Moleculin Biotech, Inc. · NASDAQ:MBRX
Moleculin Biotech — Investor Presentation (October 2019)
46 slides from Moleculin Biotech's investor presentation, Oct 29, 2019
Slide 1: Developing ground-breaking therapies for highly resistant cancers
Exhibit 99.1 Developing ground-breaking therapies for highly resistant cancers October 29, 2019 Public Corporate Presentation (Nasdaq: MBRX)
Slide 2: Disclaimer
Disclaimer All statements contained herein other than statements of historical fact, including statements regarding our future results of operations and financial position, our business strategy and plans, and our objectives for future operations, are forward-looking statements. The words “believe,”
Slide 3: Key Take-aways
Key Take-aways Robust pipeline 3 distinctly different technologies, all with blockbuster potential World-leading collaboration MD Anderson Cancer Center/Mayo Clinic/Emory Breakthrough disruptive technologies Annamycin: Next-Generation anthracycline designed to be non-cardiotoxic, avoids MDR1, organ-
Slide 4: Core Technologies
3 Core Technologies 1 2 3 Next Generation Immune / Transcription Metabolism / Anthracycline Modulators Glycosylation Inhibitor • Avoids multidrug resistance • Enables immune response and • Prodrug of glucose decoy immune memory enables drug-like properties • Little to no cardiotoxicity • Inhibits p-
Slide 5: Focus on Highly Resistant Tumors
Focus on Highly Resistant Tumors Example Common Regulatory Indications Characteristics Advantage • R/R AML • Multidrug resistance • Significant unmet need • Glioblastoma • Immune evasion • Modest gains = new • • Pancreatic Upregulation of oncogenic drug approval transcription factors • Distant metas
Slide 6: Partnerships & Collaborations
Partnerships & Collaborations Our world-leading partnerships & collaborations significantly expand our research capabilities and increase our knowledgebase 6
Slide 7: Development Pipeline
Development Pipeline In Clinic Collaboration Phase 1 Activity Phase 2 R/R AML - Europe Annamycin 2020 Next Generation, R/R AML - US Organ-targeted, Non-cardiotoxic Distant Metastases 2020 anthracycline Immune/Transcription GBM – WP1066* Modulators Ped. Brain Tumors – WP1066* 2019 Inhibit pSTAT3, HIF
Slide 8: Key Developments
Key Developments Moleculin has three drug candidates in four clinical trials. Next Generation Anthracycline – Annamycin (2 Clinical Trials) Immune/Transcription Modulators - (2 Clinical Trials) • Positive interim safety and efficacy data from Annamycin • Emory University to conduct pediatric brain t
Slide 9: Milestones & Accomplishments
Milestones & Accomplishments 9
Slide 10: Technology Review
Technology Review
Slide 11: Annamycin (Next Generation Anthracycline) Critical Advantages
Annamycin (Next Generation Anthracycline) Critical Advantages Leading AML induction therapy drugs are cardiotoxic and lose efficacy due to Annamycin Avoids MDR1 over Current multidrug resistance Anthracyclines Annamycin has little to no cardiotoxicity, is active against multidrug resistant tumors, h
Slide 12: Annamycin Avoids MDR1 Mechanisms
Annamycin Avoids MDR1 Mechanisms Cellular Uptake and Efflux of L-ANN and DOX in HL-60/DOX Cells 10000 L-ANN + VER L-ANN 1000 (L-ANN + VER) + VER (L-ANN + VER) - VER (L-ANN ) + VER DOX + VER (L-ANN ) - VER DOX 100 (DOX + VER) + VER (DOX) + VER (DOX + VER) - VER (DOX) - VER 10 Cells + M Cells + VER So
Slide 13: Annamycin is a More Potent Topoisomerase II Poison
