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GT Biopharma Announces Solid Tumor Targeting TriKe™ Kills Non-small Cell Lung Cancer (NSCLC) Tumor Cells

On October 22, 2019 GT Biopharma, Inc. (OTCQB: GTBP) (GTBP.PA) an immuno-oncology company focused on innovative treatments based on the Company’s proprietary NK cell engager (TriKE) platform, reported that Drs. Jeffrey Miller, Martin Felices and Pippa Kennedy from the University of Minnesota presented research results at the recently concluded 18th meeting of the Society for Natural Immunity concerning a solid tumor targeting TriKE which demonstrates killing of non-small cell lung cancer tumor cells (Press release, GT Biopharma, OCT 22, 2019, View Source [SID1234542426]).

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According to the American Cancer Society, non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. In 2019, it is estimated there will be 228,150 cases of newly diagnosed lung cancer. Lung cancer is the second most common cancer, and this year it is estimated that 142,670 people will die from lung cancer. The 5-year survival rate for all people with all types of lung cancer is 19%.

Mr. Anthony Cataldo, the Chairman and Chief Executive Officer of GT Biopharma commented "we are excited about the progress Dr. Miller and his colleagues are making developing a TriKE which targets solid tumors." Mr. Cataldo further stated "we believe the NSCLC TriKE has the potential to offer lung cancer patients with a treatment option that achieves targeted killing of metastatic lung cancer cells in all locations within the body, and hopefully will become part of a scalable and curative therapeutic strategy for lung cancer patients."

About GTB-3550 TriKE and GTB-3550 TriKE Phase I/II Clinical Trial

GTB-3550 is the Company’s first TriKE product candidate which is a single-chain, tri-specific recombinant fusion protein construct composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. The GTB-3550 Phase I/II clinical trial for treatment of patients with CD33-expressing, high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or advanced systemic mastocytosis opened for patient enrollment September 2019. The clinical trial is being conducted at the University of Minnesota’s Masonic Cancer Center in Minneapolis, Minnesota under the direction of Dr. Erica Warlick.

Trovagene Announces Positive Response to Treatment in Phase 1b/2 Trial of Onvansertib in Patients with KRAS-Mutated Metastatic Colorectal Cancer

On October 22, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported data demonstrating positive response to treatment in patients enrolled in its Phase 1b/2 trial of onvansertib in combination with FOLFIRI and Avastin (bevacizumab) for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Trovagene, OCT 22, 2019, View Source [SID1234542425]). Decreases in tumor KRAS mutational burden in response to treatment was observed in all four patients who completed their first cycle of therapy with the combination regimen, as measured by quantitative analysis of circulating tumor DNA (ctDNA).

Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients succumb to the disease. Therefore, improving the effectiveness of treatments is critical to changing the outcomes for this patient population. Approximately 50% of mCRC patients have the KRAS mutation. The efficacy of current second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate.

"We are pleased by the early indication of response to treatment with the addition of onvansertib to standard-of care in patients with KRAS-mutated mCRC," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "We believe the combination of onvansertib and FOLFIRI/bevacizumab has the potential to provide a much-needed safe and effective new treatment option for the approximately 50% of patients with KRAS-mutated mCRC."

"Although still early in the trial, we are encouraged by the decreases in KRAS, assessed following initial dosing with onvansertib in combination with FOLFIRI/ bevacizumab, in patients treated in the first cohort," said lead investigator Dr. Afsaneh Barzi, associate professor of clinical medicine at Keck School of Medicine of USC and medical oncologist at USC Norris Comprehensive Cancer Center. "Additionally, these patients have continued on treatment beyond the cycle 1 safety assessment, indicating that the regimen appears to be safe and well tolerated. These initial findings suggest that onvansertib may provide clinical benefit for mCRC patients who have limited therapeutic options and a poor prognosis."

An overview of the mCRC Phase 1b/2 clinical trial (NCT03829410) was also featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress in September 2019. The presentation included the supportive preclinical data, demonstrating synergy with the combination of onvansertib and irinotecan, a key component of the FOLFIRI regimen.

