Member Info for LiveLongnProsper

Lilly acquired Point for $1.4bn, now Novartis acquire Mariana for $1.75bn ($1bn upfront +$750m potentially to come). Though I wonder if Mariana’s primary candidate MC-339 is actually still pre-clinical? Noting that they raised $175m last year to bring it to trial. (Please let me know if you can find a trial running.)

Seems that the targeted RLT marketpace is ‘on fire’. But, RLT is difficult and expensive. I have previously mentioned the supply-chain challenges in particular, and then managing radioisotope targeting and half-lifes in the body.

We seem to have something that works, in that it delivers the SOC chemotherapy to the TME (for FAP expressing cancers) at much higher doses and with minimal side effects.

Just a matter of time (and the right FDA approvals) before (as someone who knows about this stuff intimated) … ‘a doxorubicin (e.g. AVA6000) better than ‘standard doxorubicin’ overnight becomes the standard of care’.

GLA

Https://www.proclinical.com/blogs/2024-2/top-10-drugs-with-patents-due-to-expire-in-the-next-5-years#:~:text=Keytruda%20is%20on%20schedule%20to,%2433.7bn%20in%202028%20estimates.

Keytruda patent expiry 2028. Merck team task – how to extend patent, how to enhance with combo’s (for patients), how to consolidate market position, etc …?

Hints …

Targeted delivery, for example (say) to FAP?

Alternative to ADC’s, for example (say) PDC’s?

Other PD-1 / PD-L1 checkpoint inhibitors, for example (say) Affimers?

Keywords – ‘Holy Grail’, ‘Paradigm Shift’, ‘It works ™’.

$30bn+ to protect guys, over to you.

GLA

“Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer” …

https://www.nature.com/articles/s41523-024-00643-5

Needs a careful read, but MSK looking at Q2W dox (combo) and with Pembrolizamab (Keytruda). But, and ‘here’s the thing’, doesn’t look like the dox is targeted.

GLA

Resistance is futile.

GLA

Yep, rockets (with star bursts).

GLA

GS Global Healthcare Conference June 10-13 2024. Wonder if this was where CC travelling to last weekend? A few ‘snippets’ …

Pfizer …

https://s28.q4cdn.com/781576035/files/doc_events/2024/June/PFE-USQ_Transcript_2024-06-10.pdf

Very interested in ADC’s (Seagen, others), also interested in CDK4 and bispecifics – Affimer ‘space’ then?

Merck …

https://s21.q4cdn.com/488056881/files/doc_events/2024/Jun/11/mrk-usq_transcript_2024-06-11-3.pdf

‘Tissue-targeting’, ‘ADC linker and payload’. Looking beyond Keytruda.

BMS – not from GS conf, but perhaps (?) worth a listen, particularly @ ~2:00 in …

https://www.bms.com/media/media-library/scientific-media-resources/anti-cancer-advanced-modalities.html

Fascinating responses from Moderna, Pfizer, Gilead, Merck (Keytruda), Baxter, Sanofi, AbbVie, Lilly, Bicycle, Incyte, and others. All on ‘standardised’ web pages, with a webcast link that requires registration. Only found Pfizer and Merck, so far, putting out a transcript.

If CC there, might explain the quiet week?

GLA

@GS, I think it demonstrates that in Coris BioConcept we have a small IVD business developing and manufacturing products to test for bacterial and viral infections – including for anti-microbial resistance. Good for humanity then.

Clear opportunity to integrate (and rationalise) Avacta’s Diagnostic R&D capability into Coris and (you never know, it’s been a long wait, etc.) produce some Affimer based test products.

Also the opportunity to sell the Coris products through the (now in Germany) Launch Diagnostics channel. Slowly building an integrated diagnostics development, manufacturing and distribution company – selling direct and through partners.

TD latest revenue projection for Avacta Group 2024E £23.9m (looks low to me) – 2023 £23.2m, with Diagnostics £21.2m. So assumes nothing from current Tx partners and only +£2,7m (+12.7%) from Diagnostics (Launch and Coris). Target is for Diagnostics to be cash positive in H2. Maybe enough to pay the CLN in cash?

Diagnostics being ‘shaped’ for sale, perhaps with the CLN on their b/s, or just paid off in the 'deal'?

Great research @gmcc

GLA

No vacancies as of today ...

https://avacta.com/careers/careervacancies/

We've either got the right scientists, or we no longer have a need?

GLA

@NFTs, I’m probably missing something here, but what is ‘coming in’ the post tomorrow?

GLA

Or Lilly are simply doing there own FAP targeting molecule (with the help of Tufts - who should be familiar) ..?

https://jnm.snmjournals.org/content/early/2023/11/30/jnumed.123.266345

Actually think it highlights the value of pre|CISION™ even more so, if maybe not Lilly at the 'front of the pack'?

Other BP's are available and 'Big Pharma' means 'Big' resources.

GLA

RNS 21 March …

“Avacta Group … is pleased to announce that yesterday the third patient was dosed in the first cohort of the two-weekly Phase 1a dose escalation study of its lead pre|CISIONTM drug AVA6000 ..."

RNS 23 May …

“Avacta Group … is pleased to announce the successful completion of the first cohort and dosing of 3 patients in the second cohort in the dose escalation study of Arm 2 of its Phase 1 trial for AVA6000 ... In addition, a sub-study utilizing FAPI-PET scanning at baseline has also commenced to further characterize the full burden of FAP-positive disease in patients.”

