Nice piece. My comment: not so much the cost per se (IMHO) but as you point out it's the massive %age of failures (>90%) even after drugs get to Phase 1 by when supposedly things are supposed to look rosy. The breakdown of failure is roughly 40% non-efficacious, 40% toxicity, 20% business reasons. THIS is what needs fixing, and until Pharma takes a SYSTEMS approach instead of doing molecular biology on supposed targets it will not get better. Successful drugs are successful because they hit multiple targets (see e.g. Mestres, J., Gregori-Puigjané, E., Valverde, S. and Solé, R. V. (2009) The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Mol Biosyst. 5, 1051-1057. https://doi.org/10.1039/b905821b), as any systems biologist will tell you, not least because folk differ massively (Williams, R. J. (1956) Biochemical Individuality. John Wiley, New York). This was and is well known in TCM etc. IMHO the failure to understand the role of transporters in drug disposition is also a major part of this (not enough = lack of efficacy; too much = tox, as per above). Latest version of that story at Kell, D. B. (2021) The transporter-mediated cellular uptake and efflux of pharmaceutical drugs and biotechnology products: how and why phospholipid bilayer transport is negligible in real biomembranes. Molecules. 26, 5629. https://doi.org/10.3390/molecules26185629.
Regeneron is interesting. It would also be good to see which startups went all the way from discovery to commercialization, and what we can learn from these.
A quick search returned these:
Krystal Biotech
Axsome Therapeutics
Madrigal Pharmaceuticals
Immunocore
Apellis Pharmaceuticals
Day One Biopharmaceuticals
Karuna Therapeutics
Common patterns appear to be:
- founded by industry veterans / repeat founders
- who were able to raise a lot of capital to bankroll both R&D and commercialization
- focus on rare diseases with concentrated, high price patient and prescriber bases
Another great essay and explanation of the staggering cost of developing a new drug in our country. Exciting to think of the "full stack" option for the passionate founders able to follow their scientific discovery all the way through the process to developing and releasing the drug in their own companies. Exciting times!
Other than the Andrew Lo Healthcare Finance book, any other interesting books on financing these companies? Also, any specific to Canada? Thank you so much. I am an undergraduate student.
Making discovery more efficient is how the "crazy guys" actually get a win before they even have to worry about the cost of a Phase 3 trial. Unsettling, but a great reality check.
Nice piece. My comment: not so much the cost per se (IMHO) but as you point out it's the massive %age of failures (>90%) even after drugs get to Phase 1 by when supposedly things are supposed to look rosy. The breakdown of failure is roughly 40% non-efficacious, 40% toxicity, 20% business reasons. THIS is what needs fixing, and until Pharma takes a SYSTEMS approach instead of doing molecular biology on supposed targets it will not get better. Successful drugs are successful because they hit multiple targets (see e.g. Mestres, J., Gregori-Puigjané, E., Valverde, S. and Solé, R. V. (2009) The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Mol Biosyst. 5, 1051-1057. https://doi.org/10.1039/b905821b), as any systems biologist will tell you, not least because folk differ massively (Williams, R. J. (1956) Biochemical Individuality. John Wiley, New York). This was and is well known in TCM etc. IMHO the failure to understand the role of transporters in drug disposition is also a major part of this (not enough = lack of efficacy; too much = tox, as per above). Latest version of that story at Kell, D. B. (2021) The transporter-mediated cellular uptake and efflux of pharmaceutical drugs and biotechnology products: how and why phospholipid bilayer transport is negligible in real biomembranes. Molecules. 26, 5629. https://doi.org/10.3390/molecules26185629.
Regeneron is interesting. It would also be good to see which startups went all the way from discovery to commercialization, and what we can learn from these.
A quick search returned these:
Krystal Biotech
Axsome Therapeutics
Madrigal Pharmaceuticals
Immunocore
Apellis Pharmaceuticals
Day One Biopharmaceuticals
Karuna Therapeutics
Common patterns appear to be:
- founded by industry veterans / repeat founders
- who were able to raise a lot of capital to bankroll both R&D and commercialization
- focus on rare diseases with concentrated, high price patient and prescriber bases
Another great essay and explanation of the staggering cost of developing a new drug in our country. Exciting to think of the "full stack" option for the passionate founders able to follow their scientific discovery all the way through the process to developing and releasing the drug in their own companies. Exciting times!
Another great read. I spent a month studying Roche and its history of capital allocation.
The rise of modern medicine is fascinating and the next step is definitely a better system to get to market. https://sparkmind.capital/podcasts/leaders/roche-here-there-and-everywhere/
Other than the Andrew Lo Healthcare Finance book, any other interesting books on financing these companies? Also, any specific to Canada? Thank you so much. I am an undergraduate student.
Making discovery more efficient is how the "crazy guys" actually get a win before they even have to worry about the cost of a Phase 3 trial. Unsettling, but a great reality check.