Breakthrough Mitochondrial Science A Source for Novel Therapeutics - - PowerPoint PPT Presentation

CohBar Corporate Presentation

NASDAQ: CWBR

Breakthrough Mitochondrial Science

A Source for Novel Therapeutics

May 2020

Q1 2020 Investor Presentation

CohBar Corporate Presentation

Forward Looking Statements

2 This presentation contains forward-looking statements which are not historical facts within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and other future conditions. In some cases you can identify these statements by forward-looking words such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “could,” “should,” “would,” “project,” “plan,” “expect,” “goal,” “seek,” “future,” “likely” or the negative or plural of these words or similar expressions. Examples of such forward-looking statements include but are not limited to statements regarding our cash forecasts; anticipated

• utcomes of research and clinical trials for our mitochondria based therapeutic (MBT) candidates; expectations regarding the timing and progression of our CB4211

clinical trial and the expecting timing of delivery of data, expectations regarding the growth of MBTs as a significant future class of drug products; and statements regarding anticipated therapeutic properties and potential of our mitochondrial peptide analogs and MBTs, including but not limited to the treatment of COVID-19

• ARDS. You are cautioned that such statements are not guarantees of future performance and that actual results or developments may differ materially from those set

forth in these forward-looking statements. Factors that could cause actual results to differ materially from these forward-looking statements include: our ability to successfully advance drug discovery and development programs, including the delay or termination of ongoing clinical trials; our possible inability to mitigate the prevalence and/or persistence of the injection site reactions, receipt of unfavorable feedback from regulators regarding the safety or tolerability of CB4211 or the possibility of other developments affecting the viability of CB4211 as a clinical candidate or its commercial potential; results that are different from earlier data results including less favorable than and that may not support further clinical development; our ability to raise additional capital when necessary to continue our operations;

• ur ability to recruit and retain key management and scientific personnel; risks related to the impact on our business of the COVID-19 pandemic or similar public health

crises; and our ability to establish and maintain partnerships with corporate and industry partners. Additional assumptions, risks and uncertainties are described in detail in our registration statements, reports and other filings with the Securities and Exchange Commission and applicable Canadian securities regulators, which are available on our website, and at www.sec.gov or www.sedar.com. You are cautioned that such statements are not guarantees of future performance and that our actual results may differ materially from those set forth in the forward- looking statements. The forward-looking statements and other information contained in this presentation is made as of the date hereof and CohBar does not undertake any obligation to update publicly or revise any forward-looking statements or information, whether as a result of new information, future events or otherwise, unless so required by applicable securities laws. Nothing herein shall constitute an offer to sell or the solicitation of an offer to buy any securities.

CohBar Corporate Presentation

Presentation Information

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Investor Update and Slide Presentation Date: May 14, 2020 Time: 5:00 p.m. (ET) 2:00 p.m. (PT) Conference Audio Dial-in U.S. and Canada: (877) 451-6152 Dial-in International: (201) 389-0879 Conference ID No.: 13702385 Slide Presentation Go to www.webex.com, click on the ‘Join’ button and enter meeting number 923 145 161 and Password CWBR, or go to www.cohbar.com and click on Q1 2020 Shareholder Presentation at top of homepage

An audio replay of the call will be available beginning at 8:00 p.m. Eastern Time on May 14, 2020 through 11:59 p.m. Eastern Time on June 4, 2020 . To access the recording please dial (844) 512-2921 in the U.S. and Canada, or (412) 317-6671 internationally, and reference Conference ID# 13702385. The audio recording along with the slide presentation will also be available at www.cohbar.com during the same period.

