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Welcome
May has just flown by in a whirlwind of Immunotoxins and abstracts. We
have decided to send out this month’s diges...
Focus on Immunotoxins
1
We have added more than 70 trials this month, most of these are Immunotoxins
(ITs). There are a va...
Focus on Immunotoxins
2
The use of a toxin rather than a chemotherapeutic agent as the payload may allow
the combination o...
Table 1: Immunotoxins in active
clinical testing
Sponsor Drug Name Phase Target Target Moiety Payload
National Cancer Inst...
Table 2: Immunotoxin compounds that
have been discontinued
Sponsor Drug Name Phase Target Target Moiety Payload
Teva Pharm...
Focus on Immunotoxins
3
The future of ITs looks promising with Zoptarelin doxorubicin, Cintredekin
besudotox, Moxetumomab ...
Things to look out for in June on
World ADC Trials Intelligence
ASCO, ASCO, ASCO! We will be updating the trials intellige...
Beacon June Digest
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Beacon June Digest

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In Brief:

1) ADCT-301, a CD25 targeting ADC from ADC Therapeutics utilising PBD payload and HuMax technology.
2) PCA062, a p-Cadherin targeting ADC from
3) We were interested to see the re-introduction of ImmunoGen’s IMGN-901 into clinical trials with two new phase II trials added this month, for leukemia and childhood cancers.

In addition we have been adding a significant number of immunotoxins, including denileukin diftitox (ONTAK®), Moxetumomab pasudotox, LMB-2, naptumomab estafenatox, VB4-845, D2C7-IT and SS1P.

