On December 21, 2016 Circle Pharma, Inc. reported a Series A financing round in which it has issued over $4.5M of shares of Series A Preferred Stock (Press release, Circle Pharma, DEC 21, 2016, View Source [SID1234635669]). The financing was led by Mission Bay Capital, with Pfizer Inc. (NYSE:PFE), ShangPharma Investment Group, Ltd. and a syndicated group of individual investors joining the round. In connection with the financing, Walter H. Moos, Ph.D., representing ShangPharma, has joined the Circle Board of Directors.

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"We are delighted with the participation of such high caliber investors in our first equity round," said David J. Earp, J.D., Ph.D., Circle’s president and CEO. "With our seed funding, we established Circle’s computational design platform, advanced our synthetic chemistry capabilities in collaboration with ChemPartner, and engaged in a target-based collaboration with Pfizer. The Series A funds will be used to support Circle’s therapeutic pipeline, which is focused on intracellular protein-protein interactions that are key drivers in oncogenic pathways. We are also now building a physical library of cell- permeable macrocycles to augment our computational design tools, and this library will later be available to our collaboration partners. We are particularly excited to welcome Walter Moos to our Board of Directors. Dr. Moos brings a wealth of life sciences R&D experience, having served most recently as the president of SRI Biosciences and previously in senior executive roles at MitoKor, Chiron and Warner-Lambert/Parke-Davis. His teams have advanced numerous pharmaceutical products from discovery to commercialization, and we are fortunate to have him join Circle."

"I am very much looking forward to taking an active role on Circle’s board," said Walter Moos. "The combination of innovative technology and the great team at Circle could help unlock high value targets that have long been considered out of reach of drug developers."

Dr. Moos has served on about 20 business and scientific boards, including Amunix, Oncologic (Aduro), Onyx (Amgen), Rigel and the Biotechnology Industry Organization (BIO).

About Macrocyclic Peptides

Macrocyclic peptides have the potential to allow drug developers to address the large proportion of known therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. In particular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited by the need for a greater understanding of how to develop macrocycles with appropriate pharmacokinetics, cell permeability and oral bioavailability. Circle’s ability to design potent macrocycles with intrinsic cell permeability could unlock access to challenging, high value therapeutic targets that have been out of reach to other approaches.

On December 12, 2016 Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, reported a new strategic collaboration with Celgene Corporation (Press release, Triphase Accelerator, DEC 21, 2016, View Source [SID1234529641]). Under the Agreement, Celgene has an option to acquire all Triphase Accelerator’s assets relating to TRPH-222 (CD22-4AP), an antibody-drug conjugate in development for lymphoma.

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Pursuant to the Agreement, Triphase Accelerator received an upfront payment from Celgene. Triphase Accelerator will control development and will retain all commercial rights to TRPH-222 (CD22-4AP). If Celgene exercises its option to acquire TRPH-222 (CD22-4AP), Celgene will become responsible for development and commercialization, and Triphase Accelerator will be eligible to receive development, regulatory and sales milestone payments. This is the third product option deal between Triphase Accelerator and Celgene.

"This collaboration is important to Triphase Accelerator in multiple ways. First, it continues to solidify the relationship we have developed over time with Celgene. They have been a valued collaborator to us and we are grateful. Just as importantly, it continues to validate our business model of acquiring early-stage assets and applying our methodology to accelerate programs through the proof-of-concept phase and into the clinic," said Mohit Trikha, Ph.D., chief scientific officer, Head of Triphase Accelerator. "As we continue to acquire and develop new assets, we look forward to finding new ways to demonstrate how our approach is uniquely science based, efficient, and cost-effective, with the ultimate goal to help patients."

TRPH-222 is a novel, site-specific antibody-drug conjugate (ADC) targeting CD22, a B-cell-restricted sialogycoprotein that is an important modulator of B-cell signaling and survival, which is expressed on nearly all B-cell malignancies. CD22 is a validated ADC target for Non-Hodgkin’s lymphoma and acute lymphoid leukemia. The compound itself combines a site-specific modified humanized antibody conjugated to a toxin payload and a 4AP linker.

