MITIGATION OF CARDIAC SIDE EFFECTS

Signpath has developed a unique, patented platform technology that makes existing drugs safer by eliminating the cardiac side effects. This platform is referred to as the CorreQT technology. The lead CorreQT compound in development is SPP4040. SPP4040 is a lipid-based drug which is administered orally. In vivo testing of SPP4040, in rats, guinea pigs, and rabbits, has shown that administration of SPP4040 concomitantly with a target drug which causes cardiac arrhythmia, will eliminate the dangerous arrhythmia side effect induced by the target drug. This mitigation of cardiac arrhythmia has been observed in conjunction with various classes of compounds, including anti-cancer agents, antibiotics, antipsychotics, antihistamines and other drugs. To date, SPP4040 has been successful in eliminating QT prolongation when given in combination with every target drug tested (more than30 different drugs.)

More Details

180+

FDA Approved Drugs are known to cause cardiac arrhythmia

2

Issued US patents protecting the CorreQT technology

$10+

Estimated market size for the first five CorreQT drugs

Chart A

Increasing oral doses of Moxifloxacin induced dose-dependent QTc prolongation in guinea pigs, as they do in human patients. (Moxifloxacin is the standard for QTc prolongation assessment in clinical trials, due to its highly predictable dose-response curve.) Since a 30-ms QTc prolongation increases the risk of Torsades de Pointes significantly in these animals, it was selected as the threshold for pro-arrhythmic concern. In identical experiments, Moxifloxacin was administered concomitantly with oral SPP4040 at a 1:1 ratio. The guinea pigs exhibited negligible (almost 0 ms) QT prolongation when dosed with the two compounds.

Chart B & C

Monitoring of QTc prolongation by 20 mg/kg oral Moxifloxacin with, and without, 20 mg/kg oral SPP4040. Moxifloxacin caused a maximal QTc prolongation of 25-30 ms approximately 2-hours post-dose; The effect was transient in guinea pig, but sustained in rabbits. In contrast, Moxifloxacin failed to prolong the QTc over the entire 6 hours of monitoring in animals having been dosed with SPP4040, confirming the successful mitigation of QTc prolongation by Moxifloxacin, a drug renowned for its predictable QTc prolonging abilities. Importantly because SPP4040 requires some enteric metabolism, the effect was also observed in rabbits, which are characterized by a more human-like gastro intestinal function than guinea pigs.

Clinical Strategy

Signpath intends to initiate a Phase 1 human safety trial for SPP4040 in 2018 with the Phase 2 trial following in Q1, 2019. If this technology proves to be successful, we believe Signpath will be uniquely positioned to take advantage of the large market opportunity for improved drugs with safer cardiac profiles.

Development of this platform technology is significantly lower risk than typical drug development.

Signpath can improve drugs with proven efficacy but which are limited by cardiac arrhythmia side effects. Clinical testing is focused on a single, objectively measurable safety side effect (QT prolongation.) There is no significant competition in this arena. No other companies have drugs which treat broad-spectrum drug-induced cardiac arrhythmia. Cardiac arrhythmia animal models are highly correlated with human results (as high as 90%.)

Signpath has broad, issued patents which provide protection in this field.

Signpath has two issued US patents that cover the use of the CorreQT technology for the treatment of cardiac arrhythmia. Signpath has numerous other US and foreign patents pending in this field.

Development and Commercialization Pathway

We do not intend to sell SPP4040 as a separate therapeutic for general use in preventing drug induced cardiac arrhythmias. Our strategy is to combine SPP4040 with known pro-arrhythmic target drugs to create improved, safer versions of these target drugs. We will market these proprietary improved drugs as safer replacements for their pro-arrhythmic predecessors.

There are two primary reasons why Signpath has adopted a strategy of co-formulation/coadministration with specific targets rather than trying to market SPP4040 as a stand-alone antiarrhythmia drug. The first reason is based on regulatory considerations. Our regulatory assessment leads us to conclude that it would be difficult or impossible to obtain a broad regulatory approval for SPP4040 for general use in alleviating drug-induced cardiac arrhythmia.

We anticipate that we will need to do human clinical trials for each target QT prolonging drug which we combine with SPP4040.

In addition to regulatory considerations, we believe that creation of proprietary co-formulated drugs is a commercially superior strategy. By selling an improved, safer product that incorporates the active target drug as well as SPP4040, we can participate in larger, more profitable markets than selling SPP4040 as a stand-alone adjuvant. The commercial objective is to provide patients and medical professionals with a lower risk replacement to currently available drugs.

Signpath’s CorreQT platform provides two distinct opportunities for development. The first is the opportunity to develop “proprietary generic” drugs; that is, patented versions of generic drugs which are safer than the generic versions due to mitigation of QT Prolongation side effects. This avenue can be pursued unilaterally by Signpath for numerous target drugs that are off patent or have limited patent life.

The second avenue for development is to pursue license agreements with other companies who are developing and/or marketing patented drugs which have QT prolongation side effects. We believe that Signpath’s CorreQT technology has the ability to mitigate these dangerous cardiac side effects, making the target drug safer. There is an additional benefit to this approach because it would provide additional patent protection for the target drug, extending exclusivity for an additional 15-20 years.