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BIND Therapeutics Presents Complete Data on Clinical Activity of BIND-014 in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) at the 2016 Genitourinary Cancers Symposium

On January 7, 2016 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called ACCURINS, reported the presentation of complete data from its phase 2 clinical trial of BIND-014, a PSMA-targeted ACCURIN containing docetaxel, in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) who either were or were not exposed to anti-androgens (abiraterone acetate and/or enzalutamide) (Press release, BIND Therapeutics, JAN 7, 2016, View Source [SID:1234508681]). BIND-014 was clinically active and well-tolerated and the study met its primary endpoint with 71 percent of patients achieving rPFS of at least 6 months. The complete data are being presented on January 7, 2016 during a poster session at the 2016 Genitourinary Cancers Symposium held in San Francisco.

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"We are encouraged by the safety and activity profile of BIND-014 in this phase 2 trial, which support its potential to be a nanomedicine alternative superior to conventional docetaxel," said Hagop Youssoufian, M.D., M.Sc., chief medical officer, BIND Therapeutics. "Although these data are encouraging, recent advances with anti-androgen therapy limit our ability to compare BIND-014 data to historical benchmarks. At this time, we are not planning further development of BIND-014 in mCRPC given the evolving treatment landscape. We anticipate additional BIND-014 data from both the iNSITE 1 trial in squamous histology non-small cell lung cancer and the iNSITE 2 trial in multiple tumor types during the first quarter of 2016, which we expect to determine our next steps in the clinical development of BIND-014."

In addition to the primary endpoint, data presented from the trial included measurements of safety and tolerability, objective response rates (ORR), prostate-specific antigen (PSA) response, changes in circulating tumor cells (CTC) and overall survival (OS). Key results include:

BIND-014 administered at 60 mg/m² on day 1 of a 21-day cycle was clinically active and well-tolerated when administered to patients (n=42) with chemotherapy-naive mCRPC, including the 74% of patients with prior exposure to abiraterone acetate and/or enzalutamide.

Median rPFS of 9.9 months (95% CI, 7.1 – 12.6) was achieved (n=42 with 8 censored).
A confirmed ORR of 21% was observed in patients with measurable disease (n=19).
A 50% reduction in PSA was observed in 30% of PSA evaluable patients (n=40).
CTC conversion from ≥ 5 cells/7.5 mL blood at baseline to < 5 cells/7.5 mL blood was observed in 50% of patients.
Median OS was 13.4 months (95% CI, 9.9 – 18.6 months [n=42 with 10 censored]).

C4 Therapeutics Enters Strategic Drug Discovery Collaboration WITH ROCHE PHARMA in the Promising New Field of Targeted Protein Degradation

On January 7, 2015 C4 Therapeutics reported that they will enter into a strategic collaboration with Roche to develop novel treatments in the field of targeted protein degradation (TPD) using C4’s Degronimid technology (Press release, C4 Therapeutics, JAN 7, 2016, View Source;c4-therapeutics-enters-strategic-drug-discovery-collaboration.html [SID:1234508696]). C4’s Degronimids represent a new class of small molecules, TPD therapeutics, which target disease-causing proteins and facilitate their rapid destruction and clearance from the cell through the ubiquitin/proteasome system (UPS).

"Roche is a leader and early adopter of innovation in drug discovery and this significant collaboration comes at a critical time in our development," said Marc Cohen, co-founder and executive chairman of C4 Therapeutics. "This partnership strengthens our leadership position in the field of TPD therapeutic drug discovery. It is part of our strategy to enter into multiple target-specific partnerships that will allow us to pursue a broad set of indications in parallel, while supporting the continued development of our proprietary platform."

Under the terms of the agreement, C4 will initially develop TPD therapeutics that utilize Degronimid technology for a specific set of target proteins. After successful completion of a defined preclinical development phase, Roche has the option to pursue further pre-/clinical development and commercialization. C4 will receive an undisclosed upfront payment and additional development, regulatory and commercial milestone payments per target, as well as sales milestone payments and potential tiered royalties on sales of products resulting from the agreement. The potential value of the deal over time is greater than $750 million.

