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Mitochondria Based Therapeutics
January 2020
WWW.COHBAR.COM
NASDAQ: CWBR
1
Forward Looking Statements
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 including but not limited to statements regarding the ability of mitochondrial peptide analogs to reduce
tumor growth in mice; anticipated outcomes of research and clinical trials for our mitochondria based therapeutic (MBT) candidates;
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. 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; our ability to recruit and retain key
management and scientific personnel; 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.
2
CohBar: Mitochondria Based Therapeutics designed to treat chronic
diseases and to increase healthy lifespan
• Mitochondria: Central role in energy production, signaling and regulation of metabolism and the immune system.
Mitochondrial dysfunction plays an underlying role in a certain chronic and age-related diseases in large and
orphan patient populations.
• Platform Technology: Discovery and evaluation of over 100 peptides encoded in the mitochondrial DNA and
their analogs for potential development into novel therapeutics. Based on over a decade of research and over
$30M in funding by the NIH and other organizations.
• Clinical Stage: CB4211 in Phase 1a/1b trial for NASH and obesity. Phase 1a complete. Improvement in NAS
score, liver fat and triglyceride levels and body weight reduction shown in preclinical models.
• Preclinical Stage: New peptides have wide range of effects in models - Tumor growth reduction by inhibition of
key chemokine CXCR4, anti-fibrotic effects in IPF, enhanced killing of cancer cells by human blood cells in vitro,
improved glucose tolerance in Type 2 diabetes by Apelin agonism
• Potential Indications: NASH, obesity, cancer, fibrotic diseases and type 2 diabetes
• 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: $14.4M 3Q 2019, runway expected into 4Q 2020
3
Research in chronic and age-related diseases and immunology
increasingly focused on mitochondrial biology (“Mitochondrial Medicine”)
A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and
Cancer: A Dawn for Evolutionary Medicine
“….. Mitochondria are the only human genetic system that embodies the features
necessary to explain the observed characteristics of the common age-relate diseases
…....mitochondrial decline and mtDNA damage are central to the etiology of the age-
related metabolic and degenerative diseases, aging, and cancer.
Douglas C. Wallace, Annual Review Genetics. 2005; 39; 359
Mitochondria as central hub of immune system
“The concept of mitochondria as being more than the powerhouse of immune cells is
relatively new. Recent studies have shown that mitochondrial metabolites and mtROS
are important regulators of signaling pathways and cell fate in both innate and adaptive
immune cells.” Redox Biol 2019 Sept; 26; 101255
4
Mitochondria: Central role in energy production, sensing, signaling,
regulation, health, aging and disease
• Produce energy for the cell - ATP
• Regulate cellular metabolism
• Apoptosis – eliminate old cells
• Calcium storage and signaling
• Heat generation
• Intracellular lipid trafficking
• Regulate signaling transduction
• Cellular differentiation
• Control cell cycle and cell growth
• Hormonal signaling
• Stem cell regulation
• Immune system regulation
5
CohBar harnessing the potential of mitochondrial biology
• Mitochondria have their own genome
• CohBar’s founders and scientists discovered
sequences for peptides in the mitochondrial DNA –
Mitochondrial Derived Peptides (MDPs)
• Certain MDPs have been found in circulation and
within cells, and shown to be regulatory and
signaling agents for metabolic and other processes
• Evolutionary biology: Certain MDPs conserved
across species
• CohBar has discovered, filed IP, and is evaluating
over 100 MDPs and related analogs for potential
therapeutic development
6
Platform Technology: Evaluation of over 100 peptides encoded in the
mitochondrial DNA and their analogs for development into novel therapeutics
Mitochondria Mitochondria Optimized Peptide Mitochondria Based
(Powerhouse of the Cell) Derived Peptide (“MDP”) (“Analog”) Therapeutic (“MBT”)
1 2 3
Identify Optimize Develop and Partner
Identify/characterize peptides Optimize drug like properties Prioritize for internal clinical
with biological activity encoded development and partnership
within mitochondria Proprietary assays,
opportunities
Disease models
File Intellectual Property Advance lead therapeutic
Match analogs with greatest
(“Own the Space”) candidates to the clinic
therapeutic potential to medical
Explore and quantify therapeutic needs and market opportunities
potential across diseases
7
Mitochondria Based Therapeutics: Potential disease targets
• Non-alcoholic steatohepatitis (NASH)
• Obesity
• Cancer
