Member Info for LiveLongnProsper

@Rory, Perhaps worth a bit of checking before statements like “Precision can’t be monetised as it isn’t approved for use.”

For example, ‘Top 20 biopharma deals of 2023’ …

https://www.nature.com/articles/d43747-023-00124-x

Platform/Discovery – 12

Preclinical/IND – 3

Phase 2 – 4

Phase 1 – 1

10 of the above Oncology.

pre|CISION™ platform and Affimer® will be ‘in play’.

GLA

Pre|CISION™ "work it's magic" - the platform work, then ...

"choice of warheads"

"the warheads"

etc.

Key message there.

GLA

Indeed, it would.

Good enough (at some point) to generate the ~£3.2m (and declining) quarterly cash to cover the CLN repayment. Then (perhaps?) we have a self-sustaining Dx business and a Tx entity backed by BP investment.

2023 numbers will be interesting, but more interesting could well be a proper (for a change) update on strategy – both Dx and Tx, along the lines above. I.e. a view on current growth, revenue, profitability, cash, etc. and pipeline, investors, partners, licensing, etc. respectively.

GLA

Good find by https://twitter.com/Mstambo999 , great summary.

Importantly, published in the ‘Onc Weekly’ segment of ‘Physicians Weekly’ and headlining Prof Banerji, our AACR24 poster presenter and Deputy Director at The ICR and Royal Marsden.

“U. Banerji and the team aimed to assess the efficacy and safety of AVA6000 in FAP-positive solid tumors. Preliminary results indicated promising antitumor activity and support ongoing dose escalation studies to further evaluate its potential in clinical settings.”

Looks like progress to date now being ‘owned’ by top oncology clinicians.

GLA

Alan has ~1.64m shares in the Joint Share Ownership Plan (JSOP), Gardiner 150k. Also ~5.1m (4m @ 10p) and ~1.6m (1m) respectively in the Executive Share Oprion Scheme.

Not sure what, if any, performance criteria are attached, but all seem ‘exercisable’ on dates alone.

RNS 23 Apr 6.5m shares in the LTIP and ESOS (this the latter above), available from 26 April. So just short of covering all the options. My understanding anyway?

So are we going to see whatever shares can be exercised actually be purchased outright and any taxes due paid with real money (i.e not covered by selling to cover costs) ahead of results or AGM?

Then some good news and SP recovery. Fate of CEO and CFO TBA.

GLA

@Alcibiades, Interesting thesis. (Heights, not Conifer).

Suspect a good number of well researched, ‘sticky’, LTH’s.

Would like to see an update on the share register, at least major holdings.

Subject to above, even with ~51m new shares to II’s in the recent raise, plus existing II holdings (per last major SH update), plus management existing and (potential) +6.5m, difficult to see PI’s below ~60%+. I suspect the majority of these will be the ‘well researched LTH’s’, many of whom will be taking the opportunity to accumulate and average down (not advice, DYOR etc.).

Happy to be corrected with more reliable, sourced, numbers.

GLA

2021 results announced 30 Mar 22 for 6 Apr 22, and 2022 on 3 Apr 23 for 25 Apr 23.

Is there a delay with 2023 results for the ’40 day blackout’ (real or imagined, whatever)?

Is our CFO not able to add up the numbers?

Are we waiting for something – science or commercial?

AACR24 poster good, Prof Banerji efforts great, CC presentation excellent, trial going well, Alan webinar solid (even if questions filtered), raise / Heights rubbish.

(Note re trial - pre|CISION™ works, we continue to test doxorubicin at dosing level never done before, i.e. to the limit, with low side effects, again pre|CISION™ works ).

What the ‘heck’ is going on? This is a really weird company.

GLA

Whether or not you fancy munching Optimers with your Unilever food product is perhaps not the point – though interesting that the regulatory ‘bar’ for food additives is, perhaps (?), lower than for Pharma products. However, the point about Optimers as a competitor to Affimers is a good one.

APTA look like they’re at least 3 years behind AVCT in terms of Optimers for Therapeutic application. Having said that, the technology platform, and certainly Optimer use in Dx, is complimentary. Have previously mused that AVCT may want to acquire APTA?

The apparent lack of interest shown is simply another indicator that reinforces my view that AVCT’s horizon is less than ~2 years. Get P2 underway, get some IP protection for pre|CISION™ +/ADC and any other new chemistry, make some progress with AVA3996 IND, AffyXell IND, sort out Dx, etc. and then we’re into licensing and acquisition discussions. Could be much sooner rather than later – ‘time is fleeting’.

GLA

Wow - some things we heard from the TP webinar …

“Yes, I can absolutely confirm that we’ve got sufficient data to partner the pre|CISION™ platform …”.

[Avacta want] “… to be in a strong negotiating position with a long cash runway, which we also now have …”.

“In terms of strategy we want to retain as much as we can right now, because we know how valuable the pre|CISION™ platform is …”.

Paraphrasing – ‘doing the right deals with BP takes some care and some time’.

