This
is the second article in my series of updates about the goings on in the world
of ADCs over the last two weeks. Thank you all for the likes and comments on
the first article. Here is what I have been watching this week.
1.
Seattle Genetics Wins
Clearly
the past two weeks were a good stretch for them. So, I've put together the
simple SeaGen 3 step plan for ADC success:
Step
1: File a press release where you say that your leading commercial ADC has
increased sales by 30%, you have filed a BLA for your second leading candidate,
and your third ADC candidate is looking good and expected to be just six months
until the release of pivotal Phase II data.
Step
2 : Tell the newly eager investors that you are going to do a round of public
financing and that they have the opportunity to give you $500M.
Step
3 : Close said round of funding 3 days later with an extra $575 million in your
pocket.
Bravo
guys, Bravo.
2.
CapEx approval for ADC manufacturing at CDMOs is on the rise
In
a very subtle move Lonza is announcing their plan to expand their commercial
conjugation facility upon approval of their third commercial ADC
(cough...cough...Polivy) with the first two being Kadcyla and my guess is they
are the secondary supplier for Adcetris. Now clearly this puts Lonza as the
unquestioned leader in ADC conjugation CDMO work, but that doesn't mean they
are the only people at the CapEx party.
ADC
Bio is just getting their $11M cGMP facility on-line to enable full production
of ADCs up to small scale commercial production. This goes along with the WuXi
news that we talked about in the last article and Aji Bio who got into the fray
at the end of 2018.
Now
the question becomes, how much capacity is needed in the ADC Conjugation space,
and does their become a point where commercial demand moves beyond the current
picture of Lonza having all ADCs not owned by Pfizer, and Pfizer making the
other two internally.
3.
Antibodies are important, but not the whole story
There
were a bunch of stories this week looking at how ADC structure beyond the
epitope binding region can affect efficacy. With each one adding a bit to the
complex ADC world that we find ourselves in.
If
you thought that linker chemistry didn't have an effect on therapeutic index,
guess again. By building and testing stereoisomers of linkers with an IGN
payload the team at ImmunoGen is showing that linkers are an active participant
in ADC therapeutic index.
Now
whenever we talk about biologics complexity, there is a legal obligation to
give the post-translational modification guys a shout out.
So
a team at Oxford developed a native mass spec method to test the structure and
function of glycosylation heterogeneity. The answer is always, "Its
complex", but a more accurate method is always valuable.
I
always find myself wondering what a dinner conversation would look like between
groups like this and companies like Sutro or Synaffix who both do away with
glycosylation (albeit by very different methods)
4.
Targeted Bacteria for Tumor Regression
This
is not about ADCs at all but I can't help but share this story because it is
just too cool.
Researchers
a Columbia have managed to take the "smart bomb" approach of ADCs and
apply it to living bacterial cells. The bacterial selectively bind to a
CD47 antigen within the tumor which then allows for the body to fight off the
"infection" which results in both bacterial cell death along with
tumor regression. I'm sure this is a long way from a real treatment, but
this is still amazing research
5.
A couple links that you shouldn't miss
Sometime
last year PBDs stopped being the cool kid at the party. And just like junior
high, that may or may not have been fair. But when the FDA feels the need to
write up a summary, it is most defintely worth a read.
TL:DR
alert. However, if you want a riveting and well-told tale about the
history and possible future of CAR-T, then check out this story
A
new book has been published covering all aspects of ADC Payloads. Plan on
having this sitting on your desk shelf as the definitive guide to ADC payloads
for the next 5-10 years.
Justin's
Thoughts:
Thanks
again for taking the time to read these things. It takes quite a while to mine
through all of the different websites, filter through the articles that are
actually interesting, and then put something together that summarizes the main
points. Hopefully it is useful for you all.
If
there is anything that you find interesting in particular or would like to see
more of, let me know in the comments and I can tailor these articles to cover
those areas.
In
the meantime, as I collect these articles, I put them on my blog:
If
you want to see all of the articles that were at least tangentially related to
the ADC world you can check them out here. It has been noted that the title is
more of a dream than a reflection on reality. A more accurate title might be
www.adcweekly-ish.com but I have a day job too.
And
speaking of the day job. I clearly love to geek out about ADCs all the time,
and if you want to chat about what your needs might be and whether or not
Novasep might be able to help please don't hesitate to reach out to me
directly. My email is Justin.Sweeley@novasep.com, or you can reach out through
LinkedIn
In
the meantime- check out our ADC offer at the following link:
Have
a great weekend everybody.
Justin.