Moleculin Biotech, Inc. · NASDAQ:MBRX
Moleculin Biotech — Investor Presentation (March 2020)
58 slides from Moleculin Biotech's investor presentation, Mar 16, 2020
Slide 1: Developing ground-breaking therapies for highly resistant cancers
Developing ground-breaking therapies for highly resistant cancers March 12, 2020 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: Investment Highlights
Investment Highlights Potential Blockbuster Technologies 3 Phase 1 clinical trials 5 Drugs showing early activity 2 2020 Phase 2 trials expected 2 World class collaboration Highly experienced team Exclusive IP/Fast Track 3
Slide 4: Three Core Technologies
Three 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 • Inhibit
Slide 5: Partnerships & Collaborations
Partnerships & Collaborations Our world-leading partnerships & collaborations significantly expand our research capabilities and increase our knowledgebase 5
Slide 6: Delivering Milestones by Year
Delivering Milestones by Year 2016 2017 2018 2019 2020 Projected First Human Data Est. 7 Trials: IND’s filed Begin 4 clinical Annamycin IPO - & 2 Phase 2 & & Approved trials Misfire 5 clinical trials 4+ Phase 1 Trials • Annamycin – Apply for • Annamycin – • Annamycin – • Annamycin – • Annamycin – OD
Slide 7: Potential 2020 Value Inflection Points
Potential 2020 Value Inflection Points 2020 2021 1H 2H 1H 2H Annamycin Complete AML Phase 1 & Meet Safety Endpoints – US Done Continue announcing cohort results in AML Phase 1 Europe 210+ mg/m2 Reach RP2D & MTD or treat 300 mg/m2 + in AML Phase 1 Europe Begin AML Phase 2 File IND Lung Mets & Begin L
Slide 8: Development Pipeline – Internally Funded
Development Pipeline – Internally Funded In Clinic Collaboration Phase 1 Activity Phase 2 Annamycin Next Generation, AML (US and EU Phase 1/2) 2021 Organ-targeted, Non-cardiotoxic anthracycline Lung Mets (US Phase 1) 2021 Immune/Transcription Modulators CTCL (WP1220 Topical) 2021 Inhibit pSTAT3, HIF
Slide 9: Development Pipeline – Externally Funded
Development Pipeline – Externally Funded In Clinic Collaboration Phase 1 Activity Phase 2 Annamycin Next Generation, Organ- Lung Sarcoma Mets (EU 2021 targeted, Non-cardiotoxic Phase 1) anthracycline GBM (WP1066 US Phase 1) Immune/Transcription Ped Brain Tumors (WP1066 Modulators 2020 Inhibit pSTAT3
Slide 10: Annamycin Status
Annamycin Status Safe and effective in R/R AML patients1 Shows activity in untreatable lung models5 Met primary endpoint in Phase 1 Trial Lower toxicity enables longer-term use • Preparing for Single Phase 2 Trial for accelerated Overall survival significantly increased in triple approval negative b
Slide 11: Annamycin – Quick Facts
Preclinical studies Annamycin – Quick Facts show potential beyond AML Prior leukemia trials 2 Two prior developers in ‘00 & ‘05 AML & ALL Prior MTD mg/m2 150 - 280 CR’s at or above MTD Prior clearing of bone marrow % 37% - 43% Total patients in these and Prior and current cardiotoxicity 0% breast ca
Slide 12: Current Trial Versus Two Previous Trials
12 Current Trial Versus Two Previous Trials Annamycin Trial (Date) Aronex (2000) Callisto8 (2005) Current (to Date1) Indications AML(17), ALL(3) ALL AML Trial design Phase 1 Phase 1/2 Phase 1/2 • Trials are not Dosage per day for MTD 190 - 230 350 190 100 - 180 TBD 3 days (mg/m2) 5,6 280 150 TBD dir
Slide 13: Key Developments
Key Developments 3 drug candidates in 5 clinical trials Next Generation Anthracycline – Annamycin (2 Clinical Trials) Immune/Transcription Modulators - (3 Clinical Trials) • Positive interim safety and efficacy data in US and Europe • Emory University FDA approved to conduct Phase 1 AML Trials pedia
Slide 14: Visible Approval Opportunities
Visible Approval Opportunities Based on results to date: If we replicate current results in larger registration trials, we believe we have 2 approvable drugs now, with more to come These would represent 2 “world’s firsts”: 1. Non-cardiotoxic anthracycline 2. STAT3 inhibitor with therapeutic effect i
Slide 15: Financial Review
Financial Review 15
Slide 16: Financial Statement Summary
Financial Statement Summary In thousands, except for share and per share data and shares For the 9 Mos For the Year Ended outstanding Ended 09/30/19 12/31/18 (Unaudited) (Unaudited) Statement of Operations Data Revenue - - • ”Capital efficient” Research and development $7,816 $9,728 approach General
Slide 17: Various Sources of Financing
Various Sources of Financing Opportunistic Approach • Approx. $20 million raised 2019; $6 million YTD 2020 • 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 pri
Slide 18: Technology Review
Technology Review 18
Slide 19: 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 20: 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 Little to no cardiotoxicity Active against multidrug resistant tumors Shown to be more pot
Slide 21: Anthracycline Cardiotoxicity is a Big Deal
Anthracycline Cardiotoxicity is a Big Deal 65% of patients who receive the equivalent Anthracycline chemotherapy regimens play a of 550 mg/m2 of doxorubicin (a current prominent role in many cancer treatments – standard of care anthracycline) exhibit sub- e.g. 32% of breast cancer patients, 57 to cl
Slide 22: Annamycin has the Answer
Annamycin has the Answer Annamycin was designed from the ground The gold standard preclinical Bertozolli up to be non-cardiotoxic. model for measuring cardiotoxicity shows Annamycin is effectively non-cardiotoxic 114 patients in 6 completed clinical trials when compared with doxorubicin. support the
