What's New in ADCs this Decade! Jan 27th, 2020

What's New in ADCs - Jan 27th, 2020

Happy New Year Everyone,

I think we can all agree that clearly we need to start off with a big round of applause for AstraZeneca, Daiichi Sankyo, and Seattle Genetics.  With a shoutout to the FDA for clearing their desk off at the end of the year for us all.

Clearly a rising tide lifts all boats, and so there is no other way to see this than an unmitigated win for the entire industry.  And now I am very optimistic that 2020 is a going to be a great year for ADCs.

On to the update.  But first:

If you want to receive these updates directly to your inbox, then all you need to do is click on the link below:
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The plan is for these articles to evolve a little bit for 2020, so stay tuned, and sign up so that you don’t miss out.

Also, these articles have been indirectly sponsored by Novasep all along, but as we begin 2020 it’s time to ensure the longevity of these articles. So, I am going to use this platform to nerd out a bit on you. I will pose a question that you need to be asking your CDMO, and hopefully at the same time shed some light on how Novasep approaches some of the problems that we all face during ADC manufacturing.

 Choosing A CDMO : ADC Regulatory Strategy As we all know, most of the ADC manufacturing work is done through CDMOs.  This came about through a combination of the particular safety requirements of ADCs in conjunction with the fact that most companies don’t have enough ADC manufacturing needs to justify a stand-alone highly potent cGMP facility.  That all is well and good, but what happens when you take your preclinical asset and hand it over to someone else?  One area that always screams high risk to me is analytical method transfer into the GMP space.So the question that I would ask is, what does the tech transfer process between analytical development and Quality Control look like?  Who defines and writes the protocol, and who tests that protocol prior to validation?  And most importantly, what is going to happen in the event of a deviation upon that first GMP campaign?At Novasep, we start all of our analytical development scientists with QA certifications so that they know exactly what is going to be needed at the GMP level even when we are working in development.  From there, we have a fully comprehensive plan to ensure a smooth tech transfer all the way from day one to material release.  I don’t want to give away all of our secrets to LinkedIn, but if you are interested in learning more about our approach, call my cell at (724) 506 – 2469, and I would love to get into the nitty gritty with you.

1. A Happy Little bit of Shameless Self-Promotion

And while we're already doing some Novasep branding, take a look at this breakdown of the ADC naming scheme. If this looks like something that would look good on your desk. Comment below and let me know. We are having some printed out now, and once they are ready I can get them to anyone interested.


ADC Naming Scheme Deconstructed by Novasep

2. Pop the Champagne, it’s party time!

Obviously, I need to put these on here.  It’s impossible to imagine that this comes as new information. 

Why wait? The FDA stamps an ultra-fast OK on a HER2+ drug expected to create AstraZeneca's next blockbuster franchise

Endpoints News

- Of course we have to mention the major news of the month in the world of ADCs.  The $7B acquisition of DS-8201 my AZ doesn't seem so crazy anymore.  Is it just me, or does this feel like when the house next to you sells for way more than you expected.  I get almost giddy, because I know that sets a new bar for the value of my own house.  ADCs have just had their Zestimate go up.

As well as:

FDA Grants Accelerated Approval to Astellas’ and Seattle Genetics’ PADCEV™ (enfortumab vedotin-ejfv) for People with Locally Advanced or Metastatic Urothelial Cancer, the Most Common Type of Bladder Cancer

SeattleGenetics

- And not to be outdone, SeaGen has secured a nod from the FDA for their enfortumab vedotin molecule (now known as Padcev).  They now have two commercial ADCs on the market and one non-ADC oncology treatment on the books as well.  Is it a coincidence that they continue to be an industry leader and that their stock went up 109% in 2019?  No.  Very clearly No.

Now if there is one thing that is clearly a good sign for our industry it’s this:

Drug Developers Take Fresh Aim at 'Guided-Missile' Cancer Drugs

The New York Times

- Success begets success, and nothing says the ADC industry is on a nice run like a long form article in the New York Times.  Obviously the content will likely not be terribly new to the audience of this blog.  But I for one do a little happy dance every time our niche breaks out into the national spotlight.

