8-K
CRESCENT BIOPHARMA, INC. (CBIO)
8-K
2023-03-02
For: 2023-03-02
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of
The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): March 2, 2023
GlycoMimetics, Inc.
(Exact name of registrant as specified in its charter)
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|---|---|---|---|---|
| Delaware | | 001-36177 | | 06-1686563 |
| (State or other jurisdiction of incorporation) | | (Commission File Number) | | (IRS Employer<br>Identification No.) |
9708 Medical Center Drive
Rockville , MD **** 20850
(Address of principal executive offices, including zip code)
( 240 ) 243-1201
(Registrant’s telephone number, including area code)
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered |
|---|---|---|
| Common Stock, $0.001 par value | GLYC | The Nasdaq Stock Market |
Indícate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
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Item 7.01. Regulation FD Disclosure.
A copy of a slide presentation that GlycoMimetics, Inc. (the “Company”) plans to use for anticipated investor meetings is attached to this Current Report as Exhibit 99.1 and is incorporated herein solely for purposes of this Item 7.01 disclosure.
The information in this Item 7.01, including Exhibit 99.1 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section. The information in this Item 7.01, including Exhibit 99.1 attached hereto, shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, except as otherwise expressly stated in such filing.
Item 9.01. Exhibits.
(d) Exhibits
| 9, | |
|---|---|
| Exhibit | **** |
| Number | Exhibit Description |
| 99.1 | GlycoMimetics, Inc. Corporate Presentation, March 2, 2023 |
| 104 | Cover Page Interactive Data File (the cover page XBRL tags are embedded within the Inline XBRL document) |
2
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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| | | GLYCOMIMETICS, INC. |
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| | By: | /s/ Brian M. Hahn |
| Date: March 2, 2023 | | Brian M. Hahn<br>Senior Vice President and Chief Financial Officer |
3
Exhibit 99.1
| © 2021 GlycoMimetics, Inc. All rights reserved.<br>Glycobiology-based therapeutics<br>Transforming lives<br>NASDAQ: GLYC March 2023 |
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| • To the extent that statements contained in this presentation are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of the management of GlycoMimetics, Inc. (“GlycoMimetics,” “we,” “us,” or<br>“our”). Forward-looking statements contained in this presentation may include, but are not limited to: (i) the expected or projected timing of events and data readout from ongoing Phase 3 clinical trials of uproleselan; (ii) the planned or potential clinical<br>development and potential indications, benefits and impact of our drug candidates, including uproleselan; (iii) the timing of receipt of<br>clinical data; (iv) 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 drug candidates by payors, physicians and<br>patients; (vi) the likelihood and timing of regulatory filings, approvals or other anticipated interactions with regulatory authorities; (vii)<br>our business and product development strategies, including our cash needs and expected cash runway; and (viii) any other statement containing 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.