September 2017 CORPORATE OVERVIEW NASDAQ: GLYC. Innovation Today, Healing Tomorrow.

Transcription

1 September 2017 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 March1, 2017, 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 - Investment Opportunity Highly differentiated clinical programs for orphan diseases Portfolio targets significant unmet needs with large commercial potential Phase 3 in vaso-occlusive crisis (VOC) of sickle cell disease Robust Phase 2 results across all endpoints Phase 3 expected to complete enrollment in 2H 2018 Partnered with Pfizer Phase 2 in acute myeloid leukemia Breakthrough Therapy Designation received May Compelling clinical outcomes and biomarker proof-of-concept from Phase 1/2 trial Multiple data readouts next 6-12 months Proven management team Pioneers in the field of glycobiology, with broad experience in drug development Strong Balance Sheet provides funding through multiple milestones June 30, 2017 cash balance $119 million 3

4 Major Announcements & Upcoming Milestones Rivipansel (Phase 3) Phase 2 data selected as Best of ASH Orphan Drug Designation & Fast Track Status (US) Special Protocol Assessment with FDA Phase 3 enrollment initiated Anticipate Phase 3 top-line results 2H-2018 GMI-1271 (Phase 1/2) Orphan Drug Designation (US & EU) & Fast Track Status (US) Completion of Phase 1 and selection of phase 2 dose Completion of Phase 2 enrollment in newly diagnosed AML cohort Breakthrough Therapy Designation granted by the FDA Completion of Phase 2 enrollment in R/R AML cohort Presentation of interim Phase 2 results at ASCO and EHA Define registration program in AML with FDA Q Anticipate announcing Phase 2 durability of response and OS Q GMI-1359 (Phase 1) Initiation of Phase 1 study Anticipate announcing optimal dose and initial cancer indication Q

5 A Balanced Portfolio of Product Candidates Compound Therapeutic Area Discovery Pre- Clinical Ph 1 Ph 2 Ph 3 Registration Partner Selectins Rivipansel (Pan-selectin Inhibitor) Sickle Cell Anemia Vaso-occlusive Crisis Pfizer GMI-1271 and Follow-ons (E-selectin Inhibitor) Acute Myelogenous Leukemia Multiple Myeloma GMI-1359 (E-selectin & CXCR4 Inhibitor) Various Tumor Types & Inflammatory Diseases Various Tumor Types Galectins Galectin-3 Inhibitor Undisclosed Galectin Inhibitor Fibrosis & Oncology -- Various Tumor Types -- 5

6 GMI-1271 Targeting the Bone Marrow Microenvironment for Treatment of AML 6

7 GMI-1271: A First-in-Class Therapeutic Disrupts Tumor Microenvironment Small-molecule, potent, selective, E-selectin antagonist Compelling efficacy, safety and biomarker data from Phase 1/2 AML study - clinical proof-of-concept established, Breakthrough Therapy designation High remission rates, low induction mortality and promising initial survival in highly pre-treated R/R AML population Biomarker correlated with achievement of remission High remission rates and low induction mortality in newly diagnosed, elderly, AML patients Benign safety profile with observed reductions in chemotherapyassociated toxicities (e.g. mucositis) Preclinical rationale for use in multiple indications and combination approaches - proteasome-rescue study underway in MM IP through

8 GMI-1271 Phase I / II Study in AML Study Design Dose Escalation: 3 dose levels tested (5, 10 & 20 mg/kg) in Relapsed/refractory AML (MEC) population Phase 2 dose selected - 10mg/kg Dose Expansion: 25 patients with newly diagnosed AML > 60 (7&3) 47 patients with R/R AML (MEC) Endpoints: Safety, PK, Biomarkers & Efficacy (ORR) Lead Investigator: Dan DeAngelo, MD, PhD Dana Farber Cancer Institute Additional centers in US, Ireland and Australia Re-Treatment Phase 2 Expansion Screening Treatment Follow-Up Long-Term Follow-Up BM Biopsy Visit Day GMI Chemo -22 to Mon 12 Mon GMI-1271 GMI

