ApoGraft (allogeneic mobilised peripheral blood cells) / Quoin Pharma - LARVOL DELTA

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Washington University School of Medicine | N=36 ➔ 4 | Trial completion date: Jun 2025 ➔ Dec 2022 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Dec 2022; Lost funding

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Transplantation

Safety and Preliminary GvHD Mitigation in First in Human Clinical Trial of Apograft in Match Related Stem Cell Transplantation (SCT) (ASH 2021) - P1/2 | "All patients received GVHD prophylaxis with short-course methotrexate and Cyclosporin A. No AEs or serious AEs (SAEs) were recorded during stem cell infusion. One MDS patient died during the study due to study unrelated secondary graft failure. Our results show evidence that the ApoGraft product was well tolerated at all FasL doses and demonstrated preliminary signs of GvHD mitigation when the higher ex-vivo doses of FasL (50 and 100 ng/ml) were used."

Clinical • P1 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD34 • FAS

Brief Ex Vivo Incubation with Fas Ligand Selectively Depletes Alloreactive T Cells and Antigen Presenting Cells from Stem Cell Grafts (ASH 2018) - P1/2; "In conclusion, in contrast to conventional T- cell depletion methods, ApoGraft, an ex-vivo FasL-treated graft, affects both the T-cells and APCs, leading to reduced GvHD, while maintaining GvL and engraftment potential (Panel I). ApoGraft is currently being evaluated in a Phase I/II clinical trial (NCT02828878) in subjects with hematologic malignancies undergoing matched related allo-HSCT."

Preclinical • Biosimilar • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation

Results of a Non-Interventional Clinical Trial of Apograft - a Novel Technology for GvHD Prevention (ASH 2017) - P1/2; "ApoGraft is an apoptosis-based selection process that eliminates mature T cells from stem cells grafts, while preserving CD34+ cells quantity, quality and functionality. In our preclinical murine model, ApoGraft reduced GvHD without impairing engraftment. Ongoing animal studies are evaluating the graft vs."

Biosimilar • Gene Therapies • Graft versus Host Disease • Leukemia

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Transplantation

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Washington University School of Medicine; Trial completion date: Dec 2023 ➔ Jun 2024; Trial primary completion date: Dec 2023 ➔ Jun 2024

Clinical • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Transplantation

Neoadjuvant talazoparib (TALA) for operable breast cancer patients with a BRCA mutation (BRCA+). (ASCO 2018) - P2; " All 20 planned pts have enrolled from 08/2016-09/2017: median age = 38 (range 23-58); BRCA1+ = 16 and BRCA2+ = 4; 17 patients had triple negative breast cancer (TNBC, ER/PR < 10%) and 3 had hormone+ disease; Clinical stage I = 5, stage II = 12, Stage III = 3 including 1 patient with inflammatory breast carcinoma (IBC) and 1 with metaplastic chondrosarcomatous carcinoma (MpBC). Single agent oral TALA once daily given preoperatively without chemotherapy produced significant pathologic complete responses with manageable toxicity. This pilot trial exceeded our expectations and is novel to demonstrate RCB0 in TNBC by a single targeted therapy. These results warrants a larger study for this pt population."

BRCA Biomarker • Clinical • PARP Biomarker • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Sarcoma • Triple Negative Breast Cancer

Cellect Bio’s ApoGraft Therapy Is Safe, Tolerable In GvHD Study (Yahoo Finance) - P1/2, N=12; NCT02828878; Sponsor: Cellect Biotechnology; "Cellect Biotechnology Ltd...has announced data from the Phase 1/2 study in Israel evaluating ApoGraft technology for Graft versus Host Disease (GvHD), a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). All eleven patients enrolled for the trial were transplanted using the ApoGraft product and were engrafted on time. The primary objective, safety, and tolerability of ApoGraft administered to patients with hemato-oncology disorders was met, and no procedure-related adverse events were reported during the study....The company announced a reverse merger agreement with...Quoin Pharmaceuticals."

