Companion Diagnostics
In 2011-12, pHLOGISTIX made a business decision to incorporate companion diagnostics (CDx), a growing trend in the pharmaceutical industry because of the emphasis on personalized medicine, into its business strategy. The basis for this was the growing public awareness of the impact of concussion in everyday life. It emanated from the explosion in lawsuits against the National Football League (NFL) by former NFL players to the situation that high school athletics departments and parents encounter with their children, girls as well as boys, suffering concussions from other sports such as basketball, volleyball, soccer as well as football and hockey.

In making this decision, the Company sought to evaluate whether it had the capacity, or could develop, a translational CDx team to develop experience in launching diagnostic products; one with experience in drafting and submitting regulatory filings of Premarket Notification (510k)and Premarket Approvals (PMAs)? The Company knew that there were no existing diagnostic technologies, well-proven and widely accepted, for such a CDx for concussion currently available. We also sought to evaluate whether in-house or collaborative external CDx team members had ever worked in clinical laboratory settings?

As such we determined that there were at least six types of diagnostics we might include as potential CDx:

1)  CDx to identify responsive or non-responsive patients to our therapeutic;
2)  CDx that would identify subgroups of the wider TBI population with poor prognosis;
3)  CDx likely to identify patients at increased risk of serious adverse events (SAEs) stemming from treatment with our therapeutic;
4)  Monitoring response to our therapeuticto adjust treatment schedule, dose, etc. and to achieve improved efficacy;
5)  CDx to individualize therapeutic dose;
6)  CDx to monitor efficacy of therapeutic in clinical trials to support market approval of our product;

Consequently, pHLOGISTIX has since embarked on a program to develop blood-based biomarkers to developconcussion diagnostics with high accuracy and validity. These biomarkers are to firmly establish that concussion, and transition to post-concussion syndrome (PCS), as having taken place, but also to enable both medically trained and untrained personnel, such as team trainers and others, to make decisions relative to a victim reentering the trauma-inducing venue. These biomarkers will also serve to monitor therapeutic efficacy, and in this sense will become part of a growing pharma category known as “theranostics”.  Theranostics can be tied to a specific drug or biologic assay/drug-diagnostic combination or can provide critical information determining dosage or continued use of such therapeutics.

Since one of the important criteria for the pHLOGISTIX portfolio of therapeutics is to prevent the development of neurodegenerative complications arising from excessive neuroinflammation following mild to moderate traumatic brain injury (TBI), having a drug diagnostic combination, or theranostic will be extremely valuable. There is evidence today that the theranostic category of pharmaceuticals represents a market exceeding $20 billion annually.  Multiple criteria have been established for this theranostic category and include:

  • at least one approved indication for this theranostic drug requires this biomarker diagnostic;
  • If the biomarker diagnostic is required describing the drug results of the test must be provided in the indication;
  • diagnostic testing must be clearly stated in the label;
  • furthermore, diagnostic testing must be needed for drug or biologic is prescribed, also in the label.

Theranostic Drugs
Therefore, one strategy the Company is pursuing once clinical trials are established is to seek IND for a newtheranostic drug. An alternate, but not mutually exclusive, strategy is to separately develop the blood–based diagnostic biomarker in parallel with the new drug/biologic. This is an important, if nuanced, difference since the new category of theranostics are tied to widely-available and standardized chemical or immunologic tests. Our platform of blood-based diagnostic biomarkers for concussion represents a new diagnostic approach utilizing hybrid nucleic acid, protein and spinning disk or microarray technology. This hybrid approach, since it will involve more than one analyte, would fall under the heading ofIn Vitro Diagnostic Multi-Analyte Assays (IVDMIAs). We anticipate that this will result in an “analyte specific reagent” (ASR) as used within the concussion situation as described above and for other neurologic disorders as well. As such, in its proprietary approach to this problem the Company is developing new specialized reagents, equipment and expertise. Within this context, the Company may seek direct FDA approval for a “test kit” and/or device.  The FDA may grant approval based on different criteria for such an ASR compared to those for standardized tests. We may seek to partner and/or joint venture with diagnostic developers or device manufacturer.  Although it takes longer then seeking an ASR approval from the FDA we might also seek approval while in Phase 2 or Phase 3 clinical trials. One advantage is a simpler reimbursement process, however, there may be other problems we might encounter such as test quality and comparison amongst different manufacturers. This might involve partnering with more than one kit manufacturer but as another advantage of providing a revenue stream for the therapeutic development portfolio.

This strategy is not without challenges especially from the marketing perspective. We seek to develop a “gold standard” diagnostic kit for concussion but are mindful of the possibility that this will detract both resources and energy from the therapeutic portfolio. We are aware that new theranostics can actually impactsales negatively ofdrugs which they are connected and, clearly, this would not be ideal. However, such tests have been developed historically not by the biotech company but by academic researchers, by third-party payers and even by large Pharma, who might be viewed as competitors for the therapeutic. At this point in time, it is the pHLOGISTIX strategy to develop the companion diagnostic in parallel with the therapeutic portfolio.

 Mitochondrial Releasates
For both a conventional CDx as well as a theranostic, thepHLOGISTIX strategy is to focus on mitochondrial components released from the brain after traumatic impact. We consider these “mitochondrial releasates” and they include mitochondrial DNA (mtDNA), both intact and degraded, as well as proteins transcribed from either mtDNA or nuclear DNA, but that are known to be highly localized to brain mitochondria. Provisional patent applications have been submitted for development of “mitochondrial releasates” for mild TBI and concussion. These tests are all currently in development stage. We anticipate going to clinical trials for the CDx within the next 36 months, while the theranostic is likely to take more time.