C4’s Degronimid technology platform was pioneered in 2010 by researchers in the Bradner Laboratory at Dana-Farber Cancer Institute, and is exclusively licensed to C4 Therapeutics from Dana-Farber. Degronimids link drug-like small molecules to the cellular ubiquitin/proteasome system to naturally eliminate targeted proteins by tagging them with ubiquitin for destruction by the proteasome. Degronimids are capable of hitting many more targets than protein inhibitors or peptide-based approaches, and are active against previously undruggable targets, while also reducing potential for drug resistance. This paradigm shift in drug development is applicable to a broad range of diseases.
C4 Therapeutics recently announced that it was launched from Dana-Farber with the closing of a $73 million Series A financing to translate the breakthrough Degronimid technology into a new class of therapeutics that target proteins for degradation. The Company’s scientific cofounders include Ken Anderson, M.D., and Nathanael Gray, Ph.D., both from Dana-Farber Cancer Institute and James "Jay" E. Bradner, M.D., a former investigator at Dana-Farber.

About C4 Therapeutics
C4 Therapeutics is developing a new class of targeted protein degradation (TPD) therapeutics for the treatment of a broad range of diseases. Our Degronimid platform incorporates highly selective small molecule binders to target disease-causing proteins and facilitate their rapid destruction and clearance from the cell through the natural ubiquitin/proteasome system (UPS). Because of this distinctive mechanism, Degronimids are capable of hitting many more targets, including those previously thought to be undruggable, while reducing the potential for drug resistance. The broad applicability of Degronimids, and our chemical biology platform designed for accelerated validation, have the potential to make an unprecedented impact across many diseases through multiple industry collaborations as well as proprietary programs.

C4 Therapeutics Launches with $73M Series A Financing

On January 7, 2016 C4 Therapeutics reported that it has launched from Dana-Farber Cancer Institute with the closing of a $73 million Series A round of financing (Press release, C4 Therapeutics, JAN 7, 2016, View Source;series-a.html [SID:1234508695]).

The Company is developing novel treatments in the field of targeted protein degradation using proprietary Degronimid technology. The Degronimid platform technology was pioneered since 2010 by researchers in the Bradner Lab at Dana-Farber Cancer Institute and described in a seminal paper published in the Journal Science in June 2015. Degronimids represent a new class of small molecule targeted protein degradation (TPD) therapeutics that target disease-causing proteins and facilitate their rapid destruction and clearance from the cell. The Company has executed a license agreement with Dana-Farber that provides worldwide exclusivity for all applications of the Degronimid technology.

The groundbreaking Degronimid platform utilizes an innovative, all-chemical solution for potent, targeted and rapid protein degradation. Degronimids are novel chemical adapters that are conjugated with selective small molecules designed to recruit the cell’s ubiquitin/proteasome system (UPS) in order to "naturally" degrade targeted proteins. Degronimids offer a promising solution for the removal of previously undruggable proteins, including those that are known to develop resistance to inhibitors.

"We are building a word-class team of pioneers in the field of targeted protein degradation who are dedicated to our mission of developing a new class of therapeutics that will have a profound effect on many diseases," said Marc Cohen, Co-founder and Executive Chairman of C4 Therapeutics. "The use of Degronimids as a strategy for targeting traditionally undruggable proteins and overcoming resistance is extremely promising. By removing the need for ongoing target inhibition from the therapeutic equation, TPD therapeutics represent a new paradigm in drug development. C4 is a company that will develop many drugs over time in proprietary and partnered development programs."

C4 Therapeutics was co-founded by Ken Anderson, M.D., Kraft Family Professor of Medicine, Harvard Medical School, Director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber, and a world-renowned expert in protein degradation and multiple myeloma; Nathanael Gray, Ph.D., Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Principal Investigator at Dana-Farber and an expert in kinase inhibitors and drug discovery; software and biotech entrepreneur Marc Cohen; and James "Jay" E. Bradner, M.D., former Associate Professor of Medicine, Harvard Medical School and former Investigator at Dana-Farber. With Dr. Bradner’s new role at Novartis Institutes for BioMedical Research, he will no longer have involvement with the Company. C4 will be located at Mass Innovation Labs in Kendall Square, Cambridge. Cobro Ventures led the Series A round, with additional investments from Cormorant Asset Management, The Kraft Group, EG Capital Group, and angel investors. Other investors include Roche and Novartis.

