8-K
CRESCENT BIOPHARMA, INC. (CBIO)
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): May 6, 2024
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 2.02 Results of Operations and Financial Condition.
On May 6, 2024, GlycoMimetics, Inc. (the “Company”) issued a press release announcing, in addition to the information described in Item 7.01 below, its financial results for the first quarter ended March 31, 2024. A copy of this press release is furnished herewith as Exhibit 99.1 to this Current Report and is incorporated herein by reference.
In accordance with General Instruction B.2. of Form 8-K, the information in this Item 2.02, and Exhibit 99.1 hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any of the Company’s filings under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing, except as expressly set forth by specific reference in such a filing.
Item 7.01.Regulation FD Disclosure.
Topline Results from Phase 3 Clinical Trial
On May 6, 2024, the Company issued a press release announcing, in addition to the information described in Item 2.02 above, topline results from its pivotal Phase 3 clinical trial of its drug candidate uproleselan in patients with relapsed/refectory acute myeloid leukemia. A copy of this press release is furnished herewith as Exhibit 99.1 to this Current Report and is incorporated herein by reference.
Updated Corporate Presentation
A copy of a slide presentation that the Company plans to use for anticipated investor meetings is attached to this Current Report as Exhibit 99.2 and is incorporated herein solely for purposes of this Item 7.01 disclosure.
The information in this Item 7.01, including Exhibits 99.1 and 99.2 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any of the Company’s filings under the Securities Act or the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing.
Item 9.01Financial Statements and Exhibits
(d) Exhibits
| 9, | ||
|---|---|---|
| Exhibit | **** | |
| Number | **** | Exhibit Description |
| 99.1 | Press Release, dated May 6, 2024, “GlycoMimetics Announces Results of Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)” | |
| 99.2 | | GlycoMimetics, Inc. Corporate Presentation, May 6, 2024 |
| 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: May 6, 2024 | | Brian M. Hahn<br>Senior Vice President and Chief Financial Officer |
3
Exhibit 99.1
GlycoMimetics Announces Results of Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
| ● | Study of uproleselan combined with chemotherapy did not meet its primary endpoint of overall survival in the intent to treat population |
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| ● | Adverse events were consistent with known side effect profiles of chemotherapy used in the study |
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| ● | Comprehensive data analysis with medical, statistical, and regulatory experts underway and will be shared as appropriate; company will submit results for presentation at an upcoming medical meeting |
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| ● | National Cancer Institute (NCI) Phase 2/3 study in newly diagnosed AML patients remains ongoing |
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| ● | Conference call and webcast to be hosted today, May 6, 2024, at 8:30 a.m. ET. |
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ROCKVILLE, Md.--(BUSINESS WIRE) – May 6, 2024-- GlycoMimetics, Inc. (Nasdaq: GLYC), a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, today announced topline results from its Phase 3 global pivotal study of uproleselan in 388 patients with R/R AML. In the study, uproleselan combined with chemotherapy did not achieve a statistically significant improvement in overall survival in the intent to treat population versus chemotherapy alone.
Patients treated with uproleselan had a median overall survival of 13 months, compared to 12.3 months in the placebo arm. Adverse events were consistent with known side effect profiles of chemotherapy used in the study.
“While the outcome of our Phase 3 study in R/R AML is not what we hoped, we wish to thank the investigators, the participating patients and their families for their dedication to this large, well-controlled randomized study,” said Harout Semerjian, Chief Executive Officer of GlycoMimetics. “We are thoroughly analyzing the data in collaboration with medical, statistical and regulatory experts and are committed to submitting a comprehensive data analysis for presentation at an upcoming medical meeting.”
The randomized, double-blind, placebo-controlled Phase 3 clinical study evaluated uproleselan in combination with MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine and idarubicin) in patients with R/R AML. Patients received either uproleselan or placebo for 8 days over 1 cycle of an induction and, if applicable, up to 3 cycles of consolidation. The primary endpoint of the study was overall survival without censoring for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission rate and remission rate. A total of 388 patients across 70 sites in nine countries were randomized 1:1 between treatment and placebo arms.
The NCI and the Alliance for Clinical Trials in Oncology are conducting an adaptive Phase 2/3 study of uproleselan in adults with newly diagnosed AML who are 60 years or older and fit for intensive chemotherapy. The randomized, controlled study is evaluating the addition of uproleselan to a standard cytarabine/daunorubicin regimen (7+3) versus chemotherapy alone. The Phase 2 portion of the study completed enrollment of 267 patients in December 2021. Results of the pre-planned Phase 2 event free survival interim analysis will be reported when available.
