On November 29, 2017 Vedanta Biosciences, an affiliate of PureTech Health (LSE: PRTC) developing a new category of therapies for immune-mediated and infectious diseases based on rationally designed consortia of human microbiome-derived bacteria, reported new translational medicine collaborations in cancer immunotherapy with Leiden University Medical Center and the University of South Alabama (USA) Mitchell Cancer Institute (Press release, Vedanta Biosciences, NOV 29, 2017, View Source [SID1234522340]). The Company also reported the expansion of its translational medicine collaborate on in cancer immunotherapy with NYU Langone Health and its Perlmutter Cancer Center. Researchers at these institutions have been collaborating with Vedanta Biosciences to analyze microbiome clinical data from interventional checkpoint inhibitor studies to identify microbiome signatures associated with response to immunotherapy and key mechanisms through which the gut microbiota modulate immunotherapeutic responses.

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"Data from our ongoing clinical collaborations in melanoma show that gut bacteria signatures could help determine if a cancer immunotherapy will work," said Bruce Roberts, Ph.D., Chief Scientific Officer of Vedanta Biosciences. "We’re pleased to expand our research collaborations into others forms of cancer, with the ultimate goal of identifying ways to change the microbiome to increase the proportion of patients and types of cancer patients who respond to immunotherapies."

Under the agreement with Leiden University Medical Center, Vedanta Biosciences will work in collaboration with Ellen Kapiteijn, M.D., Ph.D., and Ed Kuijper, M.D., Ph.D., to understand the role of the microbiome in immunotherapeutic responses against a variety of cancers, including melanoma, head and neck, and bladder. The new collaboration with the USA Mitchell Cancer Center, led by Art Frankel, M.D., will analyze associations between the gut microbiome and responses to checkpoint inhibitor treatment in melanoma and cancers of the bladder and kidneys. Building on the existing translational work with NYU Langone in melanoma led by Jeffrey S. Weber, M.D., Ph.D., and Melissa Wilson, M.D., Ph.D., the expanded agreement adds collaborations in bladder cancer and lung cancer, led, respectively, by Arjun V. Balar, M.D., and Leena Gandhi, M.D., Ph.D.

Vedanta Biosciences’ immuno-oncology programs include lead product candidate, VE800, which has been shown in preclinical models to activate CD8+ T cells, a type of white blood cell that is the predominant effector in cancer immunotherapy, improve CD8+ T cell tumor infiltration, and improve survival in several cancer models in combination with checkpoint inhibitors. Vedanta anticipates filing an investigational new drug application (IND) for this candidate in 2018.

On November 29, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with rare cancers and rare diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company’s lead development candidate IMO-2125 in combination with Ipilimumab for the treatment of anti-PD-1 refractory metastatic melanoma in combination with ipilimumab therapy (Press release, Idera Pharmaceuticals, NOV 29, 2017, View Source [SID1234522339]). FDA’s Fast Track program is designed to expedite the development and review of drugs and biologics to treat serious or life-threatening conditions with non-clinical or clinical data demonstrating the potential to address unmet medical needs. Such drugs may qualify for Fast Track designation.1

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"This Fast Track designation represents another positive step for the development of IMO-2125 and is a clear recognition of the serious unmet need that exists for patients who do not benefit from anti-PD-1 therapy," stated Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer. "We’re thrilled with the dramatic response rate that has been observed to date so far with IMO-2125 in combination with ipilimumab and are eager to continue enrolling more patients through both the Phase 2 expansion of our ongoing trial and initiating the Phase 3 trial early next year."

About Fast Track Designation1
Fast Track designation is intended to facilitate development and expedite review of drugs to treat serious or life-threatening conditions. A drug that is intended to treat a serious or life-threatening condition with nonclinical or clinical data that demonstrate the potential to address an unmet medical need may qualify for Fast Track designation. When Fast Track designation is requested later in development, available clinical data should demonstrate the potential to address an unmet medical need. There are opportunities for frequent interactions with the review team for a fast track product. In addition, such a product could be eligible for priority review if supported by clinical data at the time of BLA, NDA, or efficacy supplement submission.

About IMO-2125
IMO-2125 is a toll-like receptor (TLR) 9 agonist that received orphan drug designation from the FDA in 2017 for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors in refractory melanoma patients. Currently approved immuno-oncology treatments for patients with metastatic melanoma, specifically checkpoint inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy making them so-called "refractory." The combination of ipilimumab and IMO-2125 appears to activate an immune response in these patients who have exhausted all options. Intratumoral injections with IMO-2125 are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as the lymphatic system (metastatic disease). Because melanoma occurs in younger individuals, the years of life lost to melanoma are also disproportionately high when compared with other cancers. Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

On November 29, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration (AMD) and fibrotic diseases, reported that the first patient has been dosed in its Phase 1b clinical trial of TRC105 in combination with Opdivo (nivolumab) in patients with non-small cell lung cancer (Press release, Tracon Pharmaceuticals, NOV 29, 2017, View Source;p=RssLanding&cat=news&id=2319234 [SID1234522312]).