"Drug discovery research around the ubiquitin/proteasome system is an exciting and growing field, and the discovery of Degronimids represents the first all-chemical solution to ligand-mediated protein degradation," said Dr. Nathanael Gray. "The Dana-Farber Cancer Institute has a strong track record of fostering the advancement of groundbreaking discoveries in numerous oncology applications. By licensing these technologies to companies such as C4, we are supporting the further development of highly promising therapeutic candidates for the betterment of human health."
In conjunction with the Series A financing, C4 announced the appointment of Jason Fisherman, M.D., as Chief Executive Officer of the Company and Member of the Board of Directors. Dr. Fisherman has an extensive track record of building companies as a venture investor at Synthesis Capital and Advent International, a global private equity firm, where his team led or managed over 35 investments in biotechnology, medical technology and healthcare information services. Prior to joining Advent International, Dr. Fisherman had over ten years of drug research and clinical development experience in biopharmaceutical companies, academia, and at the National Cancer Institute. Dr. Fisherman received a B.A. in Molecular Biophysics and Biochemistry from Yale, an M.D. from the University of Pennsylvania and an M.B.A. from the Wharton School of the University of Pennsylvania.

"We are pleased to have Dr. Fisherman join our growing team and believe that C4 will greatly benefit from his extensive financial, business and clinical development expertise," said Cohen. "Dr. Fisherman has 30 years of professional experience within the healthcare and life science industry and will help build our leading Degronimid pharmacology platform."

About C4 Therapeutics
C4 Therapeutics is developing a new class of targeted protein degradation (TPD) therapeutics for the treatment of a broad range of diseases. Our Degronimid platform incorporates highly selective small molecule binders to target disease-causing proteins and facilitate their rapid destruction and clearance from the cell through the natural ubiquitin/proteasome system (UPS). Because of this distinctive mechanism, Degronimids are capable of hitting many more targets, including those previously thought to be undruggable, while reducing the potential for drug resistance. The broad applicability of Degronimids, and our chemical biology platform designed for accelerated validation, have the potential to make an unprecedented impact across many diseases through multiple industry collaborations as well as proprietary programs.

Daratumumab Data Published in The Lancet Shows Encouraging Efficacy in Heavily Pretreated and Refractory Multiple Myeloma

On January 7, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported The Lancet has published data from the Phase II study (Sirius MMY2002) of daratumumab in patients with relapsed and refractory multiple myeloma (Press release, Genmab, JAN 7, 2016, View Source [SID:1234508679]).

Patients that received 16 mg/kg of daratumumab had a median of five prior lines of therapy and 95.3% were refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs, which are current standard of care treatments for multiple myeloma. The data showed a 29.2% overall response rate (31 of 106), including three stringent complete responses, ten very good partial responses, and 18 partial responses in patients treated with 16 mg/kg of daratumumab. The median time to response was one month among patients who responded to treatment. Median duration of response was 7.4 months, and median progression free survival was 3.7 months. The 12-month overall survival rate was 64.8% and at a subsequent cutoff, median overall survival was 17.5 months. Daratumumab was well tolerated, with fatigue (40%) and anemia (33%) of any grade as the most common adverse events (AEs). No drug-related AEs led to treatment discontinuation.

"Data from the daratumumab Sirius study illustrates the significant potential of daratumumab in patients with multiple myeloma who have undergone multiple rounds of prior treatment. Data from the study, now published in The Lancet, was the basis for the approval of daratumumab in heavily pre-treated or double refractory multiple myeloma by the U.S. FDA," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

In November 2015, the U.S. Food and Drug Administration (FDA) approved DARZALEX (daratumumab) injection for intravenous infusion for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 A marketing application with data from the Sirius study and data from four other studies was submitted to the European Medicines Agency (EMA) by Janssen in September 2015 and was subsequently granted accelerated assessment.

About the Study (Sirius MMY2002)
This two-part study enrolled 124 patients who have received at least three prior lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent. Examples of proteasome inhibitors are bortezomib or carfilzomib and examples of immunomodulatory agents are pomalidomide or lenalidomide. Part 1 defined an optimal daratumumab regimen going forward, while part 2 was an expansion, based on the optimal regimen determined in Part 1. The primary objective of the study was to define the optimal dose and dosing schedule, to determine the efficacy of two treatment regimens of daratumumab as measured by overall response rate (ORR), and to further characterize the safety of daratumumab as a single agent.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 124,225 people will be diagnosed and 87,084 will die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including PIs or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.10 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,10 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,10 antibody-dependent cellular phagocytosis8,11 and antibody-dependent cellular cytotoxicity.7,10 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and a subset of regulatory T cells (Tregs) both of which express CD38. These reductions in MDSCs and Tregs were paralleled by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin’s lymphoma.