First Quarter 2024 Preliminary Financial Results
Today, the company also disclosed its preliminary financial results for the first quarter of 2024.
| ● | Cash position: As of March 31, 2024, GlycoMimetics had cash and cash equivalents of $31.3 million, compared to $41.8 million as of December 31, 2023. |
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| ● | R&D Expenses: The company’s research and development expenses increased to $6.0 million for the quarter ended March 31, 2024, as compared to $5.4 million for the same period in 2023. These increases were due to raw material acquisition costs for future manufacturing batches. |
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| ● | G&A Expenses: The company’s general and administrative expenses decreased to $5.1 million for the quarter ended March 31, 2024, compared to $5.5 million for the same period in 2023. The decrease was due to lower personnel-related and external consulting expenses. |
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| ● | Shares Outstanding: Shares of common stock outstanding as of March 31, 2024, were 64,450,835. |
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Conference Call Information
The company will host a conference call and webcast today at 8:30 a.m. ET. To access the call by phone, please go to this registration link and you will be provided with dial in details. Participants are encouraged to connect 15 minutes in advance of the scheduled start time.
A live webcast of the call will be available on the “Investors” tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.
Please note this call will replace the previously announced First Quarter 2024 Financial Results call scheduled for May 9, 2024 at 8:30 a.m. ET.
About AML
AML is the most common acute leukemia in adults. A cancer of the bone marrow, nearly 21,000 people in the United States are diagnosed with AML each year. Despite the availability of multiple treatments, disease prognosis is poor, and new treatment options are needed to improve outcomes. Newly diagnosed AML has the lowest 5-year survival rate of all leukemias at 31.7%. The five-year survival rate for people with relapsed/refractory disease is only 10%.
About Uproleselan
Discovered and developed by GlycoMimetics, uproleselan (yoo’ pro le’se lan) is an investigational, first-in-class E-selectin antagonist. GlycoMimetics has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration (FDA) and Breakthrough Therapy designation from the Chinese National Medical Products Administration for uproleselan as a potential treatment for adult AML patients with relapsed or refractory disease. E-selectin is a leukocyte adhesion molecule constitutively expressed on endothelial cells of the vasculature and bone marrow. In AML, there is evidence that E-selectin–ligand interaction between endothelial cells in the protective niche of the Bone Marrow microEnvironment (BME) and leukemic stem cells and blasts promotes leukemic cell survival and hides them from AML therapies. Uproleselan is designed to disrupt E-selectin binding and prevent leukemic myeloid cells using the protective niche of the BME.
About GlycoMimetics, Inc.
GlycoMimetics is a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers, including AML, and for inflammatory diseases. The company’s scientific approach is based on an understanding of the role that carbohydrates play in cell recognition. Its specialized chemistry platform is being deployed to discover small molecule drugs, known as glycomimetics, that alter carbohydrate-mediated recognition in diverse disease states, including cancers and inflammation. GlycoMimetics is leveraging its differentiated expertise with this scientific approach in order to advance its pipeline of wholly owned drug candidates. The company’s goal is to develop transformative therapies for diseases with high unmet medical need. GlycoMimetics is headquartered in Rockville, MD in the BioHealth Capital Region. Learn more at www.glycomimetics.com.
Forward-Looking Statements
This press release contains forward-looking statements. These forward-looking statements may include, but are not limited to, statements regarding the conduct of, and timing for analysis and presentation of data from, clinical trials; potential development and regulatory activities; and the potential benefits and impact of uproleselan. Actual results may differ materially from those described in these forward-looking statements. For a further description of the risks associated with these 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 (SEC) on March 27, 2024, and other filings GlycoMimetics makes with the SEC from time to time. Forward-looking statements speak only as of the date of this release, and GlycoMimetics undertakes no obligation to update or revise these statements, except as may be required by law.
