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Just to add (sorry, have previously posted some of this) regarding the challenges of RLT (RadioLigand Therapy). The radioisotopes used are not inert – you can’t turn radioactivity off (unlike AVA6000 where Doxorubicin is rendered inert until FAP triggered cleavage at the TME), so targeting is critical. Not to mention the supply-chain challenges of radioisotopes (like, it might help to have a nuclear waste facility or a small CERN next door).
Lily (Point) and Novartis favour 177Lu and 225Ac (maybe 161Tb). 177Lu is produced by Neutron bombardment of 176Lu, or 177Yb - which then decays to 177Lu. 177Lu has a half-life of 6.6 days, so not long to manufacture the Radioligand. 177Lu decays via beta emission (3 energy levels) and gamma (1 energy level). The beta decay is the treatment.
Most 225Ac came from the Oak Ridge National Laboratory from slowly decaying Thorium – but this source is running out. However, you can always batter 232Th with high-energy protons – just need that accelerator next door. 225Ac has a 10-day half-life and decays via alpha emission (high energy, but very short distance, so needs precise targeting). Could go on, but getting late.
So what did Lily get for their money (Point Biopharma – acquired for ~$1.4bn (~£1.1bn))?
PNT2002 – RLT PSMA target, phase 3, trial met end-point, but results not up to expectations.
PNT2003 – RLT SSTR target, phase 3, FDA accepted abbreviated new drug application (ANDA), ‘frequent grade 3 / 4 AEs’, only 180 days exclusivity.
PNT2004 – RLT FAP-α target, phase 1 (177Lu), pre-clinical (225Ac), PNT2001 – RLT PSMA target, pre-clinical, CanSEEK™ - (i.e. pre|CISION™ licenced for RLT), status unknown.
Point had a strong balance sheet arising from a licensing deal with Lantheus at end-2022 involving PNT2002 and PNT2003 (so presumably Lantheus continue with a significant stake?).
Point had no product sales.
Avacta – market value (on 351m shares @ 53p) = £186m
AVA6000 - FAP-α activated doxorubicin, phase 1, going well so far, planning for dose escalation / phase 2. Presenting results at AACR 2024 April 9.
AVA3996 - FAP-α activated proteasome inhibitor, planning for FDA IND and phase 1.
AVA028/032 – PD-L1 Affimer, research / pre-clinical.
AFX-001 – Immunomodulatory Affimer being progressed by AffyXell (JV Daewoong) to FDA IND.
Avacta now have cash funding into 2026, however there remains an outsanding £38.25m of CLN debt.
Avacta have product sales from the Dx div (Launch and Coris) expected to be EBITDA positive in H2/2024 and cash positive in 2025.
Qualitative assessment – Personally (DYOR) I think that Avacta’s pipeline / technology is much more valuable. RLT difficult (major supply-chain issues), whereas pre|CISION™ is a true ‘platfom’ technology. I would (‘qualitatively’) judge Avacta Tx value being at least, likely more than, that of the Point / Lily acquisition deal.
GLA
A Radioconjugate has four parts, a radioactive isotope, a chelating agent ( can have serious even life threatening side effects ), a linker and a targeting molecule. Tech bought by AstraZeneca for $2.4 billion.
Eli Lilly bought Point bio for $1.4 billion, question is who got the best deal.
EL have CanSEEK / pre|CISION which can be used in the linker, a clinically validated targeting technology allowing the warhead to be released on target.
AZ have a targeting molecule to release the warhead.
I am no scientist, however the validated targeting system at the sale price of $1.4 billion has the edge imo.
Got really worried for AZ when one of the targeting vehicles to be used was a mAb. To be fair they also listed small molecules or peptides.
Since pre|CISION is a simple di-peptide maybe AZ will follow a tried and tested targeting vehicle and go for the simple peptide route targeting PSMA. Whatever it still has to pass muster,
Touk, Let's face it.
Smith, and his band of PRETENDER'S have had so many over that none of this makes sense anymore.
Funny thing is TG, Avacta's present CFO once was a Director of a company called Fusion .
Or so I believe
Perhaps it's a sign??!!
Wasn’t talking about you specifically 🙄. Just saying folk need to read the RNS’s to get the simple info that’s already available before trashing the company.
Icecool
If you read my posts you will see that I’m not trashing Avacta or AVA6000 or saying Al should resign like some other posters.
Just trying to make sense of what’s going on. I don’t understand why you have such a problem with that.
Cj62
I agree. In fact I agree with most of what you say. But efficacy hasn’t been proven. That is the only thing I’m saying. Not that it won’t be proven. We have to wait for end of P2
It’s not a foregone conclusion
Touk you wonder why I continually call you a twat. Well IF ava6k does better than dox it becomes SOC and I have not made that up.
You sir are a ultra twat
That's part of the excitement of this trial. By targeting high fap expressing tumours the net is cast very wide indeed, but that requires vast resources to cover, and for each indication there will be tuning to be done. The safety profile to date also allows for a wide range of experimental dosing regimens which would ordinarily be limited by toxicity. The two combined means the market could be very large indeed, but requires time and resources to match.
