Pharma Sharing Tox Data

April 14, 2016
Moe Alsumidaie

Mike Graziano, VP of Toxicology at Bristol-Myers Squibb, sits down with Moe Alsumidaie to discuss BioCelerate’s toxicology data sharing initiative.

We recently interviewed Dalvir Gill about the launch of BioCelerate, and during this interview, Gill indicated that BioCelerate’s first initiative involves toxicology data sharing. This interview with Mike Graziano, VP of Toxicology at Bristol-Myers Squibb, will elaborate on the toxicology data sharing initiative.   Moe Alsumidaie: Can you elaborate on BioCelerate’s toxicology data sharing initiative? What is the purpose of this initiative, and what will this initiative aim to achieve?   Mike Graziano: The data-sharing project is all about sharing individual toxicology data in a standard format called Standard for Exchange of Nonclinical Data (SEND). SEND is the electronic data format that the FDA is requiring from all sponsors beginning in 2017 for all new IND’s. So, we are taking advantage of a data format that the entire industry will be using. We are not building any new databases or platforms, so that simplifies the project for now.    Pending on what we end up with for the data-sharing agreement, member companies will be able to submit their data to a repository where all the other member companies can view it. We hope to enable companies who are working on similar targets make better decisions on their compound progression. This is all done with the background that toxicologists will discover findings in their studies (i.e., lesions or toxicities that may or may not be adverse); it is often a very difficult call in terms of whether these findings are related to intended pharmacology or the design of the molecule. All of that information should give us more context as to whether the information is on or off target toxicity. This data will allow companies to make decisions on whether to terminate compounds or progress them faster. Through data sharing, across member companies, we hope to make better decisions on programs.   MA:What is the impact of the toxicology initiative on drug discovery?

MG: The impact on drug discovery is that if you determine that your toxicity of concern is off target, you will enable your chemists to go back and redesign a better molecule, so it’s an iterative process. That’s the most direct and simplest application.    MA: How does the toxicology initiative fit into clinical trials?MG: This initiative is aimed to enhance go/no-go decisions in clinical trials. Here’s a scenario: let’s say you’re Company A, and you're working on the same target as Company B. Company B may already be in Phase III and Company A is conducting a Phase I trial. Company A has completed its toxicity studies, and is not quite sure how to put certain toxicity findings into proper perspective given the limited information it has. Having access to toxicity information from Company B may help Company A make a go/no go decision. For example, Company A may want to accelerate its project because they've overcome a specific finding. Alternatively, Company A may have an adverse finding that was not seen by Company B which will lead Company A to go back and redesign a better compound.    Generally, biopharmaceutical companies continue toxicology studies on compounds throughout all phases of the drug development process, and will eventually have toxicology data in the SEND format to support clinical trials as early as Phase I (IND submissions). At BioCelerate, we have not yet decided at what stage of development compound data will be shared. However, there is consensus that we will share individual animal toxicology data from all studies in the SEND format up to that point in development. It is an enormous amount of data.    Right now, we all agreed that there is absolutely no problem sharing this data on compounds that have achieved Stage V (marketing stage). The question is how far back in the development pipeline are we willing to go to share this information. That has not been resolved or agreed to yet. Eventually the long-term goal of this is to feel comfortable with the ability to share this information much earlier in the development process, as long as we have patents filed on the compound and it is publicly released; that way, we aren’t releasing any proprietary information.    I believe that all of this will lead to benefits to patients by developing compounds that are safer and have a better chance of efficacy. That is the long-term goal of the project.     MA: If two member companies are developing a similar compound in the same phase, how will the toxicology initiative impact competitive advantages?   MG: The point of this initiative is to share data, which will enable a company to make a decision as to whether they want to develop compounds against that target. Without that information, you don't have the perspective of where you are relative to the other company. In some respect, we are increasing the competition, and making this a race to who develops the best compound. A company could be working on the same target but are not seeing sufficient efficacy or maybe more toxicity effects, requiring molecular redesign. It can also work the other way. Each company has to make its own decision on how to use the data. Ultimately, this initiative will allow companies to focus their resources to create safer and more effective compounds.     MA:How will the toxicology initiative facilitate the efficiency of discovering new medical products? What effect will this have on the industry and drug innovation?   MG: The ultimate goal is to increase efficiency in drug development by giving scientists more information to make better decisions. As a toxicologist, when I’m seeing findings in my studies, it would be very helpful to know if other companies have seen the same findings, how significant they are, and what I can do de-risk them. This initiative is aimed to help toxicology scientists put those findings into better perspective, and that, in turn, will help the company make better decisions on compound development and patient safety.