Celgene Corporation (NasdaqGS CELG ) Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.

Yes, I agree! Since others have mentioned Einstein as the greatest scientist ever (I wont debate that), we know that he denied that black holes were possible as late as 1939, 78 years ago. He changed his mind later of course, when he had more “facts”/data.

        Patients with MG present with muscle weakness that becomes increasingly severe with repeated use and recovers with rest. Weakness can be localized to specific muscles, such as those responsible for eye movements, but often progresses to affect a broader range, including head, limb, and respiratory muscles. This progression is often described as the generalized, or severe, form of the disease. gMG is estimated to affect approximately 60,000 people in the U.S. alone. gMG symptoms may become life-threatening when muscle weakness involves the diaphragm and intercostal muscles in the chest wall that are responsible for breathing. The most severe complication of gMG, known as myasthenic crisis, requires hospitalization, intubation, and mechanical ventilation.

        We are developing specific inhibitors of Factor D, a critical component of the alternative pathway of complement, as targeted drug candidates for C3GN. By blocking the alternative pathway upstream of C3, we believe that this mechanism may prevent C3 deposition and subsequent renal injury.

        At the inception of each arrangement that includes precommercial milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant cumulative revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control, such as regulatory approvals, are not considered probable of being achieved until the uncertainty related to the milestone is resolved. The transaction price is then allocated to each performance obligation on a relative selling price basis, for which the Company recognizes revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, the Company reevaluates the probability of achievement of such development milestones and any related constraint, and if necessary, adjust its estimate of the overall transaction price.

AVAX Technologies Inc. (OTCPK: AVXT ) AVAX Technologies, Inc. is a biotechnology company with operations in the United States and Europe. The Company is engaged in the research and clinical and commercial development of biological products and cancer therapeutics. The Company’s AC Vaccine platform is a therapeutic cancer vaccine. In addition, the Company performs contract-manufacturing services for biological products for other pharmaceutical and biotechnology companies.

Topologically, HCN channels are members of the pore-loop cation channel superfamily, with each subunit containing 6 transmembrane α-helices (S1–S6), a re-entrant loop between the S5 and S6 helices that forms the selectivity filter, and a C-terminal cyclic-nucleotide binding domain (CNBD) attached to the S6 via an 80 amino acid C-linker. Channels are formed by homo- or hetero-tetrameric assembly of the subunits16. Electrophysiological recordings of HCN channels have characteristic properties, including activation with sigmoidal kinetics upon membrane hyperpolarization, a lack of voltage-dependent inactivation, conduction of Na+ and K+, a shift in the activation curve as a result of direct interaction with cAMP and cGMP, and inhibition by millimolar concentrations of external Cs+17. The activation kinetics of the four mammalian isoforms vary by several fold, and differ from one another in their response to cyclic nucleotides. cAMP shifts the voltage-dependence of activation in HCN2 and HCN4 by +15 mV, while HCN1 and HCN3 are only weakly modulated by cAMP2,18,19,20.

Janatuinen, T. et al. Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults. Vascular medicine 8, 185–189 (2003).

To evaluate the possibility that TRPM2-mediated Ca2+ signaling is required for the antitumor effector function of NK cells, we first examined the tumor-induced Ca2+ change in NK cells from TRPM2+/+ and TRPM2−/− mice. We noticed robust Ca2+ signals in both TRPM2+/+ and TRPM2−/− NK cells upon contact with B16F10 cells, a melanoma tumor cell line. However, TRPM2+/+ NK cells were distinct from TRPM2−/− NK cells in their ability to sustain the Ca2+ signals. TRPM2+/+ NK cells exhibited a rapid initial increase, after which the elevated levels remained for the duration of our measurement (500 s). In contrast, TRPM2−/− NK cells were not able to sustain the initial intracellular [Ca2+] ([Ca2+]i) rise (Fig. 1a; 31.5% of area under curve (AUC) of Ca2+ trace in TRPM2+/+ NK cells). As [Ca2+]i increase is important to the degranulation of NK cells7, we investigated whether TRPM2 was involved in degranulation activity. We compared the surface expression of CD107a in TRPM2+/+ and TRPM2−/− NK cells following stimulation with B16F10. B16F10-induced degranulation was absent in TRPM2−/− NK cells (Fig. 1b). Tumor cell-induced granzyme B secretion and cytotoxicity were also completely absent in TRPM2−/− NK cells (Fig. 1c and d). We further evaluated the ability of TRPM2 to protect against B16F10 tumor growth in vivo. Consistent with our finding that TRPM2−/− NK cells have decreased cytolytic activity (Fig. 1d), we observed a defect in the ability of TRPM2 deficient mice to control B16F10 tumor formation and their consequent survival rates (Fig. 1e and f). These results suggest that TRPM2 channel-mediated Ca2+ signals are critical for the antitumor effect of NK cells.

        As of December 31, 2018, we had 72 full-time or part-time employees, including 28 employees with M.D. or Ph.D. degrees. Of these employees, 58 employees are engaged in research and development activities and 14 employees are engaged in general and administrative activities. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider the relationship with our employees to be good.

        We, and any future collaborators, are not permitted to commercialize, market, promote or sell any product candidate in the U.S. without obtaining marketing approval from the FDA. Foreign regulatory authorities, such as the EMA, impose similar requirements. We have not previously submitted an NDA to the FDA or similar drug approval filings to comparable foreign regulatory authorities for any of our product candidates. We, and any future collaborators, must complete extensive pre-clinical development and clinical trials to demonstrate the safety and efficacy of our product candidates in humans before we will be able to obtain these approvals.

“We’re continuing to investigate and take action to protect patient health and safety from products in this angiotensin II receptor blocker class that have been found to have dangerous impurities. As part of that investigation, we’ve uncovered serious manufacturing violations at ZHP, which is one of the manufacturing facilities that has been linked to these products. The issues cited in the warning letter are associated with the nitrosamine impurities found in these drugs, and these violations reveal a disturbing lack of oversight at this API manufacturer that puts patients at risk,” said FDA Commissioner Scott Gottlieb, in a press statement announcing the warning letter.