On October 02, 2017 Endocyte, Inc. (NASDAQ Global Market:ECYT), a biopharmaceutical company developing targeted therapeutics for personalized cancer treatment, reported the completion of an exclusive worldwide license of PSMA-617 from ABX GmbH. Endocyte intends to move quickly into Phase 3 development of 177Lu-PSMA-617, a radioligand therapeutic (RLT) that targets the prostate-specific membrane antigen (PSMA), present in approximately 80% of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Endocyte, OCT 2, 2017, View Source [SID1234520740]).

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177Lu-PSMA-617 delivers the short-range beta-emitting radioactive isotope lutetium (177Lu) selectively to tumor cells while by-passing non-PSMA-expressing healthy cells with encouraging efficacy and safety results. As highlighted in roughly 20 peer reviewed publications of studies in the post-chemotherapy compassionate use setting, 177 Lu-PSMA-617 has consistently demonstrated a PSA response (defined as greater than 50% decline from baseline) in 40% to 60% of patients, and a RECIST response rate in soft tissue disease of between 40% and 50%.

“This transaction is transformational to Endocyte, accelerating our path to commercialization. 177Lu-PSMA-617 has the potential to be the first-in-class RLT to address both bone and soft tissue disease, and it is profoundly important to the many patients suffering from mCRPC,” said Mike Sherman, president and CEO of Endocyte. “Our experience with PSMA targeting and companion imaging development, in addition to our relationships with distinguished prostate cancer investigators from around the world, uniquely position Endocyte to lead this therapy to registration. We intend to seek regulatory approval to initiate a Phase 3 registration trial of 177Lu-PSMA-617 in early 2018. By focusing the company’s resources on the execution of this program, we project trial completion as early as 2020.”

Mr. Sherman continued, “Endocyte remains strongly committed to careful expense management and maintaining a strong balance sheet. With the exception of a very targeted effort to generate proof-of-concept data for our CAR T-cell program, we will focus our resources on the development of 177Lu-PSMA-617. We will explore out-licensing opportunities for all other development programs.”

“Despite advances in the last decade that slow the progression of prostate cancer, once metastasized it is nearly always lethal, leading to 300,000 worldwide deaths annually. 177Lu-PSMA-617 has demonstrated the most compelling activity of any drug currently in development for these post-chemotherapy patients,” said Alison Armour, chief medical officer.

PSMA-617 was developed at DKFZ (German Cancer Research Center) and University Hospital Heidelberg and exclusively licensed to ABX GmbH in Germany for early clinical development. As a result of the enthusiasm of physician investigators and patients, the investigational therapy has been evaluated in hundreds of patients through both compassionate use studies and prospective trials.

“The data generated thus far have created significant enthusiasm for 177Lu-PSMA-617. PSMA is a promising target in prostate cancer and radioligand therapy may be the best application for this target,” said Michael Morris, MD, associate professor, Genitourinary Oncology, Memorial Sloan Kettering Cancer Center. “Particularly where disease has become resistant to current therapies, there is a tremendous need for new approaches and I look forward to working with Endocyte to investigate this innovative, first-in-class therapy for prostate cancer patients.”

Clinical Data Presented at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper)

Dr. Michael Hofman of the Peter MacCallum Cancer Center in Melbourne, Australia presented the results of an open-label, single-arm, non-randomized pilot study of 177 Lu-PSMA-617 in September 2017, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. Thirty mCRPC patients were treated with up to four cycles of 4-8 GBq. Primary endpoints included safety and efficacy as defined by PSA response, quality of life, and imaging response.

The results showed a remarkable 57% PSA response rate ( > 50% reduction) and 71% interim response rate in soft tissue lesions (as measured by RECIST criteria) in patients who had previously failed such conventional therapies as docetaxel, cabazitaxel, enzalutamide and abiraterone. Median overall survival was 12.7 months. The drug was well-tolerated, with a low rate of adverse effects and no renal toxicity. Significantly improved quality of life scores and reduction in pain scores were recorded in 37% and 43% of patients, respectively. This trial has subsequently been expanded to 50 subjects from the original 30, with updated results expected to be presented in 2018.