CohBar Corporate Presentation

Today’s Agenda

• Financials
• Overview
• Clinical & Preclinical Programs
• New Target: Acute Respiratory Distress Syndrome (ARDS), including COVID-19

Associated ARDS

• 2020: Looking Ahead
• Q&A

4

CohBar Corporate Presentation

NASDAQ: CWBR

Financials

5

CohBar Corporate Presentation

Summary Financials

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Income Statement ($000s) 1Q 2020 1Q 2019 Research & Development $1,450 $1,372 General & Administrative 1,832 1,456 Net Loss (4,218) (2,921) Net Loss Per Share – Basic & Diluted (0.10) (0.07) Balance Sheet ($000s) 03/31/20 12/31/19 Cash & Investments $10,169 $12,564 Stockholders Equity 5,647 8,137 Cash Burn 2.5M 2.2M

CohBar Corporate Presentation

NASDAQ: CWBR

Overview

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CohBar Corporate Presentation

CohBar: Leader in developing therapeutics from mitochondrial DNA

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• Harnessing the power of mitochondria biology: New major role in signaling and regulation of metabolic, immune and
• ther systems. Mitochondrial dysfunction plays an underlying role in certain chronic and age-related diseases.
• Platform technology: Discovery of over 100 peptides encoded in the mitochondrial DNA leading to a library of >1000

novel peptide analogs for potential development into novel therapeutics.

• Clinical: CB4211 in Phase 1b stage of Phase 1a/1b trial for NASH and obesity, currently paused due to COVID-19.

Improvement in NAS score, liver fat and triglyceride levels and body weight reduction shown in preclinical models. ü Preclinical: Peptides effective in a wide range of models: Tumor growth reduction by inhibition of key chemokine receptor CXCR4, antifibrotic effects in IPF , enhanced killing of cancer cells by human immune cells in vitro, targeting COVID-19 ARDS.

• IP: 65+ CohBar patent filings, 8 issued patents licensed from UCLA/Albert Einstein/Mayo Clinic.
• Experienced team: Successful track record of drug discovery, development and partnerships.
• Financial: $10.2M 1Q 2020, runway expected into 2Q 2021.

CohBar Corporate Presentation

Mitochondrial Medicine focuses on the broad role of mitochondria and mitochondrial dysfunction in health, aging and disease

Recent research in mitochondrial biology and related diseases supports a much broader role for mitochondria

• Signaling within and between cells
• Orchestrating multiple biological systems
• Regulating metabolism, immune system
• Controlling cell cycle, cell growth, cell

death (apoptosis)

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… and broader role for mitochondrial dysfunction

• NAFLD/NASH, obesity, T2D
• Cancer
• Immune system and inflammatory disorders
• Fibrotic diseases
• Cardiovascular and neurodegenerative diseases
• Other age-related diseases

CohBar Corporate Presentation Mitochondrial Genome Mitochondrial Encoded Peptides CohBar peptides

CohBar’s mitochondrial peptides have demonstrated the potential to address a wide range of therapeutic needs

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• CohBar research and development support the broad role of

mitochondria and mitochondrial dysfunction

• Earlier peptide research focused on metabolic diseases,

inflammation and cancer

• CB4211 clinical candidate peptide for NASH and obesity,

both metabolic disorders with inflammation

• New CohBar peptides target diverse diseases, cancer,

fibrosis, ARDS, T2D

• All from natural peptides originating from mitochondrial

DNA CohBar is a first mover and leader in mitochondrial medicine

CohBar Corporate Presentation

We have made substantial progress recently

• Five Programs: Since last May, we have expanded the number of programs from two

to five with the newest targeting COVID-19.

• New COVID Associated Acute Respiratory Distress Syndrome (ARDS) Target for

CB5064 Analogs: Recently, we announced the expansion of the potential indications for

• ur apelin agonist peptides by initiating preclinical testing in a model of Acute

Respiratory Distress Syndrome (ARDS), to assess their potential as therapeutics for COVID-19 associated ARDS.

• New CXCR4 inhibitor program for cancer and other indications: In January, we

announced the discovery of a novel family of CXCR4 inhibitors and shared data for one that significantly reduced tumor size in a difficult to treat preclinical melanoma model.