9 Key Phase I / II Interim Results in R/R AML Population Complete Remission Rate CR + CRi GMI High-risk, heavily pre-treated patient population All patients had intermediate or unfavorable cytogenetics >60% were either refractory or early relapsed (<6 months) AML Higher than expected CR/CRi rate and promising initial median overall survival mos 7.6 mons vs. ~5.4 mons (MEC-alone) Baseline expression of E-selectin ligand is predictive of remission MEC (Feldman) Percent of Patients For responders in Phase 1, median survival not reached at 12+ months GMI MEC well tolerated Clinical proof-of-concept established No DLTs observed - AE profile consistent with MEC alone Signs of protective effects - oral mucositis /stomatitis occurred at lower rates and intensity than expected for MEC (2% incidence Grade 3/4 vs. 25% for historical MEC-alone) Response criteria per Cheson, 2003; Dohner Feldman J Clin Oncol 2005 Jun 20:23 (18):

10 Key Phase II Interim Results in Frontline AML Population Complete Remission Rate GMI-1271 Newly Diagnosed (10mg/kg) 7 & 3 (Foran) GMI-1271 saml (10mg/kg) Vyxeos (Phase 3) CR + CRi Percent of Patients Elderly, high-risk patient population 50% had saml; >92% had intermediate - unfavorable cytogenetics GMI &3 well tolerated AE profile consistent with 7&3 alone - no obvious incremental toxicity 0% grade 3-4 mucositis E-selectin ligand broadly expressed at baseline in majority of patients - target clinically relevant Efficacy data compares favorably to wellestablished historical controls (7&3 or Vyxeos) Responses appear durable with100% of responding patients remaining in remission at 6 months Promising Complete Remission Rates in High-Risk, Elderly AML Patients Response criteria per Cheson, 2003; Dohner Foran et al. Blood :217. Lancet et al. ASCO Annual Meeting

11 GMI : Overall Response by Cytogenetic & Other Risk Factors AML Subgroup N Completing Induction Period Phase 1 R/R (MEC) Remission Rates (CR/CRi) in Defined Subgroups, n (%) Phase 2 R/R (MEC) RP2D R/R (MEC) Total R/R (MEC) Elderly Newly Diagnosed (7+3) Favorable risk (SWOG) /1 (100%) Intermediate risk (SWOG) 5/9 (56%) 6/15 (40%) 9/17 (53%) 11/24 (46%) 10/15 (67%) Unfavorable risk (SWOG) 4/10 (40%) 7/20 (35%) 9/23 (39%) 11/30 (37%) 5/8 (63%) FLT3-ITD mutated 1/2 (50%) 2/5 (40%) 3/7 (43%) 3/7 (43%) 1/1 (100%) Extramedullary disease 1/1 (100%) 1/1 (100%) 2/2 (100%) 2/2 (100%) 0 Higher than expected remission rate maintained across all subgroups, including those with unfavorable risk 11

12 GMI-1271: US Regulatory Update & Future Plans Breakthrough Therapy Designation (BTD) granted for the treatment of adult patients with relapsed/refractory acute myeloid leukemia on May 17, 2017 BTD expedites the development and review of new medicines that treat Serious or life-threatening disease demonstrate substantial improvement over existing therapy Discussions underway with FDA to determine development path forward US Fast Track status granted in June 2016 Orphan Drug Designation (USA May 2015 / Europe May 2016) Potential for expedited development program and FDA regulatory review 12

13 GMI-1271: Scientific Rational for Use in Multiple Myeloma 13

14 E-Selectin Expression is Associated with Poorer Clinical Outcomes in Multiple Myeloma E-Selectin Expression Overall Survival High ST3GAL6/low FUCA1 FISH/ISS others NDMM: Newly Diagnosed (n=33) rrmm: Relapsed/Refractory (n=50) E-selectin ligand is over-expressed in high risk MM patients and confers poor prognosis (e.g. mos of 10 months vs. 33 months) A. Natoni et al. Leukemia