Investor Contact:
Argot Partners
Leo Vartorella
212-600-1902
Glycomimetics@argotpartners.com
Exhibit 99.2
| Transforming Lives<br>Glycobiology-based Therapeutics<br>May 2024 | NASDAQ: GLYC | |
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| 2<br>Forward-Looking Statements<br>• To the extent thatstatements contained in this presentation are not descriptions of historical facts,they are forward-looking<br>statementsreflecting the current beliefs and expectations of the management of GlycoMimetics, Inc. (“GlycoMimetics,” “we,”<br>“us,” or “our”). Forward-looking statements contained in this presentationmay include, but are not limited to: (i) the expected<br>or projected timing of events, data readout and data analysisfrom clinical trials; (ii) the planned or potential clinical<br>development and potential indications, benefits and impact of our drug candidates, including uproleselan and GMI-1687;(iii)<br>the timing of receipt of clinical data; (iv) the potentialsafety, efficacy or clinical utility of our drug candidates;(v) the size of<br>patient populations targeted by drug candidateswe or our collaboratorsdevelop; (vi) the likelihood and timing of regulatory<br>filings, and plans for interactionswith regulatory authorities; (vii) our business and product development strategies, including<br>our cash needs and expected cash runway; and (viii) any otherstatement containing terminology such as “may,” “will,”<br>“should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “intends,” or “continue,” or the<br>negative of these terms or other comparable terminology.<br>• Forward-looking statements are subject to known and unknown risks, uncertainties, and other factorsthat may cause our or<br>our industry’s actualresults, levels of activity, performance, or achievements to be materially different from those discussed,<br>implied or otherwise anticipated by such statements. You are cautioned not to place undue reliance on such forward-looking<br>statements, which are current only as of the date of this presentation. Examples of risks, uncertainties and factorsthatmay<br>cause differences between our expectations and actual results include unexpected safety or efficacy data, unexpected side<br>effectsobserved during preclinical studies or in clinical trials, whether results of early clinical trials will be indicative of results<br>from later clinical trials, changesin expected or existing competition or additional market research that may cause our<br>expectations about market opportunity to change, changes in the regulatory environment for our drug candidates, failure of<br>our collaboratorsto support or advance our collaborations or drug candidates, our need for future capital,the inability to<br>adequately protect our intellectual property, and becoming a party to litigation or other disputes. For a further description of<br>the risks associatedwith forward-looking statements, as well as other risks facingGlycoMimetics, please see the risk factors<br>described in the Company’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on March 27,<br>2024, as well as other reports we file with the U.S. Securities and Exchange Commission from time to time, including those<br>factorsdiscussed under the caption “Risk Factors” in such filings. Forward-looking statementsspeak only as of the date of this<br>presentation, and GlycoMimetics undertakes no obligation to update or revise these statements, except as may be required by<br>law. | ||
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| • Phase 3 trial in R/R AML (n=388), topline<br>results announcedin Q2 2024<br>• Fully enrolled Phase 2 trial in front-line<br>AML (n=267) ongoing,NCI-sponsored<br>• Ongoing IITs in other AML populations.<br>Preliminary data presented at ASH<br>2022/2023<br>• Novel MOA/first-in-class → potential<br>broad utility with Breakthrough Therapy,<br>Fast Track, and Orphan designations<br>• Novel small molecules inhibit carbohydrate<br>signaling<br>• Potential application in multiple<br>inflammatory diseases<br>• GMI-1687<br>• Phase 1a trial in healthy volunteers<br>completed<br>• Initial indication: treatment of sickle cell<br>disease (SCD) vaso-occlusive crisis<br>(VOC)<br>• Being developed for self-administration at<br>time of VOC<br>• Galectins<br>• Targeting fibrotic diseases<br>• First oral Galectin-3antagonist<br>• Updating uproleselan plans and evaluating<br>financial guidance<br>Near-Term Catalysts and Promising, Glycobiology-based Pipeline<br>3<br>Uproleselan: Multiple<br>Late-Stage Clinical Trials<br>Promising<br>Early-Stage Pipeline<br>Targeted<br>Operational Execution | ||
