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Regeneron and Inovio Enter Immuno-Oncology Clinical Study Agreement for Glioblastoma Combination Therapy

On May 8, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported a clinical study agreement for a Phase 1b/2a immuno-oncology trial (Press release, Regeneron, MAY 8, 2017, View Source [SID1234518958]). The study will be conducted by Inovio in patients with newly-diagnosed glioblastoma multiforme (GBM) and will evaluate Regeneron’s PD-1 inhibitor, REGN2810, in combination with Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12.

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The open-label trial, which is expected to begin later this year, is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 patients. The study will be conducted at 30 U.S. sites and the primary endpoints are safety and tolerability. The study will also evaluate immunological impact, progression-free survival and overall survival.

GBM is a devastating disease for both patients and caregivers. It is the most aggressive brain cancer and its prognosis is extremely poor, despite a limited number of new therapies approved over the last ten years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than three percent.

"The unmet need for effective therapies in GBM remains extremely high. Certain immune checkpoint inhibitors have shown efficacy in certain cancers, but evidence increasingly suggests that the benefit of checkpoint inhibitors can be enhanced when used in combination with therapies that generate T cells," said David Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. "Inovio has an innovative immunotherapy platform which has shown the ability to generate antigen-specific T cells in disease areas including cancer. We look forward to exploring the potential of combining a T cell generating immunotherapy encoding multiple antigens with REGN2810, a PD-1 checkpoint inhibitor."

Under the terms of the agreement, the trial will be solely conducted and funded by Inovio, based upon a mutually agreed upon study design, and Regeneron will supply REGN2810. Inovio and Regeneron will jointly conduct immunological analyses in support of the study. Regeneron, in collaboration with Sanofi, is developing REGN2810 both alone and in combination with other therapies for the treatment of various cancers.

"Regeneron’s approach to oncology includes evaluating the combination of innovative therapies that act on diverse pathways and targets," said Israel Lowy, MD, PhD, Vice President of Translation Sciences and Oncology, Regeneron. "Using our PD-1 inhibitor as a therapeutic backbone alongside Inovio’s T cell-generating therapies offers a new path for exploration and heightens the potential to develop new, desperately-needed treatment options for patients."

"I am a strong believer in this combination regimen approach in immuno-oncology: use Inovio immunotherapies to generate killer T-cells to turn ‘cold’ tumors into ‘hot’ tumors, then block T cell suppression via checkpoint inhibition," said J. Joseph Kim, PhD, Inovio’s President and Chief Executive Officer. "This step with INO-5401 is very important for us in 2017, as we believe INO-5401 has the potential to be a powerful cancer immunotherapeutic in combination with promising checkpoint inhibitors such as Regeneron’s REGN2810, and we look forward to investigating its potential for GBM and multiple other challenging cancers."

About Glioblastoma
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most common and aggressive type of brain cancer. GBM is usually found in the area of the brain which controls some of the most advanced processes such as speech and emotions. GBM treatment is often limited by the tumor location and ability of a patient to tolerate surgery. Consequently, it is a particularly difficult cancer to treat. Worldwide there are an estimated 240,000 cases of brain and nervous system tumors per year; GBM is the most common and most lethal of these tumors.

About INO-5401
INO-5401 includes Inovio’s SynCon antigens for WT1, hTERT and PSMA and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of attractive cancer antigens, designating them as high priorities for cancer immunotherapy development. WT1 was at the top of the list. The hTERT antigen relates to 85 percent of cancers, and WT1 and PSMA antigens are also widely prevalent in many cancers.

Preclinical Data on Aptose Biosciences FLT3/BTK Inhibitor CG’806 Presented at AACR Hematologic Malignancies Meeting

On May 8, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a highly potent pan-FLT3/BTK inhibitor, exerts compelling activity against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3 and eradicates AML tumors in a murine xenograft model (Press release, Aptose Biosciences, MAY 8, 2017, View Source;p=RssLanding&cat=news&id=2270752 [SID1234518895]). The data were presented in a poster on Sunday, May 7, 2017 at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, held May 6-9 in Boston, MA.

