On January 25, 2018 Trovagene, Inc. (NASDAQ: TROV), a clinical-stage precision medicine biotechnology company, engaged in the development of targeted cancer therapies, reported the initiation of its Phase 2 clinical trial, evaluating the combination of PCM-075 and abiraterone acetate (Zytiga – Johnson & Johnson), in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Trovagene, JAN 25, 2018, View Source [SID1234523575]). This clinical trial is called UNITE, "A Phase 2 Study to Understand the Novel Combination of PCM-075 and Abiraterone and the Opportunity to Improve Treatment and Extend Response in Patients with Metastatic Castration-Resistant Prostate Cancer." The study will enroll 25 patients with mCRPC who are showing early signs of disease progression while on abiraterone/prednisone therapy and will evaluate the proportion of patients achieving disease control after 12 weeks of study treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Initiation of the UNITE trial in mCRPC marks an important milestone in the clinical development of PCM-075 and builds upon the promising data from our completed and published Phase 1 trial in metastatic solid tumor cancers, as well as preclinical data demonstrating significant synergy for the combination of PCM-075 and abiraterone in CRPC tumor cells," said Bill Welch, Chief Executive Officer of Trovagene. "We are excited to be working with leading prostate cancer specialists and the Harvard Medical Institutions to conduct this trial and believe that the highly synergistic combination of PCM-075 and Zytiga has the potential to address the medical need to extend the benefit of response to treatment in patients with mCRPC."

Trovagene filed its Phase 2 metastatic Castration-Resistant Prostate Cancer protocol to the FDA and its active solid tumor IND in December, 2017. The Company successfully passed the 30-day FDA review period and has selected PRA Health Sciences as the Clinical Research Organization (CRO) to facilitate the trial.

About the Phase 2 mCRPC Clinical Study

In the UNITE multi-center, open-label, Phase 2 trial, the combination of PCM-075 with the standard dose of abiraterone and prednisone, all administered orally, will be evaluated to determine the proportion of patients achieving disease control after 12 weeks of study treatment. Disease control is defined by the lack of Prostate Specific Antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA, but minimally symptomatic or asymptomatic) while currently receiving androgen deprivation therapy (ADT) plus abiraterone and prednisone.

The Phase 2 UNITE trial will enroll 25 patients with metastatic Castration-Resistant Prostate Cancer showing signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on abiraterone/prednisone therapy. The follow-up of patients will occur approximately every six weeks until disease progression in patients with stable disease, or better at the end of treatment assessments.

The Phase 2 trial also includes the following secondary observation endpoints:

The effects of PCM-075 in combination with abiraterone and prednisone on time to PSA progression in subjects with mCRPC;
The effects of PCM-075 in combination with abiraterone and prednisone on time to radiographic progression, based on the Prostate Cancer Working Group 3 (PCWG3) guidelines; and
The effects of PCM-075 in combination with abiraterone and prednisone on radiographic response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in subjects with mCRPC and measurable disease.
About PCM-075

PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic and solid tumor cancers. Studies have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates up to 31% were observed when used in conjunction with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of PCM-075 has been completed in patients with advanced metastatic solid tumor cancers, and published in Investigational New Drugs.

PCM-075 only targets PLK1 isoform (not PLK2 or PLK3), is oral, has a 24-hour drug half-life with reversible on-target hematologic toxicities. Trovagene believes that targeting only PLK1 with reversible on-target activity and an improved dose/scheduling protocol can significantly improve on the long-term outcome observed in previous studies with a PLK inhibitor in AML.

PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including Zytiga (abiraterone), FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK-1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in Castration-Resistant Prostate Cancer (CRPC), Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC) and Adrenocortical Carcinoma (ACC).

About Castration-Resistant Prostate Cancer (CRPC)

Castration-Resistant Prostate Cancer (CRPC) is defined by disease progression despite androgen-deprivation therapy (ADT) and may present as one or any combination of a continuous rise in serum levels of prostate-specific antigen (PSA), progression of pre-existing disease, or appearance of new metastases. Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Bone metastases occur in 90% of men with CPRC and can produce significant morbidity, including pain, pathologic fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects are also common, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection. Institution of treatment and the choice of systemic or local therapy depend on a number of factors.

