Raj Mehra, PhD
Founder, Chairman & CEO
Seelos Therapeutics, Inc.
Interview conducted by:
Bud Wayne, Editorial Executive
Published – April 10, 2023
CEOCFO: Dr. Mehra, would you tell us the vision when you founded Seelos Therapeutics, Inc. and where you are today? Has that vision changed?
Dr. Mehra: When I founded Seelos Therapeutics, our focus was on neurological and psychiatric disorders. At that time many of the large pharma, the Bristol Meyers of the world and Pfizers of the world were actually shutting down their neurological divisions in drug development and were primarily more focused on oncology and infectious diseases. We saw the opportunity and that is where we focused.
Oncology is an important arena but I think neurology is the next boot hill that we need to take. These diseases are endemic. Just think of Alzheimer’s and Parkinson’s and even depression, there are millions of patients that suffer from it not only in the US but worldwide, abandoning that area is not conducive to drug development. We saw the opportunity and took it.
There was only one small tweak that we made to our vision since we started. When we started, we were more focused on the small molecules like ketamine and trehalose, however as the genomic revolution came to be where now we understand many neurological diseases at their genomic level, we acquired gene therapy programs and we are now focused on gene therapies for those neurological disorders. Other than that, our original vision of focusing on neurological and psychiatric disorders remain true up until today.
CEOCFO: Seelos has the only program in the psychedelic drug class being developed to treat suicidal depression. Before we get into what you are developing, would you tell us about depression and the suicide epidemic in the US? What are some of the statistics?
Dr. Mehra: Both suicide and depression, and suicide is a subpart of depression. If you are continuing to suffer from major depressive disorder for a long time, sooner or later you will start to think of suicide. If that is left untreated, you will then start to attach behavior to that suicide idea and that behavior means you have a specific plan thinking about how to end your life. This is epidemic proportion worldwide. There are a lot of causes which we will leave to Harvard and Princeton professors to pontificate on why that is, but we do know for a fact that these numbers are increasingly staggering numbers throughout the world and not only confined to the western world. The Asian population is actually suffering from it worse than the western population. In the last thirty to forty years most of the drugs developed for depression and used for depression in the generic sense, the most prevalent form of depression is called Major Depressive Disorder (MDD), but there are other depressions as well such as bipolar disorder, schizophrenia and other depressions.
For MDD, the last thirty years, almost the entire focus has been on two kinds of mechanisms. They went for either serotonin base or epinephrine based; these are the neurotransmitters that are exist in our brain. Almost exclusively all of those drugs are focused on those kinds of serotonin focus. They also call it monoamine focus. All of those drugs helped initially but they were not comprehensive in their coverage. There were deficiencies in terms of efficacy. It took weeks before they showed 40% to 50% of patients that will get help. They also had side-
The etiology of depression is not fully understood but as people are thinking about newer mechanisms, they started to glom onto rapidly acting programs like ketamine. Here the focus was more on the glutamate neurotransmitter system, which was different from the earlier system. What they found unique about ketamine was that it is rapidly acting so you get the effects right away and you do not have to wait for weeks. More importantly it was able to reverse some of the effects of chronic stress and depression. It increased the synaptic connections very rapidly. This is probably one of the most exciting new developments in the entire disorders known as stress and depression related disorders. That is what we are focused on.
CEOCFO: What is the market for a product that can be used to treat people brought to a medical facility desiring to commit suicide?
Dr. Mehra: It would depend on the indications and where the drug can be used. If you look at just overall, the depressive market is almost $10 billion or more. It is a massive market and that number keeps going up, so it is a real cost to the entire society, people’s livelihood and their lives as well. This is becoming a major issue. On top of that, you look at the sub-
With suicide, believe it or not there is not therapy approved in the US or worldwide. I am sorry to say but if a patient goes to the emergency room in the US and that patient was found to be suicidal, they will be kept in the hospital for seven to ten days. Since we do not have any drug to give them, they try to confine them in a so-
A patient may have been caught when they were attempting to end their lives and were brought into the emergency room by their family, friends or neighbors, and eventually stabilized and released. However, that is not the end of the story unless we truly treat the underlying disorder. These patients will keep on trying to end their lives until either they treat this disorder or they succeed in ending their lives. And this problem is worldwide.
CEOCFO: What are the numbers?
Dr. Mehra: Approximately 20 million plus patients in the US suffer from MDD. Of those, approximately 12 million patients will suffer from suicide ideation on top of their major depression. Then a subset of that is 3.5 million have a behavior attached to this suicide ideation, so those are big numbers and these numbers are equivalent in the western world including Europe but once you go to Asia they really go up. We are talking about multiple times high numbers per capital in the populations of Japan, China, Korea and other places.
CEOCFO: Why does ketamine offer hope is the area of depression and mental health?
