Details of the Drug

General Information of Drug (ID: DMN63DZ)

• Drug Name: Moxetumomab pasudotox
• Synonyms: CAT-8015; GCR-8015; HA22; UNII-2NDX4B6N8F; Moxetumomab pasudotox [USAN]; Immunoglobulin, anti-(human CD22 (antigen)) (synthetic Mus musculus CAT-8015 heavy chain variable region fragment) fusion protein with exotoxin PE38 (Pseudomonas fragment), disulfide with immunoglobulin, anti-(human CD22 (antigen)) (synthetic Mus musculus CAT-8015 light chain fragment)

Indication

Disease Entry	ICD 11	Status	REF
Hairy cell leukaemia	2A82.2	Approved	[1]
Haematological malignancy	2B33.Y	Phase 1	[2]

• Therapeutic Class: Anticancer Agents
• Drug Type: Monoclonal antibody
• Sequence:
  >subunit 1
  MEVQLVESGGGLVKPGGSLKLSCAASGFAFSIYDMSWVRQTPEKCLEWVAYISSGGGTTY
  YPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHSGYGTHWGVLFAYWGQGTLV
  SAKASGGPEGGSLAALTAHQACHLPLETFTRHRQPRGWEQLEQCGYPVQRLVALYIAARL
  SWNQVDQVIRALASPGSGGDLGEAIREQPEQARLALTLAAAESERFVRQGTGNDEAGAAN
  GPADSGDALLERNYPTGAEFLGDGGDVSFSTRGTQNWTVERLLQAHRQLEERGYVFVGYH
  GTFLEAAQSIVFGGVRARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLR
  VYVPRSSLPGFYRTSLTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLETILGWPL
  AERTWIPSAIPTDPRNVGGDLDPSSIPDKEQAISALPDYASQPGKPPREDLK
  >subunit 2
  MDIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSILHSGVP
  SRFSGSGSGTDYSLTISNLEQEDFATYFCQQGNTLPWTFGCGTKLEIK
  >subunit 3
  PEGGSLAALTAHQACHLPLETFTRHRQPRGWEQLEQCGYPVQRLVALYLAARLSWNQVDQ
  VIRNALASPGSGGDLGEAIREQPEQARLALTLAAAESERFVRQGTGNDEAGAANGPADSG
  DALLERNYPTGAEFLGDGGDVSFSTRGTQNWTVERLLQAHRQLEERGYVFVGYHGTFLEA
  AQSIVFGGVRARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLRVYVPRS
  SLPGFYRTSLTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLETILGWPLAERTVV
  IPSAIPTDPRNVGGDLDPSSIPDKEQAISALPDYASQPGKPPREDLK
• ADMET Property:
  Clearance: The sytemic clearance of drug is 25 L/h [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.4 hours [4]
  Vd: The volume of distribution (Vd) of drug is 6.5 L [3]
• Cross-matching ID:
  DrugBank ID: DB12688
  TTD ID: D00HPD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B-cell receptor CD22 (CD22)	TTM6QSK	CD22_HUMAN	Modulator	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hairy cell leukaemia
• ICD Disease Classification: 2A82.2

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
B-cell receptor CD22 (CD22)	DTT	CD22	1.89E-11	-0.21	-0.58

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Moxetumomab pasudotox (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Moxetumomab pasudotox caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[16]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Moxetumomab pasudotox and Inotersen.	Amyloidosis [5D00]	[17]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 761104.
• [2] Advances in the Development of Anti-CD22 Immunotoxins Containing Pseudomonas Exotoxin for Treatment of Hematologic Malignancies
• [3] Wayne AS, Shah NN, Bhojwani D, Silverman LB, Whitlock JA, Stetler-Stevenson M, Sun W, Liang M, Yang J, Kreitman RJ, Lanasa MC, Pastan I: Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. Blood. 2017 Oct 5;130(14):1620-1627. doi: 10.1182/blood-2017-02-749101. Epub 2017 Aug 9.
• [4] Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3501-E3508. doi: 10.1073/pnas.1721780115. Epub 2018 Mar 26.
• [5] Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res. 2011 Oct 15;17(20):6398-405.
• [6] Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013 Aug 1;119(15):2728-36.
• [7] Safety and immunogenicity of recombinant Bacille Calmette-Gu |rin (rBCG) expressing Borrelia burgdorferi outer surface protein A (OspA) lipoprotein in adult volunteers: a candidate Lyme disease vaccine. Vaccine. 1999 Feb 26;17(7-8):904-14.
• [8] New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
• [9] ClinicalTrials.gov (NCT03196830) CAR-T for R/R B-NHL
• [10] Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial. Clin Cancer Res. 2010 Mar 15;16(6):1894-903.
• [11] ClinicalTrials.gov (NCT03289455) CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell ALL
• [12] ClinicalTrials.gov (NCT03614858) CD19/CD22-targeted Chimeric Antigen Receptor Engineered T Cell (CART) in B-Cell Acute Lymphoblastic Leukemia.
• [13] ClinicalTrials.gov (NCT03398967) A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma
• [14] ClinicalTrials.gov (NCT03098355) Interleukin-2 Following 4SCAR19/22 T Cells Targeting Refractory and/or Recurrent B Cell Malignancies
• [15] ClinicalTrials.gov (NCT03185494) Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22
• [16] Cerner Multum, Inc. "Australian Product Information.".
• [17] Cerner Multum, Inc. "UK Summary of Product Characteristics.".