On January 25, 2016 Immunocore, a world-leading biotechnology company developing novel T cell receptor (TCR) based biological drugs to treat cancer, infectious diseases and autoimmune disease, reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to its lead programme, IMCgp100, for the treatment of uveal melanoma (Press release, Immunocore, JAN 25, 2016, View Source [SID1234518904]). The Orphan Drug status qualifies Immunocore for a number of development incentives and will enable Immunocore to receive fast track registration for IMCgp100, its lead ImmTAC (Immune mobilising mTCR Against Cancer) therapeutic.

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Uveal melanoma, a rare disease in which cancer cells form in the tissues of the eye, comprises approximately 3% of all melanomas, and is the primary intraocular malignancy of the adult eye. There are currently no effective treatments on the market for this debilitating disease.

For a drug to qualify for orphan drug designation both the drug and the disease must meet certain criteria specified in the Orphan Drug Act (ODA) and FDA’s implementing regulations at 21 CFR Part 316.

IMCgp100 is Immunocore’s wholly-owned and most advanced ImmTAC, currently in Phase IIa clinical trials for the treatment of late stage cutaneous and uveal melanoma. To date, more than 85 patients have been treated with IMCgp100.

IMCgp100 was also accepted last year to participate in the European Medicines Agency’s (EMA) Adaptive Pathways Pilot Programme, part of the EMA’s strategy of providing timely access for patients to new medicines to treat serious conditions with high unmet medical need.

Eliot Forster, Chief Executive Officer of Immunocore, commented: "Immunocore now has the opportunity to fast-track this important programme, which we believe has the scope to offer a treatment option to people who currently have none. We look forward to accelerating the ongoing clinical programme with IMCgp100."

On January 26, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that the company earned a milestone payment with Bayer’s initiation of a global phase 2 clinical study designed to support registration of anetumab ravtansine (BAY 94-9343) (Press release, MorphoSys, JAN 25, 2016, View Source [SID:1234508860]). Anetumab ravtansine, an antibody-drug conjugate (ADC) targeting mesothelin, is a potential new treatment for mesothelioma developed by Bayer using MorphoSys’s HuCAL technology. Further financial details were not disclosed.

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"We are delighted to see our partner Bayer moving anetumab ravtansine into a clinical study designed to support its registration in mesothelioma, an indication with high medical need", commented Dr. Marlies Sproll, Chief Scientific Officer of MorphoSys AG. "This is the fourth antibody derived from the MorphoSys technology platform to advance into decisive stages of clinical development. This again reflects the increasing maturity and value of the MorphoSys pipeline comprising both proprietary and partnered programs."

MorphoSys’s collaboration with Bayer has resulted in two clinical programs to date. In total, MorphoSys’s partnered and proprietary clinical pipeline currently comprises 25 unique antibody molecules which are currently being evaluated in more than 50 clinical trials.

On January 25, 2016 Lixte Biotechnology Holdings, Inc. (OTCQB: LIXT) reported that a major shareholder has purchased $1,750,000 of Convertible Preferred stock (Filing, 8-K, Lixte Biotechnology, JAN 25, 2016, View Source [SID:1234508859]). If fully converted, this purchase would convert to 2,187,500 common shares at a per share price of $0.80.

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Lixte’s CEO, John S. Kovach, M.D., said, "This new investment allows Lixte to pursue opportunities that have emerged regarding our lead anticancer compound, LB-100.

First, in the Phase I trial, several solid tumor patients with a variety of recurrent progressive cancers had stabilization of their disease in the absence of dose-limiting toxicity as reported at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference in Boston. We had not anticipated that LB-100 alone would stop tumor progression in some solid tumor patients. This finding raises opportunities, currently being explored, to go directly to Phase 2 studies of LB-100 as a single agent.

Second, Lixte has licensed LB-100 to the Taiwan Medical University to determine the activity of LB-100 plus doxorubicin in Asian patients with hepatocellular cancer, beginning with a Phase 1b/2 trial planned to start this summer. This will test the ability of LB-100, demonstrated in several animal models, to enhance the effectiveness of a widely used anticancer drug against one of the most common and devastating cancers worldwide.

Third, scientists at the National Institutes of Health (NIH) reported that LB-100 enhances the anti-tumor activity of cisplatin and reduced cisplatin-resistance of human medulloblastoma cells in animal models. Previously, NIH investigators found that LB-100 enhanced the activity of cisplatin in models of cisplatin sensitive and cisplatin-resistant human ovarian cancer."

