On January 8, 2020 Intensity Therapeutics, Inc., a clinical-stage biotechnology company developing proprietary intratumoral immunotherapy products to kill tumors and increase immune system recognition of solid cancers, reported that Lewis H. Bender, President and CEO, will be a featured panelist on the "Developments in The Oncology Landscape" panel at East/West CEO (Press release, Intensity Therapeutics, JAN 8, 2020, View Source [SID1234552851]). The conference will take place January 11-12, 2020, the weekend before the 38th Annual J.P. Morgan Healthcare Conference, at the Four Seasons Hotel in San Francisco.
The panel, which will examine the next wave of innovations and developments in oncology, will be held on Sunday, January 12, 2020 from 1:45 p.m. to 2:15 p.m. PST.

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On January 8, 2020 HUYA Bioscience International CEO & Executive Chair, Dr. Mireille Gillings reported the appointment of Meiji Seika Pharma (Meiji) as an exclusive distributor for its lymphoma product, HBI-8000, in Japan (Press release, HUYA Bioscience, JAN 8, 2020, View Source [SID1234552850]). Meiji also acquired exclusive rights for HBI-8000 in Japan, South Korea, Thailand, Malaysia, Indonesia, Philippines, Vietnam and Singapore. The drug, an epigenetic immunomodulator, is the first approved oral class I-selective histone deacetylase inhibitor which is now in various stages of development globally for Peripheral T-Cell Lymphoma (PTCL) and Adult T-Cell Leukemia (ATL) in Japan and solid tumors in the United States. Increased excitement has been generated by studies that show that HBI-8000 produces cumulative effects over time that increase the receptivity of cancer cells to immunologic therapy.

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The product has orphan drug designation for PTCL granted by Japan’s Ministry of Health, Labor and Welfare. HUYABIO will complete the development of HBI-8000 for PTCL and ATL in Japan for commercialization by Meiji who will hold exclusive sales and marketing rights. Meiji will pay HUYABIO an upfront and milestones plus royalties on net sales. HUYABIO will manufacture and supply the product to Meiji for initial commercialization.

"This collaboration aligns with Meiji’s R&D commitment to oncology to develop new drugs to fulfil unmet needs of patients worldwide. By continually improving our R&D process with innovation, Meiji brings high-value and high-quality drugs to market quickly. Meiji and HUYABIO will cooperate to commercialize HBI-8000, for the benefit of cancer patients" said Daikichiro Kobayashi, President and Representative Director of Meiji Seika Pharma Co, Ltd.

"We are delighted to enter into this partnership with Meiji to bring HBI-8000 to patients with PTCL or ATL. We also look forward to advancing the development of our drug based on its immunomodulatory properties" said Dr. Mireille Gillings. "The agreement reinforces our vision to leverage assets licensed from China for global development and commercialization. Meiji Seika Pharma’s strong position in hematologic malignancy will help ensure the drug’s success in the Japanese market."

About HBI-8000
The novel epigenetic drug, HBI-8000, is a member of the benzamide class of histone deacetylase inhibitors, which regulate gene expression through histone modification, which enables the efficacy of increasing other cancer agents such as checkpoint inhibitors.

The company was the first to leverage the Tripartite Agreement between China, Japan and South Korea, which allowed Chinese clinical data to be leveraged in the other two countries. Based on clinical results, the Japanese Pharmaceutical and Medical Devices Agency allowed accelerated development of this drug in lymphoma.

On January 8, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported independent centrally reviewed top-line data for pralsetinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC) (Press release, Blueprint Medicines, JAN 8, 2020, View Source [SID1234552846]). The data from the ongoing Phase 1/2 ARROW clinical trial of pralsetinib showed a 61 percent objective response rate (ORR) and prolonged durability, with a median duration of response (DOR) not reached, in patients with RET fusion-positive NSCLC previously treated with platinum-based chemotherapy. Designed by Blueprint Medicines, pralsetinib is a potent and highly selective once-daily oral inhibitor of RET fusions and mutations, including predicted resistance mutations.

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In addition, Blueprint Medicines announced it has initiated the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for pralsetinib for the treatment of patients with RET fusion-positive NSCLC. The company expects to complete the NDA submission in the first quarter of 2020. Blueprint Medicines also plans to submit an NDA to the FDA for pralsetinib for the treatment of patients with medullary thyroid cancer (MTC) previously treated with an approved multi-kinase inhibitor in the second quarter of 2020.

