@ZacharyBrennan Thanks for writing this. I have no financial relationship with the company. Here are my thoughts:

The whole manufacturing flexbility (reusing established CMC) only kicks in after you’ve got the process fully ready for those true individualized n-of-1 therapies.

Grace’s AAV9 is basically one standard vector for everyone (even though ultra-rare), so they haven’t cleared that bar yet. FDA’s still forcing a fresh GMP run. No shortcut, unfortunately.

Grace Science (co-founded by Carolyn Bertozzi) is running out of cash and says the FDA didn't let them use the "plausible mechanism" pathway bc, although they're developing an ultra-rare gene therapy, it's not an n-of-1 therapy. The FDA is also requesting a 2nd manufacturing run prior to BLA submission - a move the co. says could end it https://endpoints.news/grace-science-says-fda-jeopardizes-rare-disease-therapy/

@RuxandraTeslo To be fair, we also need to think about better ways to deliver these medicines. Autologous Cell therapy is a fantastic proof of concept, but if we can’t figure out how to make these medicines more broadly scalable without multi billion dollar infrastructure buildout, we’ve failed

@RuxandraTeslo It’s a good drug that is already partnered. The valuation reflects the value of the company accurately. The stock price is perfectly reflecting the value of you ask me

@DrSynbio I agree. In vivo CAR Ts for example are super exciting for this reason.

However, we can't wait for a new tech to always save us. We should be efficient abt how we regulate these things from the get-go.

@RuxandraTeslo you should do an analysis of how little of the societal value biotech companies create capture vs other industries

@RuxandraTeslo yeah all these people saying that AI will solve biology have forgotten about the FDA

@incredutility how would one go about that?

QALY improvements driven by a drug vs revenue (or some measure of share price appreciation) of that drug? I’m past my undergrad global health days but would be fun to compare HEOR numbers per patient by groups like ICER/NICE * number of patients treated to pharma revenue numbers

@NEObioMATRIX It's not about whether the stock reflects the values, it's about whether the field is incentivised enough! I agree the market is rational.

And the reason it's partnered is that it's incredibly hard to bring a therapy to approval because of these complexities

seems pretty important to ensure, potency, purity, stability to support bridging to a commercial ready FDA-licensed gene therapy--if it's only for a few specific people, why even bother with a BLA. And no VC will fund? hmm Dumping on the agency for unclear reasons drowns the issues where attention is needed.

@ZacharyBrennan If they're "running out of cash", its not because of the ataxia program, which is discussed only in an appendix of their current corporate presentation. The future of the company lies with the subarachnoid hemmorhage drug, which is closer to approval and has a larger market

@ZacharyBrennan So where is the problem to warrant all this noise… let them run out of cash! Sad to see @US_FDA being treated as a transactionary agency…

@RuxandraTeslo only thing I'd add to this discussion is a bit of an educated guess that this stock movement also reflects geopolitical risks

@RuxandraTeslo 100%

@RuxandraTeslo Hard agree. Both are true.

@RuxandraTeslo That’s the game R. Enjoy the journey

@RuxandraTeslo Could it be that there is no role for private funding in this market (rare diseases)? Private markets expect substantial return on their investments, but how much can you extract from a market that has such a low number of customers (36k new patients a year in case of myeloma).

@RuxandraTeslo they should change their name to "curiome AI" and the stock would 10x