Then goes on to mention – Immunocore (said $3.1bn, $2.7bn today), AbbVie’s acquisition of ImmunoGen ($10bn) and, similar stage to Avacta, J&J’s acquisition of Ambrx for $2bn.

Wow - also from the AACR24 poster, Prof Banerji’s tweet, CC’s presentation, RNS’s, the website ...

Some Phase 1: Arm 1 patients continuing with treatment. Safety & Tolerability excellent, promising signs of Efficacy. (Better than 70% reduction in tumour size in 1 patient – wow).

Phase 1: Arm 2 C1 recruited and being dosed, RNS states – “… Avacta anticipates that the SMDC will review the two-weekly cohort 1 data by the end of April.”

Wow – so much to be updated on …

40 day reveal of US investor(s)?

The substance of the ‘talk’, ‘hints’, etc. around IP protection, apparently happening right now?

The substance of the ‘talk, ‘hints’, etc. around potential new pre|CISION™ (+, ADC) ‘warheads?

AVA3996/2727D status? Partner status – LG Chem (LR19128), AffyXell (AFX-001/002), Lily (CanSEEK™)? Affimer pipeline status – AVA028/032, AVA021?

Oh yeh, nearly forgot - DX strategy?

GLA

Re Dx.

Investor Webinar RNS 28 Mar 2024, also AVA6000 Abstract RNS 8 Apr 2024 ...

“Avacta has two divisions: an oncology biotech division harnessing proprietary therapeutic platforms to develop novel, highly targeted cancer drugs, and a diagnostics division, focused on supporting healthcare professionals and broadening access to testing. Avacta's two proprietary platforms, Affimer® and pre|CISION? underpin its cancer therapeutics whilst the diagnostics division leverages the Affimer® platform to drive competitive advantage in its markets.”

AACR Data RNS 9 Apr 2024 ...

“Avacta has two divisions focused on therapeutics and diagnostics.

Avacta Therapeutics: a clinical stage oncology biotech division harnessing proprietary therapeutic platforms to develop novel, highly targeted cancer drugs.

Avacta Diagnostics: focused on supporting healthcare professionals and broadening access to diagnostics.”

What a difference a day makes, gone are the words …

“… whilst the diagnostics division leverages the Affimer® platform to drive competitive advantage in its markets.”

Honesty, overdue correction? Or are Affimers just too good a thing to give away with (or be suggested to be part of) the (seemingly) inevitable disposal of Dx?

GLA

Excellent, eco credentials sorted, must be preparing to 'Launch' in Switzerland?

GLA

Always worth remembering that pre|CISION™ works. And pre|CISION™ is a platform – and is now, clearly, being presented to the world as such.

We are testing doxorubicin to the limit by delivering to the TME and (mostly) nowhere else. The same doxorubicin that has been the ‘first-line standard of care’ for certain cancers for many years. Not only have we not found a MTD at multiples of equivalent max dox dosage, but we are now testing dosing at more frequent (bi-weekly, compared to standard 3-4 weekly) dosing at lower (but still higher than ‘standard’) dosage levels. Maybe we will see something new?

It is the fine detail of pharmacokinetic (PK) and pharmacodynamic (PD) analysis of ‘drug’ in the body and the effect of a particular concentration respectively, which should be a particular focus of interest. Let’s see just how much ‘new’ data is released tomorrow.

GLA

Others thinking along the same lines ..,

https://www.abstractsonline.com/pp8/#!/20272/presentation/6706

“Fibroblast activation protein has emerged as an attractive biomarker for the imaging and therapy of ~90% of human epithelial cancers due to its expression on cancer associated fibroblasts (CAFs), but not on fibroblasts in healthy tissues. Not surprisingly, several small molecules and peptide-based radioligands that target FAP have been introduced into human clinical trials, but preclinical and clinical data suggest that these radioligand therapies suffer from inadequate tumor uptake, short tumor residence times, or unwanted uptake in the healthy tissues. Hence, there remains an unmet need for development of new FAP-targeted radioligands with improved therapeutic properties.”

Need pre|CISION™ RLT, again.

(FAP8-IP-DOTA pre-clinical).

Low dose chemotherapy …

https://www.abstractsonline.com/pp8/#!/20272/presentation/10576

“The results of these studies provide mechanistic insight into potential new chemotherapy partners to enhance anti-PD-1 efficacy in TNBC patients and suggest benefit to further investigating the immunostimulatory potential of low dose chemotherapy.”

Perhaps, highly targeted chemo needed, more frequent but lower doses – sounds familiar?

GLA

AACR (#AACR24) underway, 07:20 in San Diego and Novartis (Dr Alice Shaw) has already been speaking …

https://oncodaily.com/insight/44969.html

“Question about FAP+ whether radioligands have targeted mesothelin followed by CAR-T. Too early but FAP is felt to be a good target on CAFs.” (Too much enthusiasm and price of certain platform technologies might just respond).

Think they need pre|CISION™ RLT, alternatively (say) just pre|CISION™ + Dox, just to ‘cover all bases’, as RLT is quite hard (all those supply-chain challenges).