3. Self Assembled ADCs

Shout out to Ed Ha for finding this little gem. 

Computationally designed antibody–drug conjugates self-assembled via affinity ligands

Nature Biomedical Engineering

- What’s cooler than an ADC?  A self-assembling ADC that uses computational biology to build a mAb-payload combination that allows for the AD(c) to come together in as little as 8 minutes.  Yes, I am thinking about all of the logistical issues that would inevitably come up too.  But it is also undeniably cool.  Can’t wait to see what else they come up with.

4. ADCs in the clinic – We are growing up

The Evolving Role of Brentuximab Vedotin in Classical Hodgkin Lymphoma

Oncology Nurse Advisor

- This article discusses the evolution of Kadcyla through the years.  It is a pretty interesting look at seeing the life of an ADC post approval.  As will likely be the case with these new approvals, it is not a fixed quantity but a series of progressive steps and expansion which can last for years and years.

And to be honest, this set of data makes me particularly happy:

Loncastuximab tesirine appears effective for relapsed or refractory DLBCL

Immuno-Oncology Resource Center

- ADC T continues to take the lead on PBDs in the clinic.  They were pretty much written off as too potent less than a year ago, but ADC T has continued forward and here is a perfect example of why.  Their ADCT-402 Phase II trial exceeded their primary endpoint and is looking good.  I have never believed in all of the PBD pessimism, but it's easier to talk than to be like ADC T and back that belief with research and clinical dollars.

4. And my two favorite topics for 2020 will be…

First, was a trend that we saw at World ADC.  There seemed to be a heightened interest in linkers, and I expect them to get their due this year:

Bioorthogonal Tetrazine Carbamate Cleavage by Highly Reactive Trans-Cyclooctene

ChemRxiv

- Paying attention to the linker has certainly been in vogue as of late, and the team at Tagworks is leading the pack.  Their paper describes a new method of cleavable linkers which can cleave faster and more efficiently than the current tranche of products available today.

Severing Ties: Quantifying the Payload Release from Antibody Drug Conjugates

Cell Chemical Biology

- And as if on cue from the last article, here is a nice review about cleavable payload release mechanisms using novel fluorescence based linkers in order to monitor release rate.

And my second favorite topic for 2020, Tumor Microenvironment:

Cancer Drug Delivery Systems Based on the Tumor Microenvironment

Springer Nature

- I think a major trend that I will be watching this year is the evolution of this focus on tumor microenvironment.  There are a number of companies out there already looking into this, but here is a nice review with multiple chapters discussing labile linkers and the current technology in the market.

5. One last point that I don't want to leave out

FDA grants orphan drug designation to OBI-999 for pancreatic cancer

Healio

- As anyone who incessantly follows the ADC world knows - or anyone listening to Beacon Intelligence - the ADC market get the most press in the US and EU, but things are moving very fast in Asia as well.  OBI Pharma has just received orphan drug designation for pancreatic cancer.  Current trials are ongoing.

Justin's Thoughts:

Things are rolling for the ADC world right now.  Three approvals last year, and the potential to match that again this year. 

I am particularly excited to watch ADC Therapeutics this year as I think they are really in store for some good things.  Also, I will be paying close attention to Synaffix as well.  It clearly looks like their tech is being well received, so it is only a matter of time before the clinical results start coming down the pike. 

Outside of that, welcome back to the working world everyone.  Let’s go do some science!  Or to be more accurate, You go do some science, and I will keep writing about it.  Best of luck to everyone in 2020.

Have a great week everyone!

-Justin

ADC Links - Jan 16th, 2019

Regulatory -

Why wait? The FDA stamps an ultra-fast OK on a HER2+ drug expected to create AstraZeneca's next blockbuster franchise
Endpoints News
- Of course we have to mention the major news of the month in the world of ADCs.  The $7B acquisition of DS-8201 my AZ doesn't seem so crazy anymore.  Is it just me, or does this feel like when the house next to you sells for way more than you expected.  I get almost giddy, because I know that sets a new bar for the value of my own house.  ADCs have just had their Zestimate go up.