"As the clinical data for pralsetinib have matured, with deep and durable responses along with robust evidence of activity against brain metastases, our confidence has continued to grow in the potential of pralsetinib to provide lasting benefit to a broad population of patients with RET fusion-positive NSCLC, including those with newly diagnosed unresectable or metastatic disease," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "Now, with strong, centrally reviewed top-line data, we feel a profound sense of urgency and have taken the first step toward making pralsetinib broadly available to patients by initiating a rolling NDA submission to the FDA."

Top-line Data from Phase 1/2 ARROW Trial in RET Fusion-Positive NSCLC

Results from the Phase 1/2 ARROW clinical trial of pralsetinib will be used to support the NDA submission for pralsetinib for the treatment of patients with RET fusion-positive NSCLC. The registration endpoints are ORR and DOR based on independent central radiology and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria.

Top-line efficacy data were reported for patients treated with pralsetinib who were evaluable for response assessment per RECIST 1.1, as determined by blinded independent central review. All patients received the proposed indicated dose of 400 mg once daily (QD).

In 80 patients with RET fusion-positive NSCLC previously treated with platinum-based chemotherapy, the ORR was 61 percent (95% CI: 50-72%) per independent central review (two responses pending confirmation) as of a data cutoff date of November 18, 2019. Overall, 95 percent of patients had tumor shrinkage, including 14 percent of patients with complete regression of target tumors. The median DOR was not reached (95% CI: 11.3 months, not estimable).

In 26 patients with treatment-naïve RET fusion-positive NSCLC, the ORR was 73 percent (95% CI: 52-88%) per independent central review (all responses confirmed), with 12 percent of patients achieving a complete response. All patients had tumor shrinkage.

Top-line safety data were consistent with those previously reported. Pralsetinib was well-tolerated, and most adverse events (AEs) were Grade 1 or 2. Across all patients enrolled in the ARROW trial treated with the proposed indicated dose of 400 mg QD (N=354), only four percent of patients discontinued treatment with pralsetinib due to treatment-related AEs.

Blueprint Medicines plans to present the full registration dataset at a scientific meeting later this year.

Planned Phase 3 AcceleRET Lung Trial in Treatment-Naïve RET Fusion NSCLC

In addition, Blueprint Medicines plans to initiate the first clinical trial site for its Phase 3 AcceleRET Lung clinical trial in January 2020. The primary objective of the AcceleRET trial is to evaluate the potential of pralsetinib to extend progression free survival (PFS) compared to platinum-based chemotherapy with or without pembrolizumab in patients with first-line RET fusion-positive NSCLC.

The global, randomized AcceleRET trial will enroll approximately 250 patients with advanced or metastatic RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease. Participants will be randomized to receive either pralsetinib or the investigator’s choice of platinum-based chemotherapy regimen with or without pembrolizumab. The trial’s primary endpoint is PFS and secondary endpoints include overall survival, ORR and DOR. Patients may receive local testing to identify a RET fusion. In addition, patients randomized to the control arm may crossover upon progression to receive pralsetinib. Multiple trial sites are planned in North America, Europe and Asia.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer (PTC), while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant, EGFR-mutant NSCLC.

Currently, there are no approved therapies that selectively target RET-driven cancers, although there are several approved multi-kinase inhibitors (MKIs) with RET activity being evaluated in clinical trials. To date, clinical activity attributable to RET inhibition has been uncertain for these approved MKIs, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and anticipated resistance mutations.

About Pralsetinib

Pralsetinib is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing pralsetinib for the treatment of patients with RET-altered NSCLC, MTC and other solid tumors. The FDA has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET-fusion positive NSCLC that has progressed following platinum-based chemotherapy, and RET-mutant MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Pralsetinib was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, pralsetinib

demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 90-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, pralsetinib has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of pralsetinib, avapritinib and fisogatinib in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for all three drug candidates in the rest of the world.

On January 8, 2020 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported an update from several clinical development programs and a 2020 business overview (Press release, Bio-Path Holdings, JAN 8, 2020, View Source [SID1234552845]).

