Treatment of Cancer Use Patent for EP4 antagonist Approved in China

On August 17, 2017 AskAt reported that it has received a notice of allowance dated August 17, 2016 from State Intellectual Property Office of the P.R.C. (SIPO) in connection with the Application No. 201080017743.X, a use patent of EP4 receptor antagonist for the treatment of Cancer (Press release, AskAt, AUG 17, 2016, View Source [SID1234535065]).

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Immunomedics Announces Fiscal 2016 Results and Clinical Program Developments

On August 17, 2016 Immunomedics, Inc. (Nasdaq:IMMU) reported financial results for the fourth quarter and fiscal year ended June 30, 2016. The Company also highlighted recent key developments and planned activities for its clinical pipeline.

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Fourth Quarter Fiscal 2016 Results

Total revenues for the fourth quarter ended June 30, 2016, were $0.9 million, compared to $2.4 million for the same quarter last year, a decrease of $1.5 million, or approximately 63%. The decrease was due primarily to the receipt of a $1.0 million license fee in the quarter ended June 30, 2015 upon attaining a clinical development milestone in accordance with the Company’s Collaboration Agreement with The Bayer Group (Bayer) (as amended), and a $0.6 million decrease in research and development revenues in the current quarter due to fewer government funded research grants.

Total costs and expenses for the quarter ended June 30, 2016 were $15.6 million, compared to $13.6 million for the same quarter in fiscal 2015, an increase of $2.0 million, or approximately 15%. The increase was due primarily to a $1.4 million increase in research and development expenses, mainly from increased manufacturing costs for antibody-drug conjugates in clinical trials, and a $0.6 million charge to cost of goods sold for LeukoScan inventories that did not meet our quality control standards.

Interest expense related to the 4.75% Convertible Senior Notes due 2020 (Convertible Notes) was $1.4 million for both quarters ended June 30, 2016 and June 30, 2015, including amortization of $0.2 million debt issuance costs in each quarter.

Net loss attributable to stockholders was $15.9 million, or $0.17 per basic and diluted share, for the fourth quarter of fiscal year 2016, compared with net loss attributable to stockholders of $12.4 million, or $0.13 per basic and diluted share, for the same quarter in fiscal 2015, an increase of $3.5 million, or approximately 28%. The increase was due primarily to the $2.0 million increase in total costs and expenses and $1.5 million decrease in revenues, as described above.

Fiscal Year 2016 Results

Total revenues for fiscal year 2016 were $3.2 million, compared to $5.7 million for fiscal year 2015, a decrease of $2.5 million, or approximately 44%. The decrease was due primarily to a $1.2 million decrease in government funded research grants, the receipt of a $1.0 million clinical milestone payment from Bayer in fiscal year 2015, and a $0.3 million decrease in LeukoScan sales, due primarily to unfavorable fluctuations in currency exchange rates and lower sales volume in Europe.

Total costs and expenses for the fiscal year ended June 30, 2016 were $62.2 million, compared to $51.9 million for fiscal 2015, an increase of $10.3 million, or approximately 20%. The increase was due primarily to an $11.8 million increase in research and development expenses from increased clinical trial expenses and manufacturing costs for antibody-drug conjugates clinical trials and the Phase 3 PANCRIT-1 study in pancreatic cancer, a $0.9 million increase in cost of goods sold due to a $0.9 million write down of LeukoScan inventory, and a $0.2 million increase in sales and marketing expenses due primarily to employee related severance costs and the relocation of the Immunomedics GmbH offices; offset partially by a $2.6 million reduction in legal and professional fees related to the arbitration proceedings with Takeda Pharmaceutical Company Limited, which occurred in fiscal year 2015.

Interest expense related to the Convertible Notes was $5.5 million for fiscal year 2016, including $0.7 million for the amortization of debt issuance costs, compared to $2.1 million interest expense for fiscal year 2015, including the amortization of $0.3 million of debt issuance costs, an increase of $3.4 million, or approximately 162%. The increase is due to the fact that the Convertible Notes were issued in February 2015; therefore, fiscal 2015 contains interest for part of the year, while fiscal 2016 contains interest for the full year.

An income tax benefit of $5.1 million was recorded for the current fiscal year, as a result of cash proceeds received from the sale of a portion of our New Jersey State net operating losses and research and development tax credits through the New Jersey Economic Development Authority’s Technology Business Tax Certificate Transfer Program. There were no comparable sales in the previous year.

