On June 4, 2024 GlycoMimetics, Inc. (Nasdaq: GLYC), a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, reported comprehensive results from the company’s pivotal Phase 3 study of uproleselan in R/R AML (Press release, GlycoMimetics, JUN 4, 2024, View Source [SID1234644087]).

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"There is a wealth of data across large subsets of this pivotal Phase 3 study that help us understand how prespecified stratification factors such as backbone chemotherapy, disease status, and age impacted survival outcomes for patients," said Daniel DeAngelo, M.D., Ph.D., Professor of Medicine, Harvard Medical School, Chief, Division of Leukemia, Dana-Farber Cancer Institute, and Principal Investigator of the pivotal Phase 3 study. "In the primary refractory setting, uproleselan’s improvement of mOS and greater duration of remission were particularly compelling, as there is a significant unmet need for new treatment options in this setting that can extend and improve the lives of patients. These results demonstrate uproleselan has the potential to address this unmet need in primary refractory AML."

"As we have analyzed data from this large, well-balanced, and well-executed study alongside medical, statistical, and regulatory experts, it has become clear that uproleselan may offer clinically meaningful patient benefit in multiple settings, including primary refractory AML," said Harout Semerjian, Chief Executive Officer of GlycoMimetics. "We are committed to addressing unmet needs of AML patients and plan to engage with regulators and NCI to discuss potential paths forward for uproleselan."

Results of Pivotal Phase 3 Study of Uproleselan in R/R AML

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 induction and, if applicable, up to 3 cycles of consolidation. The primary endpoint was overall survival (OS), which was not censored for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission (CR) rate and CR with partial hematologic recovery (CRh). A total of 388 patients in nine countries were randomized 1:1 between treatment and placebo arms. There were 59 sites that enrolled at least one patient. Median follow up was over three years at the time of primary analysis.

Overall Survival

Primary Endpoint: mOS in the intent-to-treat (ITT) population (n=388) was 13.0 months for the uproleselan arm, compared to 12.3 months for the placebo arm (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.69-1.15); this difference is not statistically significant.
Disease Status
Primary Refractory: mOS for primary refractory patients in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58; 95% CI 0.37-0.91) for the placebo arm (n=66). This benefit was irrespective of backbone chemotherapy.
Median duration of response (DoR) for complete remission (CR) was not reached for primary refractory patients in the uproleselan arm compared to a median DoR of 12.7 months for the placebo arm.
Early Relapse: mOS for early relapse patients in the uproleselan arm (n=28) was 3.7 months, compared to 6.4 months (HR 1.50; 95% CI 0.69-3.27) for the placebo arm (n=22).
Late Relapse: mOS for late relapse patients in the uproleselan arm (n=104) was 15.4 months, compared to 18.2 months (HR 1.10; 95% CI 0.77-1.57) for the placebo arm (n=106).
Backbone Chemotherapy:
FAI: mOS for patients treated with uproleselan plus FAI (n=98) was 30.2 months compared to 12.8 months (HR 0.73; 95% CI 0.50-1.06) for patients treated with FAI alone (n=96) in the ITT population.
MEC: mOS for patients treated with uproleselan plus MEC (n=96) was 8.7 months compared to 12.3 months (HR 1.06; 95% CI 0.75-1.51) for patients treated with MEC alone (n=98) in the ITT population.
Transplantation Status:
For patients who received hematopoietic stem cell transplantation (HSCT) after study treatment, mOS was not reached for patients in the uproleselan arm (n=101). In contrast, for HSCT patients in the placebo arm, mOS for patients receiving FAI (n=53) was 26.3 months and for patients receiving MEC (n=46) was 24.4 months.
Secondary Endpoints

7.2% of patients in each arm (n=388) experienced induction emergent severe oral mucositis.
36.1% of patients in the uproleselan arm (n=194) experienced CR at the end of induction (EOI) as determined by an independent endpoint review committee (IERC), compared to 33.5% of patients in the placebo arm (n=194).
46.4% of patients in the uproleselan arm experienced CR/CRh at EOI as determined by IERC, compared to 41.2% of patients in the placebo arm.
Post-treatment HSCT rate was 52.1% in the uproleselan arm and 51.0% in the placebo arm.
Subsequent AML therapy in non-responders was 40.0% in the uproleselan arm (n=80) and 46.2% in the placebo arm (n=78).
Safety