• New antifibrotic results: In December, we announced positive results in a therapeutic

model of idiopathic pulmonary fibrosis. This further expands on our earlier prophylactic results.

• Expanded therapeutic breadth and potential

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CohBar Corporate Presentation

NASDAQ: CWBR

Clinical & Preclinical Programs

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CohBar Corporate Presentation

CB4211: Lead candidate in Phase 1a/1b trial for NASH and obesity

Phase 1a stage completed: No significant safety/tolerability issues observed since restarting

• Phase 1a design: SAD/MAD safety, tolerability and

PK in healthy subjects

• First mitochondria based therapeutic (MBT) in humans

Phase 1b stage: Currently paused due to COVID-191

• Phase 1b design: Measuring changes in liver fat, body

weight, and biomarkers in 20 obese NAFLD subjects, 10 active/10 placebo, 4-week exposure

• Three new clinical sites added to facilitate enrollment

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Preclinical evidence of efficacy in animal models of NASH and obesity

• NASH: reduced NAFLD Activity Score;

Obesity: reduced body weight/fat mass, liver fat

• Novel mechanism of action: Enhances

insulin effects on fat cells (adipocytes) leading to reduction of liver fat

• Synergistic effects with other

mechanisms used in diabetes and

• besity: GLP-1 and PPARy agonists,

potential for combination with other NASH or diabetes drug

(1) CohBar is experiencing a delay in the completion of its CB4211 Phase 1b study for NASH and obesity. This delay is a result of a pause by some of the company’s clinical research

• rganization partners in all of their activities related to the study in response to the COVID-19

pandemic and the advice of the CDC and local authorities. Given the uncertainties around this unprecedented pandemic and its impact on the Phase 1b clinical study activities, including enrollment of subjects, the company is unable to provide additional guidance at this time.

CohBar Corporate Presentation

Preclinical: Multiple new peptides with wide range of effects in models of cancer, fibrotic diseases and type 2 diabetes

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Evaluation and prioritization of these preclinical programs are ongoing, with the goal of identifying a clinical drug candidate by year end MBT5 analogs

CXCR4 antagonists for cancer &

• ther indications

CB5064 analogs

Apelin receptor agonists for type 2 diabetes & ARDS, including COVID-19 Associated ARDS

MBT3 analogs

Peptides for cancer immunotherapy

MBT2 analogs

Peptides for fibrotic diseases

CohBar Corporate Presentation

NASDAQ: CWBR

New Target:

Acute Respiratory Distress Syndrome (ARDS), including COVID-19 Associated ARDS

CohBar Corporate Presentation

Acute Respiratory Distress Syndrome (ARDS)

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ARDS: Damage to lining of lung leads to fluid accumulation in air sacs preventing absorption of oxygen

Air sac (Alveolus) Accumulation of fluid and blood cells

B l

• d

V e s s e l

Interstitial Space Damaged Cells

• Triggered by lung injury such as viral or bacterial

pneumonia, sepsis, trauma, chemical inhalation, etc.

• Presents as sudden shortness of breath, rapid breathing,

rapid heart rate, confusion, and extreme tiredness

• Major cause of morbidity and mortality
• Prolongs hospital stays and requires convalescence in the

hospital and rehabilitation

• Treated with mechanical ventilation and supportive care

for infection, inflammation, pain, anxiety, etc.

