The Unexpected Challenges Of Moving From Discovery To Clinical

By Ed Miseta, Chief Editor, Clinical Leader

Keystone Nano, a small oncology-focused company in State College, PA, recently received an IND approval from the FDA and launched its first clinical trial. The company’s nanoparticle technology targets bad cells while leaving good cells unscathed. While that transition from discovery to clinical is an exciting time for most companies, it is also a time of greater challenges as your product is used in humans for the first time. 

Jeff Davidson, CEO of Keystone Nano, has learned about many of these challenges first-hand. He recently spoke to Clinical Leader about the company’s journey from discovery to clinical, and the challenges he expects to face in getting to Phase 3 and, ultimately, and FDA approval.

The seven-person company believes it has a therapy that will eventually be used against several types of solid tumors. The product being developed uses biocompatible nanocolloids like calcium and phosphate to protect and target active compounds.

The product uses a simple design to deliver enhanced results with fewer side effects. Calcium phosphate is also a biologically compatible substance that is generally regarded as safe. So, navigating the FDA and EMA approval process can be less complicated and more affordable than other delivery systems that use multiple new components.

Miseta: Keystone Nano was formed by three partners. Were there any early disagreements on the direction of the company?

Davidson: I think our founders have been a key asset for the company, and we have been able to successfully work together towards common goals without driving each other crazy. That is not always the case in many small companies. People issues, especially in early development, are critically important. Every position in the company is important, and everyone needs to be very fluid in those early days.

We’ve been fortunate to have the right people on board. For example, the first employee we hired was Dr. Mylisa Parette, who is now our VP of Research. In the early stages of a company, continuity is important. Our three founders have stayed together, and Dr. Parette has grown to be an increasingly significant leader for us. That continuity has been helpful to our growth.

Miseta: Do the three founders have complementary functional responsibilities or are you performing similar tasks?

Davidson: We have varied backgrounds and are very different people. I serve as CEO and handle many of the day-to-day business issues, such as building our team and locating needed funding. Our Chief Science Officer is James Adair. He is a co-creator of our nano technology and has over 250 publications and 13 patents in the area of materials science. His expertise is in exotic and unusual materials, understanding them, characterizing them, designing them, and effectively building them.

Dr. Mark Tester is our Chief Medical Officer. He brings expertise in pharmacology and how our products will work in humans. He is also responsible for how we will assess, optimize, and improve them going forward. In moving from the early discovery stages through to clinical testing, he has been a great resource for us.

Miseta: Transitioning from the discovery phase to the clinical phase can be tricky, as unexpected things can arise. Were there any issues you faced?

Davidson: I do have one example. Looking back on it now it seems kind of funny, but at the time it was not funny at all. An IV is required to administer our drug, and the infusion process takes over two hours. That means we needed IV supplies, including the bag and tubing.

We went to the clinics we were working with and asked what type of supplies they preferred to work with. We then went to that manufacturer and ordered the tubing they recommended. We performed compatibility testing to ensure our materials didn’t interact badly with the clinical tubing. They worked well, so we ordered a set and had it sent to every site. All of them again said it was the tubing they preferred to use, so we placed a large order. 

Unfortunately, once the tubing arrived, we were informed by the sites that the tubing was too short and they would not be able to use it. When we went back to the manufacturer to get longer tubes, we were told they did not produce a longer one that used the same material. Since we were switching materials, we had to again perform compatibility testing with our material. The supplier could not do it right away, which would set back the trial by about two months. Luckily, we were able to work around it by doing some testing internally and finding another supplier who was able to do the testing very quickly. In the end, the delay ended up being only a week.

Miseta: That had to be frustrating.

Davidson: It was! We felt we covered all the bases. We checked it out with the clinics and we ordered the tubing they requested. We performed compatibility testing. We even contacted the pharmacies at the clinics. The only thing we didn’t do was check with the nurses at the clinics who would be administering the IV. They were the ones who noted the tubes would be too short, and would require patients to sit for two hours with their arm within six inches of the pump. 

Miseta: I have to think for a small company, any type of delay will be costly.

Davidson: That’s true. When something as simple as tubing ends up prompting an additional delay and expense, you’re like, “How can this happen?” For a big pharma company, I’m sure that’s nothing. But for us, it was a delay and an unexpected $60,000 cost for additional testing. It was something we didn’t budget for, which is an awkward problem to have.

Miseta: Was there a lesson to be learned from that experience?

Davidson: I think it taught us the importance of communicating with everyone involved in the trial process, including those involved with delivery of the drug product. We are now taking a much closer look at that and getting to know all of the individuals involved. We got the tubing approved by the pharmacies at the clinics, but those folks are not the ones administering the product. I now feel we need approval from the nurses, the doctors, and even the patients. Everyone involved in the process can have expectations for the product that we may not have considered.

Our communication is also a lot more aggressive than it was in the past. We are in Pennsylvania. Our clinics are in Maryland, Virginia, and South Carolina. We are now travelling to those clinics and meeting with everyone involved in the trial. If you want to avoid those unexpected costs and delays, you have to make sure everyone is on the same page.

Miseta: What challenges do you anticipate moving forward?

Davidson: It’s a long list. Right now our focus is on getting a good conclusion to our Phase 1 trial. We are also in the process of raising money to ensure we can get a Phase 2 trial going. Then we hope to find a pharma partner to help us prepare for a Phase 3 study.