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"We enter 2020 with robust development plans to commence several key clinical trials that are expected to advance our DNAbilize antisense RNAi nanoparticle technology in a number of important oncology indications for which there are limited treatment options," said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. "We are excited to initiate a number of important studies across our development pipeline and anticipate reporting key clinical datapoints from those studies later in the year."

Phase 2 Study of Prexigebersen in Untreated and Refractory/Resistant Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) Patients

In March 2019, Bio-Path announced a revised strategy for the Stage 2 portion of its Phase 2 clinical trial of prexigebersen in combination with frontline chemotherapy. Bio-Path’s amended Stage 2 of the Phase 2 clinical trial will treat two cohorts of patients. The first cohort is to include untreated AML patients as existed in the pre-amended trial but with the addition of untreated, high-risk MDS patients. The second cohort is to include refractory/relapsed AML patients and high-risk MDS patients. Both cohorts of patients are planned to be treated with the combination of prexigebersen, decitabine and venetoclax. The Company is finalizing amendments to add this combination treatment to Stage 2 of the Phase 2 clinical trial.

The first step in the revised strategy involved testing the safety of the combination of prexigebersen and decitabine. In November 2019, the Company announced successful completion of this safety testing in AML and MDS patients in Stage 2 of the Phase 2 clinical study. The safety segment of Stage 2 of the Phase 2 clinical trial comprised six evaluable patients who were treated with the combination of prexigebersen and decitabine. Although the combination of prexigebersen and decitabine is not the treatment currently planned for the efficacy evaluation of Stage 2 of the Phase 2 clinical trial, the efficacy profile in this safety segment of the study was very encouraging, with 50% of patients having a response, including two patients (33%) showing complete responses with incomplete hematologic recovery and one patient (17%) showing partial response. For reference, in this class of AML and MDS patients, the complete response rate to treatment with decitabine alone is approximately 20%. Some patients are continuing to receive treatment.

The next step in this Stage 2 of the Phase 2 program will be the safety testing of prexigebersen in combination with decitabine and venetoclax in six evaluable patients drawn from either of the two cohorts of untreated AML and high-risk MDS patients or relapsed/refractory AML and high-risk MDS patients. The Company currently expects to initiate this safety testing in the second quarter of 2020. Assuming successful completion of this safety testing, the Company plans that it would then initiate the efficacy testing of this triple combination in the two cohorts of patients. In 2020, Bio-Path intends to continue its efforts to expand the number of sites, including European-based sites, to enhance patient enrollment.

The clinical design of the Stage 2 portion of the Phase 2 clinical trial calls for an interim analysis of each cohort’s results after each cohort has treated 19 evaluable patients. If the results from either or both patient cohorts exceed expectations for current standard-of-care therapy, the Company expects that plans for a pivotal trial would be discussed with the FDA.

Phase 2a Study of Prexigebersen to treat Chronic Myeloid Leukemia (CML) in Tyrosine Kinase Inhibitor Failures and Accelerated and Blast Phase CML Patients

Bio-Path plans to enroll patients in a Phase 2a clinical study of prexigebersen in combination with the frontline therapy, dasatinib, for the treatment of CML in tyrosine kinase inhibitor failures and accelerated and blast phase patients in 2020. The trial is expected to be conducted at The University of Texas MD Anderson Cancer Center as a potential salvage therapy for accelerated and blast phase CML patients and will expand to other sites if feasible. Recent advances in the treatment of chronic phase CML patients with tyrosine inhibitors has limited the availability of these patients for the Bio-Path Phase 2a. As a result, the continuation of this study is being evaluated based on the potential for patient availability and clinical trial site expansion. If this Phase 2a study is advanced, it will evaluate two cohorts of three evaluable patients at two doses (60 mg/m2 and 90 mg/m2) of prexigebersen in combination with dasatinib.

Phase 1 Study of Prexigebersen in Patients with Advanced Solid Tumors

In late 2019, Bio-Path filed an Investigational New Drug (IND) application to initiate a Phase 1 clinical trial of prexigebersen in patients with advanced solid tumors, including ovarian and uterine, pancreatic and breast cancer. This trial is expected to commence after the IND has been cleared by the FDA, which we currently anticipate being in 2020, at several leading cancer centers and will evaluate the safety of prexigebersen in these patients. Assuming positive Phase 1 results, the Company expects it would advance to a Phase 1b clinical trial of prexigebersen in combination with frontline therapy in these same advanced solid tumor patients.

