On May 12, 2016 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima") and U.S.-based Sydys Corporation, Inc. (OTC: SYYC) ("Sydys"), reported an agreement through which Sydys will license Prima’s CVac immuno-oncology program and oversee its future development (Filing, 6-K, Prima Biomed, MAY 12, 2016, View Source [SID:1234512349]).

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Sydys Corporation (www.sydyscorp.com) is a publicly traded New York company that has been repurposed as a clinical stage biotechnology company in order to develop the CVac assets. Under the terms of the agreement, Sydys will license Prima’s CVac related assets, including manufacturing protocols, clinical data from Phase I and Phase II trials, patents and know-how. Prima will also sell certain assets including some equipment and inventory to Sydys. Dr Sharron Gargosky, the former Chief Technical Officer of Prima who has overseen the development of CVac since 2010, will also transition to Sydys as a consultant to continue the development of CVac. Marc Voigt, Prima’s CEO, will join the Sydys Board of Directors soon after closing.

In this spin out transaction Prima will receive a 9.9% equity stake in Sydys at the time of closing as consideration for the assets being transferred. Given the significant capital requirements for conducting clinical trials, no upfront payment will be received however should CVac be successfully commercialized, Prima could receive over A$400 million (US$293 million) in development, regulatory and commercial milestone payments payable for achievement of set commercial sales targets, in addition to low single digit royalties on sales.

Marc Voigt, Prima’s CEO, commented: "Following extensive discussions with a number of third parties, we have reached what we consider to be an entrepreneurial solution which we believe best positions CVac for clinical success and, hopefully, commercialization. Importantly, this partnership continues the CVac program development without further resource commitment from Prima, while providing the potential for considerable future milestone and royalty payments over time. The ongoing development will be contingent on further successful capital raising for subsequent trials but we are confident that the Sydys team has the ability and connections in the US to undertake this program."

Experienced biotech entrepreneur Joseph Hernandez, the newly appointed Executive Chairman of Sydys Corporation, added: "We believe that the CVac program has tremendous potential, supported by encouraging Phase I and II data in ovarian cancer patients. Studies conducted to date have reinforced CVac’s strong safety profile and demonstrated meaningful improvements in both overall survival and progression-free survival compared to standard-of-care. We look forward to further evaluating the efficacy of CVac with the goal of bringing the treatment to this underserved patient population."

About CVac
CVac therapy is a personalized immunocellular therapeutic that has been investigated for the treatment of epithelial cancers. CVac stimulates the patient’s own immune system to target and destroy tumours. It has been investigated in multiple Phase I and Phase II studies with positive results.
Development highlights for CVac include:

• Completion of a randomized Phase II trial that identified epithelial ovarian cancer patients in second remission (CR2) as the target CVac patient population

• CR2 patients receiving CVac have experienced a clinically meaningful improvement in overall survival (OS), as indicated by final data analysis. These data demonstrated median OS of standard of care patients of 25.53 months, while the CVac arm had not reached a median at 42 months (HR=0.17)

• CR2 patients receiving CVac experienced a clinically significant improvement in progression free survival (PFS) of greater than 12.91 months, compared with a PFS of 4.94 months (HR=0.32) for the standard-of-care
CR2 for ovarian cancer is a high unmet medical need; CVac has obtained Orphan Designation for the treatment of ovarian cancer by both the FDA and EMA and Fast Track Designation with the FDA.

On May 12, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the first patient has been dosed in a Phase 1 trial for ADU-S100 (also known as MIW815), a novel STING (Stimulator of Interferon Genes) pathway activator (Press release, Aduro BioTech, MAY 12, 2016, View Source [SID:1234512325]). Activation of the STING pathway in tumors has been shown to be a critical step to initiate an innate response that may lead to a systemic adaptive tumor-specific immune response. Novartis, Aduro’s collaborator for STING pathway activator compounds in the field of oncology, is conducting the study. The achievement of this milestone triggers a $35 million milestone payment from Novartis to Aduro.

