Delving into the Latest Updates on Veledimex with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Veledimex (USAN/INN)

+ [1]

Target-

Action-

Mechanism-

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [2]

Active Indication-

Inactive Indication

Breast CancerDiffuse Intrinsic Pontine GliomaGlioblastoma Multiforme+ [9]

Originator Organization

Alaunos Therapeutics, Inc.

Active Organization-

Inactive Organization

Alaunos Therapeutics, Inc.

Castle Creek Biosciences, Inc.Startup

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC27H38N2O3

InChIKeyLZWZPGLVHLSWQX-XMMPIXPASA-N

CAS Registry1093130-72-3

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

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.
The main purpose of this study is to evaluate the safety and tolerability of a single intratumoral injection of Ad-RTS-hIL-12 given with oral veledimex.

Start Date05 Sep 2018

Sponsor / Collaborator

Alaunos Therapeutics, Inc.

100 Clinical Results associated with Veledimex

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100 Translational Medicine associated with Veledimex

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100 Patents (Medical) associated with Veledimex

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5

Literatures (Medical) associated with Veledimex

01 Jun 2022·Neuro-OncologyQ1 · MEDICINE

Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial

Q1 · MEDICINE

Article

Author: Hadar, Nira ; Chen, Clark C ; Wen, Patrick Y ; Loewy, John ; Truman, Kyla ; Chadha, Kamal ; Triggs, Dan ; Chiocca, E Antonio ; Reardon, David A ; Amidei, Christina ; Buck, Jill Y ; Lukas, Rimas V ; Estupinan, Taylor ; Rao, Ganesh ; Miao, John ; Demars, Nathan ; Seften, Leah ; Tringali, Joseph ; Bi, Wenya Linda ; Gelb, Arnold B ; Peruzzi, Pierpaolo ; Cooper, Laurence ; Grant, James ; Park, Grace

AbstractBackgroundVeledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition.MethodsAn open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery.ResultsToxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months.ConclusionThe safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).

14 Aug 2019·Science Translational MedicineQ1 · MEDICINE

Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial

Q1 · MEDICINE

Article

Author: Chiocca, E. Antonio ; Demars, Nathan ; Triggs, Daniel A. ; Naik, Ajay ; Stopa, Brittany M. ; Barrett, John A. ; Lukas, Rimas V. ; Reardon, David A. ; Yamini, Bakhtiar ; Kumthekar, Priya ; Gelb, Arnold B. ; Buck, Jill Y. ; Solomon, Isaac H. ; Lebel, Francois ; Wen, Patrick ; Nakashima, Hiroshi ; Yu, John S. ; Ligon, Keith L. ; Hu, Jethro L. ; Cooper, Laurence J. N. ; Rudnick, Jeremy ; Zhou, John

An oral small molecule turns on the transcription of human interleukin-12, with biological effects in patients with recurrent high-grade gliomas.

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 ; Sharma, Geeta ; Cooper, Laurence J N ; Khare, Pranay D ; Gonzalez, Paul ; 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.

100 Deals associated with Veledimex

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External Link

KEGG	Wiki	ATC	Drug Bank
D10678	-	-	DB12170

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Scleroderma, Localized	Phase 2	United States	Castle Creek Biosciences, Inc.Startup	18 Dec 2019
Scleroderma, Systemic	Phase 2	United States	Castle Creek Biosciences, Inc.Startup	18 Dec 2019
Recurrent Glioblastoma	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Aug 2019
Diffuse Intrinsic Pontine Glioma	Phase 2	United States	Alaunos Therapeutics, Inc.	26 Sep 2017
Pediatric Cerebellar Astrocytoma	Phase 2	United States	Alaunos Therapeutics, Inc.	26 Sep 2017
Breast Cancer	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Jul 2015
Locally advanced breast cancer	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Jul 2015
Metastatic breast cancer	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Jul 2015
Melanoma	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Aug 2011
Unresectable Melanoma	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Apr 2009

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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	hfnwdjqffj(obljhfguvh) = zecjknveoo ijlxbpkhxy (krxabumcyz, aaqyxdjtuj - dkafconlzr) View more	-	24 Jun 2022
NCT03636477 (Pubmed \| Neuro Oncol) Manual	Phase 1	Recurrent Glioblastoma	21	Veledimex+Cemiplimab-RWLC+INXN-2001+Nivolumab	(xbjnjbkaqf) = ypphfohwvy zewqbpobzj (bdxroyghue ) View more	Positive	26 Nov 2021
NCT03679754 (ASCO2019)	Phase 1	Recurrent Glioblastoma	36	Ad-RTS-hIL-12 + Veledimex	(zipfiqlljw) = mild to moderate cytokine release syndrome (CRS) characterized by flu-like symptoms krekkpvgos (dufvuzhkaq )	Positive	26 May 2019
				Low-dose dexamethasone
SNO2018	Phase 1	Recurrent Glioblastoma	-	Ad-RTS-hIL-12 + Veledimex 20mg	jugzydamxf(bcwggkuasc) = increased TEAEs observed above V 20-mg ohjduchybp (lhgictsfph ) View more	Positive	05 Nov 2018
				Ad-RTS-hIL-12 + Veledimex 10mg
NCT02026271 (ASCO2017)	Phase 1	Recurrent Glioblastoma	25	Ad-RTS-hIL-12 + veledimex 20 mg	(kiqdjmrgki) = obeyxhvkau kgzblqutes (csetjjoqmv ) View more	-	30 May 2017
				Ad-RTS-hIL-12 + veledimex 30 mg	hlfnfenhne(efdpgztonk) = ochvibxzdl wxjzbpngpu (nkysqhcmni ) View more
ATIM-23 (SNO2016)	Phase 1	High grade glioma	13	Ad-RTS-hIL-12 2x10^11vp + Veledimex 20mg	svkoucnxsi(wwchslvano) = zftrksetqk tcbibjobag (tqlusdjnya ) View more	Positive	07 Nov 2016
				Ad-RTS-hIL-12 2x10^11vp + Veledimex 40mg	svkoucnxsi(wwchslvano) = stbywonsai tcbibjobag (tqlusdjnya ) View more
NCT02026271 (ASCO2016)	Phase 1	Recurrent Glioma	7	Ad-RTS-IL-12 + oral veledimex	uawkopizxa(bfgpucgnsl) = AD+V was well tolerated with expected toxicities promptly reversing with discontinuance of V puufndwxkh (utzplcvvxl ) View more	Positive	20 May 2016
NCT01397708 (Phase I, ASGCT2013)	Phase 1	Melanoma IFN-γ	14	Ad-RTS®-hIL-12 (1x10 12 viral particles)	kyuahufzvp(eqxkslyfas) = kyygdbagla qytjjkhwlr (foojxjvhov ) View more	Positive	01 May 2013
				INXN-1001 (5mg)	kyuahufzvp(eqxkslyfas) = hvmohqirmr qytjjkhwlr (foojxjvhov ) View more