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2018 NanOlogy to Present at Drug Development & Delivery Networking Summit, March 8, 2018, Parsippany, NJ

On January 17, 2018 NanOlogy reproted that it will Present at Drug Development & Delivery Networking Summit (Press release, NanOlogy, JAN 17, 2018, View Source [SID1234523294]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Event: Drug Development & Delivery Networking Summit
Dates: March 8, 2018
Location: Parsippany, NJ
Event Website: View Source

Circle Pharma Announces Publication in Journal of Medicinal Chemistry of Results from Collaboration with Pfizer Inc.

On January 17, 2018 Circle Pharma, Inc. reported that results from its collaborative work with Pfizer Inc. to develop a potent and orally bioavailable macrocycle modulator of the chemokine receptor, CXCR7, have been published in the Journal of Medicinal Chemistry (Press release, Circle Pharma, JAN 17, 2018, View Source [SID1234523306]).

The goal of the collaboration was to deploy Circle’s rational design platform for macrocycle therapeutics in order to improve the drug-like characteristics of an existing macrocycle compound, and in particular to develop a cell permeable, orally bioavailable compound with enhanced target affinity. As reported in the publication, the collaboration produced a series of permeable and potent derivative macrocycles, including a compound having >500-fold increase in potency (CXCR7 Ki of ~ 9nM versus 2 uM for the starting compound), good cell permeability and 18% oral bioavailability in rats.

Additionally, permeable CXCR7 binding compounds with novel macrocycle backbone scaffolds were discovered through the efforts of the collaboration. This finding was not described in the publication.

"Cell permeability and orally bioavailability have been long-standing and well recognized challenges in the development of macrocycle therapeutics: nearly all synthetic macrocycle compounds in clinical development are against extracellular targets and are delivered by injection," noted David J. Earp, JD, PhD, Circle’s CEO. "Circle’s rational design approach coupled with efficient, low-cost synthesis uniquely enables us to design cell permeable, bioavailable macrocycles to address therapeutic targets that have been out of reach, including intracellular protein-protein interactions. This is a large target class with significant unmet clinical need."

"This collaboration successfully achieved its very challenging objective of delivering a potent and orally bioavailable macrocycle targeting CXCR7," said Spiros Liras, PhD, Vice President, Medicinal Chemistry, Pfizer.

The open-access scientific paper, entitled "Discovery of Potent and Orally Bioavailable Macrocyclic Peptide–Peptoid Hybrid CXCR7 Modulators," is available at View Source

About Macrocyclic Peptides

Macrocyclic peptides have the potential to allow drug developers to address the large proportion of known therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. In particular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited by the need for a greater understanding of how to develop macrocycles with appropriate pharmacokinetics, cell permeability and oral bioavailability. Circle is applying its ability to design potent macrocycles with intrinsic cell permeability and drug-like characteristics to unlock access to challenging, high value therapeutic targets that have been out of reach by other approaches.

Curis Announces Initiation of Phase 1 Trial of CA-4948, a Small Molecule Inhibitor of IRAK4 Kinase in Patients with Lymphoma

On January 17, 2018 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer, reported initiation of patient dosing in a Phase 1 trial of CA-4948, an orally available small molecule inhibitor of the IRAK4 kinase, for treatment of patients with lymphoma (Press release, Curis, JAN 17, 2018, View Source [SID1234523297]). CA-4948 was discovered at Aurigene and is the second licensed program from the Curis-Aurigene collaboration to enter the clinic.

The Phase 1 study is designed to evaluate the safety, tolerability, and pharmacokinetic profile of CA-4948; identify any dose-limiting toxicities; and establish the recommended Phase 2 dose for the treatment of patients with lymphomas. The dose escalation stage of the trial will enroll patients with relapsed/refractory non-Hodgkin’s lymphoma, and the expansion stage will focus on specific populations of patients with lymphomas harboring alterations in the MYD88 gene or Toll-like receptor (TLR) signaling pathway.

"We are pleased to announce the advancement of our clinical pipeline with the initiation of the Phase 1 trial for this selective IRAK kinase inhibitor in patients with lymphomas," commented Ali Fattaey, Ph.D., Curis’s president and CEO. "Given the prevalence of activating mutations in the MYD88 gene and the TLR pathway, IRAK4 represents a significant target for the precision treatment of patients with different hematologic malignancies. In addition to its preclinical anti-tumor activity in MYD88-mutated lymphomas, we have observed encouraging effects of CA-4948 in animal models of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) as well as non-oncology inflammatory disease models. We look forward to working with our partner Aurigene to develop CA-4948 and explore clinical opportunities for these conditions in the near future."

"We are excited to have enrolled the first patient in this lymphoma clinical trial and look forward to further investigating CA-4948 as a potential new treatment option for patients with hematologic malignancies," said Mathew Lunning, DO, University of Nebraska Medical Center, an investigator for the study.

