RE:MDMA? ARE MY ETES DECEIVING ME OR IS THIS OLD FILINGS? from page 8:
The BETonMACE trial included a subgroup of patients with CKD stage 3 or worse (eGFR below 60) (n=263). Evaluation of this prespecified subgroup illustrated a significant reduction in the primary endpoint. The treatment effect in the CKD group showed a hazard ratio of 0.50 (95% CI 0.26-0.92, p=0.03). Similar to the BETonMACE study population as a whole, a statistical reduction in hospitalization for CHF was observed in this subgroup (hazard ratio 0.36, 95% CI 0.14-0.93, p=0.04). The proportion of CKD patients was 11%, lower than anticipated (possibly because of competing trials) which compares to 25-29% from similar DM post-ACS populations.
The effect of BET inhibition with apabetalone in patients with impaired renal function and the results of BETonMACE CKD subgroup validates the need to continue the clinical development of apabetalone in patients with high-risk CVD and a CKD comorbidity, an area of critical unmet need. With leading experts on our renal clinical and scientific advisory board providing input and guidance, we continue to consider conducting additional clinical trials in this therapeutic area.
from pages 8 & 9:
The BETonMACE trial included an exploratory assessment of cognition in patients over the age of 70 years (n=469). The results from this prespecified cognition assessment were announced on December 2, 2019 and presented on December 5, 2019 at the Clinical Trials on Alzheimer's Disease (“CtAD”) Congress 2019. Cognition was assessed in BETonMACE using the Montreal Cognitive Assessment (“MoCA”) which was designed as a rapid screening instrument for mild cognitive dysfunction. The test assesses eight different cognitive domains including attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Given that BETonMACE patients are recent ACS, DM patients with low HDL, the assumption is that dementia in this population is largely due to vascular cognitive impairment. In patients with a baseline MoCA below 22 (defined as mild to severe cognitive impairment), apabetalone treatment was associated with significant improvements versus placebo (mean change from baseline of 3.0 units in the apabetalone treatment group compared to 1.2 units in placebo group, p=0.02).
Further exploratory analysis of archived plasma samples planned for additional cognitive dysfunction markers including amyloid burden with plasma AB42/40 ratio, ApoE isoform, YKL40 and Neurofilament light are planned. Early observations on BET inhibition to modulate cognitive function in elderly patients with high-risk cardiovascular disease and DM warrant more research to address this critical unmet need. Preclinical analyses of brain-derived cell lines and animal models of neuroinflammation are currently being pursued. With leading experts on our neurodegenerative clinical and scientific advisory board providing input and guidance, we continue to consider conducting additional clinical trials in this therapeutic area.
Cash Burn Rate
The average monthly Cash Burn Rate, a non-IFRS measure as described on page 2 herein, for the three and six months ended October 31, 2019 was $2.2 million and $2.5 million, respectively (2018 - $3.2 million and $2.9 million, respectively), reflecting lower clinical development costs associated with the BETonMACE trial as it neared completion.
Liquidity We are a development stage company; our primary capital requirements relate to funding research and development activities, including preclinical and clinical trials, and for general working capital purposes. Our operations have been financed in recent years primarily through the sale of common shares or units (consisting of common shares and warrants) and secured indebtedness. Our primary objective when managing capital is to ensure we have sufficient funds available to carry out our research, development and commercialization programs based, in part, on continuous monitoring. As at October 31, 2019, we had $0.2 million of cash. We need to raise additional capital or we may be forced to cease operations, and to fund research, development and corporate activites within the next year. As at October 31, 2019, we were committed to pay $9.5 million of trade and other payables and $1.3 million for research and development. Furthermore, our $12.0 million debenture with Vision Leader is due on September 26, 2020. In addition, aggregate expenditures over the next twelve months under agreements with contract research organizations and central laboratories that conducted BETonMACE and other trials are estimated to total up to approximately $2 - 3 million. Our average monthly Cash Burn Rate, a non-IFRS measure, as described on page 2 herein, for the six months ended October 31, 2019 was $2.5 million. Our historical Cash Burn Rate is not indicative of our future Cash Burn Rate. Our Cash Burn Rate has decreased compared to the prior period, reflecting that the BETonMACE trial is nearing completion. Based on our planned short-term business operations, including the completion of BETonMACE, we expect our Cash Burn Rate to continue to decline. Our medium-term Cash Burn Rate will be dependent on the Company’s business operations. Our cash as at October 31, 2019, in combination with the $1.3 million raised subsequently, is not sufficient to fund our contractual commitments or our planned business operations over the next year and repay our $12.0 million debenture. We will have to raise additional capital. If we are not able to raise capital, we may be forced to cease operations. These conditions result in a material uncertainty which may cast significant doubt on our ability to continue as a going concern. We continue discussions for regional licensing opportunities with potential pharma partners including Hepalink.
We will continue to pursue and examine both non-dilutive and dilutive arrangements, with a preference for non-dilutive alternatives, in the following priority: co-development, licensing, rights (on indications or potential follow-on compounds, for instance) or other partnering arrangements, private placements and/or public offerings (equity and/or debt). However, there is no assurance that these arrangements will be completed.
from page 21:
The results of the BETonMACE study validate the need to continue the clinical development of apabetalone in patients with high-risk CVD, an area of critical unmet need. Novel medications capable of reducing this residual risk are urgently needed; therefore, apabetalone represents a novel and potentially more effective approach to this clinical issue. Based on the results of the BETonMACE study, breakthrough therapy status filings for both the FDA and EMA is underway. Additionally, partnership discussions based on the results from the BETonMACE study, including the synergistic finding with new classes of anti-diabetic therapies, the pronounced effect on patients with CKD stages 3 or worse, the improvement in cognition in cognitively impaired patients and the observed effect on CHF are ongoing. Appropriate IP filings are ongoing.
page 22
We are a development stage company. If we do not develop commercially successful products, we may be forced to cease operations.
We are a development stage company, which may require significant additional investment for research and development, manufacturing, clinical testing, and regulatory submissions prior to commercialization. Investors must evaluate our business in light of the uncertainties and complexities affecting a development stage biotechnology company and there can be no assurance that any such product will eventually be developed. Any product would be unsuccessful if it:
• does not demonstrate acceptable safety and efficacy in preclinical studies and clinical trials or otherwise does not meet applicable regulatory standards for approval;
• does not offer therapeutic or other improvements over existing drugs used to treat the same or similar conditions;
• is not capable of being produced in commercial quantities at an acceptable cost, or at all; or
• is not accepted by patients, the medical community or third party payors.
There are more risk factors listed