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BIND Therapeutics Announces Initiation of Clinical Studies with Accurin AZD2811 in Solid Tumors

On November 18, 2015 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called Accurins, reported that AstraZeneca (NYSE: AZN) has initiated patient dosing in a phase 1 clinical trial of the Accurin AZD2811 drug candidate in solid tumors (Press release, BIND Therapeutics, NOV 18, 2015, View Source [SID:1234508279]).

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AZD2811, a novel, selective inhibitor of Aurora B kinase that has been shown to be active in both solid and hematological tumors in preclinical models, is the second Accurin candidate to enter clinical development. The phase 1 trial is enrolling patients with advanced solid tumors, including patients with small cell lung cancer, and is being conducted by AstraZeneca under the companies’ 2013 collaboration agreement with BIND managing all chemistry, manufacturing and control activities. BIND earned a $4.0 million clinical milestone for dosing of the first patient.

"The preclinical data seen to date suggest Accurin AZD2811 can overcome the limitations that have hindered development of this class of potent kinase inhibitors," said Andrew Hirsch, president and chief executive officer of BIND Therapeutics. "There has been a great deal of promise in the biology of inhibiting the Aurora B pathway but success to date has been limited due to on-target but off-tissue toxicities. Based on preclinical data we’ve seen to date, we believe our Accurin technology has the potential to overcome these limitations and make AZD2811 a best-in-class therapeutic with a profile unachievable through other therapeutic modalities. This milestone further demonstrates the value of our leading nanomedicine platform and we look forward to exploring the potential benefits this product may bring to patients with cancer."

"We had already achieved clinical proof of principle with the Aurora Kinase B inhibitor in a phase 2 trial in elderly patients with acute myeloid leukemia," said Susan Galbraith, head of AstraZeneca’s Oncology Innovative Medicines Unit. "Through our collaboration we can now deliver this drug in a BIND Accurin nanoparticle. BIND’s Accurin technology has the potential to significantly improve the therapeutic activity of our Aurora B Kinase inhibitor and we look forward to sharing data from this trial as we advance AZD2811 through clinical development."

The phase 1 clinical trial is designed to evaluate the safety and tolerability of AZD2811 at increasing doses. The first part of the two-part study will evaluate the maximum tolerated dose (MTD) and the recommended phase 2 dose will be identified. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumor activity. The second part of the study will begin upon determination of the MTD and will further explore PK parameters, safety, tolerability and preliminary anti-tumor activity of AZD2811. Additional information on this study can be found at: View Source

Preclinical data on the Accurin AZD2811 were presented at the 2015 American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2015, including data that demonstrated promising in vivo and in vitro tumor growth inhibition as monotherapy in diffuse large B-cell lymphomas (DLBCL) and small cell lung cancer (SCLC) models. Additional data showed that Accurin AZD2811 delivers prolonged exposure of active drug with the flexibility to be delivered with different doses/schedules, offering the potential to adapt the therapeutic regimen to different tumors while achieving an improved therapeutic index. Previously, preclinical tumor model data were presented showing that Accurin AZD2811 minimizes the bone marrow toxicity seen with the parent compound, which has limited the clinical utility of Aurora B kinase inhibitors as a class.

Under terms of the collaboration, AstraZeneca is responsible for clinical development and commercialization and BIND is responsible for conducting clinical manufacturing. In addition to earning a $4.0 million milestone payment for the first patient dosed in a phase 1 clinical trial, BIND received an upfront payment of $4.0 million in 2013 and achieved a $1.0 million development milestone in March 2015. BIND has the potential to receive additional milestone payments totaling up to $60 million upon achievement by AstraZeneca of specified clinical events and up to $128 million in the aggregate upon achievement by AstraZeneca of all specified regulatory and commercial events, as well as tiered royalties in the low-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed product, if any.

Based on the $4.0 million AstraZeneca clinical milestone payment, the previously announced $2.5 million Pfizer option exercise fee and anticipated R&D reimbursement for the next stage of the Pfizer collaboration, BIND reiterates that it expects that its cash, cash equivalents and short-term investments will fund operating expense and capital expenditure requirements into the fourth quarter of 2016. This expectation is based on BIND’s current operating plans and research and development funding that it expects to receive under its existing collaborations, but excludes any potential milestone payments under its collaboration agreements.

