Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
I have a slightly different take on Avacta’s statement on biopsies which to me is just highlighting the fact they need to tread extremely carefully. Avacta are simply expressing confidence in having some valid assay data rather than referring to the physical act of taking biopsy samples from patients.
“The presence of Doxorubicin in the tumour tissue is also a key indicator that the proposed mechanism of FAPa-activated release of Doxorubicin is working. This information can only be obtained from tumour biopsies, which are not mandatory in the Phase I study, but the Company remains confident of gathering some biopsy data from the Phase Ia dose escalation study. The Company has worked with partners at a UK based, world-leading pathology laboratory to put in place the validated assays to analyse biopsy samples.”
Firstly, Avacta and big pharma both know that in oncology trials tumour biopsies remain the gold standard for establishing pharmacodynamic data, proof of concept and proof of mechanism.
This means Avacta ultimately needs to end up with a fully coherent set of assay data where the quality and integrity can’t be questioned. Taking a biopsy sample is one thing but I would guess it isn’t guaranteed that the sample will necessarily be suitable for analysis or that it will provide the right level of data etc. Ideally Avacta will want assay data that shows the presence of dox at levels that fit in well with the dosage regime and all their other data/models. Saying we found dox in the tumour but the levels were totally random wouldn’t be ideal especially if it were due to the assay company doing a crap job. Hence Avacta are pointing out the important fact they are partnered with a world leading path lab.
Secondly, Avacta will be acutely aware that there is a considerable amount of ethical debate surrounding the inclusion of biopsies in oncology clinical trials.
“Research related biopsies have been ethically controversial for questions around potential harm at the end of life without any concomitant benefit to the patient”
ASCO have produced a framework to provide guidance for incorporation of research biopsies in trials. Fortunately it’s very reassuring to know that the principal investigator Professor Banerji and the Royal Marsden teams are extremely focused on this aspect and the above quote comes from their recently published paper addressing such questions across all their trials. They will be advising Avacta so again we have a world class team providing the expertise required.
https://www.sciencedirect.com/science/article/pii/S2468294221000083
https://ascopubs.org/doi/10.1200/JCO.19.01479
I think Avacta have been taking biopsies all along as stated by FMcL and they’re confident that they will have some valid assay data as a result. We will see quite soon!
OK, so it looks like we’re really hoping that Takeda have an urgent need to license AVA3996, Avacta’s second pre|CISION prodrug, so I figured it worth looking at how Takeda are doing with Velcade and their replacement drug Ninlaro.
Looks like things aren’t going that well!
Firstly, I found this article
https://www.myelomacrowd.org/myeloma/community/articles/ninlaro-may-not-be-an-effective-replacement-for-velcade-or-kyprolis-following-a-myeloma-relapse
Takeda conducted a ‘head-to-head’ clinical trial in an effort to show that Ixazomib (Ninalro) their replacement product for Bortezomib (Velcade®) for Multiple Myeloma Patients is as safe and effective as their existing product.
The published study had two conclusions:
* ‘Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib.’
* ‘The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with multiple myeloma who have previously relapsed on other bortezomib/carfilzomib-containing regimens.’
Not a wonderful outcome!
Secondly, I found this article excerpt which highlights the fact that generics are now pouring onto the market hitting Velcade sales hard.
‘Thanks to multiple U.S. generic entries since May, Velcade’s global sales dropped by more than half at constant currencies to 16.5 billion yen ($120 million). That was in contrast to the 3% revenue growth Velcade pulled off in the fiscal year that ended in March.
Speaking to the popularity of the proteasome inhibitor, seven generics to Velcade have already hit the U.S. market, and Takeda expects to see another 10 “in the coming weeks,” CFO Costa Saroukos told investors during the call.
Velcade's follow-up drug, Ninalro, also suffered during the quarter, with sales dropping 13% to 23.7 billion yen as competition heats up.’
https://www.fiercepharma.com/pharma/takeda-pulls-exkivity-lung-cancer-app-eu-velcade-generics-cost-oncology-franchise-dearly
So I’ll leave you with this excerpt from the legendary MM thesis!
‘An obvious solution for Takeda to not only extend its existing proteasome inhibitor sales, but to potentially dramatically expand those sales, would be to license Avacta’s AVA3996 candidate. Assuming the AVA6000 Pa trial is a success, then the clinical development risk for AVA3996 would be significantly reduced.’
‘A ‘working’ AVA3996 would take market share from the other two existing proteasome inhibitors (Kyprolis and Ninlaro) on the market (as why would any patients use those?); would generate greater sales than Velcade (as many more doses could now be administered, and to many more patients); and would enjoy patent protection for another two decades (thus benefitting from premium pricing).’
C’mon Takeda you know you want to!
If you read the Trinity Delta report from June 2021 (specifically page 23) you would note the importance of ‘sensitivities’. This bit of the report might easily be overlooked, probably been ignored by many but certainly has some relevance to any debate on how the market might be viewing Avacta’s progress towards commercial exploitation of its Tx and Dx platforms. The market won’t simply ignore these risk factors no matter how good the science.