Dr. Mehra: The main reason is its unique rapid acting ability. If you focus on the subset of these populations where patients are imminently suicidal. It is almost like a person is on the ledge and you want them to come off the ledge, you do not have the luxury to use other drugs or other antidepressants that will not have a chance to work. The other down side of the approved antidepressants are that they already have in their label that those antidepressants most of the time lead to an increase in suicide thoughts. They are not ideal for this patient population. There is a unique ability of ketamine to work right away and profoundly differently.
CEOCFO: How does ketamine work?
Dr. Mehra: Ketamine basically creates new synaptic connections that have been depressed. There is a deficit of those connections due to chronic stress and depression. If you do not have the proper synaptic connections, and we see this lower activity not only in the prefrontal cortex but also in a part of the hippocampus, that basically the wiring is so shoddy or shot that the neurotransmission is not properly taking place.
The unique ability of ketamine is that within 24 hours they have shown images in the animal model where you show new synapsis, new dendritic spines being formed within 24 hours of dosing of ketamine. The new synaptic connections are able to get around the shoddy network and increase the activity in the prefrontal cortex, so you see a profound and rapid activity as an antidepressant when ketamine is used.
CEOCFO: So many of the drugs advertised on television mention the possibility of suicidal thoughts as a side-
Dr. Mehra: Almost any drugs that are being used for neurological disorders, FDA requires that they must do a small study to prove or not prove whether their drug leads to increased suicidal thoughts, and if it does it needs to be included in the label. FDA has a very tough job but they are the gold standard in the higher world, trying to basically do benefits risk analysis. Ketamine is so unique. We have seen pharmaceutical companies including us and we look for other drugs that mimic what ketamine does and we have yet to find it. My team believes if we can just save some souls and give them their lives back, then our job on the planet is done.
CEOCFO: Would you tell us about your SLS-
Dr. Mehra: We are working with racemic Ketamine, but ketamine is a chiral compound, which means ketamine as an atom has two forms of ketamine that have the same formulas but they are mirror images of each other. If we were to stand in front of a mirror, our left arm becomes the right arm of the image. Those mirror images are in such a way that it cannot super-
The program was originally developed by Javelin Pharmaceuticals, which eventually became a part of Pfizer. Javelin was the first company that put racemic ketamine into an intranasal device, so the patients do not have to go into a hospital clinic for IV dosing. With this program we focused on imminent suicidality in major depression and in the open label study what we showed was after a single dose after 24 hours, you see a profound effect both on anti-
No other drug other than ketamine has ever in the history of antidepressants, shown a one-
CEOCFO: Seelos is the only psychedelic company working on suicidal depression. However, Johnson & Johnson, working in Treatment-
Dr. Mehra: As I indicated earlier, our esketamine is a mixture of two isomers R and S. You need both to show profound activity both as an antidepressant and anti-
Secondly, the esketamine has a lot more side-
CEOCFO: Tell us about the intranasal device you have chosen to use. What are the advantages of this one? Is it through a partnership or do you own the device?
Dr. Mehra: Our device is partnered with a company called AptarGroup, Inc. in France. They are listed on the NYSE as well. This device is very simple. It sprays ketamine through both nostrils and it is able to go into the CNS or brains quickly. It is a simple spray and more importantly the same device is also used for esketamine that is already in the market but for depression only and treatment resistant depression. They are not approved for suicidality.
Our partnership is very strong with Aptar, who supplies the device. It is easy to administer unlike IV where you have to be hooked up there for thirty to sixty minutes. Here you are done in a couple of minutes and you spray in your nostrils and you are good to go.
CEOCFO: Acadia Healthcare Company, Inc. (NASDAQ: ACHC) and their hospitals participated in your trial for acute suicidal ideation and behavior (ASIB) in major depression. Would you tell us about that relationship and what is means for Seelos?
Dr. Mehra: Acadia is a prominent partner of us in the sense that they actually eventually if they drug gets approved will be using it for their patients. They are one of the largest psychiatric center hospital chains in the US. They have almost 230 plus chains and more in the US and they only specialize in psychiatric centers. They treat hundreds of thousands of these suicidal patients daily, both in-
CEOCFO: Where did that partnership develop?
Dr. Mehra: They reached out to us and saw that we were very innovative and they wanted to be a part of it. It is very beneficial to both of us.
CEOCFO: You also have gene therapy programs in ALS, spinocerebellar ataxia, Alzheimer’s disease, and in Parkinson’s disease. First, tell us what causes those disease and how it relates genetically?
Dr. Mehra: ALS and ataxia are both fatal polyglutamine diseases. We all have genes, which can get mutated, and that can happen two ways. One is you can inherit it from your parents, and that is less common than people think; less than 10% of the time you will inherit that mutation. Most of the time, in fact, 90% of the time, you will have it sporadically during your lifetime because either you were exposed to certain events or toxins; we still don’t fully understand that, but that is how it happens. In addition, different genes will mutate to cause ALS than ataxia, but in the end, both have similar results.
