On March 31, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported positive preclinical findings generated using the Company’s Immune Repertoire Capture technology, presented at the Gordon Research Conference: Antibody Biology & Engineering, which took place in Galveston, TX, March 20-25, 2016 (Press release, Atreca, MAR 31, 2016, View Source [SID1234522967]). In a poster titled, "Protective Anti-Malarial Human Antibodies identified from P. falciparum CSP Immunized Kymice using Immune Repertoire Capture (IRC)", a research team including scientists at Atreca and collaborators at leading institutions reported key preclinical research findings, including:

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Atreca’s Immune Repertoire Capture technology applied in combination with Kymab’s Kymice, an Ig-gene humanized mouse platform, identified and generated potent antibodies comprised of human variable genes.
•Atreca identified diverse lineages (or families) of antibodies that bind to a key target, the circumsporozoite protein (CSP) of P. falciparum. Two of these lineages provided potent protection in an in vivo malaria-challenge model, resulting in >99% reduction of liver-stage parasite load.
Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research, stated, "IRC enabled identification of multiple lineages containing potent, anti-malarial human antibodies generated by activated mouse B cells. The diversified antibody library that we generated had a high hit rate of binding against the CSP target (34%). Our analyses also provide the foundation for understanding structure-activity relationships that mediate the binding of the antibodies that are efficacious in vivo. Furthermore, we have identified many other antibody sequences in these and other lineages that are highly similar to the efficacious antibodies and may therefore also be active in vivo."

Dr. Emerling continued, "We are grateful to both the Bill & Melinda Gates Foundation and the PATH Malaria Vaccine Initiative for supporting this critical research."

"These results disclosed at the Gordon Conference demonstrate the ability of Atreca’s Immune Repertoire Capture technology to generate novel antibodies with high in vivo potency from immune responses, as well as multiple lineages containing such antibodies," commented Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "While our primary focus continues to be on cancer immunotherapy, our IRC technology allows us to mine the key phenomenon driving efficacious immune responses in humans and animals in diverse disease settings, including infectious and autoimmune diseases."

Atreca recently reported use of its Immune Repertoire Capture technology to analyze the successful anti-tumor responses in individuals with non-progressing lung adenocarcinoma. Based on this and related research, select antibodies discovered by Atreca have progressed to preclinical testing in in vivo models of cancer, with the goal of selecting candidates to enter into more advanced preclinical studies.

On March 31, 2016 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted therapies for cancer and diabetes using its live-cell encapsulation technology, Cell-in-a-Box, reported the final design of its clinical trial for patients with advanced pancreatic cancer (Press release, PharmaCyte Biotech, MAR 31, 2016, View Source [SID:1234510778]). The clinical trial design was developed with Translational Drug Development (TD2), America’s premier oncology Contract Research Organization, as well as with renowned pancreatic cancer specialists consulting with PharmaCyte.

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, stated, "The trial is designed to determine if PharmaCyte’s pancreatic cancer treatment (the combination of micro-capsules that contain genetically modified human cells which convert the cancer prodrug ifosfamide into its "cancer-killing" form at one-third the normal dose) can satisfy a clear unmet medical need that exists for patients with locally advanced, inoperable pancreatic cancer who no longer respond to the current standard of care. Most of these patients are initially treated with the combination of nab-paclitaxel (Abraxane) plus gemcitabine or the four-drug combination known as FOLFIRINOX. When these patients’ tumors no longer respond to treatment with these regimens, the next standard of care offers little to no benefit. It is then that these patients are often treated with the combination of the anticancer drug capecitabine plus radiation therapy. However, this combination is only marginally effective in stopping the progression of the disease. In PharmaCyte’s clinical trial, our pancreatic cancer therapy will be compared "head to head" with the capecitabine/radiation combination to demonstrate that it is clearly superior in treating these patients while maintaining a superior quality of life during the therapy."

Major factors in the overall trial design are:

The clinical trial will be international (United States, Europe and possibly Australia), multi-site, open-label and randomized.

