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Cracking the Glioblastoma Challenge: A CEO's Journey in Brain Cancer Treatment
John Climaco, Chairman and CEO of CNS Pharmaceuticals, elaborates on his company's dedicated mission in the research and development of new cancer treatments for the brain and the central nervous system. Climaco, an experienced entrepreneur, was drawn to the immense challenge of glioblastoma, referring to it as an "uncrackable nut" and "the toughest of the tough". He explains that glioblastoma multiforme is the most common and deadly primary brain cancer, which is "essentially uniformly fatal" and often degrades a person before their body succumbs. The standard of care for this disease has remained largely stagnant for the past two decades, and it continues to be a "black box" in oncology with no known precursors or biomarkers.
The primary obstacle in treating brain cancer is the blood-brain barrier, a highly protected sanctuary that makes it "very, very difficult to get therapies through". While glioblastoma tumors are vulnerable to conventional chemotherapies in laboratory settings, their location within the brain, shielded by this barrier, renders them largely untouchable inside the body. CNS Pharmaceuticals addresses this by focusing on molecules specifically designed to bypass this protective network. Their "back to the future" approach involves two unique compounds: Berubicin, a novel anthracycline, and TPI 287, a novel taxane. Both are distinguished by their ability to cross the blood-brain barrier, unlike other drugs in their respective classes. These drugs aim to provide much-needed options for patients experiencing their first disease recurrence, where current therapeutic choices are severely limited.
In terms of development, CNS Pharmaceuticals is advancing a Phase 2 clinical program for TPI 287, with plans to begin dosing patients in the first quarter of the next year and anticipate data by early 2027. They are also closely monitoring the FDA's potential new pathway for "conditional approval," which could be particularly relevant for drugs like Berubicin. Berubicin recently completed a global study showing a 30% improvement in overall survival in patients, although it did not meet the primary endpoint for statistical significance required for traditional approval. This conditional pathway is specifically intended for rare diseases with few to no treatment options, a description that perfectly fits glioblastoma patients.
Climaco highlights the company's lean operational philosophy, with a small team of only five remote members, ensuring that "all of the money gets poured into the programs" rather than extraneous infrastructure. This focus is paramount given the significant capital burn rate inherent in drug development. Their approach to risk mitigation emphasizes a highly collaborative and senior team that is encouraged to challenge assumptions and adapt course as needed, fostering a culture of humility and continuous improvement.
The decision to fund the company through public markets, rather than venture capital, was deliberate. Climaco notes that public funding has allowed them to continue financing their challenging work, especially given the historical reluctance of venture capital to invest heavily in glioblastoma due to high failure rates. Key performance indicators monitored include patient recruitment during trials and maintaining sufficient cash reserves. Despite the constant headwinds and inherent risks of their business, Climaco expresses that he sleeps well at night, knowing that they are "doing our very best" and remain true to their mission. He draws inspiration from the patients who face long odds with deep acceptance, stating that if they can accept what's out of their control, then he can certainly "accept what's out of mine".
Key Takeaways
1. Cultivate a Laser Focus and Embrace Immense Challenges: Climaco stresses the importance of having a "laser focus on our mission" and being drawn to "doing stuff that nobody's ever done before". He specifically chose to tackle glioblastoma because it was an "uncrackable nut" and "the toughest of the tough". For founders, this suggests identifying and passionately committing to a significant problem, ensuring that all efforts are aligned with a singular, clear objective, especially when facing long odds and high failure rates.
2. Operate Lean and Optimize Capital Allocation: CNS Pharmaceuticals runs a "really lean shop" with only five remote team members and no physical office, ensuring that "all of the money gets poured into the programs". Climaco advises against building to scale during periods of abundant capital, as this can lead to difficulties when markets tighten. This highlights the critical importance of disciplined capital management, minimizing unnecessary overhead, and directing resources primarily towards core value-driving activities, particularly in capital-intensive and long-lead-time industries like biotech.
3. Foster a Culture of Collaborative Humility and Continuous Adaptation: Climaco emphasizes building a senior team that engages in "true collaboration" and is willing to "question some of your assumptions". He advocates for regularly re-examining assumptions that might "morph into a fact" over time, even if it means acknowledging past mistakes and "changing course". This encourages CEOs to create an environment where diverse perspectives are valued, assumptions are rigorously challenged, and the team is agile enough to correct course for optimal results, regardless of when an error is identified.
