Forward Looking Statements

Transcription

1 Company Overview

2 Forward Looking Statements Safe Harbor Statement This presentation includes statements that are, or may be deemed, forward-looking statements. In some cases, you can identify forward-looking statements by terminology including anticipates, believes, can, continue, could, estimates, expects, intends, may, plans, potential, predicts, should, will, would or the negative thereof or other variations thereon or other comparable terminology. We operate in a very competitive and rapidly-changing environment and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You are cautioned not to place undue reliance upon such forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. We direct you to our Annual Report on Form 10-K for the year ended December 31, 2017, our subsequent current reports on Form 8-K and our other filings with the Securities and Exchange Commission. Any forward-looking statement included in this presentation speaks only as of the date hereof. Except as required by law, we do not undertake any obligation to update or revise, or to publicly announce any update or revision to, any of the forward-looking statements, whether as a result of new information, future events or any other reason after the date of this presentation. For all forward-looking statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of

3 GT Biopharma is a clinical-stage biotechnology company primarily focused on utilizing its proprietary platforms to develop next-generation, targeted immuno-oncology therapies for hematological malignancies, sarcomas and solid tumors 3

4 Investment Thesis Proprietary technology platforms: Tri- and Tetra-specific Natural Killer Cell Engagers (TriKE) & (TetraKE) and bi-specific Antibody Drug Conjugates (ADC) Collaboration with Dr. Jeffrey Miller, Deputy Director, The Masonic Cancer Center, University of Minnesota, a recognized leader in Natural Killer (NK) cell therapy and IL-15 biology Two clinical programs in progress/planned for most advanced immuno-oncology candidates OXS-3550, novel TriKE for CD33+ hematologic malignancies expect to initiate First-in-Human trial 2H 18 Dose finding and extended efficacy component OXS-1550, novel bi-specific antibody drug conjugate (ADC) for B-cell lymphomas and leukemias Two durable responses seen in Phase 1 dose escalation study Bi-Specific ADC Ad Board, encouraging clinical results from interim review Potential for rapid pipeline progression Targeting three TriKE/TetraKE product candidates to be in the clinic by 2H 19 Exclusive license to broad IP estate covering oncology pipeline with exclusive rights to TriKE and TetraKE platform, Bi-Specific ADC platform as well as a portfolio of CNS product candidates for potential licensing Management Team, Board of Directors and Scientific Advisory Board with track record of success 4

5 Natural Killer Cell Targeting: Potential to be the Next Frontier in Cancer Immunotherapy We are innovating a novel immunotherapy built upon 20+ years of NK and Interleukin research NK Cell Targeting IL-2 IL-2+ Autologous NK cells IL-2 + Allogeneic NK cells rhil-15 + Allogeneic NK cells IL-15 complexes TriKEs & TetraKEs Used to stimulate post- transplant immunity Approved for myeloma and kidney cancer Used to stimulate post transplant immunity Used to treat refractory AML Used to treat refractory AML Post-transplant relapse Potential for hematologic malignancies, sarcomas and solid tumors (1) NK cells are immunotherapeutic targets that we believe can be harnessed without some of the limitations associated with T-cells and/or CAR-T (1) Expect to begin First in Human clinical trial with most advanced TriKE product candidate in 2H

6 Harnessing Natural Killer (NK) Cells to Fight Cancer NK cells are cytotoxic lymphocytes of the innate immune system that have been increasingly recognized in immune surveillance against cancer Analogous to cytotoxic T cells in the adaptive immune response Provide rapid response to both viral infected cells and tumor cells Kill cancer cell by releasing cytotoxic granules TriKEs and TetraKEs designed to make NK cells antigen specific (targeted) yet do not require genetic manipulation 6