GLA

The rapidly deployed pre|CISION™ centric ‘shopfront’ explaining that “pre|CISION™ can be utilised in multiple drug formats: pre|CISION™ drug conjugate (PDC), pre|CISION+ Immuno-peptide drug conjugate, pre|CISION™ ADC” (just missing pre|CISION™ RLT) – certainly not a coincidence.

We have a cancer killing warhead targeting platform, deployable in at least 3 ‘formats’ - CanSEEK™ (‘plus, as noted, pre|CISION™ RLT – suggest trade mark quick Alan), probably more.

GLA

Novartis buying up radiotherapy assets from 3BP and Clovis (filed Ch11 and went bankrupt) ..

https://www.fiercebiotech.com/biotech/novartis-pens-425m-biobucks-deal-german-biotech-scoops-clovis-partnered-asset

This is interesting though – “In 2019, 3BP and Clovis penned a licensing deal for $12 million upfront that focused on developing a peptide-targeted radiotherapy and imaging agent targeting FAP.”

Lily’s acquisition last year of PointBiopharma may have been a response to Novartis (and others)? Not only did this deal include various radioligands in various stages of pre-clinical and trialling, but also a licensed-in ‘targeting‘ platform, i.e. CanSEEK™ (aka pre|CISION™ licenced from Avacta for certain RLT’s).

So Novartis are investing in RLT and would like this to be targeted, Lily have acquired a whole ‘bunch’ of potential RLT products – but have not (to my knowledge) as yet said anything about CanSEEK™.

We have pre|CISION™ and as of yesterday evening are advertising - pre|CISION™ drug conjugate (PDC), pre|CISION+ Immuno-peptide drug conjugate, pre|CISION™ ADC.

How long before pre|CISION™ RLT?

GLA

Https://avacta.com/precision/

pre|CISIONTM, pre|CISIONTM drug conjugate (PDC), pre|CISION+ Immuno-peptide drug conjugate, pre|CISIONTM ADC

Massive shift in focus - why ..?

https://www.biospace.com/article/adc-market-will-remain-hot-in-oncology-reaching-30b-by-2028-report/

$30bn to go for – are we going to be ‘disruptors’?

“The report calls the antibody-drug conjugate (ADC) market the “hottest real estate in oncology” that will continue to attract big pharma investment over the next few years. In 2023, ADC-focused M&A and partnership activity totaled almost $100 billion in total in 2023, more than three times the value of similar deals in 2022 and nine times more than in 2019, Evaluate said.

Among the recent big deals: Pfizer acquired Seagen for $43 billion, AbbVie invested over $10 billion in ImmunoGen and Merck committed $4 billion upfront, with a potential total of $22 billion, for a stake in three of Daiichi Sankyo’s ADCs.”

GLA

But no mention of Dx on the page footer.

Site being re-built around us for Tx.

GLA

Also, this page updated today …

https://avacta.com/careers-landing/about-avacta/

“The pre|CISION™ platform is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumours compared with healthy tissues. The pre|CISIONTM platform harnesses this tumor specific protease to activate pre|CISIONTM peptide drug conjugates and pre|CISIONTM antibody/Affimer® drug conjugates in the tumor microenvironment, reducing systemic exposure and toxicity, allowing dosing to be optimised to deliver the best outcomes for patients.”

Is this new wording ...?

“and pre|CISIONTM antibody/Affimer® drug conjugates …”.

GLA

While we wait, also at AACR ...

Old friend (Matthew Vincent) and current collaborator (William Bachovchin, Tufts - originators of pre|CISION™ chemistry) busy at AACR …

https://www.abstractsonline.com/pp8/#!/20272/presentation/8125

1874 / 18 - Common vulnerabilities of stem cells along the Barrett's-dysplasia-adenocarcinoma sequence

M. Vincent, W. Bachovchin

https://www.abstractsonline.com/pp8/#!/20272/presentation/3394

4654 / 7 - Targeting poly-resistant stem cells in high-grade serous ovarian cancer via synthetic lethal drugs

M. Vincent, None, W. Bachovchin

https://www.abstractsonline.com/pp8/#!/20272/presentation/5474

6099 / 25 - Identification of intrinsic precursors of Barrett's and gastric intestinal metaplasia

W. Bachovchin, M. Vincent

Prof Banerji has a few other ‘engagements’ …

https://www.abstractsonline.com/pp8/#!/20272/presentation/4493

6221 / 24 - First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin

Presenter/Authors U. Banerji

https://www.abstractsonline.com/pp8/#!/20272/presentation/11454

CT111 / 19 - Pharmacokinetic and pharmacodynamic evaluation of NXP800, a novel GCN2 activator, in a first in human clinical trial

U. Banerji, The Institute of Cancer Research

https://www.abstractsonline.com/pp8/#!/20272/presentation/11411

CT035 - Proof-of-concept and preliminary efficacy of triple IAP blockade to maximize immunogenic cell death and induce efficient adaptive immune response: First report on the ASTEROID phase 1 trial

U. Banerji, Chugai Pharma

GLA

(Cmon Avacta, show off the science, demonstrate the safety and efficacy with great data, and do some deals)