On November 29, 2017 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), reported the completion of enrollment in the Company’s phase II clinical trial evaluating OPRX-106, the Company’s oral antiTNF product candidate, in patients with ulcerative colitis (UC) (Press release, Protalix, NOV 29, 2017, View Source;p=RssLanding&cat=news&id=2319080 [SID1234522311]). OPRX-106 is the Company’s proprietary plant cell-expressed recombinant human tumor necrosis factor receptor II fused to an IgG1 Fc domain (TNFRII-Fc). When administered orally and while passing through the digestive tract, the plant cells function as a natural delivery capsule, having the unique attribute of a cellulose cell wall, which makes them resistant to degradation compared to proteins produced via mammalian cell expression systems. The Company expects to report top-line results from this study in the first quarter of 2018.

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"Despite a number of approved treatments for ulcerative colitis, there remains a large unmet medical need in this patient population," said Mr. Moshe Manor, Protalix’s President and Chief Executive Officer. "We look forward to reporting initial results from our phase II study, which may provide proof of concept data not only for OPRX-106 in the treatment of UC, but also for our oral-delivery protein technology. If successful, OPRX-106 will be the first ever oral protein treatment, as currently there are no other oral recombinant protein treatments available."

The phase II clinical trial is a randomized, open label, 2-arm study of OPRX-106 in 19 patients with active mild to moderate ulcerative colitis. Patients have been randomized to receive 2 mg or 8 mg of OPRX-106 protein administered orally, once daily, for 8 weeks. Key efficacy endpoints of the study, in addition to safety, include relevant disease parameters of the drug, including Mayo score and rectal bleeding.

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.

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 Apexian Pharmaceuticals, an Indiana-based clinical stage biotechnology company developing novel compounds to treat cancer, reported that they are closing their Series A round (Press release, Apexian Pharmaceuticals, NOV 29, 2017, View Source [SID1234522371]). This financing follows previous investments as well as numerous grants and awards by the company since its founding. Proceeds will be used to initiate their phase 1 clinical study for APX3330 a novel first in class oral treatment for patients with cancer.

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APX3330, the lead molecule for Apexian has a unique dual biological role targeting the APE1/Ref-1 protein. The APE1 protein is a critical molecular "switch" controlling the activity of cancer regulatory proteins, including transcription factors HIF-1-alpha, STAT3, NF-kappa B, and AP-1. The Investigational New Drug application was issued based on robust non-clinical data and a safety database of over 422 patients in non-cancer studies. In addition, the data identified APE1/Ref-1 protein also plays a critical role in the repair of neuronal DNA that has been damaged through oxidative mechanisms which are common with platinum-containing chemotherapy agents. Apexian has developed robust non-clinical data demonstrating APX3330 prevents and/or reverses such damage and is the basis for pursuing an indication for Chemotherapy Induced Peripheral Neuropathy (CIPN).

Elevate Ventures, a venture development organization based in Indiana, committed funding through their Indiana 21st Century Research & Technology Fund, a direct investment vehicle overseen by the Indiana Economic Development Corporation positioned to support early-stage high-growth companies. "Apexian Pharmaceuticals has an impressive body of preclinical work in an exciting new target to treat cancer," said Elevate Ventures Chief Executive Officer Chris LaMothe. "We look forward to joining other sophisticated investors to see this molecule tested in the clinical setting."

Apexian Pharmaceuticals President and Chief Executive Officer Steve Carchedi commented: "We are very pleased to have an Indiana group, like Elevate Ventures join with others to enable this key data to be generated for our lead molecule. Developing a first-in-class oral molecule to treat pancreatic, colon and other difficult to treat cancers, is at the core of our mission. Cancer patients are truly waiting for novel treatments to attack these deadly diseases."

On November 29, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant and for the targeting and killing of cancer cells, highlighted its planned activity at the upcoming 59th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition being held December 9 – 12, 2017 in Atlanta, Georgia (Press release, Actinium Pharmaceuticals, NOV 29, 2017, View Source [SID1234522298]). Actinium’s Actimab-A Phase 2 trial will be highlighted in a poster presentation that will discuss results to date from the multi-center, open label Phase 2 trial that has been designed to assess overall response rates of patients receiving fractionated doses of Actimab-A. Patients enrolled in this trial are newly diagnosed with acute myeloid leukemia (AML) that are over the age of 60. Preliminary results from the Company’s recently announced Actinium Warhead Enabling (AWE) Technology Program will be presented by poster. The results contrast the superior celling killing power of Actinium-225 labeled daratumumab versus the unlabeled antibody, which is a blockbuster therapy targeting CD38 for patients with multiple myeloma marketed by Johnson & Johnson. In addition, experimental results supporting targeting of the CD33 antigen in multiple myeloma patients that provides the scientific rational for the Actimab-M trial will also be presented in an abstract.

