Member Info for B2HS2L

IMO it's just a question of each individual investors timescales, simple as.

J_t - Thanks for taking the time re MMAE's tonight.

Thanks Bella 😁

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Bella6532

RE: No licence deals 21 Mar 2024 09:09

....From June 2021 Results presentation - Page 16:

The Wider pre|CISIONTM Pro-drug Opportunity

pre|CISIONTM can be widely applied to a range of other chemotherapies in a market worth

$56.5B with CAGR of 11.50% driven by increased cancer detection rates

Example:

Velcade

• Bortezomib (Velcade, Takeda Pharmaceuticals) had annual sales of $1.2bn (2018)

• BUT – approval limited to multiple myeloma because of dose limiting toxicities,

• AND - coming off patent by 2022.

• Pre-clinical development of AVA3996 pro-velcade will be restarted using placing proceeds.

Example:

Taxanes

• Taxanes, such as the generic Paclitaxel, are used to treat a range of cancers such as prostate, breast and cervical.

• Paclitaxel has global sales of $2.96bn (2018) and is expected to generate revenue of $6.63bn by end of 2025.

• BUT - significant toxicities, such as myelosuppression and peripheral neuropathy, limit the effectiveness of paclitaxel-based treatment regimens.

Ideal for pre|CISIONTM tumour activation to create safer and proprietary pro-drugs.

Conservatively assume the pre|CISIONTM prodrug versions of these can achieve similar market sizes delivering 5-10% royalty to Avacta plus development milestones.

Potential for a pipeline of pre|CISION pro-drugs, some of which have already been synthesized, with an addressable market of many $bn pa.

Including but not limited to:

• preCISION Velcade

• preCISION Paclitaxel

• preCISION Oxaliplatin

• preCISION Gemcitabine

• preCISION Capecitabine

• preCISION PARP inhibitor

• preCISION PD-1 Inhibitor

• preCISION AKT inhibitor

• preCISION Balixafortide

Page 16 https://avacta.com/wp-content/uploads/2021/09/Avacta-Group-plc-Interim-Results-Final.pdf

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From RNS 23 December 2020

..."The study (AVA6000) will provide key information about the performance of the pre|CISION chemistry in humans that will underpin the value of a substantial pipeline of safer, next-generation chemotherapies.

We have already begun development of pre|CISION pro-drug forms of Velcade, Oxaliplatin and Paclitaxel so that we can rapidly accelerate one or more of these assets into the clinic when we see the first read-out from the AVA6000 trial approximately four months into the dose escalation phase."

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R&D spotlight - Episode 1 today:

"We're highly encouraged by the early data being produced in our lead compound, and we're looking forward to those new cyotoxics, on the preCISION platform that will be in our pipeline soon."

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Likely the pipeline will reflect new projects, ie pre|CISION pro-drug forms of Velcade, Oxaliplatin and Paclitaxel.

Thanks Energy, - I've read / listened to it.

My problem is with the expectancy part.

Thanks Bella.

"...platform we are seeing in the clinic underlines our confidence in the significant opportunity to apply pre|CISION? to a range of warheads"

significant opportunity in terms of expectation is not the same as

"...on the precision platform that will be in our pipeline soon"

Soon not the same as significant opportunity methinks.

Hi Energy,

"....we're looking forward to those new cyotoxics, on the precision platform that will be in our pipeline soon"

Blow me down, - can't find that in an RNS, - anyone know of similar in a video?

We said what we were going to spend the raise on, perhaps it was in the part mentioning general working capital. 👀

Ice - 'they figured out they could get significantly better deals further on in the trial.'

They being Shaun Chilton (arrived June 2023) and CBO Dr Simon Bennett (arrived Dec 2023), as well as AS with presumably the input of Chairman Dr Eliot Forster.

IMO AS and EF, without the input of SC or SB prior to June 2023 were more liable to make the kind of mistakes they are accused of here, than they are now.

That said, the gamble to seek licensing deals this quarter was on all four watches.

SB should make a big difference to the PoV of the CEO, who would need to act with the support of the Chairman.

But CEO and Chairman have the choice whether to take his advice or not.

For me should SB leave short or medium term without a replacement, then we are back to pre June '23 times.

I see him as being key to bringing value to shareholders, and I would like to know more about the input provided by Shaun Chilton. - Like what is his raison d'être, - is he at the top table as a sounding board, of is he proactive.

