On December 14, 2015bX4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer, reported U.S. Food and Drug Administration (FDA) allowance of the Company’s Investigational New Drug (IND) application for the clinical study of X4P-001, the company’s lead drug candidate, in patients with refractory clear cell renal cell carcinoma (ccRCC). X4P-001 is a CXCR4 inhibitor designed to block non-cancerous immunosuppressive and pro-angiogenic cells from populating the tumor microenvironment, thereby restoring anti-tumor immune function (Press release, X4 Pharmaceuticals, DEC 14, 2015, View Source [SID:1234508558]).

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The first patient in the Phase 1b/2a study is expected to be dosed in Q1 2016 and the study will take place at multiple cancer centers with leading renal cell carcinoma research located in the United States. The Phase 1b portion of the trial will test the safety and tolerability of escalating doses of X4P-001 in combination with axitinib, a multi-kinase inhibitor approved for the treatment of patients with ccRCC, with the goal of establishing a maximum tolerated dose (MTD), or a recommended dose if the MTD is not achieved, for the combination. The subsequent Phase 2a portion of the trial is a randomized dose-ranging study that will explore two dose-levels of X4P-001, both in combination with axitinib. In addition to safety and tolerability, the Phase 2a portion of the trial will evaluate early signs of biological activity using biomarkers, and clinical efficacy as measured by overall response rate and progression free survival over an 18 month time frame.

"Despite the recent advances made by VEGF targeted therapies and immunotherapies, many patients with ccRCC will require additional treatment options," said Michael Atkins, MD, Deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center and Professor of Oncology and Medicine at Georgetown University School of Medicine, and the Principal Investigator of X4’s Phase 1b/2a study. "Antagonism of the CXCR4 pathway has the potential to act synergistically with existing therapies, with the goal of achieving more durable tumor responses."

CXCR4, or C-X-C receptor type 4, is the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). The CXCR4/CXCL12 pathway has been shown to play a central role in the trafficking of key immune cells such as T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment. Recent studies demonstrate that CXCR4/CXCL12 is a primary receptor-ligand pair that cancer cells and surrounding stromal cells use to block normal immune function and promote angiogenesis. 1, 2 Inhibition of CXCR4 has the potential to impact multiple mechanism of tumor growth, progression and immune surveillance.

"Pre-clinical studies have shown CXCR4 inhibition acts synergistically with approved cancer therapies including tyrosine kinase inhibitors and checkpoint inhibitors resulting in an increased tumor-specific immune response and significant delays in tumor growth," said Paula Ragan, PhD, President and CEO of X4. "FDA allowance of our IND is an important milestone for us to advance novel drugs targeting this key mechanism, allowing us to understand the clinical translation and potential impact for patients. We look forward to beginning our first clinical study and to working toward our goal of offering patients with refractory ccRCC more effective treatment options."

About Renal Cell Carcinoma
Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.3 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapaymcin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.4 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.

About X4 Pharmaceuticals
X4 Pharmaceuticals is developing novel therapeutics designed to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer cells. The company’s oral small molecule drug candidates inhibit the CXCR4 receptor, a pathway which plays a central role in promoting the immunosuppressive and pro-angiogenic microenvironment of many cancers. X4P-001, the company’s lead program, is expected to enter Phase 1/2 testing in refractory clear cell renal cell carcinoma (ccRCC) and other solid tumor indications, and its second program, X4P-002, is in pre-clinical development for oncology applications. X4 was founded and is led by a team with deep product development and commercialization expertise, including several former members of the Genzyme leadership team, and is located in Cambridge, MA.

On December 14, 2015 CTI BioPharma Corp. (NASDAQ and MTA: CTIC) reported that it has received a $10 million milestone payment from Teva Pharmaceutical Industries Ltd. (Teva) related to the achievement of sales milestones for TRISENOX (arsenic trioxide) (Press release, CTI BioPharma, DEC 13, 2015, View Source;p=RssLanding&cat=news&id=2122140 [SID:1234508566]). TRISENOX was acquired from CTI BioPharma by Cephalon, Inc. (Cephalon). Cephalon was subsequently acquired by Teva. The milestone was paid pursuant to an acquisition agreement for TRISENOX entered into with Cephalon under which CTI BioPharma is eligible to receive up to an additional $70 million in payments upon achievement by Teva of specified sales and development milestones related to TRISENOX.

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On December 14, 2015 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Genentech Inc., a member of the Roche Group, obtained approval from the U.S. Food and Drug Administration (FDA), for the anti-cancer agent, alectinib hydrochloride (brand name: Alecensa) for the indication of "anaplastic lymphoma kinase (ALK) positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or those intolerant to crizotinib (Press release, Chugai, DEC 13, 2015, View Source [SID:1234508554])."

