On May 17, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) 20, 40, 60 mg for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinoma (aRCC) (Press release, Ipsen, MAY 17, 2018, View Source [SID1234650566]). This approval allows for the marketing of Cabometyx (cabozantinib) in this indication in all 28 member states of the European Union, Norway and Iceland.

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"Today’s EC approval is a step forward for advanced kidney cancer patients in Europe who will be able to access a new oral first-line treatment option that offers significant improvement over the standard of care", said Harout Semerjian, Executive Vice President, Chief Commercial Officer, Ipsen. "Ipsen remains committed to improving patients’ lives by continuing to develop new therapies and expanding the potential of Cabometyx across different indications."

Giuseppe Procopio, M.D., Head of the Genitourinary Unit at Fondazione Istituto Nazionale Tumori Milan, stated: "The value of treatment with Cabometyx has been corroborated by the data generated in clinical trials, and since 2016 physicians have also witnessed the potential of it when treating patients following VEGF-targeted therapy. For both of these reasons, physicians will be pleased to soon have access to this new first-line treatment option for intermediate- or poor- risk advanced RCC patients."
Today’s decision is based on the CABOSUN trial, which demonstrated that cabozantinib significantly prolongs progression-free survival (PFS) compared to sunitinib in treatment-naive aRCC patients with intermediate- or poor-risk. Cabozantinib is the first and only monotherapy to demonstrate superior clinical efficacy over sunitinib in treatment-naïve aRCC patients with intermediate- or poor-risk.
The detailed recommendations for the use of this product are described in the Summary of Product Characteristics (SmPC), available here (View Source).
About the CABOSUN study
On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with intermediate- or poor-risk aRCC per IMDC (International Metastatic RCC Carcinoma Database Consortium) criteria as determined by investigator assessment. CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These results were first presented by Dr. Toni Choueiri at the meeting of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2018).i
On June 19 2017 Exelixis announced that the analysis of the review by a blinded independent radiology review committee (IRC) has confirmed the primary efficacy endpoint results of investigator-assessed progression-free survival (PFS) from the CABOSUN randomized phase 2 trial of cabozantinib as compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Per the IRC analysis, cabozantinib demonstrated a clinically meaningful and statistically significant reduction in the rate of disease progression or death as measured by PFS. The incidence of adverse events (any grade) and the incidence of grade 3 or 4 adverse events between cabozantinib and sunitinib were comparable.
CABOSUN is a randomized, open-label, active-controlled phase II trial that enrolled 157 patients with aRCC determined to be intermediate- or poor-risk per IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, four weeks on followed by two weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate- or poor-risk per IMDC criteria (Heng, JCO, 2009).ii Prior systemic treatment for RCC was not permitted.
About advanced Renal Cell Carcinoma
With the incidence predicted to rise 22% by 2020, renal cell carcinoma (RCC) threatens to become one of the fastest growing cancers in the world.iii Targeted therapies including tyrosine kinase inhibitors (TKIs) of the VEGF receptor (VEGFR) introduced a decade ago, significantly transformed the treatment landscape of aRCC.iv
The American Cancer Society’s 2017 statistics cite kidney cancer as one of the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.v Clear cell RCC is the most common type of kidney cancer in adults.vi If detected in its early stages, the five-year survival rate for RCC is high. For patients with advanced- or late-stage metastatic RCC, however, the five-year survival rate is only 12% with no identified cure for the disease.vii Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.viii
The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL, and VEGF.ix–x These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness, and metastasis.xi, xii, xiii, xiv MET and AXL may provide escape pathways that drive resistance to VEGFR inhibitors. xii – xv
About CABOMETYX (cabozantinib)
Cabometyx is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA approved Cabometyx tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.
On December 19, 2017, Exelixis received approval from the FDA for Cabometyx for the expanded indication of treatment of advanced RCC.
On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinomain the European Union, Norway and Iceland.

On May 17, 2018 Veru Inc. (NASDAQ: VERU), a urology and oncology biopharmaceutical company, reported the publication of data from preclinical studies of VERU-111, a novel oral alpha and beta tubulin inhibitor, showing potent activity in a highly resistant model of human prostate cancer (Press release, Veru, MAY 17, 2018, View Source [SID1234529113]). An abstract of the data was published as part of the upcoming 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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Oral VERU-111 was evaluated in the 22Rv1 prostate cancer model, which represents a highly resistant and aggressive form of the disease possessing androgen receptor splice variants that are commonly found in prostate cancer resistant to hormonal approaches like abiraterone and enzalutamide. In the same model, docetaxel administered by injection did not have significant effect on tumor growth. Animals receiving docetaxel lost weight on the study, a surrogate for toxicity, whereas those on VERU-111 either maintained or gained weight while receiving the drug.

