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The aggregate compensation, including share-based compensation, paid by us to all of our Office Holders as a group, with respect to the year ended December 31, 2018, was approximately $ִ3.7 million. This amount includes approximately $0.3 million set aside or accrued to provide pension, severance, retirement, vacation or similar benefits or expenses, but does not include business travel, relocation, professional and business association dues and expenses reimbursed to Office Holders, and other benefits commonly reimbursed or paid by companies in our industry. In addition to the eight members of the Board (including the Company’s President and Chief Executive), the Company considers six other individuals, namely the former Chairman of the Board, Chief Medical Officer, Chief Scientist Officer, Chief Financial Officer, Chief Operating Officer and the former VP, Legal and Strategy, to have been Office Holders in 2018.

        Upon approval of an ANDA, the FDA indicates whether the generic product is "therapeutically equivalent" to the RLD in its publication "Approved Drug Products with Therapeutic Equivalence Evaluations," also referred to as the "Orange Book." Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable for the RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the prescribing physician or patient.

        Further, conducting clinical trials in foreign countries, as we have previously done and plan to continue to do for our product candidates, presents additional risks that may delay completion of our clinical trials. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as political and economic risks relevant to such foreign countries.

Qin, W. et al. TGF-beta/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. Journal of the American Society of Nephrology: JASN. 22, 1462–1474 (2011).

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The following table presents the aggregate fees for professional services rendered by such accountants to us during their respective term as our principal accountants in 2018 and 2017.

Graeff, R. M., Franco, L., De Flora, A. & Lee, H. C. Cyclic GMP-dependent and -independent effects on the synthesis of the calcium messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate. J. Biol. Chem. 273, 118–125 (1998).

Adherex Technologies Inc. (OTCPK:ADHXF ) (TSX: AHX.TO ) Adherex Technologies Inc. is a biopharmaceutical company dedicated to the discovery and development of novel cancer therapeutics. We are in the business of solving problems for patients with cancer. We have multiple products in the clinical stage of development, including eniluracil, ADH-1 and sodium thiosulfate (STS). Eniluracil, an oral dihydropyrimidine dehydrogenase (DPD) inhibitor, is being developed to improve the tolerability and effectiveness of 5-fluorouracil (5-FU), one of the most widely used oncology drugs in the world. ADH-1 is a biotechnology compound which selectively targets N-cadherin, a protein present on certain tumor cells and the blood vessels of solid tumors. STS is a chemoprotectant being developed to reduce or prevent hearing loss that may result from treatment with platinum-based chemotherapy drugs. With a diversified portfolio of unique preclinical and clinical-stage cancer compounds and a management team with expertise in identifying, developing and commercializing novel cancer therapeutics, Adherex aims to become a leader in developing innovative treatments that address important unmet medical needs in cancer.

Rybin, V. O., Xu, X., Lisanti, M. P. & Steinberg, S. F. Differential targeting of beta -adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway. J Biol Chem 275, 41447–57 (2000).

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Rosca, M. G., Tandler, B. & Hoppel, C. L. Mitochondria in cardiac hypertrophy and heart failure. J. Mol. Cell. Cardiol. 55, 31–41, 10.1016/j.yjmcc.2012.09.002 (2013).

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(a) Schematic diagram illustrating the preparation procedure: (1) The pyrolytic carbon is formed on the PE substrate by argon plasma treatment (6.14 × 1015 ions/cm2) for 10 minutes to obtain the PAr sample and (2) The targeted nitrogen functionalities are generated by nitrogen PIII and the sample is designated as PArN. (b) Raman spectra of PE, PAr, and PArN, suggesting the formation of pyrolytic carbon structure after argon plasma treatment. (c) ATR-FTIR spectra of PE, PAr, and PArN. Some C = N and C≡N bonds are not detected at about 1650 cm−1 and 2230 cm−1. (d) Deconvoluted XPS spectra revealing that C = C, CN and CNO bonds are formed on PArN. (e) TOF-SIMS negative ion spectra of PE, PAr, and PArN, further showing CN-, CNO- and C3N- fragments attributable to C-N(C)-C and N-C = O, and but little C = N and C≡N. (f) KFM analysis showing the relative surface potential of PE, PAr, and PArN as follows: PE = 410 ± 12.2 mV; Par = 337 ± 12.5 mV, and PArN = 301 ± 7.7 mV.

In addition, no person may serve as an external director if: (i) the person’s other positions or other business activities create, or may create, a conflict of interest with the person’s service as an external director or interfere with the person’s ability to serve as an external director; (ii) at the time such person serves as a non-external director of another company on whose board of directors a director of the reciprocal company serves as an external director; (iii) the person is an employee of the Israel Securities Authority or of an Israeli stock exchange; (iv) such person or such person’s relative, partner, employer or anyone to whom such person is directly or indirectly subordinate, or any entity under such person’s control, has business or professional relations with any person or entity he or she should not be affiliated with, as described above, unless such relations are negligible; or (v) such person received compensation, directly or indirectly, in connection with such person’s services as an external director, other than as permitted under the Companies Law and the regulations promulgated thereunder. If, at the time of election of an external director, all other directors who are not controlling shareholders of such company or their relatives, are of the same gender, then the designated external director must be of the other gender.


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