Seattle Genetics

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.

ADC Bio
MabPlex
Lonza
 

Seattle Genetics Reports Second Quarter 2019 Financial Results

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.

Seattle Genetics Announces Pricing of Public Offering of Common Stock

Step 3 : Close said round of funding 3 days later with an extra $575 million in your pocket.

Seattle Genetics Announces Completion of Public Offering of Common Stock and Exercise in Full of Underwriters’ Option to Purchase Additional Shares

Bravo guys, Bravo.

  1. CapEx approval for ADC manufacturing at CDMOs is on the rise

Lonza Expands Bioconjugation Facility and Announces Approval of Third Commercial ADC

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.

CDMOs driving drug conjugate innovation, says ADC Bio

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.

  1. 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.

https://doi.org/10.1021/acsmedchemlett.9b00240

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.

Relating glycoprotein structural heterogeneity to function – insights from native mass spectrometry

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)

  1. 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.

Programmable bacteria induce durable tumor regression and systemic antitumor immunity

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

  1. A couple links that you shouldn’t miss

An FDA oncology analysis of toxicities associated with PBD-containing antibody-drug conjugates

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 definitely worth a read.

The Promise and Price of Cellular Therapies

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

Cytotoxic Payloads for Antibody–Drug Conjugates

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:

ADCDaily.com

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 [email protected], or you can reach out through LinkedIn

In the meantime- check out our ADC offer at the following link:

Antibody-drug conjugates manufacturing – bioconjugation, production of payload, linker and mAbs

Have a great weekend everybody.

Justin.


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