• Unmet need for a safe and effective treatment to reduce

time on ventilators, reduce mortality, and improve quality

• f life
• Affects approximately three million patients globally

CohBar Corporate Presentation

COVID-19 associated ARDS can lead to respiratory distress, low Blood

• xygen, cytokine storm and multi-organ damage

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CB5064

Low Blood Oxygen Multi-organ Failure Cardiac Failure

Heart Kidneys Liver Brain

Inflammation Cytokine Storm Vascular Leakage Pneumonia Fluid Accumulation

COVID-19

• Lungs

CohBar Corporate Presentation

Metabolic comorbidities like type 2 diabetes significantly increase risk of death from COVID-19

• 7,336 COVID-19 patients with or without

diabetes studied retrospectively

• Presence of type 2 diabetes (T2DM)

increased the need for medical interventions during COVID-19

• Diabetes status increased the mortality

risk of patients with COVID-19: 7.8% with T2DM versus 2.7% without this comorbidity

• In diabetics, well-controlled blood glucose

correlated with improved COVID-19 survival (figure)

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Source: Zhu L et al. Cell Metabolism 2020 May 1 [epub ahead of print]

CohBar Corporate Presentation

Stimulation of the apelin receptor leads to activation of many different pathways regulating cellular processes

Source: O'Carroll AM et al.J Endocrinol. 2013 Sep 11;219(1):R13-35

Apelin: endogenous peptide with broad protective effects in animal models of ARDS

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• Natural adipokine - peptide secreted from fat cells
• Activates the apelin receptor (APJ) broadly expressed

and abundant in lung, heart

• Multiple signaling pathways: Ras, AMPK, ERK, mTOR

eNOS

• Reduces pulmonary edema and acute lung damage

caused by chemical or bacterial toxin in animal models of ARDS

• Decreases pro-inflammatory cytokine levels in animal

models of ARDS

• Protects other organs from LPS induced damage
• Decreases body weight and fat levels in obese mice
• In vivo half-life (8 min) too short for effective clinical use

CohBar Corporate Presentation

CohBar’s CB5064 Analogs: Novel apelin agonist peptides

• Family of novel peptide analogs based on a natural human mitochondrial peptide
• Confirmed agonist effects at the APJ receptor in preclinical models
• Stimulation of beta-arrestin recruitment in APJ-transfected cells
• Dose-dependent reduction of cAMP production in cells expressing high levels of

APJ

• Metabolic stability demonstrated in human plasma in vitro
• No safety issues observed in multiple 10 to 14-day rodent efficacy studies
• Improved glucose tolerance demonstrated in diet induced obese (DIO) mice
• Reduced body weight and fat mass observed in obese mice
• Anticipated to have similar effects to apelin on acute lung injury

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CohBar Corporate Presentation

Potential benefits of CB5064 analogs in COVID-19 associated ARDS

• COVID-19 can damage lungs and other organs

by multiple pathways

• Local inflammation leads to vascular leakage

and fluid accumulation in the lung

• Fluid accumulation leads to low oxygen levels

in the blood and puts pressure on the heart

• Stimulation of the cytokine storm and low

blood oxygen together induce further damage in multiple organs, often resulting in death

21

Pneumonia Vascular Leakage Fluid Accumulation Inflammation Cytokine Storm Low Blood Oxygen Multi-organ Failure

COVID-19

• Cardiac

Failure

Apelin Receptor

CohBar Corporate Presentation

Potential benefits of CB5064 analogs in COVID-19 associated ARDS

• CB5064 analogs are novel apelin receptor

agonists that could potentially block the damaging effects of COVID-19 associated ARDS

• Reduced lung damage and fluid accumulation

could improve oxygen absorption and decrease the need for ventilation

• Blocking the cytokine storm could decrease

damage to other organs, reduce mortality related to multi-organ failure, and reduce long term morbidity

• Potentially applicable to other forms of ARDS

including future infections by novel viral or bacterial strains

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Pneumonia Vascular Leakage Fluid Accumulation Inflammation Cytokine Storm Low Blood Oxygen

COVID-19

• Cardiac

Failure

Apelin Receptor CB5064 Analog

Multi-organ Failure

CohBar Corporate Presentation

Apelin reduces extravascular lung water accumulation, vascular leakage, and inflammation induced by the bacterial toxin LPS in mice

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• Mice injected with saline (Con), LPS, LPS plus apelin-13,
• r apelin-13 alone
• A) Apelin decreases LPS-induced lung pathologies;

decreases inflammatory cell infiltration, decreases alveolar wall thickness, edema, etc.

