Susan Desmond-Hellmann
speaker
362 appearances
1 recordings
1 series
first heard Apr 2025
last heard Apr 2025
Susan Desmond-Hellmann’s voice in public audio — every appearance, attributed to the second.
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Appearances
Herceptin and Rituxan were easy.
There is one tumor where VEGF plays a seminal role, and that is renal cell carcinoma. And yet renal cells are really tough to study. It's just, it's not set up clinical trials wise.
It should be easier. It may be the sites and where the clinicians are who care for it. It may just be that pragmatic. We kept struggling to figure out how to do a good renal cell study. But we thought we could do a breast cancer study because we had a lot of networks of breast cancer patients and particularly patients who weren't eligible for Herceptin because many of them weren't.
So we wanted to do a late stage breast cancer study because if we could help these patients, we would find out right away.
Metastatic breast cancer who had already tried- Progressed through everything. Everything. So really tough high bar.
We wanted to have at least 50% shrinkage. We wanted to change time progression.
So if you start with a target, often in oncology today, we'll start with a target. There's two things you have to start with. One is, what's the best way to turn down or turn off that target? Is it a small molecule? Is it an antibody?
So here's a really simple way I think of it helps me. Small molecule is chemistry. Small molecule, it can be, not always, a pill. A small molecule, you're impacting on often pathways or enzymes or things that happen in the cell. A large molecule, whether it's a protein or especially an antibody, an antibody's biology.
An antibody, you're trying to do something that may be immune in nature, or you use the antibody as a delivery device. You're getting something to the cell. A company like Genentech and many modern companies really like antibodies. I like antibodies because when something happens, it's on target. It doesn't tend to be off target.
Small molecules, that chemistry tends to have surprises in negative ways off target, like liver toxicity or kidney toxicity.
That's really a good example. And the choice of molecule is driven by that. When I was first in product development, there was this thing of, oh, you need a pill, especially for chronic indications. You need a pill for compliance.
Look at obesity drugs. Turns out, A lot of people would take an injection if they want to. But once you have your selection, you need to make sure you can make it. And one of the critical things for a biotech company, if it's a protein or an antibody, is the small scale. production of it in small, they call it a mini firm.
The mini firm has to resemble what is actually going to be used because the next thing you start doing is a bunch of models. Judah Folkman giving a great talk doesn't mean you believe that blocking VEGF will help cancer. So we do models in mice. We may do larger animals. We do fewer animal models than we used to because they're really limited.
I would rather have a great target with good biology than an animal model, but it's still helpful. It's still helpful. And then the critical thing is the preclinical work that you do What FDA is going to want to ask you, and they should, this is not them being bad, this is them being good. They're going to want to ask you about toxicology. What's your safety plan?
Based on biology of VEGF, what are you most worried about? I'm most worried about bleeding. It's an antibody. I'm most worried about an allergy to the antibody. Did any of the tox studies show allergy to the antibody? What are you going to look for and how are you going to look? How often are you going to measure the patient?
So the preclinical safety plan is really important and based on what you find in toxicology. The other thing that's essential is, and especially modern oncology, if you have a targeted therapy, you must have a diagnostic. And that is wicked hard because you've got the therapeutic and the diagnostic at the same time.
Now, things like CD20, things like VEGF are very ubiquitous, so it's not really targeted in the sense of HER2, where we needed a diagnostic. But if you need to have that, we had what we called a clinical trials assay for Herceptin that wasn't to be marketed.
So we had an in-house clinical trials assay that we used all the way through phase three.
It was fine. It was nothing wrong with it, except it wasn't approved. So not fine. So when we went to FDA, they said, we're not approving Hercept until you have an approved diagnostic.
So we went to DACO. We went to several diagnostic companies, and DACO said, we'll make you an immunohistochemistry test for HER2. And Hercept test is made by DACO. But we had to go back. and correlate that with the clinical trials to make sure that it was the same as the clinical trials assay.
Showing 181–200 of 362 · page 10 of 19
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