Delving into the Latest Updates on T cell replacement therapy (Kiadis Pharma) with Synapse

Overview

Basic Info

Drug Type

T-lymphocyte cell therapy

Synonyms

Reviroc, Rhitol, T cell replacement therapy TH9402

+ [3]

Target-

Mechanism

Immunologic cytotoxicity, T lymphocyte replacements

Therapeutic Areas

Immune System DiseasesNeoplasmsHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaBeta-Thalassemia+ [5]

Originator Organization

University of Montréal

Active Organization-

Inactive Organization

Kiadis Pharma BV

Drug Highest PhaseDiscontinuedNDA/BLA

First Approval Date-

Regulation-

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A Phase III, Multicenter, Randomized Controlled Study to Compare Safety and Efficacy of a Haploidentical HSCT and Adjunctive Treatment With ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells, Versus a Haploidentical HSCT With Post-transplant Cyclophosphamide in Patients With a Hematologic Malignancy

The primary objective of this study is to compare safety and efficacy of a haploidentical T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.

Start Date29 Nov 2017

Sponsor / Collaborator

Kiadis Pharma BV

EUCTR2016-002959-17-GB / Not yet recruitingPhase 1/2

An exploratory, open-label study to evaluate the safety and feasibility of ATIR201, a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment), as adjuvant treatment to a T-cell depleted haploidentical hematopoietic stem cell transplantation in patients with beta-thalassemia major

Start Date02 Dec 2016

Sponsor / Collaborator

Kiadis Pharma Netherlands BV

NCT02500550 / CompletedPhase 2

An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

The purpose of this study is to determine whether a repeat dose administration of ATIR101 is safe and effective when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor. All patients are planned to receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or halted for safety reasons.

Start Date09 Oct 2015

Sponsor / Collaborator

Kiadis Pharma BV

100 Clinical Results associated with T cell replacement therapy (Kiadis Pharma)

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100 Translational Medicine associated with T cell replacement therapy (Kiadis Pharma)

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100 Patents (Medical) associated with T cell replacement therapy (Kiadis Pharma)

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3

Literatures (Medical) associated with T cell replacement therapy (Kiadis Pharma)

01 Jul 2020·LeukemiaQ1 · MEDICINE

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

Q1 · MEDICINE

Article

Author: Bonig, Halvard ; Santi, Irene ; Olavarria, Eduardo ; Wang, Kun ; Roy, Denis Claude ; Lachance, Sylvie ; Buyse, Marc ; Sandler, Andrew ; Rovers, Jeroen ; Walker, Irwin ; Maertens, Johan ; Velthuis, Jurjen ; Lewalle, Philippe ; Mielke, Stephan ; Selleslag, Dominik

AbstractOvercoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.

01 Sep 2019·British Journal of HaematologyQ2 · MEDICINE

Allodepleted T‐cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft‐versus‐host disease (GVHD) in the absence of GVHD prophylaxis

Q2 · MEDICINE

Article

Author: Ahmad, Imran ; Delisle, Jean‐Sébastien ; Sauvageau, Guy ; Boumédine, Radia S. ; Bernard, Lea ; Cohen, Sandra ; Mielke, Stephan ; Roy, Jean ; Busque, Lambert ; Perreault, Claude ; Bambace, Nadia ; Guertin, Marie‐Claude ; Kiss, Thomas ; Roy, Denis Claude ; Rezvani, Katayoun ; Lachance, Sylvie

SummaryGraft‐versus‐host disease (GVHD) is a major cause of transplant‐related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T‐cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose‐finding study, 19 adults (median age: 54 years) with high‐risk haematological malignancies were treated with T‐cell‐depleted human leucocyte antigen‐haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 × 104–5 × 106 CD3+ cells/kg (median 31 days post‐transplant). No patient received post‐transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long‐term follow ‐up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0·3–2 × 106 CD3+ cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse‐related mortality was 33% and overall survival was 67% in these patients.

