June 2016 CORPORATE OVERVIEW NASDAQ: GLYC. Innovation Today, Healing Tomorrow.

Transcription

1 June 2016 CORPORATE OVERVIEW NASDAQ: GLYC Innovation Today, Healing Tomorrow.

2 Forward-Looking Statements To the extent that statements contained in this presentation are not descriptions of historical facts regarding GlycoMimetics, Inc. ( GlycoMimetics, we, us, or our ), they are forward-looking statements reflecting management s current beliefs and expectations. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry s actual results, levels of activity, performance, or achievements to be materially different from those anticipated by such statements. You can identify forward-looking statements by terminology such as may, will, should, expects, plans, anticipates, believes, estimates, predicts, potential, intends, or continue, or the negative of these terms or other comparable terminology. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding: (i) the conduct of the ongoing Phase 3 clinical trial of GMI-1070 by Pfizer Inc. ( Pfizer ); (ii) the timing of additional clinical trials for our other drug candidates; (iii) the timing of receipt of clinical data for our drug candidates; (iv) our expectations regarding the potential safety, efficacy, or clinical utility of our drug candidates; (v) the size of patient populations targeted by drug candidates we or our collaborators develop and market adoption of our potential drugs by physicians and patients; (vi) the likelihood and timing of regulatory filings and approvals; and (vii) and our cash needs and potential royalties and milestone payments under license and collaboration agreements. Various factors may cause differences between our expectations and actual results, including unexpected safety or efficacy data, unexpected side effects observed during preclinical studies or in clinical trials, lower than expected enrollment rates in clinical trials, changes in expected or existing competition, changes in the regulatory environment for our drug candidates, failure of our collaborators to support or advance our collaborations or drug candidates, our need for future capital, the inability to protect our intellectual property, and the risk that we become a party to unexpected litigation or other disputes. For a further description of the risks associated with forward-looking statements, as well as other risks facing GlycoMimetics, please see the risk factors described in the Company s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on February 29, 2016, as well as other reports we file with the U.S. Securities and Exchange Commission from time to time, including those factors discussed under the caption Risk Factors in such filings. Forward-looking statements speak only as of the date of this presentation, and GlycoMimetics undertakes no obligation to update or revise these statements, except as may be required by law. 2

3 GlycoMimetics Highlights Highly differentiated clinical programs for orphan diseases with few or no treatment options GMI-1271 Phase 1/2 trial underway in acute myeloid leukemia Data on 19 patients in Phase 1 portion to be presented at EHA Emerging news flow in 2016 and 2017 Additional clinical applications have been identified and are being pursued in myeloma and T-cell mobilization Program wholly owned by GlycoMimetics Rivipansel Phase 3 study underway in vaso-occlusive crisis (VOC) of sickle cell disease Phase 3 being conducted and financed by Pfizer Robust Phase 2 results Clear regulatory path Strong competitive positioning GMI-1359 program preparing for IND targeting hematologic malignancies IND planned for Q Preclinical data presented at AACR and ASH Program wholly owned by GlycoMimetics 3

4 GMI-1271: Targeting the Bone Marrow Microenvironment for Treatment of Blood Cancers 4

5 GMI-1271 Program Update Initial Focus on Acute Myelogenous Leukemia Differentiated mechanism of action; first-in-class drug candidate Targets interactions in the bone marrow micro-environment Synergistic in combination with chemotherapy Preclinical proof-of-concept data chosen for multiple oral and poster presentations at ASH have shown: Improvements in survival, as adjunct to chemotherapy, in AML and multiple myeloma Reductions in chemotherapy-associated toxicities (neutropenia and mucositis) AML Phase 1/ 2 trial now underway Phase 1 data showed a higher remission rate than standard therapy among difficult to treat patients Multiple data readouts planned for coming months 5