M&A • P1/2 data • Graft versus Host Disease

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Washington University School of Medicine; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Lymphocytic Leukemia • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation

A TRIM24-like mutational signature predicts worse relapse-free survival (RFS) and overall survival (OS) in patients (pts) with metaplastic breast cancer (MpBC) (AACR 2018) - "In this cohort, pts with MpBCs that exhibit a TRIM24-like mutational signature had worse RFS and OS. This finding should be confirmed in larger, prospective studies.Table 1: Baseline Clinicopathological Characteristics by TRIM24 StatusTRIM24-like (n=5) Non TRIM24-like (n=15) p valueAge at diagnosis - Median (years, interquartile range) 55 (50-61) 56 (47-66) 0.965Clinical Tumor SizeMean (cm, standard deviation) 4.2 (1.5) 3.4 (1.6) 0.383Clinical Nodal StatusNegative - n (%) 3 (60) 11 (73) 0.570Positive - n (%) 2 (40) 3 (20)Unknown - n (%) 0 1 (7)ER/PR StatusNegative - n (%) 5 (100) 14 (93) 1.000Positive - n (%) 0 1 (7)HER2 StatusNegative - n (%) 5 (100) 15 (100) NAPositive - n (%) 0 0HistologySpindle Cell - n (%) 4 (80) 7 (47) 0.319Matrix-producing - n (%) 1 (20) 8 (53)"

Clinical • Breast Cancer • Sarcoma

Cellect Biotechnology Initiates U.S. Clinical Trial of ApoGraft (GlobeNewswire) - "Cellect Biotechnology...today announced that it has initiated its clinical trial in the U.S. to determine the safety and tolerability of the ApoGraft technology for bone marrow transplantations (BMT)….The Company has previously disclosed interim data showing that the trial unequivocally met the safety and tolerability end point, and the Company expects to publish top line data in early 2021....John DiPersio M.D., Ph.D., will act as co-principal investigators for the study."

Clinical data • Trial status • Graft versus Host Disease • Immunology

European Patent Office Grants Cellect Biotechnology Pivotal Patent for Stem Cells Activation (PRNewswire) - "Cellect Biotechnology...today announced that it has significantly strengthened its Intellectual Property (IP) portfolio as European Patent Application No. 14851547.1 has been granted. The patent will be set to expire in October 7, 2034, subject to patent term adjustment or extension....While the extensive issued patents cover the accurate elimination (negative selection) of the mature cells and therefor enables SAFETY, this patent covers the increased ACTIVITY (positive selection=efficacy) of the regenerative capacity of the stem and progenitor cells."

Patent • Graft versus Host Disease • Immunology

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Washington University School of Medicine; Trial completion date: Apr 2023 ➔ Aug 2023; Initiation date: Apr 2020 ➔ Aug 2020; Trial primary completion date: Apr 2023 ➔ Aug 2023

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma

Cellect Biotechnology's ApoGraft to empower cellular treatment of Covid-19 related pulmonary diseases (PRNewswire) - "Cellect Biotechnology Ltd....today announced that it has signed a development agreement with an international consortium to examine the therapeutic effects of ApoGraft treated stem cells on the reduction of pulmonary manifestations caused by COVID-19. The Company has completed the technology and material transfer and the pre-clinical studies are progressing....This agreement enables the Company to leverage its clinical data, regulatory approvals, and know-how to expedite the development of a Cytokine storm therapy for COVID-19 as well as CAR-T related cytokine storm conditions....Clinical Results in GvHD Studies May be Beneficial in COVID-19 and CAR-T Cytokine Storm manifestations..."

Cytokine storm • Licensing / partnership • Preclinical • Graft versus Host Disease • Immunology • Infectious Disease • Novel Coronavirus Disease

Mutational and Immune Profiling of Metaplastic Breast Cancer: Correlation with Survival (USCAP 2018) - "There was no correlation between CD3, CD4 or CD8 TILs quantification and survival. PIK3CA mutation and PDL1 expression confers poor prognosis in this small cohort of patients with MpBC. A larger cohort of patients is needed to verify these findings."

