On May 6, 2024 Pliant Therapeutics, Inc. (Nasdaq: PLRX), a late-stage clinical biotechnology company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases, reported a corporate update and announced first quarter 2024 financial results (Press release, Pliant Therapeutics, MAY 6, 2024, View Source [SID1234642682]).

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"In the first quarter, we made significant progress across our portfolio, highlighted by the positive safety and exploratory efficacy data from our Phase 2a INTEGRIS-PSC trial, as well as completion of a Phase 2a PET imaging trial evaluating bexotegrast’s effects on total lung collagen and lung function in IPF patients," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics. "Our strong execution has also allowed us to accelerate the ongoing BEACON-IPF Phase 2b trial through the implementation of an adaptive Phase 2b/3 design which will reduce the time to Phase 3 data by up to two years."
First Quarter and Recent Highlights
Bexotegrast Highlights
•Acceleration of bexotegrast development plan with implementation of BEACON-IPF as a pivotal, adaptive Phase 2b/3 trial in patients with idiopathic pulmonary fibrosis (IPF). The adaptive design implementation, based on acceptance by the European Union (EU) and other global health authorities, is expected to significantly shorten bexotegrast’s late-stage development compared to standalone Phase 2b and Phase 3 trials. As part of the adaptive Phase 2b/3 implementation, the Phase 2b portion of BEACON-IPF was upsized from 267 patients to 360 patients. Enrollment is progressing and we expect to complete enrollment of the upsized Phase 2b study expected in the first quarter of 2025.
•Completion of a 12 week Phase 2a PET imaging trial, measuring the effects of bexotegrast on total lung collagen and forced vital capacity (FVC) in IPF patients. This randomized, double-blind, placebo-controlled trial (NCT05621252) was conducted at Massachusetts General Hospital. The trial’s primary endpoint is the change in total lung collagen in 10 participants with IPF following once-daily treatment with bexotegrast at 160 mg for 12 weeks. Collagen will be evaluated with PET imaging, utilizing a collagen-binding probe. The secondary endpoint is safety and tolerability. Exploratory endpoints include change in FVC, cough severity and fibrosis biomarkers. Conduct of this trial has been completed, with topline data expected in the coming weeks.
•Completion of INTEGRIS-PSC Phase 2a trial in patients with primary sclerosing cholangitis (PSC) with data readout expected mid-year. As previously announced, at a once-daily dose of 320 mg, bexotegrast was well tolerated over 12 weeks of treatment with no drug-related severe or serious adverse events. At the 320 mg dose, bexotegrast reduced both Enhanced Liver Fibrosis (ELF) scores and PRO-C3 levels and showed improvements in hepatocyte function and bile flow by contrast MRI imaging relative to placebo at Week 12. The final 24-week data readout from the 320 mg dose group is expected in mid-2024.
Pipeline Programs
•Muscular dystrophy program cleared for conduct of Phase 1 study. PLN-101325 is a monoclonal antibody designed to act as an allosteric agonist of integrin α7β1. The Company recently received regulatory clearance from Australia’s Research Ethics Committee (HREC) for the conduct of a first-in-human Phase 1 clinical study of

PLN-101325 which is being developed as a potential treatment for muscular dystrophies, including Duchenne muscular dystrophy (DMD).
•Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts. PLN-101095 is an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The Company is currently enrolling the third of five cohorts in the Phase 1 open label, dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data could be available as early as late 2024.
Corporate Highlights
•Loan facility with Oxford Finance LLC (Oxford), upsized by $50 million to a total of $150 million of available non-dilutive capital. To date, the Company has drawn a total of $30 million from the facility. The remaining funds available under this facility, along with the Company’s March 31, 2024 cash and cash equivalents and short-term investments of $483.9 million are expected to fund Pliant’s anticipated operating expenses and capital expenditure requirements through 2026.
First Quarter 2024 Financial Results
•Research and development expenses were $37.1 million, as compared to $29.3 million for the prior-year quarter. The increase was due primarily to higher employee-related expenses and increased clinical and manufacturing-related costs associated with our lead program, bexotegrast, partially offset by a decrease in preclinical manufacturing costs for our pipeline product candidates.
•General and administrative expenses were $15.2 million, as compared to $14.2 million for the prior-year quarter. The increase was due to higher employee-related expenses.
•Net loss of $47.0 million as compared to $37.5 million for the prior-year quarter. The increase was due to higher operating expenses coupled with a decrease in collaboration revenues under the Novartis agreement during the quarter.
•As of March 31, 2024, the Company had cash, cash equivalents and short-term investments of $483.9 million.

On May 6, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended March 31, 2024 (Press release, ORIC Pharmaceuticals, MAY 6, 2024, View Source [SID1234642681]).