"We have enjoyed a long-standing relationship with Triphase Accelerator and believe in their approach to drug development," said Celgene’s President of Hematology Oncology, Michael Pehl. "This latest agreement, which closely follows our acquisition of their marizomib asset, represents our confidence in their approach to drug development, and we look forward to a continued collaboration with the company."

On December 21, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported that, following a recent independent Data and Safety Monitoring Board (DSMB) recommendation and subsequent futility analysis, it has decided to stop the Phase 2 HERMIONE study of MM-302 (HER2 antibody-targeted liposomal doxorubicin) in HER2-positive metastatic breast cancer patients who had previously been treated with trastuzumab (Herceptin), pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1, Kadcyla) (Press release, Merrimack, DEC 21, 2016, View Source [SID1234517147]).

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The decision to stop the trial was made following the DSMB’s opinion that continuing would be unlikely to demonstrate benefit over the comparator treatments. Subsequent to this recommendation, a futility assessment was performed that confirmed the DSMB’s opinion. Both the treatment and control arms were found to have shorter than expected median progression free survival.

Importantly, there were no new or unexpected safety concerns. Patients currently enrolled in the trial may choose to continue on their assigned treatment based upon discussion with their study physician.

"Late line HER2-positive breast cancer is very difficult to treat, especially in this new and previously unstudied group of patients who appear to experience rapid cancer progression following treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine," said Istvan Molnar, MD, Vice President of Clinical Development at Merrimack Pharmaceuticals. "While we are disappointed with this outcome, we would like to thank the study Steering Committee, the investigators and, most importantly, the patients who participated in the HERMIONE trial. We will report our learnings from this study at a later date."

In light of this development, Merrimack now expects to provide further details about MM-302, as well as the results of its full pipeline review, in January.

On December 21, 2016 Exosome Diagnostics, Inc. reported data that sets a new standard for EGFR-T790M resistance mutation detection in lung cancer, with the highest sensitivity reported to date (Press release, Exosome Diagnostics, DEC 21, 2016, View Source [SID1234517160]). This test is being developed to improve care and outcomes for the large population of patients who can benefit from second line EGFR Tyrosine Kinase Inhibitor (TKI) therapy but are missed with currently available tissue and liquid biopsy tests. Clinical validation data from a cohort of 160 patients, the largest of its kind in this patient population, was presented in plenary session during the recent AACR (Free AACR Whitepaper)-EORTC-NCI meeting in Munich, Germany. ExoDx Lung(T790M) has been optimally designed for ExosomeDx’s high throughput biomarker testing platform that is being deployed in 2017.

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Twenty percent of non-small cell lung cancer (NSCLC) patients test positive for an EGFR driver mutation (approximately 45,000 patients in the U.S. alone) and receive EGFR TKI therapy. Unfortunately, most will develop a resistance to EGFR TKI therapy. Tissue biopsies are the current standard for identifying T790M resistance. If a patient tests positive, they are eligible for treatment with a second line EGFR TKI therapy. Unfortunately, a tissue biopsy is not always a viable option for a large percentage of these patients.

Non-invasive liquid biopsies have emerged as a viable alternative for patients unable to have tissue biopsy procedure. Clinical studies have demonstrated that the FDA approved cobas test for liquid biopsy, only identifies 59% of patients who will respond to a second line EGFR TKI therapy. This is a direct result of lack of sensitivity and inability to test challenging intrathoracic disease. By analyzing exosomal RNA (exoRNA) and cell free tumor DNA (ctDNA) from the same sample Exosome Dx addresses current limitations by identifying 96% of the T790M positive population, with no loss of sensitivity in patients with intrathoracic disease.

"EGFR T790M mutations have previously been challenging for liquid biopsy assays. In this clinical study, we show that ExoDx Lung(T790M) has a higher clinical sensitivity and specificity than what has been reported to date for the FDA cleared test distributed by Roche. This study further demonstrates the power of our ExoLution Plus platform that combines exoRNA plus ctDNA. This result was not surprising since we have shown superior performance to ctDNA across several disease states in blinded head to head studies. Clinical samples are precious so we are thrilled to be able to offer a more sensitive test that take both exoRNA and ctDNA into consideration,"stated Dr. Johan Skog, Chief Scientific Officer at Exosome Diagnostics.
The test is the latest in a series of biofluids based diagnostic and companion diagnostic biomarker tests being developed by Exosome Diagnostics to potentially aid in therapy selection and patient monitoring in oncology and other diseases.