Biosimilar • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Non-interventional, Long-term Follow-up of Subjects Who Completed ApoGraft-01 Study (clinicaltrials.gov) - P=N/A; N=12; Recruiting; Sponsor: Cellect Biotechnology; Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cellect Biotechnology announces positive data demonstrating robust engraftment using ApoGraft was featured in Bone Marrow Transplantation; Primary data points were submitted to the FDA during investigational new drug approval process (PharmiWeb) - "Cellect Biotechnology...today announced the publication of an article in Bone Marrow Transplantation...The data from the pre-clinical research, and published in this paper, was included in the Company's Investigational New Drug (IND) application, which was approved by the U.S. Food and Drug Administration in late 2019. The Company has received all the necessary approvals to initiate the trial with its academic partner, Washington University, and plans to begin patient recruitment once the COVID-19 pandemic is mitigated and clinics can resume normal practices."

New trial • Preclinical • Graft versus Host Disease • Immunology

Cellect Biotechnology continues to achieve milestones; Receives new patent allowance in Canada (BioSpace) - "Cellect Biotechnology Ltd...received an official communication from the Canadian Intellectual Property Office regarding its intention to grant Canadian Patent Application No. 2,866,358 for Apograft....The patent covers a device and a kit adapted for selection of cells that are resistant to receptor-mediated apoptosis and a method for using the device and kit. The device enables simultaneous positive selection for both stem-cells and immune cells which support engraftment and negative selection for immune cells which induce graft versus host disease (GvHD)."

Patent • Graft versus Host Disease • Immunology

Cellect Biotechnology reports fourth quarter and full year 2019 results (PRNewswire) - "In Israel, the recruitment of patients in the final cohort for the Phase 1/2 clinical trial has been halted. Previously, the Company had anticipated completion of this trial in the second quarter of 2020....Published mid-study data from the first half of patients was positive. All patients transplanted using the ApoGraft process were engrafted and time to engraftment was not changed....Patient enrollment is continuing....Phase 1/2 clinical trial, which was scheduled to begin enrolling patients in the first half of 2020, is delayed as major academic centers have suspended trials not affiliated with COVID-19."

Enrollment status • P1/2 data

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Washington University School of Medicine; Initiation date: Jan 2020 ➔ Apr 2020

Clinical • Trial initiation date

Cellect Biotechnology receives approval for U.S. clinical trial (PRNewswire) - "Cellect Biotechnology Ltd....has received approval to initiate the trial in the U.S. to evaluate the safety and tolerability of the ApoGraft technology for haploidentical bone marrow transplantations. The company is collaborating with Washington University School of Medicine in St. Louis on the trial. A total of 18 patients are planned for this initial phase, with enrollment expected to begin in the first half of 2020. The company has received the approval of the protocol by Washington University's Institutional Review Board..."

Enrollment status • FDA event • New trial

Cellect Biotechnology reports third quarter 2019 financial and operating results (PRNewswire) - "Received an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) for the commencement of a clinical trial to determine the safety and tolerability of the ApoGraft technology for haploidentical bone marrow transplantations....designed to significantly reduce acute graft-versus-host disease (aGVHD)...In Israel, our Phase 1/2 clinical study of ApoGraft™ is progressing slowly and we expect to complete the recruitment around the end of the year."

Enrollment status • IND • New trial • Trial status

Prevention of Acute Graft Versus Host Disease in Patients Undergoing Allogeneic ApoGraft Stem Cell Transplantation (clinicaltrials.gov) - P1/2; N=12; Recruiting; Sponsor: Cellect Biotechnology; Trial completion date: Dec 2019 ➔ Jul 2020; Trial primary completion date: Dec 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date

Non-interventional, Long-term Follow-up of Subjects Who Completed ApoGraft-01 Study (clinicaltrials.gov) - P=N/A; N=12; Recruiting; Sponsor: Cellect Biotechnology; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Trial primary completion date

ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Washington University School of Medicine

Clinical • New P1 trial