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| A Portfolio of Promising Product Candidates<br>*Partnered with Apollomics in Greater China 4<br>Program Therapeutic Area Discovery Preclinical Phase 1 Phase 2 Phase 3 Market<br>SELECTINS<br>Relapsed / RefractoryAML Topline resultsannounced in Q2 2024<br>UPROLESELAN<br>(GMI-1271)* Newly Diagnosed“Fit” AML Fully enrolled 267 patients Dec 2021<br>Relapsed / Refractory<br>PediatricAML Ph1 by NCI do sed 1st patient<br>GMI-1687* SCD Vaso-occlusive Events<br>and Inflammatory diseases Ph1a completed<br>GALECTINS<br>GMI-2093 Fibrosis and Oncology Lead declared March 2022 | ||
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| Breakthrough Therapy<br>Designation in AML<br>Uproleselan (GMI-1271) | ||
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| 1. SEER 2022 Statistics 6<br>Significant Unmet Medical Need In AML1<br>All Other<br>Leukemias<br>20,380<br>New AML Cases<br>21,450 New<br>Cases<br>All Other<br>Leukemias<br>American Cancer Society. Cancer Facts and Figures 2023. Atlanta: American Cancer Society; 2023. Accessed<br>May 10, 2023. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf.<br>ESTIMATED NEW CASES (2023)<br>70.6<br>88.0<br>71.3<br>31.7<br>100<br>90<br>80<br>70<br>60<br>50<br>40<br>30<br>20<br>10<br>0<br>CML CLL ALL AML<br>Survival Rate<br>%<br>5-YEAR RELATIVE SURVIVAL (2013 – 2019)1 | ||
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| Uproleselan: First-in-Class E-Selectin Antagonist for AML<br>7<br>E-selectin:<br>✓ Leukocyte adhesion molecule<br>constitutively expressed on marrow<br>endothelial cells, also inducibly<br>expressed throughout vasculature by<br>innate inflammatory mediators<br>✓ Up-regulated by AML blasts via<br>secreted inflammatory mediators, such<br>as TNF-alpha and IL1-beta<br>CD62E<br>E-selectin/E-selectin Ligand Interaction:<br>✓ Enables AML blast and leukemia stem<br>cell sequestration in bone marrow<br>✓ Activates pro-survival NF-kB pathways<br>✓ E-selectin ligand sLex up-regulated on<br>AML cells via multiple distinct drug<br>resistance mechanisms<br>Uproleselan, a First-in-class<br>E-Selectin Antagonist:<br>✓ Releases AML blasts and leukemic<br>stem cells from vascular sequestration,<br>agnostic to AML mutational status<br>✓ Disrupts NF-kB mediated<br>chemoresistance pathways<br>✓ Potential broad utility acrossAML | ||
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| E-selectin ligand expression<br>• Detectable in every patient tested<br>• Higher levels in R/R patients achieving CR/CRi, MRD- and<br>prolonged median OS<br>8<br>Phase 1/2 Results in R/R and Newly Diagnosed AML Patients<br>0%<br>10%<br>20%<br>30%<br>R/R AML (N=16) Newly Dx AML (N=9)<br>Percent MRD Negative<br>80%<br>70%<br>60%<br>50%<br>40%<br>Results Published in<br>Blood February ‘22<br>AML population CR CR/CRi Median<br>O/S<br>MRD-negative<br>Relapsed /<br>Refractory<br>(n = 54)<br>35% 41% 8.8 mos 69%<br>Newly Diagnosed<br>(n = 25) >=60yrs 52% 72% 12.6 mos 55% | ||
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| 1. National Cancer Institute SEER Program. Cancer Stat Facts: Acute Myeloid Leukemia. 9<br>Potential Foundational Backbone Across Spectrum in AML<br>• Improve achievement /<br>depth of remission<br>• Extend overall survival<br>• Mitigate chemotherapy-related toxicity<br>Uproleselan Value<br>Proposition<br>~20,380 Newly Diagnosed AML Patients in the U.S.1<br>~12K “Fit” ~8K Unfit”<br>>8K<br>PATIENTS/YEAR<br>NEWLY DIAGNOSED,<br>ELDERLY AML<br>NCI-Sponsored Phase 2/3<br>Combinationof Uproleselan + 7&3<br>8.5K<br>PATIENTS/YEAR<br>RELAPSED /<br>REFRACTORY AML<br>GLYC-Sponsored Phase 3<br>Combination of Uproleselan + MEC/FAI<br>8K<br>PATIENTS/YEAR<br>Recent venetoclax<br>approval<br>Patients eligible for intensive<br>chemotherapy<br>+ | ||
