On March 28, 2018 Aeterna Zentaris Inc. (NASDAQ:AEZS) (TSX:AEZS) reported financial and operating results for the fourth quarter and year ended December 31, 2017 (Press release, AEterna Zentaris, MAR 28, 2018, View Source [SID1234525022]).

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All Amounts are in U.S. Dollars

Recent Key Developments

U.S. Food and Drug Administration (FDA) granted marketing approval for Macrilen

Marketing Authorization Application (MAA) for the use of Macrilen (macimorelin) for the evaluation of AGHD was accepted by the European Medicines Agency (EMA) for regulatory review

Macrilen(macimorelin) License and Assignment Agreement to Strongbridge Biopharma completed

Financial condition and capital structure improved

As of December 31, 2017, we had $7.8 million of unrestricted cash and cash equivalents at year-end and no third-party debt;

Upfront payment of $24 million received from Strongbridge in January 2018

Approximately 16,440,760 Common Shares outstanding as of March 27, 2018

Appointment of James Clavijo as Chief Financial Officer
Commenting on recent key developments, Michael V. Ward, President and Chief Executive Officer for Aeterna Zentaris, stated, "We made a positive transformation in the fourth quarter 2017 when we pursued out-licensing to maximize shareholder value and now are focused on the flawless execution of the contractual obligations with Strongbridge. We have been working with the exceptional leadership team at Strongbridge to transition Macrilen and are on target to support their efforts to successfully launch Macrilen as early as possible."

Mr. Ward continued his commentary with an update on the development of Macrilen. "We are now in a better position to maximize additional value of Macrilen by licensing in territories outside of the United States and Canada. We have continued adjustment of the operating plan in Germany and the United States to reduce non-essential expenses. We further enhanced our operations with the appointment of James Clavijo as Chief Financial Officer on March 5, 2018. James is highly-skilled at building effective financial systems, organization restructuring, and developing solutions leading to financial and operational improvements."

Financial Highlights

Revenues $0.9 million

Research and Development ("R&D") Costs $10.7 million

General and Administrative ("G&A") Expenses $8.2 million

Selling Expenses $5.1 million

Net Finance Costs Income $2.8 million

Income Tax Recovery $3.5 million

Net Loss $16.8 million

Working Capital $3.6 million

Fourth Quarter and Full-Year Highlights

Revenues

Sales commission and other were $0.1 million and $0.5 million for the three and twelve months ended December 31, 2017 and $0.1 million and $0.4 million for the same periods in 2016, and thus increased in 2017 as compared to 2016. In 2017, those revenues mainly resulted from our sales team exceeding pre-established unit sales baseline thresholds under our co-promotion agreement to sell Saizen. We also generated sales commission in connection with our promotion of APIFINY. In the corresponding periods in 2016, sales commission and other revenues were mainly related to EstroGel.

License fees were $0.1 million and $0.5 million for the three and twelve months ended December 31, 2017, as compared to $0.2 million and $0.5 million for the same periods in 2016.

The Company currently has deferred revenues at December 31, 2017 of $541,000 relating to non-refundable upfront payments it previously received for licensing and technology transfer arrangements that it entered into with respect to the development of Zoptrex in various territories. Due to events that occurred in 2018, the Company does not anticipate development of Zoptrex under the licensing agreements, therefore the Company’s remaining carrying amount of deferred revenues will be recognized in the first quarter of 2018 as income.

Operating Expenses

R&D costs were $0.5 million and $10.7 million for the three and twelve months ended December 31, 2017, compared to $4.6 million and $16.5 million for the same periods in 2016. R&D costs decreased for the three-month and twelve-month periods ended December 31, 2017 as compared to the same period in 2016. The decrease in R&D costs is mainly attributable to lower comparative third-party costs, as described below, partially offset by the recording, in the third quarter of 2017, of a provision in connection with the 2017 German Restructuring.