7 Proprietary TriKEs and TetraKEs Have Potential Broad Applicability in Oncology Recombinant fusion proteins designed to harness NK cells, stimulate NK cell activity and proliferation, and target a specific tumor antigen TriKEs and TetraKEs may have the potential to: Target a broad range of oncology indications including solid tumors Be dosed in an outpatient setting Be used alone or in combination regimens w/ potential to: Augment checkpoint inhibitors Be used in conjunction with more traditional cancer therapies 7

8 TriKE and TetraKE Technology Platform Highlights Novel, scalable Tri- and Tetra-specific Natural Killer Cell Engagers (TriKEs & TetraKEs) Constructs designed to: Bind to NK cell via CD16 receptor Provide activating cytokine (IL15) to stimulate NK cell activity and proliferation Regardless of NK-cell-inhibitor presence such as killer cell immunoglobulin-like receptor (KIR) ligands Target cancer cells for identification and attack by NK cells Antibody Directed Cell-Mediated Cytotoxicity (ADCC) scfvs targeting CD33, CD133, EpCAM, among others All TriKEs and TetraKEs contain: NK Cell Ligand: CD16 (binding and activation) IL-15 linker NK cell activity & proliferation Tumor Antigen Target(s) 8

9 Bi-specific Antibody Drug Conjugate (ADC) Technology Platform Highlights Next-Generation ADC platform Bi-specific, tumor antigen-directed single-chain fusion proteins catalytic domain Catalytic domain Simultaneously targets two antigens on select cancer cells Can modify to target numerous tumor antigens Platform amenable to multiple types of payloads Most advanced using diphtheria toxin Truncated DT390 translocation domain 1 st sfv Anti- CD22 (RFB4) 2 nd sfv Anti-CD19 (HD37) De-immunized DT (1) and other payloads available Designed for enhanced efficacy (2) Potential to minimize off-target effects Bi-specific Antibody-Drug Conjugate (ADC) Platform Example: OXS-1550 Targets: CD19 & CD22 Payload: Modified Diphtheria Toxin Status: Phase 2 ongoing - data expected 2H 18 (1) Toxins 2018, 10, 32 (2) Clin Cancer Res 2005;11(10)

10 Targeting Substantial Market Opportunities Our platform technologies have the potential to treat large patient populations and substantial markets CD22+ and CD19+ hematological malignancies ~100,000 B-cell leukemia and lymphoma patients (1) ~30,000 CD33+ myeloid malignancies (AML & MDS) (1) Broad potential solid tumor applicability targeting multiple solid tumor antigens (1) >268,000 new breast cancers >230,000 new lung cancers Our programs have the potential to provide meaningful patient benefit across many different types of cancers >160,000 new prostate cancers >140,000 new colorectal cancers CD133 cancer stem cell marker Designed to target cancer stem cells which are resistant to current therapy (2) (1) American Cancer Society: Cancer Facts and Figures 2018 (2) Exp Hematol Oncol. 2013, 2:17 10

11 Immuno-Oncology Portfolio 11

12 Immuno-Oncology Pipeline Overview Product Candidates Platform Indication Pre Clinical Phase 1 Phase 2 OXS-3550 TriKE Myeloid Malignancies OXS-C3550 TriKE Myeloid Malignancies OXS-1615 / others TriKE/TetraKE Carcinoma & Cancer Stem Cells OXS-1550 Bispecific ADC B-cell Leukemias & Lymphomas 12

13 BiKEs versus BiTEs: Different Immune Cell Engagement BiTE-Mediated Killing BiKE-Mediated Killing T Cell CD3 NK Cell CD16 Tumor Cell Tumor Cell Blinatumomab (Amgen) CD3 x CD19 BiKE s engage NK cells via CD16 binding 13

14 TriKE Construct Started with Bispecific Killer Cell Engager (BiKE) Schematic Representation of BiKE Engaging an NK Cell and Targeting a CD33+ AML Tumor Cell BiKE-Mediated Killing Anti-CD16 Antibody CD16xCD33 BiKE NK Cell CD16 Cytotoxic Lysis AML Tumor Cell CD33 Immune Synapse Anti-CD33 Antibody 14

