On March 14, 2016 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a clinical-stage biomedicine firm engaged in the development of effective treatments for degenerative and cancerous diseases, reported business highlights and financial results for the full year ended December 31, 2015 (Press release, Cellular Biomedicine Group, MAR 14, 2016, View Source [SID:1234509527]).

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"2015 proved to be a transformative year for Cellular Biomedicine Group with the Company’s entrance into the dynamic field of immuno-oncology. We now operate under dual technology platforms: Immuno-oncology (I/O) and Stem Cells. We expect to advance several of our CAR-T candidates including CBM.CD19 and CBM.CD20 into multiple indications of hematological cancer. Eventually, our effort to sponsor multi-center clinical trials in the near future should lead to servicing the large cancer market in China. We also reported encouraging Phase IIb data from our most advanced stem cell program for Knee Osteoarthritis (KOA), and we will explore the possibility of entrance into the U.S. market," commented Tony (Bizou) Liu, CBMG’s Chief Executive Officer. "The expansion of our GMP facilities into Beijing allows us to prepare for anticipated manufacturing demands from our immuno-oncology and stem cell platforms for clinical trials and future commercialization opportunities. We strengthened our operating and management capabilities with the addition of key talents, which will better position the Company to monetize our growing cell therapy pipeline. We look forward to an exciting 2016 as we leverage these strengths to execute on our clinical milestones, build an innovative pipeline and move our clinical assets into later stage clinical development."

2015 and Recent Clinical Developments

Immuno-Oncology Platform

Announced positive clinical data from Phase I of its CAR-T immuno-oncology clinical development programs of:
CBM-CD19.1 for Acute Lymphoblastic Leukemia (B-cell ALL)
CBM-CD20.1 for Advanced Diffuse Large B Cell Lymphoma (DLBCL)
CBM-CD30.1 for Stage III and IV Hodgkin’s lymphoma
CBM-EGFR.1 for the treatment of patients with EGFR expressing advanced relapsed/refractory solid tumors.
In all trials the assets were shown to be safe, feasible and efficacious.
The participants enrolled in the studies were advanced, relapsed, and/or refractory to other standard-of-care therapies. This patient population has substantial unmet medical needs.
Stem Cell Therapies Platform

Announced encouraging 48-week clinical data from the Phase IIb trial of its ReJoin haMPC therapy for Knee Osteoarthritis (KOA), revealing increase of patient’s knee cartilage volume and relief of pain;

Launched an investigator initiated Phase I clinical trial of an off-the-shelf allogeneic adipose-derived mesenchymal progenitor cell (haMPC) AlloJoinTMtherapy for KOA patients in China;

Recruited patients for a clinical study on ReJoin therapy for Cartilage Damage (CD) resulting from sports injury, which also serves as a supporting study of ReJoinfor KOA with arthroscopic evidences. We plan to release results from this study in 1H 2017.

2015 and Recent Corporate Highlights

Completed two acquisitions, which substantially increased CBMG’s immuno-oncology platform, including:
PLA General Hospital’s ("PLAGH", Beijing, also known as "301 Hospital") Chimeric Antigen Receptor T cell (CAR-T) therapies, redirected T cells against CD19, CD20, CD30 and Human Epidermal Growth Factor Receptor (EGFR or HER1), their patents (all pending), and Phase I/II clinical data of the aforementioned therapies and manufacturing knowledge;

Blackbird Bio Finance and University of South Florida’s ("Licensor") next generation GVAX vaccine’s ("CD40LGVAX") related technologies, technical knowledge and FDA IND approved clinical trial protocol
Expanded the Company’s cell manufacturing capabilities with the opening of the Company’s third GMP facility, a 15,000 square feet site in Beijing, China, approximately half of which has been designed as a GMP equipped facility to support clinical batch production and commercial scale manufacturing;

Commenced revenue generation through the Company’s T Cells Receptor ("TCR") clonality analysis and CentrixTTM adoptive cell transfer technology services provided to 9 cooperative hospitals located in Beijing, Shandong and Anhui provinces in China;
Strengthened the leadership team with the appointments of Richard L. Wang, Ph.D., MBA, PMP, formerly with GSK, as Chief Operating Officer and Yihong Yao, Ph.D., B.S., formerly with Astrazeneca/Medimmune as Chief Scientific Officer;

