On September 19, 2018 Exelixis, Inc. (NASDAQ:EXEL) reported that its partner Ipsen Biopharmaceuticals Canada Inc. received approval from Health Canada of CABOMETYX (cabozantinib) tablets for the treatment of adults with advanced renal cell carcinoma (RCC) who have received prior vascular endothelial growth factor (VEGF) targeted therapy (Press release, Exelixis, SEP 19, 2018, View Source;p=irol-newsArticle&ID=2368033 [SID1234529488]). Health Canada granted CABOMETYX priority review status, which provided an accelerated review of Ipsen’s new drug submission.

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"The approval of CABOMETYX in Canada helps address a significant unmet need for patients with advanced kidney cancer whose disease has progressed on first-line therapy and who have limited treatments available," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "We are glad to be partnering with Ipsen to bring this much needed treatment option to these patients and look forward to our continued collaboration."

The Health Canada approval was based on results of the phase 3 pivotal METEOR trial in which CABOMETYX provided a statistically significant and clinically meaningful improvement in overall survival, progression-free survival and objective response rate as compared with everolimus in patients with advanced RCC who have received prior anti-angiogenic therapy.

Under the terms of the Collaboration Agreement with Ipsen, Exelixis will receive a milestone payment of $5 million for the Health Canada approval. The payment will be made by Ipsen within the next 70 days.

Please see Important Safety Information below and full U.S. prescribing information at View Source

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 The Canadian Cancer Society estimates that kidney cancer is among the top ten most common forms of kidney cancer in Canada, with approximately 6,600 new cases diagnosed in 2017.2 Clear cell RCC is the most common type of kidney cancer in adults.3 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 percent, with no identified cure for the disease.4 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment, and an estimated 14,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.4

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.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About the Exelixis and Ipsen Collaboration

In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. Under the terms of the Collaboration Agreement with Ipsen, Exelixis is entitled to receive a tiered royalty of 22 percent to 26 percent of annual net sales.

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced RCC. CABOMETYX tablets are also approved in: the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union for previously untreated intermediate- or poor-risk advanced RCC; and in Canada for adult patients with advanced RCC who have received prior VEGF targeted therapy. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC. On March 28, 2018, Ipsen announced that the European Medicines Agency validated its application for a new indication for cabozantinib as a treatment for previously treated advanced HCC in the European Union. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On September 19, 2018 TESARO, Inc. (NASDAQ: TSRO), an oncology-focused biopharmaceutical company, reported its participation in two upcoming investor conferences (Press release, TESARO, SEP 19, 2018, View Source [SID1234529487]). The two conferences are:

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The Cantor Global Healthcare Conference at the InterContinental New York Barclay Hotel on Wednesday, October 3, 2018.Lonnie Moulder, CEO of TESARO, and Mary Lynne Hedley, Ph.D., President and COO of TESARO, are scheduled to present an overview of the Company’s business and development programs at 11:30 AM ET and will also host meetings with investors.

The Leerink Partners Roundtable Series: Rare Disease & Oncology at the Lotte New York Palace on Wednesday, October 3, 2018.Mary Lynne Hedley, Ph.D., President and COO of TESARO, and Timothy Pearson, Executive Vice President and CFO of TESARO, will participate in an analyst-led fireside chat at 1:30 PM ET and will also host meetings with investors.
Live webcasts of the presentations at the Cantor and Leerink Partners conferences will be available by visiting the Investors section of the TESARO website at www.tesarobio.com. Archived replays of these webcasts will be available on the Company’s website for 14 days following the conference.

On September 19, 2018 Galera Therapeutics, Inc., a clinical-stage biotechnology company focused on the development of drugs targeting oxygen metabolic pathways with the potential to transform cancer radiotherapy, reported it has secured $150 million in a joint, oversubscribed Series C financing and royalty purchase agreement (Press release, Galera Therapeutics, SEP 19, 2018, View Source [SID1234529486]). The financing was led by new investor Clarus, with participation from additional new investors Adage Capital Management, HBM Healthcare Investments, Nan Fung Life Sciences, RA Capital, Rock Springs Capital and Tekla Capital Management LLC. Existing investors Correlation Ventures, Galera Angels, New Enterprise Associates, Novartis Venture Fund, Novo Ventures and Sofinnova Ventures also participated. In addition, Emmett T. Cunningham, Jr., M.D., Ph.D., MPH, Managing Director at Clarus, will join Galera’s Board of Directors.

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The financing includes a $70 million equity raise and an $80 million royalty financing payable from future sales. Per the terms of the royalty purchase agreement, Clarus will receive single-digit future commercial royalties from the sales of GC4419 and a related pipeline asset until the total royalty amount achieves an undisclosed multiple of the initial $80 million, upon which the royalty terminates.

Galera plans to use the proceeds of the combined equity and royalty financings to advance the clinical development of GC4419 into and through a pivotal Phase 3 clinical trial for the treatment of severe oral mucositis (SOM) in patients with head and neck cancer, its lead indication. SOM is one of the most debilitating side effects of radiotherapy, and there are currently no effective therapies to prevent or mitigate it. In a Phase 2b clinical trial, GC4419 demonstrated reductions in the incidence and duration of radiation-induced SOM in patients with locally advanced head and neck cancer.

