Rhitol (allodepleted T-cell immunotherapeutics) / Sanofi - LARVOL DELTA

[VIRTUAL] Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid- Refractory or Dependent Chronic Gvhd - a Multicentre Phase II Clinical Trial (CARE Trial). (TCT-ASTCT-CIBMTR 2021) - "Objectives We sought to determine the safety and preliminary efficacy of TH9402-based photodynamic therapy (TH-PDT), a new type of phototherapy that does not involve frequent apheresis, in the multicentre CARE trial sponsored by the Canadian Donation & Transplantation Research Program (CDTRP)...Project funded by the Canadian Donation & Transplantation Research Program (CDTRP). Acknowledgement: Daphne Brockington (UBC), study coordinator."

Clinical • P2 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid- Refractory or Dependent Chronic Gvhd - a Multicentre Phase II Clinical Trial (CARE Trial). (TCT-ASTCT-CIBMTR 2021) - "Objectives We sought to determine the safety and preliminary efficacy of TH9402-based photodynamic therapy (TH-PDT), a new type of phototherapy that does not involve frequent apheresis, in the multicentre CARE trial sponsored by the Canadian Donation & Transplantation Research Program (CDTRP)...Project funded by the Canadian Donation & Transplantation Research Program (CDTRP). Acknowledgement: Daphne Brockington (UBC), study coordinator."

Clinical • P2 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid- Refractory or Dependent Chronic Gvhd - a Multicentre Phase II Clinical Trial (CARE Trial). (TCT-ASTCT-CIBMTR 2021) - "Objectives We sought to determine the safety and preliminary efficacy of TH9402-based photodynamic therapy (TH-PDT), a new type of phototherapy that does not involve frequent apheresis, in the multicentre CARE trial sponsored by the Canadian Donation & Transplantation Research Program (CDTRP)...Project funded by the Canadian Donation & Transplantation Research Program (CDTRP). Acknowledgement: Daphne Brockington (UBC), study coordinator."

Clinical • P2 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid- Refractory or Dependent Chronic Gvhd - a Multicentre Phase II Clinical Trial (CARE Trial). (TCT-ASTCT-CIBMTR 2021) - "Objectives We sought to determine the safety and preliminary efficacy of TH9402-based photodynamic therapy (TH-PDT), a new type of phototherapy that does not involve frequent apheresis, in the multicentre CARE trial sponsored by the Canadian Donation & Transplantation Research Program (CDTRP)...Project funded by the Canadian Donation & Transplantation Research Program (CDTRP). Acknowledgement: Daphne Brockington (UBC), study coordinator."

Clinical • P2 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid- Refractory or Dependent Chronic Gvhd - a Multicentre Phase II Clinical Trial (CARE Trial). (TCT-ASTCT-CIBMTR 2021) - "Objectives We sought to determine the safety and preliminary efficacy of TH9402-based photodynamic therapy (TH-PDT), a new type of phototherapy that does not involve frequent apheresis, in the multicentre CARE trial sponsored by the Canadian Donation & Transplantation Research Program (CDTRP)...Project funded by the Canadian Donation & Transplantation Research Program (CDTRP). Acknowledgement: Daphne Brockington (UBC), study coordinator."

Clinical • P2 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Transplantation

Addition of ATIR101, an Adjunctive Treatment Following T-Cell-Depleted Haploidentical HSCT, May Decrease Non-Relapse Mortality and May Improve Survival of Patients with Hematologic Malignancies, Irrespective of Prognostic Risk Factors (ASH 2019) - P=N/A, P2, P3; "After adjusting for potential prognostic risk factors, the multivariable analysis appears to support the clinical benefit of ATIR101 on NRM and OS at 1 year post HSCT. A large, global, randomized Phase 3 study is currently enrolling to further examine the efficacy and safety of T-cell-depleted haplo HSCT + ATIR101 compared with T-cell-replete haplo HSCT with post-transplant cyclophosphamide (HATCY; NCT02999854)."

Clinical • CD34

Depletion of Alloreactive T Cells after Haploidentical HSCT: Comparison of Outcomes for Ex Vivo Versus In Vivo Treatment Strategies (ASH 2018) - P3; "However, in these cross-study analyses, first insights into a potential advantage of ex vivo (ATIR101) over in vivo (PTCy) depletion of alloreactive T cells is suggested, including but not limited to rates of relapse, chronic GVHD, and GRFS. A large, phase III, randomized control trial is thus underway to assess the relative safety and efficacy of ATIR101 after T-cell-depleted haplo-HSCT versus PTCy after T-cell-replete haplo-HSCT (CR-AIR-009 HATCY; NCT02999854)."

