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Pritumumab - Nascent Biotech

Drug Profile

Pritumumab - Nascent Biotech

Alternative Names: ACA 11; CLN-IgG; CLNH 11; Monoclonal antibody ACA 11

Latest Information Update: 26 Mar 2020

At a glance

  • Originator University of California, San Diego
  • Developer Nascent Biotech
  • Class Antineoplastics; Antivirals; Immunotherapies; Monoclonal antibodies
  • Mechanism of Action Antibody-dependent cell cytotoxicity; Immunomodulators
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    Yes - Pancreatic cancer; Glioma
  • New Molecular Entity Yes

Highest Development Phases

  • Phase II Glioma
  • Preclinical Pancreatic cancer
  • Research COVID 2019 infections

Most Recent Events

  • 27 May 2020 Nascent Biotech in a collaboration with Hoag Memorial Hospital Presbyterian plans a phase I trial in Brain cancer (Late-stage disease, Second-line therapy or greater) in USA (IV, Infusion) (NCT04396717)
  • 19 Mar 2020 Early research in COVID-2019 infections in USA (Parenteral)
  • 01 Jan 2018 Preclinical trials in Pancreatic cancer in USA (IV)

Development Overview

Introduction

Pritumumab is a natural human IgG1κ antibody purified from the parent human hybridoma, CLNH11, being developed by Nascent Biotech (previously called Nascent Biologics) for the treatment of malignant and non malignant gliomas and pancreatic cancer. The parent hybridoma is generated by fusion of B-lymphocytes isolated from a cervical cancer patient and the human lymphoblastoid B-cell line. Pritumumab recognises altered vimentin (ecto-domain vimentin) expressed on the cell surface of epithelial tumour cells, which is restricted to various solid tumours irrespective of the germ layer where the tissues originated. The drug induces tumour cell death by antibody-dependent cell-mediated cytotoxicity. Phase II development in glioma is underway in Japan, while preclinical research for pancreatic cancer is ongoing in the US.

Nascent Biotech is also developing pritumumab for the treatment of conditions related to COVID-19. Early research is underway in the US [1]

Tobacco plants will be used as an adjunct expression system for production of pritumumab, a technology of Mapp Biopharmaceutical [2] .

Jin-En International Group Holding Co. acquired Nascent Biologics and changed its name to Nascent Biotech in July 2014 [3] .

Company Agreements

In July 2016, Nascent Biotech entered into an exclusive licensing agreement with Zhejiang Hisun Pharmaceutical Company for the development and commercialisation of pritumumab. Under the agreement terms, Hisun will develop, manufacture and commercialise pritumumab in China. Further, Nascent Biotech will provide to Hisun its Master Cell Bank and related technology, which will allow Hisun to manufacture and initiate clinical development of Pritumumab in China [4] .

In February 2015, Nascent Biotech, in conjunction with Mapp Biopharmaceutical, received SBIR grant of $US225 000 from National Institutes of Health (NIH) for initial development of tobacco plants as an adjunct expression system for pritumumab for the treatment of brain cancer [2] .

In April 2012, Nascent Biotech and Catalent Pharma Solutions entered into a product development agreement. Under the terms of the agreement, Catalent will use its GPEx® technology to engineer a cell line expressing pritumumab. Catalent will be responsible for the production of purified monoclonal antibody for Nascent's phase I/II trials [5] .

Nascent Biotech entered into a licensing agreement for pritumumab with a Japanese scientist in July 2009. Pritumumab was initially generated in 1982 by Dr. Glassy, CEO and co-founder of Nascent Biotech, then taken to Japan and licensed to a Japanese party [6] .

Key Development Milestones

Cancer

In August 2015, Nascent Biotech announced its plan to file for an Investigational New Drug exemption [7] .

In October 2014, the US FDA granted orphan drug designation to pritumumab for the treatment of patients with glioma [7] [8] . In April 2016, the company also received orphan drug designation for the treatment of pancreatic cancer [9] .