• B) Apelin reduces LPS-induced pulmonary edema

measured by lung wet/dry ratio

• C) Apelin reduces LPS-induced increase in lung capillary-

alveolar leakage as measured by BALF protein content

• D,E,F) Apelin decreases pro-inflammatory cytokines in

BALF

Source: Zhang et al. Cell Physiol Biochem 2018;49:1918-1932

CohBar Corporate Presentation

Apelin improves metabolic homeostasis and reduces body weight in obese mice

Source: Castan-Laurell I et al Endocrine (2011) 40:1–9

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Increased Insulin Sensitivity Increased Glucose Uptake by Muscle Decreased insulin, triglycerides, free fatty acids Decreased Fat Deposits Decreased Body Weight

Apelin

CohBar Corporate Presentation

CB5064 analogs are selective agonists of apelin receptor (APJ)

Figure 2: Inhibition of cAMP accumulation in CHO-K1 AGTRL1 Gi cells following 30 min incubation with forskolin (10 μM) and Apelin-13 (0.025-167 nM) or CB5064 analogs (0.005-30 μM); data plotted as percent Apelin-13 response. Data are mean (SD) n=2-3 for all data points.

Figure 1: Response of human APJ

• verexpressing cell models to Apelin-13 (500

nM) or CB5064 peptide analogs (10 μM). (A) β- Arrestin recruitment assay. Data are mean (SD) percent of Apelin-13 response.

• 10
• 9
• 8
• 7
• 6
• 5
• 4

25 50 75 100

[M] % Apelin-13 Response

IC50 Apelin-13 CB5064K CB5064AG CB5064AH CB5064EA CB5064EB CB5064MM 1.763e-009 4.492e-006 1.602e-006 2.499e-006 4.382e-006 2.069e-006 1.243e-006 Peptide Apelin-13 CB5064D CB5064K CB5064S CB5064W

25 50 75 100

% Apelin-13 Response

CB5064AF CB5064AG CB5064AH CB5064AJ CB5064BN CB5064EA CB5064EB CB5064MM

Apelin-13 CB5064D CB6064K CB5064AG CB5064AH CB5064EA CB5064EB CB5064MM

Source: Grindstaff K et al. 2019, ADA Poster

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CohBar Corporate Presentation

CB5064 analogs improve metabolic dysfunction in obese mice

Source: Grindstaff K et al. 2019, ADA Poster

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• CB5064 analogs significantly reduced body weight

and fat mass in DIO mice (dosed once daily for 10 days)

• CB5064 analogs significantly lowered blood glucose

excursion following a bolus injection of glucose (glucose tolerance test or GTT) Body Weight/Fat Mass Reduction

• 15
• 10
• 5

Δ Body Weight (%)

** *** ***

FM LM

• 6
• 4
• 2

Δ Body Mass (g) Liraglutide Vehicle CB5064D CB5064MM

* *** *** 30 60 90 120 200 300 400 500 CB5064MM CB5064D CB5064K CB5064AG CB5064AH Vehicle CB5064EA CB5064EB Time (Min) BG (mg/dL)

Improved Glucose Tolerance

V e h i c l e C B 5 6 4 D C B 5 6 4 M M C B 5 6 4 K C B 5 6 4 A G C B 5 6 4 A H C B 5 6 4 E A C B 5 6 4 E B 50 100 150 200 250 300 350

BG (mg/dL) *** *** *** *** *** ***

Lower Blood Glucose Levels at 2 hr After GTT

CohBar Corporate Presentation

Potential benefits of CB5064 analogs in COVID-19 associated ARDS

• COVID-19 can damage lungs and other organs

by multiple pathways

• Local inflammation leads to vascular leakage

and fluid accumulation in the lung

• Fluid accumulation leads to low oxygen levels

in the blood and puts pressure on the heart

• Stimulation of the cytokine storm and low

blood oxygen together induce further damage in multiple organs, often resulting in death

