Sorry BV, but I disagree, it doesn't sound ambiguous to me. "Therefore, in parallel with the completion of cohort 7, the Company intends to begin a short study to explore more frequent dosing (fortnightly) of AVA6000 AS A FIRST LINE TREATMENT in patients with soft tissue sarcoma." The emphasis is mine. The "AS A" is clearly referring to the 'more frequent dosing'. You can't explore a first line treatment, without testing it as a first line treatment.
The only ambiguous statement is "in parallel with the completion of cohort 7". Does this mean only have cohort 7 finishes, or is it during this cohort? I thought it was the former, but in the interview, AS appears to imply it is the later.
@yeboha - it depends. There are different kind of deals. If the offer is in 'cash', then yes. Sometimes the offer is say (in your example) £2B upfront and a further £2B in milestone payments. So you would get half the cash up front and half over time when the milestones are met. Finally, there are deals that give you a proportionate amount of stock in the company buying the smaller company (Avacta in this case), or a mix of cash and stock. However, for smaller deals (say sub-£20B) a buyout is typically fully in cash.
I don't think so Energy. AS stated that the posters would be available on the conference website after the conference.
Both presentations are just posters, so Fiona won't be presenting anything. Both posters will be available on the conference website after the conference.
@SNewby - quite simple. 100x times the current market cap of Avacta is ~$51 billion. If the Precision platform performs as well as we think it will (i.e., based on the evidence to date), then a market cap of $50B is easily within reach.
Pfizer's current mcap is $188B, and if it is 24x more today than it was in 1984, then it had an mcap of $7.8B at the time...i.e., already a massive company (especially at the time).
So the difference would be that by getting into Avacta today would be at a much earlier stage than Pfizer in 1984.
Good points BV. It should also be noted that for standard dox, the normal schedule is every 3 weeks, but a large fraction of the patients undergoing treatment have this schedule modified, either through dosing holidays are changing to less frequent dosing. So I agree, that it is perfectly reasonable to think that if ava6k is dosed every 2 weeks, for a subset a patients that are having trouble tolerating the drug, they will be moved to a 3-weekly dosing schedule. i.e., every 2 weeks is the maximum, but patients with weaker systems may have longer rests between treatments.
@Bella - they definitely won't increase the dosage every two weeks. The idea is to make sure that a bi-weekly dosing schedule is safe. So, like the previous cohorts, each cohort will receive the a given dosage and will remain at that dosage. The question is how many cycles do they go through (minimum 2) before they can start on the next cohort at a higher dosing level. The reason that dox is limited to 3 week cycles is that it takes the human body about that long to recover from the previous cycle. Specifically, what I learned at the AGM, is that it is the white blood cell count that often takes a nosedive after each cycle of dox (specific types of white blood cells in particular). This is one big reason why patients undergoing chemotherapy are prone to infection and sickness, often needing to be hospitalised.
Each cohort will be faster than we've seen so far (C1-C7), simply due to the dosing regimen. But the clinicians running the trial (and Avacta) will already have seen the blood work from the patients dosed so far, so they will know the average drop in white blood cells (amongst other indicators) and the 'recovery time'. This is clearly less than two weeks, but of course, there could be cumulative effects, which I believe is what they are testing for in this bi-weekly study.
FWIW, my opinion is that if the C7 patients are still not showing evidence of being near MTD, then the bi-weekly study will start at the C5 level...possibly C6 if the clinicians are very confident.
Excellent find Muck, shows just how important ODD is. Proves (to me anyway) that Avacta have a clear strategy regarding the Precision pipeline, i.e., ava6k first followed by ava3996 and others.
And if I asked the same question but about being a first line treatment in Phase 2 trials, this is what I get:
Phase 2 clinical trials in oncology typically do not serve as first-line treatments for cancer patients. Instead, phase 2 trials usually focus on evaluating the effectiveness and safety of experimental therapies as second-line or later treatments. In general, phase 2 trials in oncology are typically conducted after phase 1 and focus on patients who have already received first-line treatments and need alternative options due to disease progression or treatment resistance.
@PL - absolutely ticked that box. This has blockbuster written all over it.
@BV - From the RNS of the completion of C6: "Therefore, in parallel with the completion of cohort 7, the Company intends to begin a short study to explore more frequent dosing (fortnightly) of AVA6000 as a first line treatment in patients with soft tissue sarcoma. "
Despite coming late to the party in realising that the biweekly (versus standard 3-weekly) dosing will be a first line treatment (i.e., given to patients as a first therapy), I am still amazed by this. Here's what I got when I asked ChatGPT it is "common for an oncology trial to be a first line treatment in phase 1?":
No, it is not common for an oncology trial to use a new treatment as a first-line therapy in a Phase 1 clinical trial. Phase 1 trials are typically the first step in testing a new drug or treatment in humans, and their primary purpose is to evaluate the safety, dosage, and potential side effects of the experimental treatment. These trials are often conducted in patients with advanced cancer who have exhausted standard treatment options or have no other viable treatment alternatives.