15 BiKE to TriKE Technology Platform Advancement and Illustrative Comparison with CAR-T TriKE IL-15 linker designed to induce NK cell activity and proliferation CAR-T utilizes 41BB-L or CD28 intracellular domain to induce proliferation TriKEs effectively make NK cells tumor antigen specific without genetic manipulation while IL-15 induces potent NK cell activation and proliferation (1) (1) Clin Cancer Res Jul 15;22(14):

16 BiKE to TriKE AML Mouse Model Has Generated Compelling Data(1) Day 14 Day$14$Image! $$$$$M5$ M1$$$$$$$$$M2 $$$$$M3$ $$$$$$M4 $$$$$$$$M5$ HL-60 -luc + HL-60-luc NK + NK + BiKE 1633 M6$$$$$$$$$$$M7 $$$$$$$$$$M8$ $M9 $$M10$ M6$$$$$$$$$M7 $$$$$M8$ $$$$$$M9 $$$$$$$$M10$ $$M15$ M11$$$$M12 $$$$M13$$$$$$$M14$$$$$$M15$ 0-6 HL M11$$$$$$$$M12$$$$$$$M13$$$$$$M14 (1) Clin Cancer Res Jul 15;22(14): HL-60-luc luc + NK + NK + TriKE lu HL-60- *** 6000 c HL NK lu 16 c 33 + HL NK l 16 uc $M4 CD56+CD3- Events within 60 Sec acquisition Day 21 Day$21$Image! HL-60 HL-60-luc -luc + NK cells M1$$$$$$$$$$$M2 $$$$$$$$$$M3$ Evidence that IL-15 in the TriKE drives NK cell survival and proliferation

17 OXS-3550: TriKE for CD33+ Myeloid Malignancies Our most advanced Tri-specific scfv construct Targeting CD33+ Myeloid Malignancies IND filed June 8, 2017; transferred to GT Biopharma in October 2017 FDA requested additional non-clinical toxicology and manufacturing clarifications which we have completed Expect to file IND mid-2018 First in Human clinical trial expected to begin 2H 2018 ~60 patients Relapse/Refractory AML, High Risk MDS, and Advanced Systemic Mastocytosis Current proposed dosing: 4 days continuous infusion followed by 3 days off repeated X 3 weeks Dose finding and extended efficacy component 17

18 OXS-C3550: Next Generation AML CD33+ TriKE Next Generation TriKE with Potential for Enhanced NK cell activity (1) : fast follower to OXS-3550 Potentially More Designed with humanized, single-domain V H anti-cd16 (1) Felices et. al., Second Generation Camelid TriKE Induces Improved NK Cell Mediated Targeting of AML in Preclinical Models; American Society of Hematology 2017; Poster 18

19 OXS-1615: Example TetraKE Targeting EpCAM+ Carcinomas and CD133+ Cancer Stem Cells Working towards being in the clinic with a solid tumor product candidate in 2019 TetraKE-Mediated Cancer Stem Cell Killing 19

20 Potential Benefits of TriKE and TetraKE Therapeutics Designed to be an off-the-shelf drug Tumor antigen targeting without the need for genetic modifications as in certain cell therapies Potential in hematologic and solid tumors Expected convenience and flexibility 20 Dosing expected to be easily adjustable Broad potential applicability Attractive bio-distribution; important for solid tumor potential Non-immunogenic and quick clearance properties Can be engineered to target a variety of tumor antigens Estimated lower COGS and less labor intensive than cell therapies TriKEs are the protein version of CAR-T with multiple clinical and practical advantages Dr. Jeffrey Miller Deputy Director of the Masonic Cancer Center, University of Minnesota

