On March 14, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI), a clinical-stage biopharmaceutical company developing orally-administered therapeutics to treat autoimmune diseases, inflammatory disorders and cancer, reported financial results for the fourth quarter ended December 31, 2015 and provided an update on the Company’s corporate and clinical development activities expected in 2016 (Press release, ChemoCentryx, MAR 14, 2016, View Source [SID:1234509537]).

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"2015 was a period of significant accomplishments for ChemoCentryx, highlighted by the positive clinical results which we announced earlier this year from the Phase II CLEAR trial in ANCA Vasculitis (AAV) with our lead drug candidate, CCX168. Premature death is among the many dangers of chronic high dose steroids in the standard of care for AAV. At ChemoCentryx, we think such risks are unacceptable, and simply cannot be ignored," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "The single biggest cause of first year mortality associated with AAV is steroid-induced infections. Adding to this, there are other dangers of chronic high dose steroid use, such as bone fractures, incipient diabetes, and neuropsychiatric problems. Our data showed that CCX168 can eliminate the need for chronic high dose steroid administration in patients with AAV, and it was correlated with a rapid and sustained remission of disease symptoms, as well as improved quality of life, as reported by patients themselves."

Dr. Schall continued, "The momentum of last year has continued into 2016 as we await several important milestones, including potentially the initiation of our Phase III development program for CCX168. We also await clinical data for CCX872 in pancreatic cancer. With multiple programs advancing in the clinic, we believe that this is one of the most exciting moments in ChemoCentryx’s history."

Pipeline Developments Across Key Therapeutic Areas

Orphan and Rare Diseases: CCX168 is an orally-administered complement inhibitor targeting the C5a receptor (C5aR), and is being developed for several rare disease indications, including ANCA-associated vasculitis (AAV) and atypical Hemolytic Uremic Syndrome (aHUS). CCX168 acts by blocking the destructive action of neutrophils that are activated as a consequence of the complement protein known as C5a binding to C5aR on neutrophils during autoimmune inflammation events.

CCXI reported positive top-line data from the Phase II CLEAR trial with CCX168 in 63 evaluable patients with AAV. The objective of the trial was to eliminate chronic high dose steroids from the standard of care (SOC) regimen in AAV and replace them with CCX168. Chronic high dose steroid administration is associated with premature death and a spectrum of other harmful side effects in AAV therapy.

The trial was successful in meeting its primary endpoint based on the Birmingham Vasculitis Activity Score response at week 12 in patients receiving CCX168, compared to those patients receiving the high dose steroid-containing SOC.

All CCX168 treatment groups demonstrated a numerically superior and statistically significant (P=0.002 for non-inferiority) clinical efficacy outcome when compared to SOC.

Treatment with CCX168 led to improvements in kidney function as measured by improvements in estimated glomerular filtration rate (eGFR) as well as beneficial changes in proteinuria, hematuria and renal inflammation (based on MCP-1).

Patient reported improvements in "Quality of Life" were also significantly improved in CCX168 treatment groups, but not in the SOC group.

Completed enrollment in the CLASSIC Phase II trial in AAV in North America.

Immuno-Oncology: CCX872 is a potent and selective inhibitor of the chemokine receptor known as CCR2, which is being evaluated in patients with non-resectable pancreatic cancer. In an ongoing, multi-center clinical trial with CCX872, 54 patients with non-resectable pancreatic cancer have been enrolled. The primary efficacy measurement of this study is progression-free survival after at least 24 weeks of treatment.

Completed enrollment in the Phase Ib clinical trial of CCX872 in patients with non-resectable pancreatic cancer; and

Presented combination data with check point and chemokine receptor inhibitors at Triple Meeting and Society of Immunotherapy for Cancer meeting showing synergistic effect with combination treatment in triple negative breast cancer models.

Anticipated Milestones

Orphan and Rare Diseases:

Report top-line results from the CLASSIC Phase II trial in patients with AAV in North America with CCX168 in mid-2016;

Conduct End of Phase II meetings with regulatory agencies to review CLEAR and CLASSIC Phase II clinical results in mid-2016;

Initiate Phase III development program with CCX168 for the treatment of AAV by the end of 2016; and

Report early results from the Phase II pilot study of CCX168 in aHUS patients who are on dialysis in 2016.

Immuno-Oncology:

Advance Phase Ib pancreatic cancer trial of CCX872 in combination with FOLFIRINOX; report initial overall response data in the second quarter of 2016 and initial progression free survival data in the second half of 2016.

Chronic Kidney Disease:

Conduct End of Phase II meeting with the FDA to review the Phase II data and discuss the Phase III clinical development program for CCX140 in diabetic nephropathy.

Fourth Quarter 2015 Financial Results

Cash, cash equivalents and investments totaled $76.3 million at December 31, 2015.

