On January 7, 2020 Cellect Biotechnology Ltd. (Nasdaq: APOP), a developer of innovative technology which enables the functional selection of stem cells, reported it received official communication from two jurisdictions, the European Patent Office (EPO) and the Israeli Intellectual Property Office, regarding their intention to grant European Patent Application No. 14851547.1 and Israeli Patent Application No. 244982, respectively (Press release, Cellect Biotechnology, JAN 7, 2020, View Source [SID1234552828]). These patent applications include a cell-based product and a method of manufacturing a stem and progenitor cell population with enhanced activity by short incubation with an apoptotic ligand.

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"Continued recognition from global jurisdictions validates the breadth of Cellect’s technology. These latest acknowledgments are significant as they cover the ability to activate stem cells, therefore improving stem cell products and manufacturing processes," commented Dr. Shai Yarkoni, Chief Executive Officer of Cellect. "Our collaboration efforts with companies in Germany, Korea and Israel have each reported similar data using our process in various tissue sources (including fat derived cells). These added protections continue to create barriers to entry and allows us to advance our business development strategies to monetize our innovation."

The Company has previously published third-party data demonstrating improved "stemness" of stem cells. Specifically, it significantly improves both proliferation and functional capabilities of hematopoietic (HSC) and mesenchymal (MSC) stem cells originating from bone marrow, peripheral blood, umbilical cord and adipose tissue.

"We believe the combination of strong IP protection and validated business collaborations support our business model and will enable us to attract external resources to strengthen and expand our opportunities," concluded Dr. Yarkoni.

The patents applications cover an ex vivo method for obtaining an improved population of stem and progenitor cells (SPC) with enhanced engraftment characteristics by activation of TNF family receptors. The Company’s previous patents covered the negative selection exerted by the ApoGraft process and product translated into clinical safety superiority. The latest patent applications describe and protect the positive effect that the same molecules have on stem cells and translates to the efficacy of the transplanted cells and the yields of the manufacturing processes for clinical use).

Including this latest notification, the Company has 65 patent applications worldwide of which 33 are issued/allowed patents.

On January 7, 2020 Clovis Oncology, Inc. (NASDAQ:CLVS) reported its preliminary, unaudited revenues for the fourth quarter and full year ended December 31, 2019 (Press release, Clovis Oncology, JAN 7, 2020, View Source [SID1234552778]). The financial information presented in this news release may be adjusted as a result of completion of customary quarterly review and audit procedures.

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Unaudited preliminary results include:

$38.3-$39.3M in Rubraca product revenues for the fourth quarter of 2019 compared to $37.6M for Q3 2019 and $30.4M for Q4 2018

$142.0-$143.0M in Rubraca product revenues for the FY2019 compared to $95.4M for FY2018

Clovis plans to discuss these results with investors this week at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco.

"We are very pleased with our sales performance in the fourth quarter and the momentum it provides us going into this year," said Patrick J. Mahaffy, CEO and President of Clovis Oncology. "In mid-November 2019, we submitted the supplemental New Drug Application (sNDA) for Rubraca in BRCA1/2-mutant recurrent, metastatic castrate-resistant prostate cancer, and also during the quarter announced the first reported human experience of FAP-2286 and launched Rubraca in England and Italy. With this progress, we are looking forward to an eventful 2020. Key milestones include additional EU country ovarian cancer launches for Rubraca, a potential U.S. Rubraca launch in prostate cancer, initial data for lucitanib combination studies, and a planned IND filing for FAP-2286 in the second half of the year."

Clovis Oncology to Present at 38th Annual J.P. Morgan Healthcare Conference on January 13, 2019

Clovis’ President and CEO, Patrick J. Mahaffy, will present at the 38th Annual J.P. Morgan Healthcare Conference to be held at the Westin St. Francis hotel in San Francisco on Monday, January 13 at 10:00 a.m. PT. A live webcast of the presentation and Q&A session can be accessed through the investor relations section of the Company’s website at clovisoncology.com. Following the live presentations, replays of the webcasts will be available on the Company’s website for 30 days.

Fourth Quarter and Full Year 2019 Financial Results Release Planned for February 24, 2020

The Company plans to report financial results for the fourth quarter and full year ended December 31, 2019 on Monday, February 24, 2020, after the close of the U.S. financial markets. Clovis’ senior management will host a conference call and live audio webcast at 4:30 p.m. ET to discuss the Company’s results in greater detail.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, and lung cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

In the EU, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. This expands rucaparib’s indication beyond its initial marketing authorization in the EU granted in May 2018 and with this label expansion, rucaparib is now available to patients regardless of their BRCA mutation status. Rubraca is also approved in the EU for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Rubraca is an unlicensed medical product outside of the U.S. and the EU.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/b) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

About FAP-2286

FAP-2286 is a preclinical candidate discovered by 3B Pharmaceuticals under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein alpha (FAP). FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas. Clovis will conduct the global clinical trials and holds U.S. and global rights, excluding Europe.