Preclinical • Acute Myelogenous Leukemia • Biosimilar • Graft versus Host Disease • Myelodysplastic Syndrome • Oncology • Transplantation

Introduction of the HATCHY study: A Phase III, multicenter, randomised controlled study to compare safety and efficacy of a haploidentical HSCT and adjunctive treatment with ATIR101 with post-transplant cyclophosphamide in patients with a hematologic malignancies (EBMT 2017) - "...We have developed a T-depleted transplant approach where donor lymphocytes selectively depleted of alloreactive T-cells (ATIR101) using TH9402, arhodamidelike dye, are infused after CD34-selected haploidentical HSCT, to overcome the challenges of infectious complications, GvHD and relapse...All patients will undergo myeloablative conditioning consisting of either TBI (12 Gy) or melphalan/busulfan, in combination with thiotepa and fludarabine...Enrolment is expected to continue until mid2018 with initial results being available first half 2019. Results of this study will determine which transplant regimen provides most clinical benefit in haploidentical donor transplantation, with the promise of an effective regimen without the use of post-transplant immune suppression."

Clinical • P3 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Biosimilar • Graft versus Host Disease • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3 | N=63 | Terminated | Sponsor: Kiadis Pharma | Active, not recruiting ➔ Terminated; Insufficient efficacy, terminated by Sponsor

Preclinical • Trial termination • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Efficacy and Safety of a Single Dose of Donor Lymphocytes Depleted of Alloreactive T-Cells (ATIR101) Following T-Cell-Depleted Haploidentical HSCT: A Pooled Analysis of Two Phase II Studies (ASH 2018) - P=N/A, P2, P3; "GRFS in the pooled cohort was >2.5-fold higher than the historic control group and also seems higher than GRFS rates previously reported for other studies using post-transplant cyclophosphamide (PTCy) after T-cell-replete HSCT (Solh 2017, McCurdy 2017). To further investigate the therapeutic potential of ATIR101, a large, phase III, randomized control trial is currently underway to assess the relative safety and efficacy of ATIR101 after T-cell-depleted haplo-HSCT, versus PTCy after T-cell-replete haplo-HSCT (CR-AIR-009 HATCY; NCT02999854)."

P2 data • Retrospective data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Biosimilar • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Head-to-Head Comparison of Haploidentical HSCT Strategies for Hematologic Malignancies: Phase III Hatcy Study of T-Cell-Depleted HSCT with Adjunctive ATIR101 Versus T-Cell-Replete HSCT with Post‐Transplant Cyclophosphamide (ASH 2019) - P3; "This study will determine whether a strategy with a T-cell-depleted HSCT with adjunctive ex vivo selectively allodepleted, donor-derived, T-cell-enriched leukocytes (ATIR101) results in improved outcomes over a strategy with T-cell-replete HSCT with PTCy in patients undergoing haploidentical transplantation. The use of GRFS as a composite endpoint involving freedom of relapse and severe GVHD will allow a unique health-economic assessment and definition of value-based healthcare."

Head-to-Head • P3 data

PHASE 2 STUDY EVALUATING THE SAFETY AND EFFICACY OF ONE OR TWO DOSES OF DONOR LYMPHOCYTES DEPLETED OF HOST ALLOREACTIVE T-CELLS (ATIR101) FOLLOWING T-CELL-DEPLETED HAPLOIDENTICAL HSCT (EHA 2019) - P2, P3; "Further investigation is needed to clarify the cell number for a second dose of ATIR101 that can be administered safely post HSCT. Based on the two Phase 2 studies with ATIR101, a large, randomized, Phase 3 trial has been initiated, comparing a single dose of ATIR101 with PTCy in haplo HSCT (HATCY; NCT02999854)."

Clinical • P2 data

Theoretical Investigation of the 4,5-Dibromorodamine Methyl Ester (TH9402) Photosensitizer Used in Photodynamic Therapy: Photophysics, Reactions in the Excited State, and Interactions with DNA. (PubMed, J Phys Chem B) - "Interactions of TH9402 with the d(AGACGTCT) octanucleotide revealed that the PS can intercalate between the d(GpC)-d(CpG) base pairs in three different orientations and, upon intercalation, the π → π* transition of the PS shows a bathochromic shift up to 90 nm and up to 60% decrease in intensity. Interactions through groove binding showed a smaller bathochromic shift of 52.2 nm and a 56% decrease in intensity of the main transition band."