• Fibrotic Diseases
• Pulmonary Disease: Idiopathic Pulmonary Fibrosis
• Kidney Disease: Chronic Kidney Disease, Diabetic Nephropathy
• Cardiovascular Disease: Heart Failure
• Type 2 Diabetes
• Neurodegenerative Diseases: Alzheimer’s Disease
8
Experienced Team: Successful track record of drug discovery,
development and partnerships
Management Prior Experience
20+ years of leadership experience with public biotech companies
Steven Engle
Development of breakthrough products in metabolic, autoimmune,
Chief Executive Officer
oncologic, and infectious disease areas
30+ years of drug discovery and development experience
Kenneth Cundy, PhD. Sterling
Chief Scientific Officer Development of 15 drugs with $100B+ in sales (including Hepsera®,
Tamiflu®, Viread® and Horizant®) Winthrop
Jeffrey Biunno, CPA, MBA 30+ years of financial experience
Chief Financial Officer, Public, small, medium and large-cap companies
Secretary and Treasurer Participated in three sales transactions
Jon Stern, MBA Chief Executive Officer of CohBar from October 2013 to March 2016
Chief Operating Officer, Appointed to CohBar’s Board of Directors in May 2014
Director Experience building companies in diverse industries
9
Accomplishments 2019
ü Completed Phase 1a stage of the Phase 1a/1b clinical trial of CB4211
ü Initiated 1b stage of Phase 1a/1b study of CB4211
ü Advanced new peptides in preclinical studies - CXCR4 inhibitors for cancer, anti-fibrotic peptide for
IPF, peptide analogs for cancer immunotherapy, Apelin agonist for Type 2 diabetes
ü Presented new peptides at American Diabetes Association Conference
ü Appointed new CEO and three Board Directors
ü Presented at the 2019 Cantor Global Healthcare Conference and at the 2019 BIO Investor Forum
ü Expanded outreach to bank analysts and institutional investors
ü Advance preclinical studies in fibrotic diseases and cancer
10Goals 2020
• Clinical: Advance CB4211 through Phase 1b with a data readout anticipated in mid-2020
• Preclinical Peptides: Identify next clinical candidate and continue to advance other
peptides
• Financing: Extend financial runway and ability to invest in clinical program and preclinical
programs
• Investor Relations: Broaden institutional investor base and secure research coverage
• Partnering: Expand partnering activities around CohBar’s technology
• Intellectual Property: Expand IP portfolio to maintain leadership in mitochondrial based
therapeutics
11Financial: $14.4M, 3Q 2019
Expected Runway: 4Q 2020
NASDAQ: CWBR
2017 2018/2019
NASDAQ listed First clinical trial for CB4211
2001 2016 initiated
CB4211 IND prep
First MDP co-discovered CB4211 MOA data presented at
by CohBar founders CB4211 IND MDP evaluation
enabling activities 2018 ADA conference
and optimization
2015 New MDPs ongoing MOA data presented on new
TSXV IPO discovered peptide family targeting type 2
diabetes at 2019 ADA conference
OTCQX listed
2009 CohBar lab
Established
Founded
UCLA lab
established
12CB4211 Clinical Program
13CB4211: Lead candidate in Phase 1a/1b trial for NASH and obesity
• Phase 1a stage completed: No safety issues observed under the amended protocol
o Phase 1a design: SAD/MAD safety, tolerability and PK in healthy subjects
o First mitochondria based therapeutic in humans
• Phase 1b stage patient recruitment ongoing: Activity readout currently anticipated mid-2020
o Phase 1b design: Measuring changes in liver fat, body weight, and biomarkers in 20 obese
NAFLD subjects, 10 active/10 placebo, 4-week exposure
• Preclinical evidence of efficacy in animal models of NASH and obesity
o NASH: reduced NAFLD Activity Score; Obesity: reduced body weight/fat mass, liver fat
o Novel Mechanism of Action: Enhances insulin effects on fat cells (adipocytes) leading to
reduction of liver fat
o Synergistic effects with other mechanisms used in diabetes and obesity: GLP-1 and
PPARy agonists, potential for combination with other NASH or diabetes drug
14CB4211: Efficacy in animal models of NASH and obesity
Reduced NAS Score in STAM Mice Reduced Body Weight in DIO Mice Reduced Liver Fat in DIO MIce
NAS Score at Day 21 Body Weight Change at Day 21 Fat Mass and Liver Histology at Day 21
F at M ass vs. L ean M ass L o ss
0
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-8
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Vehicle CB4209 CB4211 Vehicle Control Liraglutide CB4209
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1Source: Cundy KC, et al. AASLD Poster, 2017
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15CB4211: Synergy with GLP-1 agonist in NASH model enhances reduction
in body weight and liver fat
More than 40% of NASH patients have diabetes and greater than 80% are obese(1)
Change in Body Weight at Day 21 Change in Fat Mass at Day 21 Liver Fat Deposits at Day 21
e c r e a s e i n BDoedcyr eWa s
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2 Cundy KC, et al. AASLD 2017, Washington, DC.
