tulmimetostat (DZR123) / Novartis - LARVOL DELTA

CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Lan Coffman | Trial completion date: Aug 2028 ➔ Dec 2028 | Trial primary completion date: May 2025 ➔ Jul 2026

Platinum sensitive • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance. (PubMed, Funct Integr Genomics) - "Inhibitors like MAK683 and EED226 disrupt EED's ability to maintain PRC2 activity, thereby reducing H3K27me3 levels and reactivating tumor suppressor genes. Valemetostat, a dual inhibitor of both EZH2 and EED, has shown promising results in aggressive cancers like diffuse large B-cell lymphoma and small-cell lung cancer, underlining the therapeutic potential of targeting multiple PRC2 components...Tazemetostat, a selective EZH2 inhibitor, has demonstrated significant clinical efficacy in EZH2-mutant cancers, such as non-Hodgkin lymphomas and epithelioid sarcoma. However, the compensatory function of enhancer of zeste homolog 1 (EZH1) in some cancers requires dual inhibition strategies, as seen with agents like UNC1999 and Tulmimetostat, which target both EZH1 and EZH2. Given PRC2's multifaceted role in cancer biology, its inhibition represents a promising avenue for therapeutic intervention. The continued development of PRC2 inhibitors and exploration of their..."

IO biomarker • Journal • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • EZH2

CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Lan Coffman | Trial completion date: Aug 2029 ➔ Aug 2028 | Trial primary completion date: Jan 2027 ➔ May 2025

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Phase II dose optimization with EZH2/EZH1 inhibitor tulmimetostat in patients with ARID1A-mutated ovarian clear cell carcinoma (ESMO 2024) - P1/2 | "This ongoing Phase II data in patients with heavily pretreated ARID1A-mutated OCCC show signs of antitumor activity across dose levels. Response requirements to open Stage 2b have been met in this fast enrolling disease cohort. The safety profile across doses is consistent with EZH2 inhibition."

Clinical • P2 data • Oncology • Ovarian Cancer • ARID1A • EZH2 • STAT3

Phase II dose optimization with EZH2/EZH1 inhibitor tulmimetostat in patients (pts) with advanced solid tumors or hematologic malignancies. (ASCO 2024) - P1/2 | "The evolving Phase II data, including early data from lower doses, continue to show signs of antitumor activity/disease stabilization. The safety profile is consistent with EZH2 inhibition. These preliminary findings in heavily pretreated pts with multiple tumor types and evolving dose-optimization data support ongoing investigation of tulmimetostat."

Clinical • Metastases • P2 data • Anemia • Endometrial Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • EZH2

Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers. (PubMed, Cancer Res) - "Tulmimetostat administration achieved efficacy in multiple ARID1A mutant bladder, ovarian, and endometrial tumor models and improved cisplatin response in chemotherapy-resistant models. Importantly, a tulmimetostat controlled gene expression signature identified in whole blood from a cohort of 32 cancer patients correlated with tulmimetostat exposure, representing a pharmacodynamic marker for the assessment of target coverage for PRC2-targeted agents in the clinic. Collectively, this data suggests that tulmimetostat has the potential to achieve clinical benefit in solid tumors as a monotherapy but also in combination with chemotherapeutic agents and may be beneficial in various indications with recurrent ARID1A mutations."

Journal • Bladder Cancer • Endometrial Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer • ARID1A • BCL11B

Novartis meets all tender offer conditions to acquire MorphoSys AG for EUR 68 per share in cash (GlobeNewswire) - "Today, Novartis BidCo AG...announced the result of its voluntary public takeover offer (the 'Offer') for the shares of MorphoSys AG ('MorphoSys'), including all shares represented by MorphoSys American Depositary Shares ('ADS'). As of the expiry of the acceptance period at 24:00 hours CEST on 13 May 2024...The settlement of the shares tendered during the initial acceptance period is scheduled for 23 May 2024....With all offer conditions fulfilled, Novartis can now begin the necessary steps to progress the integration of MorphoSys, including full access to pelabresib (CPI-0610), a novel BET inhibitor in combination with ruxolitinib for patients with myelofibrosis. The integration also allows full access to tulmimetostat (CPI-0209), an early-stage investigational dual inhibitor of EZH1 and EZH2 currently being tested in patients with solid tumors or lymphomas."

M&A • Lymphoma • Myelofibrosis • Solid Tumor

MorphoSys To Present New Phase 3 MANIFEST-2 Data on Pelabresib in Myelofibrosis in Oral Presentation at 2024 ASCO Annual Meeting (ACCESSWIRE) - "MorphoSys AG...announced that new efficacy and safety data from the Phase 3 MANIFEST-2 trial of pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis will be highlighted during an oral presentation on Friday, May 31, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.....Additionally, new data from the Phase 2 study of tulmimetostat, an investigational next-generation dual inhibitor of EZH2 and EZH1, in patients with advanced solid tumors or hematologic malignancies will be showcased in a poster presentation at ASCO 2024."

