Man, how amazing is Jennifer Doudna? First she invents the world-changing CRISPR technology, then when it's use to drive significant human results gets stymied by regulation and the positive non-academic impacts of CRISPR stall for a decade, she takes on the regulatory Beast and gets the Platform Technology Designation? A towering role model and hero for us all.
Amazingly cogent, comprehensive, and useful summary of the landscape too, sincere kudos for putting this all together and publishing it!
Another very well written article. I’d be interested in seeing the evolution of pricing for such curative medicines if the regulatory path follows the platform approach indicated by the FDA.
Great write-up! We are indeed living in interesting times and the outlook for disease fighting agents coming out of the new biotech world is fantastic!
A great read and love the "reusable rockets" analogy. Where do we think the equity value accrues if personalized gene-editing medicines like CRISPR do become commonplace? More in the launch business (picks and shovels / infra layer) OR the satellite business (end-user product / application layer)?
I think value could accrue in *both* parts of the stack. Danaher's long-term investment in picks and shovels could really benefit from this set of advancements—which is in large part why I think they are the company most motivated to move into n-of-1 cures and personalized medicine. I think there's room for a lot of new infrastructure providers across next-gen cell and gene therapies.
But the application layer should definitely also have some big winners. Think of all of the massive tech businesses built on top of AWS.
For the pharma companies that don't invest in building out the manufacturing and R&D chops for this next wave of technologies, they could see their distribution/cash advantage erode over time.
Great article. Exciting stuff, so long as the FDA or other interest groups don't get in the way.
Minor point -- I did find this phrasing peculiar: "The FDA only came into existence in 1906 and gradually evolved into its current form after two major belt tightenings in 1938 and 1962." I would not call these belt tightenings. These were large expansions of the power and scope of the FDA. The FDA's powers expanded to cover all prescription drugs and then to (expensively) evaluate effectiveness on top of safety. These expansions were met with lots of extra tax payer money. I don't see the belt tightening here!
Perhaps "belt tightening" is the wrong phrase—I'm referring to an increase in scrutiny rather than an aim at cost-savings! It was certainly the opposite, as you point out.
What an exciting and inspiring read! As you pointed out, effective delivery systems are crucial for CRISPR's success. What do you think are the most promising delivery mechanisms currently under development?
Some a little misleading statements - you need to remake chemically full guide rna for each new target and although there is a 20 nucleotides difference per target your typical RNA guide is a 100 plus RNA nucleotides . Chemical synthesis of a 100 mer RNA is getting much better with recent focus and innovations but still rather challenging . .
Agree on both in principle . The “ research “ quality guides often have impurities that can lead to potential off target editing , tightening spec on those for GMP material is indeed challenging but doable .
Overall - great and timely article , hopefully N=1 movement will gain even more momentum !
Am I missing something or does the breakdown in R & D spend not add up to 100%? FWIW my rule of thumb is that Discovery & PC research is roughly one third of total spend, and clinical spend constitutes the remaining two thirds.
From Alex's original blog: "The bulk of that spending goes towards clinical trials and associated manufacturing costs; roughly 50% of total large pharma R&D spend is apportioned to phase I, II, and III trials compared to 15% for preclinical work."
I'm not sure where the other ~30% of the spend is supposed to be accounted for in this figure, but the bulk of R&D spend is definitely in trials.
Hopefully, the Platform Technology Mandate would dramatically reduce this across diseases being treated with the same underlying technology.
Man, how amazing is Jennifer Doudna? First she invents the world-changing CRISPR technology, then when it's use to drive significant human results gets stymied by regulation and the positive non-academic impacts of CRISPR stall for a decade, she takes on the regulatory Beast and gets the Platform Technology Designation? A towering role model and hero for us all.
Amazingly cogent, comprehensive, and useful summary of the landscape too, sincere kudos for putting this all together and publishing it!
Hear, hear! Well said. Thanks for reading.
Another very well written article. I’d be interested in seeing the evolution of pricing for such curative medicines if the regulatory path follows the platform approach indicated by the FDA.
Great write-up! We are indeed living in interesting times and the outlook for disease fighting agents coming out of the new biotech world is fantastic!
A great read and love the "reusable rockets" analogy. Where do we think the equity value accrues if personalized gene-editing medicines like CRISPR do become commonplace? More in the launch business (picks and shovels / infra layer) OR the satellite business (end-user product / application layer)?
Really good question Apoorv.
I think value could accrue in *both* parts of the stack. Danaher's long-term investment in picks and shovels could really benefit from this set of advancements—which is in large part why I think they are the company most motivated to move into n-of-1 cures and personalized medicine. I think there's room for a lot of new infrastructure providers across next-gen cell and gene therapies.
But the application layer should definitely also have some big winners. Think of all of the massive tech businesses built on top of AWS.
For the pharma companies that don't invest in building out the manufacturing and R&D chops for this next wave of technologies, they could see their distribution/cash advantage erode over time.
Great article. Exciting stuff, so long as the FDA or other interest groups don't get in the way.
Minor point -- I did find this phrasing peculiar: "The FDA only came into existence in 1906 and gradually evolved into its current form after two major belt tightenings in 1938 and 1962." I would not call these belt tightenings. These were large expansions of the power and scope of the FDA. The FDA's powers expanded to cover all prescription drugs and then to (expensively) evaluate effectiveness on top of safety. These expansions were met with lots of extra tax payer money. I don't see the belt tightening here!
This is a good point!
Perhaps "belt tightening" is the wrong phrase—I'm referring to an increase in scrutiny rather than an aim at cost-savings! It was certainly the opposite, as you point out.
What an exciting and inspiring read! As you pointed out, effective delivery systems are crucial for CRISPR's success. What do you think are the most promising delivery mechanisms currently under development?
Some a little misleading statements - you need to remake chemically full guide rna for each new target and although there is a 20 nucleotides difference per target your typical RNA guide is a 100 plus RNA nucleotides . Chemical synthesis of a 100 mer RNA is getting much better with recent focus and innovations but still rather challenging . .
IDT does a pretty great job of quickly producing custom research-grade guide RNAs within 3-6 days already: https://www.idtdna.com/pages/products/crispr-genome-editing/custom-guide-rna
In my view, it seems the big technical need will be to do this with GMP quality, but people are already making good progress on this problem: https://x.com/UrnovFyodor/status/1798012519866675496
Agree on both in principle . The “ research “ quality guides often have impurities that can lead to potential off target editing , tightening spec on those for GMP material is indeed challenging but doable .
Overall - great and timely article , hopefully N=1 movement will gain even more momentum !
Am I missing something or does the breakdown in R & D spend not add up to 100%? FWIW my rule of thumb is that Discovery & PC research is roughly one third of total spend, and clinical spend constitutes the remaining two thirds.
You're right on both fronts.
From Alex's original blog: "The bulk of that spending goes towards clinical trials and associated manufacturing costs; roughly 50% of total large pharma R&D spend is apportioned to phase I, II, and III trials compared to 15% for preclinical work."
I'm not sure where the other ~30% of the spend is supposed to be accounted for in this figure, but the bulk of R&D spend is definitely in trials.
Hopefully, the Platform Technology Mandate would dramatically reduce this across diseases being treated with the same underlying technology.