Gene therapy with implanted LED device automatically corrects heart rhythm disorder

Medical Xpress | February 28, 2019

Researchers at the Leiden University Medical Center (LUMC), in collaboration with Delft University of Technology, have found a way to reset a racing heart immediately and automatically with an implanted LED device. In the scientific journal Science Translational Medicine, they describe how their bioelectronic defibrillator works in the laboratory. It could be the first step towards a pain-free treatment for patients with atrial fibrillation.
The system detects fast arrhythmias in the atrium of a rat's heart and sends a signal to an LED device placed near the heart. "The flash of light from this LED then causes the heart to generate an electric current itself to halt the arrhythmia. This is made possible by using gene therapy to introduce specific light-sensitive proteins into the heart. This restores the heart's normal rhythm immediately and automatically," says principal investigator Daniël Pijnappels of LUMC's Department of Cardiology.
According to the researchers, this could represent a great improvement on the current way of stopping atrial fibrillation. Atrial fibrillation is the most common heart rhythm disorder in clinical practice. The current treatment, known as cardioversion, is based on administering an electric shock to the heart, which has to be done in the hospital under general anesthesia because of pain. For many patients, this is the only treatment to immediately stop atrial fibrillation, because drugs or operation are ineffective.

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Flamingo Therapeutics Expands Alliance with Ionis Pharmaceuticals to Develop RNA-targeted Therapies for Oncology

Flamingo Therapeutics, Inc. | September 09, 2021

Flamingo Therapeutics, Inc., a biotechnology company pioneering RNA-targeting therapies in oncology, today announced that it has entered into an agreement with Ionis Pharmaceuticals to develop RNA-targeted therapies to treat various forms of cancer. This alliance is an expansion of an existing collaboration with Ionis on the FLAME™ discovery engine, following Flamingo's Series A financing in 2020. The agreement and discovery alliance will leverage Flamingo's deep expertise in oncology and long non-coding RNAs (lncRNAs) in combination with Ionis' expertise in RNA-targeted drug discovery and development to advance candidates against targets considered undruggable with traditional approaches. Flamingo's pipeline will include three clinical-stage programs from Ionis, inhibitors of STAT-3, Androgen Receptor (AR) and IRF4, and one preclinical-stage program that targets MALAT1, a well-characterized lncRNA target. Flamingo will also advance its proprietary discovery engine, FLAME (Flamingo LncRNA Antisense Mining Engine), that addresses lncRNAs, a large and untapped class of disease-causing targets within the dark matter of the human genome. "We're thrilled to strengthen our relationship with Ionis who has been at the forefront of RNA-targeted therapy for thirty years," said Michael Garrett, Chief Executive Officer of Flamingo. "We believe the combination of Ionis' leadership in RNA and our cutting-edge lncRNA discovery engine will expand the opportunities for applying RNA-targeted approaches to oncology." "We are pleased that Flamingo is leveraging their core strengths in developing novel cancer medicines to advance innovative Ionis-discovered oncology therapies where there is an unmet need," said Brett P. Monia, Ph.D., Ionis' chief executive officer. In connection with the alliance, Rob MacLeod, Ph.D., VP, Oncology Research & Development of Ionis, will serve as Chief Scientific Officer of Flamingo. Under the terms of the agreement, Ionis is eligible to receive milestone payments and royalties on future product sales of the STAT3, AR, IRF4 and MALAT1 programs. Flamingo retains full rights to its FLAME platform and all lncRNA programs outside of MALAT1. Flamingo Therapeutics was founded by VIB, Ghent University, KU Leuven, the University of Michigan, Kurma Partners and PMV, based on pioneering work led by Professor Jean-Christophe Marine (VIB-KU Leuven), Professor Pieter Mestdagh (Ghent University) and Professor Arul Chinnaiyan (University of Michigan). These scientific teams broke new ground on non-coding RNA genes in cancer and were among the first to show a role for lncRNAs as disease drivers in oncology. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with state-of-the art chemistries. Flamingo has the most advanced antisense RNA-targeting oncology portfolio with three clinical programs targeting undruggable transcription factors and splice variants. To support and expand its pipeline, Flamingo has a proprietary discovery engine, FLAME™ (Flamingo LncRNA Antisense Mining Engine), that addresses lncRNAs, a large and untapped class of disease-causing targets within the "dark matter" of the human genome. The Company was founded in 2020 based on pioneering work in the field of lncRNAs in oncology with our academic partners at VIB, KU Leuven, Ghent University and the University of Michigan. Flamingo has a discovery alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors Kurma Partners and PMV. The company is headquartered in Belgium with additional operations in San Diego, CA.

