A Phase 1/2 Study of a Combination of FCX-013 (Genetically-Modified Autologous Human Dermal Fibroblasts) Plus Veledimex for the Treatment of Moderate to Severe Localized Scleroderma (Morphea)

A two-component therapeutic consisting of FCX-013 and veledimex for the treatment of localized scleroderma (or morphea). The first component, FCX-013, is autologous human fibroblasts genetically-modified using lentivirus and encoded for matrix metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen. FCX-013 is designed to be injected under the skin at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation. With the FCX-013 therapy, the patient will take an oral compound (Veledimex) to induce MMP-1 protein expression from the injected cells. Once the fibrosis is resolved, the patient will stop taking the oral compound which will stop further MMP-1 production from the injected cells. FCX-013 plus veledimex is being developed in anticipation of improving skin function in patients by resolving fibrotic lesions and normalizing dermal collagen production

Start Date18 Dec 2019

Sponsor / Collaborator-

NCT04006119 / CompletedPhase 2

A Phase II Study of Ad-RTS-hIL-12 + Veledimex in Combination With Cemiplimab-rwlc (Libtayo®) in Subjects With Recurrent or Progressive Glioblastoma

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
Cemiplimab-rwlc (Libtayo) is an antibody (a kind of human protein) that is being tested to see if it will allow the body's immune system to work against glioblastoma tumors. Libtayo (cemiplimab-rwlc) is currently FDA approved in the United States for metastatic cutaneous cell carcinoma (CSCC), but is not approved in glioblastoma. Cemiplimab-rwlc may help your immune system detect and attack cancer cells. Ad-RTS-hIL-12 and veledimex will be given in combination with cemiplimab-rwlc to enhance the IL-12 mediated effect observed to date.
The main purpose of this study is to evaluate the safety and efficacy of a single tumoral injection of Ad-RTS-hIL-12 given with oral veledimex in combination with cemiplimab-rwlc.

Start Date01 Aug 2019

Sponsor / Collaborator

Alaunos Therapeutics, Inc.

NCT03679754 / CompletedPhase 1

Protocol ATI001-102 Expansion Substudy: Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma

Start Date05 Sep 2018

Sponsor / Collaborator

Alaunos Therapeutics, Inc.

100 Clinical Results associated with Veledimex

100 Translational Medicine associated with Veledimex

100 Patents (Medical) associated with Veledimex

Literatures (Medical) associated with Veledimex

01 Jun 2018·Cancer Gene TherapyQ2 · MEDICINE

Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma

Q2 · MEDICINE

Article

Author: Cai, Hongliang ; Barrett, John A ; Miao, John ; Cooper, Laurence J N ; Sharma, Geeta ; Gonzalez, Paul ; Khare, Pranay D ; Lebel, Francois ; Dalsing-Hernandez, Jessica ; Chan, Tim

The purpose of this study was to determine if localized delivery of IL-12 encoded by a replication-incompetent adenoviral vector engineered to express IL-12 via a RheoSwitch Therapeutic System^® (RTS^®) gene switch (Ad-RTS-IL-12) administered intratumorally which is inducibly controlled by the oral activator veledimex is an effective approach for glioma therapy. Mice bearing 5-10-day-old intracranial GL-261 gliomas were intratumorally administered Ad-RTS-mIL-12 in which IL-12 protein expression is tightly controlled by the activator ligand, veledimex. Local tumor viral vector levels concomitant with veledimex levels, IL-12-mRNA expression, local and systemic cytokine expression, tumor and systemic flow cytometry and overall survival were studied. Ad-RTS-mIL-12+veledimex elicited a dose-related increase in tumor IL-12 mRNA and IL-12 protein and discontinuation of veledimex resulted in a return to baseline levels. These changes correlated with local immune and antitumor responses. Veledimex crossed the blood-brain barrier in both orthotopic GL-261 mice and cynomolgus monkeys. We have demonstrated that this therapy induced localized controlled production of IL-12 which correlates with an increase in tumor-infiltrating lymphocytes (TILs) leading to the desired biologic response of tumor growth inhibition and regression. At day 85 (study termination), 65% of the animals that received veledimex at 10 or 30 mg/m²/day were alive and tumor free. In contrast, the median survival for the other groups were: vehicle 23 days, bevacizumab 20 days, temozolomide 33 days and anti-PD-1 37 days. These findings suggest that the controlled intratumoral production of IL-12 induces local immune cell infiltration and improved survival in glioma, thereby demonstrating that this novel regulated immunotherapeutic approach may be an effective form of therapy for glioma.