9
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16
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CCB4211: Development program next steps
• Complete ongoing Phase 1a/1b study with readouts for NASH and obesity
• Progress to next clinical study in NASH contingent on positive trends in liver fat, biomarkers
• Considerations for next clinical study
o Optimum dose regimen(s), design and study duration
o Evolving regulatory landscape for primary and secondary endpoints
o Patient population – e.g. fibrosis stage, diabetes and other co-morbidities
o Completion of Phase 2 preparations, including manufacturing, toxicology, etc.
o Additional Phase 1b in a diabetic population on a GLP-1 agonist to evaluate synergy?
• Continue to optimize formulation towards a commercial form
• Evaluate potential for obesity and other alternative indications
17Preclinical Programs
18Preclinical: Multiple new peptides with wide range of effects in models of
cancer, fibrotic diseases and type 2 diabetes
CXCR4 antagonists for cancer and orphan indications
• Highly potent and selective inhibition of CXCR4 (IC50 in low nM range) confirmed in
cell-based assays
• In vivo efficacy demonstrated in an aggressive melanoma immuno-oncology model
New peptides for fibrotic diseases
• Decreased biomarkers of fibrosis in cultured human cells
• Decreased fibrosis and inflammation in mouse model of idiopathic pulmonary fibrosis
• Significantly improved lung histopathology (Ashcroft Score)
Other peptide analogs for cancer immunotherapy
• Enhanced killing of cancer cells by human blood cells (PBMCs) in vitro
• Potential utility for immuno-oncology indications alone or in combination
Apelin receptor agonists for type 2 diabetes
• Improved weight loss and glucose tolerance in DIO mouse model
• MOA involves interaction with the apelin receptor, presented at ADA 2019
19Cancer and Orphan Diseases: CXC Chemokine Receptor Type 4 (CXCR4)
• Key chemokine receptor involved in tumor growth, invasion, angiogenesis,
metastasis, and resistance to therapy
• Also regulates the homing and retention of hematopoietic stem cells and malignant
cells in the bone marrow
• Overexpressed in 75% of human tumors - high levels correlate with aggressive
metastasis and negative prognosis
• Inhibition of CXCR4 mobilizes immune cells, enhances the effects of chemotherapy
and immunotherapy in various cancers, and reduces the development of metastatic
tumors by blocking the ability of tumor cells to evade immune surveillance
• Strategies to block CXCR4 signaling could lead to promising new cancer therapeutics
• Inhibition of CXCR4 also has potential for stem cell mobilization and treatment of
orphan indications where CXCR4 is dysregulated
20MBT5 Analogs: Novel peptide inhibitors of CXCR4, a key regulator of tumor
growth and metastasis
Potent and selective inhibition of CXCR4 demonstrated
• In broad range cell-based assays of receptor interactions, novel peptide analogs of a
mitochondrially encoded peptide (MBT5) showed selective inhibition of one receptor (CXCR4)
with no agonist activity
• Highly potent inhibition of CXCR4 (IC50 in low nM range) was confirmed in cell-based assays
• Potency of some analogs exceeded that of approved drug plerixafor/AMD3100 (IC50 68 nM)
In vivo efficacy demonstrated in B16F10 melanoma immuno-oncology model
• The B16F10 mouse model is a preclinical model of aggressive melanoma that is difficult to treat
• B16F10 tumors are resistant to treatment with the checkpoint inhibitor anti-PD-1 antibody
• MBT5 Analog 1 in combination with temozolomide (TMZ) reduced mean tumor volume by 61%
vs 38% for TMZ alone (PMBT5 Analogs are Potent Antagonists of CXCR4 Receptor
In Vitro Inhibition of CXCR4 Receptor Signaling in a Cell-Based Assay
Plerixafor/AMD3100 MBT5 Analog 1 MBT5 Analog 2
P le r ix a fo r /A M D 3 1 0 0 C B 5046C C B 5046B
125
100 100