<br>• Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our<br>industry’s actual results, levels of activity, performance, or achievements to be materially different from those discussed, implied or otherwise anticipated by such statements. You are cautioned not to place undue reliance on such forward-looking statements, which are current only as of the date of this presentation. Examples of risks, uncertainties and factors that may cause differences<br>between our expectations and actual results include unexpected safety or efficacy data, unexpected side effects observed during preclinical studies or in clinical trials, lower than expected enrollment rates in clinical trials, whether results of early clinical trials will be indicative of results from later clinical trials, changes in expected or existing competition or additional market research that may cause our expectations about market opportunity to change, changes in the regulatory environment for our drug candidates, failure<br>of our collaborators to support or advance our collaborations or drug candidates, our need for future capital, the inability to adequately protect our intellectual property, and becoming a party to litigation or other disputes. For a further description of the risks<br>associated with forward-looking statements, as well as other risks facing GlycoMimetics, please see the risk factors described in the<br>Company’sAnnual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 3, 2022, its Quarterly Report on Form 10-Q filed with the SEC on November 9, 2022, and 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.<br>Forward-Looking Statements<br>2 |
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| Pioneers in glycobiology-based therapies for cancers and other rare diseases<br>Strong Foundation with Near-Term Catalysts and Broad Pipeline<br>Uproleselan: Multiple<br>Late-Stage Clinical Trials<br>• Fully enrolled Phase 3 trial in<br>R/R AML (n=388), OS events<br>trigger currently projected for<br>~1H-2024<br>• Fully enrolled Phase 2 trial in<br>front-line AML (n=267) ongoing,<br>NCI-sponsored<br>• Ongoing ISTs in other AML<br>populations. Preliminary data<br>presented at ASH 2022<br>• Novel MOA potential broad<br>utility with Breakthrough<br>Therapy, Fast Track, and<br>Orphan designations<br>3<br>Broad Early-Stage<br>Pipeline<br>• Novel small molecules inhibit<br>carbohydrate signaling<br>• GMI-1687<br>• Targets sickle cell pain crises<br>• Cleared FDA 30-day IND<br>review<br>• GMI-2093<br>• Targeting fibrotic diseases<br>• First oral Galectin-3<br>antagonist<br>Targeted Operational<br>Execution<br>• Recent Key Leadership Hires<br> purpose-driven biotechnology<br>team<br>• Deep expertise in regulatory,<br>medical and commercialization<br>across hem/onc therapies |
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| PROGRAM THERAPEUTIC AREA DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MARKET PARTNER<br>SELECTINS<br>UPROLESELAN<br>(GMI-1271)<br>Relapsed / Refractory AML<br>Newly Diagnosed “Fit” AML<br>GMI-1687 SCD Vaso-occlusive Crisis and AML<br>GALECTINS<br>GMI-2093 Fibrosis and Oncology<br>DISCOVERY - PRECLINICAL CLINICAL MARKET<br>A Portfolio of Exciting Product Candidates<br>* Greater China<br>Submit Registration for<br>Regulatory Approval<br>*<br>4<br>Fully Enrolled 388 patients Nov 2021 – Events trigger projected ~1H-24<br>*<br>Fully Enrolled 267 patients Dec 2021<br>Lead declared March 2022<br>IND Cleared June 2022 |
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| Breakthrough Therapy Designation in AML<br>Uproleselan (GMI-1271) |
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| SIGNIFICANT UNMET NEED IN AML<br>Significant Lowest 5-Year Survival of all Leukemias1<br>1. SEER 2022 Statistics<br>21,450 New<br>Cases<br>All Other<br>Leukemias<br>Estimated New Cases<br>(2022)<br>5-Year Relative Survival<br>(2011 – 2018)<br>20,050<br>New AML Cases<br>All Other<br>Leukemias<br>70.4<br>87.9<br>70.8<br>30.5<br>0<br>20<br>40<br>60<br>80<br>100<br>CML CLL ALL AML<br>Survival Rate %<br>6<br>Estimated New Cases<br>(2022) |