Net loss attributable to stockholders was $59.0 million, or $0.62 per basic and diluted share, for fiscal year 2016, compared to net loss attributable to stockholders of $48.0 million, or $0.51 per basic and diluted share, in fiscal year 2015, an increase of $11.0 million, or approximately 23%. The increase was due primarily to increased research and development costs, interest expense, and lower license fee revenue, which were offset partially by the income tax benefit received and lower legal and professional fees, as described above.

Cash, cash equivalents, and marketable securities were $50.6 million as of June 30, 2016.

"We plan to spend approximately $42 million to $44 million during fiscal 2017," commented Michael R. Garone, Vice President Finance and Chief Financial Officer. "Based on this projection, we believe our current funds are sufficient to continue operations and budgeted research and development programs, which include preparations for a Phase 3 confirmatory trial of sacituzumab govitecan in triple-negative breast cancer, preparations for commercial manufacturing of sacituzumab govitecan, the continuation of the Phase 2 study of sacituzumab govitecan in certain select solid cancers, and the continuation of the Phase 1 trial of IMMU-114, for at least the next twelve months." Mr. Garone added, "We are pursuing strategic licensing or collaboration agreements as a potential source of financing to initiate the Phase 3 confirmatory trial of sacituzumab govitecan in triple-negative breast cancer, to manufacture sacituzumab govitecan for Phase 3 and commercial supplies, and to fund other research and development programs continuing or planned beyond fiscal 2017."

The Company’s key clinical developments and future planned activities:

Sacituzumab Govitecan (IMMU-132)

At a Breakthrough Therapy Designation follow-on meeting, the Company received guidance from the U.S. Food and Drug Administration (FDA) for a potential accelerated approval for sacituzumab govitecan as a treatment for patients with triple-negative breast cancer (TNBC) who have received at least two prior therapies, including taxane, for metastatic disease. The application for accelerated approval will be based on the ongoing single-arm Phase 2 trial with additional patients to be enrolled. All patients receive repeated cycles of sacituzumab govitecan at the dose of 10 mg/kg. Treatment responses, including confirmed objective response rate (ORR) and mature duration of response (DOR), are assessed with computed tomography in accordance with RECIST 1.1, and confirmed by an independent centralized and blinded group of radiology experts. In addition, a confirmatory Phase 3 clinical study based upon the Special Protocol Assessment (SPA) agreed with the FDA is expected to be underway at the time of submission of an application for accelerated approval.

Phase 2 testing of sacituzumab govitecan continues in metastatic TNBC, small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC) and urothelial cancer:

Sacituzumab govitecan provided a median survival benefit in patients with metastatic TNBC who had received a median of 5 (range, 2 – 12) prior lines of therapy. As of May 2016, the objective response rate (ORR) for this group of patients continues to be encouraging, as does the interim median duration of response (DOR) and the overall survival (OS).
Significant tumor shrinkage and disease stabilization were observed in adenocarcinoma and squamous cell carcinomas, the two major subtypes of NSCLC, and in certain patients who had failed previous anti-PD-1/PD-L1 therapy.
For SCLC, despite the aggressive nature of the disease, encouraging ORR in assessable patients were observed after receiving treatment with sacituzumab govitecan at the dose level of 8 mg/kg or 10 mg/kg. The median number of prior chemotherapies for this group of patients was 2 (range, 1-5). All patients had previous treatment with platinum-based therapy and etoposide, and 11 had received topotecan.
Interim results compare favorably with historical ORR, PFS and OS reported in the medical literature with multiple chemotherapy regimens in the second- or third-line setting of metastatic urothelial cancer.
Labetuzumab Govitecan (IMMU-130)

Our second investigational solid-tumor antibody-drug conjugate (ADC) involves our anti-CEACAN5 antibody, labetuzumab, conjugated to SN-38. The agent is currently being studied in patients with metastatic colorectal cancer (mCRC) who had received at least one prior irinotecan-containing regimen and had an elevated blood titer of carcinoembryonic antigen (CEA). Several dosing schedules were evaluated in three Phase 1 studies. Labetuzumab govitecan showed therapeutic activity in all three trials, but a more frequent dosing schedule, with administrations of the ADC once or twice-weekly for two weeks followed by a week off, appeared to be more active in patients with mCRC than when administered every other week.

In the expanded Phase 2 study, patients were being treated in three-week cycles, receiving labetuzumab govitecan at 8 or 10 mg/kg once-weekly or twice a week at 4 or 6 mg/kg for the first two weeks, followed by one week of rest. Updated results were presented at the 2016 AACR (Free AACR Whitepaper) Annual Meeting. Since then, the Phase 2 study has been completed and we are now evaluating the various measures of efficacy, especially OS.

Since there was no significant difference in safety and efficacy between the two once-weekly dosing schedules, for patient’s convenience, the once-a-week dose of 10 mg/kg was chosen for future studies in mCRC patients.