Study sites under consideration in the United States include the Mayo Clinic in Scottsdale, Arizona, the Beth Israel Deaconess Cancer Center and the Dana-Farber Cancer Institute both in Boston, Massachusetts, the Baylor Cancer Center in Dallas, Texas, the City of Hope Cancer Center in Los Angeles, California, and sites in Germany and Spain.

The randomization ratio of patients between the two study groups will be 1:1 (an equal number of patients will be randomly assigned to the capecitabine + radiation group and the PharmaCyte pancreatic cancer therapy group).

As many as 84 patients will be required to complete the study, although fewer may be required based upon the data developed during the trial.

Only patients who have locally advanced, non-metastatic, inoperable cancers and whose tumors no longer respond after 4-6 months of treatment with either the nab-paclitaxel (Abraxane) + gemcitabine or FOLFIRINOX regimens will be eligible for the study.

Unlike the earlier clinical trials using PharmaCyte’s pancreatic cancer therapy where patients received only two doses of ifosfamide, multiple cycles of ifosfamide will be given to those being treated with PharmaCyte’s pancreatic cancer therapy. This will continue until the patients’ tumors no longer respond to PharmaCyte’s therapy or until treatment-related toxicity accumulates to unacceptable levels.
Mr. Waggoner concluded, "We feel that the major factors that needed to be considered for the development of a complete clinical trial protocol have now been addressed. Of course, as we continue to move toward our clinical trial, slight changes that benefit the overall trial design could certainly be addressed and lead to further refinement of the trial. Special appreciation for reaching this point must be given to the renowned pancreatic cancer experts who have played such a major role in the trial design. With these developments, we are yet another step closer to the commencement of our clinical trial which we believe will satisfy the clear unmet medical need experienced by patients with locally advanced, but inoperable, pancreatic cancer who no longer respond to the gold standard of care."

On March 31, 2016 Cancer Research UK reported that scientists have discovered why a curable type of children’s brain tumour is so responsive to chemotherapy – paving the way to improve treatment of tumours that are harder to tackle, according to research by a Cancer Research UK scientist published in Cancer Cell* (Press release, Cancer Research UK, MAR 31, 2016, View Source [SID:1234510278]).

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"This could make chemotherapy even more effective and reduce the amount of radiation that we give to children." – Professor Richard Gilbertson
This study shows that a curable type of brain tumour in children – called WNT medulloblastoma** – grows ‘leaky’ blood vessels that allow much higher than normal levels of chemotherapy drugs to reach the cancer cells.

Healthy blood vessels in the brain can filter potentially damaging molecules and prevent them from reaching brain tissue. But this can also restricts drugs from reaching tumour cells in the brain.

But in a tumour with leaky blood vessels, like certain types of medulloblastoma, these molecules cannot be kept out.

Understanding why curable tumours are easier to treat could help find more effective treatments for less curable types of medulloblastoma. For these patients, researchers think they might be able to turn this barrier off and make the tumours more responsive to chemotherapy.

Professor Richard Gilbertson, lead author who has recently joined Cancer Research UK’s Cambridge Institute, said: "This research is exciting because it means that as well as finding kinder treatments for a curable type of brain tumour, we may also be able to manipulate brain tumours that are difficult to treat successfully to make them more responsive to treatment.

"This could make chemotherapy even more effective and reduce the amount of radiation that we give to children. This would mean fewer long term side effects for children later in life which is something we’re always working towards."

Professor Pamela Kearns, Cancer Research UK’s children’s cancers expert, said: "This research gives us valuable insight into why some brain tumours respond better to chemotherapy than others. While cancer survival overall has doubled over the past 40 years, treatments for brain tumours have seen much slower progress. And brain tumours in children remain a major challenge.

"Cancer Research UK have made these challenges areas of priority and set up a specific Kids & Teens campaign to increase the investment in research focussed on children’s cancers. More research is needed to help us find ways to diagnose and treat the disease earlier and develop more effective treatments that have less of the long term side effects that can have a major impact throughout a child’s adult life."

This research was funded by ALSAC and the National Cancer Institute and carried out at St Jude Children’s Research Hospital.