Dr. Kovach continued, "Because of these new developments, Lixte is considering several options for Phase 1b/2 trials, with recurrent platinum-resistant ovarian cancer at the top of the list. The most definitive trial design would be a randomized study of LB-100 plus a platinum compound versus the therapeutic choice of the treating doctor with an opportunity for those failing treatment with the ‘physician’s choice’ to receive the LB-100 regimen. The cost of a randomized trial would require additional financial resources beyond those of the private placement."

On January 25, 2016 Boston Biomedical, an industry leader in the development of novel compounds designed to target cancer stem cell (CSC) pathways, reported that three poster presentations were highlighted at the 2016 Gastrointestinal Cancers Symposium, held by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), January 21 to 23, 2016, in San Francisco (Press release, Dainippon Sumitomo Pharma, JAN 25, 2016, View Source [SID:1234508858]).

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"We were pleased to share these data from napabucasin (BBI608) in advanced and difficult-to-treat tumor types at this year’s ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium," said Chiang J. Li, M.D. FACP, the President, CEO and Chief Medical Officer of Boston Biomedical, and the Head of Global Oncology for Sumitomo Dainippon Pharma Group. "These studies continue to show napabucasin’s safety and early efficacy across doses and in combination with a variety of established agents. We plan to apply these findings as we advance and expand our clinical development program for this first-in-category cancer stemness inhibitor."

Data presented at the symposium support the continued development of the investigational cancer stemness inhibitor napabucasin (also known as BBI608, BB608 or BBI-608) — an orallyadministered agent designed to inhibit cancer stem cell pathways by targeting the STAT3 pathway — for anti-cancer activity when used in combination with other agents across advanced, pretreated and untreated metastatic pancreatic cancers, as well as advanced, pretreated colorectal cancer.

"These clinical studies of napabucasin in advanced gastroenterological cancers, including the presentation of data in refractory colorectal cancer specifically, show encouraging clinical activity by targeting cancer stem cell pathways that contribute to cancer recurrence, metastases and resistance to therapies," commented Axel Grothey, M.D., professor of oncology, Mayo Clinic. "I look forward to the further investigation of this innovative approach to cancer treatment in additional clinical studies."

Overview of the Boston Biomedical poster presentations:

• Abstract #284 (NCT02231723), Poster Session B Board #E8: A Phase Ib study of Cancer Stem Cell (CSC) pathway inhibitor Napabucasin (BBI608) in combination with Gemcitabine and nab-Paclitaxel (nab-PTX) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) [Safi Shahda, M.D., IU Health University Hospital]

o Data from this phase Ib study demonstrate that napabucasin (BBI608) at 240 mg twice daily was combined with gemcitabine and nab-paclitaxel, resulting in early anti-tumor activity in patients with metastatic pancreatic ductal adenocarcinoma.

Of the 31 patients enrolled, 25 patients were treatment-naïve and 6 patients had received one prior line of systemic therapy in the adjuvant setting only. Safety data was available for 18 patients and efficacy data was available for 8 patients at clinical cut off for abstract submission for the 8-patient cohort of recommended phase II dose determination. Safety and efficacy data for the rest of the patients are being followed.

Of the 8 patients enrolled to determine the recommended phase II dose, 7 patients were evaluable for response and 100% had partial response (PR) or stable disease (SD). Tumor regression was observed in 6/7 patients (85.7%) with 3 PR (41.3%, 37.1% and 33.3% regression) and 3 SD (25.8%, 21.1%, and 20.5% regression). Six of 7 evaluable patients (85.7%) had prolonged PR or SD of 24 weeks or longer.

The most common adverse events included grade 1 diarrhea, nausea, fatigue, abdominal pain and anorexia.

• Abstract #196 (NCT01325441), Poster Session B Board #A6: Phase Ib/II Study of Napabucasin (BBI608) combined with Weekly Paclitaxel in Advanced Pancreatic Cancer [Tanios Bekaii-Saab, M.D., Ohio State University Wexner Medical Center]

o Results from this phase Ib/II extension study of napabucasin (BBI608) at 480 mg twice daily plus weekly paclitaxel showed early anti-cancer activity in patients with refractory, heavily pretreated pancreatic cancer, particularly in taxane-naïve patients. Durable disease control and prolonged overall survival in this study patient population were also observed.

