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Where did you read that then.

If ever there was a post with bait 'designed in', that was it.

Replying would probably trigger FUD

Thanks for your response Thompi.

I am coming from the fact there is currently no ODD applications available, so currently there is no potential.

I think the author has made an assumption, and he is using 'potential' because Avacta has to succeed with an ODD application before being able to benefit from such an application.

Gmcc

https://x.com/sandyradders/status/1900545437901230120/photo/2 - first paragraph

"It offers the potential for a rapid route to market through an orphan indication, salivary gland cancer, prior to expansion into larger applications."

That is tosh because:

13 Mar 2025 10:19 -

If SGC is to feature large in Avacta's future, why do we not have, as yet, an ODD for Salivary Gland Cancer?

ODD is not currently available according to this link. Receipt Dates: October 22, 2024 (for new applications)

https://www.fda.gov/industry/grant-programs-support-development-medical-products-rare-diseases/funding-opportunities-rare-disease-research

13.03.2025 22:43 post

During Panmure interview :

"Great to hear CC say they are working in the background with Biologic drug conjugates (Affimers), AKA AVA7100."

Energy

Re: Pathway inhibitors very effective in a number of diseases, but carry high toxicities. 15mins 35 secs not just chemo

CC said - “We hope to see one of them come soon to the clinic”.

This quote is in direct contradiction of the following:

30.10.2024 - R&D Spotlight focusing on pipeline advances

Specifically the Q/A session that followed that presentation.

We only have a report from Jive_turkey he posted on 'X' (thanks again j_t) to advise what it contained.

"• All work on the Affimers (other than AffDC’s) platform has been paused to focus money and attention on precision."

So I assume that may mean Affyxell development work is perhaps being re-prioritised.

https://x.com/jivetur88775834/status/1851732150573568183/photo/1 - recommended reading

Lrink

These are very interesting platforms, I guess thinking about strategic opportunities with that, and how are you thinking about business development. This is the way to maximize the value of this unique drug conjugate base platform. I'm sure various strategics would be interested in their various payloads and what have you, and want to combine with how you think about that. Maybe bring in some non-dilutive funding, and otherwise what's your balance sheet looking like in terms of your runway right now.

CC

I'll start with the last one and we did disclose that with our dive investment of the diagnostics division that we now have runway into the first quarter of 2026. In terms of the IP around the second drug so around that sustained release mechanism is very fresh very new it was only filed in October. So those conversations started soon after that and as you know with any BD deal it takes multiple dates to go on multiple date, but yes the conversations are ongoing. But given that the IP is so new, we're excited about that one the chemistry there really being able to deliver that drug in the tumor micro environment and take a nine-hour half life to over 60 hours we think it's pretty special.

Lrink

Think about the rest of 2025 then, have some clinical updates coming. You think you maybe just frame our expectations on timing and the cadence of those readouts, in which tumor types, dose escalation or expansion, patient followup, whatever details you can give us.

CC

We will be going to a major medical conference in the second quarter of this year we have disclosed that, not exactly which one, but there will be an update on the salivary gland data and especially as we move towards that durability and understanding in the phase one what our PFS looked like. It's also going to take into account some of the data that we've seen on how the platform works in the clinic. And then the expansion cohorts will enroll, we've begun enrolling those over the course of 2025 and LATE this year we're going to be looking at some of the data coming out on those expansion cohorts. The three diseases that we're looking at is the salivary gland we've also seen some activity and high grade sarcoma subset and then importantly etc Triple Negative breast cancer data will be reading out.

Lrink

Roughly how many patients (data do we) look forward to.

CC

The cohorts are each written for 20 to 30 patients per. The data will read out and then we'll see how enrollment goes there.

Lrink

How important are objective responses in salivary though. Do you think as you really hone in on dose expansion and optimized regimens you can convert some of those minor responses to full objective responses, how important you think, could that be an accelerated pathway about duration of response and or are is this a quark about salivary gland where it's one where you can get long-term stable disease and minor responses without you know full objective responses.

CC

Having been a practicing oncologist I can tell you the patients the families don't ask how much did it shrink. They always ask hey doc how much time do I have. Because it's time that matters to the patients. If it's a minor response versus a true partial response I'm not sure that that matters as much as are we getting some really nice disease stabilization and delivering time to patients. What they don't get right now is that kind of time with the combination team, even if they do respond and shrink the tumors it's generally very short lived. The pfs end point we think is is highly clinically meaningful, it is associated with these minor responses, but I will tell you a story from the trial. One of the first patients that was treated in this cohort, had a very large chest wall skin metastasis, and the investigators tell us that skin metastasis are you know just a part of this disease it's one of the places that it goes and we were intending to biopsy. We didn't get a biopsy we wanted to get started with therapy we were intending to biopsy at cycle 2 with this particular patient. But the chest wall metastasis had disappeared. (One dose!). But that doesn't count in RECIST because it's a non-target lesion you know all the rules of RECIST. These are some of the complexities I would say of salivary gland and that's where the investigators continue to tell us if we can get some real time for these patients it's very meaningful in their lives.