Formed a Scientific Advisory Board (SAB) with the appointment of Alan List, M.D. as Chair of the SAB, the appointment of Scott J. Antonia, M.D., Ph.D. to advise the company on immuno-oncology and Guoping Fan, Ph.D. to advise the Company on stem cell technology and its applications;

Continued to demonstrate good corporate governance by meeting the required higher listing standards to successfully upgrade the listing of the Company’s securities from the NASDAQ Capital Market to the NASDAQ Global Market and being selected into the broad-market Russell 3000 Index;

Advanced the Company’s cash position:
Total private placement transactions of approximately $19.6 Million in 2015
Announced agreement of Wuhan Dangdai Science & Technology Industries Group Inc. to invest up to $43.13 million for 2.27 million shares of the Company’s common stock, representing a 19.4% stake investment in Q1 2016 with an initial closing of $5 million in February 2016, and the remaining $38.13 million by April 15, 2016.

Full Year 2015 Financial Results

Cash Position: The Company had working capital of $13.7 million as of December 31, 2015 compared to $12.0 million as of December 31, 2014. Cash position increased to $14.9 million at December 31, 2015 compared to $14.8 million at December 31, 2014, due to an increase in cash generated from financing activities as a result of a private placement financing in 2015 for aggregate net proceeds of approximately $19.0 million, partially offset by an increase in cash used in operating and investing activities.

Net Cash Used in Operating Activities: Full-year 2015 net cash used in operating activities was $11.8 million compared to $9.7 million in 2014. The change in operating assets and liabilities was primarily due to an increase in accounts receivables, long-term prepaid expenses combined with decreases in tax payables and non-current liabilities, partially offset by an increase in accrued expenses.

Revenue: Full-year 2015 revenue was $2.5 million compared to $0.6 million in 2014. All revenue for the year ended December 31, 2015 was derived from TCR technology services.

G&A Expenses: Full-year 2015 general and administrative expenses were $13.1 million compared $7.9 million in 2014. Increased expenses in 2015 were associated with increased corporate activities related to the management and the development of the Company’s biomedicine business, which were primarily attributed to:

An increase in stock-based compensation expense of $3.7 million, which primarily resulted from the new grants and higher fair value of unvested options in 2015 after the Company listed on Nasdaq in June 2014 compared with those unvested options as of December 31, 2014;
An increase in payroll of $0.3 million in line with the headcount increase in management in 2015;
An increase in depreciation and amortization of $0.2 million, which was mainly attributed to the technical knowledge and patents obtained from the acquisition of AG in the third quarter 2014;
R&D Expenses: Full-year 2015 research and development expenses were $7.6 million compared to $3.1 million in 2014, the increase mainly attributable to the increase of our immunotherapy research and development team, which resulted in an increase in payroll expenses of $1.2 million and an increase in stock-based compensation expenses of $1.8 million.

Net Loss: Full-year 2015 net loss allocable to common stock holders was $19.4 million compared to $15.5 million in 2014. Changes in net loss were primarily attributable to changes in operations of our biomedicine segment.

Primary 2016 Operating Objectives
The Company’s key 2016 operational objectives are to seek early possibilities of conducting multi-center Phase IIb trials with its CAR-T constructs after confirming their safety and tolerability profile, to evaluate feasibility of sponsoring a registration trial-like clinical study to support a New Drug Application (NDA) for an allogeneic haMPC Knee Osteoarthritis therapy ("Allo KOA") study in the United States, and continue to build a pipeline of advanced technologies to bolster the Company’s CAR-T China market position.

On March 14, 2016 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported company highlights and financial results for the full year ended December 31, 2015(Press release, Ignyta, MAR 14, 2016, View Source [SID:1234509529]).

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"2015 was a transformational year for Ignyta in terms of the substantial progress we made towards becoming a leading precision oncology biotechnology company focused on the development of first-in-class and best-in-class precision medicines," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We significantly grew our pipeline of molecularly targeted therapies through our transactions with Teva and Lilly, and we made substantial strides on the pre-clinical, clinical and regulatory fronts with our development programs, including initiating a potentially registration-enabling Phase 2 clinical trial of our lead product candidate, entrectinib. Furthermore, we achieved CAP accreditation of our in-house diagnostics laboratory, bolstered our balance sheet, and strengthened our team. We look forward to continuing our efforts to develop compelling therapies for the benefit of cancer patients."

