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NTM 1634

Drug Profile

NTM 1634

Alternative Names: BoNT C/D; NTM-1634

Latest Information Update: 09 Apr 2018

At a glance

  • Originator Dana-Farber Cancer Institute; Harvard Medical School; University of California at San Francisco
  • Developer Ology Bioservices
  • Class Antivirals; Monoclonal antibodies
  • Mechanism of Action Botulinum toxin inhibitors; Immunomodulators
  • Orphan Drug Status

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

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Phase I Botulism; Influenza A virus H1N1 subtype; Influenza A virus H5N1 subtype; Severe acute respiratory syndrome

Most Recent Events

  • 02 Oct 2017 Nanotherapeutics is now called Ology Bioservices
  • 20 Mar 2017 Phase-I clinical trials in Botulism (In volunteers) in USA (IV)
  • 20 Mar 2017 Phase-I clinical trials in Influenza-A virus H1N1 subtype (In volunteers) in USA (IV)

Development Overview

Introduction

Ology Bioservices (formerly Nanotherapeutics) is developing NTM 1634, a therapeutic antibody for use in various biodefence indications, including the treatment of botulinum poisoning, and protection against the viruses that cause severe acute respiratory syndrome (SARS) and pandemic viral infections such as the H1N1 and H5N1 strains of the influenza virus. NTM 1634 is a mixture of four monoclonal IgG1 antibodies (XC41, XC42, XC44, and XC84) which bind to non-overlapping epitopes on BoNT/C/D. The candidate is being developed as a countermeasure for botulism. Phase I development is underway in the US in healthy volunteers.

Antibodies that target botulinum toxins A, B, C, D and E are being developed using XOMA's proprietary antibody development and manufacturing platforms. The platforms include bacterial cell expression technology, which covers methods for expressing correctly-folded antibodies, antibody fragments and fusion proteins in bacteria. They also include Human Engineering™ technology, which allows for the humanising of non-human antibodies, while retaining their structure, function and antigen binding characteristics. XOMA also utilised an antibody phage display library comprised of custom and commercial libraries. The antibodies in development are expected to have an improved safety profile over equine-derived antitoxins currently in use.

Xoma is planning to focus its development efforts on endocrine franchise further to divestment of its biodefence programme to Nanotherapeutics [1] .

NTM 1634 has originated from the company's research programme focused on the development of antibodies for biodefence indications [See ADIS Insight Drug profile 800030698].

In October 2017, Nanotherapeutics changed its name to Ology Bioservices [2] .

Company Agreements

In November 2015, Xoma divested its biodefence programme to Nanotherapeutics, and transferred all associated assets, contracts, and materials to Nanotherapeutics. Nanotherapeutics will be responsible for advancing this programme and is eligible for related contract awards. In November 2017, Xoma receives a $US3 million milestone payment related to the clinical advancement of an anti-botulism product candidate licensed to Nanotherapeutics. XOMA is also eligible to receive a 15% royalty on net sales, if the product candidate advances from its current stage of development to production and stockpiling by governmental agencies. [1] [3] [4] [5]

In July 2009, XOMA was awarded a $US1.7 million 5-year subcontract by SRI International, to produce novel antibody drugs against the SARS virus. The project is funded under a 2006 prime contract between SRI and the NIAID. XOMA will evaluate several antibodies for growth, productivity, manufacturability and performance in bioreactors. XOMA may receive additional awards under this contract [6] . Xoma was awarded a second subcontract by SRI International worth $US2.2 million, to develop the antibody F10 for the treatment of H1N1 and H5N1 influenza A virus infection [7] .

In December 2007, XOMA entered into an agreement with The Regents of the University of California to license the rights to a number of antibodies directed against anti-botulinum toxins A, B and E. Under the agreement, XOMA will make milestone payments and The Regents will receive royalties on commercial sales of the antibody products. XOMA has an exclusive right under pending patent applications to commercialise these antibodies.

Key Development Milestones

Botulinum toxin antibodies

In October 2017, Nanotherapeutics completed a phase I trial which assessed the safety and pharmacokinetics of NTM 1634 in healthy subjects (NTM-1634-001; 272201600009C-2-0-1; NCT03046550). The double blind, randomised, dose escalation trial was initiated in March 2017, and enrolled 24 healthy volunteers in the US [8] . In September 2017, Xoma announced that it has earned a $US3 million milestone payment related to this clinical advancement of NTM 1634. The company received an initial cash payment of $US250,000 related to the milestone. The remaining amounts of the milestone payment will be received in monthly payments over the next eleven months [3] .

