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Presentation of Kura Oncology, Inc.

On January 13, 2020 Kura Oncology, Inc. prsented the corporate presentation (Presentation, Kura Oncology, JAN 13, 2020, View Source [SID1234553074]).

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Investor presentation furnished by Scholar Rock Holding Corporation on January 13, 2020

On January 13, 2020 Scholar Rock Holding Corporation presented the corporate presentation (Presentation, Scholar Rock, JAN 13, 2020, View Source [SID1234553073]).

Fate Therapeutics Announces Expansion of FT516 Clinical Investigation and Publication of Preclinical Data in the Journal Blood

On January 13, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the U.S. Food and Drug Administration (FDA) has allowed its second Investigational New Drug (IND) application for FT516, the Company’s off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel CD16 Fc receptor (Press release, Fate Therapeutics, JAN 13, 2020, View Source [SID1234553072]). This is the Company’s fourth IND from its proprietary iPSC product platform cleared by the FDA, and enables the clinical investigation of FT516 in combination with monoclonal antibody (mAb) therapy across a broad range of solid tumors.

"While monoclonal antibodies are proven therapeutic agents that are often used early in the treatment of many cancers, the functional status of the patient’s NK cells has been shown to play an important role in mediating clinical activity and prolonging survival," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In particular, stable expression of the NK cell activating receptor CD16, and its binding affinity to therapeutic antibodies, are critical to promoting antibody-dependent cellular cytotoxicity. Our first-of-kind, off-the-shelf approach with FT516 enables administration of multiple doses of CD16-engineered NK cells, and we are excited to investigate the potential of FT516 to augment the clinical efficacy of monoclonal antibody therapy in the setting of solid tumors."

FT516 expresses a novel high-affinity, non-cleavable variant of CD16 (hnCD16) that enhances its binding to therapeutic antibodies and prevents its down-regulation, which can significantly inhibit anti-tumor activity. A publication by scientists from the Company, the University of Minnesota, and the University of California, San Diego in the journal Blood (View Source), entitled "Pluripotent stem cell-derived NK cells with high-affinity non-cleavable CD16a mediate improved anti-tumor activity," highlights preclinical proof-of-concept data for FT516.

In the published studies, iPSC-derived NK cells expressing hnCD16 were shown to have superior therapeutic properties in vitro, including maintenance of CD16 expression and increased levels of cytokine production upon activation, compared to peripheral blood NK cells sourced from healthy donors. In an in vivo systemic tumor model of human lymphoma, treatment with iPSC-derived hnCD16 NK cells plus anti-CD20 mAb resulted in a significant improvement in survival (median survival exceeding 100 days) compared to treatment with anti-CD20 mAb alone or in combination with peripheral blood NK cells sourced from healthy donors (each of which showed median survival of 35 days). Additionally, iPSC-derived hnCD16 NK cells plus anti-HER2 mAb also conveyed a survival benefit in a xenograft model of SKOV-3 ovarian carcinoma.

FT516 is the first-ever cell therapy in the world derived from a genetically engineered pluripotent stem cell cleared for clinical testing. The Company intends to initiate clinical investigation of FT516 in combination with tumor-target antibody therapy in solid tumors later this year. The Company is currently conducting an open-label, multi-dose Phase 1 clinical trial of FT516 as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed mAbs for the treatment of advanced B-cell lymphoma.

Curis® and DarwinHealth Announce Scientific Collaboration to Characterize Biomarkers and Tumor Subtype Alignments for Fimepinostat in DLBCL and Solid Malignancies

On January 13, 2020 Curis, Inc (NASDAQ: CRIS) and DarwinHealth, Inc. reported a multi-year scientific research collaboration to use quantitative, systems biology-based algorithms, CLIA-approved technologies, and novel, validated approaches focused on Master Regulator (MR) proteins and tumor checkpoints to: (a) better understand and articulate the role of MYC in fimepinostat’s mechanism of action; and (b) explore additional potential novel biomarkers that may help patient selection in hematologic and solid tumors clinical studies (Press release, Curis, JAN 13, 2020, View Source [SID1234553071]).

The collaboration will deploy DarwinHealth’s proprietary compound-checkpoint-tumor subtype matching platform, its VIPER algorithm to characterize protein activity signatures that are the hallmark of regulatory network dysfunction in cancer cells, and its high-throughput drug perturbation and Plate-Seq discovery platform to analyze the potential therapeutic efficacy of fimepinostat (a synthetic, orally-available, small molecule that inhibits the activity of histone deacetylase, or HDAC, and phosphatidyl-inositol 3 kinase, or PI3 kinase enzymes) across a number of tumor subtypes.

