Research programme: oral biotherapeutics - Precigen Inc

At a glance

Originator ActoGeniX
Developer Intrexon Corporation; Precigen Inc; Theriva Biologics
Class Anti-inflammatories; Antigens; Antihyperglycaemics; Bacteria; Cytokines; Hormones; Monoclonal antibodies; Peptides; Recombinant proteins; Small molecules
Mechanism of Action Bacterial toxin inhibitors; Enzyme replacements; Helper-inducer T-lymphocyte modulators; Immunomodulators; Immunosuppressants; Interleukin 27 replacements; Microbiome modulators; Tumour necrosis factor alpha inhibitors

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
Available For Licensing Yes - Coeliac disease; Type 1 diabetes mellitus

Highest Development Phases

No development reported Digestive system disorders; Inflammatory bowel diseases; Non-alcoholic steatohepatitis; Phenylketonuria; Type 2 diabetes mellitus
Discontinued Clostridium difficile infections

Most Recent Events

28 Nov 2022 No recent reports of development identified for preclinical development in Non-alcoholic-steatohepatitis in USA (PO)
12 Oct 2022 Synthetic Biologics is now called Theriva Biologics
28 Mar 2022 No recent reports of development identified for preclinical development in Inflammatory-bowel-diseases in Belgium (PO, Capsule)

Development Overview

Introduction

Precigen Inc (formerly Intrexon Corporation) is developing next-generation of orally available protein-based biopharmaceuticals, known as ActoBiotics™, for the treatment of oral, gastrointestinal, metabolic, allergic and autoimmune diseases. Using its proprietary platform (TopAct™ technology), food-grade microbes (Lactococcus lactis) are genetically-engineered to produce biologically contained ActoBiotics™ therapeutics for in situ expression, secretion and targeted delivery of novel proteins and peptides including cytokines, enzymes, hormones, antibody fragments, antigens and monoclonal antibodies. Containment system within the technology prevents the survival of the excreted bacteria outside the human body owing to thymidine-dependent nutrition of the bacteria. The lyophilised bacteria are formulated into a capsule or an oral rinsing solution providing an advantage over protein- and peptide-based injectables. Intrexon’s multigenic engineering technologies provide additional capabilities to develop microbes that express multiple active compounds offering potential for combination treatment within a single-dose ActoBiotics™ therapeutic. Preclinical development is underway for inflammatory bowel disease, type-2 diabetes mellitus, phenylketonuria and digestive system disorders.

Precigen Inc is developing a range of ActoBiotics™ expressing and secreting different bio-therapeutics such as anti-TNF alpha monoclonal antibodies (inflammatory bowel disease) and IL-27 (inflammatory bowel disease, coeliac disease). The company is also developing oral therapeutics, which deliver a combination of small molecules for non-alcoholic steatohepatitis.

Precigen Inc is also developing oral antibody- and peptide-toxin conjugates for targeted modulation of human microbiota, whose imbalances (dysbiosis) cause many diseases. Thus, diseases caused by specific microbiome subspecies can be treated using selective microbiome modulators formulated as ActoBiotics™.

Precigen Inc, in collaboration with the University of Leuven (Katholieke Universiteit Leuven), was developing ActoBiotics™ that express and secrete toxin-neutralising antibodies at the intestinal mucosal site for the treatment of Clostridium difficile infections (Clostridium difficile-associated enteropathy infections). This approach was based on passive immunisation through the local enteric delivery of the antibodies, which neutralises luminal toxins. As of January 2018, the product for Clostridium difficile infections was not listed on the company pipeline and appears to have been discontinued.

Clinical stage ActoBiotics™ products include AG 013 that delivers a therapeutic peptide for the prevention and attenuation of oral mucositis and AG 014 that secretes anti-TNF-alpha Fab fragment called certolizumab (non-pegylated form) to treat inflammatory bowel disease with localised delivery minimising systemic exposure [see RDI profiles 800029671 and 800041458]. Another candidate being developed was AG 015, which secreted the anti-inflammatory cytokine IL-27, suppressed pro-inflammatory Th17 cell development and promoted IL-10 producing T cells for the treatment of IBD and coeliac disease. However, the development of this candidate has been discontinued as it is not reflected on the company's pipeline.

In March 2015, ActoGeniX was acquired by Intrexon^[1]. ActoGeniX was founded in 2006 as a spin-off from VIB and Ghent University^[2].

