Assuming successful completion of required clinical testing and other requirements, the results of the pre-clinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the drug product for one or more indications. Under the Prescription Drug User Fee Act, or PDUFA, as amended, the submission of most NDAs is additionally subject to an application user fee, currently exceeding $2.4 million. PDUFA also imposes an annual prescription drug product program fee for human drugs, currently exceeding $300,000. These fees are typically increased annually.

        As of December 31, 2018, we had used $84.2 million of the net proceeds from our IPO.

Anika Therapeutics Inc. (NasdaqGS: ANIK ) Headquartered in Bedford, Mass., Anika Therapeutics, Inc. develops, manufactures and commercializes therapeutic products for tissue protection, healing and repair. These products are based on hyaluronic acid (HA), a naturally occurring, biocompatible polymer found throughout the body.

QSYQ (Batch number: 20120914) and DO (Batch number: 20121101) were obtained from Tasly Pharmaceutical Co. Ltd. (Tianjin, China). QSYQ was manufactured according to the guidelines of Good Manufacturing Practice and Good Laboratory Practice, and the content of its major components was determined by high performance liquid chromatography. The proportions of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang, DO) in QSYQ are 60%, 30%, 6%, 0.4%, respectively, with the content of ASIV in Astragalus membranaceus being 1.1 mg/g, DLA in Salvia miltiorrhiza being 2.42 mg/g, and R1 in Panax notoginseng being 10 mg/g. QSYQ and DO were dissolved in saline (Beijing Chemical Works, Beijing, China) to make a solution at concentration of 0.2 g/mL21,44 and 0.8 mg/mL, respectively. ASIV, DLA and R1 (purity ≥ 99.9%) were obtained from Fengshanjian Medicine Research Co. Ltd. (Kunming, Yunnan, China), and dissolved in saline to make a solution at concentration of 0.132 mg/mL, 0.848 mg/mL and 0.12 mg/mL, respectively.

Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

There are currently no drugs approved by regulatory authorities for the treatment of NASH. Even though certain drugs, such as insulin sensitizers and antihyperlipidemic agents, are prescribed for some NASH patients, they are not approved for the treatment of NASH and their efficacy has not been proven in adequate and well-controlled clinical studies.

HUVECs (5 × 105 cells/well) in 6-well plates were incubated with or without various concentrations of β-BA. The stimulated NO production was confirmed by laser confocal fluorescent microscopy using a specific dye: 4-amino-5-methylamino-20, 70-difluoro-fluorescein diacetate (DAF-FM DA) (Beyotime, Haimen, China). Optical density was read in a micro plate reader at 540 nm. Each experiment was performed in triplicate. Micrographs were taken by the confocal microscope.

The terms of office and employment of directors (including an officer who is a director but is not a controlling shareholder) further require the approval of the shareholders by a simple majority in addition to the approval of the Compensation Committee and the Board, in that order, and under certain circumstances, a Special Majority; with respect to a chief executive officer or an officer who is a controlling shareholder, the approval of the shareholders must be made by the Special Majority. In addition, under certain circumstances, a company may be exempt from receiving the shareholders’ approval with respect to the Terms of Office and Employment of a non-affiliated candidate for chief executive officer.

The role of CD38 as an adhesion molecule in NK cell antitumor function has been demonstrated in earlier studies26. However, the proposed function of CD38 as an adhesion molecule is not likely, as evidenced by the lack of difference in the formation of conjugates between the tumor and Cd38+/+ and Cd38−/− NK cells (Fig. 2a). Our data reveal that the production of ADPR by CD38 in response to tumor cells was ablated in Cd38−/− NK cells (Fig. 4a), indicating that CD38 was responsible for the production of ADPR in response to tumor cells. Intriguingly, cADPR has been known as a Ca2+ signaling second messenger involved in IL8-induced chemotaxis in lymphokine activate killer cells35. Our data shown in Fig. 4b, which showed no significant increase of cADPR in tumor stimulated NK cells, rule out the possibility that ADPR is produced from cADPR, another one of CD38′s products. This indicates that the interaction with tumor cells through cognate receptors on NK cells transmits signals for the activation of CD38′s NAD glycohydrolase (NADase) to produce ADPR. Further studies will be required to identify the mechanisms regarding how specific enzymatic activities of CD38 are selectively activated under specific situations.

Biel, M., Wahl-Schott, C., Michalakis, S. & Zong, X. Hyperpolarization-activated cation channels: from genes to function. Physiol Rev 89, 847–85 (2009).

Catalent announces investment for its Zydis ODT technology, offering increased drug load and taste-masking capabilities.

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