Company Highlights

Strategic Positioning

In February 2016, Ignyta announced plans to prioritize certain "core" pipeline programs that have generated the most promising data to date, and to deprioritize certain "non-core" pipeline programs that fall outside of Ignyta’s focus on molecularly targeted therapies. This strategic positioning prioritizes key research and development activities, improves efficiencies and reduces operating expenses.

These plans include:

An ongoing commitment to drive value from Ignyta’s core Rx/Dx business model by prioritizing the continued development of the company’s molecularly targeted entrectinib, taladegib, RXDX-105 and RXDX-106 programs, in conjunction with complementary Dx development and laboratory operations;

Continued activities to advance Ignyta’s immuno-oncology and cancer stem cell programs that relate to its current molecularly targeted pipeline (e.g., potential immunotherapy applications of the RXDX-105 and RXDX-106 programs, and potential molecularly targeted cancer stem cell applications of the taladegib and Spark programs); and

Cessation of all development activities relating to the company’s RXDX-107, RXDX-103 and RXDX-108 programs, and certain Spark discovery programs.

Entrectinib Clinical Progress

In September 2015, Ignyta announced the initiation of its Phase 2 clinical trial of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors that harbor activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK. This clinical trial, called STARTRK-2, the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases," is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for gene rearrangements of the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types that harbor a rearrangement of one of the genes encoding any one of entrectinib’s five protein targets.

Also in September 2015, the company announced updated interim results of its Phase 1 clinical trials of entrectinib, which were presented in an oral presentation session at the 2015 European Cancer Congress (ECC 2015) in Vienna, Austria.

The clinical trials included the ALKA-372-001 study and the STARTRK-1 study. Both trials were designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant molecular alterations: NTRK1 (encoding TrkA), ROS1 or ALK for ALKA-372-001 and NTRK1/2/3 (encoding TrkA/B/C), ROS1 or ALK for STARTRK-1.

As of the August 15, 2015, data cut-off for the presentation, the findings showed:

A total of 92 patients with a range of solid tumors were dosed across both clinical trials, with nine patients treated at or above the RP2D beyond six months and one patient beyond one year;

Entrectinib was well-tolerated;

The fixed daily dose RP2D was determined to be 600 mg, taken orally once per day (QD);

18 patients across both clinical trials met the company’s Phase 2 eligibility criteria, which include:
Presence of an NTRK1/2/3, ROS1 or ALK gene rearrangement, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);

ALK-inhibitor and/or ROS1-inhibitor naïve; and

Treatment at or above the RP2D;

The response rate in the 18 patients who met these criteria across both studies was 72% (13 responses out of 18 treated patients, as assessed by the clinical sites). Nine of these responders remained on study treatment with durable responses of up to 21 treatment cycles. An additional 3 patients remained on study with stable disease. The responses included:

3 responses out of 4 patients with an NTRK1, NTRK2 or NTRK3 gene rearrangement, including patients with non-small cell lung cancer (NSCLC), colorectal cancer and salivary gland cancer;

6 responses, including one complete response, out of 8 patients with a ROS1 gene rearrangement, all of which were in NSCLC; and

4 responses out of 6 patients with an ALK gene rearrangement, including two NSCLC patients and two patients with other solid tumors.

Entrectinib had demonstrated objective tumor response in the central nervous system (CNS), a frequent site of metastases and progression of advanced solid tumors.

In July 2015, the company announced a clinical collaboration with the University of California, San Francisco (UCSF), which is conducting a multicenter, open label umbrella trial to obtain proof of concept data in patients with metastatic melanoma that is positive for molecular alterations in specific tyrosine kinase receptors. UCSF will exclusively use entrectinib for patients enrolled in the clinical trial having activating molecular alterations to NTRK1/2/3 (encoding TrkA/B/C) or ROS1.

Taladegib License Transaction with Eli Lilly and Company

In November 2015, Ignyta announced it had exclusively licensed worldwide rights relating to Eli Lilly’s taladegib oncology development program in exchange for an upfront payment of $2.0 million in cash and the issuance to Lilly of approximately 1.2 million shares of Ignyta’s common stock. Taladegib is a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved compelling clinical proof of concept and an RP2D in a Phase 1 dose escalation clinical trial.