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CELL AND GENE THERAPY

Imara Announces Primary Endpoint Change in the Ardent Phase 2b Clinical Trial of Tovinontrine (IMR-687) in Sickle Cell Disease

Imara | November 22, 2021

Imara Inc. a clinical-stage biopharmaceutical company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare inherited genetic disorders of hemoglobin and other serious diseases, today announced a change to the primary endpoint for the Ardent clinical trial, a Phase 2b study of tovinontrine (IMR-687) in patients with sickle cell disease (SCD), based on the recommendation of the U.S. Food and Drug Administration (FDA). Imara requested feedback from the FDA on the draft statistical analysis plan (SAP) for the Ardent trial in which fetal hemoglobin (HbF) response was the primary endpoint and annualized rate of vaso-occlusive crises (VOCs) was the key secondary endpoint. In reviewing the Ardent draft SAP and prior to any database lock for analysis, the FDA recommended that Imara change the primary endpoint to be annualized rate of VOCs. HbF response will continue to be evaluated as a key secondary endpoint. The endpoint revisions do not affect the conduct of the trial or operational aspects of the study. As part of its recommendation, the FDA suggested further interactions regarding the revised SAP and engagement on the potential of the current program for regulatory decision-making. “We welcome the FDA’s recommendations and are in the process of changing the primary endpoint of the Ardent trial to be annualized rate of VOCs and moving HbF response to be a key secondary endpoint. A reduction in VOC rate is an established approval endpoint, and we are engaging the FDA further on this and related topics, including possible streamlined paths to registration.” Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara Dr. Ballal continued, “In light of this endpoint revision, the previously planned fourth quarter interim analysis will no longer occur. That interim analysis had been designed to have a focus on safety and pharmacodynamic biomarkers, including HbF, but did not include a review of VOCs. The first review of data from the Ardent trial, including annualized VOC rate, will be conducted when all subjects have completed assessment at Week 24 or terminated early, and is planned for the first quarter of 2022, subject to our upcoming discussions with the FDA. Final data analysis from the Ardent trial remains on track for the second half of 2022. In June 2021, we reported promising data from our Phase 2a and open label extension clinical trials in SCD that demonstrated reduced annualized rates of VOCs in patients treated with tovinontrine versus placebo. We expect to present updated 12-month VOC data from our ongoing Phase 2a open label extension clinical trial at the American Society of Hematology Annual Meeting in December 2021.” About the Ardent Phase 2b Clinical Trial The Ardent Phase 2b clinical trial is a fully-enrolled, global, randomized, double-blind, placebo-controlled, multicenter study with approximately 115 adult patients with sickle cell disease (SCD) enrolled. The planned primary efficacy objective will be to evaluate the annualized rate of vaso-occlusive crises (VOCs) in patients dosed with tovinontrine (IMR-687) as compared to placebo. A key secondary endpoint will be to evaluate the proportion of all patients with fetal hemoglobin (HbF) response, defined as an absolute increase from baseline of at least 3% in HbF, as compared to placebo. Additional endpoints include the evaluation of the effect of tovinontrine versus placebo on other VOC-related outcome measures, HbF-associated biomarkers, markers of red blood cell hemolysis, white blood cell adhesion markers and quality of life measures over the course of a one-year treatment period. The FDA has granted Orphan Drug, Fast Track and Rare Pediatric Disease designations and the European Commission has granted Orphan Drug designation for tovinontrine for the treatment of SCD. About Tovinontrine (IMR-687) Tovinontrine is a highly selective and potent small molecule inhibitor of phosphodiesterase-9 (PDE9). PDE9 selectively degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology and hemoglobin production in red blood cells. 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SCD is characterized by debilitating pain, progressive multi-organ damage and early death. The global prevalence of SCD is estimated to be approximately 4.4 million patients, including an estimated 100,000 patients in the United States and 134,000 patients in the European Union. About Imara Imara Inc. is a clinical-stage biotechnology company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare inherited genetic disorders of hemoglobin and other serious diseases. Imara is advancing tovinontrine (IMR-687), a highly selective, potent small molecule inhibitor of PDE9 that is an oral, potentially disease-modifying treatment currently in clinical development for sickle cell disease and beta-thalassemia and preclinical development for heart failure with preserved ejection fraction, or HFpEF. Imara is also advancing IMR-261, an oral activator of nuclear factor erythroid 2–related factor 2, or Nrf2. Cautionary Note Regarding Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to (i) the Company’s plans to change the primary and secondary endpoints for the Ardent Phase 2b clinical trial of tovinontrine (IMR-687), (ii) the timing for reporting of additional data from the Ardent Phase 2b and open label extension clinical trials of tovinontrine in patients with sickle cell disease and (iii) the Company’s planned discussions with the FDA regarding the regulatory pathway for tovinontrine. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the impact of extraordinary external events, such as the risks and uncertainties resulting from the impact of the COVID-19 pandemic on the Company’s business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities and ability to readout data from the Ardent Phase 2b and open label extension clinical trials of tovinontrine in sickle cell disease; the Company’s ability to advance the development of tovinontrine under the timelines it projects in current and future clinical trials, demonstrate in any current and future clinical trials the requisite safety and efficacy of tovinontrine; and other factors discussed in the “Risk Factors” section of the Company’s most recent Quarterly Report on Form 10-Q, which is on file with the Securities and Exchange Commission and in other filings that the Company makes with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

