august 2017 - amazon s3 · tenax- late-stage specialty pharma company capital-efficient strategy...

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)


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


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


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


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


-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


-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

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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)



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



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)


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



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



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

august 2017 - amazon s3 · tenax- late-stage specialty pharma company capital-efficient strategy...

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