On November 15, 2017 LabCorp (NYSE: LH) a leading global life sciences company, reported the U.S. availability of the PD-L1 IHC 28-8 pharmDx assay as a complementary diagnostic for two newly approved indications in connection with the use of Bristol-Myers Squibb’s OPDIVO (nivolumab) to treat patients with metastatic urothelial carcinoma, also referred to as bladder cancer, and squamous cell carcinoma of the head and neck (Press release, LabCorp, NOV 15, 2017, View Source;p=RssLanding&cat=news&id=2317135 [SID1234522109]). The PD-L1 IHC 28-8 pharmDx assay was developed by Agilent’s Dako pathology division. While OPDIVO is approved for these indications without use of the test, the test provides physicians with important information about those patients who are most likely to respond positively to OPDIVO. LabCorp’s Center for Molecular Biology and Pathology laboratory performed testing for the clinical studies that supported approval of the new indications for the assay.

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The PD-L1 IHC 28-8 pharmDx assay was previously approved for use as a complementary diagnostic with OPDIVO to treat certain patients with non-squamous non-small cell lung cancer (NSCLC) and melanoma. LabCorp’s central clinical trials laboratory was the sole provider of testing to support the clinical trial for the 2015 approval of the non-squamous NSCLC treatment indication, reflecting how the combined capabilities of LabCorp’s clinical laboratory infrastructure and Covance’s central clinical trials laboratory provide integrated support for clinical trials.

"The expanded use of this PD-L1 test as a complementary diagnostic for two new cancer indications, as well as our collaboration in the studies that supported regulatory approval, demonstrate the unique solutions that only LabCorp can provide for the development and commercialization of new tests and therapies, particularly complementary and companion diagnostics," said David P. King, chairman and chief executive officer of LabCorp. "The combined expertise of LabCorp Diagnostics and Covance Drug Development makes us the industry leader in precision medicine, including the exciting area of immuno-oncology. With our extensive experience performing this test, physicians can have high confidence that the results we deliver will help them identify the most appropriate treatment for their patients and will improve the delivery of care."

The PD-L1 IHC 28-8 pharmDx assay is approved for use with patients diagnosed with advanced or metastatic bladder cancer, or recurrent or metastatic squamous cell carcinoma of the head and neck, whose cancers have returned or progressed after prior treatment with platinum-based chemotherapy. OPDIVO is an immunotherapy that helps the immune systems of certain individuals detect and kill cancer cells. The PD-L1 IHC 28-8 pharmDx assay identifies a tumor’s expression of the PD-L1 protein, which may be associated with an increased likelihood of positive immune system response to treatment with OPDIVO; however, OPDIVO is approved for use regardless of PD-L1 status.

Squamous cell carcinoma of the head and neck is the most common form of head and neck cancer, and urothelial carcinoma is the most common type of bladder cancer, accounting for approximately 90 percent of diagnoses. These cancers are often difficult to treat using traditional therapies, and immunotherapies like OPDIVO offer the hope of enhanced survival for appropriate patients.

The PD-L1 IHC 28-8 pharmDx assay is available from LabCorp and its Integrated Oncology specialty laboratory.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

On November 15, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima") reported that it held a Pre-Investigational New Drug Application (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) in November to discuss the regulatory pathway for the development of Eftilagimod Alpha (LAG-3Ig or IMP 321) in the United States (Press release, Prima Biomed, NOV 15, 2017, View Source [SID1234522106]).

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The FDA addressed Prima’s questions related to preclinical, nonclinical, and clinical data and design of clinical trials of Eftilagimod Alpha in a chemo-immunotherapy setting and in an immuno-oncology combination trial. Prima intends to file an investigational new drug application (IND) in the first half of calendar year 2018. After having successfully started clinical development of Eftilagimod Alpha in Australia and Europe, an IND would provide Prima with the opportunity to commence clinical studies and regulatory interactions in the United States.
"The U.S. is the largest pharmaceutical market in the world, so the pre-IND meeting regarding Eftilagimod Alpha was an important milestone. Our meeting with the FDA was very productive and their guidance will be most valuable in assessing the appropriate U.S. clinical and regulatory strategies for Eftilagimod Alpha," said Marc Voigt, Prima’s Chief Executive Officer.

On November 15, 2017 Pharma reported the initiation of a Phase 1 clinical trial for its novel immune-modulator, PIN-2 (Press release, PIN Pharma, NOV 15, 2017, View Source [SID1234522102]).

