Delving into the Latest Updates on Dapatifagene navolactibac with Synapse

Overview

Basic Info

Drug Type

Recombinant LBP

Synonyms

Lactococcus lactis expressing human trefoil factor 1, Lactococcus lactis secreting human trefoil factor 1

+ [2]

Target

TFF1

Mechanism

TFF1 stimulants(trefoil factor 1 stimulants), Bacteria replacements, Microbiome modulators

Therapeutic Areas

Mouth and Tooth Diseases

Active Indication

Stomatitis

Inactive Indication

Head and Neck Neoplasms

Originator Organization

Precigen, Inc.

Active Organization

MultiCare Health System

Inactive Organization

Oragenics, Inc.

Intrexon ActoBiotics NV

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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The purpose of the study is to evaluate the efficacy, safety and tolerability of topically administered AG013 compared to placebo for reducing Oral Mucositis (OM) in patients undergoing chemoradiation for the treatment of head and neck cancer, as measured by the duration, time to development, and overall incidence of OM during the active treatment phase, beginning from the start of chemoradiation therapy (CRT) until 2 weeks following its completion.
The effect of AG013 on patient-reported symptoms and analgesic use during the active treatment phase, and on the cumulative radiation dose administered before the onset of OM will also be evaluated, as will biomarkers and, in a subset of subjects, the PK (pharmacokinetic) profile of AG013.

Start Date18 Jul 2017

Sponsor / Collaborator

Oragenics, Inc.

NCT00938080

/ CompletedPhase 1

A Phase 1b, Multi-center, Single Blinded, Placebo-controlled, Sequential Dose Escalation Study to Assess the Safety and Tolerability of Topically Applied AG013 in Subjects Receiving Induction Chemotherapy for the Treatment of Cancers of the Head and Neck

The purpose of this study is to assess the safety and tolerability of AG013 (genetically modified L. lactis bacteria engineered to secrete human Trefoil Factor 1), and to explore the ability of AG013 to attenuate the course and severity of oral mucositis (OM) in subjects receiving induction chemotherapy for the treatment of head and neck cancer.

Start Date01 Sep 2009

Sponsor / Collaborator

Intrexon ActoBiotics NV

100 Clinical Results associated with Dapatifagene navolactibac

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100 Translational Medicine associated with Dapatifagene navolactibac

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100 Patents (Medical) associated with Dapatifagene navolactibac

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9

Literatures (Medical) associated with Dapatifagene navolactibac

23 Mar 2020·Angewandte Chemie International EditionQ1 · CHEMISTRY

Formation of an Alkynyl‐Protected Ag₁₁₂ Silver Nanocluster as Promoted by Chloride Released In Situ from CH₂Cl₂

Q1 · CHEMISTRY

Article

Author: Li, Jiao‐Jiao ; Guan, Zong‐Jie ; Yuan, Shang‐Fu ; Hu, Feng ; Wang, Quan‐Ming

AbstractBy directly reducing alkynyl–silver precursors, we successfully obtained a large alkynyl‐protected silver nanocluster, (C7H17ClN)3[Ag112Cl6(C≡CAr)51], which is hitherto the largest structurally characterized silver nanocluster in the alkynyl family. The cluster exhibits four concentric core–shell structures (Ag13@Ag42@Ag48@Ag9), and four types of alkynyl–silver binding modes are observed. Chloride was found to be critical for the stabilization and formation of the silver nanocluster. The release of chloride ions in situ from CH2Cl2 solvent has been confirmed by mass spectrometry. This study suggests that the combination of alkynyl and halide ligands will pave a new way for the synthesis of large silver nanoclusters.

15 Dec 2013·CancerQ1 · MEDICINE

Phase 1b, multicenter, single blinded, placebo‐controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy

Q1 · MEDICINE

Article

Author: Colevas, A. Dimitrios ; Brennan, Michael T. ; Hu, Kenneth S. ; Cilli, Fiona ; Haddad, Robert I. ; Limaye, Sewanti Atul ; Sonis, Stephen T. ; Murphy, Barbara A.