In September 2011, Nanotherapeutics was awarded a contract of $US2 049 872 (Contract No. 272201600009C-2-0-1) to support the advanced development of promising biodefense therapeutic candidates/products with broad spectrum activity. The research and development activities supported will allow candidate therapeutic countermeasures to progress through the product development pipeline, and includes preclinical/non-clinical and clinical IND development activities.

In October 2011, XOMA was awarded a contract of up to $US28 million over 5 years by the NIAID, to develop its monoclonal antibody-based antitoxins for use in the treatment of botulism poisoning. XOMA planned to use the funding primarily to expand into the development of antibody antitoxins for botulinum toxins C and D [9] [10] .

XOMA received a grant of $US977 917 in November 2010, under the Patient Protection and Affordable Care Act of 2010 (PPACA) to fund four of the company's therapeutic antibody projects, including the development of antibotulinum toxin antibodies [11] .

In September 2008, XOMA was awarded a $US65 million multiple-year contract (Contract No. HHSN272200800028C) from the NIAID to support the ongoing development of antibotulism antibodies towards clinical trials [12] . In 2005 and 2006, XOMA was awarded contracts by NIAID worth over $US31 million, for the development of antibodies against botulinum toxin A, which have since entered clinical trials [13] [14] [15] .

Influenza virus antibodies

In September 2009, XOMA expanded its biodefence programmes to include the development of a novel antibody, known as F10, as a potential therapy for the treatment of both seasonal and pandemic virus infections, particularly for patients who are immunocompromised or unvaccinated, or those infected with drug-resistant viral strains. The F10 antibody was initially developed at Dana-Farber Cancer Institute and Harvard Medical School; studies conducted there showed the F10 antibody to neutralise group 1 influenza A viruses, including the H1N1 (swine flu) and H5N1 (bird flu) strains. The F10 antibody binds to a region on which is present across group 1 influenza A viruses. Because the region undergoes less structural change due to mutation or reassortment than vaccine targets, an antibody that binds to it could potentially be used to treat multiple influenza viral strains and be useful over multiple influenza seasons. In early studies, the F10 antibody appears to stop the spread of the influenza virus by preventing replication after viral particles enter cells [7] .

By January 2010, the company had obtained $US3.9 million in new government contracts for the development of antibodies to the H1N1 and H5N1 influenza strains and SARS viruses [16] .

Patent Information

According to the XOMA 2011 20-F (filed 14 March 2012), the company owns a portfolio of patents related to its proprietary Human Engineering™ technology, inlcuding US patent No. 5 766 886, which covers methods of modifying antibody variable domains to reduce immunogenicity.

Drug Properties & Chemical Synopsis

  • Route of administration IV
  • Formulation unspecified
  • Class Antivirals, Monoclonal antibodies
  • Target Botulinum toxin
  • Mechanism of Action Botulinum toxin inhibitors; Immunomodulators
  • WHO ATC code

    J05 (Antivirals for Systemic Use)

    J05A-X (Other antivirals)

    J06A-A04 (Botulinum antitoxin)

  • EPhMRA code

    J5B4 (Influenza antivirals)

    J5B5 (Respiratory antivirals excluding influenza products)

    J6A2 (Botulism sera)

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Botulism - In volunteers Phase I USA IV / unspecified Ology Bioservices 20 Mar 2017
Influenza A virus H1N1 subtype - In volunteers Phase I USA IV / unspecified Ology Bioservices 20 Mar 2017
Influenza A virus H5N1 subtype - In volunteers Phase I USA IV / unspecified Ology Bioservices 20 Mar 2017
Severe acute respiratory syndrome - In volunteers Phase I USA IV / unspecified Ology Bioservices 20 Mar 2017

Commercial Information

Involved Organisations

Organisation Involvement Countries
Harvard Medical School Originator USA
University of California at San Francisco Originator USA
Dana-Farber Cancer Institute Originator USA
Dana-Farber Cancer Institute Owner USA
University of California at San Francisco Owner USA
Harvard Medical School Owner USA
Ology Bioservices Licensee USA
SRI International Funder USA
National Institute of Allergy and Infectious Diseases Collaborator USA

