tenalisib (RP6530) / Rhizen, Curon Biopharma - LARVOL DELTA

Efficacy and Safety of Tenalisib in Patients With Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Rhizen Pharmaceuticals SA | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Oct 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Moving Beyond Romidepsin: New Strategies for Relapsed/Refractory PTCL (SOHO 2025) - "Current FDA-approved agents include pralatrexate, 2 belinostat, 3 and brentuximab vedotin...In this study, romidepsin plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was compared to CHOP in untreated T-cell lymphomas (TCLs) but failed to show an improvement in progression-free survival (PFS) — the primary endpoint of this study 6 Brentuximab vedotin has the highest response rate of 87% in R/R anaplastic large cell lymphoma (ALCL), 4 but the response rates are lower in other subtypes...7 Duvelisib — a dual PI3K delta/ gamma inhibitor — has shown an overall response rate (ORR) of 48%, a complete response (CR) rate of 33%, and a median duration of response of 7.89 months...Other PI3K inhibitors include tenalisib 10 and linperlisisb, 11 which demonstrate similar results...Inhibitors of the JAK/ STAT pathway like ruxolitinib are showing promising results in PTCL — both as single agents and in combination...The ORACLE study compared 5-azacitidine against..."

Oncology • Peripheral T-cell Lymphoma • CD5 • CD7 • CD70 • EZH2 • GATA3 • IL2RA • KLRD1 • SIRPA • TNFRSF8

Management of Mycosis Fungoides and Sézary Syndrome With Oral Systemic Therapies. (PubMed, J Cutan Med Surg) - "FDA-approved oral therapies include bexarotene and vorinostat, both of which are effective in patients who are recalcitrant to prior topical therapies. Off-label oral therapies include methotrexate, acitretin, and chlorambucil...Chlorambucil is mainly used to treat erythrodermic MF. Investigational oral therapies for MF include tenalisib, duvelisib, cerdulatinib, lenalidomide, bortezomib, and azacytidine, and direct comparison studies between these investigational agents and FDA-approved therapies should be undertaken to better understand their role in the management of MF and SS."

Journal • Review • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Efficacy and Safety of Tenalisib in Patients With Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Rhizen Pharmaceuticals SA | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Efficacy and Safety of Tenalisib in Patients With Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Rhizen Pharmaceuticals SA | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Efficacy and Safety of Tenalisib in Patients With Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Rhizen Pharmaceuticals SA

Metastases • New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study. (PubMed, Haematologica) - "Coadministration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL."

Clinical • Combination therapy • Journal • P1/2 data • Cutaneous T-cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

Efficacy and safety of tenalisib, a PI3K δ/γ and SIK3 inhibitor, in patients with locally advanced or metastatic breast cancer: Updated results from an on-going phase II study. (ASCO 2023) - P2 | "Breast cancer cell line studies have demonstrated that tenalisib potentiated the activity of paclitaxel and doxorubicin...Pts had a median of 3 (range 1-7) prior therapies of which, 87% pts had prior endocrine therapy, which included 40% pts treated with an aromatase inhibitor and 30% of pts treated with fulvestrant as their last therapy respectively... Based on the data from the ongoing study, tenalisib shows encouraging efficacy as a single agent in pts with relapsed/refractory HR+ HER2- difficult to treat MBC patients. Updated efficacy and tolerability data will be provided at the time of presentation. Clinical trial information: NCT05021900."

Clinical • Metastases • P2 data • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Triple Negative Breast Cancer • ER • HER-2 • PIK3CD

Compassionate Use Study of Tenalisib (RP6530) (clinicaltrials.gov) - P1/2 | N=17 | Completed | Sponsor: Rhizen Pharmaceuticals SA | Trial primary completion date: Mar 2022 ➔ Mar 2023

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

Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, in Patients With Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: Rhizen Pharmaceuticals SA | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Mar 2023 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Metastases • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

Complete Response to tenalisib and romidepsin with long-term maintenance using tenalisib monotherapy in a patient with relapsed and refractory sézary syndrome. (PubMed, Invest New Drugs) - "Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway by Tenalisib presents one such emerging drug. We report a relapsed/refractory SS patient achieving complete remission using the combination of Tenalisib and Romidepsin and subsequently maintaining long-duration CR with Tenalisib monotherapy."