06 Jan 2012·Circulation ResearchQ1 · MEDICINE

The Perlecan Fragment LG3 Is a Novel Regulator of Obliterative Remodeling Associated With Allograft Vascular Rejection

Q1 · MEDICINE

Article

Author: Hébert, Marie-Josée ; Brassard, Nathalie ; Soulez, Mathilde ; Dieudé, Mélanie ; Durocher, Yves ; Madore, François ; Wu, Shyh-Jong ; Perreault, Claude ; Qi, Shijie ; Pilon, Eve-Annie ; Cardinal, Héloïse

Rationale:Endothelial apoptosis is increased in association with acute and chronic vascular rejection (VR) of solid allografts. Apoptotic endothelial cells (EC) release LG3, a C-terminal fragment of perlecan of potential importance in vascular remodeling and neointima formation.Objective:Our 2 goals were to determine whether circulating levels of LG3 are increased in association with acute VR of renal allografts and to evaluate the impact of LG3 on vascular remodeling.Methods and Results: We conducted a case-control study to compare serum LG3 levels in human renal transplant patients with acute VR, tubulo-interstitial rejection (ATIR) and normal graft function. Aorta transplantation between fully MHC-mismatched mice in association with intravenous LG3 injection was used to characterize the impact of LG3 on vascular remodeling. Scratch assays evaluated the promigratory activity of LG3 on vascular smooth muscle cells (VSMC) in vitro. Serum LG3 levels were significantly elevated in human renal transplant patients with acute VR ( n =16) compared to ATIR ( n =16) and normal graft function ( n =32, P =0.004). In patients with acute VR, graft loss was associated with elevated LG3 levels. Increasing LG3 serum levels in aortic allograft recipients significantly increased neointima formation. LG3 injection fostered accumulation of α-smooth muscle actin–positive cells and decreased the number of CD31 positive EC. LG3 increased the migration of VSMC through extracellular signal-regulated kinases 1/2-dependent pathways. Conclusion:These results indicate that LG3 is a novel regulator of obliterative vascular remodeling during rejection.

1

News (Medical) associated with T cell replacement therapy (Kiadis Pharma)

19 Aug 2016

·www.biospace.com

Kiadis Pharma Notice Of Results For The Six Months Ended 30 June 2016

Amsterdam, The Netherlands, August 19, 2016 – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company developing innovative T-cell immunotherapy treatments for blood cancers and inherited blood disorders, today announces that it will report its half year results for the six months ended 30 June 2016 on August 26, 2016. About Kiadis Pharma Kiadis Pharma is focused on cell-based immunotherapy products for the treatment of blood cancers and inherited blood disorders. The Company’s products have the potential to address the risks and limitations connected with allogeneic hematopoietic stem cell transplantation (HSCT), namely Graft-versus-Host-Disease (GVHD), cancer relapse, opportunistic infections and limited matched donor availability. The Company believes that HSCT could become a first-choice treatment for blood cancers, inherited blood disorders and possibly autoimmune diseases and solid organ transplantations. In April 2016, the Company reported positive Phase II results with its lead product ATIR101™ in patients with blood cancer. The data showed that ATIR101™ significantly reduced Transplant Related Mortality and significantly improved Overall Survival. In addition, ATIR101™ did not elicit grade III-IV GVHD in any patient. ATIR101™ has been granted Orphan Drug Designations both in the US and Europe. The Company’s second product candidate, ATIR201™, addresses inherited blood disorders with an initial focus on thalassemia, a disease which results in destruction of red blood cells in patients. ATIR201™ is expected to enter Phase I/II clinical development in the second half of 2016. Kiadis Pharma, based in Amsterdam, The Netherlands, was granted an Advanced Therapy Medicinal Product (ATMP) certificate for manufacturing quality and non-clinical data by the European Medicines Agency (EMA). The Company’s shares are listed on Euronext Amsterdam and Euronext Brussels. For more information visit