Lrink

What is that bar of investigators choice I guess it would be measured by PFS. Could you talk about what a potential registration pathway would look like. It seems like one maybe right for accelerated approval, even single arm or small randomized trial on the table here and what would the Endpoints look like.

CC

I think PFS you're 100% correct just because of how AVA6000 is working and really stopping these tumors in their tracks. There was a good series that was published it was a multi institution series published at ESMO which showed 3.5 to 4 months of PFS in the second line and greater, which is exactly where we would be going. Right now our median follow up in that cohort that I showed you is five months and so we've already essentially beat it even in phase one with pretty heavily treated patients. There's a small group of Physicians who you know this is their life's work and so we've started talking to them about putting a registry together which is exactly what I did an Immunicore with that small little disease setting of Uvial Melanoma. There's really some strategies here that are 100% correct, and we have to get creative when the disease is small like this and that's in contrast to the second opportunity which is breast cancer. Doxorubicin is used straight across the board. With that cardiac safety, you know the breast oncologists are really looking forward to working with us on this one.

Flood the tumor with payload.

Lrink

And you show that activity is corrected where they could be FAP negative on the tumor, but positive on the stroma and still get a response. So I think going to talk about Salivary glands the most immediate opportunity for you. I know you touched on this a little but could you talk about how Physicians use Doxorubicin isn't a standard of care but how close is that to a standard of care or a presently used regimen? And what's their excitement of being - yes we like this, but the Cardio tox for having a next gen Doxorubicin versus another type of cytotoxic for a Salivary gland specifically?

CC

So the first regimen that's often used is very similar to how we treat prostate cancer, it's androgen deprivation therapy, they often can get responses to this. Most salivary gland cancers express the androgen receptor. After that it becomes a little bit of the wild west there are some patients that express her2, and that can work that's a very small percentage of patients. Mostly then the investigators or you know the Physicians will move to combination chemotherapy. So carbotaxol is one regimen that's used, there's actually a triple combination that Doxorubicin fits in. Those are probably the two that are used more frequently. The reason the investigators are so excited about this and if I had Alan Ho up here he would tell you, even the minor responses are great because these appear to be quite durable. That's exactly what we see in the animal models. We give a few doses and those responses are durable for 30 days afterwards. What they don't see is prolonged duration of responses in these, so after androgen deprivation therapy has stopped working, and all of those patients have had the androgen deprivation therapy, none of those patients were first line. So that's the whole development plan. Androgen deprivation, then we're going to come in with AVA6000. Where there is such high unmet need it'll be a pi choice, randomized trial and probably go up against Carbotaxol.

Lrink

Just reminder for the second program is the exatecan payload is very common for these newer generation ADC's, sometimes that exact one to just Durextecan classic one from Daichi and Astra, you did show some preclinical data showing in the resistant models in that sense, do you anticipate any challenges sequencing, and development strategy, and rolling in a world where maybe earlier line that you see a lot more of these topo one inhibitors?

CC

Outstanding question - The way to deal with that is really through that tempus collaboration and looking for some diseases where we might expect some nice activity, and it may not be that well trodden. Small cell lung cancers actually my favorite now. You're absolutely correct if we were to take this one right into breast cancer we might not have quite the success in enrolling. And yet the thoracic oncologists are so excited to get going with this one. I think as we move into the phase one it's really looking for those settings of high unmet need, where we might actually see some nice activity. That's exactly what we've done with AVA6000 FAP Dox. We didn't see breast cancer enrollment until we're now showing activity and showing the safety data the breast oncologists were really waiting to see where we able to eliminate the cardiac toxicity and now they've jumped in with both feet. So you know I think getting started in the clinic high unmet need FAP positive and Topo one activity.

Lrink

We talked to investigators and KOL's, I seem to get the sense that there is sort of a growing appreciation for targeting the Stroma and tumor microenvironment you know given really a lot of concentration on standard cell service expression type targets. Are you seeing that scientific interests and from your perspective and how has that helped you perform your development strategy.

CC

I'll go back to a trial that was done with Inher2 looking at you know truly her2 low expression, and that really leverages then the bystander effect. That was a highly successful trial where they looked at you know really low expression, the drug being kicked out and having the effect. That trial really speaks to that this mechanism really has the potential to work. We're killing tumor cells with no expression of FAP and it's purely that bystander effect, and it's truly that differentiated approach of using the enzymatic activity as opposed to just targeting the Stroma. I think everybody would agree that it's challenging to just target the Stroma and so it's this bystander effect that we're concentrating the drug right there. The other thing that I glossed over a bit in the presentation is that the highest expression of FAP is actually right next to the tumor cells, and it leaks away. If you look at a pancreatic cancer for example, when you look at the Stroma that's further away from the tumor, - it's FAP negative. The FAP is only expressed right at the tumor cells, so it's almost exactly where we want it to be. Flood the tu

Lrink

And then obviously that plays a role in indication selection as well, so how do you think about with the data that you have, and I know maybe you can talk about some of the alerts you have been doing with Tempus.