Phase II efficacy and phase I safety trials in patients with glioma, were conducted in Japan by various institutes in a total of 249 patients. Positive overall response rates were demonstrated in early and late phase II trials. Additionally, data from the late phase II trial showed a five-year survival rate of 25%. In a phase I trial, pritumumab showed a good safety profile [10] .

Nascent Biotech is planning to conduct phase I/II clinical trials in the US, evaluating pritumumab in patients with glioma, to confirm and validate earlier clinical data [11] [7] [5] [12] .

Nascent Biotech intends to initiate trials in other epithelial cancers such as breast, lung, colon and pancreas [7] .

In April 2018, Nascent Biotech presented preclinical data for pritumumab at the 109th Annual Meeting of the American Association for Cancer Research (AACR-2018). The study evaluated ability of pritumumab mAb to target pancreatic cancer cells and inhibit pancreatic tumour growth. Pritumumab bound to the cell surface of patient pancreatic cancer tissue and to the surface of established pancreatic cancer cells in culture. This antibody binding induced antibody-dependent cell-mediated cytoxicity (ADCC). Additionally, pritumumab significantly inhibited pancreatic tumour growth in a xenograft mouse model [13] .

In April 2016, preclinical data of pritumumab were presented at the 107th Annual Meeting of the American Association for Cancer Research (AACR-2016) [14] .

Nascent Biotech completed a toxicology study of pritumumab conducted in monkey and rat, in compliance with FDA guidance, wherein no in life toxicities were observed in the two species studied [7] .

Covid-2019-infetions

In March 2020, company initiated in vitro studies of pritumumab for the treatment of patients infected with COVID-19. The testing has started to check the ability of pritumumab to interfere with the virus binding to its target cells and provide treatment against this devastating pandemic. Earlier company announced the intention to initiate research for pritumumab as a possible treatment for patients infected with the COVID-19 virus strain [1] [15] .

Financing information

Nascent Biotech raised $US2.1 million since March 2014, which was used to advance the development of pritumumab, to support the filing of an Investigational New Drug exemption [7] .

Patent Information

Pritumumab is covered by 11 issued patents in the US (4 618 577, 4 761 377, 5 093 261, 5 155 036, 5 286 647, 5 589 573, 5 602 027, 6 051 229, 6 051 387, 6 051 693, and 6 165 467).

Drug Properties & Chemical Synopsis

  • Route of administration IV, Parenteral
  • Formulation unspecified
  • Class Antineoplastics, Antivirals, Immunotherapies, Monoclonal antibodies
  • Mechanism of Action Antibody-dependent cell cytotoxicity; Immunomodulators
  • WHO ATC code

    J05 (Antivirals for Systemic Use)

    L01X-C (Monoclonal antibodies)

  • EPhMRA code

    J5 (Antivirals for Systemic Use)

    L1G (Monoclonal Antibody Antineoplastics)

  • Chemical name Immunoglobulin G, anti-(human vimentin) (human monoclonal CLN G11 gamma1-chain), disulfide with human monoclonal CLN G11 kappa-chain, dimer
  • Molecular formula C6440 H9968 N1708 O2016 S42
  • CAS Registry Number 499212-74-7

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
COVID 2019 infections - - Research USA Parenteral / unspecified Nascent Biotech 19 Mar 2020
Glioma - - Phase II Japan IV / unspecified Nascent Biotech 29 Jan 2016
Pancreatic cancer - - Preclinical USA IV / unspecified Nascent Biotech 01 Jan 2018

Orphan Status

Indication Patient Segment Country Organisation Event Date
Glioma - USA Nascent Biotech 28 Oct 2014
Pancreatic cancer - USA Nascent Biotech 25 Apr 2016

Commercial Information

Involved Organisations

Organisation Involvement Countries
University of California, San Diego Originator USA
Nascent Biotech Owner USA
Zhejiang Hisun Pharmaceutical Licensee China
Mapp Biopharmaceutical Technology Provider USA
National Institutes of Health (USA) Funder USA
Catalent Pharma Solutions Collaborator USA

Scientific Summary

Pharmacokinetics

Analysis of a blood brain barrier model showed minimal distribution of pritumumab in normal brain tissues and significant binding in tumour areas of brain tissues. This indicated that the monoclonal antibody product crosses the tumour brain barrier [14] .