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CELL AND GENE THERAPY

Cellares and Poseida Therapeutics Join Forces to Speed Up Cell Therapy Manufacturing

Cellares Corporation | July 16, 2021

Cellares Corporation, a life sciences technology company that has pioneered a revolutionary automated approach to cell therapy manufacturing announced today that Poseida Therapeutics, Inc., a clinical-stage biopharmaceutical company that uses proprietary genetic engineering platform technologies to create cell and gene therapeutics with the potential to cure, has joined its Early Access Partnership Program (EAPP). Poseida joins PACT Pharma and academic partner Fred Hutchinson Cancer Research Center as the third entity to join Cellares' EAPP. Cellares launched the EAPP in 2020 to provide participants awareness and early access to Cellares' Cell Shuttle, a next-generation cell therapy manufacturing platform that enables closed, automated, and scalable cell therapy production. Poseida's involvement in the initiative adds to the Cell Shuttle's development, range of usage, and applicability by providing insight and experience in manufacturing processes for various autologous and allogeneic cell therapies. Poseida is presently testing two autologous CAR-T product candidates in the clinic: P-BCMA-101 for relapsed/refractory multiple myeloma and P-PSMA-101 for metastatic castrate-resistant prostate cancer. The firm, which completed an initial public offering in July 2020, is also developing off-the-shelf versions of these treatments and TCR-T, anti-c-kit CAR-T, induced pluripotent stem cells (iPSCs), genetically modified hematopoietic stem cells (HSCs), and NK cells. In addition, Carl June, M.D., an immunotherapy pioneer and renowned oncologist who advised Cellares on creating the Cell Shuttle has just joined Poseida's Immuno-Oncology Scientific Advisory Board. Poseida will assess the Cell Shuttle prototypes and give statistics and written comments related to their function and performance as part of Cellares' EAPP. In addition, user studies will be conducted to assess the Cell Shuttle's hardware and software, product requirements, release criteria, and process processes to ensure product-market fit. About The Cell Shuttle The Cell Shuttle is a flexible and scalable automated and closed end-to-end production solution that allows clients to execute the precise procedures required for their cell therapy. Compared to presently existing cell therapy manufacturing methods, this next-generation platform allows for a threefold decrease in process failure rates and the ability to produce 10+ patient doses in parallel, improving manufacturing scalability by order of magnitude. For most processes, this will reduce per-patient manufacturing costs by up to 70%. About Cellares Corporation Cellares is rethinking cell therapy manufacturing and accelerating access to life-saving cell therapies. The business is working on a one-of-a-kind approach to solving the difficulties of generating cell therapies that are cheaper and broadly accessible to people in need. Cellares' proprietary platform, the Cell Shuttle, eliminates the need for biopharma companies, academic research centers, and CDMOs to choose between a manufacturing platform that is semi-automated but lacks workflow flexibility or one that provides customization but lacks the end-to-end automation required to manufacture at scale. The business is based in South San Francisco, California.

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