Sandy Radford

[Sandy Radford @sandyradders]

Great post.

Just to tie in with your point 5, the AVA6103 trial is focused on cancers with significant unmet need.

Dr Alex Spira singled out pancreatic cancer, gastroesophageal junction cancer and colorectal cancer:

“We’ve really been devoid of new drug development.”

His closing remarks perhaps summed up his view of AVA6103:

“It’s novel compared to whatever else we’ve done, and it really focuses on some of the issues that really need to be overcome, both on drug delivery and toxicity.”

“So really excited.”

#AVCT

[AM23 @AM231982]

Avacta #AVCT has a very bright future.

In recent weeks they have openly compared AVA6103 preclinical data to Enhertu and Datroway both multi billion $ drugs only weeks into the actual human trial.....That is how you poke a bear!

There is a long list of positive news items coming up fast. In no particular order.

1. SGC Fast Track approval & PFS data
2. SGC commercial deal
3. First ever data on TNBC for AVA6000
4. Full AVA6000 deal
5. SAB - Representation for specialists for all the 6 indications in the AVA6103 trial
6. New Chairman
7. AVA6207 - Dual warhead deals - Multiple possible
8. Peer reviewed data
9. 5 new sites expected for AVA6103 trial just in P1A (up to 17 more to support the next stage also)
10. Bio International conference later this month.

All of these in the coming weeks are possible. It will change this company forever. Deals Deals Deals are on the menu.

[Sandy Radford @sandyradders]

@YorkshirPuddin Agree with your posts Jake.

RIGHT PARTNER
RIGHT TIME
#AVCT

[Sandy Radford @sandyradders]

Great post.

Alex Spira highlighted a major problem with many ADCs.

“We need to get past the typical antibody-drug conjugates that we’ve seen so many of… what really limits us is the side effects… some of that payload is distributed in the system, which leads to side effects.

“And two things happen with that… you increase side effects for patients, but you also limit the amount of drug that you can give… you reach the MTD at lower doses”

With AVA6000 they never hit an MTD in Phase 1 despite doses approaching 4x the molar equivalent of doxorubicin, alongside significantly improved tolerability and the recent regulatory lifting of the lifetime dox maximum limit.

If AVA6103 demonstrates something similar clinically and replicates the translational data - then we have something very special.

#AVCT

[Sandy Radford @sandyradders]

Chris Coughlin would be a great choice as an interviewee.

An inspirational CEO who has dedicated her career to fighting cancer and making an impact in it.

Asked recently if she thinks she’s going to put a “dent” (a Chris word) in cancer? The answer was an emphatic “absolutely”.

Chris and her team sound increasingly confident & assured.

She was by all accounts brilliant at Science Day and excellent in the presentation. The #AVCT pre|CISION platform is cutting edge.

[Highly Geared @HighlyGeared]

#Avacta Therapeutics #AVCT

If you interview Christina Coughlin, the Avacta CEO, it will be the best broadcast you have ever conducted. Just look at her recent Science Day presentation for the quality of the Avacta science, and her communication skills.

[Sandy Radford @sandyradders]

Hi Myles, yes - what stood out for me was Curtis effectively suggesting the preclinical models may actually underestimate what AVA6103 could achieve in the clinic.

I will let the video do the talking - in the classic understated #AVCT way of explaining something potentially very significant.

[Sandy Radford @sandyradders]

@HighlyGeared @BigBiteNow @PJ_Crabb Thanks HG - that’s interesting and positive feedback.

#AVCT

[Sandy Radford @sandyradders]

I don’t disagree, Dom, that the maturing data and the quality of the science team are instrumental in the current SP.

But I also think it’s easy to forget just how much the CLN weighed on sentiment and the share price every quarter.

RH played a significant role in changing that narrative. At the AGM, the CLN dominated the discussion and tone until he stood up and instilled confidence that it could be managed - and backed up those words with action.

