DTRMWXHS-12 / Zhejiang DTRM Biopharma - LARVOL DELTA

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=55 | Terminated | Sponsor: Zhejiang DTRM Biopharma | N=120 ➔ 55 | Active, not recruiting ➔ Terminated; Despite the efforts of our dedicated team and initial progress, we were unable to secure the necessary financial resources to continue the study. We appreciate the support and participation of all involved.

Enrollment change • Trial termination • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Zhejiang DTRM Biopharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Zhejiang DTRM Biopharma | Trial completion date: Mar 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2024 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Extended Abstract: New BTKi (SOHO 2022) - "It has also been studied in combination with idelalisib or entospletinib in CLL and other B-cell lymphomas though without clear benefi t for the combinations over monotherapy16,17. Tirabrutinib is approved in Japan for WM, lymphoplasmacytic lymphoma (LPL), and RRPCNSL, and in South Korea for RR-PCNSL18. TG-1701 is a selective covalent BTKi that has been studied as a monotherapy and in combination with ublituximab and umbralisib with preliminary results suggesting both effi cacy and manageable safety19. Orelabrutinib, another selective covalent BTKi, has been studied as a monotherapy in CLL in addition to other B-cell malignancies, also with favorable safety and effi cacy20,21 and it is approved in China for rel/ref CLL and MCL22. Finally, DTRMWXHS-12 is a covalent BTKi that uniquely is being studied in combination with everolimus and pomalidomide (triplet referred to as DTRM-555), given that this combination was determined to lead to synthetic lethality in both in vivo..."

IO biomarker • Chronic Lymphocytic Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • FLT3 • IL2 • ITK • PLCG2

DTRMWXHS-12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: an open-label, multicenter, phase 1a/1b study. (PubMed, Am J Hematol) - "Our dose escalation study used an accelerated titration design and moved sequentially from single agent BTKi (DTRMWXHS-12), doublet (DTRMWXHS-12 + everolimus), and then to triplet therapy (DTRMWXHS-12 + everolimus + pomalidomide). Combining DTRMWXHS-12 with everolimus and pomalidomide is tolerable and shows clinical activity. Additional trials could confirm benefit of this all-oral combination therapy for relapsed/refractory lymphomas."

Combination therapy • Journal • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Lymphoma • Oncology

BTK Inhibitor DTRMWXHS-12 in Mantle Cell Lymphoma (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Zhejiang DTRM Biopharma | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • CCND1

Simultaneous Global Phase I Studies of a Differentiated BTK Inhibitor, Dtrmwxhs-12, in Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia and B-Cell Lymphomas (ASH 2017) - P1,P1a/1b; "Background: Ibrutinib is the first-in-class Bruton’s tyrosine kinase inhibitor (BTK) approved by the FDA as breakthrough therapy for the treatment of B cell lymphomas and CLL at 560 mg or 420 mg once daily. Results of two simultaneous phase I studies demonstrate that DTRM-12 monotherapy is well tolerated across B cell malignancies and CLL in 18 pts. In both studies, no DLTs occurred and an MTD was not identified. PK studies demonstrate adequate target drug exposures in all pts at all dose levels."

P1 data • Biosimilar • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hodgkin Lymphoma • Indolent Lymphoma

A phase Ia/Ib study of a novel BTK inhibitor, DTRMWXHS-12 (DTRM-12), and combination products, with everolimus and pomalidomide, in pts with CLL or other B-cell lymphomas. (ASCO 2017) - P1a/1b; "Up to 50 pts will be enrolled. Five additional sites are planned to open in the near future across the US."

Biosimilar • Chronic Lymphocytic Leukemia • Indolent Lymphoma

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Zhejiang DTRM Biopharma | Trial completion date: Mar 2022 ➔ Mar 2024 | Trial primary completion date: Mar 2022 ➔ Mar 2024

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

A Phase Ia/Ib Study Exploring the Synthetic Lethality of the Orally Administered Novel BTK Inhibitor, Dtrmwxhs-12 (DTRM-12), in Combination with Everolimus and Pomalidomide in Patients with Relapsed/Refractory CLL, DLBCL or Other B-Cell Lymphomas (ASH 2019) - P1a/1b; "Median prior therapies were 3 (range 1-10), 53% had been treated with ≥1 prior targeted agent (i.e., CD19/CD3 bispecific antibody, obtinutuzumab, pembrolizumab, nivolumab, ibrutinib, venetoclax, PI3k-i), CAR-T or HSCT. Thus synthetic lethality is a viable treatment approach. A phase II US expansion study is underway targeting pts with transformed lymphomas (follicular or prior CLL) and r/r DLBCL cohorts."

Clinical • Combination therapy • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

[VIRTUAL] A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter’s Transformation and De Novo Diffuse Large B-Cell Lymphoma (ASH 2020) - P1a/1b | "DTRM-555 is an optimized oral triple combination of a novel irreversible BTKi DTRMWXHS-12 (DTRM-12), everolimus (EV) and pomalidomide (POM). This clinical trial met its primary endpoint. The once-daily oral triple combination therapy DTRM-555 has an acceptable safety profile. Encouraging clinical activity was observed in several high-risk, multi-refractory pts with RT (median 5 prior therapies, ORR 45%) or r/r DLBCL (median 2 prior therapies, ORR 60%), including pts previously treated with targeted therapies, cellular therapies, checkpoint inhibitors and other experimental agents."

Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation

BTK Inhibitor DTRMWXHS-12 in Mantle Cell Lymphoma (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: Zhejiang DTRM Biopharma; Trial completion date: Sep 2021 ➔ Nov 2022; Trial primary completion date: Sep 2021 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CCND1 • MRI • PCR

Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas (clinicaltrials.gov) - P1a/1b; N=48; Completed; Sponsor: Zhejiang DTRM Biopharma; Recruiting ➔ Completed

Clinical • Trial completion • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Safety, Tolerability and PK of BTK Inhibitor DTRMWXHS-12 in Patients With B-Cell Lymphomas (clinicaltrials.gov) - P1; N=13; Completed; Sponsor: Zhejiang DTRM Biopharma; Recruiting ➔ Completed; N=36 ➔ 13

Clinical • Enrollment change • Trial completion

BTK Inhibitor DTRMWXHS-12 in Mantle Cell Lymphoma (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: Zhejiang DTRM Biopharma; Recruiting ➔ Active, not recruiting; Trial completion date: Jan 2022 ➔ Sep 2021

Clinical • Enrollment closed • Trial completion date • PCR

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Zhejiang DTRM Biopharma

Clinical • Combination therapy • New P2 trial • BCL2

BTK Inhibitor DTRMWXHS-12 in Mantle Cell Lymphoma (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Zhejiang DTRM Biopharma

Clinical • New P1 trial