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"In the first quarter of 2024, we continued making steady progress across our clinical and preclinical programs, while also strengthening our cash position and runway," said Jacob M. Chacko, M.D., president and chief executive officer. "Most recently, we announced the selection of provisional recommended phase 2 doses for ORIC-114 that confirm its wide therapeutic index, and we initiated three expansion cohorts in patients with EGFR/HER2 mutated non-small cell lung cancer, including those with active, untreated CNS metastases. For ORIC-944, we presented clinical and preclinical data that further reinforce its promise as a potential best-in-class treatment option for prostate cancer based upon its superior drug properties and clinical half-life versus competitor PRC2 inhibitors. We are laser focused on flawless execution as we continue to advance these two programs towards the initiation of registrational studies, which we anticipate in the second half of 2025."

First Quarter 2024 and Other Recent Highlights

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of the provisional recommended phase 2 doses.
Announced first patients dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), HER2 exon 20 insertion, and EGFR atypical mutations.
Initiated an extension cohort to evaluate ORIC-114 for the treatment of patients with first-line, treatment-naïve EGFR exon 20 insertion NSCLC.
Expect to report updated Phase 1b data in the first half of 2025.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Reported initial Phase 1b monotherapy data for ORIC-944 in metastatic prostate cancer supporting advancement into combination development and demonstrating the potential as a best-in-class PRC2 inhibitor, including a clinical half-life of ~20 hours, no signs of CYP autoinduction that was observed with first-generation PRC2 inhibitors, robust target engagement, and a well-tolerated safety profile.
Presented preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting demonstrating superior preclinical drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.
Proceeding with combination of ORIC-944 with AR inhibitor(s) in metastatic prostate cancer and expect to provide a program update in mid-2024.
ORIC-533: a highly potent, orally bioavailable small molecule inhibitor of CD73

The company is completing a Phase 1b trial and plans to pursue strategic partnership for combination studies.
Discovery Pipeline:

Presented at the 2024 AACR (Free AACR Whitepaper) annual meeting the first preclinical data on ORIC-613, a potential first- and best-in-class development candidate selectively inhibiting PLK4.
Corporate Highlights:

Strengthened cash position and runway with a $125 million private placement financing from new and existing healthcare specialist funds in January 2024.
First Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $331.5 million as of March 31, 2024, which the company expects will be sufficient to fund its operating plan into late 2026.

R&D Expenses: Research and development (R&D) expenses were $22.0 million for the three months ended March 31, 2024, compared to $19.5 million for the three months ended March 31, 2023, an increase of $2.4 million. The increase was due to a net increase in external expenses related to the advancement of product candidates and discovery programs, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million.

G&A Expenses: General and administrative (G&A) expenses were $7.0 million for the three months ended March 31, 2024, compared to $6.2 million for the three months ended March 31, 2023, an increase of $0.9 million. The increase was primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.7 million.

On May 6, 2024 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, reported financial results for the first quarter ended March 31, 2024, and highlighted recent Company progress (Press release, Omega Therapeutics, MAY 6, 2024, View Source [SID1234642680]).

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"Our consistent focus on execution in the past quarter led to meaningful progress in both our clinical and preclinical programs as we work to maximize the value and potential of our unique OMEGA platform," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "We continue to evaluate OTX-2002 in the ongoing MYCHELANGELO I trial, including the advancement to a higher dose of 0.3 mg/kg in Cohort 5. We expect to present safety and preliminary efficacy data from dose escalation as well as expand into Phase 2 settings in mid-2024. We continue to enhance our platform capabilities with the evaluation of new targets, advancement of upregulation and multiplexed epigenomic control and further progress our internal delivery efforts to the lung and other high-value tissues. We look forward to executing on these important milestones as we advance on our mission to bring programmable epigenomic mRNA medicines to patients in need."

Recent Highlights and Key Anticipated Milestones

Development Pipeline and Platform

•
Advanced to Cohort 5 in dose escalation of the Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC): The trial is currently enrolling patients in Cohort 5 at the 0.3 mg/kg dose level at clinical sites across the U.S. and Asia. The Company expects to report additional clinical data from monotherapy dose escalation and expand into monotherapy and combination settings in mid-2024.
•
Presented new preclinical data supporting the development of a MYC-targeting epigenomic controller for EGFR inhibitor-resistant non-small cell lung cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024: Data demonstrated the anti-tumor effect of a MYC-targeting epigenomic controller

(MYC-EC) in preclinical models of EGFR inhibitor (EGFRi)-resistant non-small cell lung cancer (NSCLC), regardless of the underlying resistance mechanism. These data support potential development of a NSCLC MYC-EC in EGFR-mutant NSCLC as a combination therapy with osimertinib, and as a monotherapy in osimertinib-resistant NSCLC. The Company also presented preclinical data validating a novel pharmacodynamic biomarker assay for monitoring on-target engagement and activity of OTX-2002.
•
New preclinical data demonstrating durable upregulation of gene expression, further supporting Omega’s diverse platform capabilities, to be presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting: Poster titled "Tuned Upregulation of Diverse Gene Targets Using Programmable Epigenomic Controllers" to be presented during the Epigenetic Editing and RNA Editing poster session on May 8, 2024, from 12:00 p.m. to 7:00 p.m. ET.