On March 31, 2016 Medtronic plc (NYSE: MDT) reported that the U.S. Food and Drug Administration (FDA) cleared PillCam(TM) COLON 2 capsule for an expanded indication for use (Press release, Medtronic, MAR 31, 2016, View Source;p=RssLanding&cat=news&id=2152086 [SID:1234510245]). The PillCam(TM) COLON 2 capsule is the only non-invasive diagnostic test that directly visualizes the colon for the evaluation of polyps in patients who are at major risks for colonoscopy or moderate sedation. The PillCam(TM) capsule- a vitamin-sized capsule endoscope that is taken orally – does not require sedation, anesthesia or radiation, which makes it a more convenient procedure than other invasive colon exams.

This expanded indication is for the detection of colon polyps in patients with evidence of gastrointestinal bleeding of lower gastrointestinal (Gl) origin. This applies only to patients with major risks for colonoscopy or moderate sedation, but who could tolerate colonoscopy and moderate sedation in the event a clinically significant colon abnormality was identified on capsule endoscopy.

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Colon cancer is the third most commonly diagnosed cancer and second leading cause of cancer death in both men and women combined in the U.S. An estimated 136,000 people will be diagnosed with colorectal cancer each year, but when it is caught at a localized stage, the overall 5-year survival rate is 90%.[i]

According to Gastrointestinal Endoscopy, 14 million colonoscopiesare performed in the U.S. each year – of these, more than 3 million are performed for lower GI bleeding, and 600 thousand of those patients are at elevated risk for complications. [ii] [iii]
"The ability to offer PillCam COLON capsule to an expanded patient group represents a significant breakthrough in GI healthcare," said Douglas Rex, M.D., Distinguished Professor of Medicine and Chancellor’s Professor, Indiana University School of Medicine and Director of Endoscopy, IU Health University Hospital. "The new indication allows gastroenterologists to provide their at-risk patients with a non-invasive and radiation free alternative to traditional colonoscopy."

"We are committed to the early detection and treatment of chronic GI diseases and cancers. We are pleased with the FDA’s decision to clear this expanded indication for PillCam(TM) COLON capsule which will provide access to more patients who can benefit from this technology," said Vafa Jamali, president, Early Technologies business in the Medtronic Minimally Invasive Therapies Group.

PillCam(TM) COLON 2 capsule was previously cleared by the FDA for visualization of the colon and the detection of colon polyps in patients following an incomplete colonoscopy with adequate preparation, and a complete evaluation of the colon was not technically possible. The PillCam(TM) capsule technology may also limit the risk of complications that could occur from a standard colonoscopy, such as colon perforation, bleeding or cardio-pulmonary complications.

On March 31, 2016 Marina Biotech, Inc. (OTCQB: MRNA), a leading nucleic acid-based drug discovery and development company focused on rare diseases, reported year-end corporate highlights and financial results for 2015 (Filing, Annual, Marina Biotech, 2015, MAR 31, 2016, View Source [SID:1234510244]).

"During 2015, we continued to see the clinical advancement of our SMARTICLES delivery technology through licensees ProNAi Therapeutics and Mirna Therapeutics, as well as the expansion of our intellectual property estate with key patent issuances in the U.S., Europe and Japan," stated J. Michael French, president and chief executive officer of Marina Biotech. "In addition, the past few months have presented us with some great traction within the nucleic acid sector. We recently entered into two agreements that will advanced our delivery technologies in the emerging field of gene editing. These two transactions represent the first opportunity to prove that our SMARTICLES technology would effectively deliver these types of novel compounds. Although these are not the transformative transactions that we anticipated closing in 2015, these transactions continue to build downstream success-based milestones and royalties for the company."