About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC

The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

BerGenBio Receives FDA Approval of Fast Track Designation for Bemcentinib

On October 22, 2019 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported that the U.S. Food and Drug Administration (FDA) has approved Fast Track Designation for bemcentinib for the treatment of elderly patients with acute myeloid leukaemia (AML) whose disease has relapsed (Press release, BerGenBio, OCT 22, 2019, View Source [SID1234542424]). There are currently no marketed drugs specifically approved for all relapsed AML patients, representing a significant unmet medical need. BerGenBio has ongoing phase 2 trials in this indication and plans to seek regulatory advice from the FDA and European Medicines Agency (EMA) to determine the optimal regulatory path for bemcentinib in relapsed AML.

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy. A drug that receives Fast Track designation is eligible for the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA
Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We are thrilled that bemcentinib has been granted Fast Track Designation. Not only does this make us eligible for accelerated approval and priority review, but it serves as an important validation of bemcentinib in this significant unmet medical need we are trying to address. Currently, bemcentinib is in expanded Phase II trials in the U.S. and Europe for the treatment of AML and the Company has recently announced positive interim top line data."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, as monotherapy and in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy). Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

About AML

Acute myeloid leukemia (AML) is the most common type of aggressive leukemia in adults, which has the lowest survival rate for all types of leukemia. In 2018, it is estimated there will be nearly 20,000 new cases of AML diagnosed in the United States. Many AML patients older than age 60 are unable to tolerate intensive induction chemotherapy treatment.

BERG Collaboration Identifies Novel Mechanism Of Action Of Redox Regulation By BPM 31510 In Models Of Glioblastoma

On October 22, 2019 BERG, the clinical stage biopharmaceutical company that uses artificial intelligence (AI) to discover the biology of underlying disease, reported results from a preclinical study of its investigational drug BPM 31510 (novel ubidecarenone formulation) in glioblastoma models (Press release, Berg Pharma, OCT 22, 2019, View Source [SID1234542423]). The study, presented as a poster at the Society for Neuroscience (SfN) Annual Meeting in Chicago, demonstrated a novel oxidative stress dependent mechanism of action of BPM 31510 associated with anti-cancer responses in Glioblastoma Multiforme (GBM).

"We are excited to observe independent validation by a team of researchers at Stanford University School of Medicine of novel mechanisms of redox regulation by BPM 31510 that seem largely cancer cell selective," said Dr. Niven R. Narain, BERG Co-founder, President and Chief Executive Officer. "The data are consistent with predictions by our proprietary Interrogative Biology platform that BPM 31510 affects mitochondrial-centric metabolism and can be applied to highly metabolic tumor types such as GBM. It is notable that this hallmark of cancer was awarded the 2019 Nobel Prize in Medicine1."

GBM is an aggressive type of brain cancer associated with very high morbidity and mortality rates. Currently, there are limited treatment options, thus there is an urgent need for novel therapeutic approaches to improve outcomes for this disease. BPM 31510 is a unique therapeutic modality specifically targeting cell metabolism, shifting the cancer’s glycolytic dependency toward mitochondrial oxidative phosphorylation inducing oxidative stress and cell death specifically of cancer cells. GBM’s glycolytic dependency makes it a particularly relevant target indication for BPM 31510.

"These exciting findings support an entirely novel mechanism of cancer chemotherapy," said Eric J. Nestler, MD, PhD, Past President of SfN and the Nash Family Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai in NYC. "BPM 31510 not only shows therapeutic promise for GBM in animal models, but has proven to be well tolerated in humans in a recent Phase 1 study. It will be important to establish its efficacy in human GBM patients." Dr. Nestler is a member of the Board of Directors of BERG.

The study was led by Lawrence Recht, MD, Professor of Neurology & Neurosurgery at Stanford University School of Medicine, with other Stanford researchers and in collaboration with BERG.

Details of the BERG presentation:
Date: Tuesday, October 22, 2019
Harnessing redox homeostasis as a therapeutic modality in glioblastoma
Session number 557 (Neuro-Oncology)
Location – Hall A, McCormick Place, Chicago, IL, USA
Time – 1:00 – 5:00 PM

In its commitment to serve patients afflicted with cancer, BERG has collaborated on other projects with leading institutions like MD Anderson Cancer Institute (clinical trials) and Harvard/BIDMC (Project Survival), among others.

Amgen Announces 2019 Fourth Quarter Dividend

On October 22, 2019 Amgen (NASDAQ:AMGN) reported that its Board of Directors declared a $1.45 per share dividend for the fourth quarter of 2019 (Press release, Amgen, OCT 22, 2019, View Source [SID1234542422]). The dividend will be paid on Dec. 6, 2019, to all stockholders of record as of the close of business on Nov. 15, 2019.