1stOncology™: Cancer Intelligence Service – Page 16559 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

BIND Therapeutics Reports First Quarter 2016 Financial Results and Provides Business Update

On May 9, 2016 BIND Therapeutics, Inc. (NASDAQ:BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called ACCURINS, reported financial results for the first quarter ended March 31, 2016 and provided a business update (Press release, BIND Therapeutics, MAY 9, 2016, View Source [SID:1234512102]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

Schedule Your 30 min Free Demo!

"Despite our financial challenges, we remain committed to advancing our new R&D strategy of applying our ACCURINS technology to develop innovative medicines and we have made significant progress during the first quarter," said Andrew Hirsch, president and chief executive officer at BIND Therapeutics. "In order to address these challenges, we took difficult but necessary steps to substantially reduce our operating expenses, focus the business, and explore strategic and financial alternatives. Despite these efforts, we filed for Chapter 11 protection to provide the necessary time to pursue these alternatives to the benefit of all stakeholders. While the Chapter 11 process can be distracting, we don’t anticipate any major disruptions in our business operations during this process."

Scientific Highlights:

Discovery Pipeline:

During the quarter, BIND initiated in vivo studies aimed at characterizing the ability of ACCURINS to affect pharmacokinetic, biodistribution, cellular uptake and gene silencing activity of oligonucleotide therapeutics. In addition, the Company has initiated formulation efforts to develop ACCURINS containing small molecule inhibitors of TGF-beta signaling.

In addition, BIND has recently entered into several strategic research collaborations to quickly and efficiently evaluate novel targeting ligands as part of our strategy to develop ACCURINS that incorporate combinations of targeting ligands and therapeutic payloads, including a variety of biologically active ligands. These collaborations include:

Synergy Pharmaceuticals, for access to ligands that can target gastrointestinal malignancies;
PeptiDream, to incorporate biologically active targeting ligands; and
Affilogic, to secure access to biologically active immuno-oncology related targeting ligands.
"We have an opportunity to formulate ACCURINS with oligonucleotides or potent kinase inhibitors while functionalizing the surface of our particles with a variety of biologically active targeting ligands," said Jonathan Yingling, Ph.D., chief scientific officer for BIND. "This has the potential to create ACCURINS that act as combination therapy within a single particle."

BIND-014

The Company released data from multiple phase 2 trials of BIND-014, ACCRUINS formulated with the approved cytotoxic cancer agent docetaxel. The iNSITE 1 trial is squamous histology non-small cell lung cancer exceeded the protocol defined endpoint of greater than 65 percent 6-week disease control rate. The data suggest BIND-014 continues to provide meaningful improvements in safety and tolerability, and at least similar efficacy in comparison to historical studies with docetaxel. As a result, BIND believes the new data further validate the ACCURINS platform and justify further development where improved safety and tolerability may be valuable. The company is seeking a collaborator to fund further development of BIND-014.

AZD2811

In collaboration with AstraZeneca, BIND developed AZD2811, which became the first nanoparticle containing a kinase inhibitor to begin clinical testing. The kinase inhibitor targets the Aurora B protein, which can contribute to the growth of tumor cells, and is currently in a phase 1 clinical trial. In the first quarter, preclinical data for AZD2811 was published in The Journal of Science Translational Medicine. The data highlighted the ability of ACCURINS to control release kinetics and provide increased concentration of nanoparticles to tumor sites.

Anticipated upcoming milestones and activities include:

Report initial in vivo POC data for discovery programs, with preclinical pharmacokinetic and efficacy data expected in second half of 2017
In vivo POC data for targeting guanylate cyclase-C (GC-C) receptors expressed on tumors, specifically GI malignancies
In vivo POC data for anti-tumor immunity targeted ACCURINS
Additional in vivo POC data for delivering single and double stranded RNA fragments and achieving target knock-down in tumor models
Demonstrate in vitro and in vivo POC for achieving endosomal escape with double stranded RNA
Expand pre-clinical pharmacology for KSP ACCURINS (BIND-267), including combinations with immune-oncology biologics
Additional rodent and potentially non-rodent safety evaluation of BIND-267
Identify first ACCURINS-based immuno-oncology product concept
Identify development and commercialization partner for BIND-014
Continue to support AstraZeneca’s clinical trial activities for AZD2811
Advance the Pfizer compound toward the clinic by initiating IND-enabling studies
Key Business Developments

Implemented a restructuring plan designed to streamline operations and reduce the Company’s operating expenses
Announced shift in R&D strategy to leverage the platform to develop innovative medicines and initiate a review of financial and strategic alternatives
Initiated voluntary Chapter 11 bankruptcy protection proceedings to provide for an orderly process and additional time to pursue the strategic and financial alternatives that were previously underway
First Quarter 2016 Financial Results

Cash, cash equivalents and short-term investments were approximately $21.5 million as of March 31, 2016. Given the fact that the Company is operating under Chapter 11 bankruptcy protection, the Company is suspending financial runway guidance until further notice.