FAP-2286 is an unlicensed medical product.

On January 7, 2020 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that the principal investigator of the Company’s Phase II liver cancer study, Dr. Solomon Stemmer, will deliver a presentation titled "The Safety and Efficacy of Namodenoson in the Second-Line Treatment of Advanced Hepatocellular Carcinoma (HCC) Patients with Underlying Child-Pugh B (CPB) Liver Cirrhosis: A Phase 2 , Randomized, Double-Blind, Placebo-Controlled Trial" at the Israeli Society of Clinical Oncology and Radiotherapy (ISCORT) annual conference on January 8, 2020 11:00 am (Press release, Can-Fite BioPharma, JAN 7, 2020, View Source [SID1234552795]).

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Can-Fite’s completed Phase II liver cancer study found that Namodenoson increased overall survival in HCC patients with Child Pugh B7 (CPB7), the largest subpopulation of the study, as compared to placebo, even though the trial did not meet its primary endpoint. The Company recently completed a successful End-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), in which the FDA agreed with Can-Fite’s proposed pivotal Phase III trial design to support a New Drug Application (NDA) submission and approval of Namodenoson in the treatment of HCC.

"The ISCORT is the most prestigious Israel oncology forum to discuss novel treatments in different malignancies and enable the creation of collaboration between leading investigators in the field. We are confident that Dr. Stemmer’s presentation will open the door for the participation of leading oncologists in the Company’s Phase III study", said Dr. Fishman, Can Fite CEO.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated as a second line treatment for hepatocellular carcinoma, with a recently completed Phase II trial and planned Phase III trial in this indication. The drug is currently in an ongoing Phase II trial as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On January 7, 2020 Hummingbird Bioscience, an innovative biotherapeutics company pioneering the discovery and development of new breakthrough precision antibody therapeutics for difficult-to-treat conditions, reported the publication of preclinical data for its lead candidate, HMBD-001, an anti-HER3 antibody, in Molecular Cancer Therapeutics, a high-impact peer-reviewed American Association of Cancer Research journal (Press release, Hummingbird Bioscience, JAN 7, 2020, View Source [SID1234552813]).

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HMBD-001 is a unique anti-HER3 antibody with a novel mechanism of action and favorable safety profile. HER3 is a member of the EGFR tyrosine kinase receptor family, which is responsible for driving cancer cell division and growth, and is expressed in over half of colorectal and gastric cancers, at least a third of breast cancers, as well as significant sub-populations of many other indications.[1] HER3 activation is implicated in cancer progression as well as in acquired resistance to drugs against other tyrosine kinase receptor family members such as EGFR (e.g. cetuximab or Erbitux) and HER2 (e.g. trastuzumab or Herceptin). HMBD-001 was developed using Hummingbird Bioscience’s proprietary Rational Antibody Discovery Platform to specifically bind to and inhibit a difficult-to-access region of the HER3 protein that is essential for activation.

The published findings show that HMBD-001 (also known as 10D1F) is superior at tumor growth inhibition, regardless of how HER3 is activated, compared to previous anti-HER3 drugs with different binding sites and mechanisms of action. HMBD-001 demonstrated potent efficacy in a broad panel of in vitro and in vivo tumor models that had high HER3 activity and oncogenic downstream signaling.

"Previous attempts to target HER3 with other drugs failed as they could not inhibit activation of HER3 effectively. The highly specific binding of HMBD-001 to a difficult-to-target region on HER3 allows us to completely shut off activation of this important cancer-associated protein," said Dr Jerome Boyd-Kirkup, Chief Scientific Officer and co-founder, Hummingbird Bioscience. "This preclinical data provides proof-of-concept and represents exciting therapeutic opportunities for us as we look to develop HMBD-001 in hard-to-treat conditions such as gastric, colorectal, lung and pancreatic cancers."

Hummingbird Bioscience, in partnership with Cancer Research UK, will be advancing HMBD-001 into clinical trials for the treatment of HER3 driven cancers. Manufacturing of the material for the Phase 1 clinical trial of HMBD-001 is underway and is expected to be completed in the second half of 2020.

The paper titled 10D1F, An Anti-HER3 Antibody that Uniquely Blocks the Receptor Dimerization Interface, Potently Inhibits Tumor Growth Across a Broad Panel of Tumor Models can also be accessed online at View Source

About HMBD-001

HMBD-001 represents a unique, highly-specific, anti-HER3 neutralizing antibody with a novel mechanism of action that offers significant potential for broad clinical benefit. Previous attempts to block the HER3 receptor, a key player in the signaling pathway that promotes cell division and tumor growth in cancer, have not proven to be efficacious. HER3 is activated by the binding of neuregulin (NRG1), which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.

