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Part 5

“ pre|CISIONTM technology

Many solid tumors have higher levels of FAP compared with healthy tissues. Avacta’s pre|CISIONTM technology is designed to leverage the tumor-specificity of FAP expression by rendering a therapeutic warhead inert with the bound peptide moiety attached to the warhead, until it encounters FAP and is cleaved, releasing active warhead into the TME. FAP targeted release of the warhead specifically in the TME aims to reduce damage to healthy tissues and systemic side effects, improving the tolerability for patients and allowing optimization of the dosing schedule to improve efficacy.

References

1Tap WD, et al. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020;323(13):1266-1276. doi: 10.1001/jama.2020.1707

2Jones, RL et al. Prospective evaluation of doxorubicin cardiotoxicity in patients with advanced soft tissue sarcoma in the ANNOUNCE Phase III randomized trial. Clin Ca Res 2021;27:3751-66. doi: 0.1158/1078-0432.CCR-20-4592

3Villalobos VM, et al. Pharmacokinetics of doxorubicin following concomitant intravenous administration of olaratumab (IMC-3G3) to patients with advanced soft tissue sarcoma. Cancer Med. 2020;9(3):882-893. doi: 10.1002/cam4.2728

4Kontny N et al, Population pharmacokinetics of doxorubicin: establishment of a NONMEM model for adults and children older than 3 years, Cancer Chemother Pharmacol 2013;71(3):749-63. doi: 10.1007/s00280-013-2069-1

5Pérez‐Blanco JS et al, Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non‐Hodgkin's lymphoma, Br J Clin Pharmacol. 2016; 82(6): 1517–1527”

Part 4

“ Safety and Pharmacokinetics Data

Treatment with AVA6000 continues to be well-tolerated with the addition of the Q2W dosing regimen (Arm 2) with a favorable safety profile and reduction in severe and mild-to-moderate treatment-emergent toxicities as compared with conventional dose doxorubicin. A maximum tolerated dose has not been identified in either arm of the trial.

Severe (CTCAE grade 3 or 4) neutropenia was observed in 14% of AVA6000 patients vs 49% treated with conventional dose doxorubicin (comparison made to a Ph III trial where doxorubicin monotherapy is the comparator arm in a similar patient population).1 There were no cases of febrile neutropenia in the AVA6000 trial compared to 16.5% of patients receiving conventional doxorubicin alone in a similar patient population1

The observed cardiac safety profile of AVA6000 compares favorably to conventional dose doxorubicin, with low incidence of left ventricular ejection fraction (LVEF) changes (LVEF dysfunction 12.3% v. 48.4% with conventional doxorubicin1,2) and no grade 3 or 4 severe cardiac events reported

Reductions were observed in toxicities that impact quality of life including nausea, mouth sores, decreased appetite, constipation and vomiting and similar reductions were observed with both the Q3W and Q2W dosing schedules.as compared to conventional doxorubicin dosing1

No new dose limiting toxicities were observed and neither arm has determined an MTD

Treatment with AVA6000 results in multiple fundamental changes in the PK of released doxorubicin (compared to conventional doxorubicin administration3) including:

Extension of the plasma half-life by ~40%

Reduction of approximately 40-50% in both Cmax and the peripheral volume of distribution, suggesting AVA6000-released doxorubicin demonstrates a more limited distribution into normal tissues versus conventional doxorubicin4,5

Tumor biopsies taken 24 hours after the first dose of AVA6000 reveal additional insights regarding the role of FAP, in that the level of FAP positivity in the tumor appears not to correlate with the level of released doxorubicin in the TME (n=9). This lack of correlation indicates that lower levels of FAP activity are sufficient for warhead release. These data provide evidence for targeting of the FAPmid tumor types with novel warheads.”

Part 3

“ Efficacy data

Cancer indications were categorized based on published data regarding both immunohistochemistry and FAPI-PET studies as FAPhigh (soft tissue sarcoma and salivary gland cancer) or FAPmid (pancreatic cancer, colorectal cancer, lung cancer and other malignancies). Patients with indications considered FAPlow were excluded from the trial. Patients had a median of two prior systemic cancer therapies (range 0-7) with 65% including cytotoxic exposure. Reduction in the sum of longest diameters (SLD) is used to measure response per RECIST 1.1 with partial responses of >30% reduction and minor responses of between >10% and 18 weeks, with 46.2% reduction in SLD). Tumor histology demonstrates no expression of FAP in tumor cells with only stromal cell expression noted.