Additionally, the decrease in our R&D costs for the twelve months ended December 31, 2017, as compared to the same period in 2016, is attributable to lower employee compensation and benefits costs, lower facilities rent and maintenance costs as well as lower other costs. A substantial portion of this decrease is due to the realization of cost savings in connection with our ongoing efforts to streamline our R&D activities and to increase our commercial operations and flexibility by reducing our R&D staff, which was started in 2014 (the "Resource Optimization Program"). The R&D costs for the year ended December 31, 2017 were lower than anticipated mainly because we were able to negotiate reductions to a change order received from our principal R&D third-party service provider.

Third-party costs attributable to Zoptrex decreased during the three and twelve months ended December 31, 2017, as compared to the same period in 2016, mainly since we closed out the study and related activities in the second quarter following the negative Zoptrex top-line results on May 1, 2017. The negative costs for the three-month period ended December 31, 2017 are mainly explained by lower close out costs as compared to the accrual made in the second quarter.

Third-party costs attributable to Macrilen (macimorelin) decreased during the three and twelve months ended December 31, 2017, as compared to the same period in 2016. This is mainly since we completed the Phase 3 clinical trial at the end of 2016. The costs incurred in 2017 related to the detailed analysis of the top-line results as well as the preparation of the NDA filing which was submitted on June 30, 2017. The costs reversal in the fourth quarter of 2017 are explained mainly by the reductions to close out costs.

Excluding the impact of foreign exchange rate fluctuations, we expect that we will incur overall R&D costs of between $1.0 million and $2.0 million for the year ended December 31, 2018.

G&A expenses were $2.8 million and $8.2 million for both the three and twelve-month periods ended December 31, 2017, as compared to $1.8 million and $7.1 million for the same periods in 2016. The increase in our G&A costs for the three and twelve months ended December 31, 2017, as compared to the same period in 2016, is mainly due to outside legal costs. The G&A expenses are in line with expectations.

Excluding the impact of foreign exchange rate fluctuations and the recording of transaction costs related to potential financing activities (not currently known or estimable), we expect that G&A expenses will range between $9.0 million and $11.0 million in 2018.

Selling expenses were $0.5 million and $5.1 million for the three and twelve months ended December 31, 2017, as compared to $1.5 million and $6.7 million for the same periods in 2016. Selling expenses for the three and twelve months ended December 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 elimination of sales representatives. In the fourth quarter, we eliminated all sales representatives as part of the restructuring efforts. Based on currently available information, we expect selling expenses to range between $0.2 million and $0.5 million in 2018.

Other Income (Costs)

Net finance income (costs) was $(0.4) million and $2.8 million for the three and twelve months ended December 31, 2017, as compared to $(0.6) million and $4.5 million, for the same periods in 2016. The decrease in finance income is mainly attributable to the change in fair value of warrant liability. Such change in fair value results from the periodic "mark-to-market" revaluation, via the application of pricing models, of outstanding share purchase warrants. The closing price of our common shares, which, on the NASDAQ, fluctuated from $0.84 to $3.65 during the twelve-month period ended December 31, 2017, compared to $2.67 to $4.94 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 and twelve months ended December 31, 2017 was $0.5 million and $16.8 million (or $0.03 and $1.12 per share), as compared to a net loss of $8.2 million and $25.0 million (or $0.71 and $2.41 per share) for the same periods in 2016. The decrease in net loss for the three-month period ended December 31, 2017 is a result of the reduction in third party R&D costs. The reduction is attributed to closing out the Zoptrex study and successful completion in the U.S. of the Macrilen (macimorelin) filing.

Liquidity

Our operations and capital expenditures have been financed through certain transactions impacting our cash flows from operating activities, public equity offerings and issuances under various ATM programs.

At December 31, 2017, we had $7.8 million of cash and cash equivalents. We expect existing cash balances and operating cash flows (including the upfront cash payment of $24 million from Strongbridge discussed below) will provide us with adequate funds to support our current operating plan for at least the next twelve months.

Conference Call

The Company will host a conference call to discuss these results on Wednesday, March 28, 2017, at 8:30 a.m., Eastern Time. Participants may access the conference call by telephone using the following dial-in numbers:

Toll-Free: 877-407-8029, Confirmation #13677806

Toll: 201-689-8029, Confirmation #13677806
A replay of the conference call will also be available on the Company’s website for a period of 30 days.