Teva Asset Acquisition

In March 2015, Ignyta acquired worldwide rights and assets relating to four targeted oncology development programs from Teva in exchange for 1.5 million shares of Ignyta’s common stock. The programs currently under active development include:

RXDX-105, the company’s orally available, small molecule multikinase inhibitor with potent activity against such targets as RET and
BRAF, that is currently in a Phase 1/1b dose escalation clinical trial; and

RXDX-106, the company’s small molecule, pseudo-irreversible inhibitor of Tyro-3, Axl and Mer (TAM) and cMET that is in late preclinical development.

Presentation of RXDX-105 Clinical Data

In November 2015, Ignyta announced interim results from the ongoing Phase 1/1b clinical trial of RXDX-105, which were presented at the 27th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.

The dose escalation clinical trial was designed to determine the MTD and/or RP2D, as well as preliminary anti-cancer activity, of single agent RXDX-105 in patients with advanced or metastatic solid tumors that were not selected based on any molecular alteration.

As of the October 26, 2015, data cut-off for the presentation, the findings showed:

A total of 41 patients with a range of solid tumors were dosed in the clinical trial;

RXDX-105 was well-tolerated;

The MTD and RP2D had not yet been determined;

Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to further increase exposure;

Exposure was reaching levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and

Tumor regression was observed in six patients treated with 275 mg, including one confirmed partial response (40% reduction) in a patient with NSCLC with a KRAS G12C mutation. Two additional patients with thyroid cancer and squamous cell lung cancer exhibited reductions of 20% and 27%, respectively. In patients with tumor regression, there appears to be an exposure/response correlation.

In March 2016, Ignyta announced the selection of the RP2D and initiation of the Phase 1b portion of the Phase 1/1b clinical trial of RXDX-105. The Phase 1b portion of the study utilizes a basket design focusing on patients with solid tumors that contain molecular alterations of RET or BRAF.

Dx Laboratory

In December 2015, the company announced that its San Diego diagnostic laboratory had been accredited by the College of American Pathologists (CAP) based on results of an on-site inspection. This accreditation is awarded to facilities that meet the highest standards of quality in clinical laboratory services. The U.S. Centers for Medicare & Medicaid Services (CMS) has approved CAP as an accreditation organization for clinical laboratories under CLIA (Clinical Laboratory Improvement Amendments). Ignyta had previously announced CLIA registration of its diagnostic laboratory, and CAP accreditation results in full CLIA certification for Ignyta’s diagnostic laboratory.

In June 2015, the company announced the release for clinical use of its first clinical trial assay, called Trailblaze PharosTM, to support patient identification and enrollment into its STARTRK clinical development program for entrectinib. The proprietary assay was co-developed with ArcherDx and validated within Ignyta’s San Diego diagnostic laboratory. This lab is utilizing this assay in acting as the central testing lab for patient screening for the STARTRK-2 Phase 2 clinical study of entrectinib.

Financing Transactions

Concurrently with the Lilly license transaction in November 2015, Ignyta entered into a stock purchase agreement with Lilly under which Lilly purchased 1.5 million shares of Ignyta common stock at a price of $20 per share in a private placement, which resulted in aggregate gross proceeds of $30 million.

In September 2015, Ignyta borrowed an additional $10 million under its term loan facility from Silicon Valley Bank.

In June 2015, the company issued an aggregate of approximately 4.3 million shares of its common stock in an underwritten public offering at a purchase price of $17.50 per share, which resulted in aggregate gross proceeds of approximately $75 million.

Concurrently with the Teva asset acquisition transaction, Ignyta sold to Teva and selected healthcare investors a total of approximately 4.2 million shares of its common stock at a price of $10 per share in a registered direct offering, which resulted in gross aggregate proceeds of approximately $42 million.

Financial Results

For the 2015 fiscal year, net loss was $92.5 million, or $3.44 per share, compared with $40.0 million, or $2.18 per share, for the 2014 fiscal year.

Ignyta had no material revenues during 2015 or 2014.