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The poster, entitled CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3, demonstrated the superior potency of CG’806, relative to competitive agents, against hematologic malignancy cell lines driven by various WT or mutant forms of FLT3. In addition, once daily oral dosing of CG’806 in a murine model achieved sustained micromolar plasma concentration over a 24hr period, and was accompanied by complete elimination of AML FLT3-ITD tumors in the absence of toxicity.
Results were presented by Weiguo Zhang, M.D., Ph.D., Assistant Professor of Leukemia at The University of Texas MD Anderson Cancer Center, for a research team led by Michael Andreeff, M.D., Ph.D., Professor of Leukemia.

"Given the potency of CG’806 against all of the mutant forms of FLT3 AML and the ability to eradicate AML tumors in murine xenograft models, CG’806 has demonstrated the potential to be superior to other FLT3 inhibitors and is beginning to differentiate itself as a targeted treatment for AML," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "We believe CG’806 has the potential to become the best-in-class FLT3 inhibitor, and our internal efforts now are focused on delivering CG’806 to AML patients as soon as practicable."

CG’806 and competitor FLT3 inhibitors were tested for potency to kill a series of isogenic cells, in which a specific form (WT or mutant) of FLT3 drove survival and proliferation of cells. Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with the ITD mutation, D835 mutations, the ITD plus F691I/Y842D/D835 mutations, or in FLT3 wild-type cells. The IC50s were 0.17, 0.82, 9.49, 0.30, 8.26, 9.72, and 0.43 nM for human FLT3-ITD mutated AML cells MV4-11 (FLT3-ITD) and MOLM13 (FLT3-ITD), murine leukemia Ba/F3 (FLT3-WT), Ba/F3 (FLT3-ITD), Ba/F3 (FLT3-D835Y), Ba/F3 (FLT3-ITD+D835Y), and Ba/F3 (FLT3-ITD+F691L) cells, respectively. CG’806 triggered profound apoptosis in cell lines harboring FLT3-ITD mutations and suppressed FLT3 and its downstream MAPK/AKT signaling. Moreover, CG’806 demonstrated in vivo tumor eradication without toxicity when administered orally, once daily for 14 days as a single agent in the MV4-11 AML murine xenograft model, and demonstrated sustained micromolar plasma drug levels in mice after a single oral administration.

The presentation will be published in the AACR (Free AACR Whitepaper) Hematologic Malignancies Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG’806
CG ‘806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

Aeterna Zentaris Reports First Quarter 2017 Financial and Operating Results

On May 8, 2017 Aeterna Zentaris Inc. (NASDAQ, TSX: AEZS) (the "Company"), a specialty biopharmaceutical company engaged in developing and commercializing novel pharmaceutical therapies, reported financial and operating results for the first quarter ended March 31, 2017 (Filing, Q1, AEterna Zentaris, 2017, MAY 8, 2017, View Source [SID1234518960]).

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Commenting on recent key developments, David A. Dodd, President and Chief Executive Officer of the Company, stated, "On May 1, we reported that the ZoptEC (zoptarelin doxorubicin in endometrial cancer) Phase 3 study of Zoptrex in women with locally advanced, recurrent or metastatic endometrial cancer did not achieve its primary endpoint of demonstrating a statistically significant increase in the median period of overall survival of patients treated with Zoptrex as compared to patients treated with doxorubicin. Therefore, the results of the study do not support regulatory approval of Zoptrex. Based on this outcome, we do not anticipate conducting clinical trials of Zoptrex with respect to any other indications." Regarding the Company’s plans, Mr. Dodd continued, "Our focus has now shifted entirely to filing our new drug application ("NDA") for Macrilen and, if the product is approved, to its commercial launch as soon as possible. We will also optimize our resources to be consistent with our focus on Macrilen-related efforts. Consequently, we now expect that our monthly average use of cash in operations during the remainder of 2017 will be between $1.7 million and $1.9 million, a decrease of approximately 22%, compared to the first quarter. We continue to believe in the potential that Macrilen provides for us to become a successful specialty pharmaceutical company. Our intention is to submit the Macrilen NDA in the third quarter of 2017 and, if the product receives approval from the U.S. Food and Drug Administration (the "FDA"), to commercially launching the product in the first quarter of 2018."

Exhibit 99.1

First Quarter Financial Highlights

Revenues
Revenues were $261,000 for the three months ended March 31, 2017, as compared to $242,000 for the same period in 2016. The increase is mainly explained by the amortization of the up-front payment received in connection with one of the out-licensing agreements that we entered into in 2016 for ZoptrexTM with respect to a territory outside our core areas of interest.