Journal • Monotherapy • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

Compassionate Use Study of Tenalisib (RP6530) (clinicaltrials.gov) - P1/2 | N=17 | Completed | Sponsor: Rhizen Pharmaceuticals SA | Enrolling by invitation ➔ Completed | Trial completion date: Dec 2022 ➔ Mar 2023

Trial completion • Trial completion date • Hematological Disorders • Hematological Malignancies • Oncology

The dual SYK/JAK inhibitor cerdulatinib demonstrates rapid tumor responses in a phase 2 study in patients with relapsed/refractory B- and T-cell non-Hodgkin lymphoma (NHL). (ASCO 2018) - P1/2; "Durable PRs have occurred in patients who relapsed on BTK inhibitor (CLL, 5+ months, WM, 7+ months, FL, 12 months), venetoclax (SLL, 18+ months), and tenalisib (PTCL, 3+ months) therapy. The cerdulatinib phase 2 dose of 30 mg BID demonstrates good tolerability and efficacy in heavily pre-treated r/r B and T cell NHL."

Clinical • IO biomarker • P2 data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Indolent Lymphoma • Marginal Zone Lymphoma • Peripheral T-cell Lymphoma

SAFETY AND CLINICAL ACTIVITY OF RP6530, A DUAL PI3Kδ/γ INHIBITOR, IN PATIENTS WITH ADVANCED HEMATOLOGIC MALIGNANCIES: FINAL ANALYSIS OF A PHASE 1 MULTI-CENTER STUDY (ICML 2017) - P1; "RP6530 demonstrated an acceptable safety with no DLT and a promising clinical activity in pts with advanced, heavily pre-treated relapsed/refractory hematologic malignancies. Clinical activity was manifested by a significant reduction in peripheral blood cell pAKT expression levels. Decrease in conventional and regulatory CD4+ T cells and B cells was associated with response."

Adverse events • Biomarker • Clinical • P1 data • Biosimilar • Diffuse Large B Cell Lymphoma • Dyslipidemia • Leukemia • Peripheral T-cell Lymphoma

DUAL PI3K δ/γ INHIBITOR RP6530 IN PATIENTS WITH RELAPSED/REFRACTORY T-CELL LYMPHOMA: DOSE ESCALATION FINDINGS. (ICML 2017) - P1; "Dose escalation study demonstrated an acceptable safety and tolerability up to RP6530 800 mg BID (Fasting) with promising clinical activity in pts with TCL. A dose of 800 mg BID (fasting) was considered a MTD. The results support further evaluation of RP6530 in pts with mature T-cell lymphomas."

Adverse events • Clinical • Biosimilar • Cutaneous T-cell Lymphoma • Immunology • Indolent Lymphoma • Peripheral T-cell Lymphoma

Final Results of Phase 1/1b Study of Tenalisib, Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma (ASH 2019) - P1, P1/2; "Tenalisib demonstrated promising clinical activity and an improved safety profile in patients with relapsed/ refractory TCL. Currently, a phase I/II combination study to further evaluate safety and efficacy with romidepsin is ongoing in this target population."

Clinical • P1 data

Pooled Safety Analysis and Efficacy of Tenalisib (RP6530), a PI3Kδ/γ Inhibitor, in Patients with Relapsed/Refractory Lymphoid Malignancies (ASH 2018) - P1; "Tenalisib can therefore be safely combined with a diverse array of other agents active in lymphoid malignancies. Tenalisib is currently being studied in combination with Pembrolizumab and Romidepsin and as a monotherapy in a Phase II trial in indolent NHL."

Clinical • Biosimilar • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Peripheral T-cell Lymphoma

Safety and Anti-Tumour Activity of RP6530, Dual PI3K δ/γ Inhibitor, in Relapsed/Refractory T-Cell Lymphoma: Updated Results from the Dose Expansion Cohort of an on-Going Phase I/Ib Study (ASH 2017) - P1; "Based on the updated emerging data, RP6530 shows encouraging preliminary clinical activity as a single agent and appears to have an acceptable and manageable safety profile in relapsed/refractory TCL. Recruitment in the expansion cohort is currently on-going to reach a total of 40 patients and results will be further evaluated."

Adverse events • Clinical • P1 data • Biosimilar • Cutaneous T-cell Lymphoma • Immunology • Indolent Lymphoma • Peripheral T-cell Lymphoma

Tenalisib, a dual PI3K / inhibitor:Safety and efficacy results from an on-going phase I/Ib study in relapsed/refractory T-cell lymphoma. (ASCO 2018) - P1; "Tenalisib shows acceptable safety and encouraging clinical activity in relapsed/refractory TCL. Recruitment in the expansion cohort is close to completion."