P e r c e n t In h ib itio n
P e r c e n t In h ib itio n
P e r c e n t In h ib itio n
100
75 75
75
50 50
50
25 25
25
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C o n c e n t r a t io n ( u M ) C o n c e n t r a t io n ( u M ) C o n c e n t r a t io n ( u M )
IC50 = 68 nM IC50 = 121 nM IC50 = 2.3 nM
Source: CohBar preliminary data on file (Eurofins)
22MBT5: Analog 1 in combination with Temozolomide (TMZ) reduced tumor
volume in B16F10 mouse melanoma model by 61%
Tumor Growth (Mean±SEM, N = 8 to 10) Individual TTumor
u m o r VVolumes
o l u m e D a yat1 Day
1 11
o r V o lu m e B 1 6 F 1 0 T u m o r V o lu m e
PMBT5 Analog 1 in Combination with Temozolomide (TMZ) Reduced
Tumor Growth in B16F10 Syngeneic Mouse Melanoma Model
Individual Tumor Growth Curves over 18 Days
Vehicle
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T u m o r V o lu m e (m m
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G 3 -T M Z
1500 1500
1000 1000
500 500
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2000 6C 2000 4C T M Z
1500 1500
1000 1000
500 500
0 0
0 3 6 9 12 15 18 0 3 6 9 12 15 18
T im e ( d a y s ) T im e ( d a y s )
Source: CohBar preliminary data on file (HD Biosciences)
24Fibrotic Diseases: New peptides effective in preclinical models of lung fibrosis
• Reduces production of biomarkers of fibrosis In cultured human cells
o Decreased collagen Type 1/Type 3 and αSMA in co-cultures of lung cells and fibroblasts
• Inhibits Fibrotic Process - Conversion of Fibroblasts to Myofibroblasts In Vitro
o Reduced transformation of lung fibroblasts to myofibroblasts stimulated by TGF-beta
• Anti-fibrotic and Anti-inflammatory Effects in Prophylactic Mouse Model of IPF
o IPF is a chronic, progressive, debilitating and usually fatal lung disease that affects
approximately 100,000 people in the U.S.
o Prophylaxis: immediate treatment after induction of fibrosis with bleomycin
o Decreases Ashcroft fibrosis score and lymphocytes in lung fluid after 21 days
• Anti-fibrotic and Anti-inflammatory Effects Confirmed in Therapeutic Mouse Model of IPF
o Delayed treatment – peptide dosing begins 7 days after fibrosis is established
o Positive effects on all study outcomes (fibrosis, inflammation, collagen deposition, etc.)
• Potential for Activity in Other Fibrotic Diseases
o Evaluation of this new peptide family is ongoing in additional fibrotic disease models, with the
goal of identifying an optimized drug candidate
25MBT#2: Reduced fibrosis and inflammation in prophylactic IPF mouse model
Lymphocytes in BALF
Decreased Fibrosis
Effect of CB5138O on Lung Fibrosis
Decreased Inflammation
4 pMDP#2: Effects confirmed in therapeutic IPF mouse model
• MBT #2 showed positive effects on all study
Lung Lung
Normalized Weight
Weight Leukocytes in Count
BALF Leukocyte BALF outcomes when dosed 7 days after bleomycin
300000
2.5
• Stabilized body weight loss and prevented the
Normalized Lung Wt
Leukocyte Count
2.0
* ** 200000
1.5
*
increase in lung weight caused by fibrosis
1.0 100000
0.5 • Reduced inflammation – lower leukocyte count
0.0
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of Ashcroft Score • Effects similar to nintedanib (approved drug)
0.20 5
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B o d y W e ig h t
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Bleomycin Bleomycin T im e (d a y s ) CohBar Preliminary Data on File
27Cancer: MBT#3 and analogs enhance the killing of cancer cells by human
blood cells, potential for use in cancer immunotherapy
All • MBT #3 produced a highly significant
Cancer
Cells Cells reduction in the number of cancer cells in the
presence of peripheral blood mononuclear
cells (PBMCs), including T-cells, B-cells and
NK-cells, etc. No effect seen without PBMCs.
Vehicle • Co-culture of PBMCs with human cancer cells -
Control
SKMEL28 melanoma cells, stimulated with
LPS to induce immune response.
