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Mitochondria Based Therapeutics 3Q Investor Presentation November - - PowerPoint PPT Presentation
Mitochondria Based Therapeutics 3Q Investor Presentation November - - PowerPoint PPT Presentation
Mitochondria Based Therapeutics 3Q Investor Presentation November 6, 2019 WWW.COHBAR.COM NASDAQ: CWBR 1 Presentation information Investor Update and Slide Presentation: Date: November 6, 2019 Time: 5:00 p.m. (ET) 2:00 p.m. (PT) Conference
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Presentation information
Investor Update and Slide Presentation: Date: November 6, 2019 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.: 13694507 Slide Presentation Go to www.webex.com, click on the ‘Join’ button and enter meeting number 920 124 970 and Password CWBR, or Go to www.cohbar.com and click on Annual Shareholder Presentation at top of homepage
An audio recording of the call will be available beginning at 8:00 p.m. (ET) on November 6, 2019, through November 27, 2019. To access the recording please dial 1-844-512-2921 in the U.S. and Canada, or 1-412-317-6671 internationally, and reference Conference ID No.
- 13694507. The audio recording along with the slide presentation will also be available at www.cohbar.com during the same period.
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Forward Looking Statements
This presentation includes 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
- f 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 anticipated outcomes of research and clinical trials for our lead candidate, CB4211, or other mitochondria based therapeutic (MBT) candidates; expectations regarding the future market for any drug we may develop; expectations regarding the growth of MBTs as a significant future class of drug products; statements regarding future partnership and collaboration opportunities; statements regarding anticipated therapeutic properties and potential of our MBTs or the properties, potential and effects of newly-discovered mitochondrial-derived peptides; statements regarding our capital resources and future financing plans, including our ability to successfully undertake financing activities; and expectations regarding our ability to effectively protect and expand our intellectual property. 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
- ur 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, including the “Risk Factors” set forth in our Annual Report on Form 10-K, as supplemented by our quarterly reports on Form 10-Q. The forward-looking statements and other information contained in this presentation are made as of the date hereof and CohBar, Inc. 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.
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Income Statement ($000s) 3Q 2019 3Q 2018 Research & Development $1,944 $3,436 General & Administrative 1,284 1,062 Net Loss (3,349) (4,613) Net Loss Per Share – Basic & Diluted (0.08) (0.11) Balance Sheet ($000s) 9/30/19 12/31/18 Cash & Investments $14,420 $22,183 Stockholders Equity 10,978 17,963
Summary Financials
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3Q Business Update
- Overview
- Research and Development
- Mitochondrial Medicine
- Strategic Perspective
- Plan 2019
- Goals 2020
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CohBar: Mitochondria Based Therapeutics designed to treat chronic diseases and to increase healthy lifespan
- Mitochondria: Central role in energy production, signaling and regulation. Mitochondrial dysfunction plays an
underlying role in a number of chronic and age-related diseases in large and orphan patient populations.
- Platform Technology: Evaluation of over 100 peptides encoded in the mitochondrial DNA and their analogs for
potential development into novel therapeutics
- 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 as well as anti-fibrotic effects
- Preclinical Stage: New peptides have wide range of effects in models. Anti-fibrotic effects in IPF, enhanced killing
- f cancer cells by human blood cells in vitro, improved glucose tolerance in Type 2 diabetes
- 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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CohBar: Mitochondria Based Therapeutics designed to treat chronic diseases and to increase healthy lifespan
- Mitochondria: Central role in energy production, signaling and regulation. Mitochondrial dysfunction plays an
underlying role in a number of chronic and age-related diseases in large and orphan patient populations.
