PPMX-T003 / Perseus Proteomics - LARVOL DELTA

Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia. (PubMed, BMJ Open) - P1/2 | "The results will be disseminated in peer-reviewed journals. jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov)."

Clinical protocol • Journal • P1/2 data • PK/PD data • Hematological Malignancies • Hepatology • Leukemia • Liver Failure • Lymphoma • Oncology

DIFFERENTIAL ROLES FOR CELL CYCLE REGULATIONS BETWEEN TRANSFERRIN AND FERRITIN JUSTIFY THE DEVELOPMENT OF TRANSFERRIN RECEPTOR 1 BLOCKERS AS ANTINEOPLASTIC AGENTS OVER IRON CHELATORS (EHA 2025) - "Recently, we have reported the therapeutic potential of an anti-transferrin receptor 1 (TfR1) inhibitory antibody, PPMX-T003 (T003), for natural killer (NK) cell lymphomas in in vivo experiments and now phase I/II clinical study is ongoing in Japan...Deferoxamine (DFO; 500 µM) and T003 (10 µg/mL) were applyed in culture media as an iron chelator and TfR1 blocker, respectively... Our investigations sugget one of the crucial reasons of higher toxicities of iron chelators that they affect mitochondrial functions due to severe deprivation of LIP because they are also critical for homeostasis of healthy cells. Oppositely, TfR1 blockage affect only proliferating cells via targeting the nascent DNA synthesis like conventional cytotoxic agents and succesfully avoid the mitochondrial toxicities by mainteining labile iron pool decrease. These findings provies justification for development of TfR1 blockers like T003 as novel antineoplastic agents over iron chelators."

Lymphoma • CDK4 • TFRC

Perseus Proteomics Inc. Announces PPMX-T003 Notice on Completion of Clinical Study Report of Phase I Clinical Trial Among Polycythemia Vera Patients [Google translation] (Zonebourse) - "Perseus Proteomics Inc. announced that it has completed the Clinical Study Report (CSR) for the Phase I clinical trial of an anti-transferrin receptor 1 antibody, PPMX-T003 (the 'Phase I'), in patients with polycythemia vera ('PV'). The Phase I trial was conducted with six subjects suffering from PV, a disease characterized by an abnormal increase in red blood cells, to evaluate the safety and pharmacokinetics of PPMX-T003, as well as to confirm its efficacy as secondary endpoints. As a result, no serious adverse events regarding the safety of PPMX-T001 were confirmed, and efficacy was indicated by red blood cell parameters, including hematocrit and hemoglobin."

Trial status • Polycythemia Vera

Anti-transferrin receptor antibody (JST-TFR09/PPMX-T003) induces ferroptosis in adult T-cell leukemia/lymphoma (ATLL) cells. (PubMed, Biochem Biophys Res Commun) - "Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TFRC

PPMX-T003: Selection as FY2026/3 Project Promoting Support for Drug Discovery Support Program for Orphan drug prior to the Designation by AMED (Perseus Proteomics Press Release) - "Perseus Proteomics Inc. ('the Company') is pleased to announce that the research and development of the Company on utilizing its pipeline drug candidate as treatment for aggressive NK cell leukemia ('ANKL') has been selected as Project Promoting Support for Drug Discovery Support Program for Orphan drug prior to the Designation by Japan Agency for Medical Research and Development (AMED)....The initial clinical trial was scheduled to end by the end of March 2025, however, the clinical trial coordinator assessed that completion by the date would be challenging and registered a 1-year extension of the trial period on jRCT....While this subsidy program is set to continue for three years from April 2025 to March 2028, the clinical study itself is planned to run until the end of March 2026. In FY2026/3, the Company anticipates a subsidy of 100 million yen which will be allocated towards the clinical trial expenses."

Financing • Japanese regulatory • Trial completion date • Leukemia

Safety Evaluation Study for Patients with Aggressive NK-cell Leukemia (clinicaltrials.gov) - P1/2 | N=7 | Recruiting | Sponsor: Hiroshima University Hospital | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Oncology

Announcement of Presentation of PPMX-T003 Phase I of Polycythemia Vera at 66th ASH Annual Meeting and Exposition (Perseus Proteomics Press Release) - "Perseus Proteomics Inc. is pleased to announce that the report of the phase I clinical trial of PPMX-T003, an anti-transferrin receptor 1 (TfR1) antibody, among polycythemia vera (PV) patients was presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition....The initial dosage was set at 0.25 mg/kg, with an optional escalation up to 1.0 mg/kg for additional administration if the initial effect proves insufficient. Among the five subjects excluding the sixth subject who cancelled the trial due to personal reasons, a 12-week period without the need for phlebotomy was achieved. Side effects levels were the same as those among healthy volunteers, with no serious adverse effects observed. Also, efficacy was indicated with RBC parameters including hematocrit and hemoglobin."

P1 data • Polycythemia Vera

PPMX-T003: Announcement on Extension of Investigator-led Phase I/II Clinical Trial for Aggressive NK-cell Leukemia (ANKL) (Perseus Proteomics Press Release) - "Perseus Proteomics Inc. (The Company) hereby announces that the period of investigator-led phase I/II clinical trial of PPMX-T003, an anti-transferrin receptor 1 (TfR1) antibody, for aggressive NK-cell leukemia (ANKL) has been extended until March 31, 2026. Facing challenges in subject registration due to the target being an exceptionally rare disease, the company has been preparing for the extension of the clinical trial with the clinical trial coordinators and other related parties. Recently, the clinical trial coordinator determined that it would be difficult to complete the study by March 31, 2025. Thus, an extension of the trial period until March 31, 2026 has been registered with the jRCT (Japan Registry of Clinical Trials), a system for submitting and publicizing clinical research."

