Designing a Non-Addictive Pain Medicine to Combat the Opioid Crisis

Stephen Doberstein is senior vice president and chief scientific officer at a biotech firm that is developing an opioid designed to offer pain relief without the feeling of euphoria that can lead to addiction. 

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Stephen Doberstein, who completed the Advanced Management Program in 2016, is senior vice president and chief scientific officer at Nektar, a San Francisco-based biotech firm that is developing an experimental opioid, NKTR-181. The drug is designed to offer pain relief without the feeling of euphoria that can lead to addiction and overdose. He says that the problem of prescription drug abuse, which has now reached crisis levels, was already beginning to emerge eight years ago when the company began its work on the project. Below, Doberstein discusses the future of the new medicine and his role at the company. 

How does NKTR-181 work?

One of the things that affects the euphoria that a patient, or abuser, feels when they take an opioid is how rapidly the opioid molecule gets into your brain and activates its receptors. And that’s the reason why, frequently, drug abusers will describe getting high as a “rush.” The molecule rushes into your brain and that’s what causes euphoria. That rush isn’t important for pain control — it’s only important for getting high. What we determined was that we could make a new medicine, NKTR-181, that fully engaged the opioid receptors, the target of all of these drugs inside the brain, but that got into the brain more slowly across what we call the blood-brain barrier. And that’s really the distinguishing characteristic of NKTR-181. No matter how the medicine gets into your bloodstream, it’s very slow to enter the brain across the barrier that separates your brain from your blood. And that dramatically limits the euphoria that some people feel.

Where is the drug in the pipeline now?

We recently had a very positive phase-three clinical trial for NKTR-181 in chronic low-back pain, and it very clearly demonstrated that NKTR-181 is highly effective for controlling pain. And we’ve completed some human abuse liability studies. The way that works is we take subjects who are recreational drug abusers for whom opioids are their drug of choice and we ask them in a blinded fashion to rate the experience that they get from a dose of NKTR-181 compared to a control opioid, like oxycodone. So we quite literally ask drug abusers whether the drug gives them any positive reinforcement — whether they’d want to take it again and how high it makes them feel. What we found in those studies is that, essentially, up to the very highest dose that we tested, very experienced drug abusers got no benefit at all in terms of getting high. And that’s exactly how we’d hoped the study would come out. We have one ongoing abuse liability study and then we’ll go and talk to the Food and Drug Administration to determine the appropriate clinical development path.

You have a background in science and engineering. What have you learned moving into an executive role?

I realized early on that while I love basic science — and I really do love analyzing and designing experiments — I really thrive on the feeling of bringing a good team together and finding a way to manage that team to success. Operating at a more executive level has allowed me to embrace that. At Columbia, we focused on authentic leadership, the idea that you have to really understand yourself, and in times of stress or uncertainty, go back to your core values and the core mission of your organization. This really resonated with me. It crystallized a lot of my instincts and allowed me to more completely realize them in my job. The trade-off of being in an executive role is that I don’t see the results of the experiment the day it’s done anymore — there are scientists who do the experiments and analyze the data and then they tell me about it. But being able to bring together exceptionally talented scientists who are very smart and highly dedicated to an important mission is very rewarding for me. 

What’s next for Nektar?

One thing that’s really exciting is that we have so many projects coming together at important inflection points. I think we’ll know by the end of the year what our path is for NKTR-181, what our next steps are, and how far away we are from launching that medicine. We also have a very rich pipeline of projects that are a little earlier in the clinical development process than NKTR-181 that are in the area of cancer immunotherapy — engaging the patient’s immune system to attack tumors and to eliminate them. It’s an area of very serious research right now and it’s something that I couldn’t be more excited about. Right now my goal is to continue to push. My group gets the medicines out of the research labs and into the clinic, and with our colleagues from around the organization, we then try to bring them closer to the hands of physicians and patients where they can do the most good.

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