On September 13, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), reported that the Company and its collaborators from the University of Texas MD Anderson Cancer Center presented new data in a research poster entitled "Activity of dianhydrogalactitol (VAL-083) in ovarian tumor models, sensitive or resistant to cisplatin" at the 11th Biennial Ovarian Cancer Research Symposium (Press release, DelMar Pharmaceuticals, SEP 13, 2016, View Source [SID:SID1234515118]).

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The data, presented on the evening of Monday, September 12th at the Rivkin Center for Ovarian Cancer in Seattle, Washington, support a distinct mechanism of action for VAL-083 versus platinum-based chemotherapy currently used in the treatment of ovarian cancer.

"We were pleased to present these data, which are highly supportive of VAL-083’s potential as a new therapeutic option for ovarian cancer patients whose treatment is underserved by currently available therapy. We plan to work with our advisors to develop a strategy to advance VAL-083 into clinical trials for the treatment of ovarian cancer, either as a single-agent or in combination with other approved agents," said Jeffrey Bacha, Chairman & CEO of DelMar.

The researchers also reported observations of synergy when VAL-083 was combined with platinum-based chemotherapy or PARP inhibitors and that the potency of VAL-083 is increased when a cell’s homologous recombination ("HR") DNA repair mechanism is impaired, further suggesting that VAL-083-induced DNA lesions are repaired via the HR pathway.

Dr. Dennis Brown, DelMar’s Chief Scientific Officer noted, "These data are important because they provide further support of our previous research suggesting that VAL-083 imparts its anti-cancer activity via double-strand breaks as a result of DNA cross-links at the N7-position of guanine. Homologous recombination is the mechanism generally employed by cells to repair damage resulting from DNA double strand breaks. Deficiencies in HR are a hallmark of many cancers, including ovarian cancers, while normal cells retain HR function. This may explain why VAL-083 has been observed to possess high activity against cancer yet exhibit limited toxicity against normal cells."

In summary,

VAL-083 demonstrated cytotoxic activity against all ovarian cancer cell lines tested and is substantially less dependent on wild-type p53 for cytotoxic activity.
VAL-083 was able to circumvent 70-85% of cisplatin-resistance in an ovarian cancer cell line panel with several known p53 mutations and displays synergy with cisplatin in p53 mutant cell line H1975.
VAL-083 demonstrated synergy with AstraZeneca’s PARP inhibitor Olaparib in ovarian cancer cell line A2780.
The potency of VAL-083 activity was increased when HR was impaired in A2870 cells with BRCA1 knockdown, demonstrating that VAL-083 induced DNA-lesions are repaired via HR.
"Taken together, these results support VAL-083’s potential as a treatment option for ovarian cancer patients failing platinum-based therapy particularly in an HR-impaired setting. They further suggest a potential benefit of therapeutic combination regimens containing VAL-083 plus platinum-based chemotherapy or VAL-083 in combination with a PARP inhibitor such as Olaparib," concluded Mr. Bacha.

VAL-083 is a "first-in-class" small-molecule chemotherapeutic that demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia in prior clinical trials sponsored by the US National Cancer Institutes both as a single-agent and in combination with other treatments. DelMar recently announced completion of Phase I/II clinical trials with VAL-083 as a potential treatment for refractory glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. The Company plans to advance VAL-083 into a pivotal Phase III clinical trial for refractory GBM and also plans to advance VAL-083 into clinical trials for other solid tumors such as non-small cell lung cancer and ovarian cancer.

In April 2016, the FDA Office of Orphan Products Development (OOPD) granted orphan drug designation for VAL-083 in the treatment of ovarian cancer. VAL-083 had earlier received an orphan designation for glioma and medulloblastoma in the United States and for glioma in Europe.

DelMar CEO to Present Today at 18th Annual Rodman & Renshaw Global Investment Conference in New York

Jeffrey Bacha, DelMar’s president and CEO, will deliver a corporate address today at the 18th Annual Rodman & Renshaw Global Investment Conference. Mr. Bacha’s presentation is scheduled for 10:50-11:15 AM Eastern Time in the Kennedy II Ballroom at the Lotte New York Palace Hotel. A live webcast of the presentation will be available by accessing a link that will be posted on the Company’s website (www.DelMarPharma.com). A webcast replay will be available approximately two hours after the presentation ends and will be accessible for one month.

About Ovarian Cancer

According to Evaluate Pharma, the annual market for ovarian cancer therapies is expected to reach approximately $570 million in 2016, and is projected to grow to more than $3.5 billion in 2022. The American Cancer Society estimates that approximately 22,000 women will receive a new diagnosis of ovarian cancer and approximately 14,000 women will die from ovarian cancer in the United States each year. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system.