According to TD
“Typically with innovative healthcare companies the three main sensitivities relate to clinical and regulatory aspects, commercial execution, and the financial resources required to accomplish these. More specifically for Avacta, the key near- and medium-term sensitivities relate to the steps required to create a profitable diagnostics business and to demonstrate that both the Affimer and pre|CISION platforms can be developed into attractive therapeutic assets.”
“Avacta faces uncertainties in both its businesses. Diagnostics has reached a pivotal point where its COVID LFT could determine its near-term outlook. The Therapeutic applications of the platforms face typical industry risks associated with clinical trial results, navigating regulatory hurdles, ensuring timely and sufficient financing is in place, partnering discussions and, eventually, pricing/reimbursement and commercialisation.”
So there we have it; risks associated with commercial execution for both Dx and Tx platforms and the financial resources required to accomplish these. Suspect high weighting’s currently being applied, especially in the absence of any guidance on possible Dx revenue. This will remain so until next results are released or we have presentations and interviews in which AS is more forthcoming. Let’s face it nobody’s better at explaining the science than AS and as a result Avacta’s scientific credibility and reputation is not in doubt. However maybe the same cannot be said when it comes to business execution so Avacta is now immersed in a fog of uncertainty.
Release of the AVA6000 PK data, a statement on level of big pharma interest, possibility of collaborations and licensing deals being struck, and their financial terms, selection of clinical development candidates for Affimer bispecific, PD-L1 antagonist and TMAC® programmes, notification that AffiDX issues all solved, transparency on Medusa’s activities, update on AffiDX sales and manufacturing capacities, guidance on future Dx revenue etc. All this info would contribute to a good wind to help lift the uncertainty.
AS has spoken to potential investors telling them all about our compelling IP story and clinical roadmap. No doubt he has presented a pathway offering significant potential for commercial success in both diagnostics and therapeutics.
Institutional investors will have asked very searching questions.
The really big question will remain the same; can Avacta deliver?
It’s a ‘yes’ from me! But DYOR!
*****Professor William Bachovchin*****
Wow! The guy has waited 10 years for this day to come!
High fives all round Tufts campus today!
Nice one!
Carlsberg333, is it possible your Scientist hasn’t quite understood how PreCision works? Yes it’s a drug delivery mechanism but it doesn’t involve nano particles or cage effects which offer a different approach to drug delivery. Both aim to achieve the same end result ie carry the drug to the tumour while reducing adverse side effects. Could be your scientist mistakenly thinks AVA6k falls into the nano category .
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087095/
I’m a Googlexpert. You should really check for yourself!
Here is an example from Point Bio license agreement with Bach ScI and Avacta
https://www.sec.gov/Archives/edgar/data/1811764/000110465921098307/R59.htm
Share options are involved as per Avacta rns on 02/02/2021
I would suggest it’s more a case of Bach getting a small cut from Avacta who will get the lions share.
Lots of reports on doxorubicin market size etc out there. How accurate, I don’t know but quotes like this are good in recognising the potential for delivery systems like PreCision.
“Growth in the global market is set to be driven by rising incidence of cancer, development of technologically advanced systems for drug delivery ……”
https://www.prnewswire.com/news-releases/global-doxorubicin-market-to-reach-1-3-billion-by-2026--301345933.html
If anybody wants to know a bit about Doxorubicin itself and dosing this gives a quick overview
https://www.pfizer.ca/sites/default/files/202110/Doxorubicin_PM_30Sep2021_L3_EN.pdf
AVCT share price is in the mire. Quite a number of factors and influences combining to hold it down right now. Have no doubts whatsoever it will eventually triumph but I’m expecting a longer journey than I first anticipated.
Ok, so if we get really excellent AVA6k data soon then the share price heads north. Market says great as we know it opens up a huge market for Avacta’s PreCision pipeline but then the market asks itself how are Avacta going to realise that value for shareholders. AS says no problem we’re on the verge of ‘inking deals’ with some big pharma. Yeh right! We’ve heard that one before! Those casual utterances he’s made previously were great to hear at the time but the market is unforgiving when nothing transpires. Trust and credibility are the first words that come to mind along with consistency in messaging. All will be key to attracting new investors and holding on to them which in turn will help stabilise and improve the share price performance. Whilst the size of the market opportunity of many £B is mouthwatering, sentiment and views on Avacta’s ability to commercialise will also come into play.
Maybe the penny has dropped with Avacta regarding their communication and the need for consistency and clarity. Maybe AS has been persuaded to change tact. Playing his cards close to his chest seems to be his preferred strategy but it leads to too many unanswered questions and false hopes. The market doesn’t like it. Frustration on both sides. Hoping the appearance of Capital Access Group signals an improvement in shareholder comms. We shall see!
Overall I think the share price journey going forwards will be upwards but bumpy but I also think Avacta could make things a lot less bumpy if they wished.
Don’t you just love our “googlexpert” Marik who believes he can become the foremost expert on anything Google can search. I reckon we’ve had the Doctor, Lawyer, and Scientist versions so far! What’s next? Banker with expert knowledge on buyouts.