"We are delighted with our collaboration that has led to the advancement of the second program into the clinic, an IRAK4 targeting molecule that came out of Aurigene’s discovery efforts over many years," said CSN Murthy, Aurigene’s CEO. "Our investment into Curis exhibits our belief and commitment for this program and beyond as we work with Curis to focus our collective resources to advance exciting drug candidates."

About CA-4948, a Small-Molecule Inhibitor of IRAK4 Kinase

Innate immune responses orchestrated through Toll-like receptors are important mediators of the body’s initial defense against infections, while their dysregulation is associated with certain inflammatory conditions. Toll-like receptor signaling through the adaptor protein MYD88 results in the activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression. MYD88 gene mutations occur in approximately 30 percent of activated B-cell subtype of diffuse large B-cell lymphomas (DLBCL)1,2 and in over 90 percent of cases of the B-cell malignancy Waldenstrom’s macroglobulinemia (WM).3 IRAK4 has been validated as a target in DLBCL and WM disease setting, and its inhibition by CA-4948 has been shown to provide potent in vivo anti-tumor activity in animal models.4,5 IRAK4 inhibitors are also in clinical testing for treatment of patients with rheumatoid arthritis.

1Nature. 2011; 470(7332):115–119
2Immunology and Cell Biology. 2011; 89(6):659–660
3N Engl J Med. 2012; 367(9):826–833
4Cancer Res. 2017; 77(13 Suppl): Abstract 1168
5Blood. 2015;126(23):4004–4004

CTI BioPharma to Receive $10 Million Milestone Payment for TRISENOX®

On January 17, 2018 CTI BioPharma Corp. (NASDAQ and MTA:CTIC) reported that it expects to receive a $10 million milestone payment in February, 2018 from Teva Pharmaceutical Industries Ltd. related to the achievement of a milestone for U.S. Food and Drug Administration approval of TRISENOX (arsenic trioxide) for first line treatment of acute promyelocytic leukemia (Press release, CTI BioPharma, JAN 17, 2018, View Source;p=RssLanding&cat=news&id=2327170 [SID1234523276]). The milestone will be paid pursuant to an acquisition agreement for TRISENOX previously entered into with Teva under which CTI BioPharma is eligible to receive up to an additional $50 million in payments upon achievement by Teva of specified sales and development milestones related to TRISENOX.

VBI Vaccines Announces Dosing of First GBM Patient in Phase 1/2a Clinical Study of VBI-1901

On January 17, 2018 VBI Vaccines Inc. (Nasdaq:VBIV) (TSX: VBV) (VBI), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported that the first patient has been dosed in a Phase 1/2a clinical study of VBI-1901 for the treatment of recurrent glioblastoma multiforme (rGBM) (Press release, VBI Vaccines, JAN 17, 2018, View Source [SID1234523238]). The multi-center, open-label, two-part study will enroll up to 28 patients and is designed to evaluate safety, tolerability, and the optimal therapeutic dose level of VBI-1901.

"We are excited to announce that the first patient has been dosed in this initial clinical study of VBI-1901, our first clinical study in immuno-oncology," said Jeff Baxter, President and CEO of VBI. "Recurrent GBM is a devastating CMV-associated tumor with few effective treatment options. We developed VBI-1901 to target two highly immunogenic CMV antigens, and, based on preclinical studies, we believe it has the potential to induce a strong anti-tumor immune response in these patients."

About the Phase I/IIa Study Design

This two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in approximately 28 patients with rGBM:

● Part A: Dose-escalation phase to define the safety, tolerability, and optimal dose level of VBI-1901 in rGBM patients. This phase is expected to enroll up to 18 patients.

● Part B: A subsequent extension of the optimal dose level, as defined in the dose escalation phase. This phase is expected to enroll an expanded cohort of approximately 10 additional patients.

VBI-1901 will be administered intradermally and will be adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent adjuvant that mobilizes dendritic cell function. Patients in both phases of the study will continue to receive vaccine every four weeks until tumor progression.

The study will take place at two leading sites in the U.S. – NewYork Presbyterian-Columbia University Medical Center in New York City, New York, and Inova Health System in Falls Church, Virginia. Andrew Lassman, MD, the John Harris Associate Professor of Neurology and Chief of Neuro-oncology at Columbia University, has been named as the lead investigator.

Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT03382977.

About VBI-1901 and GBM

VBI-1901 is a novel immunotherapy developed using VBI’s eVLP technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, and recent research has demonstrated that an anti-CMV dendritic cell vaccination regimen may extend overall survival in patients with GBM. Additionally, recent preclinical studies confirmed that VBI-1901 may be a potent, "off-the-shelf" therapeutic vaccine.

Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal, with median patient survival of less than 16 months.

To learn more about VBI-1901, visit: View Source