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| 7<br>E-selectin:<br> Adhesion molecule constitutively expressed in bone<br>marrow microvasculature<br> Up-regulated by Leukemic Stem Cells and AML blasts via<br>secreted inflammatory mediators<br>CD62E<br>Uproleselan: First-in-Class E-Selectin Antagonist to Address Resistance Pathways in AML<br>Uproleselan, an E-Selectin Antagonist:<br> Releases AML blasts from vascular sequestration,<br>agnostic to AML mutational status<br> Disrupts NF-kB mediated chemoresistance pathways<br> Potential broad utility across AML<br>E-selectin/E-selectin Ligand Interaction:<br> Enables AML blast sequestration in bone marrow<br> Activates pro-survival NF-kB pathways<br> E-selectin ligand sLex up-regulated on AML cells via<br>multiple distinct drug resistance mechanisms |
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| • 41% CR/CRi; 8.8 mos. Median Overall Survival in<br>Relapsed/Refractory AML<br>• 72% CR/CRi; 9.2 mos. Event Free Survival in Newly<br>Diagnosed AML<br>• MRD-negativity in >50% of evaluable patients<br>• Enhancing depth of response<br>• E-selectin ligand expression<br>• Detectable in every patient tested<br>• Higher levels in R/R patients achieving CR/CRi, MRD-and prolonged median OS<br>UPROLESELAN in R/R and Newly Diagnosed AML Patients<br>Phase 1/2 Results<br>8<br>Percent MRD Negative<br>0%<br>10%<br>20%<br>30%<br>40%<br>50%<br>60%<br>70%<br>80%<br>R/R AML (N=16) Newly Dx AML (N=9)<br>Results Published in Blood February ‘22 |
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| UPROLESELAN<br>Potential Foundational Backbone Across Spectrum in AML<br>1. SEER 2021 Statistics<br>• Improve achievement / depth of remission<br>• Extend overall survival<br>• Mitigate chemotherapy-related toxicity<br>UPROLESELAN VALUE<br>PROPOSITION<br>~12,000 “Fit” patients eligible for intensive chemotherapy ~8,000 “Unfit”<br>~20,240 Newly Diagnosed AML Patients in the U.S.1<br>NEWLY DIAGNOSED, ELDERLY AML<br>NCI-Sponsored Phase 2/3<br>Combination of Uproleselan + 7&3<br>12K<br>PATIENTS/YEAR<br>RELAPSED / REFRACTORY AML<br>GMI-Sponsored Phase 3<br>Combination of Uproleselan + MEC/FAI<br>8.5K<br>PATIENTS/YEAR<br>Recent<br>venetoclax<br>approval<br>8K<br>PATIENTS/YEAR<br>9 |
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| • Meta-analysis of 81 studies (N >11,000)<br>• MRD negativity prognostic for superior OS<br>• Average OS MRD HR 0.36,<br>• Independent of age, subtype, timing, method<br>MRD negativity and HSCT both favorably prognostic<br>10<br>Short, et al. JAMA Oncology 2020 6(12): 1890-1899<br>Overall Survival by MRD status<br>• Uproleselan Phase 1/2 overall survival by HSCT<br>• N=54 R/R AML patients at 10 mg/kg RP2D<br>• 10 longest survivors all MRD-negative<br>• Overall MRD-negative: 56% 1L, 69% R/R<br>DeAngelo et al, Blood 2022 139(8):1135-1146.<br>Overall Survival by HSCT |
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| UPROLESELAN<br>Relapsed / Refractory AML Phase 3 Study Design<br>KEY ELIGIBILITY<br>CRITERIA<br>• ≥18 and ≤75 years in age<br>• Either primary refractory or<br>relapsed (first or second<br>relapse) AML<br>• Eligible for intensive<br>salvage treatment<br>• <1 prior HSCT<br>Placebo plus MEC<br>or FAI (n=190)<br>Placebo plus<br>HiDAC or IDAC<br>Upro plus MEC<br>or FAI<br>(n=190)<br>Upro plus HiDAC<br>or IDAC<br>1:1 Randomization<br>(stratified by age, disease status and backbone chemo)<br>Induction<br>(1 Cycle)<br>Consolidation<br>(Up to 3 Cycles)<br>Follow-Up for Overall<br>Survival not censored for<br>transplant.<br>MEC: Mitoxantrone, etoposide and cytarabine<br>FAI: Fludarabine, cytarabine and idarubicin<br>HiDAC/IDAC: High-dose or Intermediate-dose cytarabine<br>Randomize<br>1:1<br>Enrollment of 388 Completed in November 2021<br>11 |