Ovarian cancers are commonly treated with a platinum-based chemotherapy regimen. Initial tumor response rates are relatively high; however, as up to 75% of ovarian cancer patients who respond to initial treatment will relapse within approximately 18 months after completing first-line therapy. In published studies, median survival in platinum-resistant recurrent ovarian cancer patients ranged from six to nine months.

On September 12, 2016 Circle Pharma, Inc., reported that it will apply its computational design and synthetic chemistry platform to design and create a physical screening library of novel macrocyclicpeptides (Press release, Circle Pharma, SEP 12, 2016, View Source [SID1234635670]). Once completed, the library is initially expected to comprise several hundred macrocycles that will be designed to potentially disrupt bioactive conformations commonly found in protein-protein interactions known to drive disease processes, and will deploy backbone scaffolds screened in silica for intrinsic cell permeability characteristics. In addition, the design of the library will permit the simple creation of derivative libraries tailored to specific features of a therapeutic target class.

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PfizerInc.(NYSE:PFE) has entered into an agreement with Circle under which Pfizer will provide support for the library build, and Circle has granted Pfizer non-exclusive rights to screen the library against certaintargets. The rights granted to Pfizer exclude specified targets for which Circle has reserved exclusive rights to screen the library.

"This physical library will complement Circle’s target-specific computational design toolkit," said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "We expect to use the library for our internal pipeline discovery work, and we will make it available to all of our collaboration partners in drug discovery."

About Macrocyclic Peptides

Macrocyclic peptides have the potential to provide access to the large proportion of therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. Inparticular, 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 to this point by the need for a greater understanding of how to design macrocycles with appropriate pharm acokinetics, cell permeability and oral bioavailability. As a result, most clinical-stage macro cyclic peptide drugs address extracellular protein targets because of the challenge of identifying cell permeable macrocycles. The ability to design potent macrocycles with intrinsic permeability is expected to give access to a large number of important therapeutic targets that have been out of reach to this point.

(Filing, 10-K, DelMar Pharmaceuticals, 2015, SEP 12, 2016, View Source [SID:SID1234515115])

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On September 12, 2016 Horizon Pharma plc (NASDAQ:HZNP) and Raptor Pharmaceutical Corp. (NASDAQ:RPTP) reported the companies have entered into a definitive agreement under which Horizon Pharma will acquire all of the issued and outstanding shares of Raptor Pharmaceutical Corp. common stock for $9.00 per share in cash, for an implied fully diluted equity value of approximately $800 million (Press release, Raptor Pharmaceutical, SEP 12, 2016, View Source [SID:SID1234515206]). The transaction is expected to close in the fourth quarter of 2016.

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"The proposed acquisition of Raptor furthers our commitment to helping people with rare diseases and is a significant step in advancing our strategy to expand our rare disease business," said Timothy P. Walbert, chairman, president and chief executive officer, Horizon Pharma plc. "Along with the potential for accelerated revenue growth, the addition of Raptor strengthens our U.S. orphan business and provides a platform to expand our orphan business in Europe and other key international markets. We look forward to working with new patient communities and building on the success of the Raptor team."

Strategic and financial benefits of the transaction:

Strengthens Horizon’s focus on rare diseases and provides expansion into Europe and other international markets.
Adds PROCYSBI delayed-release capsules and QUINSAIR (aerosolized form of levofloxacin) global rights, with PROCYSBI having strong patent protection through 2034.
Diversifies revenue with 11 medicines across three business units: orphan, rheumatology and primary care.
Bolsters rare disease revenue, which in the first half of 2016 on a pro-forma basis was 45 percent of total Horizon Pharma revenue.
Expected to be accretive to adjusted EBITDA in 2017.
"This transaction will deliver significant and immediate value to our shareholders through a compelling all-cash premium and provide ongoing value to our patients, their families and the physicians who treat them," said Julie Anne Smith, president and chief executive officer, Raptor Pharmaceutical Corp. "On behalf of the Board and management team, I extend our deepest gratitude to everyone at Raptor for their unrelenting commitment to advancing the development of our medicines and their tireless work with the patients we serve."

PROCYSBI is the first cystine-depleting agent given every 12 hours that is approved in the United States for the treatment of nephropathic cystinosis (NC), a rare metabolic disorder, in adults and children 2 years of age and older. PROCYSBI received European Commission approval as an orphan medicinal product in September 2013 for the treatment of proven NC. According to estimates, NC prevalence is as high as 1 in 100,000 live births. There are believed to be approximately 550 NC patients in the United States and 2,000 worldwide.

QUINSAIR is a proprietary inhaled formulation of levofloxacin, approved in the European Union and Canada for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in adult patients with cystic fibrosis. Cystic fibrosis is a rare, life-threatening, genetic disease affecting an estimated 21,000 adults in Europe and Canada. QUINSAIR is not approved in the United States.