6 GMI-1271 Phase 1/ 2 Clinical Trial Phase 1 Portion Data Report Data from the Phase 1 portion to be presented June 10 at the European Hematology Association annual meeting in a poster entitled: Results of a Phase 1 study of GMI-1271, a potent E- selectin antagonist in combination with induction chemotherapy in relapse/refractory AML: a novel, welltolerated regimen with a high remission rate Presented by Daniel J. DeAngelo, M.D., Ph.D., Director of Clinical and Translational Research, Adult Leukemia; Department of Medical Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School 6

7 GMI-1271 Phase 1/ 2 Clinical Trial Initial Topline Data- EHA Abstract Thirteen patients with relapsed/refractory AML have been treated and are evaluable Two dose levels: 5 mg/kg and 10 mg/kg Seven patients had adverse cytogenetic risk Six patients had intermediate cytogenetic risk None were favorable Single cycle of GMI-1271 Eight patients achieved Complete Response (CR) Seven full CR (bone marrow response and full blood count recovery) One CRi (patient transplanted before CR documented) Responders include refractory AML (3), relapsed FLT3-ITD mutated (1) and EMD (1) 30 day mortality was 0% GMI-1271 was well tolerated No DLT s were observed Mucositis developed in 5 subjects (4 at 5mg/kg) All subjects completed study treatment without dose reduction or interruption Full data set to be presented at EHA with updated data on 19 patients Dose expansion has occurred in relapsed/refractory patients 7

8 Ongoing Phase 1/2 Open-Label Study in AML Study Design Dose Escalation (Phase 1): 6 per cohort, 3 dose levels (5, 10, 20 mg/kg) Relapsed/refractory AML (MEC) Single cycle of treatment Dose Expansion (Phase 2): up to 50 patients Up to 25 R/R AML (MEC) Up to 25 newly diagnosed AML over age 60 (Ara-C & idarubicin) Certain patients may be treated with more than one cycle Endpoints: Safety, PK, Biomarkers (mobilization) & Efficacy (MRD) Lead Investigator: Dan DeAngelo, MD Dana Farber Cancer Institute Additional participating centers in USA, Ireland & Australia Screening Treatment Follow-Up Long-Term Follow-Up BM Biopsy Visit Day GMI Chemo -22 to Mon 12 Mon GMI-1271 GMI

9 GMI-1271 Disrupts Relationship Between Tumor Cells and Bone Marrow Microenvironment Tumor Cells in Quiescent Niche Tumor Cells in Quiescent Niche E-selectin is expressed on endothelial cells and is constitutively expressed in the bone marrow microvasculature Current Paradigm Chemo E-Selectin Blockade Relapse Tumor Cells Protected in Bone Marrow Microenvironment GMI-1271 Remission + Chemo Tumor Cells Mobilized From Bone Marrow Microenvironment Preclinical data with GMI-1271 Prevents trafficking of tumor cells to the bone marrow Disrupts cell adhesionmediated drug resistance (CAMDR) within bone marrow microenvironment Inhibits activation of cancer survival pathways (e.g. Wnt) Protects normal HSCs by enhancing quiescence and ability for self-renewal Protects against chemotherapy induced mucositis 9

10 Ongoing Phase 1/2 Open-Label Study in AML Anticipated Data Read-outs 4Q 2016 study update possible ASH submission Mid-2017 results from Phase 2 portion of study, both arms (relapsed/refractory and newly diagnosed patients) 10

11 GMI-1271: Potential Use in Multiple Myeloma 11

12 Multiple Myeloma Cells Express E-Selectin Ligands E-selectin Glycosyltransferase Genes (high ST3GAL6/low FUCA1) Define a Very High Risk Group Within the Accepted High-Risk MM Population (FISH/ISS) High ST3GAL6/low FUCA1 FISH/ISS others FUCA1 ST3GAL6 OH Sialyl Le a Increasing E-selectin Ligand Increased E-selectin ligand (high ST3GAL6/lowFUCA1 signature) was overrepresented in high risk compared to low risk [39% vs. 13.9%, p=0.01] patients and conferred poor prognosis with a median survival of 10 months vs. 33 months in these Very High Risk patients M. O Dwyer 12

