On December 1, 2021 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that the US Food and Drug Administration (FDA) is allowing the Company’s Investigational New Drug (IND) application to study WP1122 for the treatment of Glioblastoma Multiforme (GBM) to go forward (Press release, Moleculin, DEC 1, 2021, View Source [SID1234596322]). With this IND now cleared, Moleculin plans to initiate a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.

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The Company believes WP1122 has significant potential as both an antiviral therapy and as a cancer therapy. Moleculin recently announced its plans to initiate a Phase 1a clinical trial of WP1122 in healthy volunteers in the United Kingdom to facilitate future testing in COVID-19 patients. This new US IND sets the stage for parallel development of WP1122 as a cancer therapy. Consistent with its strategy of leveraging external funding for many of its clinical trials, Moleculin intends to seek opportunities for an investigator-initiated clinical trial of WP1122 in cancer patients in 2022.

"This IND underscores our dual pronged approach to the development of WP1122 for the treatment of both certain types of cancers and viruses. In addition to the trial in the UK designed to position WP1122 as an antiviral therapy, we can now be advancing the cancer therapy path in parallel. Along with GBM, we believe WP1122 has the potential to be well suited as a treatment for other highly glycolytic cancers such as pancreatic cancer," commented Walter Klemp, Chairman and CEO of Moleculin.

GBM is the most aggressive malignant primary brain tumor and remains as an incurable tumor with a median survival of only 15 months1. It is the most common malignant primary brain tumor making up 54% of all gliomas and 16% of all primary brain tumors,2 and despite advancements, survival rates for patients with GBM have shown no notable improvement in population statistics in the last three decades.3 The average annual age-adjusted incidence rate of GBM is 3.19 per 100,000 persons in the United States.4

1 Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ, et al. Improved survival time trends of glioblastoma using the SEER 17 population-based registries. J Neuro Oncol. 2012;107(1):207–12

2 Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol. 2013;15 Suppl:2ii–56.

3 De Vleeschouwer S, editor. Brisbane (AU): Codon Publications; 2017 Sep 27.

4 Thakkar J, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol. Biomarkers Rev. 2014;23(10):1985–96.

On December 1, 2021 Imago BioSciences, Inc. ("Imago" or the "Company") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), reported that a virtual investor event will be hosted by the company’s management team following the company’s presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition (Press release, Imago BioSciences, DEC 1, 2021, View Source [SID1234596321]).

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Individuals interested in listening to the event at 11:00 a.m. ET on Sunday, December 12 may do so by dialing (844) 348-6880 for domestic callers, or (914) 800-3944 for international callers and reference conference ID: 4488627; or from the webcast link in the investor relations section of the company’s website at: www.imagobio.com. The webcast will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

Imago will participate in two oral presentations on during the ASH (Free ASH Whitepaper) exposition and the abstracts are available on the ASH (Free ASH Whitepaper) meeting website at www.hematology.org and can also be accessed through "Events and Presentations" on Imago’s investor relations website.

The titles of the oral presentations are:

Oral Presentation Title: "A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Advanced Myelofibrosis"
Presentation Date/Time: December 11, 2021, at 12:00 PM ET
Oral Presentation Title: "A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Essential Thrombocythemia (ET)"
Presentation Date/Time: Sunday, December 12, 2021, at 9:45 AM ET

On December 1, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported the presentation of new investigational data in acute myeloid leukemia (AML) and sickle cell disease at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 11-14, in Atlanta, Ga. Astellas’ largest ASH (Free ASH Whitepaper) showing to date includes 11 AML abstracts, including four oral presentations (Press release, Astellas, DEC 1, 2021, View Source [SID1234596320]).

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"Research being presented at this year’s ASH (Free ASH Whitepaper) meeting investigates gilteritinib across the FLT3-mutation-positive AML disease continuum," said Ahsan Arozullah, M.D., M.P.H., Vice President, Medical Sciences-Oncology, Astellas. "Several presentations highlight data for gilteritinib in a wide range of patients – from newly diagnosed to relapsed or refractory patients, and in varying combination regimens."

Presentations will include results from two Phase 3 trials: three abstracts from LACEWING, a clinical trial which included patients with newly diagnosed FLT3 mutation-positive (FLT3mut+) AML who were ineligible for first-line intensive induction chemotherapy; and one from COMMODORE, a trial of gilteritinib versus salvage chemotherapy in patients with FLT3mut+ relapsed or refractory AML conducted in China, Malaysia, Thailand, Singapore, and Russia.

Astellas will also present research based on patients’ perspectives of AML symptoms, life impact and treatment. "A deeper understanding of patient experiences is vital as we seek better treatment approaches in all stages of AML," said Erhan Berrak, M.D., Vice President of Medical Affairs, Oncology, Astellas. "For example, one study to be presented at this year’s ASH (Free ASH Whitepaper) meeting investigated the patient experience after a stem-cell transplant, shedding light on both symptoms and emotional impact, which can inform efforts to better serve patients post-transplant."

