On May 9, 2016 PureTech Health plc ("PureTech," LSE: PRTC) reported the launch of Vor BioPharma, an immuno-oncology company dedicated to developing a new class of targeted cell therapies (Press release, Vor BioPharma, MAY 9, 2016, View Source [SID:1234512244]).

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The company, which is advancing a novel approach to chimeric antigen receptor (CAR) T-cell therapy, has licensed its core technology from the lab of Vor scientific co-founder, Siddhartha Mukherjee, M.D., Ph.D., Assistant Professor of Medicine at Columbia University and Pulitzer Prize-winning author of The Emperor of All Maladies: A Biography of Cancer.

"CAR T-cell therapies have shown remarkable progress in the clinic, yet their applicability beyond a small subset of cancers is currently very limited," said Sanjiv Sam Gambhir, M.D., Ph.D., Vor Scientific Advisory Board Member, Professor of Radiology and Bioengineering, Chair of the Department of Radiology, Director of the Canary Center for Cancer Early Detection and Director of the Molecular Imaging Program at Stanford University. "This technology seeks to address bottlenecks that prevent CAR T-cell therapy from becoming more broadly useful in treating cancers outside of B-cell cancers."

Researchers continue to make big advances in using the immune system to fight cancer. CAR T-cell therapy, which modifies the body’s own immune cells (T-cells) to recognize and kill cancer cells, has emerged as a promising therapy for patients with advanced B-cell leukemias. These approaches have focused on targeting markers that are present on all B-cells, both healthy and cancerous. While the body can safely function without B-cells, using CAR T-cell therapy to treat other cancers—which would involve targeting cells necessary for survival—remains elusive. Furthermore, CAR T-cell therapy has shown more limited results in treating solid tumors. Vor is developing an entirely new approach to CAR T-cell therapy that seeks to broaden its applicability in other cancers, particularly those with limited therapeutic options, by removing key barriers generated by current modalities.

"We continue to make great strides in developing new ways to treat cancer using the body’s immune system," said Dr. Mukherjee. "The positive clinical response researchers have achieved with CAR T-cell therapies in B-cell leukemias has led to great interest within the oncology community and is something we hope to achieve in other cancers over time."

"PureTech is excited to be collaborating with Sid Mukherjee and to have the support of a world-class team of immunologists and oncologists," said David Steinberg, Executive Vice President of PureTech Health and Co-Founder of Vor BioPharma. "We look forward to advancing this technology that has the potential to expand immuno-oncology to currently untreatable, fatal malignancies."

Leading oncologists and immunologists are supporting Vor in developing its pipeline of novel immunotherapies. The company’s team of scientific founders and Scientific Advisory Board (SAB) members includes:

Joseph Bolen, Ph.D. – Scientific Advisory Board member and acting Chief Scientific Officer of Vor BioPharma and former President and Chief Scientific Officer of Moderna Therapeutics. Dr. Bolen has more than 30 years of industry and research experience and has been at the forefront of cancer and immunology research. He began his career at the NIH, where he contributed to the immunotherapies pipeline discovery of a class of proteins known as tyrosine kinase oncogenes as key regulators of the immune system. Dr. Bolen most recently oversaw all aspects of research and development for Moderna. Previously, he was Chief Scientific Officer and Global Head of Oncology Research at Millennium: The Takeda Oncology Company. Prior to joining Millennium in 1999, Dr. Bolen held senior research and development positions at Hoechst Marion Roussel, Schering-Plough, and Bristol-Myers Squibb.

Sanjiv Sam Gambhir, M.D., Ph.D. – Professor of Radiology, Materials Science & Engineering, and Bioengineering at Stanford University, where he is also the Chair of the Department of Radiology, Director of the Canary Center for Cancer Early Detection and Director of the Molecular Imaging Program. His research focuses on interrogating cellular and molecular events in living subjects through imaging and on the early detection of cancer. He is the recipient of over $90M in NIH funding as the principal investigator and served on the NCI Board of Scientific advisors for eight years. Dr. Gambhir has received several awards including the Hounsfield Medal, Tesla Medal, Holst Medal, and is an elected fellow of the National Academy of Medicine, as well as the National Academy of Inventors. He has co-founded several startups and is an advisor to several large corporations and biotechnology startups.