For reference, the Management’s Discussion and Analysis of Financial Condition and Results of Operations for the fourth quarter and full year 2017, as well as the Company’s audited consolidated financial statements as at December 31, 2017, 2016 and 2015, can be found at www.aezsinc.com in the"Investors" section

On March 28, 2018 Tempest Therapeutics Inc.,a development-stage biotechnology company advancing small molecules that modulate anti-tumor immunity pathways, reported the completion of a $70 million Series B financing led by founding investor Versant Ventures and by F-Prime Capital and Quan Capital (Press release, Tempest Therapeutics, 28 28, 2018, View Source [SID1234525046]). The syndicate also includes Lilly Asia Ventures, Foresite Capital and Eight Roads Ventures.

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"We are strong believers in the promise of small molecule therapeutics that target immune cells in the tumor microenvironment," said Brad Bolzon, managing director and chair of Versant and Tempest. "With a portfolio of several high-quality drug candidates and an experienced management team, Tempest is well-positioned to introduce new therapies for multiple malignancies."

Tom Dubensky has been appointed as Tempest CEO, and has recruited an experienced development team to translate these programs into the clinic over the coming months. "We are extremely excited to debut Tempest today and look forward to rapidly advancing a superior IDO inhibitor into the clinic as the first of four new programs," said Dr. Dubensky. "It is very gratifying to have attracted a top-tier syndicate of investors who share our belief in the depth and breadth of Tempest’s pipeline. Our ongoing collaboration with Inception will not only facilitate development of the existing pipeline but also allow for discovery of complementary drug candidates that promote induction of effective anti-tumor immunity."

Tempest is developing first-in-class and best-in-class small molecules that modulate distinct immune response pathways. Proceeds from the Series B financing will support the advancement of lead program TPST-8844 into the clinic in the next 12 months as well as advancement of at least two other programs into the clinic shortly thereafter.

TPST-8844 is a potent inhibitor of IDO, an enzyme that is over-expressed in tumor cells and suppresses the activity of immune cells in the surrounding microenvironment. The combination of an IDO inhibitor and checkpoint inhibitor such as an anti-PD-1 has been shown as a synergistic combination with the potential to be the therapy of choice in multiple malignancies. Tempest’s unpublished preclinical data suggest TPST-8844 has superior features to others currently in development.

TPST-1120 is a first-in-class antagonist of the peroxisome proliferator-activated receptor alpha (PPARα) transcription factor. Tempest has shown that blocking PPARα inflames the tumor microenvironment and activates important tumor-killing immune cells. TPST-1120 has shown durable efficacy in multiple tumor models both as a single agent and in combination with other cancer therapies.

Tempest’s E-prostanoid (EP) receptor antagonists can effectively interrupt the immuno-suppressive effects of prostaglandin. The company has translated its unique insights about EP receptor subtypes to produce novel compounds with increased anti-tumor efficacy compared with pan-EP or single EP inhibitors currently in clinical development.

The company’s molecules were developed by Inception Sciences, a Versant Ventures Discovery Engine led by Peppi Prasit. In late 2017, Tempest spun out as an independent company led by Dr. Dubensky. Dr. Dubensky brings significant expertise in the development and translation of novel immune therapies, having served most recently as chief scientific officer of Aduro Biotech where he led the advancement of first-in-class STING agonists.

In connection with today’s financing Tempest has added three new members to its board of directors: Tom Woiwode, managing director at Versant, Robert Weisskoff, a partner at F-Prime Capital, and Stella Xu, managing director at Quan Capital. They join existing board members Dr. Dubensky, Dr. Prasit and Dr. Bolzon.