On October 2, 2017 Atossa Genetics (NASDAQ:ATOS), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods for breast cancer and other breast conditions, reported a new program using Chimeric Antigen Receptor Therapy, or CAR-T (Press release, Atossa Genetics, OCT 2, 2017, View Source [SID1234520739]). Atossa plans to use its proprietary intraductal microcatheter technology to deliver CAR-T cells into the ducts of the breast for the potential targeted treatment of breast cancer.

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Atossa’s novel approach uses its proprietary intraductal microcatheter technology for the potential transpapillary, or “TRAP,” delivery of T-cells that have been genetically modified to attack breast cancer cells. Atossa believes this method has several potential advantages: reduced toxicity by limiting systemic exposure of the T-cells; improved efficacy by placing the T-cells in direct contact with the target ductal epithelial cells that are undergoing malignant transformation; and, lymphatic migration of the CAR-T cells along the same path taken by migrating cancer cells, potentially extending their cytotoxic actions into the regional lymph system, which could limit tumor cell dissemination. Atossa’s approach is in the research and development phase and has not been approved by the FDA or any other regulatory body. Pre-clinical studies, and clinical studies demonstrating safety and efficacy among other things, and regulatory approvals will be required before commercialization.

“We have been encouraged by the promise that CAR-T has shown in other forms of cancer, which is usually delivered systemically. We believe that our proprietary TRAP technology could provide a potentially safer yet effective method to deliver CAR-T,” stated Steven Quay, MD, PhD, Atossa CEO. “We believe that TRAP CAR-T, as we are calling this novel approach to adaptive T-cell therapy in breast cancer, will provide another approach to breast cancer, and that it may be particularly well-suited for the deadlier forms of breast cancer such as ‘triple negative.’ Now that we have developed a foundational intellectual property position with respect to TRAP CAR-T, we intend to continue research and development through partnership with leading investigators, institutions, and organizations around the world, bringing Atossa’s technology and expertise in TRAP delivery together with experts in cancer immunology and T-cell biology. Multiple studies in both animals and humans have shown that a number of therapeutics can be delivered by the TRAP, intraductal route,” Dr. Quay added.

About TRAP CAR-T

The transpapillary (TRAP) delivery of therapeutics in breast cancer clinical trials have demonstrated “that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity” (Zhang B, et al. Chin J Cancer Res. 2014 Oct;26(5):579-87; www.ncbi.nlm.nih.gov/pubmed/25400424).

T cells are removed from a patient and modified so that they express receptors specific to the patient’s particular breast cancer. The T cells, which can then recognize and kill the cancer cells, are reintroduced into the patient using a microcatheter into the natural ducts of the breast.

Chimeric antigen receptors (or, “CARs” and also known as chimeric immunoreceptors, chimeric T cell receptors, artificial T cell receptors or CAR-T) are engineered receptors, which graft an arbitrary specificity onto an immune effector cell (T cell). Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T cell, with transfer of their coding sequence facilitated by retroviral vectors. The receptors are called chimeric because they are composed of parts from different sources.

CAR-T technology has been the subject of much attention recently as pioneer CAR-T company Kite Pharma recently announced its acquisition by Gilead, and the FDA has recently approved Novartis’s Kymriah for treatment of B-cell Acute Lymphoblastic Leukemia.

On October 2, 2017 VBL Therapeutics (NASDAQ:VBLT), reported that the independent Data Safety Monitoring Committee (DSMC) met on September 28, 2017 to conduct its third and final safety review of the Phase 3 GLOBE Study investigating ofranergene obadenovec (VB-111) in recurrent glioblastoma (GBM) (Press release, VBL Therapeutics, OCT 2, 2017, View Source [SID1234520738]). The DSMC is an independent multidisciplinary group that conducts detailed reviews of un-blinded study data, discusses potential safety concerns and provides recommendations regarding trial continuation. The committee reviewed the GLOBE safety data, including mortality data, collected through a cutoff date in August 2017 and stated that they did not identify any safety concerns. The DSMC confirmed that no additional follow up will be necessary. Accordingly, the DSMC unanimously recommended that the study continue as planned, to completion.