"This significant raise further validates the dramatic and meaningful results of our randomized Phase 2b clinical trial and the potential of GC4419 to revolutionize radiotherapy. We are grateful for the robust support from existing and new investors as we prepare to advance GC4419 into a pivotal trial for SOM in head and neck cancer patients in the fourth quarter of this year," said Mel Sorensen, M.D., President and CEO of Galera. "The funds provide Galera with ample financial resources to complete the Phase 3 clinical trial, begin commercial planning activities and further explore the potential of GC4419 beyond SOM. We look forward to initiating a supportive care trial of GC4419 in radiation-induced esophagitis and a therapeutic trial in a second cancer indication, as well as continuing to evaluate the safety and anti-tumor effect of GC4419 in our ongoing Phase 1/2 pancreatic cancer clinical trial."

"Galera has generated robust, randomized Phase 2b data supporting the efficacy and safety profile of GC4419. These data, along with Breakthrough and Fast Track designations from the U.S. Food and Drug Administration (FDA), support the promise of GC4419 to transform how radiotherapy is used to treat patients with head and neck malignancies," said Dr. Cunningham. "With its highly differentiated scientific approach and its potential in a number of indications, GC4419 is well-positioned to address serious unmet medical needs. We’re pleased to support Galera as the company moves closer to potentially bringing GC4419 to head and neck cancer patients with SOM who need a new treatment option."

About GC4419

GC4419 is a highly selective and potent small molecule dismutase mimetic that closely mimics the activity of human superoxide dismutase enzymes. GC4419 works to reduce elevated levels of superoxide caused by radiation therapy by rapidly converting superoxide to hydrogen peroxide and oxygen. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the anti-tumor efficacy of radiation therapy. Conversion of elevated superoxide to hydrogen peroxide, which is selectively more toxic to cancer cells, can also enhance the effect of radiation on tumors, particularly with stereotactic body radiation therapy (SBRT), which produces high levels of superoxide.

GC4419 has been studied in patients with head and neck cancer, GC4419’s lead indication, for its ability to reduce the incidence and duration of radiation-induced severe oral mucositis. Results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrated GC4419’s ability to dramatically reduce the duration of SOM from 19 days to 1.5 days (92 percent), the incidence of SOM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, while demonstrating acceptable safety when added to a standard radiotherapy regimen. GC4419 is currently being studied in combination with SBRT for its anti-tumor effect in a Phase 1/2 trial of patients with locally advanced pancreatic cancer. In addition, in multiple preclinical studies, GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The FDA granted Breakthrough Therapy designation to GC4419 for the reduction of the duration, incidence and severity of SOM induced by radiation therapy with or without systemic therapy. The FDA also granted Fast Track designation to GC4419 for the reduction of the severity and incidence of radiation and chemotherapy-induced OM.

1stOncology™, the leading oncology drug development surveillance and analysis platform from BioSeeker Group, now fully supports the latest release of the GLOBOCAN database (September 2018) which includes estimates of the incidence, mortality and prevalence from 36 types of cancer and for all cancers combined in 185 countries of the world. The estimates are presented for 2018, separately for each sex and for the 18 traditional age-groups.

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On September 18, 2018 Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, reported that the completion of a $2.7M financing effort, which includes an over-subscribed $2M round in venture-backed capital and over $670K in non-dilutive capital (Press release, PhoenixMD, SEP 18, 2018, View Source [SID1234536960]). The venture round is led by Pallasite Ventures and includes new angel investors and existing angel investors from prior funding rounds. PhoenixMD intends to use the proceeds to advance its lead asset PMD-026 through IND-enabling studies and to develop a sophisticated companion diagnostic test to determine which patients have high levels of activated RSK2, the protein that PMD-026 disrupts.

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"This financing is a critical step forward in bringing the first disease-modifying therapeutic treatment to women suffering from TNBC. The PhoenixMD team is committed to innovating in the breast cancer field and we are excited to deploy Pallasite’s investment to such an experienced team to solve an unmet medical need," said Chris Bissonnette, Ph.D., Managing Partner of Pallasite Ventures. In connection with the financing, Dr. Bissonnette has joined PhoenixMD’s Board of Directors.

"We are thrilled to close our first venture-backed round with such high-quality investors, which is a major achievement for the company," said Sandra E. Dunn, Ph.D., CEO of PhoenixMD. "The proceeds from this financing, and the non-dilutive capital from recent research grants will advance PMD-026 through critical IND-enabling studies and will begin planning around our upcoming Phase 1 study, which we are very excited to initiate."

About Triple Negative Breast Cancer (TNBC) and RSK Kinases

Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. It is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are still no targeted therapies available for TNBC.

There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.

RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90% of primary TNBC express high levels of RSK1 and RSK2. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer RSK inhibitors and companion diagnostics for cancer indications – initially in breast cancer – with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

Currently, there are no approved targeted therapies for TNBC, although several drugs are subject to research studies and clinical trials. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.