Research and development expenses for 2015 were $73.5 million, compared with $30.5 million for 2014. The majority of the increase was due to non-cash costs incurred in connection with the acquisition of rights to development programs from Teva and Lilly during 2015. The remaining increase was primarily attributable to an increase in activities relating to development of entrectinib and the company’s other product candidates, increased personnel expenses related to hiring and engaging additional employees and consultants, and facilities related expenses as a result of the expansion of the company’s leased facilities space.

General and administrative expenses were $17.1 million for 2015, compared with $9.5 million for 2014. The increase was primarily attributable to increases in personnel costs and additional investor relations, audit, legal and intellectual property costs.

At December 31, 2015, the company had cash, cash equivalents and available-for-sale securities totaling $172.1 million and current and long-term debt of $31.0 million. At December 31, 2014, the company had cash and cash equivalents totaling $76.6 million and current and long-term debt of $21.0 million.

On March 14, 2016 Janssen-Cilag International NV reported that data from a post-hoc analysis of the Phase 3 COU-AA-302 trial showed that ZYTIGA (abiraterone acetate) plus prednisone provided an 11.8 months overall survival (OS) benefit (53.6 months vs 41.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055), compared to an active control of placebo plus prednisone, in men with early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (Press release, Johnson & Johnson, MAR 14, 2016, View Source [SID:1234509557]).1

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Data from the post-hoc analysis, presented today at the European Association of Urology (EAU) 2016 Congress in Munich, Germany, demonstrated almost triple the OS benefit previously shown (4.4 months) in the final analysis of the COU-AA-302 trial (34.7 months ZYTIGA plus prednisone vs 30.3 months placebo plus prednisone; HR = 0.81 [95% CI, 0.70-0.93]; p = 0.0033). The final analysis was originally presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress and included a broader range of men with asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC.2

The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80 ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80 ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055) (Group 2: 2.8 months; HR = 0.84 [95% CI, 0.72-0.99]; p = 0.0321).1

"Post-hoc analyses such as this are very important in helping us to identify the patients who could benefit most from therapies such as novel hormone agents, and at what stage of a patient’s disease they could be most effective." said Professor Kurt Miller, Department of Urology, Chariteì Berlin, Berlin, Germany. "As men with prostate cancer are living longer, quality of life is an increasingly important factor for them and their families. It is therefore encouraging to see that when used earlier, patients can stay on ZYTIGA for longer and delay the need for additional, more invasive treatments," he continued.

In addition to OS benefit, the post-hoc analysis data also revealed that both groups showed improvement in disease progression, cancer-related pain and treatment duration when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone:

Time to chemotherapy use was increased by 12.7 months in Group 1 and 8.8 months in Group 2
Group 1: 37.0 months vs 24.3 months; HR = 0.64 [95% CI, 0.46-0.89]; p = 0.0073
Group 2: 23.3 months vs 14.5 months; HR = 0.71 [95% CI, 0.60-0.85]; p = 0.0001

There was an improvement in median time to opiate use for cancer-related pain in both groups
Group 1: not reached vs 41.0 months; HR = 0.69 [95% CI, 0.48-0.99]; p = 0.0409
Group 2: 30.5 months vs 19.3 months; HR = 0.70 [95% CI, 0.59-0.84]; p = 0.0001

Median time on treatment almost doubled in both groups
Group 1: 20.4 months vs 11.2 months; HR = 0.41 [95% CI, 0.31-0.54]; p < 0.0001
Group 2: 12.3 months vs 7.2 months; HR = 0.54 [95% CI, 0.46-0.62]; p < 0.0001

Jane Griffiths, Company Group Chairman, Janssen Europe, the Middle East and Africa (EMEA) said: "Janssen is proud that this study continues to deliver valuable insights as to how best to treat different stages of advanced prostate cancer. We hope that this additional analysis will help healthcare professionals to define the most effective treatment pathway for individual patients. We remain committed to continuing our research in this area with the aim of helping to improve outcomes for men affected by this disease now and in the future."

-ENDS-
NOTES TO EDITORS

About the COU-AA-302 study

COU-AA-302 is an international, randomised, double-blind, placebo controlled Phase 3 study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomised to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5 mg administered twice-daily or placebo plus prednisone 5 mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. Key secondary endpoints included time to opiate use, time to initiation of chemotherapy, time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration and time to PSA progression. The final analysis was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress.