I see our problems as being in the care of all four, not just AS as being the only visible leader prior to June '23.

ATBD

Thanks, you placed the RNS's side by side.

The comparison IMO looks like Avacta still has not finalised the orphan indication(s) statement necessary to satisfy themselves and the FDA prior to Phase 2.

That's a wise position considering what data has yet to be found in Arm 2, and the fresh cohort 5,6 and 7 data missing from presentations.

ATBD

I don't see that Avacta can be serious about selecting a single orphan indication (ie a single STS sub-type)

I agree that the FDA ODD means STS generally, not all 50 sub-types.

However Avacta don't have all 50 sub-types in the trial.

From March 21st RNS - 'The data from the expansion study will be used to inform the optimal choice of a single orphan indication for the Phase 2 efficacy study'.

So IMO the single orphan indication will have to be well defined.

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Your "Avacta will be going after a completely different Orphan designated condition for the phase 2 after the dose expansion study."

I would say that might be a surprise to the FDA, as their interest is STS, (assuming any and all sub-types)

Indeed, William Tap comments from the RNS dated 13.12.23 -

ALS-6000-101 Phase 1a Three-Weekly Dose Escalation Safety Study Data

So not concerning the start of Arm 2

From bottom of 21.03.24 RNS

Lee Cranmer MD, PhD, FACP, Curtis and Elizabeth Anderson Endowed Professor in Sarcoma Research, University of Washington and Professor and Director of Sarcoma Oncology, Fred Hutchinson Cancer Center, commented:

"I am encouraged by the initial data with AVA6000 in the Phase 1 trial and look forward to working with my fellow investigators and our collaborators at Avacta to understand better the optimal dosing for this novel approach to targeted cancer therapy."

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I wondered why no word from Dr William Tap on such an auspicious occasion.

All three Arm 2 patients are in Fred Hutchinson Cancer Center?

Jive_turkey - re your 24 March 09:55 Interesting Article thread

"ava6k received orphan drug designation for STS.

For Phase 2, Avacta will select one sub-type of STS.

Which subtype is presently unknown, but they will likely try two or three subtypes in the P1b (although it's not called this at the moment, but for simplicity, I think we can use it)."

+++

I have posted with a link that there are more than 50 different types of soft-tissue sarcoma.

The March 21st RNS states:

'The data from the expansion study will be used to inform the optimal choice of a single orphan indication for the Phase 2 efficacy study'.

The Interim results for period ending 30 June 2023 RNS states

"Doxorubicin is used as a monotherapy for the treatment of soft-tissue sarcoma ("STS"), a relatively rare mesenchymal malignancy which accounts for less than 1% of adult tumours.

Despite the successful advancement of localised therapies such as surgery and radiotherapy, these tumours can recur, often with metastatic disease.

The American Cancer Society estimates that in 2022 approximately 13,190 new soft tissue sarcomas were diagnosed and about 5,130 people were expected to die of the disease in the US."

Therefore why might Avacta limit the application of so much effort to a single STS orphan indication, when the US market for this indication is likely to be very much less than 13,900 diagnosis per year, making AVA6K either very expensive indeed or, more likely, no profit would be achievable at this level of sales.

Why would the FDA expect Avacta to be interested in persuing such an approval when finances dictate that AVA6K needs to be approved for as many STS subtypes as necessary.

Avacta can only shortlist the STS sub-types they have tested in the Phase 1 (Arm 1 and Arm 2), and they are all AFAIK high FAP sub-types.

From 13.12.23 presentation - https://avacta.com/wp-content/uploads/2023/12/AVA6000-Data-Release-13-December.pdf

Page 12 states that of the 40 Arm 1 patients, 12 had Soft Tissue Sarcoma:

* Mr 65% tumour reduction = undifferentiated pleomorphic sarcoma

* 79-year-old female with the diagnosis of angiosarcoma of the spleen

* three patients with diagnosis of solitary fibrous tumour

So there are seven STS patients where their STS subtype are unknown, (unless others can advise?)

From the above, I don't see that Avacta can be serious about selecting a single orphan indication.

I believe - so far - we have tested a maximum of nine STS subtypes

FWIW, I posted this link recently:

https://sarctrials.org/education/soft-tissue-sarcoma/#:~:text=Extrarenal%20Rhabdoid%20Tumor,%2C%20lung%2C%20and%20other%20sites.