Research and development expenses were $8.2 million for the three months ended December 31, 2015 compared to $9.1 million reported for the same period in 2014. The decrease in research and development expense from 2014 to 2015 was primarily attributable to lower expenses associated with CCX168, the Company’s C5aR inhibitor, due to the completion of the Phase II CLEAR trial in the fourth quarter of 2015 and CCX140, the Company’s CCR2 inhibitor, due to the completion of the Phase II clinical trial in patients with diabetic nephropathy in 2014. These decreases were partially offset by higher expenses associated with CCX872, the Company’s second CCR2 inhibitor, reflecting continued patient enrollment in the ongoing pancreatic cancer trial.

General and administrative expenses were $3.4 million for the three months ended December 31, 2015 compared to $3.2 million for the comparable period in 2014. The increase from 2014 to 2015 was primarily due to increases in intellectual property related expenses and professional fees.

Net loss was $11.6 million for the fourth quarter of 2015 compared to $12.2 million in the same period in 2014.

Total shares outstanding at December 31, 2015 were approximately 44.2 million shares.

2016 Financial Outlook

The Company expects to utilize cash and cash equivalents between $40 million and $50 million in 2016.

About ANCA-Associated Vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, or AAV, is a type of rare autoimmune inflammation caused by auto-antibodies. AAV encompasses granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis), microscopic polyangiitis (MPA), eosinophilic polyangiitis (formerly Churg-Strauss syndrome) and renal limited vasculitis.

AAV represents a severe and often fatal autoimmune disease that is characterized by inflammation that can destroy different organ systems. AAV is the lead indication in the Company’s orphan and rare disease program with a clinical objective of eliminating chronic high dose steroids in the standard of care (SOC) regimen, essentially replacing steroids with the complement inhibitor CCX168.

AAV affects approximately 40,000 people in the US (with approximately 4,000 new cases each year) and greater than 75,000 people in Europe (with at least 7,500 new cases each year), and is currently treated with courses of immuno-suppressants (cyclophosphamide or rituximab) combined with high dose steroid administration. Following initial treatment, up to 30 percent of patients relapse within 6 to 18 months, and approximately 50 percent of all patients will relapse within 3 to 5 years.

Current standard of care (SOC) for AAV comprises high doses of chronic steroids combined with an immunosuppressant (either cyclophosphamide or rituximab). The SOC is associated with significant safety issues. For example, first year premature death is approximately 11 to 18 percent. The single major cause of premature mortality is not disease related adverse events, but rather infection that is thought largely to be a consequence of steroid administration. Indeed, the multiple adverse effects of courses of steroid treatment (both initial courses and those that are repeated as a consequence of relapse) are major causes of both short-term and long-term disease and death. Such therapy related adverse events contribute significantly to patient care costs, as well as to the diminution of quality of life for patients.

By damaging the body’s small blood vessels, AAV affects many organ systems, mostly the kidneys, eyes, lungs, sinuses and nerves. This damage is caused by the destructive activity of inflammatory leukocytes in the body, with neutrophils considered to be the terminal effector cell. In AAV, neutrophils are attracted to sites of vascular destruction as well as activated at those sites by the activity of the complement system product known as C5a and its receptor, C5aR, which is the target of CCX168. By blocking the C5aR, CCX168 is thought to reduce vasculitis by reducing neutrophil activation, accumulation, and adhesion, as well as vascular permeability.

About Pancreatic Cancer

It is estimated that over 337,000 cases of pancreatic cancer are diagnosed worldwide every year, accounting for 2.4 percent of all cancers. The incidence of pancreatic cancer in the US is about 45,000, with prevalence being only negligibly higher owing to the poor survival rates on current therapy. Current standards of care include surgical resection and chemotherapeutic regimens such as gemcitabine and FOLFIRINOX. These regimens are limited by marked toxicities. Almost 67 percent of cases are diagnosed in people aged 65 and over. In the United States, pancreatic cancer is the fourth most common cause of deaths due to cancer. Pancreatic cancer has a low survival rate regardless of stage of disease, with 93 percent of patients dying from their disease within five years.

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.

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 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 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the fourth quarter and full year ended December 31, 2015, and provided an update on the Company’s recent progress (Press release, Bellicum Pharmaceuticals, MAR 14, 2016, View Source;p=RssLanding&cat=news&id=2148302 [SID:1234509523]).

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"In 2015, Bellicum made significant progress across all of our T-cell immunotherapy programs, reporting positive interim results with our lead product candidate BPX-501, and advancing our CAR T and TCR programs," said Tom Farrell, Bellicum’s President and Chief Executive Officer. "Data presented at ASH (Free ASH Whitepaper) from the BP-004 clinical trial with BPX-501 demonstrated disease-free outcomes in pediatric patients with genetic blood diseases. We believe that BPX-501, which was recently granted orphan drug designation by the FDA, could represent a vital treatment option for the many patients for whom a transplant is recognized as the preferred treatment, but who are not treated because they lack a perfect match donor."