Preclinical models have shown that HMBD-001 is able to effectively and uniquely bind to a
difficult-to-target region on HER3, blocking the heterodimerization of HER3 with HER2/EGFR independent of NRG1 binding. This potently inhibits the activation of the signaling pathway – and consequently, stops tumor growth.

Cancer Research UK has partnered with Hummingbird Bioscience to advance this novel antibody drug into clinical trials for the treatment of HER3 driven cancers. The clinical trial of this investigational candidate is expected to commence following the completion of manufacturing and the subsequent submission of regulatory approval.

On January 7, 2020 The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) reported how resistance to a promising targeted drug develops in patients with a rare, lethal cancer of the bile ducts called cholangiocarcinoma (Press release, The Ohio State University Comprehensive Cancer Center, JAN 7, 2020, View Source [SID1234553217]).

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The study, reported in the journal Molecular Cancer Therapeutics, also suggests that adding another drug at the time of progression might re-sensitize tumor cells to the initial drug, called an FGFR inhibitor.

"While the majority of patients with FGFR-positive cholangiocarcinoma benefit from new FGFR inhibitors in clinical trials, most patients unfortunately develop cancers resistant to the drugs," says study leader Sameek Roychowdhury, MD, PhD, a medical oncologist and researcher at the OSUCCC – James. "We believe that this study is an important step in understanding drug resistance and improving the treatment of this and other cancers caused by abnormal FGFR gene mutations."

Findings also suggest that monitoring fragments of circulating tumor DNA for acquired mutations that cause resistance to FGFR inhibitors may reveal the presence of resistance mutations and mark the time a patient should begin taking the additional drug, an mTOR inhibitor.

The successful treatment of cholangiocarcinoma is challenging because the disease is usually diagnosed at an advanced stage that has a five-year survival rate of 2%. Patients diagnosed earlier also have low, five-year survival due to high rates of disease recurrence. Abnormal activation of the FGFR gene happens in 15 to 20% of people with cholangiocarcinoma, and FGFR inhibitors show effectiveness in 70 to 80% of those patients until resistance develops. There are six studies of FGFR inhibitors in clinical trials at the OSUCCC – James.

"A better understanding of how treatment resistance develops and how to prevent it is critical for improving the treatment of cholangiocarcinoma and other cancers caused by FGFR mutations," says first author Melanie Krook, PhD, a postdoctoral fellow in Roychowdhury’s lab.

"Our findings suggest that cholangiocarcinoma patients treated with an FGFR targeted therapy could potentially benefit from combination therapies with other drugs such as mTOR inhibitors. Additional laboratory studies are needed to identify the optimal lead strategies for this combination," she adds.

For this study, Roychowdhury, Krook and colleagues examined the FGFR (fibroblast growth factor receptor) gene in the cancer cells of a cholangiocarcinoma patient who died after experiencing disease progression and developing resistance to the FGFR inhibitor infigratinib.

The researchers identified two acquired FGFR mutations in the patient’s tumor cells that conferred resistance to FGFR inhibitors. They then used cancer cell lines to learn that the mutations led to activation of the mTOR biochemical pathway. This enabled the cancer cells to grow even in the presence of FGFR inhibitors. Adding an mTOR inhibitor to the cells restored their sensitivity to FGFR inhibitors.

Key findings:

Two acquired FGFR2 mutations, p.E565A and p.L617M, were shown to drive resistance to the FGFR inhibitor infigratinib.

The p.E565A mutation upregulates the mTOR signaling pathway, which desensitizes cholangiocarcinoma cell lines to infigratinib and other FGFR inhibitors.

A drug that inhibited the mTOR pathway restored the sensitivity of the cells to infigratinib and other FGFR inhibitors.

"Overall, our findings suggest that an mTOR inhibitor administered at the time of progression may re-sensitize tumor cells to an FGFR inhibitor in patients who develop resistance to these agents," Roychowdhury says.

This study was supported by grants from the American Cancer Society (MRSG-12-194-01-TBG), the Prostate Cancer Foundation, the National Institutes of Health (HG006508, CA202971, CA216432), the American Lung Association and Pelotonia.

Other researchers involved in this study were Alexandria Lenyo, Max Wilberding, Hannah Barker, Mikayla Dantuono, Hui-Zi Chen, Julie W. Reeser, Michele R. Wing, Jharna Miya, Eric Samorodnitsky, Amy M. Smith, Thuy Dao, Dorrelyn M. Martin, John L. Hays and Aharon G. Freud, The Ohio State University; Kelly M. Bailey, University of Pittsburgh; and Kristen K. Ciombor, Vanderbilt University.