Annamycin is a More Potent Topoisomerase II Poison With a Wider Therapeutic Window than Doxorubicin Induction of DNA-protein cross-links by 4-demethoxy and 4- Topo II lesions and apoptosis induced by annamycin and WP794 in methoxy anthracyclines in CEM leukemic cells with wild-type topo normal cells
Slide 14: L-Annamycin More Potent Than Doxorubicin Against Resistant Tumor Cell Lines
L-Annamycin is Dramatically More Potent Than Doxorubicin Against Multidrug Resistant Tumor Cell Lines 400 18 356 16.3 350 16 296 14 300 263 12 250 10.5 10 200 DOX 8 L- ANN 150 117 6 100 4 Resistance Index 63 50 2 1.5 1.4 4 9 5 3 7 0 0 Squamous Lymphocytic Myeloma Myelocytic Breast Breast Small cell
Slide 15: L-Annamycin is Non-Cardiotoxic in FDA Required Tests
L-Annamycin is Non-Cardiotoxic in FDA Required Tests % of Mice with Heart Lesions 100 100 100 100 90 90 80 80 70 70 60 60 60 50 50 43 40 40 30 25 30 20 20 8 10 10 7 0 0 0 0 0 Control Doxorubicin Free L-Annamycin Doxorubicin L-Annamycin Annamycin Dose 50 50 50 20 30 40 20 30 40 (%LD10) Experiment 1 (
Slide 16: In Vivo Antitumor Activity of Annamycin
In Vivo Antitumor Activity of Annamycin Antitumor Activity Inoculation/ Tumor Treatment Tumor Site End-Point L-ANN DOX L1210 leukemia ip/ip ascitic survival +++ ++ B16 melanoma ip/ip ascitic survival ++ ++ B16 melanoma sc/iv sc TGI ++ + M5076 reticulosarcoma iv/iv liver survival ++ NONE M5076 reticu
Slide 17: Annamycin Delivered in a Previous Clinical Trial
Annamycin Delivered in a Previous Clinical Trial Relapsed/Refractory Acute Leukemia Remarkable In a proof-of-concept Phase I/II clinical trial, Annamycin was Patients Performance given to patients who had failed an average of five previous induction therapy attempts 63% Efficacy 37% of those patient
Slide 18: Annamycin is Delivering Again
Annamycin is Delivering Again • Currently in second cohort in US trial 120 mg/m2 and in third cohort in Poland 180 mg/m2 • Efficacy to date - 1 PR and 1 BTB at 120 mg/m2 • Expect third cohort in Poland results to be released in Q4-2019 • 100% of patients show no signs of cardiotoxicity (together wit
Slide 19: Annamycin – Organ Targeted Strategy
Annamycin – Organ Targeted Strategy • Now have substantial evidence that, in contrast to doxorubicin, there is elevated accumulation of Annamycin in lung, liver, spleen and pancreas • Distant metastases mouse models show remarkable efficacy • We are moving quickly to begin proof of concept clinical
Slide 20: Annamycin in Lungs is Dramatically Higher than in Plasma
Annamycin in Lungs is Dramatically Higher than in Plasma Source: Sponsored research at MD Anderson 20
Slide 21: Comparison of Efficacy in Lewis Lung Carcinoma Model
Comparison of Efficacy of L-Annamycin, F-Annamycin and Doxorubicin in Lewis Lung Carcinoma model V e h ic le 1 0 0 D o x S -A n n a 8 0 l F -A n n a a v i 6 0 L -A n n a v r u S 4 0 Source: Ling YH, Priebe W, Yang LY, Burke TG, % Pommier Y, Perez-Soler R. In vitro cytotoxicity, cellular pharmacology
Slide 22: Single Dose PK and Biodistribution
250 250 250 229.7 229.7 229.7 Single Dose PK and Biodistribution 200 200 200 250 229.7 155.7 155.7 155.7 Annamycin has 6 fold 150 150 200150121.7 127.7 121.7 127.7 greater concentration121.7 127.7 118.6 118.6 118.6 g x h/g or ml) g x h/g g x h/g or ml) g x h/g g x h/g or ml) g x h/g 106.6 100.9 in l
Slide 23: Efficacy of L-Ann in AML – Organ Distribution Study
Efficacy of L-Ann in AML – Organ Distribution Study Experiment description Female B6 albino mice injected with 1 x 10^5 AML1-MLL/ENL-FLT3/ITD-mTurquiose cells at day 1. Treatment was initiated on day 9th with injection of 4 mg/kg of L-Ann. Mouse was sacrificed 3 days after the dose. Animals were per
