US and Canada - Levosimendan
- Approved in over 60 countries for ADHF, >1.2 million patients treated to date
- FDA Fast Track status for cardiac surgery Indication
▪ LEVO-CTS phase 3 trial in cardiac surgery completed
- Primary endpoints were not achieved
- Subgroup analysis indicates divergent response by surgery type
▪ Mortality reduction of >70% in Isolated CABG patients in LEVO-CTS
- 73% relative reduction in 90-day mortality, p=0.0016 cannot be ignored
- Consistent with study hypothesis and previous Isolated CABG trials
▪ Development Strategy
- FDA has requested a confirmatory trial and alternatives are being assessed
3
Levosimendan Triple MOA Provides Strong Rationale for Efficacy in Cardiac Surgery Setting
Adapted from Pisano, Antonio, Giacomo Monti, and Giovanni Landoni. "Levosimendan: new indications and evidence for reduction in perioperative mortality?." Current Opinion in Anesthesiology (2016).
4
LEVO-CTS Study: Primary & Secondary Endpoint Results
5
LEVO-CTS Co-Primary Outcomes
24.5%
13.1%
24.5%
11.4%
0%
5%
10%
15%
20%
25%
30%
QUAD OUTCOME† DUAL OUTCOME†
Levosimendan Placebo
Odds ratio (99% CI)1.01 (0.66-1.54)
p=0.9775
Odds ratio (96% CI)1.18 (0.76-1.82)
p=0.4501
†Adjusted for covariates: type of surgery, LVEF, age, sex
105 103
5648
Quad Outcome = death, dialysis, MI or mechanical assist device useDual Outcome = death or mechanical assist device use
N=849 MITT Population
6
LEVO-CTS Individual Outcomes Components
3.5%
15.7%
2.1%
11.0%
4.5%
15.0%
3.8%
9.0%
0%
4%
8%
12%
16%
DEATH (30-DAY) MYOCARDIALINFARCTION
(5-DAY)
DIALYSIS(30-DAY)
MECHANICALASSIST(5-DAY)
Levosimendan Placebo
Odds ratio (99% CI)1.06 (0.73-1.53)
p=0.78
Odds ratio (95% CI)0.77 (0.39-1.53)
p=0.45
Odds ratio (99% CI)0.54 (0.24-1.24)
p=0.15
Odds ratio (99% CI)1.24 (0.79-1.95)
p=0.341519
67 63
9
16
47
38
N=849 MITT Population
7
LEVO-CTS Secondary Outcomes
18.2%
54.9%
25.7%
62.7%
0%
25%
50%
75%
LOW CARDIAC OUTPUT
SYNDROME
SECONDARYINOTROPE USE
>24 HOURS
Levosimendan Placebo
Odds ratio (95% CI)0.62 (0.44-0.88)
p=0.007
Odds ratio (95% CI)0.71 (0.53-0.94)
p=0.017
2.8 (1.6, 4.8)
days
2.9 (1.8, 4.9)
days
0
1
2
3
ICULENGTH OF STAY
p=0.10
78
108
235
264
N=849 MITT Population
8
LEVO-CTS 90-Day Mortality
9
N=849 As Treated Population
LEVO-CTS Study: Mortality Results by Surgery Type
10
LEVO-CTS Trial Populationn=849*
11
849 Patients EF ≤ 35%
ISOLATED CABG,CABG + Valve,
Isolated Mitral Valve,Combined Valve
Isolated CABG n=563
Any Valve Surgery (+/-
CABG)n=285
* 1 patient no surgery
12
LEVO-CTS 90-Day Mortality in Isolated CABG Patients
Isolated CABG n=563
Kaplan-Meier plot of mortality to day 90 (Safety Population, As Treated) for patients with Isolated CABG
LEVO-CTS Isolated CABG Patients Consistent Mortality Reduction at 30 & 90 Days
1.8% 2.1%
5.4%
7.9%
30-Day Mortality 90-Day Mortality
Levosimendan Placebo
-67%-73%
(n=563, as treated)
p= 0.0016
P< 0.05
5/284 6/284
22/279
15/279
13
3.9%
1.8%
12.8%
5.4%
Levin Pre-Op Trial (N=252) LEVO-CTS Isolated CABG Subgroup (N=563 as treated)
30-Day Mortality
Levosimendan Placebo
-67%
-70%
LEVO-CTS 30-Day Mortality Reduction is Consistent with Other Pre-Op Isolated CABG Trials
P< 0.05
p ≤ 0.05
15/279
5/127
16/125
Levin, Ricardo, et al. "Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left
ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass." Experimental & Clinical Cardiology 17.3 (2012): 125.
