First First-in-Human: Reflections on a Milestone
On Monday, October 21 in Sydney, Australia, the first patient was dosed with ONL1204, the therapeutic that I’ve helped develop during my time at ONL Therapeutics. This marked the official start of the company’s Phase I clinical trial in retinal detachment. Since the drug had never been used in patients, this event also signified the First-in-Human milestone for ONL1204.
This was a big moment for the company, as it marked the official transition from being a preclinical company to becoming a clinical-stage company. The company was founded in 2011, and after a lot of ups and downs, we finally made it into patients in 2019. Since the moment when we initially heard that the first patient had been dosed, there have been a lot of smiles and high-fives. There was even a cake.
While this was a transitional moment for the company, it was also a personal milestone for me. Unlike some of my coworkers who have years of experience in the biotech and pharma industries, this was my first experience with having something that I’ve worked on being dosed into patients. Essentially, it was my first First-in-Human experience, and it was, quite frankly, more emotionally impactful than I had anticipated.
In grad school, my work in science has involved playing with test tubes and cells in plastic dishes. Yes, I was vaguely aware that my work could possibly, eventually, maybe, someday contribute toward helping a patient, but the focus was mostly on solving a scientific mystery, trying to figure out how something worked. I was much more interested in solving a biological puzzle than directly helping a specific patient. As I write this, I guess that it seems quite obvious why I decided to pursue my PhD instead of going to med school. I liked learning and discovery, prioritizing that over a desire to directly treat patients.
When I joined ONL Therapeutics in 2015, the idea of treating the first patient was on a distant horizon, one that seemed to keep sliding further into the future. At the time, the development of ONL1204 was in its early stages. It had progressed only slightly beyond the chemical-structure-on-a-piece-of-paper phase. As the years marched on and the drug development continued, there were a lot of ups and downs, starts and stops, zigs and zags. During these times, the idea of treating patients was definitely a worthy goal – and was held up as such – but it remained abstract and far away. In many ways, this environment wasn’t that different from grad school: we needed to solve the scientific issue of the day, rather than focusing on the end goal of treating patients.
Fast-forwarding to this week, the idea of treating patients is no longer a distant, abstract notion. It’s real. When I initially read the email saying that the first patient had been dosed, I remember smiling and feeling excited. But then it hit me. No longer are we talking about just a mouse or some cells in a dish. This is a real person. The next thought that crossed my mind was “I really hope that the drug is safe.” While this may sound like an obvious statement and an aim that we’ve always worked toward, it nevertheless rushed to the forefront of my mind. It took on new meaning. It felt weightier.
There was a complete stranger, half a world away, making the choice to be the first person ever to be treated with this experimental drug. This patient has never heard of ONL Therapeutics before and couldn’t pick me or any of my coworkers out from a crowd. Would you have volunteered to be the first patient to be treated with a new drug that’s never been in humans, developed by a company you’ve never heard of and by strangers on the other side of the planet? I’m not sure that I would have. And yet, this patient did. This patient put their trust in us and in our work.
That’s a solemn responsibility. In my head, I found myself asking “did we do everything we could do to make sure that the drug was safe?” I believe the answer is yes, as we’ve done an extensive amount of work, and our preclinical data suggest that the drug is safe for humans. But you still never know until you try it in people. I have a new appreciation for the courage of this patient, and I’m thankful for the patient’s trust in us.
On the other side of this newfound weight of responsibility, there’s also the uplifting realization that I’ve worked on something that could honestly improve a patient’s life. Helping to take something all the way from a chemical structure on paper to a drug that’s being injected into patients is a remarkable feeling. No longer is the idea of helping patients just a framing device to give context to your research work. Or some abstract idea that your work may one day, possibly, maybe, sort of impact. The idea of treating patients is now real. The goal of helping patients and improving their lives is no longer on the distant horizon – protecting patients’ vision now feels like it’s right around the corner.
There’s still a lot more work to be done. We need to continue to monitor the drug’s safety in this first patient, as well as recruit, dose, and monitor the rest of the patients in our Phase I clinical trial. We still need to do more work to determine if our drug is effective, and we’re still years away from commercialization.
But we’ve treated our first patient. The company has changed. It reached a milestone. And so have I.
The ONL Team (from L to R): Jana van de Goor (VP, Development), David Esposito (CEO), Bob Forgey (VP, Operations), me (Director, Research), Linda Kemnitz (Executive Administrator), David Zacks (Co-Founder & CSO)