Our Perspective

Coyne Scientific Represents a New Approach to Predictive Toxicity Testing

The Unmet Need

The cost of developing a new drug has recently been estimated at $2.6 billion. This figure is driven less by the cost of the one successful compound that makes it all the way to market (i.e., about $400 million) than by the cost of the nearly two dozen other candidate compounds that fail along the way – i.e., $2.2 billion.

A critical but largely unrecognized reason why the cost of failed candidates is so high is that – until now – the first point in the drug development process at which pharma companies have been able to reliably predict whether a candidate compound that does not harm an “average person” might still harm a small but unacceptable portion of the population has been late stage clinical trials, when candidate compounds are typically exposed, for the first time, to the broad range of human genetic diversity.

Of the 6,000 compounds that are typically in pre-clinical stage testing in the U.S. at any given point in time, at least 2,500 of them will fail for toxicity reasons due to low-incidence genetic variations. In addition, of all the candidate compounds reaching clinical trials, almost half of them will fail for the same reason. In combination, this means that $1 billion of the $2.2 billion “wasted” on failed candidate compounds (per one approved compound) is spent on candidates that fail due to the intersection of toxicity and genetic diversity.

Early detection of future failures among such candidate compounds would help to significantly reduce the cost of drug development.

The CoyneSci Solution

Coyne Scientific (“CoyneSci”) provides proprietary services that enable our clients to make a large dent in that $2.2 billion of “wasted” development expense, because we can help them predict – at any point in the development process, not just during clinical trials – whether many of their compounds will harm a portion of the population.

In recent years, pharmaceutical companies have begun using stem cells and their derivatives to conduct high throughput screening for toxicity. These tests use cloned copies of one cell of one human being. Such tests can be predictive of toxicity at the level of one random human being, but such tests – as well as animal tests – are unreliable predictors of how a candidate compound will fare when introduced to large populations of human beings (e.g., during Phase 2 or 3 clinical trials, or once on the market) because such tests do not examine the impact of the key driver of such results: the broad range of human genetic diversity.

CoyneSci conducts pre-/non-clinical toxicity testing for proposed new drugs on large numbers of “people” who represent the genetic diversity of the marketplace using hiPSCs. Our tests currently target the leading cause of toxicity-related failure in clinical testing – cardiotoxicity (as well as cytotoxicity/proliferation). In the future, we will also offer hepatotoxicity testing and neurotoxicity testing, to address the second- and third-leading causes of such toxicity-related failure.

In cases where a compound does show elevated toxic reactions in a portion of the population, CoyneSci is then be able to help clients understand the consequences of the distribution of reactions, as well as the underlying genetic causes of those different reactions.

Benefits

For pharma companies, CoyneSci’s testing applies to virtually any drug under development. Furthermore, the FDA has confirmed that it will not require any reviews or approvals in order for CoyneSci’s testing service to be used immediately in pre-clinical testing.

The potential cost savings benefits of CoyneSci’s testing could be well over $200 million per approved compound, and our tests do not have to be approved (or even seen) by the FDA when tests are conducted in the pre-clinical stages of the drug development process (i.e., prior to the IND).

Beyond helping identify “doomed” compounds, CoyneSci’s testing can assist a pharma company in making a variety of decisions throughout the drug development process, including designing dosage limits, checking for drug-drug interactions, selecting clinical trial participants, and pre-testing new populations for toxicity before conducting bridging studies.

Finally, the value to both a pharma company and society of identifying a “doomed” compound early on, then redirecting any associated financial and human resources against more promising compounds, is clearly significant in terms of dollars, time, and public health.

Beyond Early Stage Drug Development

There are many (separate) potential applications of CoyneSci’s testing service for any one candidate drug – early drug development stage testing; formulation stage testing; testing on multiple ethnic groups; pediatric applications; drug-drug-interaction testing, etc.

One very important opportunity to improve world health lies in smaller and/or poorer countries whose populations are ethnically different than those in the “big three” markets of the U.S., Japan, and Western Europe. Currently, these countries generally do not have the market size and/or economic power to demand clinical trials on their particular populations – instead, they must rely on the “proxies” of clinical trials conducted in the “big three” markets. This exposes their populations to risk, as drug reaction is strongly affected by ethnicity (a genetic trait). CoyneSci testing provides an effective, affordable mechanism for significantly improving the health and safety of these populations.

Meanwhile, further opportunities include: new applications in pharmaceuticals (e.g., orphan and compassionate-use tox studies, forensic tox studies of failed compounds, drug-drug interaction studies, bio-similar studies, supplements to clinical trials); applications in new industries (e.g., toxicity testing of industrial chemicals and cosmetics); and the study of infectious diseases.