RE:RE:RE:RE:RE:RE:RE:RE:RE:Wow AstraZeneca boosts oncology credentials with breast cancer trial success
Close enough Wino!
"HER2 low is a large and previously unaddressed patient pool in breast cancer," analysts at Credit Suisse said in a note, adding they saw a 50% probability of $3 billion peak sales potential from the new patient group.
Wino115 wrote:
It's really all about your target now for oncology drugs, isn't it? The market share gains for Enhurtu have been rapid though. The estimates I've seen have a fantastic 5 year growth rate up to the $1.5 to $2 bil range. Amazing cash flow generator for them. Maybe that's optimistic if there are knockoffs coming, but it will still be a huge number just for that one type of TNBC. Then you have the other tumors.
qwerty22 wrote:
This one explains better how they've stretched the definition of treatable HER2+.
[url=https://www.businesswire.com/news/home/20220220005055/en/ENHERTU®-Significantly-Improved-Both-Progression-Free-and-Overall-Survival-in-DESTINY-Breast04-Trial-in-Patients-with-HER2-Low-Metastatic-Breast-Cancer][/url]
qwerty22 wrote:
News today showing the range of Enhurtu wrt HER2 expression levels. Pretty amazing given the drug is based on an antibody that's been in the clinic for decades. Another example why you shouldn't assume you know the relationship, you need to work it out by taking allcomers.
https://www.marketwatch.com/story/astrazeneca-reports-historic-trial-results-for-enhertu-cancer-treatment-271645428173
They seem pretty pleased with themselves.
Again they have the advantage of HER2 already being screened for, disadvantage is there's literally dozens of trastuzumab based drugs in development.
Wino115 wrote: Thanks, this makes sense now and is consistent with what you guys have been saying for a while about different possibilities to unlock sort1 expression in the future. Perhaps the fact that they are basing all this off of the various academic studies we've see published that have data around the expression level being positively correlated with the advancement level of the cancer is one factor they're just counting on by going for the refractory, unmet need patients. As Marsolais mentioned, he thought there was a 75% chance various "all-comers" would "overexpress", whatever that actually means (I guess in the "high stain" category seen in the academic studies).
Then we have the various papers with the high/medium/low studies around TNBC, ovarian and pancreatic cancers. As you say, that's probably good enough to go on for these indications and you refine that as you move forward over time. Will be very interesting to hear what they've learned in actual different patient types, but likely more robust data would have to wait until the end of phase 1b.
qwerty22 wrote: Tests exist where they enhance treatment choice. There is no enhancement associated with testing for Sortilin so no test exists. The test needs to be developed alongside the drugs development. Sometimes they are called companion diagnostics. Eventually it's all going to depend on what the drugs profile looks like. They should be developing a companion diagnostic as their drug program progress. If the data ultimately says they don't need to test for Sortilin then the test won't follow the drug into the clinical. If treatment requires knowing Sortilin levels the the test develops and gets validated as the drug get's tested and both go into the clinic. My expectation is fully understanding the relationship between Sortilin levels and drug efficacy is something that continues throughout the program. If the drug eventually gets provisional approval then it's possible it continues after that point. It's my understanding that Gilead are still working out the exact relationship between their drug and it's target's expression.
In my view we just need to know they are working on the necessary test for now, we'll see how the relationship between Sortilin expression and efficacy develops as data is gathered and we'll see just what role a companion diagnostic test will play with this technology. It should be an organic process that happens as the program develops.
The point with this KOL is that p53 is already screened for in some cancers so this new drug can just piggyback on the back of that pre-existing setup. Since THTX are breaking new ground with Sortilin then they'll have to do the work to get testing up and running (if necessary).
Wino115 wrote: Since I may have been wrong, here's what the KOL said. She may have been talking about two different tests - one genetic and one a "molecular signature". Sorry to have misquoted her.
Q:
The fact that we've got this kind of maintenance I think in ovarian, does that make it easy for physicians to kind of transition and create this essentially new paradigm for treatment or? A:
Yes, because in fact ever since we started looking at the genetics of these cancers and as you know many of these tumors are going to be associated with the Lynch 2 mutation, which places patients at risk of having other cancers including ovarian and colon cancer, it is, at least in the United States, pretty standard practice that the tumors are interrogated once you remove them in surgery or you get a biopsy to initiate treatment. We do molecular signature to look for PD1 mutations for example that would make patients eligible for drug like Keytruda or pembrolizumab. We look for different targets that are now approved by the FDA to treat these cancers.
So, both centers in the US will also offer you P53 analysis. The fact that the subset of patients in this study here that seems to be the best aid by these drugs are the ones that have wild type P53 tumors opens the doors to most of our patients.
jfm1330 wrote: These genetic test look for mutations related to cancer, they cannot tell you the expression level of a normal protein like sortilin. What they can do, in some cases, is to avoid a given chemotherapy drug, or chose one that will work. Here in Quebec it is available for free for pediatric cancers. Maybe some adults can also have it for free. But you can pay to have it from a private company, but you also need a biopsy. To me the best way to do a personalized treatment with TH19P01 based PDC would be to develop an imaging PDC for PET scans which would be TH19P01-DOTA-Ga68. I know I said it many times here, but it seems so obvious. It does not only allow to see if sortilin is overxpressed.It allows to see the PDC binding with the tumors and also distribution in other organs. If they achieve proof of concept, they need to develop that. It would be easy and quick. They have all the building blocks, and Gallium 68 has a track record of use in humans. So its toxicity is well known, and with the newest PET scanners, the needed injected dose to get good images is much lower than before.
Wino115 wrote:
By the way, in the KOL transcript for the Ovarian Endo talk I posted about, the doctor said that it's now pretty standard at Mass General that they run a tumor sample genetic test and know all the various genetic expression levels prior to talking about any treatment options. She made it sound like that was more or less standard now at any cancer oriented hospital setting. I may be wrong, but wouldn't that be where you'd find Sort1 levels too, as opposed to staining?