Slide 24: Efficacy of L-Ann in AML – Organ Distribution Study
Efficacy of L-Ann in AML – Organ Distribution Study Bone marrow Spleen Lungs Liver Lymph node vehicle Anna - L Green = AML cells Conclusion Blue = Second Harmonic Generation (bone collagen) Significant reduction of AML blasts in bone marrow and spleen. Red = Thy1-RFP (strong in neurons and weak in o
Slide 25: Multidose Toxicity of L-Ann
Multidose Toxicity of L-Ann 2 5 3 m g /k g 6 m g /k g 1 0 0 4 m g /k g 8 m g /k g l a Source: Poster at the AACR-NCI-EORTC v Molecular Targets and Cancer Therapeutics i 3 m g /k g Conference, Boston, MA.; entitled “Dose and v r g 2 0 Schedule-Dependent Efficacy of Liposomal , u 4 m g /k g Annamycin
Slide 26: Dose and Schedule Optimization – L-Ann in AML Model
Dose and Schedule Optimization – L-Ann in AML Model V e h ic le V e h ic le 1 0 0 1 0 0 L -A n n a 0 .5 m g /k g 1 -2 -3 L -A n n a 3 m g /k g o n c e a w e e k L -A n n a 4 m g /k g o n c e a w e e k L -A n n a 1 m g /k g 1 -2 -3 l l a a v v i i L -A n n a 2 m g /k g 1 -2 -3 v v r r u u s s t t n n
Slide 27: Annamycin Recap & Status
Annamycin Recap & Status • Annamycin is a “Next Generation” anthracycline designed to be non-cardiotoxic and avoid multidrug resistance • Although impressive activity was shown in prior acute leukemia trials, developer did not properly close out or establish an appropriate RP2D • Moleculin is repeat
Slide 28: WP1066 (Immune / Transcription Modulators)
WP1066 (Immune / Transcription Modulators) Based On Natural Built from chemical backbone of propolis (caffeic acid STAT3 is Activated by Multiple Upstream Compound benzyl ester) Effectors Unique Dual Action First-in-class drug to both directly inhibit tumor signaling (p-STAT3, HIF-1⍺, c-Myc) while a
Slide 29: STAT3 is a Master Regulator of Tumor Progression
STAT3 is a Master Regulator of Tumor Progression Triggering oncogenic transcription activity: • Survival Activated STAT3 • Proliferation Resulting in tumor (p-STAT3) binds to • Inflammation growth and DNA • Invasion metastasis • Metastasis • Angiogenesis • Immunosuppression 29
Slide 30: WP1066 Affects Tumors Directly & Indirectly
WP1066 Affects Tumors Directly & Indirectly WP1066 WP1066 modulates transcription factors resulting in direct tumor cytotoxicity while also Immune Transcription stimulating a natural Modulation Modulation immune response by reducing Regulatory T-cells (Tregs) Tumor 30
Slide 31: WP1066 & WP1220 Recap & Status
WP1066 & WP1220 Recap & Status • WP1066 is a small molecule that inhibits p-STAT3 by accelerating proteasomal degradation (not by blocking phosphorylation) without respect to upstream signaling; WP1220 is an analog of WP1066 formulated for topical delivery; WP1066 also inhibits HIF1-α, c-Myc and Tre
Slide 32: WP1122 (Metabolism/Glycosylation Inhibitor)
WP1122 (Metabolism/Glycosylation Inhibitor) Addicted to Sugar A brain tumor requires as much as 18 to 37 times as much Tumors are hyper-consumers glucose to survive as a healthy brain cell of glucose and can be starved to death without it Starving a Tumor to This eventually led to the theory that, i
Slide 33: WP1122 is Effective In Vivo against Gliomas
WP1122 is Effective In Vivo against Gliomas July 2017 WP1122 used alone has the same or greater activity than temozolomide (Temodar®), a current standard of care in patients diagnosed with glioblastoma Control Temodar WP1122 10 • Human brain tumors 8 injected into mice • WP1122 performed as 6 well o