21 OXS-1550: Bi-specific ADC Targeting CD19 & CD22 Bi-specific ADC product candidate OXS-1550 (DT2219) catalytic domain Catalytic domain Targets: CD19 & CD22 antigens on select cancer cells Indication: B-cell lymphomas and leukemias Payload: Modified Diphtheria Toxin 25 patient Phase 1 trial complete 18 patients enrolled in a Phase 1/2 trial Investigator-led, two-stage trial in NHL/ALL patients Being conducted at the Masonic Cancer Center, University of Minnesota Truncated DT390 translocation domain 1 st sfv Anti- CD22 (RFB4) 2 nd sfv Anti-CD19 (HD37) 21

22 OXS-1550: Phase 1 Trial Design (1) OXS-1550 Phase 1 trial design overview 25 patients enrolled across 9 dose cohorts 10 ALL, 10 NHL & 5 CLL µg/kg/day i.v. over 2 hours every other day (qod) Minimum of 3 prior lines w/ 8 failed hematopoietic stem cell transplant (HSCT) 12 patients treated at µg/kg/day qod had no detectable drug levels 13 patients treated at >40 µg/kg/day qod 9 had measurable drug levels (1) Bachanova et. al., Clin Cancer Res March 15; 21(6):

23 OXS-1550: Phase 1 Highlights (1) OXS-1550 Phase 1 trial summary results Of the 9 patients who had measurable drug levels; 2 had durable responses All adverse events (AEs) were grade 1-2 and transient Most common were weight gain, low albumin, elevated liver enzymes, and fever Panel A: 40% decrease in intra-abdominal mass in 77 year old patient with refractory chronic lymphocytic leukemia Patient had Partial Response (PR) following single course Panel B: Resolution of subcutaneous nodule in 53 year old patient with refractory marginal zone lymphoma Patient had Complete Response after 2 nd course CR is ongoing for over 3 years 1) Bachanova et. al., Clin Cancer Res March 15; 21(6):

24 OXS-1550: Phase 1/2 Trial Design currently in Phase 2 component (1) Schema 1 treatment cycle Disease Reassessment Final Rx Visit F/U* Disease & Survival Status Day yr OXS-1550 at assigned dose IV on day 1, 3, 5, and 8 and day 15, 17, 19, 22 Study Design Continuation Phase 1 dose/schedule but with a higher number of doses (4 versus 8 doses) Two-stage design to confirm safety and activity level Open label Up to 34 patients Indication: B-cell lymphomas and leukemias Clinical Site Masonic Cancer Center, University of Minnesota Principal Investigator Veronika Bachanova, M.D., Ph.D. Co-Principal Investigators Jeffery S. Miller, M.D. Aleksandr Lazaryan, M.D., M.P.H., Ph.D. 1) Toxicity and Day 29 disease reassessment measured for evaluable patients in each of two stage trial design (Phase 1 and Phase 2 components). Patients evaluable for response receive at least five doses. 24

25 OXS-1550: Preliminary Clinical Results from Phase 1/2 Interim Data Review Data snapshot included review of toxicity profile, disease reassessment at Day patients met evaluation criteria of at least 5 doses 4 ALL, 9 NHL >50% of patients (7 of 13) exhibited clinical benefit as defined by stable disease, partial remission or complete response at Day 29 Efficacy signal most pronounced in ALL 75% (3 of 4) exhibiting clinical benefit 1CR, 1PR and 1SD Bi-specific ADC Advisory Board recommendation to enroll additional ALL patients Adverse events were mostly grade-1 and grade-2 and reversible Four patients with dose limiting toxicity 1 grade-4 low platelet count, 2 grade-3 increase liver function tests and 1 grade-3 capillary leak Bi-specific ADC Clinical Advisory Board Masonic Cancer Center -- Dr. Jeffrey Miller, Deputy Director, Dr. Veronika Bachanova, Dr. Daniel Vallera Dr. Mark R. Litzow, M.D., Professor of Medicine in the Division of Hematology at Mayo Clinic Dr. Arthur E. Frankel, M.D., Chief of Medical Oncology at Mitchell Cancer Institute (USA-MCI) Note: Toxicity and Day 29 disease reassessment measured for evaluable patients in each of two stage trial design (Phase 1 component and Phase 2 component). Patients evaluable for response receive at least five doses. Expect to enroll additional ALL patients. 25

