Crossing the Brain Barrier

Kabir Nath
CEO
COMPASS Pathways

When the English-born American revolutionary Thomas Paine said, “The World is my country, all mankind are my brethren, and to do good is my religion,” he might as well have been referring to COMPASS Pathways’ CEO, Kabir Nath. A British pharma executive who likewise made his way to the US, Nath is a true citizen of the world. He has used his diverse experiences, both business- and culture-related, to manage companies and bring hope to patients. In his current position, he is driven by the need to improve upon available treatments for mental health issues, and he believes psychedelic medicine could have a strong impact. As COMPASS continues its Phase III clinical trials for COMP360 psilocybin to address treatment-related depression (TRD), Nath is on his way to making a difference.

Bringing order from chaos

Raised in the UK, Nath graduated from the University of Cambridge with an MA in math in 1986. Following that, he became a strategy consultant with Booz Allen Hamilton and another startup consultancy for approximately four years. Still not knowing what he wanted to do, he earned his MBA from INSEAD in Fontainebleau, France. In 1992, he joined the medical technology company Smith and Nephew.

Though Smith and Nephew was based in England, India was just reopening after the end of the license raj in the early 1990s, and Nath was sent abroad to “put the business back together.” In addition, he spent time in Singapore before eventually returning to London in a role focused on business development strategy.

“Smith and Nephew went from eight divisions to three, completely restructured, and became a growth company,” says Nath. “I was very much part of that. But I really loved running businesses, and it was time to get back to running a business.”

With little knowledge of the pharmaceutical industry, Nath accepted a job offer from Bristol Myers Squibb (BMS) in 2003 and moved back to Asia. At that time, the standard of care for hepatitis B was a GSK drug called Epivir (lamivudine). BMS had discovered and developed a new drug called Baraclude (entecavir), which had good efficacy and none of Epivir’s resistance profile. Nath joined as BMS was preparing to launch Baraclude throughout Asia, which was (and still is) its biggest market.

“Nearly 20 years ago, China was an incredibly challenging environment for pharmaceutical companies,” he says. “I had this opportunity to launch Baraclude six months after I arrived. I said to the team, ‘If we cannot succeed at this in China, all of us should be fired.’”

Out of that crisis, he and his team led a successful launch that ultimately yielded more than $500 million in sales in China, a coup for an innovative drug.

Eventually, Nath was relocated to Princeton, NJ. As BMS started moving toward oncology, he wasn’t sure it was a fit for him. So, in 2016, he joined Otsuka Pharmaceutical. Originally a family-run business and now a leading public company in Japan, Otsuka had taken a place on the global stage after discovering Abilify (aripiprazole), on which it had collaborated with BMS, though Nath was never part of those collaborations.

Nath joined the company as president and CEO of Otsuka North America Pharmaceuticals at a pivotal moment—one year after the loss of exclusivity of Abilify when sales in the US had dropped from $5 billion to $1 billion. It was a business that showed great potential, but there was a lack of strong leadership.

“I had the opportunity to rebuild that company in terms of first continuing the commitment to serious mental illness with the follow-on to Abilify as well as the long-acting formulation—and to be able to do a very successful launch in an orphan disease in the renal area,” says Nath.

He was recognized for his successful efforts by being asked to join the management committee of Otsuka Pharmaceutical and ultimately taking responsibility for the global pharmaceutical business as the most senior non-Japanese employee in the company.

Planting the psychedelic seed

Following the success of Abilify, Otsuka decided to focus on serious mental illness and became committed to improving this. Nath also has a strong, personal connection to overcome the challenges of mental health. His father and two close friends from school and university all died by suicide.

“As my career in pharma developed, my interest in mental health, both at Otsuka and now here at COMPASS, has very much focused around that,” he says.

Nath became familiar with COMPASS through Otsuka. In 2018, when Michael Pollan’s book, How to Change Your Mind, was released and brought the topic of psychedelics into the public eye, he told his team they needed to better understand its potential. After some research, the team reported that the science was indeed real and that the leading company was a biotech called COMPASS Pathways. Nath met with COMPASS co-founders, George Goldsmith and Ekaterina Malievskaia, in 2019.

“It became very clear very quickly that we shared a vision for the fact that there needs to be innovation in the treatment of serious mental illness,” he says. “We at Otsuka were always convinced that the science would demonstrate that there could be efficacy and safety [of psychedelics] in certain populations.”