Slide 23: 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 24: Annamycin – More Potent Topoisomerase II Poison
Annamycin -More Potent Topoisomerase II Poison, 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. A, topo
Slide 25: L-Annamycin More Potent Than Doxorubicin Against Resistant 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 26: 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 27: 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 28: Annamycin Delivered in Previous Clinical Trials
Annamycin Delivered in Previous Clinical Trials Remarkable 2 Acute Leukemia trials have Aronex Trial Callisto Trial Performance shown Annamycin to have (R/R AML/ALL) (R/R ALL) remarkable activity 63% 50% Slight differences in Efficacy Efficacy formulation resulted in Signal Signal substantial differ
Slide 29: Annamycin is Delivering Again
Annamycin is Delivering Again • Currently in second cohort in US trial 120 mg/m2 and in fourth cohort in Poland 210 mg/m2 • Efficacy to date - 1 Cri, 2 PR and 1 BTB - 40% in patients treated at/or above 120 mg/m2 (3 patients were refractory) • No evidence of cardiotoxicity (together with previous tr
Slide 30: Annamycin – Organ Targeted Strategy
Annamycin – Organ Targeted Strategy • We 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 clinic
Slide 31: Annamycin in Lungs Higher than in Plasma
Annamycin in Lungs is Dramatically Higher than in Plasma Source: Sponsored research at MD Anderson 31
Slide 32: 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 33: 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 34: 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 35: 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 36: 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 37: 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 38: Annamycin Shows Activity against TNBC Lung Mets
Annamycin Shows Activity against TNBC Lung Mets Source: Poster at the San Antonio Breast Cancer Symposium® December 10-14, 2019, San Antonio, TX.; entitled “Liposomal Annamycin Inhibition of Lung Localized Breast Cancer,” December 2019 38
Slide 39: Annamycin Also Shows Activity against Colon Cancer Lung Mets
Annamycin Also Shows Activity against Colon Cancer Lung Mets Source: Poster at the San Antonio Breast Cancer Symposium® December 10-14, 2019, San Antonio, TX.; entitled “Liposomal Annamycin Inhibition of Lung Localized Breast Cancer,” December 2019 39
Slide 40: Both Models Translate into Substantial Increase in OS
Both Models Translate into Substantial Increase in OS TNBC Lung Mets Colon Cancer Lung Mets Source: Poster at the San Antonio Breast Cancer Symposium® December 10-14, 2019, San Antonio, TX.; entitled “Liposomal Annamycin Inhibition of Lung Localized Breast Cancer,” December 2019 40
Slide 41: Annamycin Recap & Status
Annamycin Recap & Status • “Next Generation” anthracycline designed to be non-cardiotoxic and avoid multidrug resistance • Six-fold greater concentration in lungs vs. doxorubicin • Although impressive activity was shown in prior acute leukemia trials, developer did not properly close out or establis
Slide 42: 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) Stimul
Slide 43: 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 43
Slide 44: WP1066 Affects Tumors Directly & Indirectly
WP1066 Affects Tumors Directly & Indirectly WP1066 Modulates transcription factors resulting in direct tumor cytotoxicity Immune Transcription Also stimulates a natural Modulation Modulation immune response by reducing Regulatory T-cells (Tregs) Tumor 44
Slide 45: WP1066 & WP1220 Recap & Status
WP1066 & WP1220 Recap & Status • 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 • Inhibits HIF1-α, c-Myc and Tregs • Phase 1 trial at
Slide 46: WP1220 Proof of Concept Trial - CTCL
WP1220 Proof of Concept Trial - CTCL • 5 patients enrolled between March and July 2019 with 3 patients currently showing efficacy and final patient data to be updated soon • Demonstrated safety and significant efficacy after at least 3 months of topical treatment in 3 patients with progressive MF •
Slide 47: 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. Glycosylation is of of glucose and can be starved to death importance to viral virulence and immune evasion. 1
Slide 48: 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 49: WP1122 Shows In Vivo Activity Against Pancreatic Cancer
WP1122 Shows In Vivo Activity Against Pancreatic Cancer January 2018 49
Slide 50: WP1122 Recap & Status
WP1122 Recap & Status • 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 versus IV admi
Slide 51: Highly Experienced Leadership
Highly Experienced Leadership 51
Slide 52: 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 52
Slide 53: 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 53
Slide 54: 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 55: 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 56: 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 57: Key Points
Key Points Potential Blockbuster Technologies 3 Noncardiotoxic anthracycline Phase 1 clinical trials 5 STAT3 Inhibitor Drugs showing early activity 2 Inhibitor of glycolysis 2020 Phase 2 trials expected 2 World class collaboration Highly experienced team Exclusive IP/Fast Track 57
Slide 58: Developing breakthrough therapies for highly resistant cancers
Developing breakthrough therapies for highly resistant cancers Walter Klemp, Chairman & CEO / Jonathan Foster, EVP & CFO info@moleculin.com (713) 300-5160 (Nasdaq: MBRX)
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