"The findings in this clinically relevant model of prostate cancer provide us with additional support and enthusiasm for evaluating VERU-111 in a Phase 1/2 clinical trial, which is scheduled to commence later this year. This is an animal model in which few drugs have been shown to be active. In addition, VERU 111 may be effective against other tumor types known to be sensitive to taxanes that are already FDA approved," said Mario Eisenberger, MD, the Dale Hughes Professor of Oncology at The Johns Hopkins University.

"Oral VERU-111 has shown positive and encouraging signs to become an important therapeutic option for a particularly challenging form of prostate cancer. We are studying VERU-111 in multiple other cancers, the data of which is also being published at ASCO (Free ASCO Whitepaper) this year. We have begun performing the required toxicity studies and our IND submission and first clinical studies are planned for later this year," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru.

About VERU-111
VERU-111 is a novel oral therapy targeting alpha and beta tubulin for the treatment of metastatic prostate, breast, endometrial, ovarian, and other cancers. In 2017, there were approximately 161,000 new cases of prostate cancer in the U.S. and about 25% of these men will die from the disease. In the U.S., 5% of men with prostate cancer will have metastatic cancer and up to 30% of men with high-risk, localized prostate cancer will develop metastatic cancer following initial therapy. The median survival of patients with metastatic prostate cancer ranges from 3.2 to 4.5 years. For these men, the 1st line therapy is androgen deprivation therapy, or medical castration. Although most will initially respond, nearly all these patients will progress to metastatic castration resistant prostate and have a poor prognosis with an average survival of 1.5 years. New 2nd line hormonal agents, like XTANDI (enzalutamide) and ZYTIGA (abiraterone/prednisone) have resulted in an additional four to five months of average survival, but nearly all men on these agents will develop progressive metastatic prostate cancer.

Drugs like VERU-111 that target tubulin, the subunits of microtubules, have been shown to be the most effective targeted cytotoxic chemotherapy for the treatment of metastatic prostate cancer. Microtubules are critical for cancer cell replication to stimulate genes for cancer cell proliferation. Docetaxel and cabazitaxel are examples of FDA-approved chemotherapy drugs that are given intravenously (IV) that target tubulin to treat metastatic prostate cancer. Although effective, the challenges for this class of chemotherapy drugs, also known as taxanes, include that they must be given intravenously (IV) and that the cancer cells develop resistance to taxanes. There are also serious safety concerns with IV taxanes which include serious hypersensitivity reactions, myelosuppression and neurotoxicity such as peripheral neuropathy and muscle weakness.

Unlike taxanes which bind to just the beta subunit of tubulin, VERU-111 binds strongly to both the alpha and beta subunits of tubulin. VERU-111 has: high oral bioavailability; less resistance as it does not interact with multiple drug resistance proteins so it cannot be pumped out of the cancer cell; minimal drug to drug interactions and high activity against many tumor types including: prostate cancer resistant to drugs like enzalutamide, AR-V7 positive and taxanes, as well as triple negative breast cancer, ovarian cancer, pancreatic cancer, lung cancer, and melanoma. In preclinical studies, VERU-111 appears to have less toxicity and less suppression of white blood cells compared to taxanes and other chemotherapy agents.

Production of the VERU-111 active pharmaceutical ingredient and preclinical safety toxicology studies required for an IND are expected to be completed in 2018. We anticipate filing an IND in 2018 and Phase 1/2 studies are planned for late 2018. Phase 1 studies of VERU-111 are planned in men who have metastatic prostate cancer that has progressed while taking androgen deprivation therapy and abiraterone or enzalutamide as well as in patients with metastatic breast, endometrial, and ovarian cancers. In the U.S., there is a $5 billion annual market for 2nd line hormone therapies for prostate cancer and a $4.8 billion annual market for IV-given taxanes and vinca alkaloids chemotherapies (docetaxel $1 billion and cabazitaxel $500 million in prostate cancer) per Decision Resources Group and Allied Market Research. Second line hormonal therapies like enzalutamide and abiraterone/prednisone have almost complete cross-resistance and should not be used in sequence for the treatment of metastatic prostate cancer. VERU-111 could be substituted for IV given docetaxel and cabazitaxel antitubulin chemotherapies. VERU-111 could also be developed as an oral dosing alternative to chemotherapies for the treatment of metastatic breast, endometrial and ovarian cancers as these tumors that responded to IV taxane chemotherapies.

On May 17, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that clinical data from SL-801 and SL-701 trials have been selected for poster presentations at the upcoming 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), to be held from June 1-5, 2018, at McCormick Place in Chicago, Illinois (Press release, Stemline Therapeutics, MAY 17, 2018, View Source [SID1234526753]). Abstracts are now available on the ASCO (Free ASCO Whitepaper) conference website.