Research and Development ("R&D") costs
R&D costs were $2.5 million for the three months ended March 31, 2017, compared to $3.7 million for the same period in 2016. The decrease in our R&D costs for the three months ended March 31, 2017, as compared to the same period in 2016, is mainly attributable to lower third-party costs attributable to Zoptrex, which is mainly due to the fact that we completed the clinical portion of the ZoptEC clinical trial during the first quarter of 2017. Third-party costs attributable to Macrilen remained stable during the three months ended March 31, 2017, as compared to the same period in 2016.

General and Administrative ("G&A") Expenses
G&A expenses were $1.9 million for both three-month periods ended March 31, 2017 and 2016. The G&A expenses remained stable and were in line with our expectations for the first quarter.

Selling Expenses
Selling expenses were $1.5 million for the three months ended March 31, 2017, as compared to $1.7 million for the same period in 2016. Selling expenses for the three months ended March 31, 2017 and 2016 represent mainly the costs of our sales force related to the co-promotion activities as well as our sales management team. The decrease in selling expenses is explained by the reduction in the number of sales representatives from 20 to 13 in February 2017.

Net Finance Income
Net finance income was $1.5 million for the three months ended March 31, 2017, as compared to $3.3 million, for the same period in 2016. The decrease in finance income is mainly attributable to the change in fair value recorded in connection with our warrant liability. Such change in fair value results from the periodic "mark-to-market" revaluation, via the application of option pricing models, of outstanding share purchase warrants. The closing price of our common shares, which, on the NASDAQ, fluctuated from $2.45 to $3.65 during the three-month period ended March 31, 2017, compared to $2.67 to $4.40 during the same period in 2016, also had a direct impact on the change in fair value of warrant liability.

Net Loss
Net loss for the three months ended March 31, 2017 was $(4.1) million, or $(0.31) per basic and diluted share, as compared to a net loss of $(3.7) million, or $(0.37) per basic and diluted share, for the same period in 2016. The increase in net loss for the three months ended March 31, 2017, as compared to the same period in 2016, is largely attributable to lower operating expenses offset by lower net finance income, as described above. The basic and diluted loss per share decreased because the number of shares outstanding increased following an offering completed in November 2016 as well as issuances under our various ATM programs.

Liquidity
Cash and cash equivalents were $17.8 million as at March 31, 2017, as compared to $22.0 million as at December 31, 2016. The decrease in cash and cash equivalents as at March 31, 2017, as compared to December 31, 2016, is due to the net cash used in operating activities and variations in components of our working capital. The decrease was partially offset by the net proceeds generated by the issuance of common shares under our various ATM programs.

Oncolytics Biotech® Inc. Announces FDA Fast Track Designation for REOLYSIN® in Metastatic Breast Cancer

On May 8, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported that the United States Food and Drug Administration (FDA) has granted Fast Track designation for REOLYSIN, the Company’s proprietary immuno-oncology viral agent, for the treatment of metastatic breast cancer (Press release, Oncolytics Biotech, MAY 8, 2017, View Source [SID1234518954]).

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"Fast Track designation represents an important step for our clinical development plan, which is squarely focused on a registration pathway in metastatic breast cancer and advancing REOLYSIN to regulatory review as quickly as possible," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "Our goal is to conduct an End-of-Phase 2 meeting with the FDA as soon as is practical and obtain scientific guidance. We are eager to leverage this designation and use the opportunity for more frequent dialogue with the FDA, as well as the potential for an expedited review process, to support the future development of REOLYSIN."

In April 2017, data from an open-label, randomized, phase 2 study assessing the therapeutic combination of intravenously-administered REOLYSIN given in combination with the chemotherapy agent paclitaxel versus paclitaxel alone, in patients with advanced or metastatic breast cancer (IND 213) was presented at the American Association of Cancer Research Annual Meeting. The combined treatment demonstrated a statistically significant increase in median overall survival. Based on Oncolytics’ evolving understanding of REOLYSIN’s mechanism of action, along with the positive overall survival data generated to date, the Company is pursuing metastatic breast cancer as its primary focus for late-stage clinical testing.

The FDA’s Fast Track process is designed to facilitate the development, and expedite the review of drugs that treat serious conditions and fill an unmet medical need. Fast Track designation supports more frequent dialogue with the FDA on a company’s drug development plan, data requirements and clinical trial design. It also, in certain situations, enables the FDA to take action on a new drug or biologics license application more rapidly than under the standard review process.