Dan Littman, M.D., Ph.D. – Howard Hughes Medical Institute Investigator and the Helen L. and Martin S. Kimmel Professor of Molecular Immunology and Professor of Pathology and Microbiology at New York University (NYU) School of Medicine. Dr. Littman has made numerous groundbreaking discoveries in the field of virology and immunology, including identification and isolation of receptors required for human immunodeficiency virus (HIV) entry, molecular mechanisms of immune cells that mediate autoimmunity and the role of specific members of the gut microbiota in T-cell differentiation. Dr. Littman is a Fellow of the American Academy of Arts and Sciences and is a Member of the National Academy of Sciences. He was awarded the 2004 New York City Mayor's Award for Excellence in Science and Technology.

Siddhartha Mukherjee, M.D., Ph.D. – Assistant Professor of Medicine at Columbia University and oncologist. Dr. Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction, and The Laws of Medicine. He has published distinguished articles in numerous publications, including Nature, The New England Journal of Medicine, Cell and The New York Times.

Derrick J. Rossi, Ph.D. – Associate Professor in the Stem Cell and Regenerative Biology Department at Harvard Medical School and Harvard University. Dr. Rossi is an investigator in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and is also a principal faculty member of the Harvard Stem Cell Institute. TIME Magazine cited Dr. Rossi’s discovery of modified-mRNA reprogramming as one of the top ten medical breakthroughs of 2010. TIME Magazine also named Dr. Rossi as one of "People Who Mattered" in 2010, and as one of the 100 Most Influential People (Time 100) in 2011. Dr. Rossi co-founded Moderna Therapeutics and Intellia Therapeutics.


About Vor BioPharma

Vor BioPharma is an immuno-oncology company dedicated to developing a new class of targeted cell therapies to treat highly fatal malignancies. The company is advancing a novel approach to chimeric antigen receptor (CAR) T-cell therapy that has the potential to broaden its applicability and success rate in other cancers. Co-founded by PureTech Health ("PureTech", LSE: PRTC), Vor is working with some of the world’s leading oncologists and immunologists to develop a pipeline of potentially life-altering immunotherapies that extend beyond what is possible with current treatments. PureTech Health plc (PRTC.L) owns approximately 91% of the company on a diluted basis as of December 31, 2015. This calculation includes issued and outstanding shares as well as options to purchase shares and written commitments to issue shares or options, but excludes unallocated shares authorized to be issued pursuant to equity incentive plans.

On May 9, 2016 Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has approved an expansion to the IMBRUVICA (ibrutinib) U.S. Prescribing Information (PI) based on data supporting its use in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Janssen announced today (Press release, Johnson & Johnson, MAY 9, 2016, View Source [SID:1234512218]).1

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The approved label now includes overall survival (OS) data from the Phase 3 RESONATE-2 (PCYC-1115) trial in treatment-naïve CLL/SLL patients 65 years or older. The updated label also contains clinical data from the Phase 3 HELIOS (CLL3001) trial investigating the use of IMBRUVICA in combination with bendamustine and rituximab (BR) versus placebo plus BR in patients with relapsed or refractory CLL/SLL.

About the IMBRUVICA Label Update
Updated data from the RESONATE-2 trial reflect a statistically significant 56 percent reduction in the risk of death with IMBRUVICA compared to chlorambucil after a median follow-up of 28.1 months (HR=0.44 [95 percent CI, 0.21, 0.92]). The RESONATE-2 trial served as the basis for the March 2016 FDA approval of IMBRUVICA as a first-line treatment for patients with CLL.

Additionally, the first data from the HELIOS study on the use of IMBRUVICA in combination with other therapies were added to the label, highlighting the improvement in progression-free survival (PFS) and overall response rate (ORR) when using IMBRUVICA plus BR versus placebo plus BR in patients with relapsed/refractory CLL/SLL. Following a review of the November 2015 supplemental New Drug Application, the FDA has expanded the indication to include the use of IMBRUVICA for SLL patients with or without deletion of the chromosome 17p (del 17p). SLL is a slow-growing lymphoma that is similar to CLL.1,2

"The clinical development plan for IMBRUVICA is very robust and includes many Phase 2 and 3 clinical trials across various indications and combinations," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. "In partnership with Pharmacyclics, an AbbVie company, we continue to explore the clinical utility of IMBRUVICA and potential benefit it offers to patients with CLL/SLL and other hematologic malignancies."

"The update helps to affirm the established efficacy, safety and tolerability of this therapy for the treatment of patients with CLL/SLL, both as a monotherapy or in combination with other agents," said Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and RESONATE-2 study lead investigator. "It reflects the growing body of clinical evidence supporting this therapy as a potential treatment option for people living with CLL/SLL."