Adverse events were consistent with the known safety profile for backbone chemotherapy regimens.
35.9% of patients in the uproleselan arm experienced serious treatment-emergent adverse events (TEAEs) compared to 34.2% in the placebo arm.
85.9% of patients in the uproleselan arm experienced grade 3 or higher TEAEs compared to 87.6% in the placebo arm.
NCI Phase 2/3 Study of Uproleselan in Frontline AML

In addition to the company’s pivotal Phase 3 trial of uproleselan, the National Cancer Institute (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. Their 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. The Company is advancing discussions with the NCI and the Alliance for Clinical Trials in Oncology based on the results of the pivotal Phase 3 study of uproleselan in R/R AML.

Conference Call Details

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 and the corresponding slides will be available on the "Investors" tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.

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.

On June 4, 2024 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radioconjugates (RCs), reported the successful completion of the acquisition of all of the issued and outstanding shares of Fusion by a wholly-owned subsidiary of AstraZeneca AB by way of a statutory plan of arrangement under section 192 of the Canada Business Corporations Act, referred to as the Arrangement (Press release, Fusion Pharmaceuticals, JUN 4, 2024, View Source [SID1234644085]). The Arrangement marks a major step forward in AstraZeneca delivering on its ambition to transform cancer treatment and outcomes for patients by replacing traditional regimens like chemotherapy and radiotherapy with more targeted treatments.

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The Arrangement complements AstraZeneca’s leading oncology portfolio with the addition of the Fusion pipeline of RCs, including their most advanced program, FPI-2265, a potential new treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), and brings new expertise and pioneering R&D, manufacturing and supply chain capabilities in actinium-based RCs to AstraZeneca. The Arrangement is also expected to strengthen AstraZeneca’s presence in and commitment to Canada.

As a result of the Arrangement, Fusion has become a wholly owned subsidiary of AstraZeneca, with operations continuing in Canada and the US. Fusion shares will be delisted from the Nasdaq Stock Market and deregistered under the U.S. Securities Exchange Act of 1934. Fusion has submitted an application to cease to be a reporting issuer under applicable Canadian securities laws and to otherwise terminate Fusion’s Canadian public reporting requirements.

Financial Considerations

Under the terms of the definitive agreement, AstraZeneca, through a subsidiary, has acquired all of Fusion’s outstanding shares pursuant to the Arrangement for a price of $21.00 per share in cash at closing plus a non-transferable contingent value right of $3.00 per share in cash payable upon the achievement of a specified regulatory milestone prior to August 31, 2029. Combined, the upfront payment and maximum potential contingent value payment, if achieved, represent a transaction value of approximately $2.4 billion. As part of the Arrangement, AstraZeneca acquired the cash, cash equivalents and short-term investments on Fusion’s balance sheet, which totaled $211 million as of March 31, 2024.

The upfront consideration has been provided to Equiniti Trust Company, LLC, as depositary under the Arrangement, and, along with the contingent value rights, will be delivered to former securityholders (as applicable) of Fusion as soon as practicable on or after the date hereof.

On June 4, 2024 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that the European Commission (EC) has granted an Orphan Drug Designation (ODD) to its product candidate UCART22, for the treatment of Acute Lymphoblastic Leukemia (ALL) (Press release, Cellectis, JUN 4, 2024, View Source [SID1234644084]).

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UCART22 is an allogeneic CAR T-cell product candidate targeting CD22 and evaluated in BALLI-01, a Phase 1/2 open-label dose-escalation and dose-expansion study, designed to evaluate the safety, expansion, persistence and clinical activity of UCART22 in patients with relapse/refractory ALL.

ALL represents 12% of all leukemia cases, progresses rapidly, and is typically fatal within weeks or months if left untreated[1]. In 2024, the 10-year prevalence is estimated at 1.9 in 100,000 persons in the European Union (EU). Based on the preliminary clinical data generated with UCART22 in heavily pretreated patients who were relapsed or refractory to approved medicinal products, the European Medicines Agency (EMA) considered that the significant benefit of UCART22 has been demonstrated.

"Patients with relapsed/refractory ALL have limited, if any, treatment options, especially for those who have failed prior CD19 directed CAR T-cell therapy and allogeneic stem cell transplant" said Mark Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis. "The Orphan Drug Designation for UCART22 marks an important step towards developing allogeneic CAR T products that would be readily available for all patients."