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| Uproleselan Phase 1/2 overall survival by HSCT<br>• N=54 R/R AML patients at 10 mg/kg RP2D<br>• Overall MRD-negative: 56% 1L, 69% R/R<br>• 10 longest survivors all MRD-negative<br>Meta-analysis of 81 studies (N >11,000)<br>• MRD negativity favorably prognostic for survival<br>• Effect independent of age, subtype, timing, method<br>MRD Negativity and HSCT Both Favorably Prognostic<br>11<br>Overall Survival by MRD status1 Overall Survival by HSCT2<br>1. Short, et al. JAMA Oncology 2020 6(12): 1890-1899; 2. DeAngelo et al, Blood 2022 139(8):1135-1146. | ||
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| 12<br>Primary endpoint of overall survival was not achieved<br>Median overall survival: 13 months (uproleselan) vs. 12.3 months (placebo arm)<br>Adverse events consistent with known side effect profiles of chemotherapy used in the study<br>Comprehensive analysis ongoing; plan to submit for presentation at an upcoming medical meeting<br>Placebo plus<br>MEC or FAI<br>(n=190)<br>Placebo<br>plus HiDAC<br>or IDAC<br>Upro plus MEC<br>or FAI<br>(n=190)<br>Upro<br>plus HiDAC<br>or IDAC<br>1:1 Randomization (n=388)<br>(stratifiedby age, disease status<br>and backbone chemo)<br>Induction<br>(1 Cycle)<br>Consolidation<br>(Up to 3 Cycles)<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>Follow-Up for<br>Overall Survival<br>not censored for<br>transplant.<br>KEY ELIGIBILITY<br>CRITERIA<br>• ≥18 and ≤75 years in age<br>• AML – primary refractory or<br>first or second relapse<br>• Eligible for intensive<br>salvage treatment<br>• <1 prior HSCT<br>Phase 3 Global Pivotal Study of Uproleselan in R/R AML | ||
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| 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># Subjects Randomized<br># Activated Sites<br># Activated Sites # Subjects Randomized<br>FPFV<br>LPFV<br>Trial GMI-1271-301 Enrollment<br>13<br>• 380 patients<br>planned,<br>388 patients<br>enrolled<br>• 12 patients<br>(3%) lost to<br>follow- up/<br>withdrew<br>consent | ||
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| 14<br>Phase 3 Patient Characteristics Broadly Similar to Phase 2<br>301 Study | N=388 201 Study | N=66<br>Relapsed/Refractory Patient Demographics<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 56 (22%) 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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| • June 2023 FDA cleared Phase 3 time-based OS analysis after defined cutoff<br>if 295 events not reached by that date<br>• Clinically mature data in Q2 2024<br>reflects > 3 years median follow-up<br>and > 2 years post-transplant follow-up for the substantial majority of<br>remaining patients that received stem<br>cell transplants<br>• After 2 years post-transplant, AML<br>relapse becomes infrequent<br>15<br>Bolon YT, Atshan R, Allbee-Johnson M, Estrada-Merly N, Lee SJ.Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides (slide<br>79), 2022.<br>Time-Based Analysis Triggered with a March 31, 2024 Data Cutoff | ||
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| 10% 20% 30% 50% 60% 70%<br>Phase III, RCT<br>Prospective cohort study<br>Retrospective study<br>Phase I or II study<br>18mo<br>16mo<br>14mo<br>12mo<br>10mo<br>8mo<br>6mo<br>4mo<br>2mo<br>0% 40%<br>HSCT Rates<br>Median OS<br>Single center<br>(Italy); N=55; 51y<br>Single center<br>(Germany); N=132;<br>52y<br>Intensive Chemotherapy (IC) in R/R AML<br>16<br>NOTES<br>Scatter plot is not exhaustivebut includes trials<br>with similar populations to Phase 3 trial of<br>uproleselan.<br>Outcomes with intensive chemotherapymay be<br>heavily impactedby patient. characteristics<br>including age, ELN risk, disease status and<br>prior therapy, and that patient numbers are<br>small for some of the data shown.<br>Size of bubble is proportional to sample size.<br>Typical ~6-7 months mOS<br>and HSCT rates ~25-30% | ||