FDA Grants Accelerated Approval to Astellas’ and Seattle Genetics’ PADCEV™ (enfortumab vedotin-ejfv) for People with Locally Advanced or Metastatic Urothelial Cancer, the Most Common Type of Bladder Cancer
SeattleGenetics
- And not to be outdone, SeaGen has secured a nod from the FDA for their enfortumab vedotin molecule (now known as Padcev).  They now have two commercial ADCs on the market and one non-ADC oncology treatment on the books as well.  Is it a coincidence that they continue to be an industry leader and that their stock went up 109% in 2019?  No.  Very clearly No.

FDA grants orphan drug designation to OBI-999 for pancreatic cancer
Healio
- As anyone who incessantly follows the ADC world knows - or anyone listening to Beacon Intelligence - the ADC market get the most press in the US and EU, but things are moving very fast in Asia as well.  OBI Pharma has just received orphan drug designation for pancreatic cancer.  Current trials are ongoing.

FDA Accepts Immunomedics' BLA Refiling for Breast Cancer Drug
Zacks Equity Research
- Wow.  2020 is going to be a banner year.  Immunomedics has been down but never out.  Their NDA was rejected by the FDA because of manufacturing issues, not efficacy.  Hopefully that means they were able to fix the issues, and this leads to yet another ADC approval later this year.

Industry -

Drug Developers Take Fresh Aim at 'Guided-Missile' Cancer Drugs
The New York Times
- Success begets success, and nothing says the ADC industry is on a nice run like a long form article in the New York Times.  Obviously the content will likely not be terribly new to the audience of this blog.  But I for one do a little happy dance every time our niche breaks out into the national spotlight.

Boehringer Ingelheim Venture Fund and PPF lead the closing of a USD 22M Series C financing round for NBE-Therapeutics
NBE Therapeutics
- And here is the first example of what I expect will be many more articles like this.  Obviously this deal was likely worked out prior to the latest ADC approvals, but it seems inconceivable that funding doesn't start flowing towards ADCs quite a bit faster for the rest of the year.


Manuscripts -

A Convergent Total Synthesis of the Death Cap Toxin α‐Amanitin
Angewantde Chemie
- For all of you a-amanitin fans out there, here is a nice paper describing a fully synthetic route for its synthesis. 

Bioorthogonal Tetrazine Carbamate Cleavage by Highly Reactive Trans-Cyclooctene
ChemRxiv
- Paying attention to the linker has certainly been in vogue as of late, and the team at Tagworks is leading the pack.  Their paper describes a new method of cleavable linkers which can cleave faster and more efficiently than the current tranche of products available today.

Severing Ties: Quantifying the Payload Release from Antibody Drug Conjugates
Cell Chemical Biology
- And as if on cue from the last article, here is a nice review about cleavable payload release mechanisms using novel fluorescence based linkers in order to monitor release rate.

LARGE SCALE PRODUCTION PROCESS FOR CAPPED AND UN-CAPPED ANTIBODY CYSTEINES AND THEIR USE IN THERAPEUTIC PROTEIN CONJUGATION
US Patent Application
- This is a pretty cool approach from the team at Pfizer.  They are looking at producing site-specific cysteine conjugations without the need for a complete reduction and oxidation as is standard in the normal Thio-mAb process.

Cancer Drug Delivery Systems Based on the Tumor Microenvironment
Springer Nature
- I think a major trend that I will be watching this year is the evolution of this focus on tumor microenvironment.  There are a number of companies out there already looking into this, but here is a nice review with multiple chapters discussing labile linkers and the current technology in the market.

Critical considerations in the formulation development of parenteral biologic drugs
Drug Discovery Today
- A nice overview about formulation development for biologics and the inherit troubles of dealing with pesky things like tertiary structure and activity.


Clinical Results -

The Evolving Role of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Oncology Nurse Advisor
- This article discusses the evolution of Kadcyla through the years.  It is a pretty interesting look at seeing the life of an ADC post approval.  As will likely be the case with these new approvals, it is not a fixed quantity but a series of progressive steps and expansion which can last for years and years.