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"We are thrilled to embark on this landmark Phase 1 study, which we believe is the first clinical trial to specifically target the STING pathway. ADU-S100 (MIW815) has the potential to induce an anti-tumor immune response that is unique to the treated individual, an approach that potentially offers the benefits of a personalized therapy but using an off-the-shelf small molecule," said Thomas Dubensky, Jr., Ph.D., chief scientific officer of Aduro. "ADU-S100 is the first compound to enter the clinic under our collaboration with Novartis, and through this Phase 1 study, we look forward to gaining insight into the safety, tolerability and initial efficacy for several different types of cancer. We have now advanced two differentiated immuno-oncology platforms into the clinic: ADU-S100, with the start of this trial, and our LADD listeria-based immunotherapy strains in clinical studies in multiple indications, including pancreatic, ovarian, lung and prostate cancers, mesothelioma and glioblastoma."

In preclinical models, direct activation of the STING pathway through intratumoral administration of ADU-S100 (MIW815) overcame immune system suppression within the tumor microenvironment, resulting in significant anti-tumor response. These preclinical studies, which were published in Cell Reports, demonstrated that injecting tumors with ADU-S100 (MIW815) induced profound regression of diverse established tumors in mice, both in the injected tumors and distal, untreated lesions. Importantly, treatment of a single tumor initiated a systemically effective T cell response that prevented outgrowth of untreated tumors in other areas of the body (metastases). The ADU-S100-initiated response was durable and provided lasting immunologic memory and anti-tumor protection.

The Phase 1, multicenter, dose escalation study, which includes dose expansion into designated indications, will enroll patients with cutaneously accessible metastatic solid tumors or lymphomas who are in need of other treatment alternatives. The trial is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of ADU-S100 (MIW815). For more information about the clinical trial, please visit www.clinicaltrials.gov and use identifier NCT02675439.

In March 2015, Aduro entered into a collaboration with Novartis for the worldwide research, development and commercialization of novel immuno-oncology products derived from Aduro’s STING pathway activator platform. Under the terms of the agreement, Aduro received $200 million upon signing and an additional $50 million equity investment from Novartis. In addition to the $35 million milestone payment triggered by this Phase 1 trial initiation, Aduro is eligible to receive up to an additional $465 million in development and regulatory milestones if all stated objectives of the collaboration are achieved. Aduro will lead commercialization activities and will book sales in the United States for any products developed and commercialized pursuant to this collaboration, with Novartis leading commercialization activities in all other regions. The companies will share in profits, if any, in the United States, Japan and major European countries, and Novartis will pay Aduro a mid-teens royalty for sales in the rest of the world.

About the Tumor Microenvironment
The tumor microenvironment is the cellular environment in which the tumor exists, and, along with cancerous cells, includes support cells, immune cells, surrounding blood vessels, and the extracellular matrix. The tumor cells and the surrounding microenvironment are closely related and interact constantly. Tumors influence the microenvironment by releasing signals that promote tumor growth, immune tolerance and immune suppression. When tumors initially form, the body’s immune system recruits and activates a host of immune cells to fight the invading tumor. However, in cases where cancer develops, tumors are eventually able to evade the immune system by changing their microenvironment to inhibit the ability of the immune system to recognize and destroy the tumor thus allowing for tumor outgrowth and formation of metastasis.

About STING Pathway Activator Platform
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

On May 12, 2016 AstraZeneca reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation for the investigational MEK 1/2 inhibitor, selumetinib (AZD6244, ARRY-142886) for adjuvant treatment of patients with stage III or IV differentiated thyroid cancer (DTC) (Press release, AstraZeneca, MAY 12, 2016, View Source [SID:1234512292]).

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DTC is diagnosed in approximately 60,000 people in the US each year,1 and radioactive iodine (RAI) is recommended for those with known/suspected metastases at diagnosis and those at high risk of recurrence.2 A small proportion of patients do not benefit from currently available treatment with RAI because they do not express sufficient sodium/iodine symporter (NIS) which is important for RAI uptake into thyroid cells.3,4 Selumetinib is being tested for its ability to increase expression of NIS with the potential to add a treatment option for patients who do not respond well to RAI.