"The aim of this exciting collaboration," explained Professor Andrea Califano, Clyde and Helen Wu Professor and Chair, Department of Systems Biology, Columbia University and co-founder of DarwinHealth, "is to assess and characterize the role of MYC as a critical effector of fimepinostat activity in DLBCL, as well as its overall, tumor-specific Mechanism of Action (MoA), considering that both HDAC and PI3K inhibitors have been independently characterized among the strongest regulators of tumorigenic MYC activity. Additionally, the collaboration will mechanistically characterize additional therapeutic opportunities for fimepinostat across multiple hematopoietic and solid tumor subtypes, as selected by Curis for this scientific collaboration. The study will leverage the VIPER algorithm to characterize fimepinostat’s activity against key Master Regulator (MR) protein modules (tumor checkpoints) necessary for subtype-specific tumor viability."

As part of this initiative, DarwinHealth will provide a comprehensive readout of fimepinostat’s potential clinical value across a number of cancer tissue-specific contexts, including its genome-wide mechanism of action, its tumor-specific biomarkers of sensitivity and resistance, and its ability to synergize with venetoclax for combination therapy applications in DLBCL and solid tumors. Through quantitative modeling, mechanism-driven and biomarker-driven developmental trajectories for fimepinostat will be predicted to help Curis design in vivo validation studies and focused clinical studies to leverage key opportunities for this dual HDAC/PI3 kinase inhibitor that would not be apparent using conventional technologies.

"In light of promising clinical data already reported for fimepinostat, and its unique MOA, our Compound-2-Clinic (C2C) collaboration with Curis promises to be one of our most productive scientific collaborations," noted Dr. Gideon Bosker, CEO and co-founder of DarwinHealth. "Our C2C technologies are ideally suited to identify mechanistic alignment between compounds and cancer patients, based on their ability to inactivate the patient-specific master regulator proteins that are necessary for tumor state maintenance. Compounds and compound combinations prioritized by this technology can be efficiently validated, first in PDX models and subsequently in the clinic, using our NYS State, CLIA-certified DarwinOncoTreat/Target tests. In addition to achieving a more mechanistic characterization of MYC as a critical effector of fimepinostat activity in DLBCL, our goal is to delineate the range of additional tumor subtypes—many of which may be entirely unanticipated—where fimepinostat may consistently and predictably collapse tumor checkpoint activity, thus abrogating tumor growth. These discoveries can be quickly matured to precision, biomarker-driven, clinical human testing and commercial development."

"This scientific collaboration aligns with our development path for fimepinostat by deepening our understanding of the MYC mechanism of action and potentially identifying additional, novel trajectories, indications, mechanisms, and precision-focused drug-tumor alignments that can produce a more inclusive developmental roadmap for our lead compound," said James Dentzer, President and Chief Executive Officer of Curis. "The DarwinHealth team led by Drs. Andrea Califano and Mariano Alvarez, who co-developed VIPER technology in the Califano Lab at Columbia University, bring world-class expertise that will be invaluable for identifying the full commercialization pathway for fimepinostat."

"DarwinHealth’s approach to tumor checkpoint elucidation, linked to MR proteins, will help support fimepinostat’s MYC-driven mechanism of action," said Dr. Robert Martell, Head of R&D at Curis. "This approach is also ideally suited for identifying additional biomarkers in our DLBCL program and illuminating additional tumor subtypes in which fimepinostat, alone or in combination with venetoclax, may have therapeutic potential. These mechanistically relevant insights will help us to focus on, test, and prioritize with a higher likelihood of success, the comprehensive translational roadmap for fimepinostat in targeted clinical contexts."

As part of this collaboration, DarwinHealth will be eligible for milestone payments and royalties for applications that directly result from their analyses.

Magenta Therapeutics Advances Conditioning Platform and Clinical Programs, Highlights Recent Milestones and 2020 Goals

On January 13, 2020 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, reported that recent progress across several programs and outlined goals for 2020 (Press release, Magenta Therapeutics, JAN 13, 2020, View Source [SID1234553070]). These updates will be discussed during a webcast presentation at the 38th annual J.P. Morgan Healthcare Conference on Wednesday, January 15th at 11:30 a.m. PT (2:30 p.m. ET).

"In 2019 we generated landmark data from our ADC-based targeted patient preparation platform, which is delivering a new class of antibody-drug conjugates (ADCs) that have the power to bring one-time treatment to more patients with autoimmune diseases, blood cancers and genetic diseases. We also presented clinical data for our first-line stem cell mobilization program, MGTA-145, which we are developing as the new standard of care for stem cell mobilization with the potential to benefit all of the transplant-eligible patients each year," said Jason Gardner, D. Phil., President and Chief Executive Officer, Magenta. "As we begin 2020, we are particularly excited to unveil our MGTA-117 clinical candidate for targeted patient preparation for stem cell transplant or gene therapy. New results announced today highlight the potency, safety and broad therapeutic index of MGTA-117, well above that of currently approved ADCs. We believe that MGTA-117 is the optimal agent for depleting stem cells to enable safe immune reset. We look forward to moving this program into the clinic with initial clinical data expected in 2021."

Targeted Patient Preparation Programs

Current methods to condition patients before transplant and gene therapy are dependent on toxic, non-specific chemotherapy or radiation. These pre-transplant treatments are associated with significant side effects, including infertility, cancer, organ damage and death. Magenta is developing targeted, disease-modifying ADCs that are designed to precisely and rapidly remove the disease-causing cells in the body and enable immune system reset without the need for chemotherapy or radiation.