Journal • Oncology

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=69; Active, not recruiting; Sponsor: Kiadis Pharma; Recruiting ➔ Active, not recruiting; N=250 ➔ 69; Trial completion date: Feb 2021 ➔ Nov 2021; Trial primary completion date: Feb 2021 ➔ Nov 2021

Clinical • Enrollment change • Enrollment closed • Preclinical • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=250; Recruiting; Sponsor: Kiadis Pharma; Trial completion date: May 2020 ➔ Feb 2021; Trial primary completion date: May 2020 ➔ Feb 2021

Clinical • Preclinical • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=195; Not yet recruiting; Sponsor: Kiadis Pharma

Clinical • New P3 trial • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=195; Not yet recruiting; Sponsor: Kiadis Pharma; Trial primary completion date: Feb 2020 ➔ May 2020

Clinical • Preclinical • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=195; Not yet recruiting; Sponsor: Kiadis Pharma; Initiation date: May 2017 ➔ Sep 2017

Clinical • Preclinical • Trial initiation date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

HATCY: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (clinicaltrials.gov) - P3; N=195; Recruiting; Sponsor: Kiadis Pharma; Not yet recruiting ➔ Recruiting; Initiation date: Sep 2017 ➔ Dec 2017

Clinical • Enrollment open • Preclinical • Trial initiation date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia. (PubMed, Leukemia) - "Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). 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."

Clinical • Journal • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Transplantation

Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis. (PubMed, Br J Haematol) - "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 × 10  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."

Journal • Graft versus Host Disease • Hematological Malignancies • Immunology • Transplantation

Donor Lymphocytes Depleted of Alloreactive T-Cells (ATIR101) Improve Event-Free Survival (GRFS) and Overall Survival in a T-Cell Depleted Haploidentical HSCT: Phase 2 Trial in Patients with AML and ALL (ASH 2016) - P2; "Patients underwent myeloablative conditioning, consisting of a] TBI (1200 cGy: n=11) or b] melphalan (120 mg/m2: n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m2 x 5d) and ATG (2.5mg/kg x 4d). Addition of ATIR101 to a T-cell depleted HSCT protocol significantly improves transplantation outcome, with improved overall survival and favorable event-free survival (GRFS). One year GRFS for HSCT + ATIR101 also compares favorably to published data on haploidentical HSCT using post-transplant cyclophosphamide for GVHD prophylaxis (Solh et al, BBMT 2016)."

P2 data • Acute Myelogenous Leukemia • Biosimilar • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology

Kiadis Pharma provides update on second dose trial (CR-AIR-008) with ATIR101 (Kiadis Pharma Press Release) - P2, N=10; NCT02500550; Sponsor: Kiadis Pharma; "All ten patients received a first dose of the same efficacious level as the patients in the Company’s other trials, and, as in the other trials with a single dose of ATIR101™, no patient suffered from grade III/IV Graft-versus-Host-Disease (GVHD) upon infusion of the first dose. Subsequently, six of the ten patients received a second dose of ATIR101™. Following this second infusion, some of the six patients subsequently suffered from various grades of GVHD, including grade III/IV GVHD."

P2 data • Graft versus Host Disease • Immunology

ATIR101: Protection of patent for methods for reducing GVHD including composition until October 2021 (Kiadis Pharma) - Corporate Presentation: Patent protection for more rhodamine derivatives until January 2024; Patent protection for use to treat disorder until December 2024; Patent protection for improved photodynamic process until February 2036

Patent • Graft versus Host Disease • Immunology

Last patient dosed with ATIR101 in the phase II ‘008’ clinical trial (Kiadis Pharma Press Release) - "Kiadis Pharma...announces that the last patient in the Phase II CR-AIR-008 (‘008’) trial has received a single dose of ATIR101...have completed enrollment into this Phase II study and can now fully focus on enrollment of the Phase III study...Company remains on track to potentially obtain (conditional) EMA approval for ATIR101™ in Q4 2018 which would allow for a European launch in H2 2019.”

Enrollment closed • European regulatory • Launch Europe • Graft versus Host Disease • Immunology