Continued Mr. Farrell, "Building on this momentum, we look forward to achieving important milestones in 2016, with data updates from the BPX-501 program expected to be presented at several medical meetings. We also expect to launch Phase 1 clinical trials of three novel product candidates: BPX-701 and BPX-601 in mid-2016, and BPX-401 in the second half of 2016. The BPX-701 and BPX-601 programs were reviewed at the March 10th meeting of the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC) and we were pleased with the engaging discussion and meeting outcomes."

2015 HIGHLIGHTS AND CURRENT UPDATES

DEVELOPMENT PROGRAMS

BPX-501

Adjunct T-cell therapy administered after allogeneic hematopoietic stem cell transplantation (HSCT), using genetically modified donor T cells incorporating our CaspaCIDe safety switch, is being evaluated in malignant and nonmalignant blood diseases.

Enrollment in Phase 1/2 BP-004 clinical trial continues at strong pace, with 63 pediatric patients enrolled in the E.U. and 12 patients enrolled in the U.S. to date.
Granted orphan drug designation by the FDA for the combination of BPX-501 genetically modified T cells and activator agent rimiducid as "replacement T-cell therapy for the treatment of immunodeficiency and Graft versus Host Disease after allogeneic hematopoietic stem cell transplant."
Reported interim data from ongoing BP-004 trial, demonstrating disease-free outcomes in pediatric patients with genetic blood diseases who had undergone HSCT followed by BPX-501 donor T-cell replacement. Presented at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2015, the data showed that treated patients achieved immune recovery significantly faster than historical control subjects not given BPX-501, as well as a significant reduction in time to hospital discharge (21 days sooner vs. historical controls) and reduced re-hospitalizations. In addition, none of the patients had developed chronic GvHD and no patient died of transplantation-related complications. Of the 39 patients treated (as of Nov. 30, 2015), 21 had genetic blood diseases, including Fanconi anemia, beta thalassemia, SCID and Wiskott-Aldrich Syndrome, and 18 had blood cancers.
DOTTI study clinical data published in BLOOD highlighted safety and effectiveness of CaspaCIDe-modified T-cell add-back. Results of a 12-patient investigator-sponsored trial conducted by Baylor College of Medicine demonstrated that the add-back led to improved immune reconstitution and infection control. The data also showed that GvHD can be rapidly controlled and resolved by administration of rimiducid, and that the productive anti-viral cells remain, repopulate and maintain immunity.
U.S. patent issued to Baylor College of Medicine for technology exclusively licensed to Bellicum. The patent, issued for methods of inducing selective apoptosis of cells, extends Bellicum’s proprietary rights to the use of its lead product candidate until at least 2031.
BPX-701

High affinity T cell receptor (TCR) product candidate, incorporating our CaspaCIDe safety switch, is designed to target malignant cells expressing the preferentially-expressed antigen in melanoma (PRAME).

Bellicum continues to advance its next-generation, proprietary TCR product candidate targeting PRAME. The Company licensed the PRAME-specific TCR technology from Leiden University Medical Center in April 2015 and is preparing for the start of clinical trials for the initial planned indications of Refractory or Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), with an additional clinical trial planned for metastatic uveal melanoma. Each of these are orphan indications in which PRAME is highly expressed and for which current treatment options are limited.
BPX-601

GoCAR-T product candidate, containing proprietary iMC (inducible MyD88/CD40) activation switch, is designed to treat solid tumors expressing prostate stem cell antigen (PSCA).

Continued to advance the Company’s first GoCAR-T product candidate toward the clinic. The planned indication for the initial Phase 1 study is non-resectable pancreatic cancer. Preclinical data reported at ASH (Free ASH Whitepaper) 2015 showed robust anti-tumor activity, and enhanced T-cell proliferation and persistence compared to traditional CAR T constructs.
Obtained an exclusive global license from Agensys for adoptive cell therapies targeting tumors expressing PSCA.
BPX-401

CIDeCAR product candidate, incorporating novel, proprietary MC costimulatory domain and CaspaCIDe safety switch, is designed to target blood cancers expressing CD19.

