Delving into the Latest Updates on Parvovirus H-1(Oryx Gmbh & Co) with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

ParvOryx, Parvovirus-anticancer-ParvOryx, Parvovirus-antitumour-ParvOryx

+ [3]

Target-

Mechanism

Cell membrane modulators, Immunomodulators

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [4]

Active Indication

GlioblastomaPancreatic CancerMelanoma+ [2]

Inactive Indication

Glioblastoma MultiformeOvarian CancerPancreatic adenocarcinoma metastatic+ [1]

Originator Organization

Oryx Gmbh & Co

Active Organization

ORYX GmbH & Co. KGOryx Gmbh & Co

Inactive Organization

Oryx Southern Delaware Holdings LLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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The oncolytic rodent protoparvovirus H-1PV has been successfully used in phase I/II clinical trials to treat recurrent glioblastoma multiforme and pancreatic cancer. The present work focuses on the stability and environmental safety of the H-1PV drug product from production up to its use in patients. We identified hold-steps in manufacturing for up to 3 months and showed 7-years stability for the optimal product formulation. Stress testing via UV, temperature, and pH also determined that the drug product is stable. De- and rehydration for lyophilization simulation are possible without infectious virus loss. Furthermore, we prove in-use stability for 4 days at room temperature and show no virus adsorption to injection devices, guaranteeing the correct administration dose. Iodixanol in the formulation, resulting in high viscosity, protects H-1PV against UV and some disinfectants. Nonetheless, H-1PV is depleted with rapid heat deactivation, autoclavation, and nanofiltration. Assessment of chemical disinfectants that are currently recommended by the Robert Koch-Institute demonstrated that ethanol-based hand disinfectants are not effective; however, aldehyde-based disinfectants for surfaces and instruments demonstrate sufficient H-1PV deactivation in aqueous formulations by 4 to 6 log₁₀. With these results, we could establish a specific hygiene plan for all involved facilities from manufacturing to patient application. Overall, using 48% Iodixanol in Visipaque/Ringer as a drug formulation stabilizes H-1PV infectivity over years and protects against virus loss from short-term UV, low pH, and temperature exposure. KEY POINTS: • Optimal formulation of drug product protects the H-1PV protoparvovirus against UV, temperatures up to 50 °C, and low pH (> 1.25), stabilizing the virus during manufacturing, storage, transport, and application. • H-1PV is stable during in-use and does not adsorb to injection devices during patient administration. • Hygiene plan for H-1PV with physicochemical methods has been established.

17 Apr 2023·Pathogens (Basel, Switzerland)

Oncolytic Rodent Protoparvoviruses Evade a TLR- and RLR-Independent Antiviral Response in Transformed Cells.

Article

Author: Detje, Claudia N ; Nüesch, Jürg P F ; Ungerechts, Guy ; Santiago, Estelle ; Grewenig, Annabel ; Daeffler, Laurent ; Kalinke, Ulrich ; Pierrard, Kristina ; Angelova, Assia ; Rommelaere, Jean

The oncolytic rodent protoparvoviruses (PVs) minute virus of mice (MVMp) and H-1 parvovirus (H-1PV) are promising cancer viro-immunotherapy candidates capable of both exhibiting direct oncolytic activities and inducing anticancer immune responses (AIRs). Type-I interferon (IFN) production is instrumental for the activation of an efficient AIR. The present study aims at characterizing the molecular mechanisms underlying PV modulation of IFN induction in host cells. MVMp and H-1PV triggered IFN production in semi-permissive normal mouse embryonic fibroblasts (MEFs) and human peripheral blood mononuclear cells (PBMCs), but not in permissive transformed/tumor cells. IFN production triggered by MVMp in primary MEFs required PV replication and was independent of the pattern recognition receptors (PRRs) Toll-like (TLR) and RIG-like (RLR) receptors. PV infection of (semi-)permissive cells, whether transformed or not, led to nuclear translocation of the transcription factors NFĸB and IRF3, hallmarks of PRR signaling activation. Further evidence showed that PV replication in (semi-)permissive cells resulted in nuclear accumulation of dsRNAs capable of activating mitochondrial antiviral signaling (MAVS)-dependent cytosolic RLR signaling upon transfection into naïve cells. This PRR signaling was aborted in PV-infected neoplastic cells, in which no IFN production was detected. Furthermore, MEF immortalization was sufficient to strongly reduce PV-induced IFN production. Pre-infection of transformed/tumor but not of normal cells with MVMp or H-1PV prevented IFN production by classical RLR ligands. Altogether, our data indicate that natural rodent PVs regulate the antiviral innate immune machinery in infected host cells through a complex mechanism. In particular, while rodent PV replication in (semi-)permissive cells engages a TLR-/RLR-independent PRR pathway, in transformed/tumor cells this process is arrested prior to IFN production. This virus-triggered evasion mechanism involves a viral factor(s), which exert(s) an inhibitory action on IFN production, particularly in transformed/tumor cells. These findings pave the way for the development of second-generation PVs that are defective in this evasion mechanism and therefore endowed with increased immunostimulatory potential through their ability to induce IFN production in infected tumor cells.