#AVCT

[Sandy Radford @sandyradders]

Morning Gemma,

Regarding the prelim results, last year’s (June 6th) were later than usual. The results RNS at the time referenced prior CLN accounting errors, and when I spoke to Brian at the AGM he said a number of restatements had been required, alongside a lot of work relating to the Diagnostics divestment.

That may well explain why last year’s results were released later than had traditionally been the case.

Previous prelim results release dates were:
• 30 April 2024 (FY23)
• 25 April 2023 (FY22)
• 6 April 2022 (FY21)
• 22 April 2021 (FY20)

So I think today’s prelim results RNS is more of a neutral/business-as-usual announcement than anything especially significant.

#AVCT

[Sandy Radford @sandyradders]

@RAH00084 Thank you RAH - I’ve borrowed your tune 🚀

“If the sustained release mechanism works, it means that almost the sky is the limit in terms of the medicines we can make.”

#AVCT

[Sandy Radford @sandyradders]

A great set of posts.

Lung toxicity / pneumonitis is one of the biggest and most serious issues with ADCs - including Enhertu.

In contrast, there has been no pneumonitis seen with AVA6000 - a major advantage of the pre|CISION platform that Chris has highlighted multiple times.

Chris has said they are often asked:
“Why don’t you have lung toxicity? Everybody else has lung toxicity. It’s not going to be released in the lung. David (Jones) explained that other ADCs release with a protease called Cathepsins - a whole group of them expressed in the lung. FAP isn’t in the lung.”

That’s the beauty of the FAP-activated pre|CISION platform - true tumour specificity because FAP simply isn’t expressed in normal lung tissue. No off-target release, no pneumonitis.

#AVCT is playing a completely different game here.

[Sandy Radford @sandyradders]

@avacta Sorry - it’s that Bank Holiday Monday feeling 😂

The Fallen Angels are en route to the next chapter…

Which potent but toxic drug will be next in the pipeline?

Huge respect for Chris’s vision and the team. #AVCT

[Sandy Radford @sandyradders]

@avacta #AVCT

Looking forward to the Next Chapter next week!

[Sandy Radford @sandyradders]

#AVCT

Novartis’s CEO at JPM made it clear they have cash to deploy for the right deal and that oncology is an area they are looking to strengthen - “that’s going to be an active focus for us from a BD and M&A standpoint.”

They also have a deep understanding of FAP biology through their radioligand programme.

[Sandy Radford @sandyradders]

Hi James,
I’ve attached the clip where David Jones discusses this slide (Figure 10). He doesn’t specifically mention the ~500-fold figure, but Cumulus spotted it on the poster.

In simple terms, the Tumour Selectivity Index (TSI) shows there is roughly 500 times more of the active drug in the tumour than in the bloodstream.

For example, in Compound A:
• The ATR inhibitor (one of the two warheads) has a TSI of 527
• The TOP1 inhibitor from the same dual payload compound has a TSI of 340

The TSI is the ratio of total drug exposure in the tumour vs blood over time. The chart itself doesn’t explicitly say “fold”, but that’s exactly what the numbers represent.

David Jones explains that we see far more of both warheads staying in the tumour (solid lines) than in the plasma/blood (dotted lines) - exactly what you want for a targeted drug.

#AVCT

[Sandy Radford @sandyradders]

Morning Stonks - “There’s that name again” indeed!

Enhertu is the blockbuster benchmark. The preclinical head-to-head with AVA6207 looks very favourable.

David Jones:
“In this model, at least, we’re actually doing rather better than Enhertu… We seem to be doing quite well… this is quite an exciting piece of data, I think”

As @Cumulus51896691 said about the presentation - total masterclass in British understatement from Mr Jones!
#AVCT

[Sandy Radford @sandyradders]

@111BEN_111 And as was shrewdly pointed out by the interviewer, “these are all tumour types with patients where there’s still tremendous unmet need - so they all make complete sense.”

#AVCT

[Sandy Radford @sandyradders]

@RAH00084 If #AVCT were a blockbuster film…