P2 data • P3 data • Hematological Malignancies • Myelofibrosis • Solid Tumor

Novartis to strengthen oncology pipeline with agreement to acquire MorphoSys AG for EUR 68 per share or an aggregate of EUR 2.7bn in cash (GlobeNewswire) - "Novartis today announced that it has entered into an agreement to make a voluntary public takeover offer to acquire MorphoSys AG....The acquisition, which is subject to customary closing conditions, including a minimum acceptance threshold of 65% of outstanding shares tendered in the takeover offer and regulatory approvals, further expands and complements Novartis pipeline in oncology....Upon completion of the acquisition, Novartis will own pelabresib (CPI-0610), a novel and potentially practice changing treatment option with a well-tolerated safety profile provided in combination with ruxolitinib for patients with myelofibrosis (MF). It will also include tulmimetostat (CPI-0209), an early-stage investigational dual inhibitor of enhancer of zeste homolog 1 and 2 (EZH1 and EZH2) proteins currently being tested in patients with solid tumors or lymphomas."

M&A • Lymphoma • Myelofibrosis • Solid Tumor

CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Lan Coffman | Not yet recruiting ➔ Recruiting | Trial primary completion date: Dec 2027 ➔ Jan 2027

Combination therapy • Enrollment open • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Tulmimetostat (CPI-0209) in Patients With Mycosis Fungoides and Sézary Syndrome (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous T-cell Lymphoma • Dermatology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Lan Coffman | Trial completion date: Jan 2029 ➔ Jul 2029 | Initiation date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: Oct 2025 ➔ Dec 2027

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA

Tulmimetostat (CPI-0209) in Patients With Mycosis Fungoides and Sézary Syndrome (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Sep 2029 ➔ Dec 2029 | Initiation date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: Oct 2027 ➔ Jan 2028

Trial completion date • Trial initiation date • Trial primary completion date • Cutaneous T-cell Lymphoma • Dermatology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome

FIH: A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov) - P1/2 | N=286 | Recruiting | Sponsor: Constellation Pharmaceuticals | N=213 ➔ 286

Enrollment change • Metastases • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Peripheral T-cell Lymphoma • Prostate Cancer • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Urothelial Cancer • ARID1A • BAP1 • MSI • MUC16

EZH2/EZH1 INHIBITOR TULMIMETOSTAT (CPI-0209): PRELIMINARY PHASE II RESULTS AND FIRST BIOMARKER FINDINGS IN PATIENTS WITH ARID1A-MUTANT OVARIAN CLEAR CELL OR ENDOMETRIAL CARCINOMAS (OCCC/EC) (IGCS 2023) - P1/2 | "24 patients were enrolled (OCCC, n=14; EC, n=10); 50% of each cohort have received ≥3 prior treatment lines. Both cohorts are eligible for Stage 2 expansion, with 1 and 2 confirmed partial responses in patients with OCCC and EC, respectively (Table). The manageable safety profile across all 6 tumor cohorts (n=81) was consistent with known class effects; Grade ≥3 related adverse events (≥10% of patients) included thrombocytopenia, anemia, neutropenia, and diarrhea."

Biomarker • Clinical • P2 data • Endometrial Cancer • Oncology • Solid Tumor • ARID1A • EZH2 • STAT3

MorphoSys Receives U.S. FDA Fast Track Designation for Tulmimetostat in Endometrial Cancer (Morphosys Press Release) - "MorphoSys AG...announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for tulmimetostat, the company’s investigational next-generation dual inhibitor of EZH2 and EZH1, for the treatment of patients with advanced, recurrent or metastatic endometrial cancer harboring AT-rich interacting domain containing protein 1A (ARID1A) mutations and who have progressed on at least one prior line of treatment....Tulmimetostat is MorphoSys’ third clinical program to receive Fast Track designation from the FDA."

Fast track designation • Endometrial Cancer

Tulmimetostat (CPI-0209) in Patients With Mycosis Fungoides and Sézary Syndrome (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • Cutaneous T-cell Lymphoma • Dermatology • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • Solid Tumor

CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Lan Coffman

Combination therapy • New P1 trial • Oncology • Ovarian Cancer • Solid Tumor • BRCA

EZH2/EZH1 inhibitor tulmimetostat (CPI-0209) in patients with advanced solid tumors or hematologic malignancies: Preliminary phase II results. (ASCO 2023) - P1/2 | "Based on response criteria of ORR ≥1/10 pts, the ovarian (M2), endometrial (M3), and mesothelioma (M5) cohorts achieved eligibility for stage 2 expansion (not relevant in M4). The safety profile of tulmimetostat is consistent with EZH2 inhibition and previous data. These preliminary findings in heavily pretreated pts with multiple tumor types, including tumors with ARID1A alterations or BAP1 loss, support ongoing investigation of tulmimetostat."