CD117-ADC Recent Progress

Data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2019, showed the first-ever successful transplant of gene-modified cells in non-human primates using a CD117-targeted, single-agent ADC from Magenta, without the use of chemotherapy or radiation. These unprecedented results validate and advance Magenta’s conditioning platform.

Building on this work, Magenta’s new clinical candidate, MGTA-117, is a CD117 antibody conjugated to amanitin. Results published today in an abstract for the Transplant and Cellular Therapy annual meeting show that MGTA-117 potently depleted stem and progenitor cells and demonstrated a wide tolerability: potency ratio of 30 fold (therapeutic index; typical range for approved ADCs at this stage is two to six fold). This program is advancing to the clinic and further validates Magenta’s antibody drug conjugate-based conditioning platform. MGTA-117 was developed under a partnership with Heidelberg Pharma that grants Magenta exclusive worldwide development and marketing rights for ADCs using an amanitin payload and targeting CD117.

MGTA-117 in 2020

Magenta is scaling up manufacturing of MGTA-117 and completing IND-enabling studies in 2020. The Company intends to move this new product candidate into the clinic with initial clinical data expected in 2021.

CD45-ADC Recent Progress

Current standard treatment for patients with multiple sclerosis involves years of chronic dosing of medications that do not halt the progression of the disease. For patients with systemic sclerosis, a potentially fatal autoimmune disease, there are no approved therapies. Immune reset through stem cell transplant has demonstrated durable remissions in thousands of patients with autoimmune diseases such as multiple sclerosis and systemic sclerosis, and it is recommended by the European League Against Rheumatism (EULAR) in treatment guidelines for systemic sclerosis. The immune reset process involves two main steps: removing the disease-causing cells and replacing them with healthy cells to rebuild the immune system to a healthy state.

Magenta is developing targeted ADCs designed to precisely remove the disease-causing cells in the body without the need for chemotherapy or radiation. Magenta’s CD45-ADC program targets CD45, a protein expressed on immune cells and stem cells and is designed to remove the cells that cause autoimmune diseases in order to enable curative immune reset.

Data presented at the American College of Rheumatology (ACR) meeting in November 2019 showed that a single dose of CD45-ADC removed disease-causing reactive T cells, enabled successful immune reset and rebuild of the immune system and was well tolerated in three models of autoimmune disease, including the EAE model, the most reliable murine model of multiple sclerosis. Further, a single dose of CD45-ADC significantly reduced disease incidence and delayed disease onset in this model that has successfully provided preclinical proof of concept for many clinically validated standard-of-care therapies.

CD45-ADC in 2020

Magenta has identified a lead antibody and has progressed this program into IND-enabling studies, which the Company plans to further advance in 2020.

MGTA-145 First-Line Stem Cell Mobilization Therapy

MGTA-145 Recent Progress

Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases, blood cancers and genetic diseases. MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, to harness the physiological mechanism of stem cell mobilization.

Magenta is currently studying MGTA-145 and plerixafor in a Phase 1 study in healthy volunteers. Data from the Phase 1 study presented at the ASH (Free ASH Whitepaper) annual meeting in December 2019 showed that MGTA-145 in combination with plerixafor successfully enables safe, same-day dosing, mobilization and collection of sufficient high-quality hematopoietic stem cells for transplant. Further, when cells collected from the first two apheresis subjects were transplanted into humanized mice, the cells engrafted more rapidly and at a five-fold higher level than cells from G-CSF-mobilized peripheral blood.

MGTA-145 in 2020

Magenta intends to complete the Phase 1 study and move this program into multiple Phase 2 studies in patients in 2020. The Phase 2 studies will include both allogeneic and autologous transplant settings and will evaluate mobilization and collection of high-quality cells and engraftment of the cells after transplant.

MGTA-456 Cell Therapy

MGTA-456 Recent Progress

MGTA-456 is a cell therapy designed to provide a high dose of stem cells that are well matched to the patient to enable safe immune and blood system rebuild and durable remissions in patients with blood cancers. In September, the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation for MGTA-456 for the treatment of multiple inherited metabolic disorders.

Magenta is currently studying MGTA-456 in a Phase 2 study in patients with inherited metabolic disorders, including cerebral adrenoleukodystrophy (cALD) and Hurler syndrome. These are rare, rapidly progressive neurologic disorders that are fatal when left untreated. Results in the first two evaluable patients with cALD updated in December 2019 showed early and durable resolution of the disease at 12 months’ follow-up. The Loes score and NFS score, which measure progress of the disease, remained stable, suggesting that progress of the disease has been halted in these patients. The early and durable resolution of disease with MGTA-456 is not consistently seen with other therapies, including standard stem cell transplant, gene therapy or enzyme replacement therapy.

MGTA-456 in 2020

Magenta intends to complete enrollment in the Phase 2 in 2020 and continue dialogue with the FDA under the RMAT designation, and to discuss with the European Medicines Agency (EMA) for development in Europe