4. Strategically Choose Funding Sources and Maintain Resilience: CNS Pharmaceuticals deliberately chose public markets over venture capital, recognizing that the "odds are really long" for glioblastoma research, making private financing challenging. This approach allowed them to "continue to finance the company". Climaco also highlights the importance of personal resilience, stating he sleeps well knowing they are "doing our very best" and are true to their mission, drawing inspiration from patients' "deep acceptance" of their circumstances. This underscores the need for founders to select funding avenues that best suit their unique project's risk profile and to cultivate a mindset of unwavering dedication and acceptance of factors beyond their control.
Chapter Summary
(00:01:04) - CEO's Career: John Carmichael, CNS CEO, details his entrepreneurial path, leading to CNS's 2019 public listing, focused on glioblastoma.
(00:02:60) - Glioblastoma Challenge: This fatal brain cancer is hard to treat; drugs struggle to cross the blood-brain barrier. Few companies tackle this "black box".
(00:08:09) - CNS's Unique Drugs: CNS develops unique chemotherapies, Berubicin and TPI 287, designed to penetrate the blood-brain barrier, unlike other established drugs.
(00:13:56) - Development Progress: TPI 287's Phase 2 starts Q1 next year. Berubicin showed 30% improved survival, now targeting new FDA conditional approval for patients with limited options.
(00:17:15) - Lean, Publicly Funded: CNS operates with a small, remote team, directing capital primarily to drug programs. Public funding is chosen for consistency over venture capital.
(00:20:37) - Risk Mitigation: Risk is managed by a collaborative team that questions assumptions and adapts strategy. This ensures efficient trial execution.
(00:30:25) - Focus & Motivation: Key metrics are patient recruitment and cash flow. John is driven by glioblastoma patients' resilience, embracing the mission's difficulties.
Resource Mentioned in this Episode
New York Times Podcasts
https://www.nytimes.com/spotlight/podcasts
CNS Pharmaceuticals
https://cnspharma.com/
Stay Updated
Please visit Brio360 on other episodes and resources on driving value creation
https://brio360.com
Follow our host
Peter Ho
https://linkedin.com/in/peterhocm
Please note that information provided in the podcast is for informational and educational purposes only and is not a recommendation to take any particular action, nor an offer or solicitation to buy or sell any securities or services presented. It is not investment advice. Brio360 does not provide legal or tax advice.
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By Brio360
John Climaco, Chairman and CEO of CNS Pharmaceuticals, elaborates on his company's dedicated mission in the research and development of new cancer treatments for the brain and the central nervous system. Climaco, an experienced entrepreneur, was drawn to the immense challenge of glioblastoma, referring to it as an "uncrackable nut" and "the toughest of the tough". He explains that glioblastoma multiforme is the most common and deadly primary brain cancer, which is "essentially uniformly fatal" and often degrades a person before their body succumbs. The standard of care for this disease has remained largely stagnant for the past two decades, and it continues to be a "black box" in oncology with no known precursors or biomarkers.
The primary obstacle in treating brain cancer is the blood-brain barrier, a highly protected sanctuary that makes it "very, very difficult to get therapies through". While glioblastoma tumors are vulnerable to conventional chemotherapies in laboratory settings, their location within the brain, shielded by this barrier, renders them largely untouchable inside the body. CNS Pharmaceuticals addresses this by focusing on molecules specifically designed to bypass this protective network. Their "back to the future" approach involves two unique compounds: Berubicin, a novel anthracycline, and TPI 287, a novel taxane. Both are distinguished by their ability to cross the blood-brain barrier, unlike other drugs in their respective classes. These drugs aim to provide much-needed options for patients experiencing their first disease recurrence, where current therapeutic choices are severely limited.
In terms of development, CNS Pharmaceuticals is advancing a Phase 2 clinical program for TPI 287, with plans to begin dosing patients in the first quarter of the next year and anticipate data by early 2027. They are also closely monitoring the FDA's potential new pathway for "conditional approval," which could be particularly relevant for drugs like Berubicin. Berubicin recently completed a global study showing a 30% improvement in overall survival in patients, although it did not meet the primary endpoint for statistical significance required for traditional approval. This conditional pathway is specifically intended for rare diseases with few to no treatment options, a description that perfectly fits glioblastoma patients.
Climaco highlights the company's lean operational philosophy, with a small team of only five remote members, ensuring that "all of the money gets poured into the programs" rather than extraneous infrastructure. This focus is paramount given the significant capital burn rate inherent in drug development. Their approach to risk mitigation emphasizes a highly collaborative and senior team that is encouraged to challenge assumptions and adapt course as needed, fostering a culture of humility and continuous improvement.