Clinical • Metastases • P2 data • Alopecia • Anemia • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • ARID1A • BAP1 • EZH2 • STAT3

MorphoSys Highlights Potential of Its Mid- to Late-Stage Oncology Pipeline at 2023 ASCO and EHA Annual Meetings (PharmiWeb) - "The presentations on Monjuvi include: A poster presentation at EHA of final five-year efficacy and safety data from L-MIND (previously presented at American Association for Cancer Research Annual Meeting 2023). An e-publication at ASCO and EHA of a new five-year sub-group analysis from L-MIND....At ASCO, preliminary results from the Phase 2 portion of the study evaluating tulmimetostat across multiple tumor types will be presented during a poster session."

P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mesothelioma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Ongoing phase II study of EZH2 inhibitor CPI-0209 in patients with advanced solid tumors including metastatic castration-resistant prostate cancer (mCRPC) or hematologic malignancies (EAU 2023) - P1/2 | No abstract available

Clinical • Metastases • P2 data • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Prostate Cancer • Solid Tumor

Updated Findings and Biomarker Analysis From the Ongoing Phase 1 Study of Enhancer of Zeste Homolog 2 (EZH2) Inhibitor CPI-0209 in Patients With Advanced Solid Tumors (AACR-NCI-EORTC 2022) - P1/2 | "Given encouraging preliminary results from Phase 1, CPI-0209 will be further assessed in six disease-specific cohorts in Phase 2. Initial signs of efficacy from Phase 1 supported the inclusion of ARID1A and BAP1 as biomarkers in Phase 2."

Biomarker • Clinical • P1 data • Endometrial Cancer • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • ARID1A • BAP1

[VIRTUAL] Therapeutic potential of CPI-0209 (AACR 2021) - P1/2 | "In AR-dependent cells, CPI-0209 synergized with enzalutamide and overcame the anti-androgens resistance induced by AR alterations. Transcriptomic analysis revealed that CPI-0209 treatment modulated both AR-related and AR-independent pathways, which reveals a potential mechanism to explain the synergy of CPI-0209 and AR inhibitors. Thus, our results indicate that CPI-0209 may have the potential to be effective for AR-dependent mCRPC that are resistant to current AR inhibitors, supporting potential clinical development in mCRPC.Keywords: EZH2, prostate cancer, epigenetics, resistant"

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2

Preliminary Clinical Data From Ongoing Phase 2 Study With Enhancer of Zeste Homolog 2 (EZH2) Inhibitor CPI-0209 in Patients With Advanced Solid Tumors or Hematologic Malignancies (AACR-NCI-EORTC 2022) - P1/2 | "These preliminary data showed that heavily pretreated patients with multiple different tumor types may benefit from CPI-0209 treatment, encouraging further clinical investigations. The safety profile of CPI-0209 is consistent with the known mechanism of action and as expected in the underlying study population. Table."

Clinical data • P2 data • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • ARID1A • BAP1

MorphoSys Presents Preliminary Results from Phase 1/2 Study of Tulmimetostat (CPI-0209) Supporting Its Potential Application in a Broad Array of Advanced Tumors (Issuer Direct) - P1/2 | N=213 | NCT04104776 | Sponsor: Constellation Pharmaceuticals | "The data were presented during poster sessions at the 34th Symposium on Molecular Targets and Cancer Therapeutics....Of the 10 evaluable patients with ovarian clear cell carcinoma, four had a partial response and three had stable disease. Of the eight evaluable patients with metastatic castration-resistant prostate cancer, five had stable disease. Of the four evaluable patients with endometrial carcinoma, two had partial responses, one of whom later achieved a complete response after data cutoff, and two had stable disease. Two of the three evaluable patients with peripheral T-cell lymphoma had complete responses. For the nine evaluable patients with mesothelioma, there were two partial responses and four disease stabilizations....The disease control rate (complete and partial responses + disease stabilizations) at 375 mg was 66.7%. Disease control was noted across doses except at 137.5 mg."

P1/2 data • Endometrial Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Peripheral T-cell Lymphoma • Prostate Cancer • Solid Tumor • T Cell Non-Hodgkin Lymphoma • Thoracic Cancer • Uterine Cancer