• Cells treated with peptide or vehicle control for
48 hours and cells quantified by selective
staining and image analysis
MBT #3
• Additional MBTs show activity in this model
• Ongoing studies in animal models
Representative images – Phenovista Biosciences CohBar Preliminary Data on File
28Type 2 Diabetes: CB5064 analogs improve body weight and glucose tolerance
in DIO mice and demonstrate selective agonism at the apelin receptor
Body Weight/Fat Mass Reduction
FM LM • CB5064 is a new mitochondrial derived peptide
0 0
discovered by CohBar
Δ Body Weight (%)
Δ Body Mass (g)
-5 -2 • CB5064 analogs produced body weight and fat mass
** *
Vehicle reduction in DIO mice (dosed once daily for 10 days)
Liraglutide
-10 -4 CB5064D
***
CB5064MM • CB5064 analogs improved glucose tolerance in DIO
-15
***
-6 ***
***
mice after 10 days of dosing
• MOA - selective interaction with the apelin receptor
Improved Glucose Response at Apelin
Tolerance Receptor • Apelin is a natural hormone widely expressed in
Response
100
500 Vehicle
CB5064D
adipose tissue, heart, lung, kidney, liver, brain, etc.
75
BG (mg/dL)
400 CB5064MM
CB5064K
500
300 CB5064AG
CB5064AH Vehicle • Apelin plays a key role in energy metabolism,
Apelin-13
200
CB5064EA
50 CB5064D
cardiovascular function, fluid homeostasis,
BG (mg/dL)
CB5064EB
400
0 30 60 90 120
CB5064MM
Time (Min) CB5064K
300 25 CB5064AG
CB5064AH angiogenesis, and in diabetic complications
CB5064EA
%
200
0 CB5064EB
0 30 60 90 120
13
4D
4K
4S
4W
4Y
4AB
4AD
4AE
4AF
4AG
4AH
4AJ
4AL
4AP
4BC
4BG
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5BM
4BN
4 EA
506 B
4MM
4B
4E
lin-
Source: Grindstaff KG et al. ADA Poster Presentation LB-296, June 9, 2019.
506
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Time (Min)
506
506
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CB
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29New Peptide Discovery Programs: Next steps
• CXCR4 Antagonist Peptides
o Evaluate efficacy in animal models of hematological and metastatic cancer
o Evaluate efficacy in stem cell mobilization and animal models of CXCR4 dysregulation
o Continue to optimize peptide structure towards a clinical candidate
• Novel Peptides for Fibrotic Diseases
o Extend evaluation to additional models (e.g., scleroderma, kidney or cardiac fibrosis, etc.)
o Continue to optimize peptide structure towards a clinical candidate
• Novel Peptides for Cancer Immunotherapy
o Evaluate in additional immuno-oncology models in combination with I/O therapies
o Continue to optimize peptide structure towards a clinical candidate
• Apelin agonists for T2DM and metabolic disease
o Continue optimization/evaluation in additional models
30CohBar Pipeline
IND Enabling
Target Indication Preclinical Phase 1a Phase 1b
Activities
CB4211
NASH
Obesity
CohBar’s Expanding Pipeline
New Peptides
Cancer
Fibrotic Diseases
Type 2 Diabetes
Other Diseases
31CohBar: Mitochondria Based Therapeutics designed to treat chronic
diseases and to increase healthy lifespan
• Mitochondria: Central role in energy production, signaling and regulation of metabolism and the immune system.
Mitochondrial dysfunction plays an underlying role in a number of chronic and age-related diseases in large and
orphan patient populations.
• Platform Technology: Breakthrough discovery and evaluation of over 100 peptides encoded in the mitochondrial
DNA and their analogs for potential development into novel therapeutics. Based on over a decade of research and
over $30M in funding by the NIH and other organizations.
• Clinical Stage: CB4211 in Phase 1a/1b trial for NASH and obesity. Phase 1a complete. Improvement in NAS
score, liver fat and triglyceride levels, body weight reduction and anti-fibrotic effects shown in preclinical models.
• Preclinical Stage: New peptides have wide range of effects in models - Tumor growth reduction by inhibition of
key chemokine CXCR4, anti-fibrotic effects in IPF, enhanced killing of cancer cells by human blood cells in vitro,
improved glucose tolerance in Type 2 diabetes by Apelin agonism.
• Potential Indications: NASH, obesity, cancer, fibrotic diseases and type 2 diabetes
• 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: $14.4M 3Q 2019, runway expected into 4Q 2020
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