The relationship Nath fostered with COMPASS led to Otsuka investing in the company.

All eyes were on COMP360, COMPASS’ proprietary formulation of synthetic psilocybin, administered with psychological support. With Phase IIb data on the horizon and the expectation that it would move into Phase III and ultimately commercialization for TRD, the board of COMPASS recognized it was time to supplement Goldsmith’s skills with someone who had a deeper understanding of the pharma biotech space. “Over the course of nine months, it appeared I was a logical fit for this role,” says Nath. “When the opportunity came to join [as CEO last summer], I jumped at the chance.”

Moving the needle at COMPASS

While COMP360 psilocybin is the company’s lead asset, Goldsmith, Malievskaia, and (ultimately) Nath’s vision is much broader. They want to transform mental health care. For many patients, taking a long-term oral dose of a currently available antidepressant or antipsychotic brings issues of compliance, adherence, and side effects. As a result, outcomes are not great. Pair that with other issues, such as stigma, lack of access, and inequity, and there is an even greater need for innovation.

During its Phase IIb trial, COMPASS worked with one of the most difficult populations to help—those with TRD. The enrolled participants had failed at least two antidepressants or two classes in their current episode, which for most wasn’t their first episode.

“With COMP360, we saw a 37% response rate the day after administration of the drug, and [more than] 20% of patients were still in response after just one dose after 12 weeks,” says Nath. “Translating that into not only Phase III success but potential commercial uptake is challenging, but that’s exactly what I’m here for.”

The company is building a body of evidence in other indications, too. COMPASS currently has a Phase II study in anorexia, one in post-traumatic stress disorder (PTSD), and has generated signals in a number of other diseases, such as bipolar and body dysmorphic disorder through investigator-initiated studies. It also has a discovery program with some early compounds.

Other than the research of MDMA (3,4-Methyl​enedioxy​methamphetamine) for PTSD conducted by the nonprofit Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation, COMPASS’s studies are the first-ever Phase III program of a psychedelic. “Though it feels like we’ve all been talking about psychedelics for the last four or five years, we have to recognize that the level of hype is unfortunate,” says Nath. “From a clinical development evidence perspective, we’re still very early. By building COMPASS, George and Ekaterina set out to turn anecdote and experience into evidence.”

In parallel with its Phase III program, COMPASS is working hard to understand what the commercial setting will look like. It needs to demonstrate that everyone involved has an economic incentive to participate—from the manufacturer to the provider to the psychiatrist. The company also will use real-world evidence to help get payers on board and drive access.

“In the US, many people who are treated for TRD are on Medicare, Medicaid, or (in many cases) dual eligibles,” says Nath. “Unless we can find a way to get psilocybin and then other psychedelics to that population, we won’t have done our job.”

As COMPASS blazes this trail, it knows other companies are watching to see how it addresses areas such as at-scale commercialization, psychological support, and payment.

“The joy of being at the front is that everyone’s waiting to see what we do so that they can build on it,” says Nath. “That’s probably the biggest reason I took this job—knowing it was going to be different and was going to require ingenuity, creativity, collaboration, and partnership.”

Supporting patients

As part of the COMP360 protocol, COMPASS has agreed with FDA to provide psychological support. Mental health workers, who are required to undergo a minimum of 40 hours of proprietary training, prepare patients by setting expectations beforehand. They are in the room during the administration of the drug to ensure psychological safety. They are also part of the integration session afterward. “Our therapists are not intervening to direct outcomes,” says Nath. “They’re there for support [and] to redirect the patient back into themselves, but we are not offering any form of formal, evidence-based therapy.”

COMPASS also is employing digital tools for support. It encourages trial participants to use an app. Eventually, the company hopes to process relevant data from the app to generate artificial intelligence predictions. “The intersection of digital technology with [psychedelics] may ultimately enable us to unlock some markers to achieve a more personalized form of medicine for people with serious mental illness,” says Nath.

The portal through which COMPASS provides content and trains therapists is also important to build community and to learn from each other.

“One thing I know for certain is I won’t be recruiting 400 reps and detailing every psychiatrist in the US,” notes Nath. “That’s my old life. That’s not going to work at COMPASS. That’s not going to work for COMP360 psilocybin. We’re still going to need most psychiatrists to be aware of the science, but we’re not going to be detailing it to all of them in a traditional manner. We’re going to need a different mix of resources with a strong emphasis on medical affairs, patient engagement, and experience—and to work directly with health systems to understand how to scale psychedelic therapies.”

