from ice-nine to Navalny

https://www.gwern.net/Notes#highly-potent-drugs-as-psychological-warfare-weapons

powerful nanoscale chemicals, shape-shifting crystals that infect other crystals, ice-nine after all can happen, the AIDS drugs Ritonavir that was lost to this mechanism

derek lowe on Perverse Polymorphism https://blogs.sciencemag.org/pipeline/archives/2019/11/26/perverse-polymorphism

senescence in society and organism

you ought to pay respect to elder components of your society, should you also respect older components of your body, senescent cells that spread inflammation and disease ?

Unity enters phase 1 of its molecule that targets and kills senescence cells, senescent cell therapy https://blogs.sciencemag.org/pipeline/archives/2020/08/17/unity-biotechnology-and-senescent-cell-therapy

Nature just published a novel application of CAR-T therapy targeting senescent cells https://www.nature.com/articles/s41586-020-2403-9 from A16 https://a16z.com/2020/08/09/slaying-sleeper-cells-aging-car-t/

Vaccine nationalism

a bit of vaccine news and vaccine nationalism

Moderna all in one day, last Monday, first positive results of trial, collects 1,34 billion in new stocks offering at 30 billion valuation, to be used for vaccine production https://www.fiercepharma.com/manufacturing/moderna-eyes-1-34-billion-stock-offering-to-manufacture-covid-19-vaccine

Sanofi says US will be the first to get vaccine since they invested in it https://www.businessinsider.com/potential-coronavirus-vaccine-united-states-first-french-pharmaceutical-sanofi-ceo-2020-5?IR=T

Advent will give the UK government the first 30 million doses of vaccine co-developed in Italy with IRBM https://www.irbm.com/press-review/london-reserves-30-million-doses-of-the-vaccine-born-between-oxford-and-pomezia-rome/

Let’s zoom out, The EU held a funding conference 2 weeks ago, collecting almost €8 billion. Bill Gates donated but the US was not even there, China attended but did not donate. Neither did Russia nor India attend. The world is divided in 5 blocks, each block has its own vaccine strategy

A beautiful 3d on vaccine and geopolitics by Paul Poast. Vaccine nationalism is a real risk, an aspect of the power politics of pandemics https://twitter.com/ProfPaulPoast/status/1257642933949476866

In the general uncooperative and nationalistic stance on Covid and vaccine, a country like Italy, biggest pharma producer in EU, should bet on one or more vaccine candidates and start building productive capacity. It would be an effective industrial policy and would give more chances to get the vaccine early.

Will we grab a few billions off the ESM and invest it? Or will we wait for the EU to ivenst its own 8 billions and dictate the strategy?

 

 

 

how a fast learning curve looks like

Screenshot 2020-03-08 at 10.35.07

gore edition, new cases and deaths, divergence in growth as case grows and experience is built on how to treat critical patients of a novel disease

But in a “learning curve” framework that works you need to be able to cope with demand, your service should not run into some sort of “diminishing return” at the margin or in a more discrete case, being able to serve the customers in order to have the very same outcomes that you are measutring gains against

In other words, ICU’s might have overflown, critical patients might have gone untreated, mortality might have spiked as a consequence, nd thereafter kept a steeper profile

Screenshot 2020-03-11 at 00.05.17

the disaster medicine protcol was issued by the society of anestesiologists on the 6th, clearly a situation was building up and its exponential nature was not lost on doctors fighting the disease https://www.esanum.it/today/posts/covid-19-le-raccomandazioni-della-siaarti

Deeplearning and organic chemistry

there’s things so specific that you never get to know them and if you do you are not able to retrieve unless you have noted down its name or some keyword

“neural networks applied to computed molecular fingerprints or expert-crafted descriptors and graph convolutional neural networks that construct a learned molecular representation by operating on the graph structure of the molecule.”

from here https://pubs.acs.org/doi/abs/10.1021/acs.jcim.9b00237

more AI and drug discovery though

Of chimeras and their prices

Novartis Kymriah, a single dose is priced at $475,000. Steep price for a medicine, or is it a medicine ?

It is CAR-T therapy that is developed to target an increasing number of cancers

“And these price tags don’t include the delivery of post-therapy care to CAR-T patients, who typically suffer complications from the infusion. Subsequent hospital stays and supportive care can drive the total costs to a million dollars or more. Merely counting the seventy-five hundred U.S. patients who meet the current F.D.A. indications for Yescarta, the estimated annual expenditure could be three billion dollars.”

Biggest business in town, thats Why we are investing in Tmunity

Quote above is from Siddhartha Mukherjee The Promise and Price of Cellular Therapies

I am curious to know how you market and deliver a “medicine” like Kymriah

-Cost considerations: even if we treat as a procedure and not a medicine CAR-T can have 6- figures cost (Kymriah introduced a world first: performace therapy, pay if satisfied)

-treating it as a medicine could stiffen marginal improvements, procedures on the other end have more lax approval for small ietrative improvements

-a medicine is manifactured, a procedure is a surgeon’s craft, unless a way is found to mass manifacture CAR-T there will be conflicts

Cytokine Storm

Cellicon Valley