Adverse Events

A total of 10 patients with malignant gliomas were treated with pritumumab IV once or twice a week for 4 weeks, in a phase I trial. No toxicities were observed [10] .

In a phase II study, 42 patients with malignant gliomas received pritumumab IV once or twice a week for 24 weeks. Mild adverse reactions were reported in 2/21 evaluable patients [17] .

Pharmacodynamics

Summary

A concentration-dependent study of pritumumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) showed an EC50 of 39.6 ng/ml. Additional studies of pritumumab showed effective prevention of tumour growth in a xenograft model with nude athymic mice but not in SCID mice [14] .

Binding specificity evaluated using flow cytometry and immunohistochemical analysis, western blot analysis and ADCC activity confirmed the comparability of a recombinant version of pritumumab, made using the GPEx® system in CHO cells, and the original hybridoma [14] .

In preclinical immunoreactivity studies using cell lines and human tissue, pritumumab had a marked reaction with malignant glioma cell lines and tissue; however, the compound did not react to normal cell lines, or normal adult or fetal brain tissue or other extraneural tissue [10] .

Therapeutic Trials

Glioma

in a phase II study, patients with malignant gliomas were treated with pritumumab IV twice a week for 24 weeks. The overall response rate was 27%. The five-year survival rate in a group of 66 patients was 25% [10] .

In another phase II study, 42 patients with malignant gliomas received pritumumab IV once or twice a week for 24 weeks. The overall response rate for the 21 patients who could be evaluated was 38.1%. The response rates for patients who received pritumumab once or twice a week were 14.2 and 50.0%, respectively [17] .

Future Events

Expected Date Event Type Description Updated
30 Jun 2020 Trial Update Nascent Biotech in a collaboration with Hoag Memorial Hospital Presbyterian plans a phase I trial in Brain cancer (Late-stage disease, Second-line therapy or greater) in USA (IV, Infusion) (NCT04396717) (700259759) [16] 02 Jun 2020

Development History

Event Date Update Type Comment
27 May 2020 Trial Update Nascent Biotech in a collaboration with Hoag Memorial Hospital Presbyterian plans a phase I trial in Brain cancer (Late-stage disease, Second-line therapy or greater) in USA (IV, Infusion) (NCT04396717) [16] Updated 02 Jun 2020
19 Mar 2020 Phase Change Early research in COVID-2019 infections in USA (Parenteral) [1] Updated 26 Mar 2020
01 Jan 2018 Phase Change - Preclinical Preclinical trials in Pancreatic cancer in USA (IV) [13] Updated 25 Apr 2018
19 Jul 2016 Licensing Status Nascent Biotech enters into an exclusive licensing agreement with Zhejiang Hisun Pharmaceutical Company for development, manufacture and commercialisation of pritumumab in China [4] Updated 22 Jul 2016
25 Apr 2016 Regulatory Status Pritumumab receives Orphan Drug status for Pancreatic cancer in USA [9] Updated 18 May 2016
14 Apr 2016 Scientific Update Pharmacodynamics and pharmacokinetics data from preclinical studies in Cancer presented at the 107th Annual Meeting of the American Association for Cancer Research (AACR-2016) [14] Updated 30 Apr 2016
29 Jan 2016 Phase Change - II Phase-II clinical trials in Glioma in Japan (IV) Updated 29 Jan 2016
13 Aug 2015 Regulatory Status Nascent Biotech plans to file an IND exemption application with the US FDA in USA [7] Updated 20 Aug 2015
26 Feb 2015 Company Involvement Nascent Biotech and Mapp Biopharmaceutical receive SBIR grant from National Institutes of Health (USA) for pritumumab development in Brain cancer [2] Updated 04 Mar 2015
28 Oct 2014 Regulatory Status Pritumumab receives Orphan Drug status for Glioma in USA [8] Updated 20 Aug 2015
29 Jul 2014 Company Involvement Nascent Biologics is now called Nascent Biotech [3] Updated 04 Mar 2015
20 Apr 2012 Active Status Review Although no recent development has been reported for pritumumab, Nascent Biologics is planning to conduct phase I/II trials in Glioma in the US Updated 20 Apr 2012
01 Dec 2009 Scientific Update Efficacy, adverse event and pharmacodynamic data from preclinical and clinical trials published in the Journal of Human Antibodies [10] Updated 18 Apr 2012
17 Aug 2001 Phase Change - No development reported No-Development-Reported for Glioma in Japan (IV) Updated 17 Aug 2001
17 Jan 1995 Phase Change - II Phase-II clinical trials for Glioma in Japan (IV) Updated 17 Jan 1995