Phase 1 Study of BP1002 in Refractory or Relapsed Lymphoma Patients and Chronic Lymphocytic Leukemia Patients

In November 2019 the FDA cleared the IND for BP1002 (liposomal Bcl-2), the Company’s second drug candidate, to begin a Phase 1 clinical trial to evaluate BP1002 as a treatment for refractory/relapsed lymphoma and chronic lymphocytic leukemia patients. This study is expected to commence in the first half of 2020 and is expected to be conducted at several premier oncology centers, including the University of Texas MD Anderson Cancer Center, and is planned to evaluate the safety of BP1002 in several dose escalating cohorts to determine a maximum tolerated dose.

Preclinical Development of BP1003

The Company continues to advance its third investigational drug candidate, BP1003, for the treatment of advanced solid tumors, including pancreatic cancer. BP1003 is an antisense RNAi nanoparticle targeting the Stat3 protein.

In 2020 Bio-Path expects to complete several IND-enabling studies for BP1003. If those studies are successful, Bio-Path expects that it would file an IND in late 2020 for the first-in-humans Phase 1 study of BP1003 in patients with refractory/metastatic solid tumors including pancreatic, non-small cell lung cancer, and colorectal cancers.

BP1003 has demonstrated efficacy in combination with frontline therapies in animals against pancreatic tumors.

On January 8, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents that activate immune response to cancers, reported the dosing of the first patient with AGEN1223 (Press release, Agenus, JAN 8, 2020, View Source [SID1234552844]). AGEN1223 is a novel bi-specific antibody discovered by Agenus and designed to deplete regulatory T cells in the tumor microenvironment. The first patient was infused in December 2019 and the trial is underway with a plan to initiate combinations with balstilimab, Agenus’ investigational PD-1 inhibitor, in 2020.

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Dr. Anthony El-Khoueiry of the USC Norris Comprehensive Cancer Center and Keck School of Medicine was the clinical investigator dosing this first patient. Dr. El-Khoueiry is the phase I program director and a recognized expert in early drug development and translational medicine with a focus in hepatobiliary (liver, gall bladder, and bile duct) and pancreatic cancers.

"AGEN1223 is a novel bispecific antibody designed to selectively deplete specific immune-suppressive cells called regulatory T cells. The ability to deplete these cells in the tumor microenvironment may be an important treatment advantage for patients with cancer," said Dr. Anna Wijatyk, Head of Clinical Development at Agenus. "AGEN1223 is designed to eliminate the escape pathways that tumors use to continue to grow beyond multiple lines of therapy, including anti-PD-1 therapy. We believe that AGEN1223, due to its design to both selectively deplete intratumoral Tregs while sparing peripheral Tregs and to activate effector immune cells, represents an important novel therapy and promising combination agent for patients with aggressive tumors."

The Phase 1, open-label, multicenter study is designed to assess the maximum tolerated dose of AGEN1223 in subjects with advanced solid tumors. It will also evaluate the safety, tolerability, PK, and PD profiles and immunogenicity of this bi-specific antibody.

AGEN1223 was discovered by Agenus scientists and engineered to enhance immune functionality and immunogenicity. Our preclinical data show that AGEN1223 simultaneously engages two antigens that are co-expressed specifically on tumor-infiltrating Tregs thereby prompting their depletion. These data further show that cancer-fighting effector T cells and essential peripheral Tregs, which do not sufficiently co-express these targets, are largely spared from destruction. In addition to its Treg depleting capabilities, AGEN1223 can co-stimulate antigen-specific effector T cells that are essential for tumor killing in preclinical assays. Overall, AGEN1223 may represent a promising combination partner for a range of other therapeutic interventions – which could include checkpoint inhibitors, vaccines, or cell therapy. Gilead Sciences, Inc. has an exclusive option to license AGEN1223 as part of our December 2018 collaboration agreement with the company. Agenus is currently responsible for the development of AGEN1223. AGEN1223 and balstilimab are investigational agents. Their safety and efficacy are being evaluated in a Phase 1 clinical trial.