Clinical • P1 data • Cutaneous T-cell Lymphoma • Indolent Lymphoma • Peripheral T-cell Lymphoma

Tenalisib, a dual PI3K / inhibitor:Safety and efficacy results from an on-going phase I/Ib study in relapsed/refractory T-cell lymphoma. (ASCO 2018) - P1; "Tenalisib shows acceptable safety and encouraging clinical activity in relapsed/refractory TCL. Recruitment in the expansion cohort is close to completion."

Clinical • P1 data • Cutaneous T-cell Lymphoma • Indolent Lymphoma • Peripheral T-cell Lymphoma

Efficacy and Safety of Tenalisib, a PI3K _/_ and SIK3 inhibitor in Patients with Locally Advanced or Metastatic Breast Cancer: Initial results from a Phase II study (ESMO-BC 2022) - P2 | "Tenalisib's major metabolite (IN0385) shows potent SIK3 inhibition Preclinical studies in breast cancer cell lines have demonstrated that tenalisib potentiates activity of taxol and doxorubicin.Methods This randomized, open-label study was designed to evaluate 2 doses (800 mg BID and 1200 mg BID) of tenalisib in HR+/HER2- locally advanced or MBC patients whose disease had progressed following at least one line of therapy. Two pts were discontinued due to related AEs (rash and GGT elevation).Conclusions Based on the data from the ongoing study , Tenalisib showed encouraging preliminary efficacy as a single agent in patients with advanced MBC. Updated efficacy and tolerability data will be provided at the time of presentation."

Clinical • P2 data • Breast Cancer • Fatigue • Hematological Disorders • Hematological Malignancies • HER2 Breast Cancer • Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • HER-2

Efficacy and safety of tenalisib, a PI3K delta/gamma and SIK3 inhibitor in patients with locally advanced or metastatic breast cancer: Results from a phase II study (ESMO 2022) - P2 | "Preclinical studies in breast cancer cell lines have demonstrated that tenalisib potentiates the activity of taxol and doxorubicin. Tenalisib potentiated the activity of fulvestrant by inhibiting cell growth and causing cell cycle arrest in both MCF-7 and ZR.75.1 breast cancer cell lines...Based on the data from the ongoing study, overall efficacy response as a single agent in both primary and secondary resistant MBC continues to be encouraging and supports further development in MBC. Updated efficacy and tolerability data will be presented at the conference."

Clinical • P2 data • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • HER-2

Safety and Efficacy of Tenalisib Given in Combination with Romidepsin in Patients with Relapsed/Refractory T-Cell Lymphoma: Final Results from a Phase I/II Open Label Multi-Center Study (ASH 2021) - P1/2 | "The combination of tenalisib and romidepsin demonstrates a favorable safety profile and promising anti-tumor activity in patients with R/R TCL. Based on these encouraging results, further development of this combination in PTCL patients in being planned."

Clinical • Combination therapy • P1/2 data • Cutaneous T-cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • Septic Shock • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • Transplantation

Efficacy and safety of tenalisib, a PI3K δ/γ and SIK3 inhibitor in patients with locally advanced or metastatic breast cancer: Initial results from a phase II study. (ASCO 2022) - P2 | "Preclinical studies in breast cancer cell lines have demonstrated that Tenalisib potentiated the activity of taxol and doxorubicin...Pts had a median of 3 (range 1-7) lines of prior therapy; of these, 87% pts had prior endocrine therapy, and 40% and 30% pts had aromatase inhibitor or fulvestrant as their last prior therapy respectively... Based on the data from the ongoing study, Tenalisib showed encouraging preliminary efficacy as a single agent in patients with advanced MBC. Updated efficacy and tolerability data will be provided at the time of presentation."

Clinical • P2 data • Breast Cancer • Fatigue • Hematological Disorders • Hematological Malignancies • HER2 Breast Cancer • Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Triple Negative Breast Cancer • HER-2

A Study of CN1 in Combination With CN401 in Adult Patients With Relapsed/Refractory Lymphoid Malignancies (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: Curon Biopharmaceutical (Australia) Co Pty Ltd | N=78 ➔ 7 | Trial completion date: Jul 2023 ➔ Sep 2022 | Recruiting ➔ Terminated; Sponsor decided that there was no benefit in the drug treatment and due to company change in landscape in the new year.

Combination therapy • Enrollment change • Trial completion date • Trial termination • Hematological Malignancies • Oncology