- Platform Technology: Evaluation of over 100 peptides encoded in the mitochondrial DNA and their analogs for
potential development into novel therapeutics
- 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 as well as anti-fibrotic effects
- Preclinical Stage: New peptides have wide range of effects in models. Anti-fibrotic effects in IPF, enhanced killing
- f cancer cells by human blood cells in vitro, improved glucose tolerance in Type 2 diabetes
- 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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CB4211 Clinical Program
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CB4211: Lead candidate in Phase 1a/1b trial for NASH and Obesity
- Phase 1a stage completed: No safety issues observed under the amended protocol
- Phase 1a design: SAD/MAD safety, tolerability and PK in healthy subjects
- First mitochondria based therapeutic in humans
- Phase 1b stage patient recruitment ongoing: Activity readout currently anticipated mid-2020
- 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
- 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 obesity: GLP-1 and
PPARy agonists, potential for combination with other NASH or diabetes drugs
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CB4211: Efficacy in Animal Models of NASH and Obesity (Review)
L i r a g l u t i d e C B 4 2 0 9
- 8
- 6
- 4
- 2
L o s s ( g )
L e a n M a s s F a t M a s s
STAM Mice
Vehicle Control Liraglutide CB4209
Fewer Fat Deposits
C I P I P
- 2 0
- 1 5
- 1 0
- 5
C h a n g e i n B W ( % )
* * *
Vehicle CB4209 CB4211
Reduced NAS Score in STAM Mice NAS Score at Day 21 Reduced Body Weight in DIO Mice Body Weight Change at Day 21 Reduced Liver Fat in DIO MIce Fat Mass and Liver Histology at Day 21
1Source: Cundy KC, et al. AASLD Poster, 2017
NAS = steatosis + inflammation + ballooning
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CB4211: Synergy with GLP-1 Agonist in NASH model enhances reduction in body weight and liver fat (Review)
- 5
- 4
- 3
- 2
- 1
Change in Fat Mass at Day 21
Change in Fat Mass (g)
*
C I P
- 1 5
- 1 0
- 5
% C h a n g e i n B W
g
* *
Liraglutide QD IP Vehicle BID SC CB4211A 5 QD SC + Lirag
Liraglutide Liraglutide + CB4211 5 mg/kg QD SC Change in Body Weight at Day 21 Liver Fat Deposits at Day 21 Change in Fat Mass at Day 21
1 Diehl NEJM 2017 2 Cundy KC, et al. AASLD 2017, Washington, DC.
More than 40% of NASH patients have diabetes and greater than 80% are obese(1)
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CB4211: Acts on the Foundational Event in NASH
CB4211 reduces fatty acid (FFA) accumulation in liver - the foundational event in NAFLD- NASH progression
- Insulin normally regulates metabolism in liver,
muscle, and fat cells
- NAFLD: loss of insulin sensitivity in fat cells,
excess lipolysis, release of FFA into blood
- Excess fatty acid taken up by liver leads to fat
deposits (steatosis), inflammation, and fibrosis
- CB4211 enhances signaling via the insulin
receptor and decreases lipolysis in fat cells
- Results in decreased liver fat and NAS score in
mouse models of NASH and obesity Insulin CB4211 TG Fat Cells FFA
Lipolysis
Liver FFA
Lipotoxicity Steatosis Inflammation Fibrosis Blood
X
CB4211: Acts on the Foundational Event in NASH
Source: Grindstaff KG et al. ADA Poster Presentation, June , 2018
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Preclinical Programs
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Preclinical: Multiple new peptides with wide range of effects in models of fibrotic disease, cancer, and type 2 diabetes
Fibrotic Diseases, new peptide analogs
- Decreased biomarkers of fibrosis in cultured human cells
- Decreased fibrosis and inflammation in mouse pulmonary fibrosis model
- Significantly improved lung histopathology (Ashcroft Score)
Cancer, new peptide analogs
- Enhanced killing of cancer cells by human blood cells (PBMCs) in vitro
- Potential utility for immuno-oncology indications alone or in combination