On January 25, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that a development milestone for cabiralizumab has been achieved, triggering a $25 million payment from Bristol-Myers Squibb Company (BMS, NYSE:BMY) under the license and collaboration agreement between the companies established in 2015 (Press release, Five Prime Therapeutics, JAN 25, 2018, View Source [SID1234523577]). The milestone was triggered by initiation of a multi-arm Phase 2 clinical trial (NCT03336216), sponsored by Bristol-Myers Squibb Company, evaluating cabiralizumab and Opdivo (nivolumab) with and without chemotherapy in patients with advanced pancreatic cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Effective treatment for patients with pancreatic cancer remains a significant unmet need and is a cancer for which existing immunotherapies have not been successful to date," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "We are encouraged by the preliminary data presented at SITC (Free SITC Whitepaper) 2017 and are pleased to see this trial underway."

The Phase 2 trial is expected to enroll approximately 160 patients with locally advanced or metastatic pancreatic cancer that has progressed during or after one line of chemotherapy.

About Cabiralizumab (FPA008)

Cabiralizumab is an investigational antibody that inhibits the CSF-1 receptor and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. Inhibition of CSF1R in preclinical models of several cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment, thereby facilitating an immune response against tumors. Cabiralizumab is currently in clinical trials in oncology indications and in pigmented villonodular synovitis (PVNS). Cabiralizumab is being developed under an exclusive worldwide license and collaboration agreement entered into with Bristol-Myers Squibb (BMS) in October 2015.

On January 24, 2018 Varian (NYSE: VAR) reported its first-quarter fiscal year 2018 results. All comparisons in this announcement are year-over-year unless noted otherwise (Press release, Varian Medical Systems, JAN 24, 2018, View Source [SID1234523571]). As a reminder, Varian adopted revenue Accounting Standard Codification 606 at the beginning of fiscal year 2018. First quarter fiscal year 2018 also reflects the impact from the new Tax Cuts and Jobs Act. As such the GAAP effective tax rate for the first quarter is 191.5 percent; Non-GAAP effective tax rate is 22.5 percent, which excludes the tax expense due to the mandatory deemed repatriation of foreign earnings and lower corporate tax rate’s impact on our deferred tax assets. The results that we disclose today, and any forward-looking statements, including guidance, reflect the new accounting standard and tax legislation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased with the strong start to the new fiscal year," said Dow Wilson, Chief Executive Officer of Varian. "We generated healthy orders, revenues and operating earnings growth in our Oncology business, and added two more proton therapy orders."

The company ended the quarter with $823 million in cash and cash equivalents and $340 million of debt. Net cash provided by operating activities was $179 million. During the quarter, the company invested $57 million to repurchase 525,000 shares of common stock.

"I’m delighted with our operational focus and execution in delivering these strong financial results during the quarter" added Gary E. Bischoping Jr., Chief Financial Officer of Varian.

Oncology Systems Segment

In the fiscal first quarter, Oncology revenues for the segment totaled $649 million, up 14 percent in dollars and 12 percent in constant currency. Gross orders were $620 million, up 7 percent in dollars and 6 percent in constant currency. Gross orders in the Americas increased 2 percent in dollars and in constant currency. In EMEA, gross orders rose 19 percent in dollars and 13 percent in constant currency, to $190 million; in APAC gross orders increased 6 percent in dollars and in constant currency with strong orders growth in Greater China and Japan. Operating earnings for the segment increased 19 percent.

Particle Therapy Segment

Revenues in the first quarter were $29 million, down 4 percent. In the quarter, the company booked ProBeam Compact orders from the University of Alabama at Birmingham and the Sylvester Comprehensive Cancer Center at the University of Miami totaling $46 million.

FY18 Annual Guidance Updated
Considering the financial and operational performance in the first quarter, and the impact of the new Tax Cuts and Jobs Act, fiscal year 2018 guidance is updated and increased to the following:

Revenue growth range of 4 percent to 7 percent
Non-GAAP Operating earnings as a percentage of revenues range of 18 percent to 19 percent
Non-GAAP effective tax rate of 21 percent
Weighted average diluted shares of 93 million
Non-GAAP Earnings per diluted share range of $4.24 to $4.36
Cash flow from operations range of $475 million to $550 million

Please refer to "Discussion of Non-GAAP Financial Measures" below for a description of items excluded from expected non-GAAP earnings.

Investor Conference Call

Varian Medical Systems is scheduled to conduct its first quarter fiscal year 2018 conference call at 2 p.m. PT today. To hear a live webcast or replay of the call, visit the investor relations page on our web site at www.varian.com/investor where it will be archived for a year. To access the call via telephone, dial 1-877-869-3847 from inside the U.S. or 1-201-689-8261 from outside the U.S. The replay can be accessed by dialing 1-877-660-6853 from inside the U.S. or 1-201-612-7415 from outside the U.S. and entering confirmation code 13674372. The telephone replay will be available through 5 p.m. PT, Friday, January 26, 2018.