Perceptions and progress

Another challenge is appealing to a mainstream audience and overcoming the idea that psychedelics are dangerous. However, an investigator-initiated study of bipolar II disorder using COMP360 psilocybin found that in 14 patients, there were no episodes of mania, hypomania, or suicidal ideation. In addition, 12 out of 14 patients were in remission at 12 weeks after administration of a single 25 mg dose.

Generating evidence, responsibly sharing the data, and educating patients and providers will help bring these drugs forward, but it will take time. Nath is encouraged by the positive momentum of the industry though. Many psychiatrists are increasingly interested and motivated to consider psychedelics for their patients.

“I tend to joke that every psychiatrist over the age of 70 says, ‘Sure, I did LSD. This is a great idea. Let’s go for it,’” says Nath. “And the younger generation is picking up on the zeitgeist and is extremely interested. But you have this big cohort of psychiatrists in between from when [psychedelics] went completely underground who really don’t have much experience.”

Having support from regulatory authorities is also key. COMP360 was designated a breakthrough therapy by FDA and received innovative licensing and access pathway designation in the UK for TRD. “FDA has been engaged, supportive, yet also appropriately skeptical at times because this is unprecedented; and whatever we agree, it’s going to be a precedent for other people coming behind us,” he says.

Nath hopes within 15 years that psychedelics will be a mature industry. Along that journey, here are some elements he believes should stand out:

• COMPASS and other organizations will continue to generate compelling evidence.
• Drugs will start being approved—first MDMA and then psilocybin.
• There will be a winnowing of companies in the space.
• The treatment infrastructure will start to scale rapidly, particularly in the US, where private money can fund infrastructure in a more direct way.
• With a number of governments already interested and motivated, the European market will be active. But given the tighter connection with the government on the provider side, working out how that will scale or where the money will come from could be a challenge.
• Beyond TRD, there will be increasing interest in studying other areas of serious mental illness, such as postpartum depression, eating disorders, and substance use disorders. There are multiple small-scale studies already underway in these areas.

Experience-based leadership

The diverse roles Nath has held have created a strong leadership foundation. In addition to his work, the lessons he has learned from living abroad have been invaluable. When he is recruiting, he looks for similar experiences, knowing how it has helped his own career.

“I think the best general managers have spent significant time out of their own culture,” says Nath. “Having to adapt to working in a different culture, even a different language or somewhere where you don’t speak the language, in terms of resilience and clarity of communication, puts a real premium on those things.”

Nath also can translate past experiences to current situations. For example, amid massive disruption during the COVID-19 pandemic, he thought back to how Smith and Nephew dealt with the economic crisis in Asia in 1996. At that time, the company decided to quadruple the quantities of food it distributed to employees in eastern Java because it was the only food their families had access to. That experience reinforced for Nath the importance of understanding and responding to employee emotions and needs in times of crisis.

He believes the most successful leaders are those who can combine the benefits of their successes and failures with humility and personality to lean in and get things done collaboratively.

“One of the joys of COMPASS is that we have a lot of people in their first healthcare job who don’t know what they don’t know,” he says. “We have to educate them on GCP [good clinical practices] and compliance, the US healthcare system, and so on. We have to have leaders who know how to do that and enjoy developing others. That’s the big difference from Big Pharma. I’m not going to hire a whole bunch of middle managers because we can’t afford it, and it’s the wrong thing to do.”

The person behind the science

Nath currently splits his time between NJ, elsewhere in the US, and London. Given his background and the fact that COMPASS is a true US-UK company, the cultural fit couldn’t be closer.

When he’s not traveling for work, he travels for pleasure. He and his wife have a home in South Africa, where she is from, and they enjoy continuing to explore the world together.

Despite his busy schedule, Nath stays grounded through the arts, including playing the piano and the eclectic collecting of mid-century furniture, art, glass, and ceramics. He also keeps his mind fresh through exercise. Nath enjoys taking his two dogs out first thing in the morning, and he runs three to four times per week.

“I’m not a competitive runner, but I like to start the weekend with a long run because that clears my head,” he says.

Nath knows the value of both physical and mental health, and he looks forward to continuing his journey to bring healthy, whole living to those in need around the world.

— Elaine Quilici is a freelance content specialist based in New Jersey. She was formerly editor-in-chief of Pharmaceutical Executive.