Type 2 Diabetes, CB5064 peptide analogs
- Improved weight loss and glucose tolerance in DIO mouse model
- MOA involves interaction with the apelin receptor, presented at ADA 2019
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Fibrotic Disease: MBT #2 shows anti-fibrotic effect in Idiopathic Pulmonary Fibrosis (IPF) mouse model
- MBT #2 protects mouse lung from
bleomycin-induced fibrosis
- Decreased fibrosis measured by
histopathology (Ashcroft Score) after 21 days
- Decreased inflammation – reduced
lymphocyte count in bronchiolar lavage fluid (BALF)
- Comparable effect size to late stage anti-
fibrotic in the same model (Medicinova)
- Ongoing confirmatory studies in lung
fibrosis and other animal models
- Further optimization of analogs in process
Lung Tissue of Normal Mice (Day 21) Exposed to Bleomycin - Treated with Vehicle Exposed to Bleomycin Treated with New MBT #2 Normal Healthy Lung Tissue Damaged Lung and Fibrous Changes Protection from Fibrosis
V V
Decreased Fibrosis in Lung Tissue
Red arrows – fibrous knots V – blood vessel
1 2 3 4
Ashcroft Score CB5138O Bleomycin Normal Vehicle p<0.05
New MBT #2
Ashcroft Score
CohBar Preliminary Data on File
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CohBar Preliminary Data on File
- Significant reduction in inflammatory cells in
lung based on broncho-alveolar lavage
- Anti-fibrotic effect could result from early
anti-inflammatory effects in this prophylaxis model
- Ongoing study of direct anti-fibrotic effect in
a therapeutic model in BLM induced fibrosis. Peptide will be dosed 7 days after BLM injury to allow inflammatory stage to subside
- Ongoing studies in other models of fibrotic
disease
CONFIDENTIAL
Normal Vehicle CB5138O(X) 10 20 30 40
Percent of Total Cells
NEW MBT #2 Bleomycin p<0.01
% Lymphocytes in BALF
Decreased Inflammatory Cells in Lung
MBT #2: Anti-inflammatory activity in Idiopathic Pulmonary Fibrosis mouse model
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Preliminary Data for MBT #2 Published Data for MN-001 (tipelukast) in the Same Bleomycin-Induced Fibrosis Model at 3 weeks1
MBT #2: Anti-fibrotic activity vs published data
1Source: Matsuda K. ICLAF Meeting, 2017.
- MN-001 (Medicinova):
- In Phase 2 clinical trial for IPF and entering P2 for NASH
- Down-regulates fibrotic genes: LOXL2, Collagen Type 1
and TIMP-1
- MBT #2: Down-regulates expression of fibrotic
proteins: Collagen Type 1, Collagen Type III, and αSMA
1 2 3 4
Ashcroft Score MBT #2 Bleomycin Normal Vehicle p<0.05
2CohBar Preliminary Data on File
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Cancer: MBT#3 and analogs enhance the killing of cancer cells by human blood cells, potential for use in cancer immunotherapy
CohBar Preliminary Data on File
- MBT #3 produced a highly significant
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.
- Co-culture of PBMCs with human cancer cells -
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
- Additional MBTs show activity in this model
- Ongoing studies in animal models
Vehicle Control MBT #3 All Cells Cancer Cells
Representative images – Phenovista Biosciences
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Type 2 Diabetes: CB5064 analogs improve body weight and glucose tolerance in DIO mice and demonstrate selective agonism at the apelin receptor
- CB5064 is a new mitochondrial derived peptide
discovered by CohBar
- CB5064 analogs produced body weight and fat mass
reduction in DIO mice (dosed once daily for 10 days)
- CB5064 analogs improved glucose tolerance in DIO
mice after 10 days of dosing
- MOA - selective interaction with the apelin receptor
- Apelin is a natural hormone widely expressed in
adipose tissue, heart, lung, kidney, liver, brain, etc.
- Apelin plays a key role in energy metabolism,
cardiovascular function, fluid homeostasis, angiogenesis, and in diabetic complications
Source: Grindstaff KG et al. ADA Poster Presentation LB-296, June 9, 2019.