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"Alecensa was created by Chugai and in July 2014, Japan became the first country in the World to receive approval. We believe that the FDA’s priority review of Alecensa will bring fresh hope for patients in the US living with this disease." said Chugai’s Director and Executive Vice President, Dr. Yutaka Tanaka. "We are extremely pleased that Alecensa can contribute to the treatment of patients with ALK positive NSCLC."

Alecensa was granted Breakthrough Therapy Designation by FDA in June 2013 for patients with ALK positive NSCLC who have progressed on crizotinib. And FDA also granted priority review for Alecensa in September 2015.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. The indication for Alecensa is approved under accelerated approval based on tumour response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ALEX is a global, randomized phase III study comparing Alecensa to crizotinib as an initial treatment for people with advanced ALK-positive NSCLC. This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

Alecensa is a highly selective ALK inhibitor created by Chugai. It has been reported that 2 to 5 percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene1. ALK kinase signaling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumor cells and transforming the cells into tumor cells2, 3. Alecensa exerts its anti-tumor effect by selectively inhibiting ALK kinase activity to inhibit tumor cell proliferation and induce cell death4. In addition, Alecensa is not recognized by the transporter proteins in the blood brain barrier that actively pump molecules out of the brain. Alectinib is active in the central nervous system and has proven activity against brain metastases.

In Europe, Roche filed the NDA to the European Medicines Agency for the approval of "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" in September 2015. Chugai has out-licensed the rights of Alecensa to Roche in overseas countries including Europe and the US.

In Japan, Alecensa capsule 20mg, 40mg and 150mg is available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" and is marketed by Chugai.

1) Biomarker committee of The Japan Lung Cancer Society, Guidelines for ALK gene tests in lung cancer patients
2) Soda et al., Nature. 448: 561-566 (2007)
3) Takeuchi et al., Clin Cancer Res. 15: 3143-3149 (2009)
4) Sakamoto et al., Cancer Cell. 19: 679-690 (2011)

Overview of two pivotal clinical phase I/II trials based on the U.S. approval

The NP28761 study is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 87 people with ALK positive NSCLC whose disease progressed on crizotinib. (Data cut-off: October 24, 2014)
The NP28673 study is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 138 people with ALK positive NSCLC whose disease progressed on crizotinib. (Data cut-off: primary data cut-off including safety: August 18, 2014, updated IRC data cut-off: January 8, 2015)
People in the phase II studies received 600 mg of Alecensa orally twice daily. In both trials, the primary endpoint was ORR according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1), and evaluated by an Independent Review Committee (IRC). Secondary endpoints included DOR and efficacy against disease that had spread to the CNS (CNS ORR and CNS DOR).

The most common Grade 3 or higher adverse events in the pooled analysis of both studies were an increase in muscle enzymes (creatine phosphokinase; 4.6 percent), shortness of breath (dyspnea; 3.6 percent), increased liver enzymes (aspartate transaminase; 3.6 percent, and alanine transaminase; 4.8 percent), evidence of liver dysfunction (hyperbilirubinemia; 2.4 percent), increased blood glucose (hyperglycemia; 2 percent), decreased levels of minerals (hypokalemia; 4 percent, hypophosphatemia; 2.8 percent, and hyponatremia; 2 percent), decreased red blood cells (anemia; 2 percent) and decreased white blood cells (lymphopenia; 4.6 percent).

On December 13, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) granted accelerated approval to Alecensa (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib (Press release, Hoffmann-La Roche , DEC 13, 2015, View Source [SID:1234508556]). In the pivotal studies, Alecensa shrank tumours in up to 44 percent of people with ALK-positive NSCLC who progressed on crizotinib (objective response rate [ORR] of 38 percent [95 percent CI 28-49] and 44 percent [95 percent CI 36-53]).

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In a subset of people with tumours that spread to the brain or other parts of the central nervous system (CNS), Alecensa shrank CNS tumours in about 60 percent of people (CNS ORR of 61 percent [95 percent CI 46-74]).

"Alecensa is now approved as a new option for people with ALK-positive NSCLC who progress on or are intolerant to crizotinib," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "Sixty percent of people enrolled in our studies had tumours that had spread to their central nervous systems, and Alecensa shrank tumours in many people in a subset of patients with CNS disease."

