Clinical trials inevitably require overcoming a series of challenges. This is especially true when a therapeutic is truly innovative and has no prior precedent.
In the second Trial Trailblazers podcast, initially hosted on BioPharma Dive, Nicole Latimer, CEO of Medrio, is joined by Dr. Paul Song, CEO of NKGen Biotech. They discuss a novel treatment for Alzheimer’s disease and beyond, overcoming skepticism, and why good science wins in the end.
In this conversation, Nicole and Paul covered a range of topics, including:
- Receiving FDA compassionate use approval and running trials outside the US
- Writing protocols for regulatory approval
- Viewing data from a commercialization angle
- Understanding the shifting regulatory environment
- Making sense of a shifting funding landscape
- Navigating innovative clinical trials
- Contemplating the impact of scientific breakthroughs
Note: Not all questions are included below. Responses have been edited for conciseness. We’ve included time stamps so you can check out the recorded audio to hear more.
How did you navigate the FDA’s compassionate use approval process?
[6:10]
We had already finished our Phase I trials in cancer and found that our treatment was incredibly safe. So, we needed to show some sort of scientific rationale why this could be used for other diseases, particularly for patients who were end-stage and out of options. We found the FDA to be very compassionate and also very open-minded because we had shown that our cell therapy was so safe.
Certain countries, like Japan, Korea, Mexico, and Thailand, view our treatment—which is a non-genetically modified but activated natural killer cell therapy that uses the patient’s own cells as a treatment—not as a drug. In several countries, we don’t even need to obtain approval to administer our treatment. So the first patient that we treated was really not on compassionate use. It was perfectly legal for us to do.
After that example of one, we didn’t know whether or not this was a coincidence, or whether or not it was a placebo effect. We were introduced to a few other patients here in the United States who had more advanced Alzheimer’s disease, and in that situation, we applied to the US FDA for single compassionate use INDs. And the FDA was very accommodating and granted that to us.
Are there any lessons that you would share about protocol writing?
[9:20]
Try to keep things as simple as possible. You have to really have good, solid science. But if you are trying to present something that is without any prior precedent and has really extensive, complicated explanations, it’s going to potentially delay your approval process.
Hand [your protocol] to somebody who has a clinical element because, a lot of times, these are scientific discoveries that are first put forward by somebody who’s never actually treated a patient. They came up with something brilliant, but they don’t know how to articulate why it meets a certain need in the medical field. So find somebody who has maybe had a little bit of that experience that they can articulate. It could really accelerate the process.
How have you thought about data in terms of funding or commercialization?
[14:07]
Absolutely. In fact, we were presented with a term sheet that essentially stated that once we reached Phase II, if the data was promising, they would provide a substantial amount of money to move forward.
Having an EDC system that allows you to have control over your data is so important. Groups that are interested in our work can hire independent people to look at the data to say, “Yeah, this makes sense.” This approach makes the process so much easier in every aspect. I think that gives them more comfort that this is real data, versus somebody trying to just tweak it in a way that’s favorable to them.
In our current shifting environment, what would you recommend for working with regulators?
[22:56]
For all of the flak the FDA gets for being obstructionist, we have never felt that at all. They’ve been very, very kind and respectful and also accommodating. They’ve really tried to help us get into the clinic to help as many patients as possible.
When we recently got our Fast Track designation, it really spoke to how they see our science and the potential for unmet need, which is moderate-stage Alzheimer’s disease.
But I do think some of these companies that are doing gene editing, gene therapies, and particularly the vaccines using lentiviral vectors may have a more challenging environment under the new administration.
What are you seeing in the funding environment? Any major shifts from previous years?
[25:34]
If you look at the number of IPOs that have happened in the last nine months in the biotech industry, it’s quite paltry. And I think for a lot of these biotech VCs rely on those [IPOs] to have their exits and cash out.
Also, I’ve seen that quite a few of them are underwater. That has been a big challenge. There were a few funds that we were talking to that were very interested several months ago, who are in a much more difficult, precarious financial situation today than they were back then. I think that’s made it difficult for them.
Then again, you have quite a few other funds that have gone on to raise an additional 600 million. It’s really impressive to see those funds and the amount of money that’s still there waiting to be deployed.
But I do think there is difficulty for more and more sectors, as they say. I think cell therapy is one that has fallen out of vogue right now. So many investors in the cell therapy space have either seen their companies close or are underwater. But I do think that, like anything, all it takes is one or two companies to show real success in the space to revitalize it.
What we’re seeing time and time again is that ‘the science’ is really dictating what’s happening. I think now more and more people are paying attention to it. So again, some funds that never would talk to us, because of one reason or another, are now starting to say, “Hey, let’s talk to you guys. We think there’s something here now.” But it is a matter of persistence.
If you have something that really works and are willing to really keep moving along, then eventually, people will see that it does.
What advice do you have for biotechs on navigating innovative clinical trials?
[28:06]
I can just tell you what makes our situation unique is we’re taking a therapy that no one believed made any sense to now people saying, “Oh, this does make sense.”
I think that the challenge was that we just had to overcome so much skepticism or herd mentality. Everyone was focused on a single way to treat Alzheimer’s, which was, “Let’s all focus on the amyloid protein. Nothing else matters.”
So if you’re proposing something novel that was not launched at one of these cathedrals of higher learning, then people are less likely to want to even work with you.
I think we need to have a more open mind now with regard to getting FDA approval because, again, there was no prior precedent. It wasn’t like you had five or six trials that had done this. We just had to be very innovative in our pre-clinical work.
If you are in this constant sort of structure following the industry norms, then many times you will dismiss things that maybe do have some potential merit.
What’s the most exciting scientific finding or result that you’ve seen so far?
[32:10]
When we didn’t know the mechanism of action, I didn’t fully understand the breadth of how this could be used. We have now found that this can greatly reduce autoreactive T cell neuroinflammation, which exists across numerous diseases, such as Parkinson’s, Frontotemporal dementia, ALS, and multi-system atrophy. This is the tip of the iceberg in terms of how your own immune cells can work across numerous diseases.
I’d say the greatest thing that I’m seeing is we’re just starting. We’re about to file an expanded access program where we’re including everything from ALS to multi-system atrophy to cerebral palsy to frontotemporal dementia, Lewy body dementia. These are diseases for which there is no known treatment.
Where can our listeners learn more?
[33:58]
They can find information on our company website. It’s www.nkgenbiotech.com, where you can find links to our clinical trials, as well as presentations we’ve given, our news, and data.
And if anyone has a loved one that has one of these diseases, they can certainly reach out to our company through the website. We can put them in touch, where they can be considered for compassionate use, or the expanded access program, which we hope to have up and running sometime this summer.
Want more resources on running clinical trials? Read our eBook, “How to Run a Nimble, Cost-Effective Trial.”