In addition, Astellas plans to present new preclinical data on sickle cell disease (SCD) for ASP8731, a novel BACH1 inhibitor that potentially induces fetal hemoglobin (HbF). The data show potential to increase expression of antioxidant and HbF genes and reduce SCD-related pathophysiology. This may result in the reduction of hemolysis, inflammation, and vaso-occlusive pain crises in patients living with the condition.

"We are pleased to have the opportunity to present our preclinical data supporting further development of ASP8731, our BACH1 inhibitor," said Itsuro Nagase, Ph.D., D.V.M., Vice President and Primary Focus Lead, Mitochondrial Biology, Astellas. "These data further support our focus on mitochondrial disease research and the advances we are making across the Astellas research pipeline to develop novel therapies for patients with unmet medical needs."

Oral Presentations

Title: Symptoms and Impacts Reported by Patients with Acute Myeloid Leukemia (AML) in Remission Post-Stem Cell Transplant (Abstract 278).

Presenting author: Thomas Leblanc, M.D., M.A., Department of Medicine, Duke University School of Medicine, Durham, N.C., USA
Session Date/Time: Saturday, Dec. 11, 2:15 p.m. ET
Title: Phase 3, Open-Label, Randomized Study of Gilteritinib and Azacitidine vs Azacitidine for Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in Patients Ineligible for Intensive Induction Chemotherapy (LACEWING) (Abstract 700).

Presenting author: Eunice S. Wang, M.D., Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., USA
Session Date/Time: Monday, Dec. 13, 3:30 p.m. ET
Title: Gilteritinib Versus Salvage Chemotherapy for Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia: A Phase 3, Randomized, Multicenter, Open-Label Trial in Asia (COMMODORE) (Abstract 695).

Presenting author: Jianxiang Wang, M.D., State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Session Date/Time: Monday, Dec. 13, 3:45 p.m. ET
Title: Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of FLT3 Mutation in Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia (Supported by AbbVie, Astellas and Genentech) (Abstract 691).

Presenting author: Naval Daver, M.D., Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Session Date/Time: Monday, Dec. 13, 2:45 p.m. ET
Title: ML-0207/ASP8731: A Novel BACH1 Inhibitor That Induces Fetal Hemoglobin in Treatment of Sickle Cell Disease (Abstract 854).

Presenting author: Greg Vercellotti, MD, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minn., USA
Session Date/Time: Monday, Dec. 13, 6:30 p.m. ET
Poster Presentations

Title: A Phase 1, Dose-Escalation Study of Gilteritinib Combined with Chemotherapy in Patients Aged 6 Months to <21 Years with FLT3 Internal Tandem Duplication-Positive Relapsed or Refractory AML (Abstract 2315).

Presenting author: Philip Connor, M.B.B.S., Department of Pediatric Hematology/Oncology, Noah’s Ark Children’s Hospital for Wales, Cardiff, Wales, UK
Session Date/Time: Sunday, Dec. 12, 6-8 p.m. ET
Title: Impact of FLT3 Mutation Clearance After Front-Line Treatment with Gilteritinib Plus Azacitidine, or Gilteritinib or Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: Results from the Phase 3 LACEWING Trial (Abstract 3445).

Presenting author: Eunice S. Wang, M.D., Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., USA
Session Date/Time: Monday, Dec. 13, 6-8 p.m. ET
Title: Patient Reported Outcomes in Patients with Newly Diagnosed FLT3mut+ Acute Myeloid Leukemia Ineligible for Intensive Induction Chemotherapy From LACEWING: A Randomized Phase 3 Trial of Gilteritinib and Azacitidine Versus Azacitidine Alone (Abstract 3058).

Presenting author: Eunice S. Wang, M.D., Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., USA
Session Date/Time: Sunday, Dec. 12, 6-8 p.m. ET
Title: First Salvage Therapy for Relapsed or Refractory Acute Myeloid Leukemia: Associated Health Care Resource Use and Costs (Abstract 1936).

Presenting author: Lori Muffly, M.D., M.S., Division of Blood and Marrow Transplantation, Stanford University, Stanford, Calif., USA
Session Date/Time: Saturday, Dec. 11, 5:30-7:30 p.m. ET
Title: Gilteritinib Can Be Safely Combined with Atezolizumab for The Treatment of Relapsed or Refractory FLT3-Mutated AML: Results of a Phase 1 Study (Abstract 2343).

Presenting author: Jessica K. Altman, M.D., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, Ill., USA
Session Date/Time: Sunday, Dec. 12, 6-8 p.m. ET
Title: Patient and Physician Preferences for Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) in Patients Not Candidates for Intensive Chemotherapy (Abstract 4047).

