Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Quite a few questions have hit my inbox recently from people wanting to know more about Antibody Drug Conjugates (ADCs) and how they work.

They basically consist of three things:

  1. Monoclonal antibody
  2. Linker
  3. Cytotoxic agent

Antibody Drug Conjugate (ADC)

Source: Roche

The goal is to create a new molecule that essentially is greater than the sum of its parts by making it more targeted, like a guided missile against the cancer cells.

With normal monoclonal antibodies, they bind to atarget antigen that is a tumor-specific antigen on the surface of a tumour cell. With an ADC, the monoclonal antibody part of the molecule still latches onto the target antigen in the same way, but in this case it now has a powerful cytotoxic attached to potentiate the effect.

As Emeril would say, “Bam!”

You can see a video of how the ADC technology works HERE.

Unfortunately, the site only allows you to watch it there or download the video; it’s not easily sharable with others, short of emailing it.  Sadly, I couldn’t embed it here on the blog post for easy consumption either.

A nicer way would have been to put the educational videos on a company YouTube channel and allow it to be shared through social media via Facebook, Twitter etc. Imagine clicking on a link in Twitter and being taken to YouTube on your iPad, iPhone or Android smartphone?  Or watching an embedded video on someone’s blog post?

That’s a much more fun and immediate way to communicate ideas and technology from a medical or scientific learning perspective than a old fashioned static website.

It is good to see Pharma and Biotech companies active on social media, but they have a long way to go yet in terms of how they can help improve learning about the science behind new cancer research and development in an integrated way that helps the end users, ie the scientists, healthcare professionals, patients in clinical trials and analysts who might be interested.

We really do need to get away from the old web 1.0 world into the 21st century of sharing ideas, tools and medical or scientific information using social media in the web 2.0 era.

That said, there are some advanced ADC’s in clinical development at the moment.  The three leading compounds I’ve come across so far are:

  • Brentuximab vedotin (Seattle Genetics) in Hodgkin Lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL) targets CD30 and now has a brand name, Adcetris.
  • T-DM1 (Roche/Genentech) in HER2+ breast cancer
  • SGN-75 (Seattle Genetics) in RCC and NHL

Overall though, Roche/Genentech probably have the largest active research in this area, with a large portfolio of agents in development across a multitude of different tumour types.  You can check out this full ADC pipeline here.

Seattle Genetics have a couple of abstracts on their ADCs at ASCO this year and Roche have an abstract on the phase III EMILIA trial comparing T-DM1 with lapatinib plus capecitabine in metastatic breast cancer, all on Monday 6th that I hope to check out, that is if the sessions don’t clash!

14 Responses to “Antibody Drug Conjugates (ADCs) in cancer research: what are they?”

  1. James Eslea-macdonald

    Pfizer have an additoinal compound CMC-544 in Phase III.  You could also check out Agensys and Celldex who have compounds in Phase II further on than SGN-75 

    • maverickny

      Ah yes, inotuzumab, how could I forget that?  Well, I wasn’t very impressed with the early data, it didn’t really stand out as particularly impressive.  

      Agensys was acquired by Astellas back in 2007 and the compounds are still in phase I it seems (see  Until we see some decent data, I’m going to hold onto my hat with their ADCs.  

      Celldex do have one in development, CDX-014, but it’s being tested in RCC and that is now one very crowded market with 6 or 7 drugs already approved and more on the way for a relatively small indication in a very tough market.  I think it would be fair to say I’m a lot less enthusiastic than many investors for that reason.  There are not trials mentioned in the clinical trials database, so not sure if they are ahead.

  2. Anonymous

    Hi Sallie,
    Your forgot to mention that the ADC technology (linker and cytotoxic agent) in T-DM1 is from ImmunoGen, Inc. You may also want to check out SAR3419, Sanofi/ImmunoGen ADC for NHL at ASCO.

    • sally

      Good point, thanks.

      Oddly, I was reading about the sanofi agent yesterday afternoon – given the recent success with brentuximab in HL, it will be interesting to see how SAR3419 does in NHL.

  3. James Eslea-macdonald

    I’ve seen some recent presentations on CDX-011 which is another MMAE based conjugate but this time targeting GPNMB in melanoma and breast cancer.  You can see the Phase II trial details here

  4. mickey999

    Not easily shareable, huh? You mean like blogs that block the highlighting/copying of text? Annoys me that I can’t easily pick up drug names and do further searches on them.

    • maverickny

      I hear you Mickey, but it also annoys me when people plagiarise my content as their own with no credit or attribution.

        • maverickny

          In the original post credit was given to Roche/Genentech for the graphics but when we changed blog hosts, many of the graphic attributions/source unfortunately got lost in the file transfer.  I’ve been working through them and adding that information back, but haven’t got to that one yet.  

          The reference to the Gene/Roche pipeline was included in the post above and is still there though.  Thanks for letting me know that one was missed.

          • David Linsemayer

            Just keeping you on your toes…  Thanks for the information, anyway.  Very interesting.

          • maverickny

            No worries, I appreciate you pointing out one I had missed!

            There will likely be some new ADC information at SABCS from Roche, Celldex and others, so hope to do a clinical update soon.

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