Marik says he has “a very good understanding of timelines and production of lateral flow antigen tests” you know!
It’s a bit of a shame Avacta didn’t go to Marik initially rather than Cytiva!
I did hear Dorling Kindersley have produced some Covid test picture books which Marik will be eager to add to his collection.
Ffs we’re still not on the list.
I really don’t get it!
https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_en.pdf
The EU HSC common list always comes with a separate addendum update.
https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_addendum_en.pdf
The Avacta test has never been on the rejected list. Also, it has never appeared in the list of tests that are currently under discussion (currently those submitted up to 19 November 2021) which sort of suggests Avacta are content to be on the JRC database but are not seeking to be on the EU HSC common list for some reason.
Presumably not being on this list isn’t limiting sales of the professional test.
Really weird!
1marcr, thanks for the info. Try slipping a couple of random letters and numbers into your next post. Something like YO41 or DN4? You know the sort of thing I mean ;)
Cheers!
https://ec.europa.eu/health/sites/default/files/preparedness_response/docs/covid-19_rat_common-list_en.pdf
Still not on the list but Mologic now are!
Grrrrrrrrrrr!
Avacta business update 30 sept 2021
“ADC Therapeutics: Avacta has provided Affimer® molecules to ADC Therapeutics under the evaluation agreement. This evaluation agreement has now concluded, and ADC Therapeutics is not taking this programme further.”
Marik be a good boy; try and keep up to date!
His arrogance knows no bounds
“There is info out there - those of us who can communicate without the attitude and agenda share it”
What little credibility he had left went down the toilet when he made this statement to Monkshood:
“there are multiple papers detailing where the linker in use in AVA6000 accumulates in the body in mouse and primate models”
Genuinely respectful request for the refs made by a valued poster didn’t deserve his arrogant response which was…“he will find them”
So much for him sharing info!
This episode tells you all you need to know regarding his motives!
Sorry couldn’t find the link before!
Here is the link to the patent that contains the data displayed. It’s fig23
https://patentimages.storage.googleapis.com/42/93/08/f6604918926779/US20160346401A1.pdf
Thanks Poirot but I just wanted to point out that the impressive data coming out of Tufts for the AVA3996 is not new data but part of the original data generated by William Bachovchin and Arisaph Pharmaceuticals. It was generated over a period of many years 2010-2015. It’s all part of the extensive amount of work carried out on FAP-activated proteasome inhibitors relating to prodrug feasibility around Velcade and Doxorubicin. No doubt this data helped prompt Avacta to establish their collaboration with Professor William Bachovchin at Tufts University Medical School to develop the pre|CISIONTM technology for tumour targeting.
https://grantome.com/grant/NIH/R41-CA156930-01A1
https://grantome.com/grant/NIH/R42-CA156930-02
https://grantome.com/grant/NIH/R42-CA156930-03
Emphasises the amount of under pinning work that had already been carried out prior to Avacta picking up the reins and then doing their own pre clinical studies. All bodes well!
Really not sure about this so I present this info without making any real judgment.
It’s for you to digest if you’ve not seen it before.
This document could be very relevant to us gaining HUA from the notified body conformity assessment process.
“This guidance document concerns performance evaluation of SARS-CoV-2 in vitro diagnostic medical devices (IVDs) in the context of conformity assessment under either Directive 98/79/EC or Regulation (EU) 2017/746.”
https://ec.europa.eu/health/sites/default/files/md_sector/docs/mdcg_2021-21_en.pdf
“Self-tests
SARS-CoV-2 IVDs for self-testing should meet the same requirements for sensitivity and specificity as respective devices for professional use. Relevant parts of the performance evaluation should be carried out (or repeated) by appropriate lay persons to validate the operation of the device and the instructions for use. The lay persons selected for the performance evaluation should be representative of the intended users groups.”
Table 4 and Table 6 are the ones relevant to our antigen test.
Here again we seem to need 300 negative specimens?
On a slightly different note some may be interested in this paper.
The use of pooling means there is no direct comparison to our sensitivity data but just look at how sensitivity varies wildly in the range Ct>25-<30
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.44.2100441#r14
Who are bored!
Pumping and dumping
Selling and buying
Shorting our share
Gonna leave you crying
Ramping and trolling
Baiting and fighting
Everyone hates it
Nobody laughing
Pumping it up
Dragging it down
Who wants to sell
Get out of town
Some want to share
Some like to guess
The info’s out there
But it’s all a mess
The lying and denying
Not trusting a finding
Prefer grandstanding
One is sealioning
We could all agree to do it
Let’s bury the hatchet
As for Avacta
Nothing can touch it!
Amen!
Looks like Avacta will have been in good company at their recent US conference.
Being able to exchange views and sympathise with other small US biotechs who are also struggling to bring tests to their home market by fighting against deliberate interference from gov agencies and accusations they played a role in determining which testmakers became the most important players in the market.
https://www.propublica.org/article/heres-why-rapid-covid-tests-are-so-expensive-and-hard-to-find