Novartis receives FDA approval for first-of-its-kind Kisqali® Femara® Co-Pack for initial treatment of HR+/HER2- advanced or metastatic breast cancer

On May 8, 2017 Novartis reported that the US Food and Drug Administration (FDA) has approved the Kisqali Femara Co-Pack (ribociclib tablets; letrozole tablets) for the treatment of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in postmenopausal women1 (Press release, Novartis, MAY 8, 2017, View Source [SID1234518952]). The Kisqali Femara Co-Pack is the first, and only currently available, combination pack with two prescription products in advanced breast cancer.

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With this FDA approval, physicians in the United States now have the flexibility to prescribe Kisqali two different ways: via the new Co-Pack or as two separate prescriptions of Kisqali and any aromatase inhibitor.

"As we strive to keep the patient at the center of every decision that we make at Novartis, we are pleased that collaborating closely with the FDA has resulted in our being able to offer this unique combination pack of two prescription cancer medicines," said Bill Hinshaw, Executive Vice President and Head, US, Novartis Oncology. "Providing physicians a convenient one package prescribing option for their patients underscores our commitment to deliver innovative treatment solutions to the metastatic breast cancer community."

The innovative packaging of the Kisqali Femara Co-Pack allows patients the convenience of obtaining a full 28-day cycle of the two medicines in one package with one prescription and one co-pay. The Kisqali Femara Co-Pack is available at the same cost as Kisqali alone.

The Kisqali Femara Co-Pack is available in three dosage strengths: Kisqali 600 mg plus Femara 2.5 mg, Kisqali 400 mg plus Femara 2.5 mg, and Kisqali 200 mg plus Femara 2.5 mg. The Kisqali Femara Co-Pack will be available in the US later this month at both specialty and retail pharmacies, and does not change the indication for either medicine.

Kisqali was approved on March 13, 2017 in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer2. Femara is an aromatase inhibitor approved for first-line treatment of postmenopausal women with HR+ or unknown advanced breast cancer3. Developed by Novartis, Femara has been a standard of care option for more than a decade in early and advanced breast cancer.

About Kisqali (ribociclib)
Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Femara (letrozole)
Femara (letrozole) is a form of hormone therapy known as an aromatase inhibitor, which works by reducing the amount of estrogen produced in the bodies of postmenopausal women. Femara was first approved in 1997 for treatment of postmenopausal women with HR+ or unknown advanced breast cancer that progressed after antiestrogen therapy. In 2001, Femara was approved as first-line treatment of postmenopausal women with HR+ or unknown locally advanced or metastatic breast cancer.

Femara has been available for nearly 20 years and research by Novartis has continued during this time.

Kisqali (ribociclib) and Femara (letrozole) Important Safety Information
Kisqali (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor as the first hormonal-based therapy to treat women who have gone through menopause with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The Kisqali Femara Co-Pack (ribociclib tablets; letrozole tablets) is a prescription medicine used as the first hormonal based therapy to treat women who have gone through menopause with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. The Kisqali Femara Co-Pack contains 2 different types of medicines: Kisqali and Femara. It is not known if Kisqali or the Kisqali Femara Co-Pack is safe and effective in children. Kisqali or the Kisqali Femara Co-Pack can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali or the Kisqali Femara Co-Pack can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali or the Kisqali Femara Co-Pack and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali or the Kisqali Femara Co-Pack, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali or the Kisqali Femara Co-Pack can harm an unborn baby. Females who are able to become pregnant and who take Kisqali or the Kisqali Femara Co-Pack should use effective birth control during treatment and for at least 3 weeks after the last dose. Do not breastfeed during treatment with Kisqali or the Kisqali Femara Co-Pack and for at least 3 weeks after the last dose. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid pomegranate or pomegranate juice, and grapefruit or grapefruit juice while taking Kisqali or the Kisqali Femara Co-Pack. The most common side effects (incidence ≥20%) of Kisqali + letrozole are white blood cell count decreases, nausea, tiredness, diarrhea, hair thinning or hair loss, vomiting, constipation, headache, and back pain. The most common grade 3/4 side effects in the Kisqali + letrozole arm (incidence >2%) were low neutrophils, low leukocytes, abnormal liver function tests, low lymphocytes, and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

Please see full Prescribing Information for the Kisqali Femara Co-Pack, available at View Source

About Novartis in Advanced Breast Cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in collaboration with the global community. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.