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This first-in-human, proof-of-concept study is being conducted in oncology patients with solid tumors by PIN Pharma’s wholly owned Australian subsidiary, PIN Pharma Pty Ltd. The study is designed to show changes in the human immune system utilizing specific biomarkers that will both demonstrate and support PIN-2’s ability to link the innate and adaptive immune systems via antigen presenting cell activation (monocyte-derived dendritic cells) resulting in the generation of endogenous killer T cell immunity (CD8 cells).

"This study is supported by physiological and immunological data generated in our preclinical studies as well as in silico. We are confident that the study will confirm PIN-2’s mechanism of action and validate our preclinical models," said Colin Bier, President and CEO. "We anticipate having interim data by the upcoming JP Morgan conference this January, and are already seeing interest from pharma and venture funds to discuss the potential of this next generation immune-oncology therapy."

With the recent issues arising out of the current generation of immune-oncology compounds both in the clinic and on the market, PIN-2 has the potential to improve response rates that will allow better safety and tolerability either alone or in combination with existing treatments by enhancing innate immunity.

On November 15, 2017 ONCODESIGN (Paris:ALONC) (ALONC – FR0011766229), a biopharmaceutical group specialized in , precision medicine, reported that it has obtained positive results opening the way for the ALK1 kinase inhibitor discovery program to move on to the lead optimization phase (Press release, Oncodesign, NOV 15, 2017, View Source [SID1234522101]).

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ALK1 is a kinase involved in angiogenesis. Tumoral angiogenesis is the mechanism by which new blood vessels form and infiltrate tumors to provide nutrients and oxygen and to dispose of the tumor’s cellular waste products. Inhibiting this mechanism is a promising line of research in the quest for new treatments for most types of cancer.

The ALK1 program has produced positive cellular results in a mechanistic model as part of the probe to lead phase. Oncodesign has thus decided to advance it to the lead optimization phase and commence an exhaustive series of in vivo biological tests, while conducting medicinal chemistry optimization of the inhibitor molecules identified. A medicinal chemistry team dedicated to the project will be set up to implement this decision.

"At the end of the Lead Optimization phase a drug candidate could be selected for preclinical trials and then clinical development", said Jan Hoflack, Oncodesign’s Chief Scientific and Operating Officer. "Today, our preclinical portfolio contains no fewer than 12 programs, and ALK1 is joining our most advanced programs. Our goal is to develop a best-in-class drug from this program with the potential to complement other anti-angiogenic approaches, currently a market worth over $10 billion. The addition of the drug discovery expertise of the François Hyafil research center in Paris-Saclay has enabled us to accelerate our most promising programs significantly. ALK1 is the first example of a project successfully moving on to a major new stage in its development by harnessing this new expertise."

After exploring molecules’ therapeutic potential in the probe qualification and probe orientation stages, molecules move on to the probe to lead phase. Molecules then undergo a further selection stage after medicinal chemistry optimization of their structure, and the programs are prioritized according to their activity in relevant cell models and their potential to become a drug.

The lead optimization phase aims to identify a drug candidate, a molecule meeting a large number of very exacting criteria to determine its suitability as a future drug. The selection of a drug candidate takes place at the end of the drug discovery phase, and the regulatory development phases then begin. Lead optimization can take up to 36 months, and the success rate is typically around 50%.

About kinases and Nanocyclix technology:

Kinases are a family of enzymes that play a key role in regulating most cell functions, such as proliferation, cell cycle progression, metabolism, survival/apoptosis, repair of damaged DNA, motility and response to the microenvironment.
Using its Nanocyclix technology module, Oncodesign identifies macrocyclic molecules capable of inhibiting both known and unexplored kinases in a powerful and targeted manner. A large variety of kinase inhibitors are thus explored continuously, and only the most promising inhibitor/targeted kinase combinations are selected for more in-depth investigations.
Oncodesign has built a project portfolio with tremendous potential to treat diseases with very substantial unmet medical needs. This portfolio contains both molecules already at an advanced stage of clinical development (a PET tracer for a specific type of lung cancer) and molecules at an earlier stage of development.

On November 15, 2017 Moderna Therapeutics, a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported that it has started dosing patients in a Phase 1 study of mRNA-4157, an mRNA-based personalized cancer vaccine (Press release, Moderna Therapeutics, NOV 15, 2017, View Source [SID1234522100]). The Phase 1 open-label, dose escalation, multicenter study in the United States (KEYNOTE-603) will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, marketed by Merck (known as MSD outside the U.S. and Canada) in subjects with unresectable solid tumors.