01 Dec 2021·Applied Microbiology and BiotechnologyQ3 · ENGINEERING & TECHNOLOGY

Upstream process optimization and micro- and macrocarrier screening for large-scale production of the oncolytic H-1 protoparvovirus

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Müller, Marcus ; Leuchs, Barbara ; Vogel, Martin ; Phan, Linh Minh Phuc ; Wohlfarth, Daniel ; Brunecker, Adrian ; Frehtman, Veronika

AbstractThe oncolytic virus H-1PV is a promising candidate for various cancer treatments. Therefore, production process needs to be optimized and scaled up for future market release. Currently, the virus is produced with minimum essential medium in 10-layer CellSTACK® chambers with limited scalability, requiring a minimum seeding density of 7.9E3 cells/cm2. Production also requires a 5% fetal bovine serum (FBS) supplementation and has a virus yield up to 3.1E7 plaque-forming units (PFU)/cm2. Using the animal-free cell culture medium VP-SFM™ and a new feeding strategy, we demonstrate a yield boost by a mean of 0.3 log while reducing seeding density to 5.0E3 cells/cm2 and cutting FBS supplementation by up to 40% during the production process. Additionally, FBS is completely removed at the time of harvest. Eleven commercial micro- and macrocarriers were screened regarding cell growth, bead-to-bead transfer capability, and virus yield. We present a proof-of-concept study for producing H-1PV on a large scale with the microcarrier Cytodex® 1 in suspension and a macrocarrier for a fixed-bed iCELLis® bioreactor. A carrier-based H-1PV production process combined with an optimized cell culture medium and feeding strategy can facilitate future upscaling to industrial-scale production.Key points• Virus yield increase and FBS-free harvest after switching to cell culture medium VP-SFM™.• We screened carriers for cell growth, bead-to-bead transfer capability, and H-1PV yield.• High virus yield is achieved with Cytodex® 1 and macrocarrier for iCellis® in Erlenmeyer flasks.

100 Deals associated with Parvovirus H-1(Oryx Gmbh & Co)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 2	DE	ORYX GmbH & Co. KG	30 Jan 2022
Non-Small Cell Lung Cancer	Phase 2	DE	ORYX GmbH & Co. KG	30 Jan 2022
Pancreatic Ductal Adenocarcinoma	Phase 2	DE	ORYX GmbH & Co. KG	30 Jan 2022
Glioblastoma	Phase 2	-	Oryx Gmbh & Co	-
Pancreatic Cancer	Phase 2	-	Oryx Gmbh & Co	-
Ovarian Cancer	Discovery	DE	Oryx Southern Delaware Holdings LLC	21 Oct 2019
Pancreatic adenocarcinoma metastatic	Discovery	DE	ORYX GmbH & Co. KG	01 Dec 2015
Pancreatic Ductal Carcinoma	Discovery	DE	ORYX GmbH & Co. KG	01 Dec 2015
Secondary malignant neoplasm of pancreas	Discovery	DE	ORYX GmbH & Co. KG	01 Dec 2015
Glioblastoma Multiforme	Discovery	DE	ORYX GmbH & Co. KG	01 Sep 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02653313 (Pubmed \| Clin Cancer Res) Manual	Phase 2	Metastatic Pancreatic Ductal Adenocarcinoma	-	ParvOryx	(xlpjechltg) = pumwgffbrn gbypvaihpt (tdhqmdxqgv ) View more	Positive	15 Oct 2021
NCT01301430 (ParvOryx01, ASCO2014)	Phase 1	Recurrent Glioblastoma	18	parvovirus h-1 (Arm A)	iemhkzemuf(klsbpiizqe) = vjgipamfgo ezbghdqyaz (kkypwzvznm )	-	20 May 2014
NCT01301430 (ParvOryx01, ASCO2014)	Phase 1	Recurrent Glioblastoma	18	parvovirus h-1 (Arm B)	iemhkzemuf(klsbpiizqe) = yfdorwockb ezbghdqyaz (kkypwzvznm )	-	20 May 2014