Sean Bohen Executive Vice President, Global Medicines Development and Chief Medical Officer, at AstraZeneca, said: "Uptake of RAI is crucial for patients with thyroid cancer where no other therapies have proven beneficial. Selumetinib could significantly enhance currently available treatment options for these patients. The Orphan Drug Designation is an important achievement as we advance our development plans for this potential treatment in differentiated thyroid cancer."

The Orphan Drug Designation programme provides orphan status to drugs and biologics, which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.5

Selumetinib inhibits the MEK pathway in cancer cells to prevent tumour growth. It is being tested in the Phase III ASTRA trial in patients with DTC who are at high risk of recurrence.6 In a Phase II study of selumetinib in patients with advanced thyroid cancer, clinically meaningful increases in iodine uptake and retention were seen in patients with thyroid cancer that was refractory to RAI.7

In addition to DTC, selumetinib is being tested in SELECT-1, a Phase III trial of patients with KRAS-mutant advanced non-small cell lung cancer (NSCLC) and in a Phase II registration trial of paediatric and adolescent patients with neurofibromatosis Type 1 in collaboration with the US National Cancer Institute.

NOTES TO EDITORS

1 American Cancer Society. Key statistics for thyroid cancer. Available at: View Source Accessed May 2016.

2 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Thyroid Cancer. Version 2.2015

3 Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer.Ther Adv Med Oncol. 2014 Nov;6(6):267-79.

4 Lakshmanan A et al. Modulation of sodium iodide symporter in thyroid cancer. Horm Cancer. 2014 Dec;5(6):363-73.

5 US Food and Drug Administration. Developing Products for Rare Diseases & Conditions View Source Accessed May 2016.

6 National Institutes of Health. Study Comparing Complete Remission After Treatment With Selumetinib/Placebo in Patient With Differentiated Thyroid Cancer. (ASTRA) View Source Accessed May 2016

7 Ho AL et al. Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer N Engl J Med. 2013 February 14; 368(7): 623–632.

8 Durante C et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006 Aug;91(8):2892-9.

About thyroid cancer

Cancer of the thyroid gland is diagnosed in approximately 60,000 people in the US each year.1 Nearly 95% of patients have differentiated tumours with an associated five-year survival of over 90%.2 DTC is usually treated by surgery and thyroxine hormone replacement therapy, and radioactive iodine treatment (RAI) is recommended for patients with known/suspected metastases at diagnosis and for those at high risk of recurrence.2 Up to 30% of patients experience recurrence of DTC after initial treatment.2

Approximately 5-15% of patients with DTC do not respond to RAI.3 Ten year survival in patients who fail to take up radioactive iodine into tumour cells is 10% compared to nearly 60% in those with normal uptake.8 Traditional chemotherapy has minimal efficacy in patients with metastatic DTC.2

About selumetinib

Selumetinib is an oral, potent, selective inhibitor of MEK, part of the mitogen-activated protein kinase (MAPK) pathway which is frequently activated in cancer, including those with the KRAS mutation, which is present in 20% of human cancers and 20-30% of non-small cell lung cancer tumours.

MAPK activation also inhibits expression of thyroid hormone biosynthesis genes, including the sodium/iodine symporter (NIS) which facilitates iodine uptake into cells. 7 Pre-clinical studies have suggested that following MAPK inhibition, iodine uptake by thyroid tumour cells is regained.7

AstraZeneca acquired exclusive worldwide rights to selumetinib from Array BioPharma Inc. in 2003.

About the ASTRA trial

ASTRA is a Phase III randomised, double blind study which is comparing the complete remission rate following a 5-week course of selumetinib or placebo and single dose adjuvant radioactive iodine therapy in patients with differentiated thyroid cancer.5