A minor response (14.6% reduction in SLD at first 8-week scan) in a 65-year-old female patient with SGC who remains on the trial. This patient was dosed in the 250 mg/m2 Q2W cohort of the trial and had progression on a prior line of therapy. This patient continues on study. Similarly, the histology shows FAP-negative tumor cells and FAP expression only in the stromal compartment.

A partial response (40.5% reduction in SLD) in a 55-year-old male patient with dedifferentiated liposarcoma who had progressed on two prior lines of therapy in the metastatic setting. After an initial minor response this patient experienced a partial response with SLD change of -40.6%. The patient experienced new lesions at their latest follow-up scan.

Eight patients remain on study in the Phase 1a cohorts with a diagnosis of FAPhigh cancers

Among patients with FAPmid cancers (n=26), two minor responses were observed.”

Part 2

“ Professor Chris Twelves, Lead Investigator and Professor of Medicine, University of Leeds, commented:

"The AVA6000 data presented at ESMO continue to demonstrate encouraging efficacy with several ongoing, durable responses. The observed efficacy aligns with a highly favorable safety profile including a lack of the significant cardiac toxicity that is often seen with doxorubicin treatment.

“The mechanism of action of the pre|CISION™ peptide drug conjugates with the observed warhead release in tumors with lower FAP activity together speak to the potential of this platform to treat a broad range of solid tumor patient populations with clinical needs that are not being met. I am looking forward to working with the Company, colleagues and patients on the continued development of AVA6000."

Christina Coughlin MD, PhD, Chief Executive Officer of Avacta, added:

“With nearly six months of added follow-up, these compelling data strengthen the clinical validation for AVA6000 and the pre|CISIONTM drug delivery platform to challenge current drug delivery methods and expand the reach of highly potent therapeutics using peptide drug conjugates.

“We believe our platform has the potential to revolutionize cancer treatment by enabling patients to achieve improved outcomes with fewer side effects by leveraging the tumor specific enzyme FAP to protect normal tissues from toxic drugs. The observation of warhead release in the tumor even in the setting of lower FAP activity is highly encouraging for our pipeline. We are excited to move our Company into the next stage of development, implementing these findings of this drug release mechanism across our innovative pipeline.”

Trial Results Summary

As at the latest data cut-off date, ten dose cohorts (n=57) have completed the Phase 1a trial under the Arm 1 dosing schedule of every three weeks (“Q3W”) and the Arm 2 dosing schedule of every two weeks (“Q2W”). In total, 57 patients were enrolled and are evaluable for safety (primary outcome measure) and 49 patients formed the efficacy evaluable dataset (secondary outcome measure).”

Part 1.

“ Avacta Reports Updated Phase 1 Clinical Data of AVA6000 at the European Society for Medical Oncology (ESMO) Congress Demonstrating Multiple Ongoing, Durable Responses in Solid Tumors

14/09/2024 8:00am

UK Regulatory

Avacta (LSE:AVCT)

Intraday Stock Chart

Monday 16 September 2024

Click Here for more Avacta Charts. Avacta Reports Updated Phase 1 Clinical Data of AVA6000 at the European Society for Medical Oncology (ESMO) Congress Demonstrating Multiple Ongoing, Durable Responses in Solid Tumors

This announcement contains inside information for the purposes of Article 7 of the UK version of Regulation (EU) No 596/2014 which is part of UK law by virtue of the European Union (Withdrawal) Act 2018, as amended ("MAR"). Upon the publication of this announcement via a Regulatory Information Service, this inside information is now considered to be in the public domain.

14 September 2024

Avacta Group plc

(“Avacta” or “the Group” or “the Company”)

Avacta Reports Updated Phase 1 Clinical Data of AVA6000 at the European Society for Medical Oncology (ESMO) Congress Demonstrating Multiple Ongoing, Durable Responses in Solid Tumors

AVA6000 is safe and well-tolerated in both study arms: every three weeks (Q3W) and every two weeks (Q2W) dosing, with an early lack of serious cardiac safety signal and preliminary evidence of efficacy

Multiple ongoing and durable RECIST responses observed in patients with FAPhigh and doxorubicin sensitive diseases including in patients with stroma-only expression of FAP

pre|CISION-enabled doxorubicin (AVA6000) results in multiple fundamental changes in the pharmacokinetics of released doxorubicin in plasma and tumor versus conventional doxorubicin

Avacta Group plc (AIM: AVCT), a life sciences company developing innovative, targeted cancer treatments and powerful diagnostics, is today presenting updated data from the ongoing Phase 1a trial of AVA6000 in patients with FAP-positive solid tumors at the 2024 European Society for Medical Oncology (ESMO) Congress, in Barcelona, Spain.