13 GMI-1271 Restores Sensitivity of Bortezomib in an Animal Model Simulating Very High Risk MM Parental MM1s cells (~5% HECA ) Enriched Population MM1s cells (~85% HECA ) Very High Risk Patient Model Percent Survival 50 Percent Survival Rx Days post tumor injection Rx Days post tumor injection Female NOD SCID mice injected iv with 5 x 10 6 human tumor cells (n= 8/group) Rx - 3 days post tumor injection saline GMI-1271 Bortezomib GMI Bortezomib 13

14 Multiple Myeloma Next Steps Clinical protocol in development targeting bortezomib rescue Testing whether GMI-1271 can be used to restore sensitivity to bortezomib Regulatory approval has been received in Ireland Clinical sites being established to conduct small proof of concept study 14

15 GMI-1271: Application in Adoptive Cell Therapy & Immuno-Oncology 15

16 Current Limitations of Adoptive T-cell Therapy Problem Possible solutions Limitations inherent to product quality Need for a better selection of tumor-direct T-cells Poor effector cell-survival capacities Modification of effector cells or APCs by genetic engineering (CARs, TCRs) Use of naïve T-cell populations Modification of effector cells by genetic engineering (expression of co-stimulatory molecules on T cells ) In vivo support of ATCT with cytokines or peptide vaccines Limitations inherent to product activity in vivo Immune evasion strategies/inhibitory effect of regulatory T cells, MDSCs, and checkpoint ligands Cytokine-release syndrome Modification of effector cells or APCs by genetic engineering (induce resistance to inhibitory cytokines) Limitations inherent to production Personalized ATCT generation Limited GMP standardization Production costs Centralization by contract cell-producing/banking biotechs Creation of ATCT networks Centralize production of specific ATCT Bone Marrow Transplantation (2012) 47,

17 Enhanced Responses with Primitive T-Cells Strongly Supported in the Literature Using Adoptive T-Cell Therapy Increased Proliferative Capacity, Survival and Antitumor Activity of T SCM cells 1 1 Gattinoni et al., Nat Med Sep 18; 17(10):

18 GlycoMimetics Primitive T-Cell Enriching Strategy Using GMI-1271 ASH GMI-1271 significantly improves the in vivo reconstitution potential and regenerative properties of CD8+ T-cells from the donor blood allowing a valuable source of desired T-cells for use in adoptive immunotherapy and T-cell engineering 18

19 Rationale and Current Status E-selectin acts as a gatekeeper driving activation and differentiation of cells from the bone marrow microenvironment Short-term treatment with GMI-1271 can selectively block this gatekeeper to significantly skew the mobilization of primitive T-cells & HSCs with enhanced stem-like qualities Incorporating GMI-1271 into mobilization and harvest regimen may serve as a simple approach for boosting the therapeutic potential of adoptive cell approaches Pilot testing in humans now underway 19

20 Rivipansel (GMI-1070) for Sickle Cell Crisis 20

21 Rivipansel Value Proposition Significant unmet medical need with quantifiable clinical and healtheconomic endpoints Defined regulatory path to approval in US agreed under Special Protocol Assessment with FDA Sickle Cell Anemia Healthcare Utilization for VOC Outpatient Treatment in ER & Clinic Settings (~140,000 Events/Yr 3 ) Initial US Approval Inpatient Hospitalizations (80-100,000 Events/Yr 1,2 ) Attractive commercial positioning with opportunity for substantial market expansion On-demand approach avoids historical noncompliance challenges with chronic, prophylactic therapy Longer term potential to treat VOC earlier in the ER/clinic setting (1) Hassell KL. (2010) Am J Prev Med.;38(4 Suppl):S (2) Brousseau D et. al. (2010) Am J Hematol. 85(1) 77-8 (3) Yusuf HR et. al. (2010) Am J Prev Med. 38(4 0) 21