Raptor’s previously disclosed total net sales guidance for full-year 2016 is $125 million to $135 million, which includes both PROCYSBI and QUINSAIR. Horizon will provide additional detail regarding its guidance for full year 2017 net sales and adjusted EBITDA in the first quarter 2017.

Transaction Terms and Approvals
The acquisition is structured as an all cash tender offer for all the issued and outstanding shares of Raptor common stock at a price of $9.00 per share followed by a merger in which each remaining untendered share of Raptor common stock would be converted into the $9.00 per share cash consideration paid in the tender offer. The transaction, which has been unanimously approved by the boards of directors of both companies, is subject to the satisfaction of customary closing conditions and regulatory approvals, including antitrust approval in the United States.

Financing
Horizon intends to finance the transaction through $675 million of external debt along with cash on hand. The company has put in place fully committed financing with BofA Merrill Lynch, JPMorgan Chase Bank, N.A., Jefferies Finance LLC, and Cowen Structured Holdings, an affiliate of Cowen and Co. LLC. As of June 30, 2016, the company had $424.5 million of cash and cash equivalents on its balance sheet.

Advisors
MTS Health Partners L.P. and Citigroup Global Markets Inc. are co-lead financial advisors to Horizon Pharma in the transaction. BofA Merrill Lynch, J.P. Morgan, Jefferies LLC and Cowen and Company, LLC are financial advisors to Horizon Pharma in the transaction. Horizon Pharma’s legal advisors are Cooley LLP and McCann FitzGerald.

Centerview Partners LLC and Leerink Partners LLC are financial advisors to Raptor Pharmaceutical Corp. in the transaction. Raptor Pharmaceutical Corp.’s legal advisor is Latham & Watkins LLP.

Conference Call Today at 8 a.m. ET
At 8 a.m. Eastern Time today, Horizon’s management will host a conference call and live audio webcast to review the transaction and related matters. The live webcast and a replay may be accessed by visiting the investor relations section of the Horizon website at View Source Please connect to the company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call 1-888-338-8373 (U.S.) or 1-973-872-3000 (international) to listen to the conference call. The conference ID number for the live call is 80632193. Telephone replay will be available approximately two hours after the call. To access the replay, please call 1-855-859-2056 (U.S.) or (404) 537-3406 (international). The conference ID number for the replay is 80632193. An archived version of the webcast will be available for at least one week on the investor relations section of the Horizon website at View Source

About PROCYSBI
PROCYSBI is approved in the United States for the treatment of nephropathic cystinosis in adults and children 2 years of age and older. In Europe, PROCYSBI gastro-resistant hard capsules of cysteamine (as mercaptamine bitartrate) received European Commission approval as an orphan medicinal product in September 2013 for the treatment of proven nephropathic cystinosis.

PROCYSBI acts within the lysosome, converting cystine into cysteine and a cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis. Adherence to treatment regimens is associated with improved outcomes, but the timing of doses is critical, as cystine levels can rise quickly if patients delay, miss, or stop taking their prescribed treatment regimen. PROCYSBI is contraindicated in patients with a hypersensitivity to cysteamine or penicillamine. The most commonly reported side effects are vomiting, nausea, abdominal pain, breath odor, diarrhea, skin odor, fatigue, rash and headache.

About Nephropathic Cystinosis
Nephropathic cystinosis is an inherited autosomal-recessive disease affecting lysosomal storage processes within cells; the amino acid cystine is not transported out of the lysosome, but instead accumulates and eventually crystallizes within the lysosomal lumen. Without treatment, high intracellular cystine concentrations can occur in virtually all organs and tissues, leading to irreversible cellular damage, progressive multi-organ failure and death.

About QUINSAIR
QUINSAIR is a proprietary inhaled formulation of levofloxacin, approved in the EU and in Canada for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in adult patients with cystic fibrosis. QUINSAIR, a twice-daily treatment, contains an aerosolized form of levofloxacin, a broad-spectrum fluoroquinolone antibiotic with proven activity against a wide range of both gram-negative and gram-positive bacteria. The fluoroquinolones rapidly inhibit replication and transcription of bacterial DNA, which leads to bacterial cell death. QUINSAIR is not approved in the United States.

QUINSAIR is contraindicated in patients with hypersensitivity to levofloxacin, a history of tendon disorders related to fluoroquinolones, epilepsy or who may be pregnant or breast feeding. The safety profile of QUINSAIR has been evaluated in two double-blind, placebo-controlled studies and in an active comparator study in which the most frequently reported adverse reactions were cough/productive cough, dysgeusia and fatigue/asthenia.

About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening, genetic disease affecting an estimated 21,000 adults in Europe and Canada. Cystic fibrosis causes persistent lung infections due to the buildup of thick, sticky mucus in the lungs and progressively limits the patient’s ability to breathe. The lung infections are mostly caused by bacteria with 75 percent of cystic fibrosis patients suffering from chronic pseudomonas aeruginosa infections.