The results demonstrate that AVA6000 is well-tolerated across the every 2 weeks and every 3 weeks dosing schedules with early evidence of efficacy supported by ongoing and durable RECIST responses in patients with FAPhigh disease. AVA6000 is the first peptide drug conjugate (PDC) in the Avacta pipeline and consists of doxorubicin conjugated with a peptide moiety that is specifically cleaved by Fibroblast Activation Protein (FAP) in the tumor microenvironment (TME).”

On the ADVFN site (L2), there is an RNS showing, apparently posted at 8am on Saturday 14/9? I came on here just to read comments about it, but there seem to be none. On checking, the “RNS” appears nowhere else (here, AVCT site, LSE site). It looks legit so I’m assuming somehow ADVFN have messed up by posting it. That being the case I’ll post it here in parts. If I’ve missed something and people are aware of it then I’m sorry.

And of course, it should save many lives.

Thought some might find this interesting. It’s a paper published last year by a number of authors, predominantly from MIT, Harvard Medical School, and Brigham and Women’s Hospital, but also including Eduardo Gaude, the CSO and co-founder of Pockit Diagnostics (which trades as Upfront Diagnostics).

It seeks to discover the global, national, and regional economic consequences of stroke in 2019, and does so by calculating Value of Lost Welfare (VLW).

Upfront has developed an LFT (with us) for early detection of large vessel occlusion (LVO) a type of ischemic stroke. Early detection is critical for effective LVO treatment. If you read the paper you will see the sheer scale of cost, in terms of VLW that all strokes cause - 1.66% of GLOBAL GDP. But for our purposes I think this is the highlight;

“One pertinent example is that of ischemic stroke which had macroeconomic losses of over $100 billion in the United States alone. Among ischemic stroke, large vessel occlusion (LVO) is estimated to make up ≈1/3 of cases.”

So in 2019 LVO cost the US c$33bn. Just the US.

Globally, LVO costs will be much much higher.

It really is little wonder that the Upfront test made its way onto IDAP. It has the potential to save nations and insurance companies billions of dollars.

https://www.ahajournals.org/doi/10.1161/STROKEAHA.123.043131

Final trial results should be this quarter. There has been nothing to suggest the test doesn’t work. On that basis, it really does seem we will be making a test primed for global demand.

And that’s just one of the tests we have on the IDAP scheme.

Just my views!

To try and be helpful BD, Salistick is the worlds first Saliva pregnancy test. We make it (or at least parts of it) for its developer, an Israeli company called Salignostics. We have exclusive U.K. and NI distribution rights. It received U.K. approval last year and we subsequently got into Superdrug, then Tesco, and on Amazon. Subsequently we got into Boots as an own brand product.

It’s currently also on the market in Israel, and distributed in the Nordics (through a company called Addeira) to all major Nordic retailers. It’s currently not yet available in mainland Europe or the US, to some confusion and frustration.

I hope that helps. I would also stronly recommend that anyone on here registers with LinkedIn so you can access postings from ABDX and others, notably it’s CEO and Sales Director. Often that is the place best news snippets are found.

You may not see the value in LFT’s Paul, but plenty do and they are buying them.

But LFT’s really isn’t where MHC is positioning itself. They are looking to attract business from people trying to understand their own bodies so they can make healthy changes personal to them. Yes that comes at a cost many can’t afford. But many can.

In truth, I don’t even know if Salignostics are even keeping that site updated. It’s had a banner on it saying it’s undergoing review and update, with some information not up to date, for months if not years, and the ISO certificates all posted there expired in a June last year!

They did, however, build out this new one just devoted to Salistick

https://salistick.co.il/english/

My local Boots, which is a really small store, only has three pregnancy tests for sale, Salistick being one.

I’m afraid to say that the bit about Salistick seeking distributors has been on their site for years. What we really need to look at is if and when they add a distributor to those already disclosed, preferably a US one!

As always - no problem, but thanks!

Its like searching around for the dregs though. My sense at the moment is;

Loop - they were aiming for first UK sales in Q2. They haven't updated their site to say that's been achieved, and I've seen nothing from them celebrating sales. So you have to think they're struggling. Might change if they can get CE mark, which their timeline suggests should be this quarter.