BACKGROUNDOral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5‐fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained.METHODSA total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 1011, 6 × 1011, and 1.2 × 1012 colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted.RESULTSAG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013‐subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement.CONCLUSIONSAG013 was safe and well tolerated. Preliminary efficacy data support further study. Cancer 2013;119:4268–4276. © 2013 American Cancer Society.

01 Jul 2010·Oral OncologyQ2 · MEDICINE

AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis

Q2 · MEDICINE

Article

Author: Stephen Sonis ; Lothar Steidler ; Sam Corveleyn ; Bernard Coulie ; Klaas Vandenbroucke ; Pieter Rottiers ; Silvia Caluwaerts ; Sabine Neirynck ; Peter Vanhoenacker ; Brynmor Watkins

Non-clinical studies, focusing on the pharmacodynamics (PD), pharmacokinetics (PK) and safety pharmacology of genetically modified Lactococcus lactis (L. lactis) bacteria, engineered to secrete human Trefoil Factor 1 (hTFF1), were performed to provide proof-of-concept for the treatment of oral mucositis (OM) patients. L. lactis strain sAGX0085 was constructed by stably inserting an htff1 expression cassette into the bacterial genome, and clinically formulated as a mouth rinse (coded AG013). PD studies, using different oral dosing regimens, were performed in a clinically relevant hamster model for radiation-induced OM. The PK profile was assessed in healthy hamsters and in hamsters with radiation-induced OM. In addition, in vitro and in vivo safety pharmacology studies were conducted, in pooled, complement-preserved human serum, and in neutropenic hamsters and rats respectively. Topical administration of L. lactis sAGX0085/AG013 to the oral mucosa significantly reduced the severity and course of radiation-induced OM. PK studies demonstrated that both living L. lactis bacteria, as well as the hTFF1 secreted, could be recovered from the administration site for maximum 24h post-dosing, without systemic exposure. The in vitro and in vivo safety pharmacology studies confirmed that L. lactis sAGX0085 could not survive in systemic circulation, not even under neutropenic conditions. The results from the PD, PK and safety pharmacology studies reported here indicate that in situ secretion of hTFF1 by topically administered L. lactis bacteria provides a safe and efficacious therapeutic tool for the prevention and treatment of OM.

100 Deals associated with Dapatifagene navolactibac

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Head and Neck Neoplasms	NDA/BLA	BE	Oragenics, Inc.	18 Jul 2017
Stomatitis	NDA/BLA	US	Oragenics, Inc.	18 Jul 2017
Stomatitis	NDA/BLA	DE	Oragenics, Inc.	18 Jul 2017
Stomatitis	NDA/BLA	BE	Oragenics, Inc.	18 Jul 2017
Stomatitis	NDA/BLA	GB	Oragenics, Inc.	18 Jul 2017
Stomatitis	Phase 1	US	Oragenics, Inc.	18 Jul 2017
Head and Neck Neoplasms	Discovery	BE	Oragenics, Inc.	18 Jul 2017
Stomatitis	Discovery	GB	Oragenics, Inc.	18 Jul 2017
Stomatitis	Discovery	DE	Oragenics, Inc.	18 Jul 2017
Stomatitis	Discovery	BE	Oragenics, Inc.	18 Jul 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03234465 (CTgov)	Phase 2	Stomatitis \| Head and Neck Neoplasms	200	AG013 (AG013)	yesyiqcmpf(pgghhrvfja) = tybhyflhln kgtuqmemgw (xwoolixuel, rbnglsythu - kipypptbws) View more	-	23 Nov 2020
				placebo (Placebo)	yesyiqcmpf(pgghhrvfja) = aptmopgapp kgtuqmemgw (xwoolixuel, wsqoogkbcx - uqtfyyltjo) View more
NCT00938080 (Pubmed \| Cancer) Manual	Phase 1	Head and Neck Neoplasms	52	AG013	ijljumkrnm(zqbytzjtwm) = xicjdzwsss ezjdovpkbu (chjtlzjmyh ) View more	Positive	15 Dec 2013
				Placebo	-