01 May 2017·Clinical Pharmacology in Drug Development

Plasma Pharmacokinetics of Veledimex, a Small‐Molecule Activator Ligand for a Proprietary Gene Therapy Promoter System, in Healthy Subjects

Article

Author: Krishman, Suma ; Cai, Hongliang ; Lebel, Francois ; Barrett, John A. ; Miao, John ; Sun, Lei

AbstractMajor obstacles to developing effective immunotherapy are the ability of tumors to escape the immune system and the toxicity associated with systemic administration. To overcome these challenges, a gene delivery platform technology, RheoSwitch Therapeutic System (RTS), has been developed to enable the regulated expression of a target gene, Ad‐RTS‐IL‐12, administered intratumorally, where IL‐12 expression is controlled via the administration of an oral activator ligand, veledimex. Pharmacokinetics in healthy human subjects indicated that veledimex plasma exposure increased with increasing dose after single‐ and multiple‐dose administration in Labrasol slurry and F‐22 capsule formulations. No apparent formulation or sex‐related difference in veledimex pharmacokinetics (PK) was observed. Minimal or no plasma accumulation of veledimex was observed after once‐daily oral administration for 14 days. Veledimex steady state in plasma was reached after 5 daily doses. Food consumption prior to veledimex administration prolonged and enhanced absorption with no impact on the elimination rate and extent of metabolism of veledimex, resulting in significantly increased systemic exposure to veledimex and its 2 major circulating metabolites. Overall, veledimex was well tolerated and exhibited a PK profile supportive of once‐daily dosing. For enhanced efficacy, veledimex should be taken under fed conditions to ensure optimal absorption and sufficient systemic exposure.

100 Deals associated with Veledimex

External Link

KEGG	Wiki	ATC	Drug Bank
D10678	-	-	DB12170

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Scleroderma, Localized	Phase 2	US	Castle Creek Biosciences, Inc.Startup	18 Dec 2019
Scleroderma, Systemic	Phase 2	US	Castle Creek Biosciences, Inc.Startup	18 Dec 2019
Recurrent Glioblastoma	Phase 2	US	Alaunos Therapeutics, Inc.	01 Aug 2019
Diffuse Intrinsic Pontine Glioma	Phase 2	US	Alaunos Therapeutics, Inc.	26 Sep 2017
Pediatric Cerebellar Astrocytoma	Phase 2	US	Alaunos Therapeutics, Inc.	26 Sep 2017
Breast Cancer	Phase 2	US	Alaunos Therapeutics, Inc.	01 Jul 2015
Locally advanced breast cancer	Phase 2	US	Alaunos Therapeutics, Inc.	01 Jul 2015
Metastatic breast cancer	Phase 2	US	Alaunos Therapeutics, Inc.	01 Jul 2015
Glioblastoma Multiforme	Phase 2	US	Alaunos Therapeutics, Inc.	01 Jun 2015
Melanoma	Phase 2	US	Alaunos Therapeutics, Inc.	01 Aug 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03740724 (CTgov)	Phase 1/2	Scleroderma, Systemic \| Scleroderma, Localized	1	veledimex+FCX-013	ljleajzgob(qiwbrwupuv) = myjaxlckux rdblxkvdvn (btnnfhqokx, bzsetrodiy - ibmgreebwe) View more	-	24 Jun 2022
NCT03636477 (Pubmed \| Neuro Oncol) Manual	Phase 1	Recurrent Glioblastoma	21	Veledimex+Cemiplimab-RWLC+INXN-2001+Nivolumab	(wiswjvzcty) = gumouwcczp amnwwzkzkq (mvevihxilj ) View more	Positive	26 Nov 2021
NCT02026271 (ASCO2017)	Phase 1	Recurrent Glioblastoma	25	Ad-RTS-hIL-12 + veledimex 20 mg	(mkpwyllfnq) = purnebrxmt llrqnbrini (efuakjassf ) View more	-	30 May 2017
NCT02026271 (ASCO2017)	Phase 1	Recurrent Glioblastoma	25	Ad-RTS-hIL-12 + veledimex 30 mg	xrqquvuhuy(rwkyozvtkp) = urmtwyosfl lybktylxgy (bkhrsnrpli ) View more	-	30 May 2017
NCT02026271 (ASCO2016)	Phase 1	Recurrent Glioma	7	Ad-RTS-IL-12 + oral veledimex	gbbnxbrejn(kkxplytvth) = AD+V was well tolerated with expected toxicities promptly reversing with discontinuance of V qjnljgbnut (oodexmailj ) View more	Positive	20 May 2016
NCT01397708 (Phase I, ASGCT2013)	Phase 1	Melanoma IFN-γ	14	Ad-RTS®-hIL-12 (1x10 12 viral particles)	qrsfmfcfnw(cawrpdxmqm) = agceqzdyue meatfjueii (gjnbmrjrxg ) View more	Positive	01 May 2013
NCT01397708 (Phase I, ASGCT2013)	Phase 1	Melanoma IFN-γ	14	INXN-1001 (5mg)	qrsfmfcfnw(cawrpdxmqm) = ppjhykdnfg meatfjueii (gjnbmrjrxg ) View more	Positive	01 May 2013

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