Insights in Treating Anxiety and the Pharmaceutical Perspective

Freda Lewis-Hall, MD, a clinician with extensive experience in practice and pharmaceutical development surveyed the persistent unmet need in anxiety and depression treatment. We spoke with Lewis-Hall to learn more about the pipeline of novel serotonergic agonists, particularly HLP-004 for generalized anxiety disorder and HLP003 for major depressive disorder, which recently showed positive results.^1,2 HLP-004 is an investigational intramuscular deuterated serotoninergic agonist, being developed for treatment resisted anxiety.²

Psychiatric Times: What are you looking forward to in terms of meeting unmet needs in treatments for anxiety and depression?

Freda Lewis-Hall, MD: Well, I am so excited about the opportunity to add tools, to a toolkit that's been wanting. There are so many patients today that suffer from anxiety and depression that still have unmet needs, and they're suffering still. So adding new tools to that toolkit is a really important opportunity for them and for the clinicians who seek to serve them.

Helus is developing a novel serotonergic agonist. Our recent phase 2 results with HLP-004 in generalized anxiety disorder suggest that this approach may potentially offer meaningful and durable symptom improvement for patients when added to their existing treatment. So advancing the science and this opportunity in later phase gets me really excited. I came into this work on the front lines in a health manpower shortage area, where we had very few opportunities to help patients with unmet need.

Here we are, several decades later, and still, of the 20 million patients who suffer from anxiety or generalized anxiety disorder, nearly half of them have treatment that does not completely provide them the help that they need. And again, looking at some of the research that we're doing as the Helus organization, HLP-004 in generalized anxiety disorder is evaluated as an adjunct to existing therapies. And our expectation and hope is that we will be able to add to favorable outcomes for patients who, up to now, have continued to suffer.

PT: With your decades of experience in practice and pharmaceutical spaces, what major ways has psychiatry developed in the last 10 years?

Lewis-Hall: I graduated from medical school in 1980 and went into my internships and residencies. So I have been practicing, either as a frontline clinician or in the pharmaceutical industry, for that many decades. One of the things that I've noticed over the last 10 years is that we are evolving the capability to look forward and to look back.

So, we're thinking out of the box, I think, a little bit in terms of diagnosing and understanding patients and the causes of their illness. The diagnoses themself, for example, we know now that depression is not related to an isolated aspect—it is a number of things. And our work moving forward is figuring out what has contributed to this, what is the biology, what are the biomarkers, what are the opportunities for treatment, and how is one patient different from another, or one group of patients different from another, and how might we serve all of them well.

I am also applauding us for looking backwards, and that is looking back to things that we have used, in the past that have served us well, that we may be able, in the new context, to apply in a very different way. And I would use some of the work of Helus as an example. So in psychedelics, the conversation has shifted from stigma to science, and we are beginning to understand this technology in a way and to study it in a way that we believe will apply to patients in a very positive way. We are kind of looking back and taking some things that are valuable, either insights or science, and bringing it forward to today, and then marrying that to our forward-thinking new technologies and new opportunities.

PT: What are some of the most interesting treatments you are seeing in the psychiatric pipeline right now?

Lewis-Hall: With serotonergic pathways, we are beginning to understand so much better, how they interface, how they affect neural activity and circuitry; we are taking those insights and then applying them to research to bring medications to the forefront that can then help supplement what we have today.

Again, exploring this through the novel serotonergic agonist platform, is exciting. I started back in the days of early selective serotonin reuptake inhibitors, and we were getting a deeper, clearer understanding about the serotonergic pathways and their potential impact for patients. We have some great examples looking at HLP-003 for major depressive disorder and HLP-004 for generalized anxiety disorder. The early clinical data that we have seen has been really inspiring, and we are excited and looking forward to shaping development pathways so that we can deliver value to patients who still have unmet needs.

PT: What have you learned in your transition from being a practicing clinician to the pharmaceutical leadership space that you want to share with clinicians?

Lewis-Hall: Well, I have to tell you, the transition was really interesting. I was not sure what I was getting into, and it was different. In coming from the clinical environment, I had this, you know, “how hard can it be developing a new drug” mindset. But that is not how it works.

It becomes very clear that drug development is rigorous, it is lengthy, it is fraught with setbacks and unfortunately, in some cases, failures. So it requires a real tenacity, focus, and openness to learning, to evolving. Agility becomes really important if you want to serve patients the way that we do. When I got into the industry, I realized that the opposite of what I had thought was true: people in the industry were thinking, "how hard could it be?" about clinical practice. And our partnerships and understanding have grown much stronger today.

PT: What is a piece of advice you would offer to practicing clinicians working with patients with anxiety and/or depression?

Lewis-Hall: One of the biggest learnings that I had as a clinician, and again as I came into the industry, I often felt I knew a lot and so I should be sharing what I know; I'm not sure that my listening skills were as good as they needed to have been. So, learning to listen and to really think carefully, take seriously and ponder, what patients share with you—it is often corner-turning. Those “aha” moments come many times when you are sitting across from, a patient and they share something, and it dawns on you and it has been shape-shifting. Listening well is something that I wish I had learned earlier.

The second element is partnering. We do a lot as clinicians of face-to-face with patients. We give a lot. We try to help. Partnering with patients, creating the trust, with their caregivers and families, all of that is extremely important. Reaching out even further than that, others in the field and others that are in adjacent environments may have learnings, understanding, or insights that would be helpful to you.

Dr Lewis-Hall is on the board of directors and is chair of the scientific committee for Helus Pharma.

References

1. Kuntz L. New phase 2 signal detection results: HLP004 for moderate-to-severe generalized anxiety disorder. Psychiatric Times. March 5, 2026. https://www.psychiatrictimes.com/view/new-phase-2-signal-detection-results-hlp004-for-moderate-to-severe-generalized-anxiety-disorder

2. Helus Pharma announces topline results in phase 2 signal detection study for HPL004 in patients with generalized anxiety disorder. Press release. March 5, 2026. Accessed April 3, 2026. https://www.globenewswire.com/news-release/2026/03/05/3250048/0/en/Helus-Pharma-Announces-Topline-Results-in-Phase-2-Signal-Detection-Study-for-HLP004-in-Patients-with-Generalized-Anxiety-Disorder.html