On January 8, 2016 Moderna Therapeutics, a pioneer in the development of messenger RNA (mRNA) Therapeutics, and Pharmaceutical Product Development, LLC (PPD), a leading global contract research organization (CRO), reported a strategic collaboration to support Moderna’s evolution as a clinical-stage company (Press release, PPD, JAN 8, 2016, View Source [SID:1234508705]). Covering a broad expanse of drug modalities and therapeutic areas, Moderna’s pipeline has the potential to address the unmet needs of numerous patients worldwide. PPD will be a key partner in advancing Moderna’s proprietary pipeline as it rapidly scales up its clinical efforts in the coming months and years.

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Under the terms of the agreement, PPD will play a significant role in Moderna’s clinical development efforts, including support for investigational new drug (IND) strategic planning, as well as for clinical trial design and execution. The collaboration is built around a unique risk-sharing model that incentivizes both organizations to achieve shared milestones.

"We are excited to partner with PPD as we rapidly progress multiple mRNA candidates toward the clinic across our ventures," said Stéphane Bancel, Chief Executive Officer of Moderna. "We are building a high-quality, scalable clinical development capability to match the accelerated output of our mRNA research, which will require the ability to test many mRNA therapeutics in clinical trials in parallel each year. PPD is an ideal partner for Moderna because of its proven track record of quality and delivery at every phase of clinical development. Further, PPD is uniquely positioned to help us achieve our goals because of its ability to be nimble while scaling to our evolving pipeline needs."

Moderna’s pipeline is composed of a series of novel drug modalities, each representing a distinct application of the company’s proprietary core expression mRNA platform to encode proteins that achieve a therapeutic benefit. Moderna’s current modalities include infectious disease vaccines, personalized cancer vaccines, intracellular/transmembrane liver proteins, intratumoral cancer therapy, and secreted antibodies and proteins. Moderna is leveraging these modalities to advance drugs across a broad spectrum of therapeutic areas via its four ventures, including Valera, focused on infectious diseases; Elpidera, focused on rare diseases; Onkaido, focused on oncology; and Caperna, focused on personalized cancer vaccines.

With more than 30 years of CRO industry leadership, PPD offers a comprehensive portfolio of services featuring integrated development consulting, Phase I-IV delivery, and laboratory services. PPD Biotech, the company’s best-in-class, custom-built offering, provides emerging companies with tailored services that are flexible, innovative and nimble. Through PPD Biotech, PPD offers biopharma companies high-quality delivery, broad global scale and top-notch therapeutic and medical development expertise.

"We are pleased that Moderna has selected PPD to be its premier clinical development partner," said David Simmons, Chairman and Chief Executive Officer of PPD. "We recognize the breakthrough nature of Moderna’s novel mRNA platform and its unique business model. We look forward to applying our deep capabilities and expertise in the emerging biopharma space to help Moderna progress its pipeline through the clinic with the ultimate goal of delivering novel drugs to address unmet medical needs."

On January 08, 2016 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for LV305 and G305 for the treatment of soft tissue sarcoma (Press release, Immune Design, JAN 8, 2016, View Source [SID:1234508704]). LV305 and G305 are the complementary agents that comprise CMB305, Immune Design’s "prime boost" cancer immunotherapy product candidate.

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Orphan Drug Designation is granted by the FDA Office of Orphan Drug Products to products that treat rare diseases. The FDA defines rare diseases as those affecting fewer than 200,000 people in the United States. Orphan Drug Designation provides the sponsor certain benefits and incentives, including a period of marketing exclusivity for the first marketing application, if regulatory approval is received for the designated indication, potential tax credits for certain activities and waiver of certain administrative fees.

CMB305 is a cancer immunotherapy product candidate that involves the sequential dosing of LV305 and G305. LV305 is a hybrid vector from the ZVex discovery platform that specifically targets dendritic cells (DCs) in vivo and delivers the RNA for NY-ESO-1, enabling the DCs to express the entire tumor antigen and potentially induce a diverse set of CTLs targeting NY-ESO-1 in tumors. G305, in contrast, is designed to boost the CTL response via the induction of antigen-specific CD4 "helper" T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of the GLAAS platform. CMB305 is intended to be an "off-the shelf" therapy that does not require patient-specific manufacturing or ex vivo manipulation of patient samples. Immune Design has conducted prior studies to establish the safety and individual immunologic activity of LV305 and G305. CMB305 is currently being evaluated in a Phase 1B trial in patients with locally advanced, relapsed or metastatic solid cancers whose tumors express NY-ESO-1 and a randomized Phase 2 trial of CMB305 combined with Genentech’s investigational cancer immunotherapy, atezolizumab (MPDL3280A; anti-PD-L1) in patients with soft tissue sarcoma, pursuant to a collaboration with Genentech.