Loncastuximab tesirine appears effective for relapsed or refractory DLBCL
Immuno-Oncology Resource Center
- ADC T continues to take the lead on PBDs in the clinic.  They were pretty much written off as too potent less than a year ago, but ADC T has continued forward and here is a perfect example of why.  Their ADCT-402 Phase II trial exceeded their primary endpoint and is looking good.  I have never believed in all of the PBD pessimism, but it's easier to talk than to be like ADC T and back that belief with research and clinical dollars.

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study
The Lancet
- GSK continues to make progress on their BCMA ADC candidate.  This paper discusses the results from the DREAMM-2 study which is still ongoing.  But it is clearly yet another sign that this is a good candidate for approval in the very near future.

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Thats it for today. There are always more coming down the pike. Is there something I missed? Contact me. [email protected]
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What's New in ADCs : World ADC Wrap-up

Hello ADC World:

We have something a little different in store for today. Today is a feature on World ADC San Diego that I have been wanting to write for all of the scientists in lab who create the data behind the wonderful slides presented at World ADC but might not get to actually attend the conference itself.

This conference is clearly the best place for ADC folks to get together and discuss the latest and greatest in the world of ADC. The talks range from an always great clinical trial overview from the team at Beacon, to detailed analytical advancements, and of course, the CDMOs giving their updates on the latest advancements in the realm of custom manufacturing.

I was able to get approval from Letrishka Anthony at Beacon Intelligence to show this slide from her always awesome update on the landscape of ADCs in development. While her deck is not public, they always share it with all attendees of World ADC, so if anyone in your company has attended, then you can ask them to share it with you, and I would highly recommend that you do.

Source: Letrishka Anthony, Beacon Intelligence, www.beacon-intelligence.com

Since I end up doing a significant amount of opining on the world of ADC here in these articles, I thought that I would get some other opinions involved so that you can see the perspectives of people beyond just myself. So for this article, we have a panel of ADC experts who were willing to humor me and to participate in one of these articles along with me. Their responses are mostly unedited, and then my commentary follows below. So without further delay, you expert panel is:

GS: Ganapathy Sarma - Magenta Thx - Principal Scientist, and Process Development Guru

EH: Ed Ha - AngieX - Founding Principal Scientist, and Payload Guru

MS: Mike Sun - Crux CMC Consulting - Principal, and ADC CMC Expert

CL: Charley Lu - PanLabs Biologics - Managing Director, and World ADC First Timer

JL: Jens Lohrmann - Novartis - Disease Area Head Oncology, and Senior Big Pharma Voice 

JS: And me, Justin Sweeley - Novasep - Sr. Technology Manager, your CDMO representative

1) The dominant theme of World ADC 2019 was ....

GS : Too difficult to wrap everything up into one theme

EH : Improving Safety/Tox via linkers & via non-microtubule inhibitors like DS8201a, PBD prodrugs/hybrids, and side-shield linkers with PEG attachments

MS : Widespread success, some spectacular, across multiple indications can be achieved with the right combination of target and proven linker-payload technology (vedotin, DXd)

CL : Expanding the therapeutic window/index for ADCs

JL: ADCs are alive, we will see more approvals!

I agree with Mike on this one, as the broad theme for me was “Optimism”. The ADCs that are in late-stage trials and beyond are really showing promise and the excitement in the room was palpable.

2) What presentation stands out in your mind the most?

GS : Philip Howard’s and David Thurston’s talks stood out. Both these talks were focused on one thing: To understand the reasons for the failures and then designing newer and potentially safer molecules. Howard’s glucuronide-capped PBDs and Thurston’s sequence-specific DNA alkylators and cross-linkers have the potential to be safer molecules.

EH: Tie: Brian Mendlesohn - AjiCap & Bioatla’s Bill Boyle

MS: Peter Senter, SeaGen : Peter Senter’s (always entertaining) talk on recent lessons learned, what they tell us about the complexity of ADCs in vivo, and how they can shape future development

CL: John Lambert and Peter Senter played off each other quite well. Their dynamic was fun to watch from the audience given the history and recent progress with both Immunogen and Seattle Genetics.