Mr. French continued, "Although we have pursued, and continue to pursue, additional licensing and partnering opportunities, our limited cash runway necessitated the initiation of a formal process to identify potential strategic partners to allow for the continued advancement of our proprietary nucleic acid drug discovery platform and clinical pipeline. The proposed sale of our RNA assets to Microlin Bio, with whom we entered into a term sheet in March 2016, provides such an opportunity. We believe that our proprietary chemistries and delivery technologies are best suited for development of therapeutic compounds that modulate non-coding RNA. Therefore, we feel strongly that these technologies are synergistic and complimentary to Microlin’s novel microRNA assets and that Microlin is in a stronger position to advance these assets. As we go through this process with Microlin, we will continue to pursue licensing and partnering opportunities in order to increase value to our shareholders."

KEY 2015 AND RECENT ACTIVTIIES

· Sale of RNA assets to Microlin Bio, Inc.
o In March 2016, we announced that we had entered into a term sheet whereby Microlin Bio, Inc. would acquire Marina’s nucleic acid therapeutics assets for 6.7 million shares of Microlin’s common stock and approximately $1 million in cash. Microlin’s purchase of Marina’s nucleic acid therapeutics assets is expected to close by July 1, 2016, pending execution of a definitive asset purchase agreement and the satisfaction or waiver of customary closing conditions, including the approval by Marina’s stockholders and the completion by Microlin of a financing yielding aggregate gross proceeds of not less than $5 million.
· Established two transactions for the delivery of gene-editing approaches

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o In March 2016, we announced the execution of two agreements – an Option Agreement and a Licensing Agreement – for the delivery of gene-editing cargoes. In both cases, our partners were private and declined to disclose their names and their proprietary gene-editing approach. The Licensing Agreement provided Marina with an upfront amount which funds our continued operations through June 2016.

· Fast Track designation for CEQ508 for the treatment of Familial Adenomatous Polyposis

o In August 2015, we announced that CEQ508 had received Fast Track designation from the U.S. Food and Drug Administration. Fast Track is a process designed by the FDA to facilitate the development, and expedite the review of new drugs to treat serious conditions and fill an unmet medical need. Fast Track designated drugs are eligible for more frequent communication with the FDA and may receive Accelerated Approval and Priority Review.
· Continued clinical advancement of our SMARTICLES nucleic acid delivery technology

o In May 2015, we announced that our licensee, Mirna Therapeutics, reported that a molecular analysis of white blood cells from patients treated with MRX34 showed a dose dependent repression of several key oncogenes previously identified as direct miR-34 targets including FOXP1, BCL2, HDAC1 and CTNNB1. These data suggest delivery of miR-34 into human white blood cells and engagement of several biological targets of miR-34. The complete data were presented at the 2015 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April 2015.

o In November 2015, our licensee, ProNAi Therapeutics, enrolled the first patient into the "Brighton" study, a Phase 2 clinical trial evaluating PNT2258 in patients with Richter’s transformation. The international multi-center trial is expected to enroll approximately 50 patients with this rare form of cancer for which there are currently no approved therapies. PNT2258 is one of two nucleic acid-based therapeutics in clinical development which are formulated with our proprietary SMARTICLES delivery technology.
· Availability of Conformationally Restricted Nucleotide amidites for further development

o In September 2015, we announced a License Agreement with Hongene Biotechnology whereby Hongene will develop, supply and commercialize certain oligonucleotide amidites using Marina’s Conformationally Restricted Nucleotide (CRN) chemistry. Marina will receive royalties from the sale of CRN-based reagents.

KEY 2015 AND RECENT IP ISSUANCES AND ALLOWANCES

· SMARTICLES
o Patent allowance in Europe (EP No. 07856910.0) which broadly covers SMARTICLES amphoteric liposomes made with a wide range of novel sterol amphiphiles.

o Patent allowance in Canada (Canada Pat No. 2,665,783) which covers processes for making a broad range of amphoteric liposomes, including the SMARTICLES formulation – Nov340 – currently in Phase 1 and Phase 2 clinical studies.

o Patent allowance in Japan (Pat No. 2010-528325) covering delivery technologies based on SMARTICLES amphoteric liposomes adapted for the release of therapeutic cargos, including Marina’s RNA-based therapeutics having conformationally restricted nucleotides.

o Patent allowance in Japan (Pat No 2012-518924) covering lipid assemblies composed of novel imino compounds with a broad range of the charge ratios between the cationic and anionic amphiphiles.