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| • 380 planned, 388 enrolled<br>• FPFV- November 2018<br>• LPFV- November 2021<br>• 11 patients (3%) lost to follow-up<br>Study GMI-1271-301 Enrollment<br>388<br>0<br>50<br>100<br>150<br>200<br>250<br>300<br>350<br>400<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>70<br>80<br>Oct 2018<br>Nov 2018<br>Dec 2018<br>Jan 2019<br>Feb 2019<br>Mar 2019<br>Apr 2019<br>May 2019<br>Jun 2019<br>Jul 2019<br>Aug 2019<br>Sep 2019<br>Oct 2019<br>Nov 2019<br>Dec 2019<br>Jan 2020<br>Feb 2020<br>Mar 2020<br>Apr 2020<br>May 2020<br>Jun 2020<br>Jul 2020<br>Aug 2020<br>Sep 2020<br>Oct 2020<br>Nov 2020<br>Dec 2020<br>Jan 2021<br>Feb 2021<br>Mar 2021<br>Apr 2021<br>May 2021<br>Jun 2021<br>Jul 2021<br>Aug 2021<br>Sep 2021<br>Oct 2021<br>Nov 2021<br># Subjects Randomized<br># Activated Sites<br># Activated Sites # Subjects Randomized |
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| 13<br>UPROLESELAN<br>Phase 3 Patient Characteristics Broadly Similar to Phase 2<br>Relapsed/Refractory Patient Demographics<br>301 Study<br>N=388<br>201 Study<br>N=66<br>Age, median (range) 58 (20-75) 59 (26-84)<br>Refractory, n (%) 129 (33%) 22 (33%)<br>Relapsed, n (%) 259 (67%) 44 (67%)<br>Duration of prior remission ≤6 mos 49 (19%) 18 (41%)<br>Prior Therapies<br>HSCT 70 (18%) 12 (18%)<br>≥2 Induction Regimens 63 (16%) 22 (33%)<br>ELN Risk Category<br>Adverse 42% 50%<br>Intermediate 23% 17%<br>Favorable 21% 11%<br>Unknown 14% 22% |
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| 10% 20% 30% 40% 50% 60% 70% 80% 90%<br>RCT<br>Prospective cohort study<br>Retrospective study<br>Phase I or II study<br>Note: outcomes with intensive<br>chemotherapy may be heavily<br>impacted by patient<br>characteristics including age,<br>ELN risk, disease status and<br>prior therapy, and that patient<br>numbers are small for some of<br>the data shown. Size of bubble is<br>proportional to sample size.<br>18mo<br>16mo<br>14mo<br>12mo<br>10mo<br>8mo<br>6mo<br>4mo<br>2mo<br>0%<br>Median OS<br>HSCT Rates<br>Single center<br>(Italy); N=55; 51y<br>Single center<br>(Germany);<br>N=132; 52y<br>AlloHSCT rates in R/R AML are highly variable and depend largely on efficacy of salvage regimen and patient/disease characteristics.<br>Intensive Chemotherapy (IC) in R/R AML<br>Typical ~6-7 months mOS and HSCT rates ~25-30%<br>14 |
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| 5.1<br>3.3<br>6.3<br>5.4<br>6.8<br>7.7<br>5.1<br>3.5<br>6.6 6.4 6.8<br>0<br>2<br>4<br>6<br>8<br>10<br>12<br>14<br>Lintuzumab + MEC vs. MEC Elacytarabine vs. Inv. Choice IDAC +clofarabine vs IDAC Guadecitadine vs Inv. choice Various salvage regimens Idasanutlin + IDAC vs. IDAC<br>Upro Phase 1/ 2 ≈ 8.8 mos.1<br>1 Follow-up period cutoff at 9.7 mons to focus on Phase 3.<br>15 patients (28%) in RP2D population were censored for OS<br>15<br>Historical Intensive Chemotherapy benchmarks for mOS are ~6 months<br>Phase 3, RCT, N=191<br>Feldman et al, JCO 2005<br>Phase 3, RCT, N=381<br>Roboz et al, JCO 20142<br>Phase 3, RCT, N=320<br>Faderl et al, JCO 2011<br>Retrospective Review<br>N=850+ 4, Megias-Vericat et<br>al, Ann Hematol 2018<br>Phase 3, RCT, N=302<br>Roboz et al, Blood 20213<br>Phase 3, RCT, N=447<br>Konopleva et al,<br>Blood Advances 2022<br>mOS<br>Historical IC benchmark ≈ 6 mos.2<br>2 Historical OS reflects control arms<br>Note: patient outcomes for IC eligible populations often vary depending upon patient and disease characteristics<br>3 Control group includes patients on MEC and FLAG-IDA 4 All patients in this analysis received MEC<br>Control<br>Investigational |