IMMU-114

IMMU-114 is a novel humanized antibody directed against an immune response target, HLA-DR, under development for the treatment of patients with B-cell and other HLA-DR-expressing cancers. Increased presence of HLA-DR in hematologic cancers has made it a prime target for antibody therapy. By targeting HLA-DR, a receptor that is different from the antigen targeted by rituximab or other antibodies in development for non-Hodgkin lymphoma (NHL) and other B-cell malignancies, IMMU-114 may represent a new tool in the arsenal to combat these cancers. The anti-HLA-DR antibody is being evaluated as a subcutaneously-administered monotherapy for patients with NHL or chronic lymphatic leukemia (CLL) in a Phase 1 study.

Milatuzumab

Milatuzumab is a humanized monoclonal antibody targeting tumors that express the CD74 antigen, which is present on a variety of hematological tumors and even on some solid cancers, with restricted expression by normal tissues. It has received orphan drug designation from the FDA for the treatment of patients with multiple myeloma or CLL. Milatuzumab is the first anti-CD74 antibody that has entered into human testing and we have completed initial Phase 1 studies in patients with relapsed multiple myeloma, NHL or CLL. The anti-CD74 antibody is currently being studied subcutaneously in a Phase 1b study in patients with active systemic lupus erythematosus (SLE), supported by a three-year research grant from the U.S. Department of Defense with a potential funding of $2 million.

Final results of the Company’s clinical trials will be presented at medical meetings and/or in medical publications.

Cerulean Announces Results from Phase 2 Clinical Trial of CRLX101 and Avastin® Combination in Relapsed Renal Cell Carcinoma

On August17, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported top-line results from the Company’s Phase 2, randomized, multi-center clinical trial of its lead candidate, CRLX101, in combination with Avastin (bevacizumab) in the treatment of patients with advanced renal cell carcinoma (RCC) (Press release, Cerulean Pharma, AUG 17, 2016, View Source [SID1234514632]).

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The trial was conducted at 43 sites in the US and South Korea, and enrolled 115 patients with RCC who progressed through two or three prior lines of therapy. Patients were randomized to receive CRLX101 in combination with Avastin or investigator’s choice standard of care (SOC) therapy. SOC agents included axitinib, bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. The primary endpoint was progression free survival (PFS) in the clear cell population (n=102) assessed by independent radiological review. Secondary endpoints included overall response rate, duration of response and overall survival.

The study demonstrated no statistically significant difference in median PFS and objective response rate for the CRLX101 combination compared to SOC. Median PFS was 3.7 months for the CRLX101 combination compared with a median PFS of 3.9 months for SOC (hazard ratio: 1.25, p=0.822). The 95% confidence interval for PFS for the CRLX101 combination was 2.0 months to 4.3 months and for SOC was 2.2 months to 5.4 months. Objective response rate by independent radiological review for patients who received the CRLX101 combination was 5% (2/42) compared to 14% (6/43) for SOC (p=0.836). The CRLX101 and Avastin combination appeared to be safe and well-tolerated and the safety and tolerability profile of the combination was consistent with that observed in previous studies. The full data set from the trial are expected to be submitted for presentation at an upcoming medical conference.

"We are disappointed with this outcome and will undertake a thorough analysis of the data to understand why CRLX101 plus Avastin underperformed compared to the results we saw in an earlier investigator-sponsored trial," said Christopher D. T. Guiffre, President and Chief Executive Officer of Cerulean. "This outcome did not support our hypothesis that targeting hypoxia inducible factor (HIF) in combination with VEGF inhibitor in RCC, a HIF-overexpressing tumor type, would be beneficial, so we will not pursue HIF as a target going forward. We will continue to focus on the potent topoisomerase 1 inhibition of CRLX101’s payload, camptothecin, in topoisomerase 1-sensitive tumors. Our combinations with weekly paclitaxel and LYNPARZA (olaparib) are examples of ongoing trials that leverage CRLX101’s topoisomerase 1 inhibition in combination with chemotherapies and DNA damage repair agents."

Conference Call Details

Cerulean will host a conference call today at 4:30 pm Eastern Daylight Time to discuss the results and provide an update on the CRLX101 development program. The call can be accessed by dialing (844) 831-3031 or (443) 637-1284 prior to the start of the call and referencing conference ID: 67807137. The conference call will also be webcast live over the Internet and can be accessed on the "Investors" section of the Cerulean website, www.ceruleanrx.com. The webcast will be available on Cerulean’s website for two weeks.