The decision to fund the company through public markets, rather than venture capital, was deliberate. Climaco notes that public funding has allowed them to continue financing their challenging work, especially given the historical reluctance of venture capital to invest heavily in glioblastoma due to high failure rates. Key performance indicators monitored include patient recruitment during trials and maintaining sufficient cash reserves. Despite the constant headwinds and inherent risks of their business, Climaco expresses that he sleeps well at night, knowing that they are "doing our very best" and remain true to their mission. He draws inspiration from the patients who face long odds with deep acceptance, stating that if they can accept what's out of their control, then he can certainly "accept what's out of mine".
Key Takeaways
1. Cultivate a Laser Focus and Embrace Immense Challenges: Climaco stresses the importance of having a "laser focus on our mission" and being drawn to "doing stuff that nobody's ever done before". He specifically chose to tackle glioblastoma because it was an "uncrackable nut" and "the toughest of the tough". For founders, this suggests identifying and passionately committing to a significant problem, ensuring that all efforts are aligned with a singular, clear objective, especially when facing long odds and high failure rates.
2. Operate Lean and Optimize Capital Allocation: CNS Pharmaceuticals runs a "really lean shop" with only five remote team members and no physical office, ensuring that "all of the money gets poured into the programs". Climaco advises against building to scale during periods of abundant capital, as this can lead to difficulties when markets tighten. This highlights the critical importance of disciplined capital management, minimizing unnecessary overhead, and directing resources primarily towards core value-driving activities, particularly in capital-intensive and long-lead-time industries like biotech.
3. Foster a Culture of Collaborative Humility and Continuous Adaptation: Climaco emphasizes building a senior team that engages in "true collaboration" and is willing to "question some of your assumptions". He advocates for regularly re-examining assumptions that might "morph into a fact" over time, even if it means acknowledging past mistakes and "changing course". This encourages CEOs to create an environment where diverse perspectives are valued, assumptions are rigorously challenged, and the team is agile enough to correct course for optimal results, regardless of when an error is identified.
4. Strategically Choose Funding Sources and Maintain Resilience: CNS Pharmaceuticals deliberately chose public markets over venture capital, recognizing that the "odds are really long" for glioblastoma research, making private financing challenging. This approach allowed them to "continue to finance the company". Climaco also highlights the importance of personal resilience, stating he sleeps well knowing they are "doing our very best" and are true to their mission, drawing inspiration from patients' "deep acceptance" of their circumstances. This underscores the need for founders to select funding avenues that best suit their unique project's risk profile and to cultivate a mindset of unwavering dedication and acceptance of factors beyond their control.
Chapter Summary
(00:01:04) - CEO's Career: John Carmichael, CNS CEO, details his entrepreneurial path, leading to CNS's 2019 public listing, focused on glioblastoma.
(00:02:60) - Glioblastoma Challenge: This fatal brain cancer is hard to treat; drugs struggle to cross the blood-brain barrier. Few companies tackle this "black box".
(00:08:09) - CNS's Unique Drugs: CNS develops unique chemotherapies, Berubicin and TPI 287, designed to penetrate the blood-brain barrier, unlike other established drugs.
(00:13:56) - Development Progress: TPI 287's Phase 2 starts Q1 next year. Berubicin showed 30% improved survival, now targeting new FDA conditional approval for patients with limited options.
(00:17:15) - Lean, Publicly Funded: CNS operates with a small, remote team, directing capital primarily to drug programs. Public funding is chosen for consistency over venture capital.
(00:20:37) - Risk Mitigation: Risk is managed by a collaborative team that questions assumptions and adapts strategy. This ensures efficient trial execution.
(00:30:25) - Focus & Motivation: Key metrics are patient recruitment and cash flow. John is driven by glioblastoma patients' resilience, embracing the mission's difficulties.
Resource Mentioned in this Episode
New York Times Podcasts
https://www.nytimes.com/spotlight/podcasts
CNS Pharmaceuticals
https://cnspharma.com/
Stay Updated
Please visit Brio360 on other episodes and resources on driving value creation
https://brio360.com
Follow our host
Peter Ho
https://linkedin.com/in/peterhocm
Please note that information provided in the podcast is for informational and educational purposes only and is not a recommendation to take any particular action, nor an offer or solicitation to buy or sell any securities or services presented. It is not investment advice. Brio360 does not provide legal or tax advice.