Development revenue for the first quarter of 2016 was $1.9 million, compared to $4.4 million for the first quarter of 2015. The decline was primarily due to lower reimbursed collaboration expenses related to clinical trial manufacturing activities for AZD2811, which were performed in the first quarter of 2015 to support initial clinical testing as part of the Company’s collaboration with AstraZeneca.

Research and development expenses totaled $11.2 million for the first quarter of 2016, compared to $8.2 million for the first quarter of 2015. The increase was primarily related to BIND-014 expenses of approximately $7.2 million. In addition, there was an increase in manufacturing costs related to an engineering manufacturing run of ACCURINS completed at the 15kg scale at our contract manufacturer in Germany.

General and administrative expenses totaled $3.6 million for the first quarter of 2016, compared to $4.8 million for the first quarter of 2015. The decline was partially due to one-time severance and stock-based compensation charges for our former chief executive officer in the first quarter of 2015 as well as a decrease in general consulting expenses of $0.4 million.

Net loss for the first quarter of 2016 was $12.7 million, compared to a net loss of $8.3 million for the first quarter of 2015. The increase in net loss was mostly the result of the aforementioned increase in clinical trial activities and the decrease in collaboration revenue during the first quarter of 2016.

U.S. FDA Expands IMBRUVICA® (ibrutinib) Label to Include Overall Survival Data in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and New Indication for Small Lymphocytic Lymphoma (SLL) Patients

On May 9, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported the U.S. Food and Drug Administration (FDA) updated the IMBRUVICA (ibrutinib) Prescribing Information (PI) to include new data from two Phase 3 trials supporting its expanded use in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, AbbVie, MAY 9, 2016, View Source [SID:1234512091]).[1] The label now includes overall survival (OS) results in previously-untreated CLL/SLL patients from the Phase 3 RESONATETM-2 (PCYC-1115) trial.

The IMBRUVICA label has also been updated with safety and efficacy data from the Phase 3 HELIOS (CLL3001) trial assessing the use of IMBRUVICA in combination with bendamustine and rituximab (BR) versus placebo plus BR in relapsed/refractory patients with CLL/SLL. As well, following a review of the November 2015 supplemental New Drug Application (sNDA), the FDA has approved a new IMBRUVICA indication to include the treatment of patients with SLL with or without the deletion of chromosome 17p (del 17p).1 IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc.

The RESONATE-2 trial served as the basis for the March 2016 FDA approval of IMBRUVICA for the first-line treatment of CLL patients. Notably, the OS data now included in the IMBRUVICA PI provide a longer-term update to results published in The New England Journal of Medicine, with a median follow-up of 28.1 months. The label updates based on HELIOS represent the first-ever data demonstrating an improvement in progression-free survival (PFS) and overall response rate (ORR) with IMBRUVICA when combined with BR versus placebo plus BR in patients with relapsed/refractory CLL/SLL.

"This update helps to affirm the established efficacy, safety and tolerability of this therapy for 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 the RESONATE-2 lead study investigator.* "It reflects the growing body of clinical evidence supporting this therapy as a potential treatment option for people living with CLL/SLL."

"We are pleased the FDA has added the survival data observed with IMBRUVICA as a first-line therapy for CLL to its Prescribing Information and that the indication has been expanded to include patients with SLL. Moreover, the positive results seen in the HELIOS study provide additional evidence supporting the compelling safety and efficacy seen with IMBRUVICA in CLL and SLL patients," said Danelle James, M.D., M.S., Head of Oncology at Pharmacyclics. "We believe the IMBRUVICA label is very strong for the treatment of certain hematologic malignancies and is now reinforced not only by data evaluating its use as a single agent, but also in combination with other commonly used chemotherapy regimens."