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“The positive DSMC recommendation supports the safety of VB-111 and represents an important milestone reached successfully in the GLOBE study,” said Dror Harats, M.D., chief executive officer of VBL Therapeutics. “No additional interim analyses are planned, and we currently expect top-line results from the study to be available in Q1 2018.”

Corinne Epperly, M.D., MPH, U.S. chief operating officer, added, “This trial has the potential to be the first ever study with a systemic drug candidate to help people with recurrent GBM live significantly longer compared to a standard-of-care regimen. We will work with the health authorities to bring this novel therapy option to the patients who need it as quickly as possible.”

About the GLOBE study
The Phase 3 GLOBE study is proceeding under a Special Protocol Assessment (SPA) granted by the FDA, with full endorsement by the Canadian Brain Tumor Consortium (CBTC). VB-111 has received orphan drug designation in the United States and Europe and was granted Fast Track designation by the FDA for promising and meaningful long-term survival in patients with glioblastoma that has recurred following treatment with standard chemotherapy and radiation. The study in recurrent GBM is comparing VB-111 in combination with Avastin (bevacizumab) to Avastin alone and has recruited 256 patients in the US, Canada and Israel.

About Glioblastoma (GBM)
GBM is the most common and most aggressive form of primary brain tumors. In 2017, it is estimated there will be approximately 12,000-13,000 new cases diagnosed in the United States. Median overall survival (OS) from diagnosis averages 12 to 15 months with patients treated usually with surgery, chemotherapy and radiation. Progression occurs within approximately 6 months in virtually all patients, and upon progression median OS is about 6-8 months. Although significant research and clinical efforts have focused on improving treatments for recurrent GBM, no systemic therapy has shown an OS benefit, resulting in a significant unmet medical need.

About Ofranergene Obadenovec (VB-111)
Ofranergene obadenovec is a unique biologic agent that uses a dual mechanism to target solid tumors. Based on a non-integrating, non-replicating, Adeno 5 vector, ofranergene obadenovec utilizes VBL’s proprietary Vascular Targeting System (VTS) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, ofranergene obadenovec does not aim to block a specific pro-angiogenic pathway; instead, it uses an angiogenesis-specific sensor (VBL’s PPE-1-3x proprietary promoter) to specifically induce cell death in angiogenic endothelial cells in the tumor milieu. This mechanism retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and shows activity even after failure of prior treatment with other anti-angiogenics. In addition, ofranergene obadenovec induces specific anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells.

Ofranergene obadenovec completed a Phase 2 study in recurrent GBM, which showed a statistically significant improvement in overall survival in patients treated with ofranergene obadenovec through progression, compared to either patients treated with ofranergene obadenovec followed by bevacizumab alone, or to historical bevacizumab data. In a Phase 2 trial for recurrent platinum-resistant ovarian cancer, ofranergene obadenovec demonstrated a statistically significant increase in overall survival and 60% durable response rate (as measured by reduction in CA-125), approximately twice the historical response with bevacizumab plus chemotherapy in ovarian cancer. In a Phase 2 study in recurrent, iodine-resistant differentiated thyroid cancer, ofranergene obadenovec met the primary endpoint providing evidence of disease stabilization with a positive safety profile, along with a dose-response and evidence of an overall survival benefit. Ofranergene obadenovec has received Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.