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| Duration of Follow-Up and Outcomes in Key AML Trials<br>16<br>Sanofi – Clofarabine<br>(CLASSIC I Trial); mOS 6.6 v. 6.3 mo.<br>Roche – Idasanutlin<br>(MIRROS Trial); mOS 6.8 v. 7.7 mo.<br>Astellas - XOSPATA (Gilteritinib) – ADMIRAL Trial; mOS 9.3 v. 5.6 mo.<br>Jazz - VYXEOS (CPX-351); mOS 9.5 v. 5.9 mo.<br>6.2 mos<br>6.7 mos<br>17.8 mos<br>20.7 mos<br>Succeeded on OS<br>Failed on OS<br>Uproleselan 301 Trial<br>Current<br>projected<br>events trigger<br>1H 2024 ≥25 months median follow-up (as of March 2023)<br>Clavis – Elacytarabine (CLAVELA<br>Trial ); mOS 3.5 v. 3.3 mo.<br>Sunesis – Vosaroxin<br>(VALOR Trial); mOS 7.5 v. 6.1 mo.<br><6 mos*<br>~6 mos*<br>R/R<br>N=388<br>R/R<br>N=447<br>R/R<br>N~320<br>R/R<br>N=711<br>R/R<br>N=381<br>FLT3+ R/R<br>N=371<br>sAML<br>N=309<br>* Median follow-up stated at time of event trigger and derived from protocol and/ or final results as it was not included in the publication |
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| Follow-Up Versus Outcome in Select AML Trials<br>17<br>Trial Median<br>Survival (mos)<br>Enrollment<br>(mos)<br>Median Follow-up<br>(mos)<br>Enrolled<br>(N) Events OS HR P-value<br>CLAVELA 3.5 vs 3.3 mos 28 < 6 381 302 0.97 0.96<br>VALOR 7.5 vs 6.1 mos 33 ~ 6 711 562 0.87 0.0610<br>CLASSIC I 6.6 vs 6.3 mos 38 6.2 320 258 1.00 1.00<br>MIRROS 6.8 vs 7.7 mos 48.5 6.7 436 296 1.09 0.52<br>VIALE-A 15 vs 10 mos 27 20.5 433 270 0.66 < 0.001<br>VYXEOS 9.6 vs 6.0 mos ~24 20.7 309 236 0.69 0.003<br>ADMIRAL 9.3 vs 5.6 mos 28 17.8 371 258 0.64 < 0.001<br>Uproleselan TBD 36 >25 (Mar 23) 388 295 TBD TBD |
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| UPROLESELAN<br>Potential Foundational Backbone Across Spectrum in AML<br>1. SEER 2021 Statistics<br>• Improve achievement / depth of remission<br>• Extend overall survival<br>• Mitigate chemotherapy-related toxicity<br>UPROLESELAN VALUE<br>PROPOSITION<br>~12,000 “Fit” patients eligible for intensive chemotherapy ~8,000 “Unfit”<br>~20,240 Newly Diagnosed AML Patients in the U.S.1<br>NEWLY DIAGNOSED, ELDERLY AML<br>NCI-Sponsored Phase 2/3<br>Combination of Uproleselan + 7&3<br>12K<br>PATIENTS/YEAR<br>RELAPSED / REFRACTORY AML<br>GMI-Sponsored Phase 3<br>Combination of Uproleselan + MEC/FAI<br>8.5K<br>PATIENTS/YEAR<br>Recent<br>Venetoclax<br>approval<br>8K<br>PATIENTS/YEAR<br>18 |
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| UPROLESELAN<br>NCI / Alliance Frontline “Fit” AML Phase 2/3 Study Design<br>KEY ELIGIBILITY<br>CRITERIA<br>• ≥ 60 years in age<br>• AML and fit for 7+3<br>• Includes sAML<br>• Excludes FLT3+ 7&3<br>(n=131) IDAC<br>Upro plus 7&3<br>(n=131) Upro plus IDAC<br>Induction<br>(1 Cycle)<br>Consolidation<br>(Up to 3 Cycles)<br>Follow-Up for EFS &<br>Phase 3 Go/No-Go<br>7&3: Cytarabine and daunorubicin<br>IDAC: Intermediate-dose cytarabine<br>Randomize<br>1:1<br>Phase 2 portion fully enrolled in December 2021<br>19 |
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| UPROLESELAN<br>HMA Resistance is Driven by E-selectin, Broken by Uproleselan<br>*SOHO September 2020<br>Control 5-azacytidine 5-azacytidine → GMI-1271<br>KG1 AML cells were incubated for 96 hours in the absence or presence of 100 nM<br>5-azacytidine, labeled with calcein and allowed to adhere to E-selectin coated<br>plates (control and 5-azacytidine above). After 45 minutes of adhesion,<br>Uproleselan was added to the wells and fluorescence determined after 30 minutes<br>(5-azacytidine → Uproleselan above).<br>UPROLESELAN INHIBITS BINDING OF BLASTS<br>358<br>561<br>55 0<br>100<br>200<br>300<br>400<br>500<br>600<br>700<br>Fluorescence<br>20 |
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| UPROLESELAN / VENETOCLAX / HMA COMBINATION<br>Significantly Reduces Leukemia Burden*<br>*ASH December 2020<br>AML-PDX FROM A VENETOCLAX / HMA RESISTANT PATIENT<br>Venetoclax<br>Uproleselan<br>Ven+5Aza<br>Combination<br>21 |
