On October 08, 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-214, a LADD immunotherapy in development for the treatment of non-small cell lung cancer (Press release, Aduro BioTech, OCT 8, 2015, View Source [SID:1234507677]).

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The IND will enable Janssen, Aduro’s license partner for ADU-214, to initiate a multi-center Phase 1 trial to evaluate the safety and immunogenicity of intravenous administration of ADU-214.

"We are pleased to support Janssen in their advancement of ADU-214 into clinical trials in non-small cell lung cancer," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "We believe there is tremendous potential with our LADD immunotherapy platform and our partnerships, like this one with Janssen, supplement our own efforts and provide additional resources to evaluate the clinical value of our technology in multiple tumor types."

Janssen expects to initiate a Phase 1 trial by the end of 2015 to evaluate the safety and immunogenicity of intravenous administration of ADU-214 in patients with non-small lung cancer.

In October 2014, Aduro entered into its second agreement with Janssen Biotech, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, granting an exclusive, worldwide license to ADU-214 and other product candidates engineered for the treatment of lung cancer and certain other cancers based on its novel LADD immunotherapy platform. Under the agreement facilitated by the Johnson & Johnson Innovation center in California, Aduro received a $30 million up-front payment and a milestone payment associated with submission of the IND, and is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $786.5 million. In addition, Aduro is eligible to receive royalties at a rate ranging from high single-digits to low teens 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.

On October 8, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported that the European Medicines Agency (EMA) has completed its review of the proposed amendment to the company’s Phase 3 AFFINITY protocol and statistical analysis plan (Press release, OncoGenex Pharmaceuticals, OCT 8, 2015, http://oncogenex.com/oncogenex-announces-ema-support-phase-3-affinity-trial-protocol-amendment [SID:1234507674]).

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The amendment, which was agreed to by the U.S. Food and Drug Administration (FDA) earlier this year, includes the addition of a co-primary endpoint designed to prospectively evaluate the survival benefit of custirsen in men who are at increased risk for poor outcomes when treated with cabazitaxel for metastatic castrate-resistant prostate cancer (mCRPC). The EMA supported plans for prospectively defining a poor prognostic subpopulation in the Phase 3 AFFINITY trial and suggested additional supportive analyses to show benefit for the po or prognostic subpopulation beyond the broader AFFINITY trial population. Following support from the FDA and EMA, the company is proceeding with its planned protocol amendment globally.

"We are pleased that we now have feedback from both U.S. and European regulatory authorities on our plan to prospectively evaluate this group of mCRPC patients wo have increased risk factors for poor outcomes and who therefore are more likely to have shorter survival times," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "As we continue to gather insights from the SYNERGY trial, we are gaining a better understanding of the role clusterin plays in this vulnerable patient group and how custirsen may provide a survival benefit."

OncoGenex, in collaboration with study investigators, has defined a simple five-criteria characterization for poor prognostic patients with prostate cancer to be treated with custirsen based on the Phase 3 SYNERGY trial, which includes: 1) poor performance status, 2) elevated prostate specific antigen (PSA), 3) elevated lactate dehyrdogenase (LDH), 4) decreased hemoglobin and 5) the presence of liver metastasis. AFFINITY patients with poor prognosis will be identified as having two or more of these five well-recognized high-risk criteria. The proposed change for AFFINITY is also consistent with custirsen’s mechanism of action, as custirsen was designed to address treatment resistance which may be more prevalent in this subpopulation.

In the revised statistical analysis plan for the AFFINITY trial, the hypothesized hazard ratio (HR) for the poor prognosis subpopulation is specified to be 0.69 with the critical HR ≤ 0.778. The hypothesized HR for intent-to-treat patients (ITT population) remains unchanged as 0.75 with the critical HR ≤ 0.820.

Timing for the final analysis of the poor prognosis subpopulation is projected to occur by the end of 2015, while the final analysis of the ITT population is projected to occur in the second half of 2016. An interim analysis of the ITT population will coincide with the final analysis of the poor prognosis subpopulation. This interim analysis will have both futility and early efficacy criteria defined for the ITT population. If the final analysis of the poor prognostic subpopulation shows a survival benefit for custirsen, OncoGenex may initiate a regulatory submission.

A retrospective analysis of data from the Phase 3 SYNERGY trial presented earlier this year showed a benefit with custirsen therapy when added to first-line docetaxel chemotherapy in men with mCRPC who had a poor prognosis. The analysis showed that over 40 percent of men in the SYNERGY trial had at least two of the five common risk factors for poor prognosis as stated above. In these men, the analysis found a 27 percent lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.

In addition, exploratory SYNERGY data analyses recently presented at the 2015 European Cancer Congress (ECC 2015) demonstrated that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with mCRPC. In addition, these data showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes.

AFFINITY is being conducted at 95 global clinical trial sites. Earlier this year, the IDMC recommended the trial continue following the completion of an interim futility analysis. The trial is fully accrued and the protocol amendment does not affect the conduct of the study. Custirsen has Fast Track designation by the FDA for the poor prognosis and overall AFFINITY trial populations, as well as non-small cell lung cancer (NSCLC).

