On December 6, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported preliminary tolerability and PK data from its ongoing Phase 1 dose-finding study of fimepinostat, a small molecule dual inhibitor of PI3K/HDAC and suppressor of MYC, in combination with venetoclax, a BCL-2 inhibitor, for the treatment of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including patients with double-hit/double-expressor (DH/DE) lymphoma (Press release, Curis, DEC 6, 2019, View Source [SID1234551998]).

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"We are very pleased with the progress in our ongoing Phase 1 study, with the combination of fimepinostat and venetoclax demonstrating a favorable tolerability profile thus far," said James Dentzer, President and Chief Executive Officer of Curis. "We believe demonstrating that this combination is generally well-tolerated for patients is a significant milestone, as both drugs have shown activity as monotherapies in this patient population and we believe activity will be improved by combining the two agents. Based on these data, we plan to initiate an expansion of the current study in 2020."

To date, the study has enrolled 11 patients, 6 patients in the first cohort and 5 patients in the second cohort. Patients in the first cohort received 30mg once-daily (QD) of fimepinostat and 400mg QD of venetoclax, while the patients in the second cohort received 60mg QD of fimepinostat and 400mg QD of venetoclax. To date the combination has been generally well-tolerated by patients.

"There is an urgent need for therapies targeting MYC and BCL-2 alterations, particularly in DH/DE lymphoma, a disease defined by these alterations and one of the deadliest types of lymphoma," said Robert Martell, M.D, Ph.D, Head of R&D at Curis. "We believe fimepinostat is unique in its ability to target MYC through simultaneous inhibition of both PI3K and HDAC. Venetoclax is a rapidly-acting inhibitor of BCL2, the other key abnormality in DH lymphoma. Supported by synergistic anti-cancer effects observed in preclinical models, we believe this is an ideal combination to target DLBCL and we look forward to gaining further insights on the combination from this study.

Dr. Martell continued: "The study was designed with initial patients undergoing a several-week run-in period allowing detailed PK interaction analysis and venetoclax ramp-up to be performed. In preliminary analyses, we found the combination to be generally well tolerated, with no dose-limiting toxicity (DLT) in the first cohort and one DLT of transient grade 3 diarrhea in the second cohort. Importantly, we found no drug-drug PK interaction that required dose modification of either agent. Drug-drug interactions are a major problem for many drugs combining with venetoclax, and we are encouraged that we have not seen such interaction to date with fimepinostat."

Curis’ ongoing Phase 1, open-label, multi-center, dose-finding 3+3 study is designed to evaluate the safety and tolerability, PK and pharmacodynamics, and preliminary activity of the fimepinostat and venetoclax combination in patients with DLBCL, including those with DH/DE lymphoma. Patients are enrolled in two cohorts in the study, with fimepinostat administered on a 5-days-on-2-days-off schedule in combination with venetoclax in 21-day cycles. Curis plans to initiate an expansion of the current study in 2020.

Conference Call Information

Curis management will host a conference call today, December 6, 2019, at 8:00 a.m. ET, to discuss these results. To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 8:00 a.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section.

On December 6, 2019 Beijing Hygea Medical Technology reported that it closed a $28 million Series B funding to develop its minimally invasive cryogenic treatment for cancer (Press release, Hygea Medical Technology, DEC 6, 2019, View Source [SID1234551996]). The round was led by Jianxing Medical Fund under the management of CCB International, with participation from Kunying Capital and Shuncheng Capital. Hygea holds 14 patents for its proprietary HYG KB Cryosurgical System and HYG KBD Sterile Cryosurgical Probes. It is also developing cancer diagnostics. An affiliate of the China Academy of Sciences, Division of Physics and Chemistry, Hygea has been supported by China’s 863 program and other China national and Beijing funds.

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On December 6, 2019 Bristol-Myers Squibb Company (NYSE: BMY) and bluebird bio, Inc. (Nasdaq: BLUE) reported positive top-line results from KarMMa, a pivotal, open-label, single arm, multicenter, Phase 2 study of idecabtagene vicleucel (ide-cel; bb2121) (Press release, bluebird bio, DEC 6, 2019, View Source [SID1234551995]). KarMMa, which evaluated the efficacy and safety of the companies’ lead investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy candidate for patients with relapsed and refractory multiple myeloma, met its primary endpoint and key secondary endpoint.

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KarMMa enrolled 140 patients, of whom 128 patients were treated with ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells. All treated patients were exposed to at least three prior therapies, including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and all were refractory to their last regimen. Ninety-four percent of patients were refractory to an anti-CD38 antibody and 84% percent were triple refractory (refractory to an IMiD agent, PI and anti-CD38 antibody).

Results for the primary endpoint (overall response rate [ORR]) and key secondary endpoint (complete response rate [CR]), as well as duration of response (DoR) and progression-free survival (PFS) across the target dose levels and at each of the three target doses explored in the study are presented in the table below. The median follow-up duration for all subjects was 11.3 months.

Median DOR and median PFS are not reported for the 150 x 106 CAR+ T cells

dose group due to the small number of evaluable patients

Overall, the safety results were consistent with those observed in the phase 1 CRB-401 study, which evaluated the preliminary safety and efficacy of ide-cel. Instances of grade 3 or higher cytokine release syndrome (CRS) occurred in 5.5% (7/128) of patients, including one fatal CRS event. Investigator identified grade 3 or higher neurotoxicity events (iiNT) occurred in 3.1% (4/128) of patients and there were no Grade 4 iiNT events reported. Grade 3 or higher CRS and iiNT events were reported in <6% of subjects at each target dose. CRS of any grade occurred in 83.6% (107/128) of patients and iiNT of any grade occurred in 18% (23/128) of patients.