First Quarter 2024 Financial Results

As of March 31, 2024, the Company had cash and cash equivalents totaling $60.0 million. This cash balance, along with a cost reduction and strategic prioritization initiative that occurred during the first quarter, is expected to fund operations into Q1 2025.

Research and development (R&D) expenses for the first quarter of 2024 were $15.4 million, compared to $20.1 million for the first quarter of 2023. The $4.7 million decrease in R&D expenses was primarily driven by a decrease in external research and manufacturing costs, personnel-related expenses, and clinical development costs, partially offset by an increase in facilities expenses.

General and administrative (G&A) expenses for the first quarter of 2024 were $7.4 million, compared to $6.2 million for the first quarter of 2023. The $1.2 million increase in G&A expenses was primarily driven by an increase in facilities expenses.

Net loss for the first quarter of 2024 was $20.1 million, compared to $25.3 million for the first quarter of 2023. The decrease in net loss was driven predominantly by the decrease in R&D expenses.

On May 6, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported financial results and business highlights for the first quarter ended March 31, 2024 (Press release, Lyell Immunopharma, MAY 6, 2024, View Source [SID1234642679]).

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"The initial clinical and translational data from the Phase 1 trial of LYL797, our lead CAR T-cell product candidate, will provide the first insights into our ability to reprogram ROR1 CAR T cells that can expand, infiltrate solid tumors and kill cancer cells in patients," said Lynn Seely, M.D., Lyell’s President and CEO. "Our strong cash position is expected to fund operations through multiple milestones into 2027, including initial clinical data from our lead TIL program in the second half of this year, and to the continued advancement of multiple product candidates with potential to offer better options for patients with cancer."

First Quarter Updates and Recent Business Highlights

Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845 are in Phase 1 clinical development. Two additional product candidates, LYL119, a ROR1-targeted Chimeric Antigen Receptor (CAR) T‑cell product candidate and a second-generation tumor infiltrating lymphocyte (TIL) product candidate, are in preclinical development.

LYL797 – A ROR1-targeted CAR T-cell product candidate genetically reprogrammed to overexpress c-Jun and epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol designed for differentiated potency and durability

Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study includes patients with relapsed or refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC).
Initial data from at least 20 patients from the Phase 1 clinical trial of LYL797 are expected this quarter.
LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability

Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The study includes patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.
Initial clinical and translational data from the Phase 1 trial of LYL845 are expected in the second half of 2024.
LYL119 – A ROR1-targeted CAR T-cell product candidate incorporating Lyell’s four stackable and complementary reprogramming technologies designed for enhanced cytotoxicity

LYL119 is a ROR1-targeted CAR T-cell product enhanced with Lyell’s four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑R T-cell activation technology.
An investigational new drug (IND) application for LYL119 is expected to be submitted this quarter.
Presented a poster with new nonclinical data on LYL119 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024. In this study, LYL119, compared to ROR1 CAR T cells reprogrammed with only two or three technologies, demonstrated reduced CAR T‑cell exhaustion, enhanced CAR T‑cell function, enhanced proliferation capacity and sustained antitumor activity in a mouse xenograft tumor model across a 10-fold dose range, including at very low cell doses. In addition, following repeated rounds of tumor cell killing, LYL119 displayed reduced expression of exhaustion-related gene signatures and retained unique cell subsets characterized by upregulation of memory and effector-associated gene signatures.
First Quarter Financial Results

Lyell reported a net loss of $60.7 million for the first quarter ended March 31, 2024, compared to a net loss of $67.0 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash stock-based compensation, non‑cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, was $37.5 million for the first quarter ended March 31, 2024, compared to $44.8 million for the same period in 2023.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $43.2 million for the first quarter ended March 31, 2024, compared to $44.6 million for the same period in 2023. The decrease in first quarter 2024 R&D expenses of $1.5 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the first quarter ended March 31, 2024, were $38.9 million, compared to $40.6 million for the same period in 2023. The decrease in first quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.
General and administrative (G&A) expenses were $13.5 million for the first quarter ended March 31, 2024, compared to $19.3 million for the same period in 2023. The decrease in first quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the first quarter ended March 31, 2024, were $8.1 million, compared to $10.0 million for the same period in 2023. The decrease in 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under "Non-GAAP Financial Measures."

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of March 31, 2024, were $526.3 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.

On May 6, 2024 GlycoMimetics, Inc. (Nasdaq: GLYC), a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, reported topline results from its Phase 3 global pivotal study of uproleselan in 388 patients with R/R AML (Press release, GlycoMimetics, MAY 6, 2024, View Source [SID1234642677]). 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.

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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.
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.
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.
Shares Outstanding: Shares of common stock outstanding as of March 31, 2024, were 64,450,835.
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.