About CRLX101

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication. CRLX101 has shown activity in multiple tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 400 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer, Fast Track designation in combination with paclitaxel for platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer, and Fast Track designation in combination with Avastin in metastatic renal cell carcinoma.

Inspyr Therapeutics Announces the Initiation of a Phase 2 Clinical Trial of Mipsagargin for Newly Diagnosed Prostate Cancer Patients

On August 17, 2016 Inspyr Therapeutics, Inc. (OTCQB: NSPX), a biotech company developing a novel prodrug therapeutic for the treatment of cancer, today reported that the first patient has been treated in a Phase 2 investigator-sponsored clinical trial to evaluate the safety and activity of mipsagargin in patients newly diagnosed with prostate cancer (Press release, Inspyr Therapeutics, AUG 17, 2016, View Source [SID:1234514631]). The trial is being conducted at The University of Texas Health Science Center (UTHealth) at Houston with Robert Amato, D.O., Professor and Director, University of Texas/Memorial Hermann Cancer Centers, as principal investigator. Mipsagargin is a first-in-class agent with a novel mechanism of action that targets prostate-specific membrane antigen (PSMA), a highly expressed enzyme on the surface of prostate cancer cells.

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The open-label, single-arm Phase 2 clinical trial will enroll patients with treatment-naïve prostate cancer prior to surgical removal of the tumor. Patients in the trial will be administered mipsagargin by intravenous infusion on the first three consecutive days of a 28-day cycle, over a total of three cycles. The trial will evaluate the effect of mipsagargin on the perfusion and volume of the prostate. Inspyr expects top-line results in mid 2017.

"Mipsagargin presents a novel tumor-targeting approach to treating patients newly diagnosed with prostate cancer," said Dr. Amato. "My colleagues at UTHealth are focused on improving treatment options for prostate cancer patients, and we look forward to evaluating mipsagargin’s effectiveness in disrupting the blood supply of prostate tumors and killing prostate cancer cells, which could lead to tumor regression and potentially improved survival rates for patients diagnosed with this type of cancer."

"Dr. Amato and his colleagues at UTHealth have identified a potentially novel application of mipsagargin for prostate cancer patients, and we look to continuing our collaboration," said Chris Lowe, Inspyr’s President and Chief Executive Officer. "We believe mipsagargin’s unique mechanism of action delivers a potent therapy to the tumor site while maintaining an attractive safety profile. We look forward to reviewing the results from this study."

About the University of Texas Health Science Center at Houston

Established in 1972 by The University of Texas System Board of Regents, the University of Texas Health Science Center at Houston (UTHealth) is Houston’s Health University and Texas’ resource for health care education, innovation, scientific discovery and excellence in patient care. The most comprehensive academic health center in The University of Texas System and the U.S. Gulf Coast region, UTHealth is home to schools of biomedical informatics, biomedical sciences, dentistry, medicine, nursing and public health and includes The University of Texas Harris County Psychiatric Center and a growing network of clinics throughout the region. For more information, visit www.uth.edu.

Genmab Announces Submission of Supplemental Biologics License Application to FDA for Daratumumab in Relapsed Multiple Myeloma

On August 17, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its licensing partner, Janssen Biotech, Inc. has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the use of daratumumab (DARZALEX) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who received at least one prior therapy (Press release, Genmab, AUG 17, 2016, View Source [SID:1234514628]).

In July 2016, daratumumab was granted a Breakthrough Therapy Designation (BTD) in this patient population. The submission of the application triggers milestone payments totaling USD 15 million to Genmab from Janssen. The milestone payments were included in Genmab’s financial guidance for 2016 that was published on August 9, 2016. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"We are thrilled that an application to expand the current label to include treatment of multiple myeloma patients who received at least one prior therapy has been submitted so soon after the initial FDA approval of daratumumab in November 2015. The data from the Phase III CASTOR and POLLUX studies on which the submission is based was unprecedented, meriting a Breakthrough Therapy Designation from the FDA. We believe that if approved, daratumumab has the potential to make a substantial positive impact in the treatment of patients with multiple myeloma who have relapsed on their previous therapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

A request for Priority Review has been submitted by Janssen with this sBLA. The FDA will inform Janssen whether a Priority Review has been granted by calendar day 60 of their review starting today. If the FDA grants Priority Review, the review should be completed within 6 months from today.

The submission includes data from two Phase III studies: the CASTOR study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma, and the POLLUX study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The submission also included data from the Phase I study of daratumumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma. These data will also be used as the basis for a potential regulatory submission to the European Medicines Agency (EMA).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,8 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,8 antibody-dependent cellular phagocytosis9,10 and antibody-dependent cellular cytotoxicity.7,8 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.7,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.