JL: The patient story at the 10th anniversary celebration was very inspiring! (and of course my workshop... haha, just kidding)

It looks like the crowd has spoken, and clearly Peter Senter was a hit. His presentation was really good, as would be expected from a true founder of the ADC industry. For me, I agree with Ed on this one, as the concept of CABs is very intriguing as a way to get around off-site toxicity in ADCs. And yes Jens, seeing an actual beneficiary of our efforts was incredibly impactful.

3) Were there any unexpected trends that you noticed this year?

GS: ADCs with PBD payloads have not showed any promising results in the past year and the absence of PBD ADC-related presentations and posters were not surprising.

EH: Interesting absence of big biotech/pharma and the equal counter-force of maturing small innovative biotechs.

MS : A new wave of investment into ADCs from startup novel technologies to established big biotech/biopharma

CL: Increasing early-stage discussions regarding developability with target knowledge, known tox/clinical data, and site-specific technologies.

JL: I was intrigued by the fact that the ADC platform moves from “simple” chemo-payloads to a true versatile platform to couple various agents, incl. immune stimulatory molecules

Did anyone else notice that Ed and Mike are almost completely diametrically opposed on their response to this question? If that doesn’t demonstrate the value of a panel, nothing will. For me, I was surprised by the recognition that Linkers matter in an ADC. For so long they have either been stable or cleavable and that was the end of the story. This year there was much more talk about how they are active participators in internalization and plasma stability.

4) What was the most innovative new idea you came across?

GS: Ajinomoto’s AJICAP technology. The Fc-region targeting peptide was designed using a structure-based approach. The resulting reactive handle is attached a single, native Lys amino acid thereby eliminating the need to engineer the Ab to achieve DAR 2 site-specific ADC.

EH: AjiCap

MS: There were too many to single out one, but I was pleasantly surprised at the novel ideas at the poster session

CL: The Conditionally Active Biologics (CABs) concept by BioAtla, and also to see how CABs will stack up against ProBodies by CytomX

I am in complete agreement with Mike here. The people participating in the poster session had some really interesting ideas. In particular, I liked the poster about using 2D LC-MS to separate different DAR species and then to clean up the samples prior to MS analysis. Also, the work that Ganapathy is doing with his group at Magenta was very interesting in that they need to make ADCs which are specifically unstable in the plasma for fast clearance, instead of the polar opposite for most other projects.

5) What in your mind is the biggest hurdle that ADCs still need to tackle?

GS: Developing better and more robust models to predict various aspects of PK/PD and ADME considerations is and always has been a challenge

EH: Defeating/decreasing non-specific uptake of ADCs which cause dose-lowering tox. There are several strategies coming to a head.

MS: The notion that ADCs have exhausted their utility and are not worth investing compared to the latest technologies (e.g., cell and gene therapy)

CL: Overcoming negative public sentiment. ~60% of drug candidates fail in Phase I

JL: We still are way too far from a true magic bullet: we didn’t achieve to widen the Ti as hoped/expected

I think the panel nailed this one. Ganapathy, Ed, and Jens are effectively saying therapeutic window, and Mike and Charley are saying that people are getting tired of waiting for ADCs to be the “magic bullet”. I find both to be true, but I’m also fully expecting the shine of cell and gene therapy to come down a little bit when the reality of their difficulties start setting in.

6) Complete the sentence: One year from today, the ADC landscape will be different because of ...

GS: alternate format ADCs (bispecifics, biparatopics etc.) and the emergence of non-chemotherapeutic payloads such as agonists.

EH: improved tox/potency/TI control via several ideas initiated 3-5 years ago.

MS: multiple new approvals and smashing early-phase success of next-gen technologies

CL: trastuzumab deruxtecan (DaiichiSankyo) and enfortumab vedotin (SeaGen)

JL: We will see new MoAs coming along and move beyond Oncology

I’m with Mike and Charley here. New approvals is followed by new money, which will fund the next evolution of ADC development that Ganapathy and Ed are talking about.


