focusIR May 2024 Investor Webinar: Blue Whale, Kavango, Taseko Mines & CQS Natural Resources. Catch up with the webinar here.
Best conspiracy theory…
The short has been orchestrated by the CLN provider to maximise the number of shares in the next payment… cos they know a huge deal has been agreed and they’re about to get paid off in cash in full!! Go on, beat that!!!
I’ve just been through all the RNSs about attending the AACR. Avacta updates the market via an RNS late March about its plans to attend and what it will be presenting. Nothing out of the ordinary in no updates so far. Personally I want them to take as much time as possible, and incorporate as much data as they can. Presenting the completed P1 Arm1 dataset is bound to generate interest.
T&F! Trials and funding.
Concerns have been raised about the financial position of the company, and a possible dilutional fund raise. Al made it clear in a pre Christmas Q&A funding isn’t an issue, but the closer we get to hypothetically running out of money, with no news, people are selling.
Trials: no updates on Arm 2, the fortnightly dose, or Cohort 7 and hence completion of Arm 1 has left a news vacuum. People get bored/ frustrated / concerned. They sell and move to the next shiny thing.
Recruiting:
Sarcomas are rare cancers, hence the Orphan Drug Status for AVA6000. Not sure if the recruitment for fortnightly dosing is for all sarcomas, or a particular type. If it is a subtype, rare has got even rarer. Then it’s going to be only those patients presenting to SKM, and who agree, will get recruited. Even rarer. So I’m not surprised we haven’t heard anything.
https://www.gleneagles.com.sg/health-plus/article/what-is-sarcoma-how-rare-is-it
Also… all of AIM is taking a kicking at present ( well… the market is down across the board), so again a further reason for the SP to be where it is.
Obviously the company needs ongoing funding, I just think there’s more to the present SP being where it is than simply a need for a potential share dilution.
Looking at the use of joining canSEEK = preCISION with Actinium 225:
“Alpha emitters such as actinium-225 are favored in cancer treatment because of the short range (a few cell diameters) of alpha particles in tissue and their high energy, rendering them highly effective in targeting and killing cancer cells—specifically, alpha particles are more effective at breaking DNA strands. The 10-day half-life of 225Ac is long enough to facilitate treatment, but short enough that little remains in the body months after treatment.[10] This contrasts with the similarly investigated 213Bi, whose 46-minute half-life necessitates in situ generation and immediate use. Additionally, 225Ac has a median lethal dose several orders of magnitude greater than 213Bi because of its longer half-life and subsequent alpha emissions from its decay products. Each decay of 225Ac to 209Bi nets four high-energy alpha particles, greatly increasing its potency.[10][13]
Despite its limited availability, several clinical trials have been completed, demonstrating the effectiveness of 225Ac in targeted alpha therapy.[8][13] Complexes including 225Ac—such as antibodies labeled with 225Ac—have been tested to target various types of cancer, including leukemia, prostate carcinoma, and breast carcinoma in humans.[13] For example, one experimental 225Ac-based drug has shown effectiveness against acute myeloid leukemia without harming the patient. Further clinical trials of other drugs are underway.[10]”
Good find @gmcc. It all adds to the importance of the research and development Avacta is pursuing.
https://avacta.com/license-agreement-with-point-biopharma-inc/
Ice: totally agree. The Orphan Drug Status for STS offers us a quick route to approval and market. Once there, every research oncologist worth their salt will want to show AVA6000 has a beneficial effect. Others will be funding the research! Avacta just needs to make sure the trials meet the threshold for Product License inclusion.
I forgot to add, my bad, cancers are excellent at angiogenesis - growing their blood supply - delivery of drug to the cancer shouldn’t be a problem. I know this seems to go against what I said about dox and breast cancer. But there the problem is the low safe level of dox in the blood.
Fair points. Some people do metabolise drugs at different rates to others. A very well known fact. Plenty of patients have regular drug levels checked to make sure the dosage is right. Or the drug’s metabolic pathway varies very little between patients. The trials will establish this. It isn’t something to overly worry about.
Blood flow and delivery, if anything AVA6000 is the answer to this problem, as opposed to it being a problem for the drug.
Obviously I’m only going on what has been published so far. If I’m wrong, very sorry. But everything so far is supportive of safety and some efficacy.
But… what you suggested about blood supply and uptake of drug into the cancer is VERY important. There’s good research showing a concentration gradient between the periphery of breast cancer and the core with respect to the uptake of doxorubicin. AVA6000 should stop this occurring.
I’m all for the fortnightly dose interval and trial. I think it’s an excellent idea. It allows a larger cumulative dose of ‘free’ as well as total doxorubicin to be given to the patient in unit time.
The concentration of AVA6000 will be much much higher than plain doxorubicin. But also think of it like this: if all the AVA6000 were to give up its doxorubicin at once, everywhere, the blood concentration would be catastrophic.
It obviously doesn’t do this. It’s only releasing free doxorubicin in the presence of FAP. The free doxorubicin gets taken up into the cancerous cells and TME. The used up AVA6000 is immediately replaced by fresh AVA6000 - because there’s so much of it in the blood.
Sorry for being a pedant, flushing and excretion of drugs are different processes.
Depending on the exact excretion pathway- liver / kidney / both, simple blood tests will give an indication of rate of removal of the drug. Technically called its clearance. But because we already know how safe AVA6000 is, there will be a wide therapeutic window for it.
Thorn: I don’t know. Time will tell. If the cancer bank data can be analysed and shows high FAP is a universal finding in tumours, specific analysis won’t be necessary. If it is needed it will get done.
“Uncleaved AVA6000 gets excreted from the body. I imagine this depends on many factors: characteristics of the tumour itself, volume of blood supply to the tumour, patient’s health, metabolism etc. Just suppose the AVA6000 in some cases is being flushed from the body thus diluting the dosage level in the blood, too quickly to be cleaved by the FAP as quickly as is desired? It would make sense to try dosing fortnightly thus keeping AVA6000 levels in blood higher for longer and achieving better results. Also this information would be a must in order to inform P2 dosing regime. And of course the safety of AVA6000 allows this more frequent dosing.”
Excretion of uncleaved AVA6000 is independent of the tumour size and its blood supply. But will be a function of the blood supply to the excreting organ, liver or kidney. The evidence I can find suggests no metabolic pathway for AVA6000, it’s excreted unchanged. This is the Pharmakinetics (Pk) of the drug. That’s what makes it so very special.
Plain doxorubicin has complex Pk pathways through the liver and kidney, showing toxicity to these organs. As well as the heart. Nasty stuff.
Slide 4 shows specific cancers and their associated FAP expression:
https://avacta.com/wp-content/uploads/2021/11/IWC-2021-Avacta-Presentation.pdf