The post-hoc analysis used the final dataset for the intent-to-treat population (n = 1088), to stratify patients into Group 1 (BPI 0-1, PSA < 80 ng/ml and GS < 8) and Group 2 (BPI = 2 and/or PSA = 80 ng/ml and/or GS = 8). OS, radiographic progression-free survival (rPFS), time to CT use, time to opiate use, and time on treatment with ZYTIGA plus prednisone vs placebo plus prednisone were analysed by the Kaplan–Meier method and Cox proportional hazards regression.

About ZYTIGA (abiraterone acetate)

ZYTIGA is the only approved therapy that inhibits production of androgen, which fuels prostate cancer growth, via inhibiting the CYP17 enzyme complex present at three sources: the testes, adrenals and the tumour itself.

ZYTIGA has been approved in more than 90 countries and to date, has been prescribed to more than 269,500 men worldwide.

Indication3

In 2011, ZYTIGA in combination with prednisone/prednisolone was approved by the European Commission (EC) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

In December 2012, the EC granted an extension of the indication for ZYTIGA permitting its use, in combination with prednisone or prednisolone, for the treatment of mCRPC, in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.3

Further Information3

For a full list of side effects and for further information on dosage and administration, contraindications and other precautions when using ZYTIGA, please refer to the summary of product characteristics, which is available at: View Source;mid=WC0b01ac058001d124

On March 14, 2016 SRI International reported that it has been awarded a contract worth up to US$19.8m from the National Cancer Institute (NCI) in the US to support the development of potential preventative cancer agents or vaccines (Press release, SRI International, MAR 14, 2016, View Source [SID:1234509560]).

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Under the three-year contract, which is part of the PREVENT Cancer Preclinical Drug Development Programme, the Menlo Park, CA-based firm’s SRI Biosciences will conduct preclinical studies to assess the efficacy of specific compounds or vaccines for preventing invasive-cancer development.

Researchers will also identify biomarkers to help quantify the effectiveness of the experimental compounds and vaccines.

The PREVENT Cancer Drug Development Program is an NCI-supported pipeline to bring new cancer preventing interventions and biomarkers through preclinical development towards clinical trials.

‘The discovery and development of cancer preventative agents is an area that is underserved, primarily because the length of required clinical trials can be resource-prohibitive for many companies. Our work in biomarker discovery may provide validated surrogate endpoints that can help to shorten clinical trials in cancer prevention,’ said Lidia Sambucetti, Senior Director of Cancer Biology, Centre for Discovery Technologies, SRI Biosciences, and principal investigator for the NCI contract. ‘The PREVENT programme is an opportunity to identify and advance novel strategies for cancer prevention.’

Under the PREVENT programme, for efficacy and biomarker testing, two NCI task orders in the area of cancer prevention have already been awarded to SRI Biosciences: the first to develop a mesothelin-based vaccine against ovarian cancer, and another to develop novel models for testing preventative agents against ovarian cancer.

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For the ovarian cancer programme, SRI Biosciences optimised a vaccine strategy designed to mount both antibody-based and cellular immunity against mesothelin tumour antigen. SRI researchers are currently testing whether the vaccine can help prevent ovarian cancer. In addition, SRI generated encouraging data supporting the development of a new model that will be used to test experimental drugs for ovarian cancer prevention.

On March 14, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported positive results from the Phase 3 trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared to the standard of care regimen of cytarabine and daunorubicin known as 7+3 (Press release, Celator Pharmaceuticals, MAR 14, 2016, View Source [SID:1234509534]). The trial met its primary endpoint demonstrating a statistically significant improvement in overall survival. Data will be submitted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting.

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The median overall survival for patients treated with VYXEOS in the study was 9.56 months compared to 5.95 months for patients receiving 7+3, representing a 3.61 month improvement in favor of VYXEOS. The hazard ratio (HR) was 0.69 (p=0.005) which represents a 31 percent reduction in the risk of death versus 7+3. The percentage of patients alive 12 months after randomization was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm. The percentage of patients alive 24 months after randomization was 31.1% on the VYXEOS arm compared to 12.3% on the 7+3 arm.