On January 8 2016 Pfizer Inc. (NYSE: PFE) and Adaptive Biotechnologies Corporation reported that they have entered into a translational research collaboration to leverage next generation sequencing of the adaptive immune system to advance Pfizer’s growing immuno-oncology franchise (Press release, Pfizer, JAN 8, 2016, View Source [SID:1234508703]).

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Under the terms of the agreement, Pfizer and Adaptive will seek to combine drug development and platform technology biomarker expertise to identify patients who may preferentially benefit from immunotherapy.

Understanding and reliably measuring each patient’s immune response to their cancer before and after therapy is critical to defining the most appropriate immunotherapy for that patient. Adaptive’s immunosequencing platform quantitatively and reproducibly measures the patient’s immune-cell repertoire, providing a powerful translational tool to accelerate Pfizer’s immuno-oncology biomarker and drug development programs.

"Immunotherapy is one of the most important advances in cancer therapy and offers the potential for long term disease control for many patients," said Chris Boshoff, Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology. "Pfizer is investing significantly in this space. The collaboration with Adaptive Biotechnologies supports our strategy of accelerating the development of potentially innovative new combination treatments by allowing us to develop a differentiated and competitive understanding of the immune landscape in specific tumor types."

Adaptive Biotechnologies, the leading experts in profiling the immune cell repertoire, will work with Pfizer to apply their proprietary immunosequencing platform technology, bioinformatics capability, and scientific expertise to advance Pfizer’s rapidly expanding immuno-oncology pipeline.

"This collaboration with Pfizer is evidence of the immense impact immune repertoire profiling may have on the immuno-oncology space," said Chad Robins, President, Chief Executive Officer and Co-Founder at Adaptive Biotechnologies. "Adaptive’s ability to precisely measure a patient’s immune response to cancer before and after treatment provides a universal tool that will help bolster our understanding of immuno-oncology approaches."

About Adaptive Biotechnologies

Adaptive Biotechnologies is the pioneer and leader in combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. Adaptive is bringing the accuracy and sensitivity of its immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.

On January 08, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics reported the publication of a manuscript in Cancer Research describing OncoMed’s efforts to develop novel therapeutics against R-spondin (RSPO) targets and elucidating the link between expression of the RSPO cancer stem cell pathway and tumor growth (Press release, OncoMed, JAN 8, 2016, View Source [SID:1234508702]). OncoMed is currently conducting a Phase 1a/b clinical trial of its anti-RSPO3 (OMP-131R10) antibody.

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The article "Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates beta-Catenin Signaling and Tumorigenesis in Multiple Cancer Types" (released online December 30, 2015) describes the generation of neutralizing monoclonal antibodies against RSPO-1, -2 or -3 and the successful use of these antibodies to treat diverse types of patient-derived xenografts, including colon, ovarian, pancreas and lung tumors. Of note, these anti-RSPO antibodies were effective in the tumor models regardless of whether the tumors overexpressed RSPO because of gene translocations or because of other tumor-intrinsic pathways. OncoMed is utilizing biomarker assays to prospectively screen patients for RSPO gene expression as part of its Phase 1a/b clinical program.

Mechanistically, the paper establishes a functional link between RSPO expression and tumor growth. Tumor-derived RSPO can activate beta-catenin, and antibody-mediated blocking of RSPO binding to its receptor potently inhibits tumor growth. This anti-tumor activity is associated with the modulation of beta-catenin and cancer stem cell pathways.

"R-spondins are emerging as an important cancer target. As key stimulators of beta-catenin activity in a variety of human tumor types, targeting the RSPO pathway may prove to be an effective approach to modulating this fundamental signaling axis," said John Lewicki, Ph.D., OncoMed’s Chief Scientific Officer. "Our first anti-RSPO candidate is being studied in Phase 1a/b clinical trials with a strong biomarker hypothesis and we expect to establish a single-agent dose and treat biomarker-positive patients this year."