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Details of Actinium’s abstract poster presentations are as follows:

Title: A Phase 2 Study of Actinium-225 (225Ac)-Lintuzumab in Older Patients with Previously Untreated Acute Myeloid Leukemia (AML) Unfit for Intensive Chemotherapy
Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II
Date: Sunday, December 10, 2017
Time: 6:00PM-8:00PM
Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Title: Actinium Labeled Daratumumab Demonstrates Enhanced Killing of Multiple Myeloma Cells over Naked Daratumumab
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster III
Date: Monday, December 11, 2017
Time: 6:00PM-8:00PM
Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

An online abstract has been accepted highlighting experimental results supporting the rationale for targeting CD33 in patients with multiple myeloma, which will be accessible on December 8, 2017. Details for the online abstract are as follows:

Title: CD33 Is Expressed in a Significant Subset of Multiple Myeloma Patients in the US and May Represent a Viable Therapeutic Target
Session: 651. Myeloma: Biology and Pathophysiology, excluding therapy

"This year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition represents an inflection point for Actinium’s clinical development and research progress," said Dr. Mark Berger, Actinium’s Chief Medical Officer. "As shown in our abstract, Actimab-A generated strong response rates exceeding 50% in a tremendously difficult to treat AML patient population as a single agent and I look forward to the detailed results being presented at ASH (Free ASH Whitepaper) via our poster presentation. In addition to its strong efficacy, we have gained further insights into Actimab-A’s safety profile, namely its minimal extramedullary toxicities. I believe that this strength of Actimab-A will allow us to utilize Actimab-A in additional indications where patients have high unmet needs that can be addressed with strong single agent efficacy, a unique mechanism of action and robust myelosuppressive capabilities with minimal effects outside of the hematopoietic system."

Key Highlights of Actinium’s Activities Include:

Poster presentation highlighting data from Actinium’s Phase 2 trial of Actimab-A, a CD33 targeting agent, in patients newly diagnosed with AML unfit for intensive chemotherapy
Poster presentation highlighting new data from Actinium’s recently announced AWE Technology Platform
Abstract supporting the targeting of CD33 in multiple myeloma and the scientific rationale for Actimab-M
The Clinical Advisory Board will review the progress of the multi-center, Phase 2 trial of Actimab-A, Actinium’s CD33 targeting antibody radio-conjugate for AML
The Scientific Advisory Board will review the progress of the Phase 3 Iomab-B SIERRA trial for patients 55 and older with relapsed and refractory AML
Meeting with investigators from the 15 participating SIERRA clinical trial sites
Sandesh Seth, Actinium’s Chairman and CEO said, "This year’s ASH (Free ASH Whitepaper) annual meeting will be the most active in the Company’s history and will showcase Actinium’s strengthened capabilities in clinical development and research and development. I am proud of our team’s ability to leverage our AWE technology platform and drive our drug development strategically. As a result, we have demonstrated the potential of utilizing Actinium-225 with established commercial products as a means of developing biobetters, which we will be offering to potential biopharmaceutical partners. We have also identified via our clinical results additional strengths of our CD33 program. We believe that these findings offer additional clinical opportunities where we can leverage our strengths, experience and know-how in the field of bone marrow transplant and targeted alpha particle therapy. We look forward to the ASH (Free ASH Whitepaper) annual meeting where our clinical and experimental work on Actimab-A, Actimab-M and the AWE platform will be showcased via the posters and publications, and also in our meetings with the scientific and business community. In addition, we look forward to revealing new clinical opportunities at our December 5th Webinar."

About Actimab-A

Actimab-A, Actinium’s most advanced alpha-particle therapy product candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above that are ineligible for standard induction chemotherapy. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer cells. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML in patients 60 and above by the U.S. Food and Drug Administration.

About Actimab-M

Actimab-M is being investigated in patients with refractory multiple myeloma. Multiple myeloma is a currently incurable cancer of plasma cells, which are white blood cells that produce antibodies. Actimab-M is currently being studied in a Phase 1 dose escalation study in up to 12 patients that is designed to establish safety, maximum tolerable dose and proof of concept. Actimab-M consists of actinium-225, an alpha-emitting radioisotope coupled to the anti-CD33 monoclonal antibody, HuM-195. CD33 has been shown to be expressed on myeloma plasmocytes in 25% to 35% of multiple myeloma patients and has also shown to be correlated with poorer outcomes.

About Our AWE Technology Platform

The Actinium Warhead Enabling (AWE) Technology Platform enables a highly potent and selective form of targeted therapy that combines the powerful alpha-emitting radioisotope actinium-225 with targeting agents, which are designed to seek out cancer cells in the body that express particular markers. Actinium-225 emits significant alpha radiation making it a potent treatment modality against targeted cancer cells while limiting damage to healthy tissues as its radiation travels extremely short distances in the body. When labeled to targeting agents, actinium-225 can be delivered directly to cancer cells where the high linear energy transfer resulting from the emission of alpha particles results in irreparable DNA double stranded breaks and ultimately cancer cell death. Despite this superior cell killing power, actinium-225 when delivered in a targeted manner is sparing of the surrounding environment in the body due to the short path length of its alpha-particle radiation and can result in a superior safety profile. Actinium Pharmaceuticals owns or has licensed the rights to several issued and pending patents that pertain to its AWE Technology Platform including technology to manufacture actinium-225 in a cyclotron. In addition, the Company obtains actinium-225 from various sources such as the U.S. Department of Energy at Oak Ridge National Laboratories and has developed considerable know-how, expertise and validated processes related to production of radioimmunoconjugates, management of the supply chain and dealing with various regulatory bodies. The AWE Technology Platform can be utilized to potentially improve the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. via labeling with actinium-225. In addition to increased efficacy, these actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents provide an opportunity to extend intellectual property protection by the creation of "Biobetters" or improved versions of the approved agent. The Company’s Actinium Warhead Enabling (AWE) Program can be accessed by biopharmaceutical companies that are interested in creating Biobetters through the utilization of the AWE Platform Technology. To learn more about the AWE Technology Platform or the AWE Program please contact Keisha Thomas, Ph.D., Corporate Development at [email protected].