About the RESONATE-2 Study
Building on existing positive PFS results from the RESONATE-2 trial, the updated labeling includes information from an additional analysis of the OS data. IMBRUVICA demonstrated a statistically significant 56 percent reduction in the risk of death after a median follow-up of 28.1 months (HR=0.44 [95 percent CI, 0.21, 0.92]). This analysis included 41 percent of patients in the chlorambucil arm who crossed over to receive IMBRUVICA therapy after progressing.

RESONATE-2 is a Pharmacyclics-sponsored, randomized, open-label, international, multi-center Phase 3 study which evaluated the safety and efficacy of IMBRUVICA versus chlorambucil in 269 treatment-naïve patients with CLL/SLL aged 65 years or older. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil 0.5 to 0.8 mg/kg on days 1 and 15 of each 28-day cycle for up to 12 cycles, with an allowance for intrapatient dose increases up to 0.8 mg/kg based on tolerability. The primary endpoint of the study was PFS as assessed by an Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. OS was a key secondary endpoint assessed in the study.

Results from RESONATE-2 were presented in an oral session at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in Orlando, FL in December 2015 and simultaneously published in The New England Journal of Medicine. The results were also part of the official press program at ASH (Free ASH Whitepaper) 2015.

About the HELIOS Study
Results showed the combination of IMBRUVICA plus BR was associated with an 80 percent reduction in the risk of progression or death (HR=0.20 [95 percent CI, 0.15, 0.28, P

HELIOS is a Janssen-sponsored, randomized, double-blind, placebo-controlled, international, multi-center, Phase 3 study conducted in 21 countries, which evaluated the safety and efficacy of IMBRUVICA in combination with BR in 578 patients with relapsed/refractory CLL/SLL who had received at least one prior therapy. Patients were randomized to receive either the combination of 420 mg IMBRUVICA orally once daily and six cycles of BR, or matching regimen of placebo orally once daily and six cycles of BR, with IMBRUVICA or placebo continued until disease progression or unacceptable toxicity. The primary endpoint was IRC-assessed PFS using the iWCLL 2008 criteria with modification for treatment-related lymphocytosis. Secondary endpoints included IRC-assessed ORR and safety.

Data from an interim analysis of HELIOS were presented during the official press program at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in Chicago, IL in May 2015. The results were also published in The Lancet Oncology in December 2015.

IMBRUVICA Safety in CLL/SLL
Warnings and Precautions include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome and embryo-fetal toxicity. Four to 10 percent of patients receiving IMBRUVICA in the studies supporting the CLL indications (PCYC-1102, RESONATE [PCYC-1112], RESONATE-2 [PCYC-1115] and HELIOS [CLL3001]) discontinued treatment due to adverse reactions (ARs). These included pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (one percent each). ARs leading to dose reduction occurred in approximately six percent of patients.

The ARs from the RESONATE-2 trial reported in the IMBRUVICA U.S. PI reflect exposure to IMBRUVICA with a median duration of 17.4 months versus a median exposure to chlorambucil of 7.1 months. The most common ARs (>20 percent) of any Grade in the RESONATE-2 trial for IMBRUVICA were diarrhea (42 percent), musculoskeletal pain* (36 percent), cough (22 percent) and rash* (21 percent). The most common Grade 3/4 AR (>five percent) was pneumonia* (eight percent).

The ARs from the HELIOS trial reported in the IMBRUVICA U.S. PI reflect exposure to IMBRUVICA plus BR with a median duration of 14.7 months versus a median exposure to placebo plus BR of 12.8 months. The most common ARs (>20 percent) of any Grade in the HELIOS trial for IMBRUVICA plus BR were neutropenia* (66 percent), diarrhea (36 percent), thrombocytopenia* (34 percent), musculoskeletal pain* (29 percent), pyrexia (25 percent), rash* (32 percent) and bruising* (20 percent). The most common Grade 3/4 ARs (>five percent) were neutropenia* (61 percent), thrombocytopenia* (16 percent) and hypertension* (five percent).

IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Janssen and Pharmacyclics continue to support an extensive clinical development program for IMBRUVICA, including a number of Phase 3 study commitments in a variety of patient populations.

About CLL/SLL
CLL is a slow-growing blood cancer that most commonly arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow.3,4 SLL is a slow-growing lymphoma biologically similar to CLL in which too many immature white blood cells cause lymph nodes to become larger than normal. 2 CLL/SLL are predominantly a disease of the elderly, with a median age of 71 at diagnosis.5

About IMBRUVICA
IMBRUVICA was one of the first therapies to receive U.S. approval after having received the FDA’s Breakthrough Therapy Designation. IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK).1 The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.1,6 IMBRUVICA targets and blocks BTK, inhibiting cancer cell survival and spread.1 For more information, visit www.IMBRUVICA.com.