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| 3.3<br>6.3<br>5.4<br>6.8<br>7.7<br>5.1 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>Lintuzumab + MEC vs. MEC Elacytarabine vs. Inv. Choice IDAC +clofarabine vs IDAC<br>Phase 3, RCT, N=320<br>Faderl et al, JCO 2011<br>Upro Phase 1/ 2 ≈ 8.8 mos<br>Follow-up period cutoff at 9.7 mons to focus on Phase 3.<br>15 patients (28%) in RP2D populationwere censored for OS<br>17<br>Various salvage regimens<br>retrospectivereview<br>N=850+ 4, Megias-Vericat et al,<br>Ann Hematol 2018**<br>Guadecitadine vs Inv. choice<br>Phase 3, RCT, N=302<br>Roboz et al, Blood 2021*<br>Idasanutlin + IDAC vs. IDAC<br>Phase 3, RCT, N=447 (All<br>comer ITT)<br>Konopleva et al,<br>Blood Advances 2022<br>mOS<br>14<br>Historical Intensive Chemotherapy benchmarks for mOS are ~6 months<br>Phase 3, RCT, N=191<br>Feldmanet al, JCO 2005<br>Phase 3, RCT, N=381<br>Roboz et al, JCO 2014<br>Historical IC benchmark ≈ 6 mos<br>Historical OS reflectscontrol arms<br>Note: patient outcomes for IC eligiblepopulations often vary depending upon patient and disease characteristics<br>*Control group includes patients on MEC and FLAG-IDA<br>** 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>*Median follow-up at time of event trigger for CLAVELA and VALOR estimated from protocol and/or final results as it was not included in the publication 18<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>Topline<br>results<br>reported<br>in Q2 2024<br>37 months median follow-up (as of March 2024)<br>Clavis – Elacytarabine (CLAVELA<br>Trial ); mOS 3.5 v. 3.3 mo.<br>Sunesis – Vosaroxin<br>(VALOR Trial); mOS7.5 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 | ||
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| Follow-Up Versus Outcome in Select AML Trials<br>19<br>Trial Median Survival (mos) Median<br>Follow-up (mos) Enrolled (N) Planned Events OS HR P-value<br>CLAVELA 3.5 vs 3.3 mos < 6* 381 302 0.97 0.96<br>VALOR 7.5 vs 6.1 mos ~ 6* 711 562 0.87 0.0610<br>CLASSIC I 6.6 vs 6.3 mos 6.2 320 258 1.00 1.00<br>MIRROS 6.8 vs 7.7 mos 6.7 436 296 1.09 0.52<br>VIALE-A 15 vs 10 mos 20.5 433 270 0.66 < 0.001<br>VYXEOS 9.6 vs 6.0 mos 20.7 309 236 0.69 0.003<br>ADMIRAL 9.3 vs 5.6 mos 17.8 371 258 0.64 < 0.001<br>Uproleselan 13 vs.12.3 mos 37 (Mar ‘24) 388 295 TBD TBD<br>*Median follow-up at time of event trigger for CLAVELA and VALOR estimated from protocol and/or final results as it was not included in the publication | ||
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| 1. National Cancer Institute SEER Program. Cancer Stat Facts: Acute Myeloid Leukemia. 20<br>Potential Foundational Backbone Across Spectrum in AML<br>• Improve achievement /<br>depth of remission<br>• Extend overall survival<br>• Mitigate chemotherapy-related toxicity<br>Uproleselan Value<br>Proposition<br>~20,380 Newly Diagnosed AML Patients in the U.S.1<br>~12K “Fit” ~8K Unfit”<br>>8K<br>PATIENTS/YEAR<br>NEWLY DIAGNOSED,<br>ELDERLY AML<br>NCI-Sponsored Phase 2/3<br>Combinationof Uproleselan + 7&3<br>8.5K<br>PATIENTS/YEAR<br>RELAPSED /<br>REFRACTORY AML<br>GLYC-Sponsored Phase 3<br>Combination of Uproleselan + MEC/FAI<br>8K<br>PATIENTS/YEAR<br>Recent venetoclax<br>approval<br>Patients eligible for intensive<br>chemotherapy<br>+ | ||
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| NCI / Alliance Frontline “Fit” AML Phase 2/3 Trial Design<br>21<br>Enrollment of 267 Patients in Phase 2 Portion Completed in December 2021<br>KEY ELIGIBILITY<br>CRITERIA<br>• ≥ 60 years in age<br>• AML and fit for 7+3<br>• Includes sAML<br>• Excludes FLT3+<br>7&3<br>(n=131) IDAC<br>Upro plus 7&3<br>(n=131)<br>Upro plus<br>IDAC<br>Induction<br>(1 Cycle)<br>Consolidation<br>(Up to 3 Cycles)<br>Follow-Up<br>for EFS & Phase 3<br>Go/No-Go<br>7&3: Cytarabine and daunorubicin<br>IDAC: Intermediate-dose cytarabine<br>Randomize<br>1:1 | ||