Ch1 – 20 Mar to 23 May (latest) – 64 days, applying the same duration, and no delays – patient dropout, adverse events, MTD, in-depth analysis of biopsies, FAP-PET impact, etc., end dates would be …

Ch2 – 26 July, Ch3 28 Sept, Ch4 01 Dec.

Interesting that, since AACR24 poster, no further new info on efficacy, patients continuing ‘on drug’, etc. Being managed ‘tightly’, no doubt a few NDA’s in place for more up-to-date data access for ‘interested parties’? Trust Simon still ‘quite’ busy.

(Don’t think I’m on an ‘Alan calendar’, but please correct dates / assumptions as appropriate).

GLA

Avacta CEO highly motivated .

GLA

Posted in bioRXiv a couple of days ago …

https://www.biorxiv.org/content/10.1101/2024.05.31.596836v2

Quite ‘deep’ science to say the least.

ChatGPT 4.o says about the TACC3 gene …

‘TACC3 is often implicated in cancer. Its overexpression or mutation can lead to chromosomal instability and aneuploidy, common features in many cancers. TACC3 has also been studied as a potential biomarker and therapeutic target in oncology due to its involvement in cell division.’

Reviewing the paper ChatGPT 4.o says…

‘The paper provides a detailed structural understanding of the TACC3-ch-TOG interaction and introduces molecular tools to inhibit this interaction, revealing its critical role in mitosis. This research could pave the way for targeted therapies in diseases characterized by abnormal cell division, such as cancer.’

‘This study demonstrates the potential of Affimers as tools for disrupting protein-protein interactions and as possible therapeutic agents in targeting specific cellular processes involved in mitosis’.

GLA

Maybe Lily are waiting to see how this trial goes …

https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS3161

“PNT6555, a potent FAP-targeting compound with rapid clearance from normal tissues and prolonged tumor retention in preclinical models1, is a radioligand consisting of a DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) and a FAP-targeting moiety (Bz-D-Ala-boroPro) connected via an aminomethyl linker.” Note that the PNT6555 molecule is out Tufts

Not a ‘million miles’ from pre|CISION™ then? Bearing in mind that ‘AVA6000 consists of a doxorubicin molecule covalently bonded to a dipeptide (pyridine-4-carbonyl)-D-Ala-L-Pro).’

But then we have ?

https://www.pharmaceutical-technology.com/data-insights/lutetium-lu-177-dotatate-point-biopharma-global-neuroendocrine-tumors-likelihood-of-approval/?utm_source=lgp5-loa&utm_medium=24-181531&utm_campaign=recommended-articles-pi

“POINT Biopharma Global overview”

“It utilizes CanSEEK platform technology to develop cancer treatments.”. So perhaps Lily still working on a CanSEEK based RLT?

All in a pay for report. How up-to-date, or accurate, who knows?

What is clear is that FAP targeting interest is significant in BP and we are at the ‘leading edge’ at least for Chemo, if not RLT.

GLA

Revenue projection 2024E £23.9m looks low – 2023 £23.2m, with Diagnostics £21.2m. So assumes nothing from current Tx partners – LG Chem and AffyXell, and only +£2,7m (+12.7%) from Diagnostics. Would expect much better, as Diagnostics being ‘shaped’ for sale. From ARA – “the appointment of Shaun Chilton as a Non-executive Director to the Board, bringing with him a wealth of pharmaceutical and pharmaceutical services experience from global companies across Europe and the US to support the Diagnostics Division as it progresses with its growth strategy …”.

Also worthy of note that TD value Diagnostics at £42.5m and the CLN principal stands at £35.7m, so big ‘safety net’. Personally, would like to see CLN paid in cash on prospect of (stated) expectation that Diagnostics cash positive in H2 2024.

Mon – R&D Spotlight part 3,

Tue – June 2024 presentation slides,

Wed – June 2024 presentation video,

Thur – TD update,

Fri and next 3 weeks to AGM - ???

GLA

Quite (American ‘meaning’) a few ‘other matters’ to achieve a ‘quate’ (old English) state. For example - ARA Page 12 Chaiman’s Statement …

“We are also aware of the need to continue to evolve the Board of Directors to best suit the needs of an AIM-listed clinical stage cancer treatments company, to strategically manage the Diagnostics Division for the best outcome for our staff, customers and shareholders alike, and to create financial optionality with respect to the company bond. The Board of Directors and I are excited about what is to come for Avacta”.

Recent updates suggest science looking great, now for the commercials.

GLA

Https://avacta.wistia.com/medias/5kvz3qxd5d

Just posted om twiX.

GLA

@Bella, re AXA, try this - Avacta Fund / II ownership from MSN …

https://www.msn.com/en-in/money/compare?id=ao67k2&view=chart&comps=-%2C-%2C-

Select AVCT, then Investors.

GLA

Great innovation and long-term potential.

Just for context – post chemotherapy and / or surgery, cancer cells extracted, DNA analysed for mutations, personalised vaccine manufactured for that specific patient.

GLA

@Hurst10, simple question, how does this work ..?

“The company could risk being taking private prior to a NYSE listing.”

I mean, other than being acquired at a price agreed by the majority of shareholders (and that would be quite a high price, so OK with that).

Bearing in mind (my speculation, DYOR, etc.) that PI’s probably account for >70% of share ownership and those with a reasonable holding probably number in the low 000’s.

GLA

(Just as an aside, it is, perhaps, worth looking at the ASCO schedule – plenty of dox combo trials, ‘peptide talk’, ADC’s, etc., etc.).