As at March 2019, no recent reports of development had been identified for research development in Digestive system disorders in Belgium (PO).

As at October 2019, no recent reports of development had been identified for preclinical development in Type-2-diabetes-mellitus in USA (PO), research development in Phenylketonuria in USA (PO).

In February 2020, Intrexon Corporation has changed its name to Precigen Inc^[3].

As at March 2022, no recent reports of development had been identified for preclinical development in Inflammatory-bowel-diseases in Belgium (PO, Capsule).

In October 2022, Synthetic Biologics changed its name to Theriva Biologics^[4].

As at November 2022, no recent reports of development had been identified for preclinical development in Non-alcoholic-steatohepatitis in USA (PO).

Key Development Milestones

In its corporate presentation of September 2014, ActoGeniX announced its plan to develop ActoBiotics™ expressing IL-10 for the treatment of inflammatory bowel disease (IBD) and colon cancer. Preclinical development is planned for 2015 with IND filing and phase I development is anticipated in 2016.

Positive efficacy data in animal models for allergic diseases, type 2 diabetes, as well as autoimmune disorders such as coeliac disease and type 1 diabetes were demonstrated by respective ActoBiotics™ biotherapeutics being developed by Intrexon (Intrexon website, August 2015).

Type-1 diabetes mellitus

In April 2012, ActoGeniX reported results from a research study conducted at the University Hospitals of Leuven, Belgium, which showed that normal serum glucose levels could be reinstated in newly diagnosed non-obese diabetic (NOD) mice when administered the oral therapeutic consisting of Lactococcus lactis secreting proinsulin and IL-10, and demonstrated long-lasting beta cell specific tolerance. These results were published in the Journal of Clinical Investigation. The study was supported by European Community's Health 7^th Framework programme (NAIMIT), the Juvenille Diabetes Research Foundation and the Agency for Innovation by Science and Technology in Flanders (IWT)^[5].

Financing information

In February 2011, ActoGeniX were awarded a €0.53 million ($US0.7 million) grant from the Agency for Innovation by Science and Technology (IWT) in Flanders to support the discovery and development of an ActoBiotics™ therapy for the treatment of Clostridium difficile infections (Clostridium difficile associated enteric disease)^[2].

ActoGeniX reported in March 2009 that it had extended an equity financing round by €2 million to a total of €15.5 million to enable timely execution of its ongoing and planned clinical development programs and to fund the company's operations until mid-2011^[6].

Patent Information

Intrexon owns a portfolio of 147 granted and 56 pending patent applications covering platform and specific applications of ActoBiotics™, technology platform, production process and various therapeutics indications. Broad claims were secured in the US, the EU, Japan and China.

Drug Properties & Chemical Synopsis

Route of administration PO
Formulation Capsule, unspecified
Class Anti-inflammatories, Antigens, Antihyperglycaemics, Bacteria, Cytokines, Hormones, Monoclonal antibodies, Peptides, Recombinant proteins, Small molecules
Target Bacterial toxin; Enzyme; Helper-inducer T-lymphocyte; Interleukin 10; Interleukin 27; Microbiome; Regulatory T-lymphocyte; Tumour necrosis factor alpha
Mechanism of Action Bacterial toxin inhibitors; Enzyme replacements; Helper-inducer T-lymphocyte modulators; Immunomodulators; Immunosuppressants; Interleukin 27 replacements; Microbiome modulators; Tumour necrosis factor alpha inhibitors
WHO ATC code
A (Alimentary Tract and Metabolism)

A05 (Bile and Liver Therapy)

A10X (Other Drugs Used in Diabetes)

A16A (Other Alimentary Tract and Metabolism Products)

A16A-B (Enzymes)

L (Antineoplastic and Immunomodulating Agents)

L01 (Antineoplastic Agents)
EPhMRA code
A (Alimentary Tract and Metabolism)

A10X9 (Other drugs used in diabetes)

A16A (Other Alimentary Tract and Metabolism Products)

A5 (Cholagogues and Hepatic Protectors)

L (Antineoplastic and Immunomodulating Agents)

L1 (Antineoplastics)