26 CNS Pipeline Summary GTP-004 Myasthenia Gravis PainBrake Chronic Neuropathic Pain GTP-011 Motion Sickness ~60,000 patients in US Patients can become wheelchair bound Pyridostigmine is the primary drug prescribed for treatment of muscle weakness GI side effects may lead to noncompliance or decreased dose Fixed dose combination of pyridostigmine and ondansetron IND filed results of POC study announced 1Q 2018 ~16 MM diagnosed in US Peak dose-limiting side effects of carbamazepine may cause patients to be under-dosed Patented protected tablet designed to provide frequent, small accurate doses 72-hour patch containing a potent selective muscarinic receptor antagonist Does not act in the brain Current SOC for prevention is 72 hour scopolamine patch Acts both in and outside the brain Can cause sedation and cognition effects Investigator-led concept study data and next steps expected 2H

27 2018 Milestones/Catalysts for Growth Applied for NASDAQ uplisting OXS-3550 expectations IND filing mid-2018 Begin First in Human clinical trial 1H 19 OXS-1550 Final data expected 4Q 18 or 1Q 19 Possible End-of-Phase 2A meeting with FDA in first half of 2019 OXS-C3550 IND-enabling studies & TetraKE pre-clinical program CNS next steps and concept study results Other potential corporate and business development opportunities 27

28 Management and Independent Directors with Relevant Experience Raymond W. Urbanski, M.D., Ph.D. Chairman and Chief Executive Officer 25+ years of pharmaceutical, drug development and management experience Chief Medical Officer, MannKind Corporation Chief Medical Officer, Mylan Vice President, Business Unit CMO and Sr. Medical Director, Oncology Clinical R&D at Pfizer Geoffrey B. Davis, Esq. Founding partner Barker Davis, LLC Ropes & Gray, LLC; partner for over 25 years; significant role in establishing internationally recognized Life Sciences group Numerous corporate partnering, licensing, capital markets and strategic transactions for major pharmaceutical companies (e.g. Pfizer), and public and private biotechnology companies Peter Kiener, D.Phil. Most recently Chief Scientific Officer at Sucampo; sold to Mallinckrodt for ~$1.2bn Formerly Chief Scientific Officer of Ambrx Inc. (Antibody Drug Conjugate company) and Executive Vice President and Global Head of Biologics Research and Development, MedImmune LLC 20+ years experience in all aspects of drug development, including discovery, regulatory approval, and post marketing and execution of multiple deal types, including private placements, IPO, M&A, strategic partnerships, and licensing deals; NK experience (board of NKT) John N Bonfiglio, Ph.D., MBA 30+ years of pharmaceutical and management experience including President, COO and CEO roles President and COO of TapImmune Inc.; previous Board member President and CEO of Oragenics, Argos Therapeutics and The Immune Response Corporation 28

29 Advisors Provide Additional Resource Depth Oncology Scientific Advisory Board Jeffrey Miller, M.D. Professor of Medicine, Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center Bruce Blazar M.D. Professor of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota James J. Mulé, Ph.D. Associate Center Director and Michael McGillicuddy Endowed Chair in Melanoma Research/Treatment at Moffitt Cancer Center Robin Parihar, M.D., Ph.D. Assistant Professor, Department of Pediatrics, Section of Pediatric Hematology-Oncology Center for Cell and Gene Therapy Texas Children's Hospital Baylor College of Medicine Ad Hoc Oncology Scientific Advisory Board Members Sarah Cooley, M.D., M.S. Associate Professor of Medicine, Division of Hematology, Oncology and Transplantation, Director of Investigator Initiated Clinical Research, Masonic Cancer Center Martin Felices, Ph.D. Assistant Professor of Medicine, Co-director of the Translational Therapy Laboratory, Division of Hematology, Oncology, and Transplantation, University of Minnesota 29