Trial completion date • Leukemia

Phase I Safety Study of Anti-Transferrin Receptor 1 Antibody (PPMX-T003) in Patients with Polycythemia Vera and Erythrocythemia (ASH 2024) - P1 | "Except for an antibody drug conjugate (CX-2029), this is the first-in-class trial of an unmodified human antibody other than a P1a trial using a murine antibody conducted in the 1990s. The clinical effect of PPMX-T003 on human erythroid production is expected to offer an alternative to PLB treatment for patients with PV or erythrocythemia. In the future, it will help further develop its potential for a variety of cancer patients."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Oncology • Polycythemia Vera • JAK2 • TFRC

Announcement of Presentation of PPMX-T003 Phase I at 66th ASH Annual Meeting and Exposition (Perseus Proteomics Press Release) - "Perseus Proteomics Inc. is pleased to announce that the report of the phase I clinical trial of PPMX-T003, an anti-transferrin receptor 1 (TfR1) antibody, among polycythemia vera (PV) patients has been accepted for presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, to be held on December 7-10, 2024, in San Diego, California and online."

P1 data • Polycythemia Vera

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia. (PubMed, Leukemia) - "We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut."

Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

AMINO ACID INFLUX VIA LAT1 REGULATES IRON DEPENDENCY OF AGGRESSIVE NATURAL KILLER CELL LEUKEMIA (EHA 2024) - "Taken together, we discovered that the amount of extracellular sulfur amino acid influx through LAT1 was thekey environmental factor determining the iron dependency of ANKL cells, which provides a good explanationfor the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoidcontains abundant amino acids absorbed from the gut."

Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • SLC7A5

Interim Phase I Safety Study of Anti-Transferrin Receptor Antibody(PPMX-T003) in Patients with Polycythemia Vera (ASH 2023) - P1, P1/2 | "Except for an antibody drug conjugate (CX-2029), this is the first-in-class trial of an unmodified human antibody other than the murine P1a trial conducted in the 1990s. AEs are mild as observed within the level of previous healthy volunteer's trial. Efficacy observed in all erythroid parameters including hematocrit, hemoglobin and other parameter shown symptoms seen in iron deficiency anemia. This antibody can specifically suppress erythrocyte differentiation by inhibiting iron influx in the target erythroid lineage, which cells are highly expressed TfR1, without any significant AE on other normal organs with low expression level of TfR."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Polycythemia Vera • TFRC

Perseus Proteomics results, anti-TfR antibody Phase 1 to be completed in March 2024 [Google translation] (Nikkei) - "Regarding the development status of PPMX-T003, an anti-transferrin receptor (TfR) antibody in the main pipeline, the development for polycythemia vera (PV) is progressing smoothly and is scheduled to be completed in March 2024, and the development status for FY2024 is progressing smoothly."

Trial completion date • Hematological Malignancies • Oncology • Polycythemia Vera

Perseus continues to grow significantly, enrolling subjects in PPMX-T003 phase 1 trial completed (Minkabu Press Release) - "After the close of trading on the 20th of the previous weekend, subjects (target number of patients of 6) were announced for a phase 1 trial in polycythemia vera (PV) patients of the anti-transferrin receptor 1 (TfR1) antibody 'PPMX-T003' under development. Announced that the incorporation has been completed. This is considered a material....The company plans to administer the drug to newly enrolled patients and complete the study within this fiscal year."

Enrollment closed • Trial completion date • Hematological Malignancies • Oncology • Polycythemia Vera

Perseus begins administration of “PPMX-T003” to ANKL patients [Google translation] (Minkabu Press Release) - "After the close of trading on the same day, Perseus Proteomics...announced that it had begun administering PPMX-T003, its pipeline product under development, to patients with aggressive NK cell leukemia (ANKL). In the investigator-initiated Phase 1/2 trial for ANKL in the same pipeline, the first dose was administered to the first patient on this day."

Trial status • Hematological Malignancies • Leukemia • Oncology

Safety Evaluation Study for Patients With Polycythemia Vera (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Perseus Proteomics Inc. | Trial completion date: Oct 2023 ➔ Mar 2024

Trial completion date • Polycythemia Vera

Safety Evaluation Study for Patients With Aggressive NK-cell Leukemia (clinicaltrials.gov) - P1/2 | N=6 | Recruiting | Sponsor: Hiroshima University Hospital

New P1/2 trial • Hematological Malignancies • Leukemia • Oncology

Hepatic niche leads to aggressive natural killer cell leukemia proliferation through transferrin-transferrin receptor 1 axis. (PubMed, Blood) - "PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a non-canonical hematopoietic organ in adults, serves as a principal niche for ANKL, and that inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Leukemia • Oncology • TFRC

Phase 1 Clinical Trial of PPMX-T003, a Novel Human Monoclonal Antibody Specific for Transferrin Receptor 1, to Evaluate Its Safety, Pharmacokinetics, and Pharmacodynamics. (PubMed, Clin Pharmacol Drug Dev) - "PPMX-T003 in the 0.25 mg/kg group showed apparent (>50%) decreased serum levels of reticulocytes from day 3 and sustained moderate (<10%) fall of hematocrit and hemoglobin counts from day 7. In conclusion, the antibody-mediated blockade of TFR1 elicited the expected fall in blood cell levels and showed an acceptable safety profile, supporting the continuing development of PPMX-T003 as a new candidate for polycythemia vera treatment."

Journal • P1 data • PK/PD data • Polycythemia Vera • TFRC

Safety Evaluation Study for Patients With Polycythemia Vera (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Perseus Proteomics Inc. | Initiation date: Feb 2022 ➔ Jul 2022

Trial initiation date • Polycythemia Vera