Indication	Qualifier	Patient Segment	Phase	Countries	Route / Formulation	Developers	Event Date
Clostridium difficile infections	-	-	Discontinued (Research)	Belgium	PO / Capsule	Intrexon Corporation	29 Jan 2018
Digestive system disorders	-	-	No development reported (Research)	Belgium	PO / unspecified	Precigen Inc	28 Mar 2019
Inflammatory bowel diseases	-	-	No development reported (Preclinical)	Belgium	PO / Capsule	Precigen Inc	28 Mar 2022
Non-alcoholic steatohepatitis	-	-	No development reported (Preclinical)	USA	PO / unspecified	Precigen Inc	28 Nov 2022
Phenylketonuria	-	-	No development reported (Research)	USA	PO / unspecified	Precigen Inc, Theriva Biologics	28 Oct 2019
Type 2 diabetes mellitus	-	-	No development reported (Preclinical)	USA	PO / unspecified	Precigen Inc	28 Oct 2019

Licensing Organisation	Available Indication	Available Phase	Region	Date
Precigen Inc	Type 1 diabetes mellitus	Clinical Phase Unknown	-	14 Jan 2014
Precigen Inc	Coeliac disease	Clinical Phase Unknown	-	13 Jan 2014

Event Date	Update Type	Comment
28 Nov 2022	Phase Change - No development reported	No recent reports of development identified for preclinical development in Non-alcoholic-steatohepatitis in USA (PO) Updated 28 Nov 2022
12 Oct 2022	Company Involvement	Synthetic Biologics is now called Theriva Biologics ^[4] Updated 14 Oct 2022
28 Mar 2022	Phase Change - No development reported	No recent reports of development identified for preclinical development in Inflammatory-bowel-diseases in Belgium (PO, Capsule) Updated 28 Mar 2022
03 Feb 2020	Company Involvement	Intrexon Corporation is now called Precigen Inc Updated 11 Feb 2020
28 Oct 2019	Phase Change - No development reported	No recent reports of development identified for preclinical development in Type-2-diabetes-mellitus in USA (PO) Updated 28 Oct 2019
28 Oct 2019	Phase Change - No development reported	No recent reports of development identified for research development in Phenylketonuria in USA (PO) Updated 28 Oct 2019
28 Mar 2019	Phase Change - No development reported	No recent reports of development identified for research development in Digestive system disorders in Belgium (PO) Updated 28 Mar 2019
05 Oct 2018	Phase Change - Preclinical	Preclinical trials in Non-alcoholic steatohepatitis in USA (PO) (Intrexon pipeline, October 2018) Updated 05 Oct 2018
29 Jan 2018	Phase Change - Discontinued	Discontinued for Clostridium difficile infections in Belgium (PO) Updated 29 Jan 2018
16 Jul 2016	Phase Change - No development reported	No recent reports of development identified for research development in Clostridium difficile infections in Belgium (PO, Capsule) Updated 16 Jul 2016
29 Aug 2015	Phase Change - Preclinical	Preclinical trials in Type-1 diabetes mellitus in Belgium (PO) before August 2015 Updated 15 Oct 2015
29 Aug 2015	Phase Change - Preclinical	Preclinical trials in Type-2 diabetes mellitus in USA (PO) before August 2015 Updated 15 Oct 2015
10 Aug 2015	Phase Change	Early research in Phenylketonuria in USA (PO) Updated 15 Oct 2015
02 Mar 2015	Company Involvement	ActoGeniX has been acquired by Intrexon Corporation Updated 24 Mar 2015
19 Feb 2015	Phase Change	Early research in Digestive system disorders in Belgium (PO) before February 2015 Updated 15 Oct 2015
16 Oct 2014	Scientific Update	AG 014 completes a phase I trial in healthy volunteers Updated 22 Oct 2014
14 Jan 2014	Licensing Status	Oral type 1 diabetes therapy - Intrexon is available for licensing as of 14 Jan 2014. http://www.actogenix.com/ Updated 15 Oct 2015
14 Jan 2014	Phase Change	Early research in Type-1 diabetes mellitus in Belgium (PO) ^[5] Updated 15 Oct 2015
13 Jan 2014	Licensing Status	Coeliac disease therapy - Intrexon is available for licensing as of 13 Jan 2014. http://www.actogenix.com/ Updated 15 Oct 2015
13 Jan 2014	Phase Change - Preclinical	Preclinical trials in Coeliac disease in USA (PO) Updated 13 Jan 2014
13 Jan 2014	Phase Change - Preclinical	Preclinical trials in Inflammatory bowel disease in Belgium (PO) Updated 13 Jan 2014
01 Feb 2011	Phase Change	Early research in Clostridium difficile infections in Belgium (PO) (Actogenix Pipeline, February 2011) Updated 15 Oct 2015

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