N Sayers

Geology, board games, investing, dad jokes. In no particular order.

[N Sayers @nsayers1]

@PJ_Crabb @bloodstockstats @TVR5AVCT And the TSI metric even gives the ADCs an easy ride, since it doesn’t account for how they actively concentrate their warhead in the lungs, leading to severe toxicity. #AVCT

[N Sayers @nsayers1]

@Mike182035 Good question re naming MMAE- no idea. Perhaps there isn’t a more generic way to describe it that doesn’t give it away? Also the original molecule patents are near end of patent life. There are later patents covering their use in ADCs. I don’t know if these would apply to PDCs…

[N Sayers @nsayers1]

@Mike182035 As to why they showed tunability with MMAE but not for DDRi, maybe they tried that one first and had gotten a bit further? It was all quite hot off the press. For the platform, they only needed to show they can still tune the PK in 6207.

[N Sayers @nsayers1]

@Mike182035 It will take in vivo data before they start to get an indication of therapeutic window. These plots show that Compound B required a higher concentration to achieve the same level of cell-kill in vitro (as they slowed the rate of release by modifying the linker).

[N Sayers @nsayers1]

@Mike182035 Valid points. You might be right! Or possibly the evasiveness around DDR warheads may indicate they are working with one or more different potential partners already on different DDRi options. I think fair to say, they likely have multiple suitors for collab.

[N Sayers @nsayers1]

@Mike182035 However, this is comparing the FAP-released drug vs free warheads (not a fair comp), and doesn’t necessarily translate into clinical benefit or lack thereof. And in fairness they also showed more work on MMAE/ExD linker modification to deliberately slow the rate of release. 2/2

[N Sayers @nsayers1]

@Mike182035 4-5x is from the concentration vs cell-kill (inhibition) plots which define the IC50. The MMAE/ExD combo didn’t show any significant uplift vs the individual warheads. Hence it isn’t highlighted.
1/

[N Sayers @nsayers1]

@Mike182035 Around slide 21 in the first half here, but you should check out the whole thing if you haven’t already.

https://t.co/ns430gCVlL

[N Sayers @nsayers1]

@Mike182035 Lower part of the third column. Also check out CC’s explainer video.
https://t.co/sdaQjzKhJB

[N Sayers @nsayers1]

@tom_the_bomb__ Sub-300 or sold for >500? If things pan out as expected, 300-500p will just be part of a one-way upwards gap at some point.

[N Sayers @nsayers1]

@transplant30 @Blueberrymgmnt Unfortunately the full picture is even less rosy. Each vertical bar on the left represents tumour growth/shrinkage for one patient on the trial. Those 8 on the right represent only confirmed responses - in theory the best outcomes (according to the metric of tumour shrinkage).

[N Sayers @nsayers1]

@AgathaChocolats Once more: “It’s SquirREL, not Squirl.”

[N Sayers @nsayers1]

@RobertB49362750 @monstroso Look up Staithes - you may recognise the view!

[N Sayers @nsayers1]

@MylesMcNulty A beautiful tribute to one heck of a dog. Really sorry to read your news. It looks like you gave him a very happy life, returned in kind manifold, no doubt.

[N Sayers @nsayers1]

@RAH00084 @111BEN_111 @Blueberrymgmnt The key difference being that in that case the seller obviously didn’t know what they had on their hands! Avacta know exactly what they’ve got in 6103.

In this case I guess the stock market valuing Avacta is analogous to whoever signed off sale of Keytruda for $1000.

[N Sayers @nsayers1]

@jivetur88775834 @KMrk464656 @JStonker Perhaps we can infer it by comparison of the waterfall plots over time, if the best result for a patient is reached early, but progression not observed even months later.

[N Sayers @nsayers1]

@Robin25461631 @MylesMcNulty Raising enough to clear out the CLN at 30p/share would be a heck of a lot of dilution. There will come a time to pay it off (likely to break resistance before passing the 88p conversion price), and if it is done through a raise it will be well above 30p.

[N Sayers @nsayers1]

@haveigotnews rebelling against then slowly turning into their parents.