27

Pneumonia Vascular Leakage Fluid Accumulation Inflammation Cytokine Storm Low Blood Oxygen Multi-organ Failure

COVID-19

• Cardiac

Failure

Apelin Receptor

CohBar Corporate Presentation

Potential benefits of CB5064 analogs in COVID-19 associated ARDS

• Apelin signaling protects animals from acute

lung injury, reducing fluid accumulation, vascular leakage and cytokine release

• CB5064 analogs are novel apelin receptor

agonists with similar effects to apelin in animal models of metabolic dysfunction

• CB5064 analogs could potentially block many
• f the damaging effects of COVID-19

associated ARDS

• CB5064 Analogs are potentially applicable to
• ther forms of ARDS, including future

infections by novel viral or bacterial strains

• CB5064 Analogs are now being evaluated in

animal models of ARDS

28

Pneumonia Vascular Leakage Fluid Accumulation Inflammation Cytokine Storm Low Blood Oxygen

COVID-19

• Cardiac

Failure

Apelin Receptor CB5064 Analog

Multi-organ Failure

CohBar Corporate Presentation

CohBar Pipeline

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MBT Programs Potential Indications Preclinical IND Enabling Activities Phase 1a Phase 1b Clinical CB4211 NASH Obesity Preclinical MBT5 Analogs Cancer, Orphan MBT2 Analogs IPF , Fibrotic Diseases MBT3 Analogs Cancer Immunotherapy CB5064 Analogs COVID-19 ARDS, ARDS, T2D

CohBar Corporate Presentation

NASDAQ: CWBR

2020: Looking Ahead

CohBar Corporate Presentation

Goals 2020

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• Clinical: Advance CB4211 through Phase 1b targeting NASH and obesity
• Preclinical programs
• Identify next clinical candidate

ü Continue to progress our preclinical programs ü Initiation of new COVID-19 ARDS target with apelin agonist analogs ü New program MBT5, a CXCR4 inhibitor

• Continue screening CohBar’s peptide library to generate new MBTs
• Financing: As always, we are evaluating multiple options for future fundraisings
• Investor Relations: Increase visibility in the investor community
• Partnering: Expand partnering activities around CohBar’s portfolio
• Intellectual Property: Expand IP portfolio to maintain leadership in mitochondrial based therapeutics

Magnified mitochondria

CohBar Corporate Presentation

CohBar: Leader in developing therapeutics from mitochondrial DNA

32

ü Harnessing the power of mitochondria biology: New major role in signaling and regulation of metabolic, immune and

• ther systems. Mitochondrial dysfunction plays an underlying role in certain chronic and age-related diseases.

ü Platform technology: Discovery of over 100 peptides encoded in the mitochondrial DNA leading to a library of >1000 novel peptide analogs for potential development into novel therapeutics. ü Clinical: CB4211 in Phase 1b stage of Phase 1a/1b trial for NASH and obesity, currently paused due to COVID-19. Improvement in NAS score, liver fat and triglyceride levels and body weight reduction shown in preclinical models. ü Preclinical: Peptides effective in a wide range of models: Tumor growth reduction by inhibition of key chemokine receptor CXCR4, antifibrotic effects in IPF , enhanced killing of cancer cells by human immune cells in vitro, targeting COVID-19 ARDS. ü IP: 65+ CohBar patent filings, 8 issued patents licensed from UCLA/Albert Einstein/Mayo Clinic. ü Experienced team: Successful track record of drug discovery, development and partnerships. ü Financial: $10.2M 1Q 2020, runway expected into 2Q 2021.

CohBar Corporate Presentation

NASDAQ: CWBR

Q&A

April 2020