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| HMA Resistance is Driven by E-selectin, Broken by Uproleselan<br>22<br>Targeting E-selection with GMI-1271 Overcomes Microenvironment-mediated Resistance to Venetoclax/HMA Therapy K.H. Chang, M. Muftuoglu, W.Zhang, M. Basyal,<br>L. Ostermann, W.E.Fogler, J.L. Magnani, M. Andreeff, 2020<br>Control 5-azacytidine 5-azacytidine →<br>uproleselan<br>KG1 AML cells were incubated for 96 hours in the absence or presence<br>of 100 nM 5-azacytidine, labeled with calcein and allowed to adhere to<br>E-selectin coated plates (control and 5-azacytidine above). After 45<br>minutes of adhesion, Uproleselan was added to the wells and<br>fluorescence determined after 30 minutes<br>(5-azacytidine → Uproleselan above).<br>358<br>561<br>55<br>0<br>100<br>200<br>300<br>400<br>500<br>600<br>Control 5-azacytidine 5-azacytidone +<br>Uproleselan<br>Fluorescence<br>UPROLESELAN INHIBITS BINDING OF BLASTS<br>700 | ||
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| Uproleselan/ Venetoclax/ HMA Combination Significantly<br>Reduces Leukemia Burden, Compared to Ven+5Aza Alone1<br>1. ASH December 2020 23<br>Venetoclax<br>Uproleselan<br>Ven+5Aza<br>Combination<br>AML-PDX FROM A VENETOCLAX / HMA RESISTANT PATIENT | ||
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| A Phase I Study of Uproleselan Combined with Azacitidine<br>and Venetoclax for the Treatment of Older or Unfit Patients<br>with Treatment Naïve Myeloid Leukemia B.A. Jonas, J.L. Welborn,<br>N.S. Esteghamat,R.T. Hoeg, A.S. Rosenberg, L. Molnar, A. Linh Dang-Chu, S.L. steward, and<br>J.M. Tuscano, 2022<br>PublicationNumber: 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 cycle 1<br>• 4 CR/CRi MFC MRD negative<br>• 50% overall MRD negative rate<br>• 67% amongCR/CRi responders<br>24<br>ASH 2022/2023: First Clinical Uproleselan Data Generated<br>Outside of GLYC-Sponsored Trials<br>Uproleselan data from two investigator-initiated trials presented at ASH in December 2022/2023<br>Uproleselan added to Cladribine Plus Low Dose Cytarabine<br>(LDAC) in Patients with Treated Secondary Myeloid<br>Leukemia (TS-AML) E.A. Huante, H. Kantarjian,K.S. Chien, C.D. DiNardo, N. Short,<br>A. Maiti, G. Montalban, N. Daver, J.D. Kawedia, K. Bowie, S.A. Pierce, F. Ravandi, M. Konopleva,<br>G. Garcia Manero, and T. M. Kadia, 2023<br>PublicationNumber: 2992<br>39% ORR in very high-risk patient population<br>• 18 evaluable patients<br>• All patients had unfavorablecytogenetics and had previously received<br>treatmentwith a hypomethylating agent.<br>• 11 patients (55%) had receivedprior treatmentwith venetoclax,and five<br>(25%) had undergonestem cell transplantation.<br>• Data outcomes<br>• Combinationof Cladribine + LDAC with uproleselan overall well tolerated with<br>few treatment-relatedAEs<br>• Combinationreduced bone marrow blasts in 13 (72%) patients<br>• Three patients went on to receivea potentially curative hematopoietic cell<br>transplantation (HCT)<br>• Study investigators concluded data support this low-risk approach to marrow<br>blast reduction and disease control in preparationfor HCT | ||
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| Treatment of<br>Vaso-occlusive Crisis<br>(VOC) in Patients with<br>Sickle Cell Disease<br>GMI-1687 | ||
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| Front. Immunol., 28 April 2021Sec. https://doi.org/10.3389/fimmu.2021.663886; Clin Hemorheol Microcirc. 2018; 68(2-3): 263–299.; Image adapted from https://www.rethinkscd.com 26<br>E-Selectin Mediates Multicellular Adhesion and Vaso-Occlusion<br>Data Supporting E-Selectin Role<br>in Cellular Adhesion and Clotting<br>Preclinical<br>• E-selectin leads to rolling and cell arrest<br>• Blocking E-selectin inhibits leukocyte<br>adhesion<br>• BlockingE-selectin restores blood flow in<br>animal models of vessel occlusionin sickle<br>cell disease<br>Clinical<br>• sE-selectin correlates with frequency of VOC<br>• sE-selectin correlates with poor survival<br>• Reduced sE-selectin correlatedwith clinical<br>benefit in RESET trial (time to discharge)<br>Inflammation<br>& Activation<br>Multicellular Adhesion<br>& Vaso-occlusion<br>E-Selectin<br>P-Selectin<br>VASCULAR DAMAGE<br>RBC rigidityand<br>hemolytic byproducts<br>promote endothelial<br>inflammation<br>ADHESION MOLECULE<br>EXPRESSION<br>Inflammationdrives<br>expression of<br>E-selectin, an<br>adhesion molecule<br>MULTICELLULAR<br>ADHESION<br>E-selectin binds sticky<br>clusters of blood cells<br>that interact with<br>endothelium<br>VASO-OCCLUSIVE<br>CRISIS<br>Blood flow occlusion<br>and resulting hypoxia<br>leads to pain and<br>organ damage<br>E-selectin Antagonism Provides a Unique Therapeutic Target to Interrupt VOC in SCD patients | ||