Presenting author: Mo Zhou, Ph.D., Analysis Group, Boston, Mass., USA
Session Date/Time: Monday, Dec. 13, 6-8 p.m. ET
Online-Only Publication

Title: Real-World Use of FLT3 Tyrosine Kinase Inhibitors in Patients with Relapsed/Refractory FLT3 Mutation-Positive Acute Myeloid Leukemia in the United States (Abstract 5033).

About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is an aggressive cancer that affects the bone marrow and blood, and its incidence increases with age.1,2 Of patients newly diagnosed with AML and tested for FLT3 mutations, approximately one-third have an alteration to the FLT3 gene. FLT3-ITD mutations have been associated with worsened disease-free survival and overall survival, and a higher risk of getting the disease more than once. FLT3 mutation status can change over the course of AML treatment, even after relapse.3-6

About Gilteritinib
Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-TKD mutations.7 It was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global development, commercialization and manufacturing rights to gilteritinib.8

On December 1, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN) (Press release, BeyondSpring Pharmaceuticals, DEC 1, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-receives-complete-response-letter-from-the-fda-for-plinabulin-new-drug-application-for-prevention-of-chemotherapy-induced-neutropenia-cin [SID1234596319]). The FDA issued the CRL to indicate that they have completed their review of the application and have determined that it cannot be approved in its present form.

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The FDA’s CRL indicated that the results of the single registrational trial (106 Phase 3) was not sufficiently robust to demonstrate benefit and that a second well controlled trial would be required to satisfy the substantial evidence requirement to support the CIN indication.

"BeyondSpring strongly believes that plinabulin in combination with G-CSF has significant potential to raise the standard of care in CIN, a devastating side effect of chemotherapy," said Dr. Lan Huang, BeyondSpring’s co-founder, chief executive officer and chairwoman. "The Company plans to request a meeting with the FDA and remains committed to its goal of bringing plinabulin to cancer patients in need globally."

BeyondSpring remains confident in the efficacy and safety data for plinabulin in combination with G-CSF for the prevention of CIN. The Company expects to work closely with the FDA to consider the possible future clinical pathway for CIN, which may include a second study.

Plinabulin is the first drug candidate submitted for FDA approval that has the potential to work in the critical first week of chemotherapy treatment before G-CSF is effective, to prevent the onset and improve clinical outcomes of CIN.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA-stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation and priority review from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

On December 1, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the Company has initiated a Phase 2, single arm, open-label study of trilaciclib in patients with early-stage triple negative breast cancer (TNBC) designed to further investigate the role of trilaciclib in modulating the anti-tumor immune response (Press release, G1 Therapeutics, DEC 1, 2021, View Source [SID1234596317]). Pathologic complete response endpoints are also being evaluated in this trial. Initial results of this study are expected in the second half of 2022.

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"Data from our Phase 2 TNBC trial of trilaciclib in combination with chemotherapy showed clinically meaningful and substantial improvements in overall survival as well as enhanced measures of immune system function compared to chemotherapy alone," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "Those preliminary data support the important role trilaciclib may play in treating cancer by enhancing T cell activation and favorably altering the tumor microenvironment. This Phase 2 clinical study will support trilaciclib’s mechanistic effects potentially responsible for enhanced anti-tumor immune responses in patients and generate important data that will help guide our future development decisions across additional tumor types and new treatment combinations."

Patient recruitment in this trial is now underway. Approximately 30 patients will be enrolled in this Phase 2 multicenter, open-label, single-arm, neoadjuvant study. Up to three tumor tissue samples will be collected for assessment. Tumor tissue will be obtained at baseline prior to study drug administration. Patients will receive a single dose of monotherapy trilaciclib, followed by a tumor biopsy approximately one week later. Following the biopsy, patients will enter the treatment phase in which trilaciclib will be administered on Day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on Day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Immune checkpoint inhibitor and/or carboplatin may be added to therapy at the discretion of the investigator. Three to five weeks after the last dose of chemotherapy, patients will proceed to surgery at which time a third tumor tissue sample will be collected if the patient has residual disease.

Study treatment will continue as per protocol to completion or early discontinuation of chemotherapy, until unacceptable toxicity, Investigator’s decision to withdraw the patient from study treatment, consent withdrawal, or the end of the study, whichever occurs first.

The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single-dose as measured by the change in the ratio of CD8+ tumor-infiltrating lymphocytes (TILs) to regulatory T cell (Tregs) in the tumor microenvironment. Key secondary and exploratory endpoints include:

Assessment of pathologic complete response (pCR) rate at the time of definitive surgery.
Evaluation of the safety and tolerability of trilaciclib in combination with standard neoadjuvant systemic therapies.
Tumor mRNA analyses and immunohistochemistry and peripheral blood immune profiling following trilaciclib.
Identification of molecular and cellular biomarkers in tumor or blood samples that may be indicative of clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib and other systemic treatments.
About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.