To assure future access to the company’s novel biomarker tests worldwide, Exosome Diagnostics also announced that it has developed a high throughput version of its proprietary ExoLution Plus system to prepare samples that can be analyzed with exoRNA and cfDNA analysis test kits. This system utilizes Exosome Diagnostics’ patented technology and has been developed with high throughput capability to be integrated with leading clinical laboratory analytical systems including those marketed by Roche and Thermo Fisher

"This data illustrates one of the many indications for which Exosome Diagnostics can leverage its extremely sensitive liquid biopsy technology to improve patients’ lives by guiding therapy, where other technologies could not in a reliable fashion" stated John Boyce, President and CEO of Exosome Diagnostics. "Exosome Diagnostics has proven that its technology is extremely robust and can scale on a variety of existing commercial platforms in diagnostic laboratories," Boyce continued.

On December 20 2016 Opsona Therapeutics Ltd (‘Opsona’), the innate immune drug development company focused on novel therapeutic approaches to treat oncology, autoimmune and other inflammatory diseases, reported the preliminary results from its ongoing prospective, open label Phase I/II study being conducted with OPN-305 in secondline lower (Low and intermediate-1) risk myelodysplastic syndrome (MDS) which created interest when presented recently at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego by Prof Garcia-Manero from the MD Anderson Cancer Center (Press release, Opsona Therapeutics, DEC 20, 2016, View Source;n=154&a=130 [SID1234517143]).

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OPN-305 is a novel proprietary humanized IgG4 monoclonal antibody (MAb) against Toll-Like Receptor 2 (TLR2), a key target within the innate immune system. Opsona has recently received orphan drug designation from the United States Food and Drug Administration for MDS.

The study in patients with lower risk, red cell transfusion dependent, MDS who have failed hypomethylating agents (HMA) ± an erythropoiesis stimulating agent is ongoing in collaboration with MD Anderson Cancer Center in Houston USA with additional sites now being added in the USA.

As of December 2016, 24 eligible patients have been enrolled, 11 at 5 mg dose and 13 at 10 mg/kg. A total of 15 (75%) patients are evaluable for response. Hematological improvement has been seen in 53% (8/15) with 3 (20%) patients achieving transfusion independence and of these 2/5 (40%) were receiving 10 mg/kg while on OPN-305 monotherapy. 12 patients remain on study.

Median age was 72 years (range 42-87). Nine (43 %) patients were classified as Low risk and 15 (63%) as Intermediate-1 risk by IPSS. Thirteen patients (61%) had diploid cytogenetics, 8 (38%) RAEB,5 (23%) RCMD, 3 (14%) RA, 2 (10%) RARS, and 1 (4%) 5q-, RCMD-RS, CMML.

The median number of prior HMA therapies was 2 (range 1-4) with a median duration of prior therapies from time of diagnosis to enrollment of 22.7 months (range 6.3-56.1). The median number of OPN-305 cycles administered is 5 (2-22) with 5 of 9 (55.5%) patients having received azacitidine add-back after 16 weeks of OPN-305 monotherapy. A total of 5 (29%) patients developed AEs related to OPN-305 all grade 1 with gastrointestinal disorders being the most frequent (23.5%). At this point, no significant drug related toxicity or unexpected infectious complications have been seen and combination with azacitidine has been well tolerated.

To date three (20%) patients were taken off study due to progression to AML and 4 (27%) due to no response all at the 5 mg/kg dose. There is no evidence of treatment related anti-drug antibodies or statistically significant dynamic changes in cytokines in any of the patients.

Myelodysplastic syndromes are a complex and heterogeneous group of bone marrow failure disorders characterized by ineffective hematopoiesis and poor prognosis. There is an urgent need for the development of well tolerated, novel therapies in the treatment of MDS which can delay progression, improve patient survival and quality of life and reduce the social and economic burden of transfusion dependence.

Commenting on today’s announcement Mary Reilly VP Pharmaceutical Development & Operations said "OPN-305 data emerging in this heavily pre-treated group of patients is very encouraging, the unmet need for a safe and tolerable product for this patient population is significant and we are happy to be in collaboration with the MD Anderson Cancer Center one of the leading clinical center’s in this hematological area"