On March 28, 2018 Exelixis, Inc. (NASDAQ:EXEL) reported that its partner Ipsen received validation of the application for variation to the CABOMETYX (cabozantinib) marketing authorization from the European Medicines Agency (EMA), the European regulatory authority, for the addition of a new indication for patients with previously treated advanced hepatocellular carcinoma (HCC) (Press release, Exelixis, MAR 28, 2018, View Source;p=RssLanding&cat=news&id=2340047 [SID1234525465]). The filing is based on results of the global pivotal phase 3 CELESTIAL trial, which met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with advanced HCC who had been previously treated with sorafenib (pre-specified critical p-value ≤ 0.021).

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"We are excited by the potential benefit CABOMETYX may offer patients in the European Union diagnosed with previously treated advanced hepatocellular carcinoma, a patient community that has very limited treatment options," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "This milestone represents significant progress in our collaboration and development program with Ipsen to expand the use of CABOMETYX to additional patient populations outside of the currently approved indication."

Under the terms of the Collaboration and License Agreement with Ipsen, upon the acceptance of this filing, Exelixis earned a $10 million milestone payment. Due to new revenue recognition standards the company adopted in the first quarter of 2018, Exelixis will not record this amount as revenue but expects the milestone to be paid by Ipsen in the second quarter of this year.

On March 6, 2017, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to cabozantinib for the treatment of advanced HCC. On October 16, 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis.

On March 15, 2018, Exelixis announced the completed submission of a supplemental New Drug Application (sNDA) to the FDA for CABOMETYX for previously treated advanced HCC based on findings from CELESTIAL. An sNDA is an application to the FDA that, if approved, will allow a drug sponsor to make changes to a previously approved product label, including modifications to the indication.

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

About the CELESTIAL Study

CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

About HCC

Liver cancer is the second-leading cause of cancer death worldwide, accounting for more than 700,000 deaths and nearly 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated nearly 42,000 new cases in the U.S. in 2018.2 HCC is the fastest-rising cause of cancer-related death in U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced renal cell carcinoma (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 vascular endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted to the EMA the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on March 23, 2018, the CHMP provided a positive opinion for CABOMETYX for the first-line treatment of intermediate- or poor-risk advanced RCC. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. 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, including RCC.

CABOMETYX is not indicated for previously treated advanced HCC.

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

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.
Please see accompanying full Prescribing Information View Source

On March 28, 2018 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small-molecule drugs that address cancer, liver disease and inflammatory diseases, announced today that it will be presenting at the MicroCap Conference, being held on April 9-10 at the Essex House, New York City (Press release, Can-Fite BioPharma, MAR 28, 2018, View Source [SID1234525023]). Can-Fite’s Chief Financial Officer, Motti Farbstein will be delivering the corporate presentation and showcasing the Company’s lead drug candidate, Piclidenoson (CF101), which is in a Phase III trial for rheumatoid arthritis, and Namodenoson (CF102), a liver cancer drug in Phase II trials. Mr. Farbstein will also be hosting a Q&A session with investors and conducting one-on-one meetings.

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On March 28 bluebird bio, Inc. (Nasdaq: BLUE) and Celgene Corporation (Nasdaq: CELG) reported that the companies have entered into an agreement to co-develop and co-promote bb2121, an investigational anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy for the potential treatment of patients with relapsed/refractory multiple myeloma in the United States (Press release, Celgene, MAR 28, 2018, View Source [SID1234525025]).

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This press release features multimedia. View the full release here: View Source

"Entering into this co-development and co-promotion partnership with Celgene is a significant step forward in building a fully integrated oncology franchise for bluebird and together, we are committed to rapidly advancing development of bb2121 for patients," said Joanne Smith-Farrell, Ph.D., oncology franchise leader and senior vice president, corporate development and strategy, bluebird bio. "The collaboration builds upon our extensive research and development capabilities in oncology and is a testament to the strong partnership that exists between our two companies."

The companies originally entered into a broad, global strategic research collaboration in 2013 to discover, develop and commercialize novel therapies in oncology, which included bb2121.

"We are extremely pleased to advance our collaboration with bluebird on bb2121 and we believe this therapy has the potential to significantly impact the treatment approach and outcomes for patients with multiple myeloma," said Nadim Ahmed, President, Hematology and Oncology for Celgene.