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| ASH 2022: First Clinical Uproleselan Data Generated Outside of<br>GlycoMimetics-Sponsored Trials<br>22<br>Uproleselan data from two investigator-sponsored trials presented at ASH in December 2022<br>A Phase I Study of Uproleselan Combined with<br>Azacitidine and Venetoclax for the Treatment of Older<br>or Unfit Patients with Treatment Naïve Acute Myeloid<br>Leukemia<br>Brian Jonas, M.D., Ph.D., of the University of California, Davis<br>Publication Number: 2764<br>Encouraging safety and evidence of disease activity<br>• 8 evaluable patients with poor prognosis<br>• 6/8 (75%) were ELN 2017 adverse risk disease<br>• 3/8 (38%) had complex cytogenetics<br>• Data outcomes<br>• 6/8 (75%) CR/CRi<br>• 5/8 (63%) full CR<br>• 1/8 (13%) CRi<br>• 5/8 (63%) CR/CRi responses occurred with<br>cycle 1<br>• 4 CR/CRi MFC MRD negative<br>• 50% overall MRD negative rate<br>• 67% among CR/CRi responders<br>Uproleselan added to Cladribine Plus Low Dose<br>Cytarabine (LDAC) in Patients with Treated Secondary<br>Acute Myeloid Leukemia (TS-AML)<br>Emmanuel Almanza-Huante, M.D.<br>Publication Number: 1448<br>62% ORR in very high-risk patient population<br>• 9 evaluable patients<br>• All patients had unfavorable features by ELN 2017<br>• Data outcomes<br>• Combination of Cladribine + LDAC with uproleselan overall<br>well tolerated with few treatment-related AEs<br>• No dose-limiting toxicities observed on dose levels -1 or 1 |
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| Treatment of Acute Vaso-occlusive Crisis (VOC) in<br>Patients with Sickle Cell Disease<br>GMI-1687 |
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| Significant Unmet Need Remains in SCD<br>24<br>Prevalence<br>~100K<br>SCD patients in the US<br>~1 in 365<br>Black Americans affected at birth<br>25-30yr<br>Reduction in average life<br>expectancy<br>Symptoms<br>Vaso-occlusive crises (VOCs),<br>also referred to as pain crises,<br>are the clinical hallmark of SCD<br>>90%<br>of hospitalizations due to VOC<br>↑Risk of<br>Stroke<br>Acute Chest Syndrome<br>Renal failure<br>Current Treatments<br><1<br>VOC improvement per yr (From<br>3.19 to 2.77 VOCs/yr)<br>Centers for Disease Control and Prevention. Sickle cell disease (SCD) accessed May 4, 2021 Lanzkron S, et al. Pub Health Rep.<br>2013;128:110-116. Ballas, S.K. American Journal of Hematology DOI: 10.1002/ajh.21443. Centers for Disease Control and<br>Prevention. Sickle cell disease (SCD) accessed Aug, 2022; Sins JWR, et al.,. Blood Adv. 2017;1(19):1598–616<br>~1<br>VOC improvement per yr (From 3<br>to 1.6 VOCs/yr)<br>Voxeletor<br>Crizanlizumab-tmca |
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| Even with Prophylactic and Gene Therapy Approaches, Acute<br>VOC Will Remain A Significant Unmet Medical Need<br>25<br>Prophylactic<br>Therapies<br>(Approved & Selected In<br>Development)<br>220,000 – 450,000 VOCs/year<br>(in the era of prophylactic therapies)<br>Dampier et al. 2017 American Society of Hematology Annual Meeting. Abstract# 4660.<br>N Engl J Med 2019; 381:509-51; N Engl J Med 2017; 376:429-439<br>SUBCLINICAL<br>Ongoing, Silent VOCs<br>0-1 VOC<br>CLINICALLY<br>VISIBLE VOCs<br>2-5 VOCs<br>6+ VOCs<br>20%<br>50%<br>30%<br>30% reduction in VOC<br>(ASH 2021 Real World Data)<br>50% reduction in VOC<br>45% reduction in VOC<br>(SUSTAIN Study)<br>Gene Therapies<br>(Selected In Development)<br>E-selectin mAb<br>(Phase 1)<br>P-selectin mAb<br>(Likely 45% reduction in VOC)<br>PF-07209326 (Pfizer)<br>Vertex/CRISPR<br>EXA-CEL<br>EDITAS<br>EDIT-301<br>On-Demand Acute<br>VOC Therapies<br>(Selected In Development)<br>Intellia<br>BCL11A<br>Sangamo<br>BCL11A<br>GMI-1687 E-selectin antagonist<br>Use impacted by disparities in access to care,<br>socioeconomic factors and toxicity (e.g. HU-myelosuppression; Advakeo – liver pathologies)<br>Voxeletor Hydroxyurea<br>Crizanlizumab-tmca Inclacumab |