Orphan DrugImmunotherapy

100 Deals associated with T cell replacement therapy (Kiadis Pharma)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Myelodysplastic Syndromes	NDA/BLA	NL	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	IT	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	IL	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	SE	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	BE	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	DE	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	HR	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	GB	Kiadis Pharma BV	29 Nov 2017
Myelodysplastic Syndromes	NDA/BLA	US	Kiadis Pharma BV	29 Nov 2017
Graft vs Host Disease	NDA/BLA	EU	Kiadis Pharma BV	19 Apr 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02999854 (CR-AIR-009 HATCY \| HATCY, CTgov)	Phase 3	Acute Myeloid Leukemia \| Acute Lymphoblastic Leukemia \| Myelodysplastic Syndromes	63	T-cell depleted HSCT from a related, haploidentical donor+ATIR101 (ATIR101)	slpsqwgfbi(ycyepyvpzv) = shvdfuhmio mnwgitayts (awaequcvos, vyflgvcpyw - pcmzbreizz) View more	-	24 May 2022
				T-cell replete HSCT from a related, haploidentical donor+Cyclophosphamide (PTCy)	slpsqwgfbi(ycyepyvpzv) = mtlnexgebd mnwgitayts (awaequcvos, zyrmiltgvv - yawnjfijpl) View more
NCT00967343 (CTgov)	Phase 2/3	Acute Lymphoblastic Leukemia \| Multiple Myeloma \| Myeloid Leukemia \| Myeloproliferative Disorders \| Myelodysplastic Syndromes	40	Donor lymphocyte preparation depleted of host functional alloreactive T-cells	jtubmwkibr(bevssmaetk) = bhgjqvirge vadgdykqnz (glvifjsskt, obgvnnevvn - qolmuxgtha) View more	-	12 Jan 2021
NCT02500550 (CR-AIR-008, CTgov)	Phase 2	Acute Myeloid Leukemia \| Acute Lymphoblastic Leukemia \| Myelodysplastic Syndromes	15	Non-TBI regime+ATIR101	qrozznmyzc(pbmtfrbprg) = pdplmscxyc yvocwtttgs (mbuqchwivd, fewmrksodl - tycccfzkpa) View more	-	12 Jan 2021
NCT01794299 (CTgov)	Phase 2	Acute Myeloid Leukemia \| Acute Lymphoblastic Leukemia \| Myelodysplastic Syndromes	31	ATIR	(gnkampzugc) = ezchzvhaax vcmlpzuydk (ayjcgypcmu, hzwtsmnvle - oknrxopyai) View more	-	12 Jan 2021
NCT02500550 (CR-AIR-008, EHA2019)	Phase 2	-	17	ATIR101 single dose	(ixbnfsipxw) = ohorrpjeez lemzmpupqc (swjyvvflrx ) View more	-	14 Jun 2019
				ATIR101 double dose	(ixbnfsipxw) = swlgcarrag lemzmpupqc (swjyvvflrx ) View more
NCT01794299 \| NCT02500550 (CR-AIR-007 \| CR-AIR-008, Tandem Meetings ASTCT and CIBMTR2019)	Phase 2	-	37	ATIR101	fhtxzswfdd(jaychjszch) = exhrtgwpdq yteupoxesb (tqweledaku, all grade III) View more	Positive	01 Mar 2019
				ATIR101 (Control group)	fhtxzswfdd(jaychjszch) = bkvyprtynk yteupoxesb (tqweledaku ) View more
NCT01794299 (CR-AIR-007, EBMT2018)	Phase 2	-	23	ATIR101	lizcclqzah(necevfyxke) = hkgyialclo artluczuil (gulplczyet ) View more	Positive	24 Sep 2018
				ATIR101	lizcclqzah(necevfyxke) = vdigtbqpsd artluczuil (gulplczyet ) View more
PI-01 (AUA2014)	Not Applicable	Multiple Endocrine Neoplasia	300	Testosterone replacement therapy (TRT)	lsbhpnvaop(ivniwdewok) = ommpdefigc jgkfinotyx (sbkumuzjpf )	-	01 Apr 2014