About Clusterin

A major barrier to extending survival in patients with advanced cancer is treatment failure due to the ability of tumor cells to exploit fundamental cellular mechanisms that allow them to evade destruction by anti-cancer therapies. The production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients.

About Custirsen

Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells. Custirsen binds to clusterin mRNA to block the production of clusterin protein and has enhanced the tumor cell destructive effects of multiple anti-cancer therapies across a variety of tumor models. By inhibiting clusterin, custirsen is designed to alter tumor dynamics by slowing tumor growth and inhibiting tumor resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

On October 8, 2015 Nektar Therapeutics (Nasdaq: NKTR) reported that it will present an overview of the Company’s pain and oncology portfolio during an Investor and Analyst R&D Day being hosted today from 12:30 – 3:30 p.m. Eastern Time in New York City (Press release, Nektar Therapeutics, OCT 8, 2015, View Source [SID:1234507672]).

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Leading experts in immuno-oncology will provide an overview of the current landscape in immuno-oncology and the need for new T-cell stimulatory agents, such as NKTR-214 and NKTR-255. For the first time, Nektar will announce new data for single-agent NKTR-214, including data in a preclinical model of Lewis Lung carcinoma. Details of the NKTR-214 Phase 1/2 clinical program and biomarker strategy will be presented. NKTR-214 is a CD122-biased immune-stimulatory cytokine designed to preferentially stimulate the production of CD8-positive T-cells. The Company will present new preclinical data for its next immuno-oncology candidate, NKTR-255, a new immune-stimulatory cytokine designed to improve T-cell memory by targeting the IL-15 pathway. The company will also discuss its new IDO inhibitor program, NKTR-218, which could increase IDO inhibition activity within the tumor micro-environment.

Pain management specialists will discuss opioid-induced constipation and new first-in-class medicine MOVANTIK, as well as review the regulatory landscape for abuse-deterrent analgesics. New in vitro manipulation and extraction data will be presented for NKTR-181, a first-in-class, mu-opioid analgesic investigational drug candidate with a novel molecular structure designed to reduce abuse liability.

The experts will also participate in two separate panel discussions on current treatment practices and share their perspectives on the medical need for new treatment options.

"Today’s presentations will highlight the significant promise of our internally discovered programs, particularly in immuno-oncology, which have the potential to drive the next stage of growth for Nektar," stated Howard W. Robin, President and Chief Executive Officer of Nektar. "We are leveraging our technology to create compelling new immuno-oncology drug candidates that access new cytokine biology to expand T-cell populations and improve T-cell memory in order to train the immune system to fight cancer. In the area of pain, NKTR-181 is a new opioid molecule that represents a completely new class of pain medicine which could allow us to maintain the efficacy of traditional opioids, while potentially reducing the serious risks of misuse, abuse and diversion."

On October 08, 2015 Dynavax Technologies Corporation (NASDAQ: DVAX) reported that it has initiated patient dosing in the company’s trial evaluating the combination of two immunotherapies: Dynavax’s SD-101 and Merck’s (NYSE: MRK) KEYTRUDA (pembrolizumab) (Press release, Dynavax Technologies, OCT 8, 2015, View Source [SID:1234507670]). The multicenter, open-label trial is enrolling patients with advanced or metastatic melanoma and will investigate the safety and potential efficacy of Dynavax’s investigational toll-like receptor 9 (TLR9) agonist, SD-101, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA.

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SD-101 and KEYTRUDA are immunotherapies designed to modulate the patient’s own immune response to fight cancer. SD-101 is designed to mediate anti-tumor effects by triggering both innate and adaptive immune responses, including inducing high levels of Type 1 interferon. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. Preclinical data suggest that combining SD-101 and antibodies targeting PD-1 may lead to a stronger anti-tumor immune response compared to either agent alone.

The Phase 1b dose-escalation portion of the study is enrolling up to 12 patients with advanced or metastatic melanoma. Patients will receive intratumoral administrations of SD-101 at pre-specified dose levels and intravenous doses of KEYTRUDA. Patients will be monitored for safety and tolerability while an optimal dose of SD-101 is determined. Upon completion of dose escalation, the study will be expanded into a Phase 2 study that will enroll up to 85 patients. The patients enrolled in the expansion study will either have disease that is progressing while receiving an anti-PD-1 therapy or will have baseline characteristics associated with lower rates of response to anti-PD-1 therapy.

Antoni Ribas, M.D., Ph.D., of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, is the primary investigator on this clinical trial. More information on this clinical trial can be found at View Source

Dynavax expects to complete the Phase 1b dose escalation and expand into the Phase 2 portion of the clinical trial with the selected dose of SD-101 by mid-year 2016.

About SD-101

SD-101 is a proprietary, second-generation, TLR 9 agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its preliminary safety and activity.