Slide 34: WP1122 Shows In Vivo Activity Against Pancreatic Cancer
WP1122 Shows In Vivo Activity Against Pancreatic Cancer January 2018 34
Slide 35: WP1122 Recap & Status
WP1122 Recap & Status • WP1122 is a prodrug of 2-DG that increases circulation time and ability to cross BBB and provides other drug-like properties • Utilizing Warburg principle, WP1122 converts to 2-DG in highly glycolytic tumor cells causing autophagy due to energy starvation • Evaluating oral ve
Slide 36: Financial Review
Financial Review
Slide 37: Financial Statement Summary
Financial Statement Summary In thousands, except for share and per share data and shares For the 6 Mos For the Year Ended outstanding Ended 06/30/19 12/31/18 (Unaudited) (Unaudited) Statement of Operations Data Revenue - - • ”Capital efficient” Research and development $5,031 $9,728 approach General
Slide 38: Various Sources of Financing
Various Sources of Financing Opportunistic Approach • Approx. $20 million raised YTD • Three analysts have reported on MBRX – Roth, Maxim, & Opco • Overnight and intraday deals • ATM – Opco • Equity Line - Lincoln Park Capital • Successful out-licensing of technology in low priority areas The above
Slide 39: Highly Experienced Leadership
Highly Experienced Leadership
Slide 40: Executive Management Team
Executive Management Team Selected Prior Experience Walter Klemp, Chairman, President & CEO Don Picker, PhD Chief Science Officer Jonathan P. Foster, CPA, CGMA EVP & CFO Robert Shepard, MD, FACP Chief Medical Officer Sandra Silberman, MD & PhD Chief Medical Officer – New Products 40
Slide 41: Science Advisory Board
Science Advisory Board Waldemar Elihu Estey, Priebe, PhD MD John Paul Waymack, Marty MD, SCD Tallman, MD Jorge Cortes, James Abbruzzese, MD MD 41
Slide 42: Board of Directors
Board of Directors Robert E. George - Chair of Audit and Nominating & Governance Committees Mr. George joined our board of directors upon our IPO. He was a partner with the international accounting firm of PricewaterhouseCoopers (PWC) for 27 years until 2010. Mr. George currently serves as Chairman
Slide 43: Partnerships & Collaborations
Partnerships & Collaborations The University of Texas MD Anderson Cancer Center Moleculin actively sponsors ongoing research at The University of Texas MD Anderson Cancer Center. MD Anderson is the largest cancer research center in the world and one of the country’s largest recipients of NIH medical
Slide 44: Partnerships & Collaborations
Partnerships & Collaborations Medical University of Gdansk The Medical University of Gdańsk (MUG) is the largest medical university in northern Poland, located in one of the most beautiful cities in Europe with an old town and beautiful sandy beaches. The MUG educates nearly 6,000 undergraduate and
Slide 45: Key Take-aways
Key Take-aways Robust pipeline 3 distinctly different technologies, all with blockbuster potential World-leading collaboration MD Anderson Cancer Center/Mayo Clinic/Emory Breakthrough disruptive technologies Annamycin: Next-Generation anthracycline designed to be non-cardiotoxic, avoids MDR1, organ-
Slide 46: Developing breakthrough therapies for highly resistant cancers
Developing breakthrough therapies for highly resistant cancers Walter Klemp, CEO / Jonathan Foster, CFO info@moleculin.com (713) 300-5160 (Nasdaq: MBRX)
Moleculin Biotech — Investor Presentation (October 2019) on 6ix