Rapid-Fire:

Ganapathy	Ed	Mike	Charley	Jens	Justin
1) What company do you expect the most out in the next year?
Daiichi	SeaGen	Tie: Daiichi and SeaGen	Daiichi		Daiichi
2) Last year, PBDs and their narrow therapeutic window were dominant themes.  One year later, are PBDs dead?
No	NO! Prodrugs/ Hybrid PBDs	Yes… for now.	Loncastuximab tesirine is still going		No way.  Never trust small sample sizes
3) Currently there are 5 ADCs on the market, and 4 in late stage review.  How many commercial ADCs will we see at World ADC 2020?
6	6 (plus Moxy-mAb)	8	7	8	7
4) Which of the following subsection of ADCs is showing the most innovation: payloads, linkers, mAbs
mAbs (ie. bispecifics)	Linkers	Linkers	Linkers	Payloads	Linkers

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And that's a wrap for the first annual World ADC Wrap-up Article. For all of those who both attended World ADC and saw my presentation, thanks for the support. It was my first chance to represent Novasep on the World ADC stage so I appreciate all of you who attended.

Hopefully this was interesting for everyone that doesn't get to attend these meetings on a regular basis. As usual, if it was, comment and let me know.

What's New in ADC's This Week - Oct 28th, 2019

International Space Station

Hello all,

I'm back, and in record time.  As promised, I have completed my link aggregation to get us all back up to date with the world of ADC.  So please enjoy the latest news and happenings related to antibody-drug conjugates.

If you want to receive these updates directly to your inbox, then all you need to do is click on the link below:

Click Here to Subscribe to ADC Daily

Yes, this will get you this article in your inbox.  Also, you will get the full list of links that I have found and thought was interesting.  But coming very soon, I am working on how to get you all involved in this with me.  So if you are interested in being directly plugged in to the latest ADC news, and contributing on anything from answering a poll question to who knows what, then sign up here.  

As a first example of subscriber participation.  Coming soon, I will be putting out a summary of World ADC San Diego highlighting all of the most interesting points from the conference this year.  But instead of just my opinions, I am enlisting the help of some fellow readers who were also conference attendees.  It should be fun.  So expect to see that article coming soon.

And as always, please reshare this article to spread the love and keep these articles coming.  But for now, lets go to the links

1. ADCs in Space!!!

Pioneering the Wild West of Spaceflight Research

International Space Station

I cannot describe how happy this article makes me.  On one hand I can espouse the logic of testing cancer therapies in microgravity because it more closely mimics a tumor microenvironment than a typical cell culture would.  But the reality is, this is just combining two awesome things to make for something even awesome-er.  

A smart man once proposed a theory to me:  You can take anything in the world, and make it cooler by putting it in space.  
Pen --> Space Pen.  
Monkey --> Space Monkey.  
And now, 
Tumor Regression --> Space Tumor Regression.

Way to go AngieX team, you have made my day

2. Lots of New Companies Jumping into the ADC Space

There is a ton of new companies jumping into the fold.  And while their each coming from a very different place.  It's great to see all of the diversity and interest coming into the space: 

First-in-Class Antibody-Drug Conjugate Advances to Clinical Trial

Cancer Therapy Advisor

- Oxford has been in the oncology space for a long time, but this is their first forray into ADCs. They have received approval to start a clinical trial for their ADC targeting CD205 with a DM4 payload in pancreatic cancer in partnership with Menarini. All I can say is, Welcome to the ADC party Oxford. Best of luck with your trials

Now for the next company, I saw their presentation at World ADC and was really impressed.  It does sound like an added complication on top of a complicated process, but it is an interesting approach along with prodrugs like CytomX is working on.  The benefit here is that the change is reversible so it can go back to inert when it leaves the area:

Conditionally Active Biological Proteins

USPatent Office

- I generally don't report on patents, but I just love the technology of BioAtla. The primary technology allows for mAbs which are only active in the tumor microenvironment, but this patent is leveraging their tech to enable crossing through the blood-brain barrier. As far as unique approaches, BioAtla, is looking pretty interesting right now

And last but not least, another conjugation technology focused company is bringing in the big guns to its Board of Directors

Araris Biotech AG establishes Scientific Advisory Board

Biospace

- Rakesh Dixit and John Lambert are joining the board at Araris.  Both of whom can bring an extensive amount of experience to the table and a long rolodex of connections as well.  Paired with some cool conjugation tech, it will be fun to watch what types of moves Araris takes next.