The genes only function is to create proteins, but those proteins, instead of being X amino acid in length, they will have extra repeats of polyglutamine amino acids. For ALS it will be X plus 30 extra polyglutamine repeats and in ataxia it will be an extra 200 polyglutamine amino acid repeats. Therefore, these are polyglutamine diseases and once those proteins are now longer in length, they do not properly fold themselves into alpha helical structures. Once these proteins misfold within the cells, and in the brain the cells are called neurons, they will cause toxicity. These misfolded proteins will then cause ALS or ataxia and lead to common patterns and eventually neuronal death. The common patterns will be difficulty in walking, difficulty in swallowing and difficulty in speech.
In ALS it is much more aggressive, where 70% of the patients will not survive four years from the diagnosis, whereas ataxia patients will have similar symptoms in walking and speaking, but they can live more than 10 to 15 years after diagnosis. However, their quality of life will deteriorate.
CEOCFO: Would you tell us about your SLS-
Dr. Mehra: We have a program SLS-
CEOCFO: When will the data be out for your ALS study?
Dr. Mehra: Our ALS study was fully enrolled with 160 patients in February, and we will have the data out after our ketamine data, which will be out in Q3. Then the ALS data will be out towards the end of the year. That is a pivotal study. On top of that, the ataxia study that we are doing will take longer to read out. It is a global study, and we are enrolling patients worldwide.
CEOCFO: Are gene therapy programs showing any advantages when it comes to side-
Dr. Mehra: Yes. We have our SLS-
What they found amazing about this CRISPR program at Duke is that once they correct this error, and the error involved in this case was a protein called alpha-
Our focus is that you and I can dream about the potential of Parkinson’s patients who have these neurons either being repaired or dying, and then bring them to life. Remember this, you do not have to bring them to life 100%. The tremors that you see initially can take almost 60% to70% of the neurons to be impaired before you see the effect. It can bring them back to life to 30% to 50% and that is enough for us to not see the manifestations of Parkinson’s and we can dream that people will die of their old age before they die of disease. Tremendous progress and promise, and time will tell and our team will continue to work on this.
CEOCFO: What about your team that will enable you to be successful in your goals?
Dr. Mehra: A drug company is nothing without the team. Our team under the able direction of Timothy Whitaker, MD who cut all his teeth at Shire Pharmaceuticals. There were a lot of people that worked together and they were looking for a new place and found their place at Seelos. These people have already known each other for decades and they worked together at Shire so they know each other’s nuances. Dr. Tim Whitaker I think has like 25 plus drugs approved worldwide in their neurological division. These are gray hair, hardworking, nose to the grindstone, humble people and with their help we are accomplishing what we are in suicidality, ALS, ataxia and now CRISPR for Parkinson’s.
CEOCFO: Developing therapeutics is expensive. Where are you with funding today? Are you looking for investors, partnerships and attending conferences?
Dr. Mehra: The good news about Nasdaq is that it is a highly liquid market. For the last 3.5 years we raised almost $200 million give or take. For CRISPR for Parkinson’s I think that program is so massive that it belongs not at Seelos but large pharma. Therefore, we will certainly seek out a partnership for that one, but thank God for the Nasdaq and the liquidity.
CEOCFO: In closing, why is Seelos Therapeutics a company to follow? How will you make a difference in the area of mental health?
Dr. Mehra: The reason Seelos is important although we are a small company, is that our focus is in unique indications and large unmet needs. Suicidality in major depression, as far as we know we are the only one focused on that indication and it is a worldwide need. Secondly, ALS is a fatal disease, so we really need to bend the curve on that. For ataxia, we are the only one in Phase 3 worldwide, there is no other drug. We have had patients from Asia who wanted to come and move to the US and stay here for a year long enough to participate in the ataxia study. We thought that would be a burden on those patients so we said no we would open a center in Asia and that is why we went to the Chinese and Korean centers as well. On top of that is CRISPR that could potentially disease modify Parkinson’s; there is nothing else that is being done that way. There are some efforts done in a sub-
We reached out to even the Japanese regulators PMDA (Pharmaceutical and Medical Device Agency), which is the equivalent of FDA in the US, but they are in Japan. They were very impressed and thought it was very innovative. They have a massive unmet need, so they actually ok’d us to start studying ketamine in the Asian population which we just finished, with the ethno-
For those reasons, we want good investors and able partners. If we succeed in one or two of them, we actually add to the humanity and our job on the planet will be well served.
Seelos Therapeutics, Inc. | Raj Mehra, PhD | Racemic Ketamine for Depression | Racemic Ketamine for Suicidal Patients | Ketamine Suicidal Ideation | Ketamine Suicidal Thinking | Nasdaq: SEEL | As the Numbers Rise Worldwide for Suicides, Seelos Therapeutics is Bringing Hope with Their SLS-