On October 2, 2017 KSQ Therapeutics reported that they emerged with $76 million in financing and a world-class executive team to advance the development of drugs empowered by the unique biological insights of its proprietary CRISPRomics drug discovery engine (Press release, KSQ Therapeutics, OCT 2, 2017, View Source [SID1234520709]). With CRISPRomics, KSQ is pioneering high-confidence drug development utilizing a suite of CRISPR-based technologies that industrialize, for the first time, a high-throughput, systematic way to elucidate the precise function that each human gene plays across a multitude of diseases. Based on this deep and comprehensive approach, KSQ is advancing a pipeline of oncology and immunology drug development programs against novel therapeutic nodes to create a new set of disease-tailored medicines. KSQ was founded in 2015 by David Sabatini, MD, PhD, of the Whitehead Institute and MIT, William Hahn, MD, PhD, of the Broad Institute and Dana-Farber Cancer Institute, Jonathan Weissman, PhD, of UCSF, and Tim Wang, PhD, of MIT, along with founding investors Flagship Pioneering and Polaris Partners.

KSQ also announced today the appointment of David Meeker, MD, as Chief Executive Officer. Dr. Meeker most recently served as Head of the Specialty Care Business Unit of Sanofi-Genzyme and previously was Chief Executive Officer and President of Genzyme, a Sanofi Company. He brings more than 20 years of industry leadership experience, from leading-edge R&D programs to global operational roles.

“We have a clear goal with CRISPRomics: empower the drug development process to strategically focus on high-confidence, patient-tailored, novel drug candidates,” said Dr. Meeker. “There is a compelling need to improve the quality of drug targets and to identify patients most likely to respond because our industry and our health care systems are challenged by the sheer volume of potential new medicines. With our proprietary CRISPRomics engine, KSQ is positioned to play a leading role in shortening drug development timelines, increasing the rate at which meaningful medicines can reach patients, and ultimately, improving the sustainability of our health care systems.”

KSQ also announced Frank Stegmeier, PhD, as Chief Scientific Officer and George Golumbeski, PhD, as Executive Advisor and Board Member. Dr. Stegmeier is a leading expert in industrialized functional genomics who led Oncology Target Discovery at Novartis prior to joining KSQ. He has led KSQ’s platform development and R&D efforts since the company’s formation in 2015, demonstrating the early productivity of CRISPRomics. Dr. Golumbeski is a business development executive with an outstanding track record of success in the pharmaceutical industry. During his more than 25-year career, he has identified and evaluated innovative technologies and drug candidates from early-stage biotech companies and accelerated their drug innovation potential through creative partnerships.

“The human genome harbors more than 20,000 genes, however for most diseases we have yet to discern which genes represent the best therapeutic targets. For the first time, CRISPRomics allows us to systematically pinpoint the optimal nodal targets of disease with extraordinary precision and speed,” said Dr. Stegmeier. “The genome-scale insights that are possible with CRISPRomics are enabling KSQ to most efficiently focus our drug discovery efforts on the development of medicines with the greatest potential to intervene in disease and, therefore, impact the lives of patients.”

KSQ’s financing is led by Flagship Pioneering; Polaris Partners, ARCH Venture Partners, and Alexandria Equities also participated. Since the company’s formation in 2015, KSQ has deployed its CRISPRomics engine to complete the functional assessment of each gene in more than 600 tumor and immune models. The company has compiled new insights in disease biology to identify novel drug targets and new drug combinations designed to elicit maximal impact on disease. This approach has produced KSQ’s initial pipeline of drug development programs, and will serve as a product engine across a wide range of disease areas for the company and future collaborators. KSQ has grown to a team of more than 40 employees.

“KSQ is a pioneering company, unleashing high-confidence drug development for the first time — a step change in the way drugs are discovered and developed,” said David Berry, General Partner, Flagship Pioneering. “Led by proven industry leaders, KSQ is uniquely positioned to translate its breakthrough biological insights into therapeutics that can impact the core of many important diseases.”

High-Confidence Drug Development
Powered by CRISPRomics, KSQ has elucidated the function that each human gene plays in a multitude of diseases providing a unique and more comprehensive understanding of disease biology. The quality of these insights enables KSQ to identify a multitude of high-confidence, patient-tailored, novel programs for drug development and rapidly rule-out thousands of less relevant targets from the outset; thereby, focusing R&D investment on the development of medicines with the greatest potential to meaningfully impact the treatment of human disease.