Access to IMBRUVICA
Janssen and AbbVie are striving to make access to IMBRUVICA easy by helping patients understand their insurance benefits for IMBRUVICA. The YOU&i Support Program is a personalized program that includes information on access and affordability, nurse call support and resources for patients being treated with IMBRUVICA. This includes the YOU&i Instant Savings program, which provides co-pay support to eligible commercially insured IMBRUVICA patients. This program is not valid for patients with Medicare or Medicaid. Patients can access the program by contacting 1-877-877-3536, option 1 or by visiting www.IMBRUVICA.com.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS
The most common adverse reactions (>20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia* (64%), thrombocytopenia* (63%), diarrhea (43%), anemia*(41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (>5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and nuetropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS
CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS
Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

On May 9, 2015 Boehringer Ingelheim reported the enrolment of the first patient in the global Phase III trial evaluating the efficacy and safety of nintedanib in combination with pemetrexed/cisplatin, followed by continuing nintedanib monotherapy, as a first-line treatment for patients with unresectable malignant pleural mesothelioma (MPM) (Press release, Boehringer Ingelheim, MAY 9, 2016, View Source [SID:1234512157]). Patients will qualify for enrolment in the trial if they are not eligible to undergo surgical resection, have received no prior first-line therapies for MPM and hold an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

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Lead investigator, Professor Giorgio V. Scagliotti, Chair of the Department of Oncology, University of Torino, Italy, commented, "Malignant pleural mesothelioma is a rare cancer and despite years of research, patients continue to have a poor prognosis – less than 10% survive for five years following diagnosis. Due to the mode of action of nintedanib, it has the potential to be an effective treatment option for patients with pleural mesothelioma."

LUME-Meso [NCT01907100] will randomise 397 patients in a double-blind, multi-centre, global comparison of nintedanib in combination with pemetrexed/cisplatin or matching placebo in combination with pemetrexed/cisplatin as a first-line treatment. For patients whose disease has not progressed after a maximum of six cycles of chemotherapy, nintedanib or matching placebo will continue to be administered orally as a monotherapy on a daily basis, until disease progression or unmanageable side effects. The primary endpoint of the trial is progression-free survival and overall survival is the key secondary endpoint. Other secondary endpoints include objective tumour response and disease control.

Through its mode of action nintedanib targets the receptors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and proto-oncogene tyrosine-protein kinase (Src) pathways which play a role in tumour growth and the development of metastasis in MPM. No targeted therapies are currently approved for the treatment of this rare and difficult-to-treat cancer.

Dr Jörg Barth, Corporate Senior Vice President, Therapy Area Head Oncology, Boehringer Ingelheim said, "Over the last few years Boehringer Ingelheim has accumulated considerable expertise in the field of thoracic oncology. With the approval of Giotrif and Vargatef as well as a broad clinical pipeline we are building up a strong presence in this setting. The effort to develop a potential efficacious treatment for malignant pleural mesothelioma demonstrates our long-term commitment for patients with significant unmet medical need."

Nintedanib is also being evaluated in the LUME-Colon 1 trial [NCT02149108], a global Phase III trial in patients with advanced colorectal cancer. Recruitment is now complete and data are expected to be available later in 2016.

Nintedanib (Vargatef) in combination with docetaxel was approved in the EU in 2014 for use in adults with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy.

* Nintedanib is approved in the EU under the brand name Vargatef for use in combination with docetaxel in adult patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first-line chemotherapy. Nintedanib is under regulatory review by health authorities in other countries outside the EU. Nintedanib is not approved in other oncology indications.

On May 9, 2016 X4 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 dosing of the first patient in a Phase 1/2 study of X4P-001, the Company’s lead CXCR4 inhibitor, in patients with advanced clear cell renal cell carcinoma (ccRCC) (Press release, X4 Pharmaceuticals, MAY 9, 2016, View Source [SID:1234512156]).

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The Phase 1 portion of the study will test the safety and tolerability of escalating doses of X4P-001 in combination with Inlyta (axitinib), a kinase inhibitor approved for the treatment of advanced RCC after failure of one prior systemic therapy. The study is designed to establish a maximum tolerated dose (MTD), or a recommended dose if the MTD is not achieved, for the drug combination. Preliminary results from the Phase 1 portion of the study are expected in early 2017, followed by the initiation of the Phase 2 portion of the study. Multiple U.S. cancer centers with leading renal cell carcinoma researchers will participate in the study. Pfizer is providing axitinib for use in the study.