Possible serious side effects with Alecensa include liver problems, lung problems, slow heartbeat, muscle pain, tenderness and weakness. The most common side effects of Alecensa include tiredness, constipation and swelling in the hands, feet, ankles and eyelids.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. The indication for Alecensa is approved under accelerated approval based on tumour response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In addition, Alecensa is being studied for use as an initial (first-line) treatment for people with advanced ALK-positive NSCLC. ALEX is a global, randomised phase III study comparing Alecensa to crizotinib as an initial treatment for people with advanced NSCLC whose tumours were characterised as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry (IHC) test developed by Roche Diagnostics. This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

About NP28761 (Study 1) and NP28673 (Study 2)
Study 1 is a phase II North American, single-arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. Study 2 is a phase I/II global, single-arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib. People in the phase II studies received 600 mg of Alecensa orally twice daily. In both trials, the primary endpoint was ORR according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1), as evaluated by an Independent Review Committee (IRC). Secondary endpoints included DOR and efficacy against disease that had spread to the CNS (CNS ORR and CNS DOR). A summary of the efficacy and safety data from both studies that support this approval is included below.

The most common Grade 3 or higher adverse events in the pooled analysis of both studies were an increase in muscle enzymes (creatine phosphokinase; 4.6 percent), shortness of breath (dyspnea; 3.6 percent), increased liver enzymes (aspartate transaminase; 3.6 percent, and alanine transaminase; 4.8 percent), evidence of liver dysfunction (hyperbilirubinemia; 2.4 percent), increased blood glucose (hyperglycemia; 2 percent), decreased levels of minerals (hypokalemia; 4 percent, hypophosphatemia; 2.8 percent, and hyponatremia; 2 percent), decreased red blood cells (anemia; 2 percent) and decreased white blood cells (lymphopenia; 4.6 percent).

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an investigational oral medicine created at Chugai and is being developed for people with NSCLC whose tumours are identified as ALK+. ALK+ NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma.

Early studies with Alecensa have shown activity on brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise Alecensa, which means that it may travel into and throughout brain tissue.

The Global phase III studies of Alecensa include a companion test developed by Roche. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

On December 11, 2015 BioTime, Inc. (NYSE MKT and TASE: BTX), a clinical-stage regenerative medicine company with a focus on pluripotent stem cell technology, reported that its Board of Directors has set the record date, the distribution ratio, and expected distribution date for the distribution of a portion of the shares of common stock of BioTime’s subsidiary OncoCyte Corporation ("OncoCyte") to BioTime shareholders (Press release, BioTime, DEC 11, 2015, View Source;p=RssLanding&cat=news&id=2122004 [SID:1234508538]). The record date for determining holders of BioTime common shares entitled to receive shares of OncoCyte common stock in the distribution will be the close of business on December 21, 2015.

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BioTime shareholders will receive one share of OncoCyte common stock for every 20 BioTime common shares held as of the close of business on the record date. The distribution will be made in book-entry form. BioTime expects the distribution to occur on December 31, 2015. BioTime shareholders will not be required to do anything to receive the OncoCyte distribution, meaning that they will not have to surrender or exchange BioTime common shares in order to receive their OncoCyte shares.

Any holder of record who sells their shares of BioTime on or before the distribution date of December 31st will be selling their entitlement of OncoCyte shares to the buyer of their BioTime shares. Holders are encouraged to talk to their financial advisor before selling their shares of BioTime.

After this distribution of OncoCyte shares, BioTime’s ownership will be reduced from approximately 76.4% to approximately 58.6%.

Currently, there is no trading market for OncoCyte common stock. However, OncoCyte plans to apply to list its common stock for trading on the NYSE MKT under the symbol OCX. In the event that a listing application is not approved, OncoCyte plans to arrange for the trading of its common stock on the OTC Bulletin Board market no later than the completion of the distribution.

Completion of the distribution of OncoCyte shares to BioTime shareholders is subject to the satisfaction of certain conditions, including that a Registration Statement on Form 10 filed by OncoCyte with the Securities and Exchange Commission is declared effective.

OncoCyte is engaged in the development of new "liquid biopsy" diagnostic tests for cancer based on analyzing patient blood or urine samples for specific gene or protein markers indicative of the presence of particular types of cancer. OncoCyte is presently developing diagnostic tests for lung cancer, breast cancer, and bladder cancer. For more information about OncoCyte, please visit www.OncoCyte.com.

More information about OncoCyte and the planned share distribution can be found in the Information Statement filed as an exhibit to OncoCyte’s Form 10 Registration Statement filed with the SEC on November 23, 2015, which is available on the Investor Relations page of BioTime’s website: www.biotimeinc.com and the website maintained by the SEC at www.sec.gov.

This press release does not constitute an offer to sell or a solicitation of an offer to buy any OncoCyte securities. The distribution of OncoCyte common stock by BioTime will be made only in those states and other jurisdictions where permitted or not prohibited by law.