Our general and administrative expenses amounted to approximately $3.8 million for the year ended December 31, 2017, representing an increase of approximately $0.7 million, or 23%, compared to approximately $3.1 million for the year ended December 31, 2016. The increase primarily resulted from an increase in salaries and benefits expenses of approximately $0.6 million as well as an increase in investor relations and business development expenses of approximately $0.2 million. 

A “Substantial Shareholder” is generally a person who alone, or together with his or her relative or another person who collaborates with him or her on a regular basis, holds, directly or indirectly, at least 10% of any of the “means of control” of a corporation. “Means of control” generally include the right to vote, receive profits, nominate a director or an officer, receive assets upon liquidation or instruct someone who holds any of the aforesaid rights regarding the manner in which he or she is to exercise such right(s), all regardless of the source of such right.

Section 422 of the Code allows employees, directors and officers, who are non-controlling shareholders (e.g., less than 10% shareholders) and are considered residents of the United States or those who are deemed to be residents of the United States for purposes of the payment of tax, or are otherwise subject to taxation in the United States with respect to the grant of awards, to receive favorable tax treatment for compensation in the form of shares or ISOs. 10% shareholders or persons which are not service providers will receive NSOs, which do not entitle them to receive similar tax benefits. Section 422(b) of the Code provides for the ISO track such that the individual does not have to pay ordinary income tax (nor employment taxes) on the difference between the exercise price and the fair market value of the shares issued (however, the holder may have to pay U.S. alternative minimum tax instead). However, if the shares are held for one year from the date of exercise and two years from the date of grant, then the profit (if any) made on sale of the shares is taxed as long-term capital gain. Section 422 of the Code requires that any grant of awards shall not be made at a price which is less than 100% of the fair market value of such awards on the date of the grant, all pursuant to the terms of Section 409A of the Code. However, under this ISO track, we are not allowed to deduct any expense with respect to the issuance of the options or shares. In order to comply with the terms of the ISO track, the option granted thereunder must meet the requirements of Section 422 of the Code when granted and at all times until the exercise thereof.

There is no law of physic that force natural processes to be irreversible as long as they can receive energy from outside. In practice, I agree that most biological processes might be very hard to reverse though.

I agree that the purpose of biotech companies is to make money, whether they have a useful drug or not. From time to time, a few turn out to have a useful drug. For example, I am thinking of CAR-T (Kite, Juno). But no doubt there are lots of scam out there.

        4.     The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:

Some of these persons or entities may have interests different than yours. For example, because many of these stockholders purchased their shares at prices substantially below the current market price and have held their shares for a longer period, they may be more interested in selling our company to an acquirer than other investors or they may want us to pursue strategies that deviate from the interests of other stockholders.

        The FDA may not approve an ANDA for a generic product until any applicable period of non-patent exclusivity for the reference-listed drug has expired. The Federal Food, Drug, and Cosmetic Act, or FDCA, provides a period of five years of non-patent exclusivity for a new drug containing a new chemical entity, or NCE. Specifically, in cases where such exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification that a patent covering the reference-listed drug is either invalid or will not be infringed by the generic product, in which case the applicant may submit its application four years following approval of the reference-listed drug. It is unclear whether the FDA will treat the active ingredients in our product candidates as NCEs and, therefore, afford them five years of NCE data exclusivity if they are approved. If any product we develop does not receive five years of NCE exclusivity, the FDA may approve generic versions of such product three years after its date of approval, subject to the requirement that the ANDA applicant certifies to any patents listed for our products in the Orange Book. Three year exclusivity is given to a drug if the NDA includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the NDA. Manufacturers may seek to launch these generic products following the expiration of the applicable marketing exclusivity period, even if we still have patent protection for our product.

What do you think of Brand’s comment that rapamycin may have a detrimental effect on stem cells? Have you heard of that before Mark?

Combining results of retrieved RCTs indicated a significant reduction in plasma ADMA concentrations following treatment with statins compared with placebo (WMD: − 0.104 μM, 95%CI: − 0.131 to − 0.077, Z = − 7.577, p < 0.0001). Forest plots detailing the meta-analysis of RCTs assessing the impact of statin therapy on plasma ADMA levels is illustrated in Fig. 2. Subgroup analysis revealed a significant impact of hydrophilic statins (rosuvastatin, pravastatin and fluvastatin; n = 403; WMD: − 0.207 μM, 95%CI: − 0.427 to + 0.013, Z = − 7.250, p < 0.0001), and a non-significant effect of hydrophobic statins (simvastatin and atorvastatin; n = 321; WMD: − 0.101 μM, 95%CI: − 0.128 to − 0.074, Z = − 1.845, p = 0.065) (Fig. 3).

Our employees, independent contractors, consultants, collaborators and contract research organizations may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.

Eul, B. et al. Impact of HIF-1alpha and HIF-2alpha on proliferation and migration of human pulmonary artery fibroblasts in hypoxia. FASEB J. 20, 163–165 (2006).