First-line treatment in oncology trials usually occurs in later phases, such as Phase 2 or Phase 3 trials, after the experimental treatment has shown promising safety and efficacy results in earlier phases. However, there can be exceptions in certain situations, such as when a new experimental therapy is expected to provide a substantial benefit over existing treatments, and there are compelling reasons to use it as a first-line option in a Phase 1 trial.
Thanks PL! great spot gmcc…dont know how I missed this thread…
Haha, looks like i'm last to the party (don't know how i missed this)...but wow, what a result!
Thanks to Icecool for point this out, I had overlooked this. The "6th cohort completion RNS" states that the upcoming shorter dosing frequency (fortnightly) study is to use "AVA6000 as a first line treatment in patients with soft tissue sarcoma".
This is a massive change! We are no longer dealing with the terminally ill, or those that have undergone multiple previous treatments with limited success, we are now talking about (relatively) healthy patients, where ava6k is *expected* to show efficacy. In fact, we will have patients who would normally be given straight dox, but will now be given ava6k.
The FDA would not approve such a step without serious evidence of expected efficacy. While straight dox isn't overly effective in STS, it is the standard of care, and statistically extends life. So you don't pass on this without good reason.
So even this extended P1a (or short P1b?) trial (or whatever you want to call it) is effectively a P2 trial. They are looking for efficacy and offering this as a first line treatment for patients.
For reference, all the Phase 2 Keytruda studies that I've found (although perhaps not an exhaustive search) were done on patients that have undergone previous therapies that were unsuccessful. ava6k is skipping that, jumping the queue into first line patients. amazing!
@MCB55 - a drug can be approved by the FDA at anytime, including during a Phase 1 study. It is just very rare. When accelerated approval is given, that means that there is evidence that the drug is filling an unmet medical need. In order to turn accelerated approval into 'full approval', a company still needs to complete enough clinical studies to file for approval in the normal way. This normally means carrying out a full Phase 2 and 3 studies.
However, phase 3 trials are often not needed in the case of pro-drugs, so if ava6k works as well as it did in the mice trials in humans (and there are strong indications that it is), full approval will be sought after Phase 2.
If the data are looking very good at the beginning of Phase 2 (of which Avacta should have a very good view on already during the bi-weekly dosing study) they can apply for accelerated approval then. Or if the data are so overwhelming, the clinicians can actually stop the Phase 2 trial and recommend the FDA to approve the drug before Phase 2 completes. Again, these are rare cases...but if Avacta are truly sitting on a paradigm shift in chemotherapy (AS's words) then this is definitely within the realm of possibility.
@Moneysponge: From google: "A Pivotal study that is a trial designed & executed to get statistically significant evidence of efficacy and safety as required for approval."
So yes, this means that a Phase 3 will not be required (unless the data from Phase 2 don't support the application...i.e.., if the results are marginal).
Morning Timmy - While I'm sure Lilly looked through all the current and future assets of Point in extreme detail, of which Canseek will feature prominently, Point of a number of promising treatments in development. Marty, on twitter, pointed out yesterday PNT6555, with is FAPa binding (not releasing) and the pre-clinical data look pretty amazing.
Morning CJ. I think a takeover is a possibility anytime, and as we have seen, it can come out of the blue. That said, my feeling is that, given the optionality of the Precision platform (i.e., attaching any number of generic or proprietary warheads), a series of license deals (potentially with multiple companies) would be the preferred option for Avacta and big pharma companies.
But this is just my guess, I do not have any first hand knowledge. I guess that it depends, at least to some degree, what Avacta will charge for access to Precision.
Hi wcotter - Yes, Precision and ADCs are both delivery mechanisms, attempting to bring chemical warheads directly to the tumours, thereby sparing healthy tissue. Think of ADCs being the current state-of-the-art with Precision aiming to replace them.
I posted the below a couple weeks ago:
Antibody-drug conjugates (ADCs) are all the rage in oncology today. There was a good article in the economist today about them (https://www.economist.com/business/2023/09/21/big-pharma-cant-get-enough-of-one-class-of-cancer-drugs). Effectively, ADCs are very similar to Precision. They take a chemo warhead, attach it to a monoclonal antibody which subsequently binds to a particular receptor on a cancer cell (https://www.astrazeneca.com/our-therapy-areas/oncology/antibody-drug-conjugates.html).
The market in 2022 for ADCs was worth ~$7.5B, which is expected to grow to ~£30B by 2028. The problems with ADCs is that they are very complex to make and their selectivity isn't great, i.e., there is still a lot of off-target (healthy tissue) damage.
The beauty of Precision is it is 1) highly specific, 2) easy to make, 3) cheap and stable.
Hence the future of oncology is clearly targeted therapies, bringing treatment directly to the tumour. But I'd wager that ADCs will soon be outclassed.
@Richob - no, the vast majority of Point Bio's pipeline is not related to Canseek/Precision. It is based on their own technology, with different programmes in different stages of clinical development.
Yes, they have licensed the Precision chemistry from Avacta/Bach, which they call "Canseek", but all this is still in the research stage (i.e., before pre-clinical). However, Point are/were very keen on the possibilities of Canseek and have mentioned them as potentially greatly expanding their pipeline in the future.