Aduro Biotech Receives Milestone Payment From Janssen for Submission of Investigational New Drug Application for ADU-741 in Prostate Cancer

On November 18, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has received a milestone payment from Janssen Biotech, Inc. for Aduro’s submission of an Investigational New Drug (IND) Application to the U.S. Food and Drug Administration for ADU-741, a LADD immunotherapy product candidate for the treatment of prostate cancer (Press release, Aduro BioTech, NOV 18, 2015, View Source [SID:1234508278]). The IND will enable Janssen, Aduro’s license partner for ADU-741, to initiate a multi-center Phase 1 trial to evaluate the safety and immunogenicity of intravenous administration of ADU-741 in patients with metastatic castration-resistant prostate cancer (mCRPC).

"We are very pleased with our productive partnerships with Janssen," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "ADU-741 for prostate cancer is the second LADD-based therapy that Janssen plans to advance into the clinic, in addition to ADU-214 for lung cancer. We believe this further validates the power of combining our innovative LADD technology platform with Janssen’s expertise in oncology clinical development. We look forward to continued development of these compounds in collaboration with Janssen, while at the same time, progressing our internal pipeline of immuno-oncology therapeutics toward commercialization."

In May 2014, Aduro entered into an agreement granting Janssen an exclusive, worldwide license to certain product candidates specifically engineered for the treatment of prostate cancer based on Aduro’s novel LADD immunotherapy platform. Under the agreement facilitated by Johnson & Johnson Innovation, Aduro received an upfront payment, milestone payments associated with submission of the IND, and is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $346 million as well as royalties on worldwide net sales upon successful launch and commercialization.

About LADD

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.

Threshold Pharmaceuticals Enters Into Definitive Co-Promotion Agreement for Evofosfamide With Merck KGaA, Darmstadt, Germany

On November 18, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported that it finalized a definitive Co-Promotion Agreement for evofosfamide with Merck KGaA, Darmstadt, Germany pursuant to the companies’ License and Co-Development Agreement entered into on February 2, 2012 (Press release, Threshold Pharmaceuticals, NOV 18, 2015, View Source [SID:1234508277]). Under the terms of the License and Co-Development Agreement, Threshold may co-promote evofosfamide (previously known as TH-302) in the U.S. subject to Food and Drug Administration (FDA) approval of evofosfamide. Evofosfamide is Threshold’s investigational hypoxia-activated prodrug, which is currently the subject of two fully enrolled Phase 3 clinical trials in advanced soft tissue sarcoma and advanced pancreatic cancer for which Threshold expects to announce top-line data around the end of 2015.

Under the commercial leadership of Merck KGaA, Darmstadt, Germany, the terms of the License and Co-Development Agreement give Threshold the right, at its own cost, to field and be responsible for its own sales force in collaboration with Merck KGaA, Darmstadt, Germany’s sales force in the U.S. pursuant to the terms of the new Co-promotion Agreement. Merck KGaA, Darmstadt, Germany remains responsible for all other commercial and medical affairs functions associated with the launch and promotion of evofosfamide. The development milestone payment and royalty payment portions of the License and Co-Commercialization Agreement remain the same. To date Threshold has received upfront and milestone payments of $110 million and can earn additional potential milestone payments of up to $440 million.

"We are pleased to have reached an agreement with our partner Merck KGaA, Darmstadt, Germany on definitive terms for our option to co-promote evofosfamide in the U.S.," said Barry Selick, Ph.D., Chief Executive Officer at Threshold. "The ability to co-promote and field a sales force represents one of two key options allowing Threshold to participate in the commercial phase of evofosfamide’s lifecycle should it receive FDA approval. Importantly, the license agreement also provides us with an option to co-commercialize evofosfamide in the U.S., depending upon achieving certain milestones, which would allow us to share in up to fifty percent of the profits from the sale of the drug. Threshold is well positioned to integrate a commercial arm to its oncology discovery and development organization."

About Evofosfamide

Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug that is thought to be activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Evofosfamide is currently in two Phase 3 trials, both of which are fully recruited: one in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS) (the TH-CR-406 trial), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with locally advanced unresectable or metastatic pancreatic cancer (the MAESTRO trial). Top-line data for both trials are expected around the end of 2015. Both Phase 3 trials are being conducted under Special Protocol Assessment (SPA) agreements with the FDA. The FDA and the European Commission have granted evofosfamide Orphan Drug designation for the treatment of STS and pancreatic cancer. The FDA has also granted Fast Track designation for evofosfamide for both STS and pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 trial designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical trials of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany, which includes an option for Threshold to co-commercialize in the U.S.

Merck and Pfizer Receive FDA Breakthrough Therapy Designation for Avelumab in Metastatic Merkel Cell Carcinoma

On November 18, 2015 Merck and Pfizer reported that the US Food and Drug Administration (FDA) has granted avelumab*, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, Breakthrough Therapy designation for the treatment of patients with metastatic Merkel cell carcinoma (MCC) who have progressed after at least one previous chemotherapy regimen (Press release, Merck KGaA, NOV 18, 2015, View Source [SID:1234508276]).