The 41 patients enrolled had received a median of two prior lines of treatment including FOLFIRINOX (71%), gemcitabine/nab-paclitaxel (44%) or both (37%).

The 31 evaluable patients had a response rate (partial response, PR + complete response, CR) of 6% and disease control rate (stable disease, SD + PR + CR) of 48%. The 19 evaluable taxane-naïve patients had a response rate of 11% and disease control rate of 63%, and 16% were progression-free at 24 weeks. Overall for the 41 patients, median progression-free survival (mPFS) was 2.2 months and median overall survival (mOS) was 6.0 months, while the 23 taxane-naïve patients demonstrated mPFS of 3.9 months and mOS of 7.4 months.

The most common adverse events included grade 1 and 2 diarrhea, fatigue and abdominal pain, and grade 1 nausea, anorexia and vomiting.

• Abstract #569 (NCT02024607), Poster Session C Board #D18: A Phase Ib study of first-in-class cancer stemness inhibitor Napabucasin (BBI608) in combination with FOLFIRI with and without Bevacizumab in Patients with Advanced Colorectal Cancer [Joleen Hubbard, M.D., Mayo Clinic]

o This phase Ib study showed that napabucasin (BBI608) at 240 mg twice daily can be combined with FOLFIRI with and without bevacizumab, and demonstrated early anti-tumor activity in heavily pretreated colorectal cancer patients, even in those with prior progression on FOLFIRI-based therapy.
Of the 18 enrolled heavily pretreated patients (average of >3 prior lines of therapy), 10 patients previously progressed on FOLFIRI. Of the 17 evaluable patients, 8 patients received FOLFIRI and 9 received FOLFIRI with bevacizumab, both in combination with napabucasin.

Disease control (partial response, PR + stable disease, SD) was observed in 94% of evaluable patients (16 of 17). Ten evaluable patients (59%) achieved prolonged disease control (PR and SD) of 24 weeks or more.

The most common adverse events included grade 1 and 2 diarrhea, fatigue, nausea, vomiting, abdominal pain and anorexia; no dose limiting toxicity or new adverse events were seen and the safety profile was similar to that of each regimen as monotherapy.

The full posters of the above studies are available on the R&D publications page of the Boston Biomedical website.

On January 25, 2016 ArQule, Inc. (NASDAQ:ARQL) reported that an analysis of preliminary baseline tumor MET status of patients screened in the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) confirms previously presented data from the company’s phase 2 trial in the same patient population (Press release, ArQule, JAN 25, 2016, View Source [SID:1234508855]). In both trials MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy and was a predictive and prognostic biomarker in the phase 2 trial. The data was presented in an oral presentation and poster at the 2016 Gastrointestinal Cancers Symposium (ASCO GI) on January 22, 2016.

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The METIV-HCC trial screened patient tumor biopsies for MET status as an inclusion criteria for Met-high patients. Approximately half of the more than 1,000 samples tested were MET-high. A higher MET-high rate (73%) was observed in those samples from patients analyzed following first-line treatment with sorafenib while a lower MET-high rate (39%) was observed in those samples analyzed prior to sorafenib treatment.

An additional analysis found that 70% (50 out of 71) of patients who tested MET-low before sorafenib treatment became MET-high after receiving sorafenib. The presentations can be accessed in the "Publications and Presentations" section of our website, www.arqule.com.

"The totality of the biomarker data presented further enforces our confidence in the design and target patient population that we have chosen for the METIV-HCC trial," said Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. "Having recently completed enrollment, we look forward to the planned interim analysis early in the second quarter."

The METIV-HCC trial, being conducted in western countries in partnership with Daiichi Sankyo, has completed enrollment and a planned interim analysis, which is triggered when 60% of events occur, is expected to take place early in the second quarter of 2016. The trial enrolled over 300 patients, is randomized 2:1 treatment to best supportive care, and has overall survival as its primary end-point.

The phase 2 study, completed in the third quarter of 2011 and published in The Lancet Oncology medical journal in November 2012, enrolled 107 HCC patients who progressed or were intolerant to one prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and tumor MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib response.

About Hepatocellular Carcinoma (HCC)

Liver cancer is the sixth most common cancer globally with about 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 746,000 deaths in 2012.i HCC accounts for about 90 percent of primary liver cancers.ii Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.ii

About MET and Tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in two phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.