Friday, October 25, 2019

ADC Links - Oct 23rd, 2019

Finance -

Sutro Biopharma to Receive Milestone Payment for Novel Bispecific Antibody Drug Conjugate Targeting Solid Tumors
- Sutro is hitting payday in their collaboration with Merck KGaA on their bispecific ADC collaboration.  Their ADC has been approved for IND enabling studies using Sutro's cell-free tech along with Merck's bispecific-like molecule

ADC Therapeutics isn't going public in the US after all, while three other biotech IPOs bring in $319M
Endpoints News
- ADC T is pulling back from their planned IPO.  As I mentioned in a previous post, they are having no trouble generating cash, so maybe this isn't too surprising.  But I guess with the luxury of a strong bank account, the allure of FOMO can be held back for a little while longer.

Regulatory -

Daiichi Sankyo Submits New Drug Application for Trastuzumab Deruxtecan to Japanese Regulators
- Daiichi continues to be the odds-on favorite for the next commercial ADC approval

The FDA will hustle up an expedited review for AstraZeneca’s next shot at a blockbuster cancer drug franchise
Endpoints News
- And with the priority review designation, the DS-8201 review should be completed in Q2 of next year.

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


Conditionally Active Biological Proteins
USPatent Office
- I generally don't report on patents because many of them are not likely to become real, 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

First-in-Class Antibody-Drug Conjugate Advances to Clinical Trial
Cancer Therapy Advisor
- Oxford Bio has received approval to start a clinical trial for their ADC targeting CD205 with a DM4 payload in pancreatic cancer.  All I can say is, Welcome to the ADC party Oxford.  Best of luck with your trials

CEO Paul Hudson's turning 'clear eyes' on Sanofi—and hinting at changes ahead
-There's a new chief in town at Sanofi.  And that inevitably means a company reorg can't be too far away. (Just ask the people at AstraZeneca).  Other than just being interesting to pay attention to what CEO's do when they are objectively looking as an outsider about how to make their mark.  There is also a strong chance that changes come along to their ADC portfolio as well.  Stay tuned...

Araris Biotech AG establishes Scientific Advisory Board
- 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.

Immunomedics plans to refile its new drug application
The Motley Fool
- You'll need to scroll down about half-way to find the part about Immunomedics - Here is a lesson in cognitive dissonance between the researchers and the financiers.  No one who had ever touched this process, or worked with these people could write this article.  But such is the price that must be paid for the fat IPO paycheck.

Sanofi U.S. plant sets new bar for biologics production
-Is this the biologics plant of the future.  Corobots, automation, PAT all resulting in "intensified, continuous biologics production technology."  Very Cool

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.  Way to go AngieX team, you have made my day

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

Manuscripts -

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

FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC)
Annals of Oncology
- As mentioned in the last post, here is the paper discussing the results from ImmunoGens Phase III FRa study which did not meet its primary endpoints.  Hopefully the next study shows the efficacy that we are all hoping to see

An anti-CD103 antibody-drug conjugate prolongs the survival of pancreatic islet allografts in mice
Cell Death and Disease
- Here is another cool use of ADCs for non-oncology.  This team shows that they can use an ADC to fight back against allograft rejection through the administration of the CD103-MC-MMAF ADC.  In mouse models they were able to see allograft survival extend from <18 days="" to="">60 days with addition of the ADC.  Pretty cool, and very novel

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

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

Sacituzumab govitecan: antibody-drug conjugate in triple-negative breast cancer and other solid tumors
Drugs of Today
-A nice paper discussing all of the information to date regarding sacituzumab govitecan and TNBC

Clearance of solvents and small molecule impurities in antibody drug conjugates via ultrafiltration and diafiltration operation
Biotechnology Progress
- A nice summary paper about TFF in ADC purification.  Their conjugates are all well behaved, so this is a nice example of ideal clearance in an ADC.  But be wary in assuming that everything will be this well behaved because every conjugate has it's own particularities and often there is trouble at this step

VISTA is an acidic pH-selective ligand for PSGL-1
- BioAtla isn't the only player in the conditionally active antibody game.  Here is a paper in Nature describing the characteristics behind their pH sensitive Tcell activating mAb targeting PSGL-1.  True it's not an ADC, but seeing work that specifically looks at the tumor microenvironment is definitely a trend worth keeping an eye on

Chemoselective Methionine Bioconjugation on a Polypeptide, Protein, and Proteome
- Sure, cysteine gets all of the attention for chemical conjugation to a peptide residue.  But it's not the only amino acid with a conjugatable sulfur residue.  This paper gives methionine a look at a conjugatable amino acid

Excipients for room temperature stable freeze-dried monoclonal antibody formulations
Journal of Pharmaceutical Sciences
- For any formulation scientists out there, here is a cool paper trying to find alternatives to sucrose as a stabilizing agent prior to lyophilization.  Their goal is to be able to store mAbs at RT instead of cold.  I doubt we see this in ADCs anytime soon, but interesting idea nonetheless

Clinical Results -

Seattle Genetics Announces Positive Topline Results from Pivotal Trial of Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer
- The team at SeaGen just keeps on cranking out good data.

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?

Early data look promising for sacituzumab govitecan in metastatic urothelial carcinoma
- Sacituzumab govitecan is showing promising results in metastatic urothelial carcinoma.  ORR was only 29%, but treatment was well tolerated by patients and for those who it was effective, the treatment continued to be effective for the full 8 month study

Brentuximab vedotin for the treatment of patients with relapsed or refractory Hodgkin lymphoma after autologous stem cell transplantation
British Journal of Haematology
- Not to be crass, but the goal of this paper is to determine if the therapeutic benefits of Adcetris justify the costs for the Australian Pharmaceutical Benefits Advisory Committee.  This seems a bit cold, but this is probably the single most important issue for the uptake of novel therapies like ADCs, and outcomes of studies like this will largely justify implementation of ADCs around the world.  (This of course excludes the US, because we are a whole different beast when it comes to pharmaceutical pricing)

Preliminary Results of Safety and PK of Telisotuzumab Vedotin (T) in Japanese Patients with Advanced Solid Tumors
Annals of Oncology
- Preliminary results for Abbvie's ABBV-399 Telisotuzumab Vedotin molecule in 9 Japanese patients show promise in their early stages

Enfortumab vedotin–pembrolizumab duo has potential in urothelial carcinoma
- Chalk up another win for SeaGen with an ORR of 71% when used in combination with pembrolizumab for first-line treatment of metastatic urothelial cancer

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

Thats it for today. There are always more coming down the pike. Is there something I missed? Contact me.
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