"Many ccRCC patients do not achieve durable responses when treated with the currently approved targeted therapies or immunotherapies" said David McDermott, M.D, study investigator and lead of the Dana Farber/Harvard Cancer Center Kidney Cancer Program. "Based on the pre-clinical evidence in models of kidney cancer and a safety profile generated in prior clinical studies, X4P-001 has the potential to provide a meaningful new treatment option for ccRCC patients in combination with axitinib."

"Since our recent Series A financing, our team at X4 has rapidly executed on our clinical plan to initiate the study of X4P-001 as a potential treatment for patients with advanced ccRCC, a cancer with serious unmet needs." said Paula Ragan, PhD, President and CEO of X4. "Given the growing evidence that CXCR4 inhibition plays an important role modulating the tumor microenvironment, we see this as the beginning of multiple opportunities that we will pursue with our portfolio of CXCR4 inhibitors."

About X4P-001

X4P-001 is an oral, small molecule inhibitor of CXCR4, or C-X-C receptor type 4, the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). 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 through the trafficking of T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment.1, 2 Pre-clinical studies have demonstrated X4P-001 activity alone and in combination with approved cancer therapies including tyrosine kinase inhibitors and checkpoint inhibitors resulted in an increased tumor-specific immune response and significant delays in tumor growth. X4P-001 was previously tested in over 70 subjects in four prior clinical trials in healthy volunteers and HIV-infected patients and was shown to be safe and well tolerated.

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 rapamycin (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.

On May 09, 2016 NewLink Genetics Corporation (NASDAQ:NLNK) reported results of its Phase 3 clinical trial for algenpantucel-L for patients with resected pancreatic cancer (Press release, NewLink Genetics, MAY 9, 2016, View Source [SID:1234512136]).

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The IMPRESS Phase 3 study of algenpantucel-L for patients with resected pancreatic cancer did not achieve its primary endpoint. Overall survival from time of randomization was 29.3 months for both groups combined. There was no statistically significant difference between the two groups. The median survival was 30.4 months and 27.3 months for the control and study groups, respectively. There was also no statistical difference for long-term survival. Three year survival was 41.4% and 42.1% and four year survival was 32.6% and 32.7% for the control and study groups, respectively.

"We are deeply disappointed for patients that the IMPRESS Phase 3 study was not successful," said Nicholas N. Vahanian, M.D., President and Chief Medical Officer of NewLink Genetics. "We want to extend our sincere appreciation to all the patients, caregivers, investigators, research nurses, employees and others who contributed to the study. Given these results, we are evaluating the future of the HyperAcute platform. We remain committed to achieving our mission of developing immunotherapies to bring patients with cancer better treatment options."

The IMmunotherapy for Pancreatic RESectable cancer Study (IMPRESS) trial is a randomized, controlled, two-arm Phase 3 trial for patients with resected pancreatic cancer testing algenpantucel-L (300M cells every two weeks for six months followed by every month for another six months) in combination with the standard of care versus standard of care alone. A total of 722 patients with surgically removed cancers were enrolled at more than 70 sites in the United States from May 2010 to September 2013.

"Immunotherapy is rapidly establishing a role in the management of multiple malignancies," said George Fisher, M.D., Ph.D., Professor of Medicine at Stanford University, one of the investigators in the IMPRESS study. "The median overall survival of 29.3 months in this study represents a significant increase compared with prior trials and may be due to multiple factors, including the emergence of more effective treatment regimens for recurrent or metastatic disease. Although a negative study, these results represent an important and meaningful contribution to the understanding of the modern treatment of resected pancreatic cancer."

"In light of these negative results, our scientific and clinical teams will focus on other promising opportunities in our pipeline," said Charles Link, Jr., M.D., Chairman and Chief Executive Officer. "Our lead projects focus on our IDO checkpoint inhibitor technology employing indoximod and GDC-0919. We have substantial near-term catalysts in 2016 for these IDO inhibitor programs, including multiple trial updates from our proprietary and partnered IDO pathway inhibitors, and the financial resources to realize the potential of our product pipeline."

NewLink Genetics ended the first quarter on March 31, 2016, with cash, cash equivalents, and certificates of deposit totaling $178 million. The Company reiterates that its goal and expectation is to finish 2016 with two years of cash on hand.