22 Rivipansel Clinical Development Highlights Improvements observed in every efficacy endpoint evaluated across all subgroups studied in Phase 2 study Reduction in time in to hospital discharge by > 3.5 days Probability Time to Discharge From Hospital Placebo Rivipansel Efficacy data supported by improvements on biomarkers of inflammation and coagulation in patients in biomarker study Time to Discharge (Hours) Benign safety profile Phase 2 data recognized as Best of ASH Median time to discharge reduced by 84 hours (p=0.092; Kaplan-Meier) 22

23 Phase 2 Results Substantial Reduction in Time to Resolution of VOC and Opioid Use Time to Resolution of VOC Opioid Use Over Time 1.0 Placebo 1.0 Placebo Probability Rivipansel Hourly IV Opioid Use *** 24 hour reduction p<0.001 Rivipansel Time to Resolution (Hours) 0.0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Mean Hourly Opioid Use Median time to resolution of VOC reduced by 63 hours (p=0.187; Kaplan-Meier) Cumulative opioid analgesic administered reduced by 83% (p=0.010) 23

24 SPA Agreed for Phase 3 RESET Trial Only FDA-agreed SPA for any drug to treat sickle cell crisis Single registration study in patients ages 6 and older Primary efficacy outcome is time to readiness for discharge Secondary outcomes are: Time to discharge Cumulative opioid use Time to discontinuation of opioids Cumulative opioid use within first 24 hours Re-hospitalization within three days of discharge Target enrollment of 350 patients 24

25 Pfizer Deal Economics Rights Pfizer responsible for all further clinical development, regulatory approval and potential commercialization for all indications worldwide Upfront Future Milestones $22.5 million Total Milestones: up to $320.0 million Development: up to $115.0 million $35.0 million upon start of Phase 3 $15 million advance payment received in May 2014, $20 million received August 2015 with dosing of the first patient. Regulatory: up to $70.0 million Commercial: up to $135.0 million Royalties Tiered, ranging from low double digits to low teens 25

26 GMI-1359: Dual-Function (E-Selectin & CXCR4) Antagonist for Hematology-Oncology 26

27 GMI-1359 Program Overview First-in-class drug candidate, novel mechanism of action targeting both E-selectin and CXCR4 Overlapping functions associated with tumor cell migration and desmoplasia of the tumor microenvironment Preclinical data presented at ASH and AACR demonstrates: Improved outcomes in synergy with chemotherapy in Flt-3 + AML Reduction in metastasis in pancreatic cancer Reduction in bone lytic lesions in prostate cancer Preparing for IND Q Healthy volunteer study to initiate in Q

28 Upcoming Milestones 3Q 2016 Initiation of GMI-1271 myeloma study in Europe Publication opportunities of additional data from Phase 2 rivipansel study, based on further subgroup analysis Effects on pain and opioid use Effects in pediatric sub-populations 4Q 2016 Additional data read outs from GMI-1271 AML study Initiation of GMI-1359 clinical trial Mid-2017 Data from Phase 2 portion of AML study, both arms Relapsed refractory and de novo elderly patients 28

29 Summary Multiple data readouts from ongoing GMI-1271 AML program expected in next 12 months Data on 19 patients in Phase 1 portion to be presented at EHA Novel and highly differentiated approach to treatment of AML, added on backbone of generic standard of care Clinical program targeting cancer-related outcomes such as CR rate and following for effects on tolerability of chemotherapy Follow-on uses of GMI-1271 to enter clinic in 2016 setting up for potential additional data readouts in 1H Combination E-selectin- CXCR4 antagonist entering clinic Q Rivipansel sickle cell program now enrolling in Phase 3 being conducted and financed by Pfizer Attractive competitive positioning with potential to provide therapy in a variety of treatment settings SPA in place with FDA supports study design Substantial economics to GlycoMimetics from Pfizer deal 29

30 June 2016 CORPORATE OVERVIEW NASDAQ: GLYC Innovation Today, Healing Tomorrow.