Immune Design and Gritstone Oncology Announce Clinical Collaboration for Neoantigen Cancer Immunotherapy

On May 09, 2016 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, and Gritstone Oncology, a private cancer immunotherapy company developing next-generation, personalized cancer therapeutics, reported a clinical collaboration for development of novel, personalized immunotherapies combining both companies’ leading technologies (Press release, Immune Design, MAY 9, 2016, View Source [SID:1234512088]).

The collaboration will involve the application of Immune Design’s ZVexTM discovery platform with Gritstone’s proprietary genomics and proteomics platform for identification of patient-specific tumor antigens to develop neoantigen-based immunotherapies. Immune Design and Gritstone will be jointly responsible for development activities, with an initial likely focus in non-small cell lung cancer. The first clinical trial is expected to commence in 2017.

"The emerging tumor neoantigen field holds great potential for the successful application of cancer immunotherapies, and we are pleased to be working with Gritstone, a company that we believe is a pioneer in the field," said Carlos Paya, M.D., Ph.D., president and chief executive officer of Immune Design. "Having validated our two platforms in clinical trials targeting conserved tumor antigens, we believe their application to patient specific tumor antigens is a natural next step."

For the first trial of their technologies, the companies are evaluating combining the Gritstone and Immune Design neoantigen vaccine with a checkpoint inhibitor, to optimize the vaccine-induced immune response at several levels and maximize the likelihood of clinical efficacy.

"We are excited to work with Immune Design and their novel immunotherapy approach," said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone Oncology. "There is good evidence that viral vectors are one of the most effective means of generating high titer CD8+ T cells that recognize encoded antigens, and so this is a logical move for our company, as our neoantigen prediction platform starts to deliver immune targets for individual patients with lung cancer."

Intravenous Busulfan-Based Myeloablative Conditioning Regimens Prior to Hematopoietic Cell Transplantation for Hematologic Malignancies.

Busulfan (Bu)-containing regimens are commonly used in myeloablative regimens prior to allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (four times a day, Q6 or daily, Q24) and the combination with other chemotherapeutic agents (cyclophosphamide, Cy or fludarabine, Flu). A prospective cohort study of recipients of Bu-based conditioning according to contemporary practices was used to compare different approaches in using Bu (BuCy Q6 N=495; BuFlu Q24 N=331; BuCy Q24 N=96; BuFlu Q6 N=91) in patients with myeloid malignancies from 2009 to 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and higher comorbid burden. The cumulative incidence of hepatic veno-occlusive disease (p=0.4), idiopathic pneumonia (p=0.5) and seizures (p=0.5) did not differ across groups. One-year HCT related mortality ranged from 12% to 16% (P=0.8), three-year relapse incidences ranged from 32% to 36% (p=0.8) and three-year overall survival ranged from 51% to 58% (p=0.2) across groups. This study demonstrates that the use of intravenous Bu Q6 or Q24 or accompanied by Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.
Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Population Pharmacokinetic/Pharmacodynamic Modeling of Sunitinib by Dosing Schedule in Patients with Advanced Renal Cell Carcinoma or Gastrointestinal Stromal Tumor.

Sunitinib is a multi-targeted tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma (RCC) and imatinib-resistant/intolerant gastrointestinal stromal tumors (GIST).
A meta-analysis of 10 prospective clinical studies in advanced RCC and GIST was performed to support the development of pharmacokinetic (PK) and PK/pharmacodynamic (PD) models that account for the effects of important covariates. These models were used to make predictions with respect to the PK, safety, and efficacy of sunitinib when administered on the traditional 4-weeks-on/2-weeks-off schedule (Schedule 4/2) versus an alternative schedule of 2 weeks on/1 week off (Schedule 2/1).
The covariates found to have a significant effect on one or more of the PK or PD parameter studies included, age, sex, body weight, race, baseline Eastern Cooperative Oncology Group performance status, tumor type, and dosing schedule. The models predicted that, in both RCC and GIST patients, Schedule 2/1 would have comparable efficacy to Schedule 4/2, despite some differences in PK profiles. The models also predicted that, in both indications, sunitinib-related thrombocytopenia would be less severe when sunitinib was administered on Schedule 2/1 dosing compared with Schedule 4/2.
These findings support the use of sunitinib on Schedule 2/1 as a potential alternative to Schedule 4/2 because it allows for the management of toxicity without loss of efficacy.