References

  1. Nascent Biotech has Begun In Vitro Studies as a Potential Therapeutic Agent Against COVID-19.

    Media Release
  2. Nascent Biotech Announces $225,000 NIH Grant Award in Conjunction with Mapp Biopharmaceutical.

    Media Release
  3. Jin-En International Group Holding Co. Acquires Nascent Biotech Inc. and Changes Name to Nascent Biotech Inc.

    Media Release
  4. Nascent Biotech and Hisun Announce an Exclusive License Agreement for the Development and Commercialization of Nascent's Primary Asset, Pritumumab, in Mainland China .

    Media Release
  5. Nascent and Catalent Sign Cancer Antibody Development Deal.

    Media Release
  6. Proven Cancer Cure Back in the Hands Of U.S. Inventor After 27 Years In Japan.

    Media Release
  7. Nascent Biotech Achieves Two Key Milestones in Development of its Novel Brain Cancer Treatment.

    Media Release
  8. Orphan Drug Designations and Approvals - pritumumab. Internet-Doc 2015;.

    Available from: URL: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=448514
  9. Nascent Biotech Announces Orphan Drug Designation for Pancreatic Cancer.

    Media Release
  10. Glassy MC, Hagiwara H. Summary analysis of the pre-clinical and clinical results of brain tumor patients treated with pritumumab. WWW 2012;.

    PubMed | CrossRef Fulltext
  11. Hoag is First in Nation to Test Innovative Antibody Brain Cancer Drug.

    Media Release
  12. A Phase 1, Sequential Cohort, Open-Label, Dose-Escalation Study of the Safety and CNS Exposure of Pritumumab in Patients With Brain Cancer

    ctiprofile
  13. Babic I, Nomura N, Glassy E, Nurmemmedov E, Yenugonda V, Glassy M, et al. Pritumumab mAb binds cell surface expressed vimentin on pancreatic cancer cells and inhibits tumor growth. AACR-2018 2018; abstr. 3828 / 18.

    Available from: URL: http://link.adisinsight.com/Db23Q
  14. Babic I, Mukthavaram R, Nomura N, Pingle S, Glassy MC, Kesari S. Therapeutic potential of the natural human IgG1k antibody pritumumab. AACR-2016 2016; abstr. 2357.

    Available from: URL: http://www.abstractsonline.com/plan/AbstractPrintView.aspx?mID=4017&sKey=a65f6d89-0e10-484a-9aa2-7bcb496111ea&cKey=3e5440a0-abf3-4c4d-b3a6-e9267e3f5971&mkey=%7b1D10D749-4B6A-4AB3-BCD4-F80FB1922267%7d
  15. NASCENT BIOTECH INVESTIGATION DRUG PRODUCT, PRITUMUMAB, TO BE STUDIED AS A POTENTIAL THERAPEUTIC AGENT AGAINST (CORONAVIRUS) COVID-19.

    Media Release
  16. Nascent Biotech to begin Phase 1 Human Trials for Brain Cancer Drug.

    Media Release
  17. Matsumoto S, Nagai M, Takahashi H, et al. Early phase II study of human monoclonal antibody, ACA 11(CLN-IgG)m against malignant brain tumors. Kiso-Rinsho-Clin-Rep 1994;281073.

    PubMed
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