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Details on the presentations are as follows:

Phase 2 Trial of SL-701 in Relapsed/Refractory Glioblastoma (GBM): Correlation of Immune Response with Longer-Term Survival

Abstract: 2058
Session: Central Nervous System Tumors
Presenter: David Peereboom, MD; Cleveland Clinic
Date: Saturday, June 2, 2018
Time: 1:15 – 4:45 PM CT
Interim Results from A Phase 1 Trial Of SL-801, A Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors

Abstract: 2560
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Presenter: Judy Wang, MD; Florida Cancer Specialists and Research Institute
Date: Monday, June 4, 2018
Time: 8:00 – 11:30 AM CT
About BPDCN
Please visit the BPDCN disease awareness booth (#4125) at ASCO (Free ASCO Whitepaper) 2018 and www.bpdcninfo.com.

On May 17, 2018 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical-stage biotechnology company with a fully human antibody discovery platform focused on the development of antibody-based products to address unmet medical needs in the treatment of cancer, reported that the Company has been issued Patent No. 9,856,324 by the United States Patent and Trademark Office (USPTO) for a patent titled, "HUMAN MONOCLONAL ANTIBODIES TO GANGLIOSIDE GD2 (Press release, MabVax, MAY 17, 2018, View Source [SID1234526770])."

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This is the second patent issued in the antibody portfolio created through MabVax’s unique discovery platform, which uses blood samples from patients vaccinated with selected tumor associated carbohydrate antigens. The recovery of human antibodies directly from vaccinated cancer patients makes the antibodies discovered by MabVax highly unique and potentially useful while reducing the kinds of toxicities induced by non-human antibodies. Similar to the Company’s sialyl lewis A (sLea) and Thomsen-nouveau (Tn) antigen targeting antibodies, the ganglioside GD2 targeting antibodies have the potential to be developed as therapeutic and diagnostic products. Additional disease targets for anti-GD2 antibodies include sarcoma, melanoma, and neuroblastoma.

"The issuance of this patent represents another valuable intellectual property asset brought forward by MabVax and is an important component of our unique discovery strategy and expands our robust patent estate. Importantly, this filing is timely as we evaluate additional product candidates that have the potential to address significant unmet needs in the treatment of cancers to fuel our pipeline and expand our partnering discussions," stated David Hansen, MabVax’s President and Chief Executive Officer.

The Company has already made substantial progress required to translate the GD2 preclinical development program into clinical development. In collaboration with St. Jude Children’s Research Hospital, data from the preclinical development program were presented as a poster at the World Molecular Imaging Conference last year. The results of the study demonstrated the anti-GD2 antibodies had high specificity and antibody drug conjugates based on these antibodies were readily internalized and cytotoxic. Immuno-PET agents developed with these antibodies showed good accumulation on osteosarcoma tumors and demonstrated potential utility as a diagnostic imaging agent.

On May 17, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking to treat cancer and rare disease, reported that an abstract highlighting X4P-001-RD, the company’s CXCR4 antagonist, has been selected for poster presentation at the 23rd Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), taking place June 14-17 in Stockholm, Sweden (Press release, X4 Pharmaceuticals, MAY 17, 2018, View Source [SID1234526787]). The presentation will describe interim clinical results from the ongoing Phase 2/3 study of X4P-001-RD in patients with WHIM syndrome, a rare genetic, primary immunodeficiency disease.

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X4 Pharmaceuticals will present clinical data from a PH2 study of X4P-001-RD in WHIM syndrome at the annual European Hematology Assoc. meeting #EHA23

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Details of the presentation on X4P-001-RD in WHIM syndrome are as follows:

Title: Phase 2 Study of X4P-001: A Targeted Oral Therapy for Patients with WHIM Syndrome

Author: David Dale, M.D., University of Washington

Abstract #: PS1056

Poster Session: Bone marrow failure syndromes incl. PNH – Clinical

Date and Time: Saturday, June 16, 5:30-7:00 p.m. CEST

About WHIM Syndrome

WHIM syndrome is a primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene resulting in susceptibility to certain types of infections. WHIM is an abbreviation for the characteristic clinical symptoms of the syndrome: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Within the overall category of primary immunodeficiencies, there are between 15,000 and 100,000 patients in the US that are classified with primary immunodeficiency disease of unknown origin – of which WHIM is one.1,2,3 WHIM syndrome is a rare disorder and the precise prevalence or incidence of patients that have the genetic mutation responsible for WHIM syndrome is unknown. Because patients are highly susceptible to infections, WHIM syndrome is associated with significant morbidity beginning in early childhood and continuing throughout life. Current therapy is limited to treatment of acute infections with antibiotics or prevention through the use of intravenous immunoglobulin or G-CSF. There is no approved therapy for the treatment of WHIM syndrome.