“To me it’s still not worth losing my shirt over”
That’s totally fine 👍👍💯 your opinion.
On a side note Avacta don’t care about the short term action on its share price, they are concentrating on the day job and have said they will give updates on the 3w/2w study late Q2. They have hired commercial expertise and seem to be wanting to go solo rather than partnering up. Dox is a multi billion dollar drug. So 18-20% dilution won’t affect the endgame that much if AVA6000 replaces it, when AVA6000 gets approved either by surrogate endpoint (PFS) or normal phase 2. This will be a total game changer for the company, you can either wait till FDA approval and buy in then or you can understand the research and be an early investor. Doesn’t put me up or down either way but try read the RNS’s first before trashing the company on a BB at least get the basics correct, would appreciate that 💯👍.
"It's cleaving dox a drug that's been in use for 50 years. In the safety and tolerability study phase 1 efficacy has already been observed.. Will it been seen in phase 2 targeting tumours that are selected as a final tumour target for the drug? These three twats would have you believe it won't."
Accept none of us have ever said that.
We can all play that silly game.....
'The most likely thing is that the results aren’t as predictable as had been expected'
That would be material for sure!
Think I'll just repeat this over and over all day everyday.
It's working as designed i.e when encountering a fap rich environment dox is cleaved.
Next phase is to identify the best cancer type to target and then see if it's efficacious.
It's cleaving dox a drug that's been in use for 50 years. In the safety and tolerability study phase 1 efficacy has already been observed.
Will it been seen in phase 2 targeting tumours that are selected as a final tumour target for the drug?
These three twats would have you believe it won't.
Make up your own mind with the factual evidence to date.
Crowfoot
It isn’t black and white. I’m not saying it doesn’t work. The most likely thing is that the results aren’t as predictable as had been expected and there is a lot more to be done on tuning the dosing regime.
Icecool
That is good but what some are refusing to recognise is that there are still high risks:
1. Does it work well enough across a large number of patients
2. Will it generate enough profit to support development of the ensuing platform and pay us a decent dividend
3. Will BP buy it and any profits be watered down supporting the rest of their product range.
To me it’s still not worth losing my shirt over.
Yes Ice it's all a bit tedious day in day out. If they knew something material has gone awry and raised money without saying then they are in big trouble if/when found out. It does seem crazy not to address the low placing as some calming words would certainly help the short term share price. Obviously they may not care but AS must be getting annoyed cleaning out his forever bulging inbox! On a positive note the churn is becoming less and we are (slowly) moving higher.
GLA
Oh for sure that is the case. That is the pharmacokinetics aspect of all of this. Some tumours won't express high fap, others are in low blood zones, such as bone cancers. Part of the challenge of oncologists has always been finding the right treatment for a tumour.
Jeez Touk - You're either thick as two short planks or you're the gold medal holder for the Olympic long distance facile argument event (or both)!
Gje306
I’ve never argued that it hasn’t been released to the TME or that patients have died. What I am considering is the reasons why we might be where we are and one of those could be slower than expected cleaving in patients with certain characteristics
Use some common sense Touk, do you really need everything spelled out to you, patients are still getting treated outwith the cohort structures if it wasn’t working properly as expected on the biopsy data, this would be unethical and stopped by the patients Dr’s, (chemo toxic and deadly) good thing is, us as private investors can do some due diligence and research and make up our own minds if it’s working or not. That’s called getting ahead of the game (spotting an opportunity) we don’t actually need to wait till the FDA formally approves something to make a decision. Once this is approved you won’t be able to invest at these levels so that opportunity is gone. Pretty simple to understand. Don’t really get your negativity all the time though it’s very strange even when this has been discussed before.
"How does it compare to 1540mg/m2 ?"
Of what exactly?
"It's cleaving dox a drug that's been in use for 50 years. In the safety and tolerability study phase 1 efficacy has already been observed.. Will it been seen in phase 2 targeting tumours that are selected as a final tumour target for the drug? These three twats would have you believe it won't."
Accept none of us have ever said that.
They went into the levels in the science day. You should also watch that again. The biopsies were optional, so not all 40 patients gave permission, and others are still alive and receiving treatment! Of those that were obtained, they all demonstrated doxorubicin had been released.
How does it compare to 1540mg/m2 ?
Just asking
For a friend
Smeag
If MTD in mice was 2mg/kg then what are the equivalent doses in humans in C7?
It's working as designed i.e when encountering a fap rich environment dox is cleaved.
Next phase is to identify the best cancer type to target and then see if it's efficacious.
It's cleaving dox a drug that's been in use for 50 years. In the safety and tolerability study phase 1 efficacy has already been observed.
Will it been seen in phase 2 targeting tumours that are selected as a final tumour target for the drug?
These three twats would have you believe it won't.
Make up your own mind with the factual evidence to date.