15 P e r c e n t s u r v i v a l P e r c e n t s u r v i v a l Addition of GMI-1271 Restores Sensitivity of Bortezomib in an E-Selectin Overexpressing Model of MM 100 Parent Treatment MST (days) % survival P vs saline saline GMI-1271 (40 mg/kg IP qd x 21 days Bortezomib (0.75 mg/kg IP qw x 3 wks Days post tumor injection GMI Bortezomib 60 b a P= vs. bortezomib 100 E-Selectin Enriched Treatment MST (days) % survival saline P vs saline 50 GMI-1271 (40 mg/kg IP qd x 21 days Bortezomib (0.75 mg/kg IP qw x 3 wks Days post tumor injection a additional study at lower tumor inoculum gives similar outcome GMI Bortezomib 56.5 c a P= vs. bortezomib A. Natoni et al. Leukemia

16 Proof-of-Concept Study in MM Ongoing Proteasome Inhibitor Rescue Study Design: Phase I Dose Escalation Patient Population Patients with relapsed/refractory MM continuing on bortezomib/carfilzomib-based regimen 4 Dose Levels (5, 10 & 20 mg/kg) - 6 patients/cohort Weekly or Bi-weekly bortezomib/carfilzomib backbone Endpoints: Safety, PK, Biomarkers & Efficacy Lead Investigator: Michael O Dwyer, MD: NUI Galway Screening Treatment (Up to 6 Cycles) Follow-Up Bort/Carf Weekly or Bi-Weekly Standard Regimen Bortezomib/Carfilzomib GMI-1271 QD dosing same time and 24 hrs following each dose of Bort/Carf Bone Marrow Biopsy Baseline Cycle 3 Cycle 6 Folllow-Up 16

17 Rivipansel (GMI-1070) for Sickle Cell Crisis 17

18 Rivipansel Value Proposition Significant unmet medical need Quantifiable clinical and healtheconomic endpoints Defined regulatory path to approval US FDA Special Protocol Assessment Excellent economics to GLYC from Pfizer Sickle Cell Anemia Healthcare Utilization for VOC Outpatient Treatment in ER & Clinic Settings (~140,000 Events/Yr 3 ) Initial US Approval Goal Inpatient Hospitalizations (80-100,000 Events/Yr 1,2 ) Attractive commercial opportunity; substantial market expansion potential On-demand approach Avoids historical noncompliance challenges with chronic, prophylactic therapy Longer term potential: Treat VOC earlier in ER/clinic (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) 18

19 Probability 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 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) Telen, Blood Apr 23;125(17):

20 Probability Hourly IV Opioid Use 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 0.8 Rivipansel 0.8 Rivipansel *** 24 hour reduction p< 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; ANCOVA) Telen, Blood Apr 23;125(17):

21 Pfizer Deal Economics Rights Pfizer responsible for all further clinical development, regulatory approval and potential commercialization for all indications worldwide Upfront $22.5 million Milestones Total Milestones: up to $320.0 million Development: up to $115.0 million $35.0 million received upon start of Phase 3 $15.0 million advance payment received in May 2014, $20.0 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 21

22 GlycoMimetics is Positioned for Success Promising Pipeline Significant Revenue Opportunities Rivipansel: Sole on-demand treatment in late-stage, registration trial for acute VOC; SPA in place with FDA GMI-1271: Clinical outcomes and biomarker demonstrate clinical proof-of-concept in AML; Breakthrough Therapy Designation granted by the FDA GMI-1359: Simultaneous blockade of CXCR4 & E-Selectin inhibits established pathways of cancer cell trafficking Rivipansel: ~100,000 patients in USA GMI-1271: > 40,000 AML patients in 7MM Strong Investment Base Cash balance provides runway through key milestones Top-tier biotech investors Experienced Team Pioneers in the field of glycobiology and small-molecule, therapeutic mimetics Relationships with leading KOLs and national / international oncology networks 22

23 September 2017 CORPORATE OVERVIEW NASDAQ: GLYC Innovation Today, Healing Tomorrow.