On January 24, 2018 Sorrento Therapeutics, Inc. (NASDAQ:SRNE) ("Sorrento"), reported the expansion of its Good Manufacturing Practices (GMP) CAR-T manufacturing capacity, with an exclusive agreement to operate the "Cellular Immunotherapy and Gene Therapy Facility" at Roger Williams Medical Center (Providence, RI) under Sorrento management (Press release, Sorrento Therapeutics, DEC 24, 2018, View Source [SID1234532248]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Sorrento estimates that the combination of its East and West Coast manufacturing capacity will allow the company to process CAR-T treatments for over 300 patients a year without the use of a third-party contract manufacturer. Sorrento believes that the current capacity should be sufficient to meet its lead candidate CD38 CAR-T multiple myeloma development needs through and up to FDA approval, and support other upcoming CAR-T development programs.

This latest facility addition brings the total GMP manufacturing sites of Sorrento and its subsidiaries to 5 separate facilities: Judicial Facilities (San Diego, CA) for CAR-T therapies and antibody production, Providence Facilities (RI) for CAR-T therapies, Camino Santa Fe Facilities (San Diego, CA) for oncolytic virus production, Suzhou Facilities (China) for antibody-drug conjugate (linker toxin synthesis and bio conjugation) production and Bioserv Corporation (San Diego, CA) for small molecule and biologics fill and finish, medical devices and high potency compound fill and finish (expected completion later in the year).

"We decided a long time ago that internal manufacturing capability would be a strategic asset for Sorrento," stated Henry Ji, Chairman and CEO. He also noted, "Many biotech companies learned the hard way the risks of entering into a new therapeutic area without internal manufacturing capabilities and having to compete with other companies for limited numbers of third party manufacturers. With all the recent activity in the CAR-T space we are extremely pleased to be in control of our own GMP manufacturing and not have to rely on outside parties for our supply needs for our current and future development work."

As Sorrento moves towards non-viral CAR manufacturing, it also expects both the Judicial and Providence Facilities to be able to increase their capacity throughput and handle multiple CAR-T development programs in parallel.

On January 24, 2018 Apexian Pharmaceuticals, a clinical-stage biopharmaceutical company, has reported the opening of a clinical trial for patients with advanced solid tumors (Press release, Apexian Pharmaceuticals, JAN 24, 2018, View Source [SID1234523543]). The study involves APX3330, an orally administered inhibitor of APE1/Ref-1, a dual-function protein that plays a critical role in promoting and maintaining a broad variety of cancers. Details of the study, including eligibility criteria, the location of participating clinical centers and referral contact information can be found at www.ClinicalTrials.gov, a website maintained by the National Institutes of Health.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initiation of the APX3330 study is a significant step forward in Apexian’s mission to develop safe and effective treatments for cancer patients" said Steve Carchedi, President and CEO of Apexian Pharmaceuticals. "Despite recent advancements in cancer treatments, there continues to be a need for treatments that improve the survival of cancer patients. Apexian is committed to "moving mountains" to help these patients."

The APE1/Ref-1 protein regulates the activity of other cancer-associated proteins, including transcription factors HIF-1-alpha, AP-1, NF-kappa B, and STAT3, proteins that control the aggressiveness of many cancers. Data indicate that Apexian’s drug APX3330 inhibits the cancer-promoting activity of APE1/Ref-1 without causing the side effects normally associated with many types of chemotherapy. Additionally, in a variety of pre-clinical studies, APX3330 has been shown to not only have an anti-cancer effect, but to also prevent, and reverse the nerve damage caused by certain forms of chemotherapy.

The clinical study is the first to explore APX3330 use in patients with advanced cancer, and is the culmination of extensive research on APE1/Ref-1 and APX3330 conducted by Dr. Mark Kelley, Professor and Associate Director of Basic Science Research at Indiana University’s Simon Cancer Center as well as other scientists worldwide. Dr. Kelley’s work on APE1/Ref-1 and APX3330 has previously resulted in significant research grants provided through the National Cancer Institute in order to explore the potential benefit to cancer patients receiving APX3330.

According to Dr. Richard Messmann, Apexian’s Chief Medical Officer, "Apexian’s research, led by Dr. Kelley, has provided us with a clear path to understanding, and an ability to measure, the clinical benefit that may be obtained when cancer patients are treated with APX3330. It also lays the foundation for determining whether patients with chemotherapy-induced peripheral neuropathy (CIPN) may benefit when receiving APX3330. The clinicians involved in the study, including those at the Simon Cancer Center and at START SA (San Antonio, TX) and START Midwest (Grand Rapids, MI) have uniformly expressed excitement regarding their participation in the study."