5/284
14
LEVO-CTS 90-Day Mortality in Valve Surgery Patients (with or without CABG)
15
Isolated CABG N=563
Any Valve SurgeryN=285
Kaplan-Meier plot of mortality to day 90 (Safety Population, As Treated)
for patients with Surgery Other than Isolated CABG
LEVO-CTS Study: Consistency of Response by Surgery Type
16
Consistent Response in Isolated CABG Patients
17
10%
-20%
-46%
-72%-67%
-73%
-80%
-70%
-60%
-50%
-40%
-30%
-20%
-10%
0%
10%
20%
p< 0.05
Patients Requiring
Conventional Inotropes Hour 24
Low Cardiac Output
Syndrome
Mortality at
Day-30
Mortality at
Day-90
P<0.0001
Dialysis
Cardiac Index
p=0.0014
p=0.0016p<0.05NS
% R
elat
ive
Dif
fere
nce
(Le
vosi
men
dan
vs
Pla
ceb
o)
LEVO-CTS Isolated CABG Patients Response to Levosimendan
Cardiac index based on N= 460, All other Variables based on n=563
NS =Non-statistically Significant
LEVO-CTS Reveals Divergent Hemodynamic Responses to Levosimendan - Varies by Surgery Type
18
10%
-20%
-46%
0%
-1.50%
-8%
-50%
-40%
-30%
-20%
-10%
0%
10%
20%Isolated CABG Any Valve
p ≤0.0001
NS
p< 0.05
Mean Post Op Cardiac Index
Patients Requiring ConventionalInotropes at Hour-24
Low Cardiac Output Syndrome NS
NS
p = 0.0014
% R
elat
ive
Dif
fere
nce
(Le
vosi
men
dan
vs
Pla
ceb
o)
Cardiac index based on N= 460, All other Variables based on n=563
NS =Non-statistically Significant
Divergent Outcomes By Surgery Type Align with Divergent Hemodynamic Response
19
Cardiac IndexInotrope at
Hour 24LCOS Dialysis
Mortality atDay-30
Mortality atDay-90
Isolated CABG 10% -20% -46% -72% -67% -73%
Any Valve 0% -1.50% -8% -25% 138% 70%
10%
-20%
-46%
-67%-73%
-100%
-50%
0%
50%
100%
150%
% R
ELA
TIV
E D
IFFE
REN
CE
(LE
VO
SIM
END
AN
VS
PLA
CEB
O)
Isolated CABG
Any Valve
P<0.0001
NS
p=0.0014
NSNS
p<0.05
p=0.0016p<0.025
NS
NS
NS
NS
Cardiac index based on N= 460, All other Variables based on n=563
NS =Non-statistically Significant
Pathophysiology May Provide Possible Explanation for Divergent Responses in Low EF Isolated CABG vs Valve Surgery Patients
Cardiac Dysfunction Characteristics
Low EF Isolated CABG Patients
Low EF Valve Surgery Patients
EtiologyIschemic
(usually reversible)Structural and/or Ischemic (heterogenous population)
PathophysiologyIschemia/ Stunning/
Hibernating Myocardium
Myocyte disarray and irreversible fibrosis secondary
to chronic wall stress, including some patients with
ischemic component
Contractile FunctionCardiac Dysfunction
Frequently ReversibleCardiac Dysfunction
Frequently Irreversible
1. Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med 2011;364:1617-1625.2. Hein, Stefan, et al. "Progression from compensated hypertrophy to failure in the pressure-overloaded human heart." Circulation 107.7 (2003): 984-991.3. Starling, Mark R., et al. "Impaired left ventricular contractile function in patients with long-term mitral regurgitation and normal ejection fraction." Journal of the
American College of Cardiology 22.1 (1993): 239-250.
20
Additional Published Levosimendan Mortality Data : Consistent Mortality Data in Prior Trials
21
LEVO-CTS Hypothesis (Reduced Mortality and Morbidity) was Based on Prior Cardiac Surgery Studies
22
3.9%
12.8%
(N=252)
Levosimendan Placebo
5/127
Levin, Ricardo, et al. "Preoperative levosimendan decreases mortality and the development of low cardiac output in
high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with
cardiopulmonary bypass." Experimental & Clinical Cardiology 17.3 (2012): 125.
16/125
70%
p ≤ 0.05
Levin et al 2012, 30-Day Mortality
Bayesian Network Analysis of Inotropes Supports Levosimendan Mortality Benefit in Cardiac Surgery
23
From: A Bayesian network meta-analysis on the effect of inodilatory agents on mortalityBr J Anaesth. 2015;114(5):746-756. doi:10.1093/bja/aeu446
Bayesian Network Analysis of Highlights Lack of Data for FDA Approved Products
24
From: A Bayesian network meta-analysis on the effect of inodilatory agents on mortalityBr J Anaesth. 2015;114(5):746-756. doi:10.1093/bja/aeu446
Only 3 “un-blinded” placebo controlled
trials of Dobutamine in Cardiac Surgery
totaling just 70 Patients
Levosimendan - Bayesian Network Meta Analysis
25
Br J Anaesth.