What kind of expression profile does the tumor type need for you to feel that that is an attractive opportunity for the program, and are there any of these where you might think a diagnostic approach, versus just all commers would be better served.

CC

So you're right we do have a strategic collaboration with Tempus to look at this. If you believe the literature, 90% of solid tumors express some degree of FAP, and there's quite a bit of published ihc we've also done quite a bit of ihc. The tempus collaboration because there's a nice correlation between protein expression and RNA we were able to Leverage their database 160,000 solid tumors and we developed two cut points. That which would correlate with a zero expression, and two plus three plus expression, and we looked across those 160, 000 which is essentially every solid tumor and it turns out the literature is correct. About 90% of human tumors will express some degree of FAP. Now some of them are like gastric cancer, half of the patients are low you know let's call it 1 plus 2 plus, half of the patients are two plus three plus, and some of them are like breast cancer where it's just high across the board. So the first thing that we've used that data for are exactly as you mentioned, you know do we need a companion diagnostic cancer no. Gastric cancer we don't understand yet exactly what the floor is, even in the phase 1 trial with patients who had lower expression of FAP, we're still seeing that 100x concentration. Now taking it a step further with exetecan, what we've done now is do almost a two-dimensional look with the Tempus folks, and we take a gene schlafen11, (which predicts for sensitivity to topoisomerase one (topo one)), and asks the question: what indications would be more susceptible to topo one AND have FAP expression, and there's where a few interesting ideas just sort of dropped out. Small cell lung cancer you know there were a few of them that look like they would be quite susceptible to a FAP enabled topo one.

Leerink's Global Healthcare conference March 2025

https://wsw.com/webcast/leerink38/avctf/2396932

Transcription of Q/A session only

If any glaring errors please advise.

I could have happily have shot Leerinks questioner.

The full text of his questions really stank, much work required to make sense.

CC Lets have a conversation

Lrink

I think an important point to drill into is FAP.

What really was the Ah-ha moment insight that made you think that your platform could solve this problem that others have not been able to address before.

CC

If you think about the field of Oncolgy - we've kind of thrown the kitchen sink at FAP.

What's very different about the Avacta approach and the Precision platform is that instead of just targetting FAP, we're actually leveraging the protease activity.

So it's the mask, and treating the peptide as a mask, the peptide drug conjugate is inert in the bloodstream, it can't get into any normal tissues, and it's not until it encounters the enzymatic activity that it is cleaved. Now it's only a di-peptide, and so FAP is a post-Proleen cleaving enzime, but our invention is that it actually prefers Alanine than ProLine, and we have an engineered cap. So it's all three of those and so it's highly specific for FAP. It's not cleaved anywhere else. Importantly we don't see pneumonitis, we don't see liver toxicity, we don't see ocular toxicity, because this is a truly tumor specific release mechanism and that's what's different. We're not just binding to FAP, but it's actually going to release the payload right in the tumor.

It will be a big buying signal when they close out the short.

At 38 p there's hardly anything to stay in for.

I guess they are wanting to test their algorithm, but you'd think they would reduce if testing.

Great to hear CC say they are working in the background with Biologic drug conjugates (Affimers), AKA AVA7100.

Any and all developments on this project will enhance the company value should a T/O approach materialise.

Dr Julie Simmonds, video states she is a Research Analyst, Healthcare Panmure Liberum.

LinkedIn has her listed as PL's Managing Director. (!)

Thanks to thevid and gmcc 😊😊

ODD designation provides tax credits and other incentives for drug developers addressing rare diseases.

Most notably the Orphan Drug Designation would give Avacta, if AVA6000 was approved for treatment of SGC, seven years of market exclusivity in the US.

So that's not available at present, but I hope a new opportunity to apply will be available soon.

However, not if Trump / Musk prevail.

If SGC is to feature large in Avacta's future, why do we not have, as yet, an ODD for Salivary Gland Cancer?

ODD is not currently available according to this link. Receipt Dates: October 22, 2024 (for new applications)

https://www.fda.gov/industry/grant-programs-support-development-medical-products-rare-diseases/funding-opportunities-rare-disease-research

Silence appears to be golden in the Avacta camp I'm afraid.

If they have already started 'conspicuousness by absence', what must occur to stop them using it again.

I'd say successful STS Phase 1b triggers the deal.

Yes indeed.

Do not respond to their posts.

Yet more FUD results.

YOU KNOW it makes sense