· transKingdom RNAi

o Patent issuance in the United States (Pat No 9,012,213) expanding upon the nature of the fundamental invasive bacterium for delivering RNA therapeutics, as well as the specific sequence and function of the prokaryotic promoter contained within the delivery plasmid. The tkRNAi technology has existing patent protection in Europe, Japan, Korea, Australia, and Canada.

· Di-terminal Amino Acid Lipids

o Patent issuance in Japan (Patent No. 2012-538001) covering DILA2 compounds having double bonds in chains on each terminus of the amino acid, a preferred structure for lipid packing and liposome formation.

o Patent issuance in Israel (Israel Ser. No. 201785) broadly covering DILA2 compounds, as well as compositions containing therapeutic nucleic acids, and uses for delivering drugs to cells, tissues, organs, and subjects having a wide range of diseases.

o Patent issuance in Europe (EP Patent 2,349,210) broadly covering the synthesis and formation of liposomes for RNA delivery utilizing DILA2 molecules. Marina has filed continuing coverage for additional formulations with other lipids, for example, the lipids for our SMARTICLES technology.

o Patent allowance and issuance in Japan (Pat No. 2014-021044) covers a broad genus of histidine-based DILA2 molecules, as well as compositions containing therapeutic nucleic acids and uses thereof in gene silencing and treating disease.

· Lipopeptide Delivery Technologies

o Patent issuances in the United States (Pat No 8,299,236) covering Marina’s peptide-enhanced delivery formulations.

o Patent issuance in Europe (EP Pat No 2,145,957) covering Marina’s peptide-enhanced delivery formulations.

o Patent issuance in United States (Pat No 9,220,785) covering part of Marina’s proprietary lipopeptide delivery technology; the claims of which cover lipopeptide compounds effective for delivery, as well as pharmaceutical compositions thereof, and methods for gene silencing.

2015 FINANCIAL RESULTS

Cash
At December 31, 2015, we had cash of $0.7 million compared to $1.8 million at December 31, 2014..

Net Income (Loss)
Net income for the year ended December 31, 2015 was $3.3 million compared to a net loss of $6.5 million for the year ended December 31, 2014. This change was due primarily to changes in the fair value of certain warrant liabilities and derivatives, interest expense charges in 2014, and increased operating expenses related to limited growth of business operations in 2015. Operating losses for the year ended December 31, 2015 increased slightly from $3.5 million for the year ended December 31, 2014, to $4.0 million for the year ended December 31, 2015.

Revenue
Revenue of $0.7 million was recorded for the year ended December 31, 2015 from milestone payments with Mirna Therapeutics and MiNA Therapeutics, compared to revenues of $0.5 million representing the upfront fee for execution of the MiNA licensing agreement during the year ended December 31, 2014.

Operating Expenses
Research and development (R&D) expense increased slightly from $0.7 million for the year ended December 31, 2014, to $0.8 million for the year ended December 31, 2015. R&D expenses were primarily related to increased preclinical and clinical development expenses, as well as an increase in sublicense fees. General and administrative (G&A) costs increased from $3.3 million for the year ended December 31, 2014 to $3.9 million for the year ended December 31, 2015. G&A increases were primarily due to an increase in legal fees for corporate legal services, SEC filings, patent filings and licensing activities, as well as an increase in stock-based compensation expenses, partially offset by a decrease in travel-related costs.

Other Income and Expense
Net other income and expense increased from $3.0 million in the year ended December 31, 2014 to $7.3 million for the year ended December 31, 2015. Net other income in 2015 relates to the change in the fair value liability for price adjustable warrants. Net other expense in 2014 relates primarily to changes in fair value measurements of certain liabilities of $2.5 million for the year ended December 31, 2014. These changes in fair value are related to stock price changes over each period impacting the fair value of certain liabilities and derivatives. Additionally, we recorded an expense of $1.0 million related to the fair value of an embedded feature in the Series C Convertible Preferred Stock recorded as interest expense and a $0.5 million gain on settled liabilities in the year ended December 31, 2014.