Presented preclinical data at ASH (Free ASH Whitepaper) 2015 highlighting the potent anti-tumor effects of BPX-401. The preclinical in vivo results showed that tumors can be eliminated quickly and safely with CIDeCAR cells. Notably, BPX-401 elicited dose-dependent elevation of cytokines, analogous to cytokine release syndrome, but cytokine levels were rapidly normalized upon administration of rimiducid, without loss of tumor control.
CORPORATE UPDATES

Committed to build-out of in-house U.S. manufacturing capabilities. The Company leased an additional 27,000 square feet at its current location and completed the design phase for the build-out of manufacturing space. The facility is designed to support the efficient manufacturing of our novel cellular immunotherapies for clinical trials and early commercial requirements.
Recently closed on a debt financing agreement with Hercules Capital to support the build-out of the Company’s U.S. manufacturing facilities. Under the loan terms, Bellicum can borrow up to $30 million, of which the final $10 million tranche is contingent upon achievement of specified milestones and approval by Hercules’ investment committee.
ANTICIPATED 2016 MILESTONES

BPX-501

Expect to provide an update on the nonmalignant patient cohort from the BP-004 clinical trial, as well as initial data for patients with blood cancers treated at the lead European clinical trial site, during the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) which takes place April 3 – 6, 2016.
Expect to meet with regulators in Europe and the U.S. in the second quarter of 2016, with the goal of defining the path to regulatory filing and approval initially for nonmalignant pediatric genetic diseases.
Anticipate presenting updated data from the BPX-501 program at ASH (Free ASH Whitepaper) in December 2016.
BPX-701

Expect to begin enrolling patients in a Phase 1 clinical trial for refractory or relapsed acute AML and MDS in mid-2016.
BPX-601

Expect to begin enrolling patients in a Phase 1 clinical trial in mid-2016 for non-resectable pancreatic cancer.
BPX-401

Expect to move a CIDeCAR product candidate directed to the CD19 antigen into the clinic in the second half of 2016.
Corporate

Expect to complete build-out of the U.S. cGMP viral vector and cellular therapy manufacturing facility by the end of 2016.
Expect to establish a European presence and initiate activities in anticipation of the potential commercialization of BPX-501 in future years.
Fourth Quarter and Full Year 2015 Financial Results

Cash Position and Guidance: Bellicum ended the year on December 31, 2015 with cash and investments totaling $150.4 million, compared to $191.6 million at December 31, 2014. Based on current operating plans and capital available under its loan facility, Bellicum expects to end 2016 with approximately $80 to $90 million in cash, cash equivalents and investments, and anticipates that current cash resources will be sufficient to meet operating requirements through 2017. The Company also expects that in 2016 it will invest approximately $25 to $30 million for capital projects to enable in-house U.S. manufacturing and to support the Company’s growth.

Grant Revenues were $34,000 and $282,000 for the fourth quarter and year ended December 31, 2015, respectively, and $14,000 and $1,780,000 during the comparable periods in 2014. The decrease in full year 2015 grant revenues was primarily due to the June 2014 expiration of the Company’s grant award from the Cancer Prevention and Research Institute of Texas.

R&D Expenses: Research and development expenses were $10.2 million and $33.6 million for the fourth quarter and year ended December 31, 2015, respectively, compared to $4.2 million and $12.1 million during the comparable periods in 2014. The higher expenses in the 2015 periods were primarily due to an increase in BPX-501 clinical and manufacturing costs as a result of increased patient enrollment in clinical trials, an increase in costs related to preclinical product candidates BPX-701, BPX-601 and BPX-401’s IND-enabling activities, and an increase in general research and development costs including personnel costs, and allocated overhead.

License fees were $3.0 million and $3.2 million for the fourth quarter and year ended December 31, 2015, respectively, compared to no license fees in 2014. The increase in fees was primarily due to a new license agreement with Agensys, an affiliate of Astellas, as consideration for rights granted to Bellicum under the agreement related to its BPX-601 product candidate, whereby Agensys was paid a non-refundable upfront fee of $3.0 million.

G&A Expenses: General and administrative expenses were $3.8 million and $12.7 million for the fourth quarter and year ended December 31, 2015, respectively, compared to $2.0 million and $4.3 million during the comparable periods in 2014. The increased G&A expenses in 2015 were primarily due to overall growth and public company related costs, including an increase in personnel, legal and accounting expenses and costs related to facilities, insurance and travel.

Net Loss: Bellicum reported a net loss of $16.8 million for the fourth quarter of 2015 and $48.5 million for the year ended December 31, 2015, compared to a net loss of $74.3 million and $84.0 million for the comparable periods in 2014. The net loss amounts for the 2014 periods included a charge of $43.2 million incurred in the fourth quarter of 2014 in conjunction with the ARIAD license restructure transaction and a non-cash accounting charge of $24.4 million recorded for the change in fair value of warrants that were exercised in conjunction with Bellicum’s December 2014 initial public offering, of which $23.2 million was a fourth quarter expense. The results also included non-cash, share-based compensation charges of $2.5 million and $8.4 million for the fourth quarter and year ended December 31, 2015, respectively, and $0.7 million and $0.9 million for the comparable periods in 2014.

Shares Outstanding: At December 31, 2015, Bellicum had 26,931,881 shares of common stock outstanding.