"The overall survival advantage seen with CPX-351 compared to 7+3, along with a superior response rate and no increase in serious toxicity indicates that we’ll likely have a new standard of care for treating older patients with secondary AML," said Jeffrey E. Lancet, M.D., senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center and the principal investigator for the study. "This represents a major step forward for a very difficult-to-treat patient population."

VYXEOS also demonstrated a statistically significant improvement in induction response rate (CR+CRi of 47.7% versus 33.3%; p=0.016) and this significance was maintained for the analysis of CR alone (CR of 37.3% versus 25.6%, p=0.040).

Sixty-day all-cause mortality was 13.7% versus 21.2%, in favor of patients treated with VYXEOS.

No substantial difference in Grade 3 or higher adverse events was observed between VYXEOS and 7+3. In the intent-to-treat population, Grade 3 or higher, hematologic adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, Grade 3 or higher, non-hematologic adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin and renal.

"These findings confirm that VYXEOS provides the first opportunity we’ve had in decades to extend survival for patients with high-risk AML," added Gail Roboz, M.D., Professor of Medicine and Director of the Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York. "Also, more patients in remission means more who are eligible for potentially curative therapy."

Based on these results the company expects to submit a New Drug Application (NDA) for VYXEOS with the U.S. Food and Drug Administration (FDA) later this year and submit a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in the first quarter of 2017.

"The successful outcome of this Phase 3 trial represents an important advance for AML patients, their families and clinicians," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "It also marks a major milestone for Celator, for VYXEOS, and for our CombiPlex platform. We offer our sincere thanks to the patients and investigators who participated in this study and we will work closely with regulatory authorities to make this new treatment available to the AML community as soon as possible."

The clinical trial was conducted in partnership with The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP), which has supported the clinical development of VYXEOS beginning in Phase 2.

About VYXEOS

VYXEOS (cytarabine:daunorubicin) Liposome for Injection, also known as CPX-351, is a nano-scale co-formulation of cytarabine and daunorubicin at a synergistic 5:1 molar ration. VYXEOS represents a novel approach to developing combinations of drugs in which molar ratios of two drugs with synergistic anti-tumor activity are encapsulated in a nano-scale liposome in order to maintain the desired ratio following administration. VYXEOS was granted orphan drug status by the FDA and the European Commission for the treatment of acute myeloid leukemia (AML). VYXEOS was also granted Fast Track designation for the treatment of elderly patients with secondary AML. In addition to the Phase 3 trial, Celator published results from two randomized, controlled, Phase 2 trials with VYXEOS. The first trial was conducted in newly diagnosed elderly AML patients and the second trial was conducted in patients with AML in first relapse.

Phase 3 Trial Design

The randomized, controlled, Phase 3 trial (Protocol NCT01696084), enrolled 309 patients at 39 sites in the United States and Canada, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients with high-risk (secondary) AML. Patients were stratified for age (60 to 69 and 70 to 75 years of age) and AML type; treatment-related AML, AML with documented history of MDS with prior treatment with hypomethylating agent therapy, AML with documented history of MDS without prior hypomethlyating agent therapy, AML with a documented history of chronic myelomonocytic leukemia (CMMoL), and de novo AML with a karyotype characteristic of myelodysplastic syndrome (MDS).

Patients were randomized 1:1 to receive either VYXEOS or 7+3. Patients could receive one or two inductions, and responding patients could receive one or two consolidations. First induction for VYXEOS was 100u/m2; days 1, 3, and 5 by 90-minute infusion and for the control arm was cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3 (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days 1 and 3 and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

Only patients with documented CR or CRi were eligible to receive chemotherapy consolidation. Consolidation for VYXEOS-treated patients was 65u/m2 on days 1 and 3 and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

About AML

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. AML is generally a disease of older adults, and the median age of a patient diagnosed with AML is about 67 years. The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016. In Europe the number of new cases is estimated to be 18,000 and in Japan the number is 5,500. The Company estimates that nearly 70 percent of AML patients are over the age of 60, and approximately 75 percent are intermediate or high risk. Furthermore, approximately half of those patients are considered suitable for intensive treatment.

Even with current treatment, overall survival for AML is poor. In patients over 60 years of age, the 5 year survival rate is less than 10%. In high-risk (secondary) AML, overall survival is lower, resulting in an acute need for new treatment options for these patients.