Hello all,
It’s been almost
three weeks since my last update which means that there is a massive amount of
material to cover and I can’t get to it all in this little update.
If you want to
check out all of the links that I have aggregated over the past three weeks, go
over to https://www.adcdaily.com/ and click on the ADC Links Section Header. In these posts I just aggregate all of the
relevant links that I find before winnowing down for these update
articles. But it you want to quickly see
anything and everything that I thought was related to ADCs, then this is the
place.
While you’re there, click on the list to join the mailing list, and
then you can get every post directly to your inbox. We had quite a few people join after the last
posting, so come join the cool kids and gets your ADCDaily posts automatically.
And one last thing. I am
excited to announce that I will be hosting a Webinar next month. It will be chock full of ADCs and DoEs. I will do my best not to get too excited, but
I most certainly love geeking out with DoEs and we have some pretty cool case
studies planned for you. It’s being held
on Sep 24th at 11 EST. Hope
to see you all there.
And with that, it’s
time for our five things this week…
1. Cue the Funeral Procession :
RovaT is officially Dead
I’m sad to say that
today we are seeing news that AbbVie is pulling the plug entirely on RovaT after
failing another drug trial.
I don’t think it’s
too much of a surprise to anyone at this point to see the program getting shut
down. But still, it’s always sad to see
them go.
Can anyone else
hear Taps playing on a bugle in the background?
Farewell friend. Thank you to
everyone at AbbVie who has been working on this for the past many years. Even clinical failures help to progress the ADC industry and
RovaT is no exception.
2. Silicon Valley is looking at
Biotech
*Full disclosure, I grew up in the middle of Silicon Valley, so I
am afflicted with equal parts awe and disdain for The Valley fixing all the world’s
problems*
This is an interesting take on the potential future of
biotech. The argument is that through CROs, lab robots, and in silico testing, the development cycle
of biotech can be shortened, cheapened, and (…wait for it…) Disruptive. Although
this ignores the fact that there is the inherit difference between YC software
types who make apps and algorithms; while we make complex chemicals for use in
even more complex systems and that will always be true. You don't see YC
startups trying to upend Exxon or Anheiser-Busch because it took them 100 years
to build the distribution network that they currently have, and the YC model expects
nothing less than 10x growth in 3-5 years.
Despite my cynicism, innovation is good, and if their sights get set on
biotech, then all the better.
But still, after reading this, I found a couple of examples that
are too spot on to ignore. The first is
a partnership involving ADC T
Global Newswire
- SOPHiA GENETICS is trying to bring some deep learning into ADC
clinical trials. This looks like a fishing expedition for now, but if
this bears fruit and they can use this to improve patients outcomes, then this
could be a really interesting collaboration
And while the YC model for biotechs is very 2019, there are still
people who see massive movements in the more traditional 1999 style Silicon
Valley capitol plan
Endpoints News
- As I always say, the best leading indicator for our market is
$$$. So signs like this are a good thing. Investment is up, and so
is M&A. All of these things make it more profitable to be a biotech
startup, and since that is where a big portion of ADC companies live, this is a
good thing
3. ADC Manuscripts are on fire
There are too many
great articles to cover here, but as mentioned above, go check out my links
post at https://www.adcdaily.com/ and they are all
there. Here are a couple of my
favorites:
Mol Pharmaceutics
- The trend in ADCs for the past couple of years is to move away
from stochastic conjugation and towards site-specific. The argument goes
that greater homogeneity will result in greater effectivity. However,
this paper serves as a case in point to the contrary. And as might be
expected. The final result is: its complicated. Take a look if you
are willing to buck dogma and go against the ADC orthodoxy for a bit
Cancer Chemotherapy and Pharmacology
- Here is a fantastic review of Prodrugs in oncology. The
timing is perfect as in the last article I proposed this topic as something
that I could cover in more detail but this article is better and more complete
than anything I would be able to do. So
for those of you who voted for this one, take a look
Cancers
- Here is a pretty cool example of a novel payload mechanism on an
ADC. Here the authors were looking at a transcription factor inhibitor
(TFIIH) bound to an antibody. They showed some success in their model but
while this is still a long way off, it is interesting to see research moving
away from HPAPI as this might be a way to open up that therapeutic window
4. The Late Stage crew continues forward
It is always big
news when a new ADC gets to market, so of course we need to pay attention to
the molecules that are next in line to attempt to make the jump. First on the list is GSK and the anti-BCMA
molecule belantamab mafodotin.
Endpoints News
- The pressure is on for GSK to have some success with their
belantamab mafodotin ADC currently in Phase III trials. So far, all signs
are positive, but win or lose, this is a major event for GSK. There is a
lot of competition for BCMA targets, but as the CEO of SeaGen states, "Its
in a vial." Which at the end of the day is worth way more than any
mouse models could be.
Did I mention
SeaGen? Of course, because they are
everywhere, including in a combination study showing that Adcetris in
combination with Nivolumab yields an ORR of 73% and a full remission rate of
37%
5. T-DM1 in the Brain?
Critical Reviews in Oncology/Hematology
So I can’t say that I have ever thought of the problem addressed in
this article. As we all know, ADCs are
smart missiles which can find cancer anywhere in the body and kill it. But what about the part of the body where
even blood cannot go? It turns out that
there are two more facts to the story – HER2 overexpression is what makes
Kadcyla effective, but it also comes with an increased chance of brain
metastases. And Kadcyla cannot cross the
blood-brain barrier to get at those tumors.
This article takes a deep dive into this issue and tries to offer some
explanations about what is going on and what might be done to solve the
problem.
Speaking of T-DM1, let’s not forget about its upcoming competitor for
Daiichi.
OncLive
- Dr. Bhave talks about the steady progression of Daichii's
progress through the clinic as well as the competition with T-DM1
Justin's Thoughts:
First off, I would
like to thank everyone for your comments and suggestions after the last
article. In combination with ADC Review
and their poll results, it looks like we have a clear winner. You guys want to see a deep dive into non-oncology
applications for ADCs. So let’s do
this.
And on that note, I
can do all of the digging around the literature in the world, but if you work
on one of these projects, I want to talk to you. It would be much more fun to get an insider’s
look, than to regurgitate other articles and marketing material that is
distributed around the internet.
Secondly, there has
been a major occurrence in the world of ADCDaily. A couple of articles ago, I mentioned a new
book about ADC Payloads
Well it turns out they
noticed, and sent me a copy of the book to check out in detail. So, for the first time ever, I will be
publishing an ADCDaily book report in the near future as well. It takes a special type of person to get
excited about 200 pages of Cytotoxic Payload articles, but I am just that type
of person.
So now that is two
new articles coming in the near future.
And yes, expect the news updates to continue. And please keep, liking, or especially
commenting or resharing as those are the most effective ways to tell LinkedIn
to keep spreading the ADC word.
Have a great week
everyone!
-Justin
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