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"Endoglin is expressed on activated myeloid derived suppressor cells, a cell type implicated in tumor resistance to immunotherapy. To date, we have observed promising signs of activity with our endoglin antibodies in combination with PD-1 inhibitors in a number of preclinical syngeneic mouse tumor models," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We are excited to advance a combination of TRC105 with an immune oncology agent into the clinic to further assess our antibody’s immunomodulatory activity."

About the Phase 1b Clinical Trial of TRC105 and Opdivo in Lung Cancer

The Phase 1b clinical trial is an open-label, dose-escalation and expansion cohort study of TRC105 and Opdivo in patients with non-small cell lung cancer that have received prior chemotherapy. The primary objectives of the Phase 1b study are to assess the safety of TRC105 when given with Opdivo, determine its recommended Phase 2 dose with Opdivo and evaluate the response rate. The trial incorporates tumor biopsy testing to correlate tumor myeloid cell infiltration with response, in order to allow for potential biomarker-directed therapy of lung cancer patients.

Further details of the study are available on www.clinicaltrials.gov, identifier NCT03181308.

About Carotuximab (TRC105)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in the pivotal Phase 3 TAPPAS trial in angiosarcoma and multiple Phase 2 clinical trials, in combination with VEGF inhibitors. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a randomized Phase 2 trial for patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

On November 29, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that post-hoc analysis of data generated from its phase 2b trial of VGX-3100 identified immune correlates and biomarker signatures predictive of treatment success (Press release, Inovio, NOV 29, 2017, View Source [SID1234522304]). VGX-3100, Inovio’s lead product now in a pivotal phase 3 trial, would be the first non-surgical treatment for HPV-associated high grade cervical dysplasia (squamous intraepithelial lesions or HSIL) which frequently progresses to cancer.

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Details of the new biomarker and immunologic data are highlighted in the peer-reviewed journal Clinical Cancer Research in the article, "Clinical and Immunologic Biomarkers for Histologic Regression of High-grade Cervical Dysplasia and Clearance of HPV-16 and HPV-18 after Immunotherapy," by Inovio and its academic collaborators.

In this paper, Inovio has identified biomarker signatures which predicted success of VGX-3100 treatment as early as two weeks after the completion of treatment which was a full 22 weeks prior to the formal efficacy assessment. The company believes these biomarkers will aid physicians in guiding patient care during VGX-3100 treatment, and is pursuing the confirmation of these predictions in its phase 3 program. Inovio is also researching pre-treatment biomarkers which could identify patients most likely to respond to treatment with VGX-3100, increasing absolute efficacy of the product.

Dr. J. Joseph Kim, President and CEO, said: "Inovio will transform the treatment of HPV-associated disease with the first immunotherapies to treat both pre-cancer and cancer caused by HPV which infects more than 70% of sexually active adults. Today’s advancement in discovering a successful treatment biomarker moves us closer to that goal."

Inovio previously reported that VGX-3100 eliminated high grade dysplasia in 50% of women in its phase 2b randomized, placebo-controlled trial. In 80% of the women whose high grade dysplasia was eliminated, the HPV infection was also cleared by VGX-3100. Further data analysis revealed that the combination of HPV typing and cervical cytology (Pap smear) following dosing was predictive for both elimination of the high grade dysplasia and clearance of HPV.

Overall, Inovio is well positioned to comprehensively treat HPV-associated diseases across the continuum of HPV infection, from pre-cancerous conditions through to cancer in both women and men, with VGX-3100 — already the most advanced product for treating these diseases.

Inovio’s phase 3 clinical program to evaluate the efficacy of VGX-3100 to treat high grade cervical dysplasia caused by HPV is enrolling as scheduled with over 35 clinical sites open. By the end of the year, the company expects to open approximately 50 sites in at least six countries. The pivotal data from this program will support the licensure application of VGX-3100.

Extending its HPV franchise, Inovio is enrolling women into a phase 2 trial at more than 10 sites to evaluate the efficacy of VGX-3100 in women with high-grade vulvar dysplasia, another disease caused by HPV with a high unmet medical need.