Breakthrough Therapy designation is designed to accelerate the development and review of medicines that are intended to treat a serious condition, and preliminary clinical evidence indicates that the therapy may demonstrate a substantial improvement over current available therapies. MCC is a rare and aggressive type of skin cancer.1,2 Each year, there are approximately 1,500 new cases of MCC diagnosed in the US.3 There is currently no therapy approved specifically for the treatment of metastatic MCC.4

The Breakthrough Therapy designation is based on the preliminary evaluation of clinical data from the global Phase II study, JAVELIN Merkel 200, which is assessing the safety and efficacy of avelumab in patients with metastatic MCC whose disease has progressed after at least one prior chemotherapy regimen. Results from this Phase II study are planned for presentation at upcoming scientific congresses in 2016. The designation represents a significant milestone and has the potential to speed the development of avelumab for metastatic MCC patients.

JAVELIN Merkel 200 is a multicenter, single-arm, open-label Phase II study with a primary objective of overall response rate. Secondary endpoints include duration of response, progression-free survival, overall survival and safety. The study, which enrolled 88 patients, is being conducted in sites across Asia Pacific, Australia, Europe and North America.

"Metastatic Merkel cell carcinoma is a devastating disease with limited treatment options currently available for patients," said Dr. Luciano Rossetti, Head of Global Research & Development at Merck’s biopharma business. "With this Breakthrough Therapy designation, we are one step closer to our goal of making a significant difference to patients living with difficult-to-treat cancers, such as metastatic Merkel cell carcinoma, by researching and developing potential new treatment options."

"In less than two months, the alliance between Merck and Pfizer has achieved its third regulatory milestone for avelumab, including Orphan Drug designation and Fast Track designation granted in September and October," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology. "We are very pleased with the progress of the JAVELIN clinical development program and we are looking forward to presenting additional data on the potential of this investigational compound in Merkel cell carcinoma and other tumor types in 2016."

The clinical development program for avelumab now includes more than 1,400 patients who have been treated across more than 15 tumor types, including breast cancer, gastric/gastro-esophageal junction cancers, head and neck cancer, MCC, mesothelioma, melanoma, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and urothelial (e.g., bladder) cancer.

Spectrum Pharmaceuticals Divests Rights to ZEVALIN® (ibritumomab tiuxetan) in Japan and Select Other Ex-US Countries to Mundipharma

On November 18, 2015 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the divestment of ZEVALIN rights in Japan and other countries in Asia Pacific (excluding China and India), Middle East, Africa and Latin America, to Mundipharma (Press release, Spectrum Pharmaceuticals, NOV 18, 2015, View Source [SID:1234508275]). Spectrum will receive an up-front payment of $15 million plus $5 million in profits on initial ZEVALIN supply. Spectrum will continue to own ZEVALIN rights for US, Canada, and Europe.

"This divestiture is consistent with Spectrum’s strategy of focusing on our strong late state pipeline and increasing our operational effectiveness," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "While providing non-dilutive cash, this deal lets us concentrate our efforts on developing drugs like SPI-2012 and poziotinib that have the potential to compete in blockbuster markets. This deal also helps us lower our cost of operations related to territories that are not strategic for Spectrum’s growth. Mundipharma will be able to take over Spectrum’s operations in Japan, and with reinvigorated efforts be able to better serve non-Hodgkin lymphoma patients in select ex-US countries."

About ZEVALIN and the ZEVALIN Therapeutic Regimen

ZEVALIN (ibritumomab tiuxetan) injection for intravenous use, is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL). ZEVALIN is also indicated for the treatment of patients with previously untreated follicular non-Hodgkin’s Lymphoma who achieve a partial or complete response to first-line chemotherapy.

ZEVALIN is a CD20-directed radiotherapeutic antibody. The ZEVALIN therapeutic regimen consists of two components: rituximab, and Yttrium-90 (Y-90) radiolabeled ZEVALIN for therapy. ZEVALIN builds on the combined effect of a targeted biologic monoclonal antibody augmented with the therapeutic effects of a beta-emitting radioisotope.

Important ZEVALIN Safety Information

Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion. ZEVALIN administration can result in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the ZEVALIN therapeutic regimen.

Please see full Prescribing Information, including BOXED WARNINGS, for ZEVALIN and rituximab. Full prescribing information for ZEVALIN can be found at www.ZEVALIN.com.