Soft-tissue sarcomas are more common than bone sarcomas.

The 50 different types of soft-tissue sarcomas differ in terms of their tissue of origin, clinical behaviour, age of occurrence, aggressiveness, the way they spread, genetic alterations, and their sensitivity to certain therapies.

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From a recent RNS

Mr 65% tumour reduction = undifferentiated pleomorphic sarcoma

Three patients with the diagnosis of solitary fibrous tumour have been treated at the dose levels of 250 mg/m2 and 200 mg/m2. All 3 patients with prolonged stable disease of 4-8 months with 2 of 3 patients ongoing, having experienced rapid progression prior to enrolment.

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The above patients diagnosis are described in the link.

On the other hand, this RNS dated - 5th Sep 2022 states

AVA6000 receives Orphan Drug Designation from the US Food and Drug Administration

Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer® and pre|CISION™ platforms, announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to the company's lead pre|CISION drug candidate, AVA6000, for treatment of soft tissue sarcoma.

+++

FDA interest for ODD status is STS.

Page 9 of the recent Turner-Pope document contains a comparison of AVA6000 Q3W/ and prior Doxorubicin trial results, - (Data reported from previous Doxorubicin trials containing Monotherapy Arms).

One caveat is that Avacta's Phase 1a trial contains only 40 patients.

Another is that the data cut-off for Phase 1a is 27.11.2023.

This comparison should be revisited after cohorts 5,6 and 7 data is made available at AACR (hopefully).

Hi Go Sushi

"While optimistic, it is possible that FDA approval could come after the P1b study (i.e., before P2 begins). To be clear, P2 will still be required, but ava6k could be on the market while P2 is being carried out.

Hi JT

You posted the above

I have never read of a DRUG being brought to market after phase one..."

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That's as may be.

But because AVA6K is a platform, and Doxorubicin is the well known DRUG in use for 50 years, I can see it being easier for it's approval, because of the relatively inferior performance of pure Doxorubicin.

Dr William Tap declared -

‘if we can come up with a better (treatment), then overnight it could become the standard of care.’

Let all Phase 1 a+b data do the talking (including Biopsies) when the data is complete.

Let's see if it's good enough for FDA approval.

Manufacturing

New Position - Manufacturing Technical Assistant

... "The role will have a particular focus on the introduction of **new products** and technologies into our Production and Quality Management (QMS) Systems, ...."

Key Accountabilities

"...Set up Sage codes and bill of materials for new products, sub-assemblies, and raw materials in the Sage manufacturing system

* Communicate with key stakeholders to ensure their requirements are met in the successful technical transfer of new products and technologies into the Manufacture Team

* Liaise with R&D on any redesigns and improvements as appropriate

* Brief the manufacture team on any design changes and improvements

* Sage administration and maintenance to ensure the system is kept up to date and stock levels are accurate and controlled

Label setup for new products

* Working closely with stakeholders to identify any product cost changes for business as a result of process and product changes

* Working to challenging deadlines as part of an ambitious pipeline of new product launches

* Contribute towards the technical transfer of manufacturing processes to sub-contractors

* Support the wider operations team in supply chain, stores and dispatch to ensure timely product delivery to customer.

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If they have got this far, the new products, a decision to put the products into production has been made.

Timster - A good friend sells aircraft simulators for a living.

He used to lead a team of maintainers, but found himself roped in to support when the sales team needed answers to technical questions.

Over a long period of time he now leads the sales teams, as his breadth of knowledge enhanced the sales teams pitch as well as answered potential customers questions.

Dr Simon Bennett joined Avacta on 19.12.23 and had this to say in the RNS announcing his appointment:

"Avacta is at a pivotal point, having recently announced clinical data that have already begun to generate interest from potential commercial partners. I am delighted to be joining at such an exciting point in the journey of the business, to help the team optimise the commercial opportunities of their technologies and assets."

Avacta could do worse than fly out PL to AACR, to provide technical backup in discussions with any and all interested parties.

Https://guoncologynow.com/podcast/episode-305-the-fda-and-oncology-clinical-trials

This one is working for me and my Bourbon poured over ice..

No Apple facilities necessary.

Bella - Because, if it was a while ago, we would know that data for that patient would be well ahead of the third patient. Weeks even a month or two ahead.

Yes they did tell us they would advise third dose. Nothing wrong with comms on that score then.

Did you really mean incestors. - I'm using the right chat board aren't I?