Some interesting excerpts from the 10K:
Page 9:
"We believe that deficient activity or low concentrations of PKCe in aging subjects is one of the main causes of the neurodegeneration seen in AD."
"PKCe activation reverses most, if not all, of the pathological processes leading to the progression of Alzheimer's Disease, and represents a unique singular point for therapeutic intervention which could arrest further development of the disease in either early or late stage patients"
Page 10:
"The morphology of the damaged neurons in these animal models looks strikingly different after they are treated with experimental drugs that activate PKCe. The new growth of dendritic trees on the damaged neurons creates a multiplicity of new synaptic connections, basically re-wiring the damaged neurons and restoring their function. Earlier therapeutic intervention with a PKCe activator produces markedly improved outcomes in tests measuring restored animal cognitive function."
Page 11:
"Upon activation, PKCe migrates from the intraneuronal cytoplasm to the cell membrane, where it activates signal-regulating enzymes (specifically the m-RNA stabilizing protein, HUD, and downstream growth factors such as BDNF, NGF, IGF, etc.; MAP kinases Erk1/2; the BCl-2 apoptosis cascade; and NF-?ß), causing a series of changes leading to increased DNA transcription, synaptic maturation, a consequent increase in levels of growth factor proteins (such as nerve growth factor and brain-derived neurotrophic factor), an inhibition of programmed cell-death and a reduction of ß amyloid, and hyperphosphorylated tau."
Page 12:
"CRE has developed a new chemical family of polyunsaturated fatty acid (“PUFA”) analogs, which appear to be effective in the activation of PKCe."
"These molecules activate PKCe by binding to two different and distinct active sites on the enzyme. The natural ligands that bind to these sites are diacylglycerol and phosphatidylserine. Bryostatin acts as a mimetic (mimic) for diacylglycerol by binding to the diacylglycerol site and, similarly, the PUFA analogs act as mimetics for phosphatidylserine by binding to the phosphatidylserine site."
Page 28:
"We believe we are the only company currently pursuing PKCe activation (with consequent prevention of neuronal death and induction synaptic network growth) as a mechanism to treat AD and neurodegenerative disease. Although we believe that we have no direct competitors working in this same field at the present time, we cannot provide assurance that our competitors will not discover compounds or processes that may be competitive with our products and introduce such products or processes before us."
Page 29:
"While we anticipate our current cash resources on hand will be sufficient to sustain operations and a follow-on clinical trial for the next approximately 18 months, we do not have sufficient capital to complete all necessary clinical trials in order to have a product approvable for commercial sale. As a result, we will need to raise additional capital and/or obtain a strategic partner to facilitate bringing a product to market."
Page 33:
"We currently do not have an FDA approved manufacturing facility. We expect to rely on contract manufacturers to produce quantities of products and substances necessary for product commercialization."
Page 34:
"We currently have no experience in sales, marketing or distribution. We do not anticipate having the resources in the foreseeable future to allocate to the sales and marketing of our proposed products. As a result, if our product development is successful, our future success will likely depend, in part, on our ability to enter into and maintain collaborative relationships with one or more third parties for sales, marketing or distribution, on the collaborator’s strategic interest in the products we have under development and on such collaborator’s ability to successfully market and sell any such products. We intend to pursue collaborative arrangements regarding the sales and marketing of our products as appropriate."
Page 36:
"The pressure to grow revenues while containing the escalating costs of basic research and development has resulted in an increase in mergers and acquisitions in our industry. More consolidation in the pharmaceutical industry is expected over the next five years. We could become an acquisition target by a larger competitor and, as a consequence, suffer serious disruptions to our business model or even lose control of our ability to operate as an independent entity."
"There is currently a limited public market for shares of our common stock, and an active trading market may not continue to develop or be maintained. Our common stock has been listed on The Nasdaq Capital Market since March 29, 2017 and was quoted on the OTC Market prior to such time. The average daily trading volume in our common stock was approximately 40,000 shares during the 90-day period ended February 28, 2018. If an active market for our common stock does not continue to develop or is not sustained, it may be difficult for investors to sell shares without depressing the market price for the shares, or at all."
Page 40:
"Since May 17, 2017, two purported class action lawsuits have been commenced in the United States District Court for the Southern District of New York (the “NY Litigation”). On August 10, 2017, the lawsuits were consolidated and Plaintiffs filed their Amended Consolidated Complaint on October 9, 2017. The Amended Consolidated Complaint names as defendants us, our former Chief Executive Officer and our co-founder and President/Chief Scientific Officer. The lawsuit alleges violations of the Securities Exchange Act of 1934, as amended, in connection with allegedly false and misleading statements made by us in certain press releases and in our Annual Report on Form 10-K relating to the results stemming from our Phase 2 clinical trial for bryostatin. Plaintiffs seek, among other things, damages for purchasers of our securities between January 7, 2016 and July 18, 2017. Because each of the pending actions is in the early stages, no reasonable estimate of possible loss, if any, can be made.
We and our directors and officers believe that this action is without merit and intend to defend the lawsuit vigorously. On November 21, 2017 we and the other named defendants filed a motion to dismiss all of the claims. The motion to dismiss is now fully briefed and we await a decision from the Court."
Page 48:
"We have formed and are advancing our discussions with an experienced clinical advisory board to assist us with protocol development for a planned Phase 2a study in FXS patients. We seek resources to initiate the first clinical trial with bryostatin in patients with FXS. We have been granted orphan drug designation by the FDA for the use of bryostatin in the treatment of Fragile X Syndrome."
Page 52:
"As of February 28, 2018, we have paid WCT approximately $9 million relating to our recent Phase 2 clinical trial. We estimate that we will pay an additional approximately $750,000.
As of February 28, 2018, we had approximately $15.2 million in cash, cash equivalents. We expect that our existing capital resources will be sufficient to support our projected operating requirements for approximately the next 18 months, including the continuing development of bryostatin, our novel drug targeting the activation of PKC epsilon. Funds are anticipated to be used to complete the current Phase 2 study treating moderate to severe Alzheimer's patients, plus the potential initiation of a follow-on clinical study treating patients similar to those in our most recent Phase 2 study. We also plan to possibly initiate an open label study in Fragile X syndrome. The balance of the funds will be used for general corporate and working capital purposes."