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The first-in-human dosing of mRNA-4157 marks a key milestone in the strategic collaboration between Moderna and Merck to advance the novel mRNA-based personalized cancer vaccine in combination with KEYTRUDA for the treatment of multiple types of cancer.

"When we combine the potential for robust T-cell response stimulated by our mRNA vaccine, which encodes for 20 patient-specific mutations, with Merck’s checkpoint inhibitor, Keytruda, we have a unique opportunity to make a transformative difference for patients with cancer," said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna. "Having now successfully designed, manufactured and dosed a completely customized personalized cancer vaccine, we look forward to progressing the Phase 1 clinical study and gathering important human data on mRNA-4157 in the months ahead."

KEYNOTE-603 is expected to enroll up to 90 patients across multiple clinical study sites in the United States. Part A of the study will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors (in the adjuvant setting). Part B of the study will evaluate mRNA-4157 in combination with KEYTRUDA in subjects with unresectable solid tumors. The ClinicalTrials.gov Identifier for the mRNA-4157 study is: NCT03313778. A link to the ClinicalTrials.gov listing for the study can be found here.

"Our goal in this important collaboration is to deliver personalized vaccines to patients suffering from malignant disease, with the hope that this stimulus will generate a tumor-specific immune response in the presence of Keytruda, our approved immune-stimulatory cancer therapy," said Roger M. Perlmutter, M.D., Ph.D., President, Merck Research Laboratories. "This trial leverages advances in genomics, advanced data analytics, and immunology to permit the generation of personalized cancer vaccines, a potentially transformative approach to cancer treatment. We are hopeful that this collaboration with Moderna, now entering clinical trials, will yield tangible benefits for cancer patients."

"Checkpoint inhibitors and other immuno-oncology therapies are continuing to revolutionize how we treat cancer. However, despite the strong and durable responses we see in some patients, many other patients’ disease continues to progress," said Howard A. "Skip" Burris III, MD, President, Clinical Operations & Chief Medical Officer at Sarah Cannon, and a Principal Investigator of the mRNA-4157 Phase 1 study. "An individualized medicine designed to help each patient’s immune system better recognize cancer as foreign and attack it would be a critical addition to oncologists’ treatment arsenal, potentially helping many more patients respond more effectively to treatment."

About mRNA-4157

Moderna is creating an individualized, mRNA-based personalized cancer vaccine to deliver one medicine for one patient at a time. Through next-generation sequencing, Moderna identifies mutations found on a patient’s cancer cells, called neoepitopes. Neoepitopes can help the immune system distinguish cancer cells from normal cells. Using algorithms developed by its in-house bioinformatics team, Moderna predicts 20 neoepitopes present on the patient’s cancer that should elicit the strongest immune response, based on unique characteristics of the patient’s immune system and particular mutations. Moderna then creates a vaccine that encodes for each of these mutations and loads them onto a single mRNA molecule.

Once injected into the patient, the vaccine should direct the patient’s cells to express the selected neoepitopes. In turn, this may help the patient’s immune system better recognize cancer cells as foreign and destroy them. Leveraging its rapid cycle time, small-batch manufacturing technique and digital infrastructure, Moderna plans to manufacture and supply each individually manufactured personalized cancer vaccine to patients within weeks.

mRNA-4157 also has the potential to enhance clinical outcomes associated with checkpoint inhibitor therapies. In 2016, Moderna and Merck formed a collaboration to develop mRNA-4157 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA.

About the Moderna and Merck Collaboration to Advance mRNA-4157

Under the terms of the agreement announced in June 2016, Merck made an upfront cash payment to Moderna of $200 million, which Moderna is using to lead all research and development efforts through proof of concept. The development program will entail multiple studies in several types of cancer and include the evaluation of mRNA-4157 in combination with KEYTRUDA. Moderna is also utilizing the upfront payment to fund a portion of the ongoing build-out of its GMP mRNA clinical manufacturing facility in Norwood, Mass., for the purposes of personalized cancer vaccine manufacturing.

Following human proof of concept studies, Merck has the right to elect to make an additional undisclosed payment to Moderna. If exercised, the two companies will then equally share cost and profits under a worldwide collaboration for the development of mRNA-4157. Moderna will have the right to elect to co-promote mRNA-4157 in the U.S. The agreement entails exclusivity around combinations with KEYTRUDA. Moderna and Merck will each have the ability to combine mRNA-4157 with other immuno-oncology (non-PD-1) agents.