"For multiple myeloma patients who have relapsed and become refractory to current treatment options, there remains a high unmet need, as these patients typically experience low response rates, short response durations and poor survival," said Kristen Hege, M.D., Senior Vice President, Hematology/Oncology and Cell Therapy, Early Clinical Development for Bristol-Myers Squibb. "The KarMMa study provides further support for ide-cel as a potential therapeutic option in this heavily pre-treated patient population, and we are encouraged by these data, especially the outcomes observed at the highest target dose of 450 x 106 CAR+ T cells. We are actively preparing for submission of these data to Health Authorities for proposed initial registration of ide-cel as a first-in-class BCMA-targeted CAR T cell therapy."

"Multiple myeloma is a relentless disease and there is significant need to find new treatment options for patients who advance through the current therapies available to them," said Joanne Smith-Farrell, Ph.D., oncology franchise lead and chief business officer, bluebird bio. "With these data in hand, bluebird bio and Bristol-Myers Squibb remain fully focused on advancing ide-cel as quickly as possible for patients in late-line myeloma, while continuing to execute our broad development program to understand the potential benefits of ide-cel across earlier lines of therapy."

More comprehensive data from KarMMa will be submitted for presentation at a future medical meeting.

About KarMMa

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multi-center phase 2 study evaluating the efficacy and safety of ide-cel in adult patients with relapsed and refractory multiple myeloma, in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival and minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an IMiD agent, a PI and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

About Ide-cel

Ide-cel is a CAR T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The ide-cel CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta activation domain, and a 4-1BB co-stimulatory domain hypothesized to increase T-cell activation, proliferation and persistence. Ide-cel CAR T cells are proposed to recognize and bind to BCMA on the surface of multiple myeloma cells leading to apoptosis.

In November 2017, ide-cel was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration and PRIority Medicines (PRIME) eligibility by the European Medicines Agency based on preliminary clinical data from the phase 1 CRB-401 study.

Bristol-Myers Squibb and bluebird bio’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3) in earlier lines of treatment for patients with multiple myeloma. For more information visit: clinicaltrials.gov.

Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between BMS and bluebird bio.

Ide-cel is not approved for any indication in any geography.

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

On December 6, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported that highlighted three upcoming ELZONRIS (tagraxofusp), presentations, including an oral presentation of ELZONRIS clinical data in myelofibrosis, at this year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, that is being held from December 7-10 in Orlando, FL (Press release, Stemline Therapeutics, DEC 6, 2019, View Source [SID1234551990]).

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Details on the ASH (Free ASH Whitepaper) presentations are as follows:

Myelofibrosis – ELZONRIS monotherapy, clinical; oral presentation
Title: Results from a Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate, or High Risk, Relapsed/Refractory Myelofibrosis
Presenter: Naveen Pemmaraju, MD; MD Anderson Cancer Center
Abstract: 558
Session: 634. Myeloproliferative Syndromes: Clinical: Emerging and Novel Targeted Therapies
Date/Time: Monday, December 9, 2019 8:15 AM ET
Location: Orange County Convention Center, W304EFGH

Multiple Myeloma – ELZONRIS in combination with Pom+Dex, clinical; poster presentation
Title: Results from Phase 1/2 Trial of Tagraxofusp in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Presenter: Paul G. Richardson, M.D.; Dana-Farber Cancer Institute
Abstract: 3145
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
Date/Time: Sunday, December 8, 2019 6:00 PM–8:00 PM ET
Location: Orange County Convention Center, Hall B

Myeloproliferative Neoplasms – ELZONRIS in combination with ruxolitinib, preclinical; poster presentation
Title: Evaluation of Tagraxofusp (SL-401) Alone and in Combination with Ruxolitinib for the Treatment of Myeloproliferative Neoplasms
Presenter: Aishwarya Krishnan, MD; Memorial Sloan Kettering Cancer Center
Abstract: 2967
Session: 635. Myeloproliferative Syndromes: Basic Science: Poster II
Date/Time: Sunday, December 8, 2019 6:00 PM–8:00 PM ET
Location: Orange County Convention Center, Hall B

About ELZONRIS
ELZONRIS (tagraxofusp-erzs), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

On December 6, 2019 MSD K.K. (president and CEO Jannie Oosthuizen, Chiyoda-ku, Tokyo) and Taiho Pharmaceutical Co., Ltd. (president and CEO Masayuki Kobayashi, Chiyoda-ku, Tokyo) reported that they have agreed to terminate their co-promotion contract in Japan at the end of December 2019 for KEYTRUDA (pembrolizumab [genetical recombination]), anti-PD-1 therapy manufactured and marketed by MSD (Press release, Taiho, DEC 6, 2019, View Source [SID1234551969]).

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KEYTRUDA was launched on February 15, 2017 and has been co-promoted by MSD and Taiho Pharmaceutical in Japan. From January 2020, MSD will continue manufacturing, distribution and promotion of KEYTRUDA.

MSD and Taiho Pharmaceutical believe that they could make a significant contribution to patients and healthcare professionals by providing a novel cancer treatment option through the co-promotion activities. The companies will continue their commitment to the advancement in cancer therapy in the course of their business activities.