Development History

Event Date Update Type Comment
30 Oct 2017 Trial Update Nanotherapeutics completes a phase I trial in Healthy volunteers in USA (NCT03046550) Updated 09 Apr 2018
02 Oct 2017 Company Involvement Nanotherapeutics is now called Ology Bioservices Updated 06 Oct 2017
20 Mar 2017 Phase Change - I Phase-I clinical trials in Botulism (In volunteers) in USA (IV) Updated 11 May 2017
20 Mar 2017 Phase Change - I Phase-I clinical trials in Influenza-A virus H1N1 subtype (In volunteers) in USA (IV) Updated 11 May 2017
20 Mar 2017 Phase Change - I Phase-I clinical trials in Influenza-A virus H5N1 subtype (In volunteers) in USA (IV) Updated 11 May 2017
20 Mar 2017 Phase Change - I Phase-I clinical trials in Severe acute respiratory syndrome (In volunteers) in USA (IV) Updated 11 May 2017
20 Feb 2017 Trial Update Nanotherapeutics plans a phase I trial for NTM 1634 in volunteers in USA (NCT03046550) Updated 11 May 2017
05 Nov 2015 Licensing Status Nanotherapeutics acquires biodefence antibodies programme from XOMA [1] Updated 11 May 2017
14 Mar 2012 Patent Information XOMA has patent protection for Human Engineering™ technology in USA (XOMA 20-F, March 2012) Updated 11 May 2017
07 Oct 2011 Phase Change - Preclinical Preclinical trials in Severe acute respiratory syndrome in USA (IV) Updated 11 May 2017
03 Oct 2011 Company Involvement Xoma receives grant from NIAID for continued development of antibotulism antibodies [9] Updated 11 May 2017
01 Sep 2011 Company Involvement Nanotherapeutics receives grant from NIAID for advanced development of promising biodefense therapeutic candidates (NCT03046550) Updated 11 May 2017
01 Oct 2010 Regulatory Status XOMA receives grant under the Patient Protection and Affordable Care Act of 2010 (PPACA) for the development of antibotulism antibodies [11] Updated 11 May 2017
23 Sep 2009 Phase Change - Preclinical Preclinical trials in Influenza-A virus H1N1 subtype in USA (IV) Updated 11 May 2017
23 Sep 2009 Phase Change - Preclinical Preclinical trials in Influenza-A virus H5N1 subtype in USA (IV) Updated 11 May 2017
30 Jul 2009 Phase Change Early research in Severe acute respiratory syndrome in USA (IV) Updated 11 May 2017
07 Sep 2008 Regulatory Status XOMA receives grant from NIAID for continued development of antibotulism antibodies [12] Updated 11 May 2017
22 Mar 2005 Phase Change - Preclinical Preclinical trials in Botulism in USA (IV) Updated 11 May 2017

References

  1. XOMA Announces the Sale of Its Manufacturing Facilities to Agenus.

    Media Release
  2. Nanotherapeutics Announces Name Change to Ology Bioservices, Reflecting the Companys Ongoing Transformation into One of the Top Contract Development and Manufacturing Organizations of Vaccines and Biologics.

    Media Release
  3. XOMA Earns $3 Million Milestone Payment from its License Agreement with Nanotherapeutics.

    Media Release
  4. XOMA Reports Third Quarter 2017 Financial Results.

    Media Release
  5. XOMA Reports First Quarter 2016 Operational Achievements and Financial Results.

    Media Release
  6. XOMA Announces New U.S. Government Biodefense Subcontract for Development of Therapeutic Antibodies to Treat SARS.

    Media Release
  7. XOMA to Develop Therapeutic Antibody for H1N1 and H5N1 Influenza Viruses Under $2.2 Million U.S. Government Program Managed by SRI International.

    Media Release
  8. A Phase I, Double-Blind, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1634 vs Placebo Administered Intravenously in Healthy Adults

    ctiprofile
  9. XOMA Secures Federal Contract to Expand Its Next-Generation Human Botulism Antitoxin Portfolio.

    Media Release
  10. XOMA Presents Data on Novel Antitoxins in Development for Botulism Poisoning.

    Media Release
  11. XOMA Awarded $977,917 in Grants Under the Patient Protection and Affordable Care Program.

    Media Release
  12. XOMA Awarded $65 Million Biodefense Contract by NIAID to Advance Drug Candidates Against Botulism Toxins Into Clinical Trials.

    Media Release
  13. XOMA Successfully Completes Initial $15 Million BioDefense Contract with NIAID.

    Media Release
  14. XOMA Awarded New $16 Million BioDefense Contract with NIAID; Contracts Now Total $31 Million for XOMA to Produce Anti-Botulism Antibodies to Support Human Clinical Trials.

    Media Release
  15. XOMA Awarded $15 Million Contract from NIAID to Help Fight Bioterrorism; XOMA to Develop Three Anti-Botulinum Neurotoxin Monoclonal Antibodies.

    Media Release
  16. XOMA Reviews Priorities for 2010 and 2009 Accomplishments.

    Media Release
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