Upfront - seem to be going great guns. Hopefully we will get the last set of trial results this quarter and, if they are as hoped and expected, I'm confident we will see this taken up into the NHS. That's the point of IDAP. Then we might also hear something about breakthrough designation in the States - remember, there is now an aligned regulatory approval process such that approval here by MRHA should also mean the same with the FDA. This ones a real potential money spinner for us.

Salistick - I'm as frustrated as others that this isn't yet available in more jurisdictions, notably mainland Europe and the US. It has been out of stock at Tesco (online) for a while now (having been on the discount rails), and most Superdrug stores have had no stock for a while either. Don't really know what to make of that. Are those outlets ditching it? Or are we retaining stock for Boots and potentially a launch in another jurisdiction(s)? Crest did take it to the US, which would seem a little pointless if a launch wasn't coming, and their Linkedin post suggested the product was US bound.

FOFH - little to say there. It remains an enigma to me, but I am very hopeful it has something special about it.

Hormona - everything is indicating that will launch soon, Don't discount it!. Hormona already have registrations for their app from people in 185 countries and these tests won't just be once and that's it, they will be for ongoing hormone monitoring. Potentially a lot of sticky repeat business.

Quiet at the mo, but all it will take is some really nice commercial news and this free float will see some real action.

NHS services will move into the pharmacy and the community. It’s already happening, and is necessary as part of NHS reform.

And people want to know more about their bodies and to take control of their own health. The wellness market is booming.

So, build a trusted wellness brand, offer it through retail partners the public trust and who will come to be considered part of the NHS, add in digital platforms and connectivity, and people will buy.

MHC are in a really good space.

Not much reaction on here to my last, but the reaction the Upfront post has had on LinkedIn suggests industry peers think it’s a pretty big deal.

Also found this today, confirming that LVOne was granted a U.K. patent on 17 July

https://www.ipo.gov.uk/p-pj/p-pj-ukappgrant.htm?startYear=2024&startMonth=July&startDay=17th+-+7052&endYear=2024&endMonth=July&endDay=17th+-+7052&filter=Pockit&sort=Publication+Date&status=undefined&perPage=10

Things really do seem to be developing well for that ABDX customer.

As you say, the Swiss now look very unlikely as a finance option.

We’ve not been told about any other re-finance options, and my bet is there are none.

So another standstill is the best we can hope for.

Will what’s in this RNS give any reason for Alpha to agree that? Who knows, but I don’t think so.

So, we’re left with a company no doubt running on fumes, struggling to secure paltry revenue streams because it’s unlikely to be able to raise given current SP, and using reduced workforce to get that revenue at what must be to the added detriment of BP production.

Add to that all the outstanding trade creditors, including the tax man, no PGM revenue, and Takob issues and I’m really struggling to see anything positive here.

Exactly Dicko80 - that was the most telling part of the RNS.

For to my last, Upfront posted this today.

Given we are making their test, you do have to wonder if the excellent results of our audit resulted in this award to Upfront. I certainly suspect we had a lot to do with putting their QMS in place.

https://www.linkedin.com/posts/upfrontdiagnostics_stroke-lvone-iso13485-activity-7239232118080327680-SB_V?utm_source=share&utm_medium=member_desktop

I've come in betting it will Jamrock.

We know from the IMC presentation that something was afoot, but could not be discussed.

That presentation suggested to me it has something to do with Phlebotomy.

The fact we have had no trading update (as in previous years) as a precursor to the half year report is telling I think

There is of course the linkedin post celebrating a fantastic year so far and exciting news which can't yet be announced.

Everything just seems "secret squirrel" at the moment. Points to something material for us and probably Boots.

We are seeing share sales resulting in a gentle uptick to the dummy bid rather than a fall as you might expect.

No problem!

Another little observation. A company called Mira Vista diagnostics put this out earlier today.

https://www.linkedin.com/posts/miravista-diagnostics_miravistadiagnostics-activity-7238926349120249858-ODIO?utm_source=share&utm_medium=member_desktop

It’s pretty benign stuff really.

But what is interesting is that of the seven reactions to it since posting, 2 are from ABDX, and they’re our CEO and COO.

So whilst getting excited about fungal diagnostics is difficult for me, I would not be surprised if we have involvement, and it’s a sizeable company based in the US.

https://miravistalabs.com/clinical-resources/forms/