And, in 2018, Inovio will initiate a phase 2 "proof-of-concept" study for the treatment of high grade anal neoplasia, also caused by HPV with limited treatment options.
In this paper, Inovio has revealed immune responses in the phase 2b trial that were significantly associated with treatment success with VGX-3100 that had not been previously reported. Analysis of data from patient blood samples showed that when focusing on immune responses specific for the HPV type patients were infected with, a significant increase was seen in killer T cells that expressed perforin – a protein known to be a key mediator in killer T cell function. These significant increases were noted only in patients who clinically responded to VGX-3100 and were present at week 14 of treatment, which is 22 weeks prior to the efficacy assessment. Cervical tissue samples from these same patients also showed an influx of immune cells that expressed perforin after treatment, further strengthening the association between the induction of perforin by VGX-3100 and clinical response. This understanding of the immune mechanism of action could also aid in the advancement of Inovio’s broader immunotherapy product pipeline.

About HPV and Cervical HSIL

HPV is the most common sexually transmitted infection, with over 14 million new infections annually. While many of these are transient infections, persistent high-risk infections can cause the formation of pre-cancerous lesions. Left untreated, women diagnosed with cervical HSIL are at increased risk of developing cervical cancer. HPV types 16 and 18 are responsible for 70% of cervical cancers, with more than 400,000 new cases of HPV 16/18 cervical HSIL annually in the US and Europe. Cervical cancer is a major global health problem, causing 260,000 deaths annually. While cervical HSIL and cervical cancer are the most well-known HPV related diseases, HPV is also a major cause of HSIL and cancer in the entire anogenital region and oropharynx. Currently there are no treatments available for HPV infection and surgery is the only approved treatment for cervical HSIL. While surgery is effective at removing lesions, it does not treat the underlying HPV infection and it carries increased risk of cervical incompetence and pre-term birth, which can result in fetal morbidity and mortality.

About VGX-3100

VGX-3100 is a DNA-based immunotherapy under investigation for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (phase 3) and vulva (phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

On November 29, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene and cell therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported it has acquired a 125,000-square foot manufacturing facility in Durham, North Carolina (Press release, bluebird bio, NOV 29, 2017, View Source [SID1234522300]). Once construction and validation is complete, the site will produce lentiviral vector for the company’s gene and cell therapies, including: Lenti-D for the treatment of cerebral adrenoleukodystrophy; LentiGlobin for the treatment of transfusion-dependent β-thalassemia and severe sickle cell disease; and bb2121 and bb21217 for the treatment of multiple myeloma.

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"Our goal is to bring multiple therapies to market over the next four years that can transform the lives of people suffering from severe genetic diseases and cancer. Investing in a world-class manufacturing infrastructure is a crucial step in accomplishing that mission on behalf of the people who need these novel treatments," said Derek Adams, bluebird bio chief manufacturing and technology officer. "The North Carolina manufacturing site will complement our important external manufacturing partnerships. By simultaneously establishing multiple lentiviral vector manufacturing partnerships and pursuing in-house manufacturing, bluebird is uniquely positioned to adeptly, robustly, and reliably provide our current gene and cell therapy products in development, as well as future pipeline therapies to patients in need."

The company is making a significant investment in its manufacturing infrastructure as it advances multiple products into late-stage development and potential commercial launch. Expanding in-house expertise, creating an extensive manufacturing network, and increasing manufacturing capacity ensures that bluebird can deliver on the promise of these product candidates.

In addition to the internal manufacturing capacity that this site will provide, bluebird bio also has now entered into multi-year agreements with three manufacturing partners in the United States and Europe: Brammer Bio (Cambridge, MA), Novasep (Gosselies, Belgium) and MilliporeSigma, the Life Science business of Merck KGaA (Carlsbad, CA). Each of these partners are collaborating with bluebird bio on production of lentiviral vector across all programs. bluebird bio also partners with Lonza (Houston, TX) and apceth Biopharma (Munich, Germany) to produce drug product for Lenti-D and LentiGlobin.

The initial North Carolina site build-out will allow for production of clinical and commercial supply of lentiviral vector, which is a critical component of the company’s gene and cell therapies. The facility is large enough to accommodate significant potential future expansion, including the possibility of commercial drug product production.

North Carolina is among the leaders in the U.S. in the number of biologics manufacturing jobs, providing access to a highly-skilled workforce. It also is home to top university researchers at Duke University, University of North Carolina, North Carolina State University and other universities required for such specialized operations. The North Carolina Community College System’s custom training program will assist bluebird in recruiting, screening and training employees for this facility. The state’s gene therapy, rare disease and manufacturing assets also include initiatives to develop precision health capabilities and to provide academic fellowships to help advance North Carolina’s fast-growing expertise in gene therapy.

NCBiotech created the Economic Development Award to assist companies to expand and grow their operations in North Carolina. NCBiotech has committed financial resources to this expansion, when bluebird bio meets specific job creation targets.