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| 27<br>Even with Prophylactic and Gene Therapy Approaches, VOC<br>Will Remain A Significant Unmet Medical Need<br>Dampier et al. 2017 American Society of HematologyAnnual 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+<br>VOCs<br>20%<br>50%<br>30%<br>On-Demand<br>VOC Therapies<br>(Selected In Development) Vertex/CRISPR<br>EXA-CEL<br>Editas Med.<br>EDIT-301<br>bluebird bio<br>LOVO-CEL<br>Beam Ther.<br>BEAM-101<br>*Authorizationrevoked in EU<br>220,000 – 450,000 VOCs/year (in the era of prophylactic therapies)<br>Pfizer<br>Voxeletor<br>Novartis<br>Crizanlizumab-tmca*<br>Pfizer<br>Inclacumab;<br>GBT021601<br>Novo<br>Nordisk<br>Etavopivat<br>Agios Pharma<br>Mitapivat<br>Prophylactic Therapies<br>APPROVED<br>Multiple (generic)<br>Hydroxyurea<br>PHASE 3<br>Gene Therapies (In Development)<br>GMI-1687<br>E-selectin antagonist<br>First-in-class<br>Novel MoA | ||
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| 28<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>Dampier et al, Blood 2023<br>Early Treatment Resulted in Clinical Benefit<br>For patients treated within first<br>quartile of treatment (<26.4hrs), a<br>meaningful, statistically significant<br>benefit was seen across study<br>endpoints | ||
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| GMI-1687 Seeks to Empower Patients to Take Control<br>1 Morikis et al, Frontiers in Immunology, April 2021, Vol. 12, Article 663886 29<br>Lessons Learned GMI-1687<br>E-selectin<br>drives VOC1<br>• Fast-acting, small molecule E-selectin<br>antagonist to eliminate vaso-occlusion<br>Early treatment in<br>VOC is critical<br>• Potential self-administration of GMI-1687 after<br>patient recognizes VOC episode<br>• 100% bioavailable in preclinical models<br>following subcutaneous administration<br>Deliver full dose to<br>stop VOC<br>• Optimize dose and regimen based on<br>reductions in sE-selectin<br>• Agreed to as part of FDA Pre-IND Meeting<br>Potentially<br>revolutionizing<br>the treatment<br>paradigm to on-demand disease<br>modifying therapy<br>Phase 1a Study Completed | ||
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| Potential Treatments in<br>Oncology, Inflammation<br>and Fibrosis<br>GALECTIN-3 INHIBITORS | ||
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| 31<br>The Promise of Targeting Galectins<br>Potential to modulate the immune and inflammatory response to cancer and fibrosis<br>Target<br>Galectin-3 carbohydrate-binding protein<br>Chemistry<br>Rationally designed with<br>proprietary platform<br>Differentiation<br>Compounds have high binding affinity<br>and specificity for Galectin-3<br>Orally Bioavailable<br>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 Relevance | ||
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| • Phase 3 trial in R/R AML (n=388), topline<br>results announcedin Q2 2024<br>• Fully enrolled Phase 2 trial in front-line<br>AML (n=267) ongoing,NCI-sponsored<br>• Ongoing IITs in other AML populations.<br>Preliminary data presented at ASH<br>2022/2023<br>• Novel MOA/first-in-class → potential<br>broad utility with Breakthrough Therapy,<br>Fast Track, and Orphan designations<br>• Novel small molecules inhibit carbohydrate<br>signaling<br>• Potential application in multiple<br>inflammatory diseases<br>• GMI-1687<br>• Phase 1a trial in healthy volunteers<br>completed<br>• Initial indication: treatment of sickle cell<br>disease (SCD) vaso-occlusive crisis<br>(VOC)<br>• Being developed for self-administration at<br>time of VOC<br>• Galectins<br>• Targeting fibrotic diseases<br>• First oral Galectin-3antagonist<br>• Updating uproleselan plans and evaluating<br>financial guidance<br>Near-Term Catalysts and Promising, Glycobiology-based Pipeline<br>3<br>Uproleselan: Multiple<br>Late-Stage Clinical Trials<br>Promising<br>Early-Stage Pipeline<br>Targeted<br>Operational Execution | ||
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| Thank You<br>www.glycomimetics.com | NASDAQ: GLYC | |
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