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| For patients treated within<br>first quartile of treatment<br>timeliness (<26.4hrs), a<br>meaningful, statistically<br>significant benefit was seen<br>across study endpoints<br>RESET<br>Early Intervention Resulted In Clinical Benefit<br>26<br>TTRD = time to readiness for discharge; TTD = time to discharge;<br>TTDIVO = time to discontinuation of IV opioids; CIVO = cumulative IV opioid use<br>T. Wun, ASH 2020 |
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| 27 1 Morikis et al, Frontiers in Immunology, April 2021, Vol. 12, Article 663886<br>GMI-1687 leverages years of research to empower patients to take control of their disease<br>Lessons Learned GMI-1687<br>E-selectin drives acute VOC1 • Fast-acting, small molecule inhibitor against E-selectin to block endothelial activation<br>and multicellular adhesion that are the foundation of acute VOC<br>• >500-fold more potent than rivipansel<br>Treatment early during VOC<br>is critical<br>• Patients (or caregiver) can potentially self-administer GMI-1687 via an autoinjector<br>upon recognition of an acute VOC episode<br>• 100% bioavailable following subcutaneous administration<br>Too little, too late - must give full<br>doses<br>• Optimize dose and regimen based on reductions in sE-selectin – drive and sustain<br>• Agreed to as part of FDA Pre-IND Meeting<br>Potentially changing the<br>treatment paradigm to<br>convenient, early, on-demand<br>disease modifying therapy<br>FDA “Safe to Proceed” Clearance for IND in June 2022 |
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| Potential Treatments in Oncology, Inflammation and Fibrosis<br>GALECTIN-3 INHIBITORS |
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| • Target: Galectin-3 carbohydrate-binding protein<br>• GMI-2093 development candidate<br>• Relevance: Central role in fibrosis and cancer<br>• Inflammation, aberrant cell activation/proliferation, fibrogenesis<br>• Blockade may prevent/reverse fibrosis following organ damage<br>• Antifibrotic/antitumor activity in various disease models<br>• Chemistry: Rationally designed with proprietary platform<br>• Differentiation: Compounds have high binding affinity and specificity for<br>Galectin-3<br>• Orally bioavailable<br>The Promise of Targeting<br>The Galectins:<br>Modulating The Immune<br>And Inflammatory<br>Response to Cancer and<br>Fibrosis<br>GALECTIN-3 ANTAGONISTS<br>Highly Potent and Highly Differentiated<br>29 |
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| Pioneers in glycobiology-based therapies for cancers and other rare diseases<br>Strong Foundation with Near-Term Catalysts and Broad Pipeline<br>Uproleselan: Multiple<br>Late-Stage Clinical Trials<br>• Fully enrolled Phase 3 trial in<br>R/R AML (n=388), OS events<br>trigger currently projected for<br>~1H-2024<br>• Fully enrolled Phase 2 trial in<br>front-line AML (n=267) ongoing,<br>NCI-sponsored<br>• Ongoing ISTs in other AML<br>populations. Preliminary data<br>presented at ASH 2022<br>• Novel MOA potential broad<br>utility with Breakthrough<br>Therapy, Fast Track, and<br>Orphan designations<br>30<br>Broad Early-Stage<br>Pipeline<br>• Novel small molecules inhibit<br>carbohydrate signaling<br>• GMI-1687<br>• Targets sickle cell pain crises<br>• Cleared FDA 30-day IND<br>review<br>• GMI-2093<br>• Targeting fibrotic diseases<br>• First oral Galectin-3<br>antagonist<br>Targeted Operational<br>Execution<br>• Recent Key Leadership Hires<br> purpose-driven biotechnology<br>team<br>• Deep expertise in regulatory,<br>medical and commercialization<br>across hem/onc therapies |
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