Baxalta Announces Priority Review Status Granted by Health Canada for irinotecan liposome injection (nal-IRI) for New Drug Submission

On January 7, 2016 Baxalta Incorporated (NYSE: BXLT), a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, reported that Health Canada has granted Priority Review status for its New Drug Submission (NDS) for irinotecan liposome injection, also known as "nal-IRI" (Press release, Baxalta, JAN 7, 2016, View Source [SID:1234508678]).

Baxalta is seeking marketing approval of nal-IRI from Health Canada for the treatment of patients with metastatic adenocarcinoma of the pancreas previously treated with gemcitabine-based therapy.

Priority Review allows for expedited review of critical new drugs faster than the standard timeline. Review by Health Canada is expected to be conducted in the second half of 2016. Baxalta is responsible for the development and commercialization of nal-IRI outside of the U.S. and Taiwan under the exclusive licensing agreement with Merrimack Pharmaceuticals, Inc.

"We are encouraged by the decision Health Canada has made to review our NDS of nal-IRI on an expedited timeline," said Salim Yazji, M.D., vice president and global therapeutics head, Oncology, Baxalta. "Pancreatic cancer is one of the few cancers for which survival has not improved substantially over the last few decades, largely due to late diagnosis, aggressiveness of the disease and limited treatment options. This is an important milestone for our joint efforts to bring nal-IRI to more patients worldwide and fight this devastating cancer of the pancreas to help fill a significant unmet medical need."

The application is based upon the results of an international Phase 3 study (NAPOLI-1) conducted among patients with metastatic pancreatic cancer (mPaC) who previously received gemcitabine-based therapy. In combination with 5-fluorouracil (5-FU) and leucovorin (LV), nal-IRI achieved its primary and secondary endpoints by demonstrating a statistically significant improvement in overall survival, progression free survival and overall response rate compared to the control group of patients who received a combination of 5-FU and LV. The most common Grade 3 or higher adverse events in patients receiving nal-IRI and 5-FU/LV were neutropenia, fatigue and gastrointestinal effects. This was the first global Phase 3 study in a post-gemcitabine setting to demonstrate a survival benefit in the treatment of this aggressive disease.

Baxalta and Merrimack recently enrolled the first patient in an exploratory Phase 2 clinical study of nal-IRI in previously untreated, metastatic pancreatic adenocarcinoma to assess the safety and efficacy of the combination of nal-IRI, 5-FU and LV, with or without the addition of oxaliplatin, versus nab-paclitaxel and gemcitabine. Based on the current design of this study, data is expected in the first half of 2017. In addition to studying nal-IRI in patients with pancreatic cancer, there are ongoing Phase 1 studies of nal-IRI in patients with pediatric sarcoma, glioma, breast and gastric cancer.

A Marketing Authorization Application submitted by Baxalta is also under review in the European Union for the treatment of adult patients with metastatic adenocarcinoma of the pancreas who have previously been treated with gemcitabine-based therapy. The decision from Health Canada follows the recent U.S. Food and Drug Administration (FDA) approval of nal-IRI, Merrimack’s (Onivyde) New Drug Application for the same indication using the same clinical efficacy and safety data.

About Pancreatic Cancer

Pancreatic cancer is rare and deadly – accounting for less than three percent of all cancer cases worldwide, but the seventh leading cause of cancer death1. An estimated 340,000 new cases are diagnosed every year around the world1, about two-thirds of which are among people aged 65 or older2. It is estimated that there were 4,800 new cases of pancreatic cancer this past year in Canada specifically3.

Because the signs and symptoms of pancreatic cancer are non-specific and may not appear until the disease has spread to other sites, approximately 80 percent of patients are not candidates for surgery; these patients instead receive chemotherapy as the mainstay of their therapy4. This contributes to the five-year survival rate for all patients being less than six percent5. There is no consensus on the standard of care for patients with mPaC previously treated with a gemcitabine-based therapy.

About irinotecan liposome injection (nal-IRI)

nal-IRI is an investigational nanoliposome consisting of the chemotherapeutic, irinotecan, encapsulated in a liposomal sphere. Merrimack received FDA approval for nal-IRI under the brand name Onivyde for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. nal-IRI was granted Fast Track designation and Priority Review by the FDA for this indication. The FDA also granted nal-IRI orphan drug designation for patients with mPaC. Baxalta is responsible for the development and commercialization of nal-IRI outside of the United States and Taiwan under an exclusive licensing agreement with Merrimack. PharmaEngine holds the rights to commercialize Onivyde in Taiwan, following TFDA approval in October 2015.