2015;114(5):746-756.
doi:10.1093/bja/aeu446
LCOS an Unmet Need: Increased Mortality and Costs
26
Unmet Need in LCOS
▪ Significant unmet medical need
- LCOS incidence 5-10% of cardiac surgery patients (1)
- 14-15 fold operative mortality (2)
- 2-Fold Increase in Vent Time, ICU Time and Hospital Time
▪ Cardiac surgery patients at risk for LCOS
- LV dysfunction, prior CABG, female, diabetes, age > 70
▪ Isolated CABG patients are at risk for LCOS(3)
- 38% of Isolated CABG have 2 or more pre-operative risk factors for LCOS
▪ No drug currently indicated for prevention/treatment of LCOS
1. Rao et al, J Thorac Cardiovasc Surg 1996;112:38-512. Cardiac Surgery in the Adult / Edition 3 by Lawrence H. Cohn3. Source: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome, conducted by Premier, funded by Tenax
27
28
Adjusted Index Admission Hospital Mortality for Isolated CABG Surgeries
No LCOS(n=33,463)
LCOS(n=3,603)
In-Hospital MortalityN (%) N (%) OR 95% CI
P-Value
Unadjusted 244 (0.7%)
436 (12.1%) 18.74
15.96, 22.01 <.0001
Multivariable Regression Adjusted 13.61
11.43, 16.20 <.0001
LCOS is Associated with Increased Risk ofIn-Hospital Mortality in Isolated CABG Patients
Source: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome,
conducted by Premier, funded by Tenax
LCOS is Associated with Increased Mortality and Post Op Complications in Isolated CABG Patients
29
In-hospitalMortality
PerioperativeMI
HemorrhagicBleed
RequiringReop
HemodialysisAcute RenalFailure (no
dialysis)
AcuteRespiratory
Failure
No LCOS (n=33,463) 0.70% 1.30% 0.50% 0.90% 10.80% 14%
LCOS (n=3,603) 12.10% 4.10% 2.80% 5% 27.10% 36.50%
0.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
40.00%
Co
mp
licat
ion
Rat
e %
Post Op Complications in Isolated CABG Patients Who Develop LCOS vs No LCOS (unadjusted)
Chi-square Test, p-value <0.0001 for in-hospital mortality and all complicationsSource: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome, conducted by Premier, funded by Tenax
LCOS is Associated with Increased Hospital Costs in Isolated CABG Patients
30
Adjusted Cost and Resource Utilization for Isolated CABG Surgeries
No LCOS(n=33,463)
LCOS(n=3,603)
Index Admission Total Hospital Costs ($)
Mean STD Mean STD P-Value
Unadjusted 37,794.63 18,457.91 60,246.48 36,396.68 <.0001
Multivariable Regression Adjusted
38,544.11 10,256.41 51,132.43 13,606.10 <.0001
+ $12,500Incremental
Index Admission
Cost Estimate
Source: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome,
conducted by Premier, funded by Tenax
31
Adjusted All-Cause Inpatient Readmission Ratesfor Isolated CABG Surgeries
No LCOS LCOS
(n=33,219) (n=3,167)
30-day All-Cause Readmissions
N (%) N (%) OR 95% CI P-Value
Unadjusted 4,019 (12.1%) 608 (19.2%) 1.76 1.57, 1.90 <.0001
Multivariable Regression Adjusted 1.34 1.21, 1.49 <.0001
6-Month All-Cause Readmissions
N (%) N (%) OR 95% CI P-Value
Unadjusted 6,748 (20.3%) 950 (30.0%) 1.68 1.55, 1.82 <.0001
Multivariable Regression Adjusted 1.27 1.16, 1.38 <.0001
LCOS is Associated with Increased Hospital Readmission in Isolated CABG Patients
Source: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome,
conducted by Premier, funded by Tenax
Isolated CABG represents 68% of all Major Heart Surgery Procedures Performed in the US
68%
13%
3%8%
1% 1%
4%
2%
Isolated CABG Isolated Aortic Valve Replacement
Isolated Mitral Valve Replacement Aortic Valve Replacement + CABG
Mitral Valve Replacement + CABG Aortic+ Mitral Valve Replacements
Mitral Valve Repair itral Valve Repair + CABG
Isolated CABG
1) Society of Thoracic Surgeons (STS Database) Full Year 2015, most recent update (March 2016)
2) Source: Resource Utilization for Cardiovascular Surgery Patients at Risk for Development of Low Cardiac Output Syndrome, conduct by Premier, Funded by Tenax
38% of Isolated CABG Patients have
2 or more Pre-Operative
Risk Factors for LCOS
(1)
(2)
32
Tenax- Late-Stage Specialty Pharma Company
▪ Capital-efficient strategy with low R&D spend
- Search, Develop and Commercialize
- Executed by experienced management team
▪ Late stage product with commercial rights In US and Canada - Levosimendan
- Approved in over 60 countries for ADHF, >1.2 million patients treated to date
- FDA Fast Track status for cardiac surgery Indication
▪ LEVO-CTS phase 3 trial in cardiac surgery completed
- Primary endpoints were not achieved
- Subgroup analysis indicates divergent response by surgery type
▪ Mortality reduction of >70% in Isolated CABG patients in LEVO-CTS
- 73% relative reduction in 90-day mortality, p=0.0016 cannot be ignored
- Consistent with study hypothesis: ↓LCOS, results in ↓mortality
- LEVO-CTS results are consistent with previous Isolated CABG trials
▪ Development strategy
- FDA has requested a confirmatory trial and alternatives are being assessed.
33