Body Weight/Fat Mass Reduction Improved Glucose Tolerance
- 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
Time (Min) BG (mg/dL)
A p e l i n
- 1
3 C B 5 6 4 D C B 5 6 4 K C B 5 6 4 S C B 5 6 4 W C B 5 6 4 Y C B 5 6 4 A B C B 5 6 4 A D C B 5 6 4 A E C B 5 6 4 A F C B 5 6 4 A G C B 5 6 4 A H C B 5 6 4 A J C B 5 6 4 A L C B 5 6 4 A P C B 5 6 4 B C C B 5 6 4 B G C B 5 6 4 B L C B 5 6 5 B M C B 5 6 4 B N C B 5 6 4 E A C B 5 6 4 E B C B 5 6 4 M M
25 50 75
% Apelin-13 Response
Response at Apelin Receptor
CB5064MM CB5064D CB5064K CB5064AG CB5064AH Vehicle CB5064EA CB5064EB
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CohBar Pipeline
CohBar’s Expanding Pipeline
Target Indication Preclinical IND Enabling Activities Phase 1a Phase 1b CB4211 NASH Obesity New Peptides Fibrotic Diseases Cancer Type 2 Diabetes Other Diseases
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Mitochondrial Medicine: Increasing results and recognition
Other Companies: Mitochondria targeted, focused on defects in mitochondrial DNA
- Positive clinical results: Reata Pharmaceuticals’ Phase 2 success in targeting
mitochondrial dysfunction in Friedreich’s Ataxia, a degenerative neuromuscular disorder. $6.4B current market capitalization.
- Partnering
2019: Alexion partners with Stealth Biotherapeutics to co-develop and commercialize late- stage therapy for mitochondrial diseases 2019: Reata exercises repurchase rights for Nrf2 and pays AbbVie $330M. Partnership signed in 2009 for $850M. 2018: Astellas purchases MitoBridge, $225M upfront + $225M milestones
- Healthcare fund investments: MPM, Longwood Founder’s Fund, Deerfield, Novo Holdings,
CMOG and others CohBar: Mitochondria Based Therapeutics affecting signaling and regulation
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Strategic perspective
- Major diseases with metabolic impairment including CVD, diabetes, obesity, NASH, cancer
and Alzheimer’s are driving medical, financial and social costs, and reducing healthspan and longevity.
- Mitochondria are critical to metabolic health and mitochondrial dysfunction is a likely cause
- f these diseases.
- Academic research and pharmaceutical interest in mitochondrial medicine is increasing.
Investor awareness is also growing.
- Breakthrough discoveries by CohBar’s world-renowned founders and scientists over the
past two decades have revealed mitochondrial encoded peptides regulating major systems in the body.
- We believe CohBar’s translation of these discoveries into Mitochondria Based Therapeutics
will provide novel treatments for chronic and age-related diseases.
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Plan 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 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 Evaluate funding alternatives
- Advance preclinical studies in fibrotic diseases and cancer
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Goals 2020
- Clinical: Advance CB4211 through Phase 1b with a data readout anticipated in
mid-2020
- Preclinical Peptides: Identify our next clinical candidate
- Financing: Maintain financial runway and ability to invest in our clinical program and
preclinical programs
- Investor Relations: Broaden our institutional investor base and secure research
coverage
- Partnering: Expand partnering activities around CohBar’s technology
- Intellectual Property: Expand our IP portfolio to maintain our leadership in
mitochondrial based therapeutics
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CohBar: Mitochondria Based Therapeutics designed to treat chronic diseases and to increase healthy lifespan
- Mitochondria: Central role in energy production, signaling and regulation. Mitochondrial dysfunction plays an
underlying role in a number of chronic and age-related diseases in large and orphan patient populations.
- Platform Technology: Evaluation of over 100 peptides encoded in the mitochondrial DNA and their analogs for
potential development into novel therapeutics
- 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 as well as anti-fibrotic effects
- Preclinical Stage: New peptides have wide range of effects in models. Antifibrotic effects in IPF, enhanced killing
- f cancer cells by human blood cells in vitro, improved glucose tolerance in Type 2 diabetes
- 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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