About Anti-RSPO3
OncoMed’s anti-RSPO3 (OMP-131R10) is the first drug in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers. The company’s ongoing Phase 1a/1b clinical trial is initially enrolling patients with advanced refractory solid tumors to assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of the anti-RSPO3 antibody. Once a single-agent dose has been identified, biomarker-selected patients will be enrolled in a Phase 1a expansion arm to evaluate possible anti-tumor activity. In the Phase 1b portion of the trial, anti-RSPO3 will also be tested in second-line colorectal cancer patients in combination with chemotherapy.

In preclinical studies OncoMed’s anti-RSPO3 antibody demonstrated robust in vivo anti-tumor efficacy as a single agent and in combination with standard of care across a range of solid tumors, including colon, lung, ovarian, and pancreatic cancers, among others. The anti-RSPO3 antibody delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of cancer stem cells. Anti-RSPO3 antibody represents the third product candidate in the clinic that is part of OncoMed’s collaboration with Celgene.

On January 8, 2016 Otsuka Pharmaceutical Co., Ltd. (Headquarters: Chiyoda-ku, Tokyo; President and CEO: Tatsuo Higuchi; "Otsuka")reported that it has filed the NDA in Japan for "ponatinib (brand name outside Japan is Iclusig), a known tyrosine kinase inhibitor (TKI) developed by ARIAD Pharmaceuticals, Inc. (Headquarters: Massachusetts, United States; "ARIAD") used to treat resistant and intolerant chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (Press release, Otsuka, JAN 8, 2016, View Source [SID:1234508699]).

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ARIAD conducted a multicenter Phase I / II trial in Japan to confirm efficacy, safety and tolerability of ponatinib. Otsuka filed the NDA based on these results and the results of overseas clinical trials. Furthermore, ponatinib was designated in Japan to be an orphan drug in September 2015.

Ponatinib is a TKI discovered and developed by ARIAD that targets BCR-ABL expressed in CML and Ph+ ALL. This drug is a new chemically synthesized oral TKI, and is specifically designed to inhibit unmutated BCR-ABL as well as T315I mutation, a mutant-type BCR-ABL that manifests and induces resistance after patients are treated with other TKIs. Ponatinib demonstrates efficacy in currently available TKI-resistant and in patients who are intolerable CML as well as relapsed or refractory Ph+ ALL, but it also demonstrates efficacy for isoforms of BCR-ABL that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs. Ponatinib was approved by the US FDA in December 2012, and was approved in Europe in July 2013.

In Japan, CML occurs in approximately 1 out of 100,000 people among all age groups. It is estimated that there are approximately 11,000 patients.*3 Although the mortality rate has decreased with the advancement of TKI treatment, the number of patients is steadily increasing with an aging population. Initial symptoms are rarely seen in CML patients from disease onset to the chronic phase (5-6 years); however, white blood cell count and the blast cell ratio increase and, as the disease progresses, patients begin experiencing symptoms such as general malaise, weight loss, and bloating due to hepatosplenomegaly. In the accelerated phase (6-9 months), patients experience bone pain and exacerbation of hepatosplenomegaly; in the blast phase (3-6 months), patients experience anemia, bleeding tendencies, infections, etc. For CML, symptoms gradually worsen and risk of treatment resistance increases as the disease progresses*4. In contrast, Ph+ALL is seen in pediatric and elderly patients, and prognosis is extremely poor for patients who relapse after receiving initial ALL treatment and is an area where needs are still unmet.*5,6

Although TKI is used as a first-line drug for CML and Ph+ ALL, resistance to treatment can develop as the disease progresses because of amplification, overexpression or mutation of BCR-ABL genes, which are causal factors of the disease. In such cases, an adequate patient response to therapy may not be obtained even after several TKI products are used. In addition, there are patients who must discontinue treatment as they become intolerant of the side effects of other TKIs. A new TKI treatment is desired in Japan and other Asian countries in order to treat such resistant or intolerant patients.

Otsuka is currently expanding its product portfolio and is focusing on CNS (neuropsychiatry), cardiovascular, ophthalmology, and oncology fields. The company will continue to develop and commercialize pharmaceuticals aimed to improve survival of hematological cancer patients with insufficient treatment options by undertaking operations to provide a wide range of products from diagnostics to treatment.