At BIO2024, I spoke Sam Clark, CEO and founder of Terran Biosciences, about their development of new long-duration dosage forms for the treatment of schizophrenia . We discussed the development of prodrugs, the potential of psychedelics, and the journey of founding a biotech company.
The Genesis of Terran Biosciences
Sam's journey into biotech was personal. Growing up around friends and family members with severe mental illnesses like bipolar disorder and Alzheimer's disease, he saw the limitations of existing treatments. Through his studies at MIT and Columbia, he recognized the slow pace of development and the significant side effects of available medications. Existing treatments for mental illnesses have many unpleasant side effects from cause weight gain to Parkinsonian symptoms and hormonal disruptions. All of that led to his decision to found Terran Biosciences hoping to transform the standard of care.
Terran's Pipeline
Terran's lead asset, TerXT, is a novel combination of prodrugs of xanomeline and trospium, compounds that have been around for a long time, but with less than ideal pharmacokinetics. They also have Idazoxan XR, an adjunctive treatment for schizophrenia, and several new forms of psychedelics like psilocybin and MDMA with differentiated pharmacokinetics aimed at making these treatments more accessible and affordable.
Sam explained the significance of prodrugs in their approach. Unlike simple reformulations, prodrugs are entirely new compounds created by attaching a side chain to the original molecule. This attachment improves pharmacokinetics, allowing for more effective absorption and longer-lasting effects. For example, the older compounds xanomeline and trospium, which need to be taken twice daily, have been modified into prodrugs that can be administered once daily or as long-acting injectables with multi-month durations. This innovation not only simplifies the regimen for patients but also leverages the FDA's accelerated 505(b)(2) pathway, potentially bringing these new treatments to market faster.
Overcoming Development Challenges
Creating effective prodrugs is no small task. Sam described the extensive process, involving a team of world experts and over 200 FTE chemists working tirelessly. They designed over 10,000 prodrugs, synthesized 700, and conducted 500 preclinical studies to refine their approach. This massive undertaking, though challenging, has led to promising results.
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The Potential of Psychedelics
I also wanted to explore psychedelics, a field that has generated significant interest in recent years. Terran is developing new forms of MDMA, psilocybin, and 5-MeO-DMT, aiming to improve their pharmacokinetics and make these treatments more accessible. Sam highlighted MDMA's potential, currently under FDA review for treating PTSD, with a decision expected soon. (Right after we spoke, the FDA advisory panel recommended rejecting approval for MDMA. The decision has not been made yet.) By creating new forms and leveraging the 505(b)(2) pathway, Terran aims to overcome patent barriers and ensure these treatments are affordable.
Insights into Brain Function
I am particularly curious about anything we can learn about neurobiology from studies around these therapeutic compounds and psychedelics. Here is the challenge: Psychedelics, for example, act on multiple receptors. Teasing out different pathways in the brain is complicated. Functional MRI studies of people undergoing psychedelic trips show reproducible changes in brain pathways, suggesting potential mechanisms but the circuitry is complicated. There are no simple answers yet.
The Journey of a First-Time Founder
I asked Sam about his experience as a first-time founder. Terran's success is in large part due to its corporate structure, modeled after fast-moving Silicon Valley companies. By avoiding traditional hierarchical structures and instead utilizing a flat organization with world experts leading sub-teams, Terran has managed to solve complex problems efficiently.
Team building has been essential to Terran's achievements. Sam's approach involves creating specialized teams for different facets of a problem, ensuring a comprehensive and collaborative effort.
“Workflows” for the Win
I have seen a pattern in several interviews recently. Changing a process can have as big of an effect on solving a problem (and creating success for a company) as developing a new product. In this case, it’s a bit of both. The problem being solved by TerXT is the patient regimen. Prodrugs with longer-duration pharmacokinetics make adherence easier for the patient. At the same time, I appreciate the enormous amount of development effort that went into creating those prodrugs. A different approach to assembling teams and managing them is also a significant change in the workflow that will have an impact.
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