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Beacon June Digest

  1. 1. Welcome May has just flown by in a whirlwind of Immunotoxins and abstracts. We have decided to send out this month’s digest a little early so that you can read it on the plane to ASCO! Don’t worry if you aren’t going to ASCO– all the new and exciting data will be added to World ADC Trials Intelligence as soon as possible, with a round up next month. New Clinical Trials for May New compounds that have recently initiated their first phase I trials and have been added to the trials intelligence database: • ADCT-301, a CD25 targeting ADC from ADC Therapeutics utilising PBD payload and HuMax technology. • PCA062, a p-Cadherin targeting ADC from Novartis. • We were interested to see the re-introduction of Immunogen’s IMGN-901 into clinical trials with 2 new phase 2 trials added this month, for leukemia and childhood cancers. A previous trial was terminated in 2013 due to concerns over infection rates and infection-related deaths as well as a lack of PFS benefit in patients with small cell lung cancer.
  2. 2. Focus on Immunotoxins 1 We have added more than 70 trials this month, most of these are Immunotoxins (ITs). There are a variety of different toxin based payloads that the immunotoxins are utilising and are reviewed in Alewine C., et al., 2015. Many of the early ITs generated very rapid and strong neutralising antibodies to both target and toxin, preventing repeated cycles of treatment which impeded effective responses (e.g. LMB-1 , RFT5-dgA and RFB4-SMPT-dgA). More recently, attempts to reduce the immune response to treatment without altering the clinical response has been the focus of several trials. Pre-treatment with cyclophosphamide, cyclosporine A or rituximab proved to be not effective at preventing the development of neutralising antibodies, but using a combination of pentostatin and cyclophosphamide (as in GvHD) has been shown to delay the neutralising antibodies to immunotoxins (e.g. SS1P).
  3. 3. Focus on Immunotoxins 2 The use of a toxin rather than a chemotherapeutic agent as the payload may allow the combination of chemotherapy and IT without overlapping toxicities. Alternatively, they may prove effective in chemo-refractory tumors. In addition, ITs can kill non-dividing cells. However, this capacity to target non-dividing cells is also likely responsible for many of the off target toxicities, particularly vascular leak syndrome, a frequently reported dose limiting toxicity. Like ADCs there are many ITs in clinical development, but the only IT to be licenced currently is denileukin diftitox (Ontak®) which is indicated for use in chronic T cell leukemia, and is currently showing efficacy for other conditions such as B cell non- Hodgkin Lymphoma and chronic lymphocytic leukemia, but not for melanoma. In the pipeline are several other agents of interest (Table 1), with the same targets as the ADCs, including CD22(Moxetumomab pasudotox), CD25 (LMB-2), 5T4 (naptumomab estafenatox), EpCAM (VB4-845), EGFR (D2C7-IT) and mesothelin (SS1P).
  4. 4. Table 1: Immunotoxins in active clinical testing Sponsor Drug Name Phase Target Target Moiety Payload National Cancer Institute (NCI), Medimmune LLC CAT-8015, Moxetumomab Pasudotox, GCR-8015, High affinity BL22 (HA22) 3 CD22 Moxetumomab, Fv Portion Pseudomonas Exotoxin-A (PE38), BL22 Immunotoxin Aeterna Zentaris Zoptarelin doxorubicin, AEZS-108 3 LHRH D-Lys6-LHRH PE Insys Cintredekin besudotox, IL13- PE38QQR 3 IL13R IL13 PE38QQR Eisai Ontak, E777, denileukin diftitox 3 CD25 IL2 Diptheria Toxin Active Biotech AB Naptumomab Estafenatox, Anyara, ABR-217620, 5T4FabV18- SEA/E-120 2, 3 5T4 Naptumomab, Fab fragment Staphylococcal Enterotoxin A & E (SEA/E-120) Angimmune LLC A-dmDT390-bisFv(UCHT1), Resimmune 2 CD3 bisFv(UCHT1) Diptheria Toxin - dmDT390 National Cancer Institute (NCI) LMB-2, Anti-Tac(Fv)-PE38 2 CD25 Tac Pseudomonas Aeruginosa exotoxin (PE38) Viventia Biotech VB4-845: Proxinium 2 Epithelial cell adhesion molecule (EpCAM) EpCAM targetting fragment Truncated form of Pseudomonas exotoxin A Viventia Biotech VB4-845: Vicinium 2 Epithelial cell adhesion molecule (EpCAM) EpCAM targetting fragment Truncated form of Pseudomonas exotoxin A National Cancer Institute (NCI) SS1P, SS1 (dsFv)-PE38 1, 2 Mesothelin (MSLN) Unknown Pseudomonas Aeruginosa exotoxin (PE38) Masonic Cancer Center DT2219 1 CD19, CD22 HD37, RFB4 Diptheria Toxin - dmDT390 Darell D. Bigner, Duke University Medical Center D2C7-(scdsFv)-PE38KDEL, D2C7 1 EGFRvIII and wt PE Oslo University Hospital MOC31PE, ImmunoPeCa 1 Epithelial cell adhesion molecule (EpCAM) PE Alfred Einstein College of Medicine of Yershiva University Combotox 1 CD19, CD22 HD37, RFB4(dsFv) deglycosylated ricin A (dgA) Molecular Templates MT-3724 1 CD20 scFv Fragment Shiga-like toxin A (SLTA) Viventia Biotech VB6-845 1 Epithelial cell adhesion molecule (EpCAM) Fab fragment DeBouganin
  5. 5. Table 2: Immunotoxin compounds that have been discontinued Sponsor Drug Name Phase Target Target Moiety Payload Teva Pharmaceutical Industries TP38 2 Epidermal growth factor receptor (EGFR) TGF-alpha Pseudomonas Aeruginosa exotoxin (PE38) Simmons Cancer Center RFT5-dgA 2 CD25 RFT5 deglycosylated ricin A (dgA) National Cancer Institute (NCI) LMB-1 2 Lewis Y antigen B3 Pseudomonas Aeruginosa exotoxin (PE38) Duke University Medical Center LMB-7 1 Lewis Y antigen scFv of B3 Pseudomonas Aeruginosa exotoxin (PE38) M.D. Anderson Cancer Center HuM-195/rGel 1 CD33 Hum195 recombinant Gelonin (rGel) Darell D. Bigner, Duke University Medical Center MR1-1 1 Unknown Unknown Unknown Medimmune LLC BL22, CAT3888 1 CD22 RFB4(dsFv) Pseudomonas Aeruginosa exotoxin (PE38) National Cancer Institute (NCI) LMB-9 1 Lewis Y antigen dsFv of B3 Pseudomonas Aeruginosa exotoxin (PE38) National Cancer Institute (NCI) IgG RFB4 SMPT 1 CD22 RFB4 deglycosylated ricin A (dgA)
  6. 6. Focus on Immunotoxins 3 The future of ITs looks promising with Zoptarelin doxorubicin, Cintredekin besudotox, Moxetumomab pasudotox and Naptumomab estafenatox all currently in phase III trials . As you would expect, we will be adding novel date an compounds to the trials intelligence database as soon as we hear it.
  7. 7. Things to look out for in June on World ADC Trials Intelligence ASCO, ASCO, ASCO! We will be updating the trials intelligence database on a daily basis during ASCO with all new relevant information, and will continue adding data as it comes in throughout June. If you are presenting any new data or would like your posters added to the database then please do email them to me. Have a great month, and don’t forget, you can email me any time for any specific queries you have regarding the database or ADCs in general Heather Contact the World ADC Research Team on: research@hansonwade.com

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