3. Unique Applications of ADC technologies

Clearly this is my favorite category of new stories to write about.  Each one coming with their own complexities and novel modalities.  First up, Oncomatrix:

Tumour stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumours

Annals of Oncology

- Oncomatryx is yet another company looking at a novel approach to ADC treatments.  For them the focus is not the tumor itself but the stromal cells surrounding it.  They looked a individual treatment and a combination with Pembrolizumab and showed decent results in both cases.  Is this going to be a fruitful avenue for cancer treatment?  I don't know, but I'm glad that someone is trying to find out

And if oncomatryx is going down a more traditional ADC path, this team was going in a completely different direction entirely.  One could argue that this isn't an ADC, but one can't argue that this isn't really cool:

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation

Systems and Synthetic Biology

- OK, the chemical engineer in me is very happy right now.  This team out of the University of Alabama is attempting to harvest exosomes from cell culture which include integrated mAbs in the outer membrane that can specifically bind to cancer cells.  This sounds ridiculously complicated to me, but that complication is matched in equal amounts by cool factor that must be appreciated

4. PBDs aren't dead

Until a PBD based ADC is commercially approved, there will always be the sting of some recent failures hanging around in the background. However, that doesn't mean that great stuff isn't underway:

Developing Potent Affimer-drug Conjugates

Technology Networks

- ADC T and Avacta are partnering up to attach PBD payloads to their proprietary affimer technology that builds small peptide strands that are specific to certain targets.  It's an interesting approach to ADCs without all of the mess of mAbs, and the ADC T partnership makes a bunch of sense since they can provide the payload

And if one collaboration was not enough for ADC T, they are continuing along the approval path with internal products as well:

ADC Therapeutics Doses First Patients in Pivotal Phase 2 Clinical Trial of ADCT-301 in Patients with Relapsed or Refractory Hodgkin Lymphoma

Biospace

- ADC T is starting dosing of their cohort of patients in their pivotal trial for ADCT-301 which means that their PBD is going to be tested for efficacy instead of just safety for the first time.  Fingers crossed for good results

And lastly, Iksuda is using some Femtogenix tech to push forward their folate receptor candidate:

IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor expression

Annals of Oncology

- Iksuda (formerly Glythera) is coming into the ADC space with some high powered help.  Bob Lutz from Immunogen has joined the team, and they have an incredible tagline : "We build superior ADCs"  They are using a combination of their proprietary permalink tech along with Femtogenix unique take on PBD warheards to target FRa with their ADC.  Models are showing good response with pM potency, but as any statistician will tell you.  All models are wrong...some are useful.  Only time will tell which on Iksuda has on their hands

5. When the FDA speaketh - thou shalt Listen

Drug Regulation in the Era of Individualized Therapies

New England Journal of Medicine

- When the directors of CDER and CBER come together to write an op-ed about individualized therapies.  Its probably worth taking the time to read.  Gene and Cell therapies are certainly big right now, but like ADCs they are an unknown quantity and everyone is proceeding cautiously

Justin's Thoughts:

If you ask most people in the industry, they will tell you that there are 5 commercial ADC products right now.  But Wikipedia says that there are 6. And while using Wiki as a primary source is never a good idea, it makes you wonder why Moxteumomab pasudotox is flying under the radar of our general consciousness.  Well not anymore:

Moxetumomab pasudotox for hairy cell leukemia: preclinical development to FDA approval

Blood Advances

- Moxetumomab pasudotox, the mystery ADC which doesn't ever get invited to the ADC party.  There is an Fv antigen binding region, a linker section, and a toxin.  All of which are internalized into a cancer cell, and broken apart in order to induce apoptosis.  It has shown a 30% complete remission rate and is commercially available right now, so why don't we ever talk about it as an ADC?

And if you have made it this far, then maybe you would be willing to go one step further and answer a question for me:
What is the next ADC related event that you are planning to attend?  Be it conference, seminar, industry happy hour, or whatever.  Obviously World ADC is the big one, but beyond that is there anything else that you look forward to attending?

Have a great week everyone!

-Justin

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Thats it for today. There are always more coming down the pike. Is there something I missed? Contact me. [email protected]
- - - [Main]