The last clinical data presented by Cellectis at the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2023 were encouraging and suggested that UCART22-P2 (fully manufactured in-house) is more potent with a preliminary response rate of 67% at Dose Level 2, compared to a 50% response rate at Dose Level 3 with UCART22-P1 (manufactured by an external CDMO). Cellectis expects to provide updates on the progress of BALLI-01 by year-end 2024.

The Orphan Drug Designation in the EU is granted by the EC based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products. Medicines intended for the treatment, diagnosis or prevention of seriously debilitating or life-threatening conditions that affect fewer than five in 10,000 people in the EU are eligible for the designation. The Orphan Drug Designation allows companies certain regulatory, financial, and commercial incentives to develop medicines for rare diseases where there are no satisfactory treatment options.

On June 4, 2024 Bristol Myers Squibb (NYSE: BMY) reported the first presentation of results from the Phase 3 CheckMate -9DW trial evaluating the dual immunotherapy combination of Opdivo (nivolumab) plus Yervoy (ipilimumab) compared to investigator’s choice of lenvatinib or sorafenib as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC) (Press release, Bristol-Myers Squibb, JUN 4, 2024, View Source;9DW-Trial/default.aspx [SID1234644082]). Results from the study will be featured in a late-breaking oral presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting today, June 4, at 9:45 a.m. CDT (#LBA4008).

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With a median follow-up of approximately 35.2 months, treatment with Opdivo plus Yervoy demonstrated:

A statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS). Median OS was 23.7 months (95% CI: 18.8–29.4) for Opdivo plus Yervoy compared to 20.6 months (95% CI: 17.5–22.5) with lenvatinib or sorafenib (HR: 0.79 (0.65–0.96); p = 0.018). The overall survival benefit was generally consistent across patient subgroups.
A statistically significant and clinically meaningful improvement in the key secondary endpoint of objective response rate (ORR), which was 36% (95% CI: 31-42) for Opdivo plus Yervoy compared to 13% (95% CI: 10-17) with lenvatinib or sorafenib.
A higher complete response (CR) rate of 7% for Opdivo plus Yervoy vs. 2% with lenvatinib or sorafenib. Responses were durable; among responders, median duration of response was 30.4 months for Opdivo plus Yervoy (95% CI: 21.2-NE) and 12.9 months for lenvatinib or sorafenib (95% CI: 10.2-31.2).
Opdivo plus Yervoy demonstrated a significantly reduced risk of symptom deterioration of 24% compared to lenvatinib or sorafenib (HR: 0.76, 95% CI: 0.62-0.93; p = 0.0059)
The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols. Treatment-related adverse events (TRAEs) of any grade were reported in 84% of patients with Opdivo plus Yervoy and 91% in patients with lenvatinib or sorafenib. Grade 3/4 TRAEs occurred in 41% and 42% of patients, respectively.

"Despite recent advances in the treatment of HCC, prognosis remains poor for patients with advanced HCC, and therapies that improve survival and help delay disease progression are needed," said Peter R. Galle, M.D., of the University Medical Center, Mainz. "These data from CheckMate -9DW confirm the efficacy of the combination of nivolumab and ipilimumab and ability to extend survival, which is very encouraging."

"The combination of Opdivo plus Yervoy has been an established second-line treatment for patients with advanced HCC and, with these results, we can demonstrate that Opdivo plus Yervoy significantly increases survival and other key efficacy measures in the first-line setting for patients with advanced disease," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "We look forward to discussing these data with health authorities and potentially bringing the dual immunotherapy combination of Opdivo plus Yervoy to more patients."

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -9DW clinical trial.

About CheckMate -9DW

CheckMate -9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.

Approximately 668 patients were randomized to receive Opdivo plus Yervoy (Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg Q4W) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm. The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration.

About Hepatocellular Carcinoma

Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 90% of all liver cancers. HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.

Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC.

On June 4, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in the Goldman Sachs 45th Annual Global Healthcare Conference (Press release, Bristol-Myers Squibb, JUN 4, 2024, View Source [SID1234644081]).

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Christopher Boerner, Ph.D., Board Chair and Chief Executive Officer, will take part in a fireside chat on Tuesday, June 11, 2024. He will answer questions about the company beginning at 11:20 a.m. ET.

Investors and the general public are invited to listen to a live webcast of the session by visiting View Source An archived edition of the session will be available following its conclusion.