Probing new targets for treating the most lethal form of pancreatic cancer

Fiercebiotech | September 09, 2019

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and also one of the most difficult cancers to treat, because the tumors evolve to evade chemotherapy, and they often spread rapidly throughout the body. Two new studies are reporting progress in the ongoing effort to find new targets for treating PDAC. One seeks to disrupt the metabolism of cancer cells, while the other blocks a key protein that PDAC cells need to grow. Monday, Tyme Technologies presented data from a small phase 2 study of its lead drug candidate, SM-88 (racemetyrosine), which is designed to kill cancer cells by exposing them to oxidative stress. During the study, the investigators tracked an 80% decline in circulating tumor cells and observed a correlation between that decline and overall survival. The median overall survival rate among the 38 patients who were evaluated was six months. The results prompted Tyme to announce that it will launch a pivotal phase 3 trial of SM-88 this quarter. The company discussed the results of the phase 2 trial at the American Association for Cancer Research (AACR) Special Conference on pancreatic cancer in Boston.

Spotlight

Who Benefits from IP Rights for Agricultural Innovation, a Steward Redqueen study, follows the
journey of a single agricultural innovation, Ogura, through its life cycle. The study examines the
time and money innovators invested, the benefits to farmers and consumers, and the role of
intellectual property in making it all possible.

Spotlight

Who Benefits from IP Rights for Agricultural Innovation, a Steward Redqueen study, follows the
journey of a single agricultural innovation, Ogura, through its life cycle. The study examines the
time and money innovators invested, the benefits to farmers and consumers, and the role of
intellectual property in making it all possible.

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Matica Bio Announces Joint Research Agreement with Sartorius for the Development of Advanced Viral Vector Manufacturing Technology

Matica Biotechnology, Inc. | October 19, 2021

Matica Biotechnology, Inc, (Matica Bio) a contract development and manufacturing organization (CDMO) specializing in the clinical and commercial production of cell and gene therapies, today announced a joint research agreement (JRA) with Sartorius, a leading international partner of the biopharmaceutical industry. Under this agreement, Matica Bio and Sartorius will work on a number of studies together to streamline and optimize PAT technologies, automation software, and single-use platforms offered by Sartorius for large scale vector production. Michael Stewart, Chief Technology Officer at Matica Bio explained, "The generation of in-line real-time process data is one of the most significant obstacles to achieving consistent, high-producing viral vector titers during development that can be translatable to large scale production. In many respects, what is going on inside a bioreactor or within downstream operations is still a black box to us." Mr. Stewart continued, "Matica Bio's development, manufacturing and quality teams have decades of viral vector production experience. Applying our expertise together with Sartorius' industry-leading single-use and PAT technologies will allow us to provide more robust, consistent results for our clients, guiding informed decision-making throughout the manufacturing process and accelerating the overall development timeline to the clinic and market." "We are extremely excited to initiate this partnership with Sartorius. Our number one priority is to deliver for our clients. Our expert staff will be working to integrate more fully automated processes leading to an increase in the speed of information flow and a reduction in preventable errors. The end result will be increased product yields, higher quality as well as improved flexibility and responsiveness to our clients' ever-changing needs." Dr. Yun Jeong Song, Chief Executive Officer of Matica Bio The JRA with Sartorius underscores Matica Bio's commitment to applying integrated technology and bioprocess solutions to address production complexities like reduction of labor and risk while improving output efficiencies in the production of advanced therapies, including viral vector products. Together Sartorius and Matica Bio are dedicated to solving the challenges of large-scale cell culture and viral vector production, improving manufacturability and reducing the costs of novel cell and gene therapies, oncolytic vectors and vaccines. About Matica Biotechnology, Inc. Matica Bio is a contract development and manufacturing organization for gene therapies, cell therapies, vaccines, oncolytic vectors and other advanced biotherapeutic products. Our GMP facility in College Station, TX is designed for the rapid development, scale-up and production of clinical and commercial supply. Matica Bio offers process development, GMP production, product release and stability assessment, together with the quality oversight and regulatory guidance necessary to ensure our clients' success.

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INDUSTRIAL IMPACT

BioNTech and Medigene Announce Global Collaboration to Advance T Cell Receptor Immunotherapies Against Cancer

BioNTech SE | February 22, 2022

BioNTech SE and Medigene AG a clinical-stage immuno-oncology company focusing on the development of T cell immunotherapies, announced that they have entered a multi-target research collaboration to develop T cell receptor (TCR) based immunotherapies against cancer. The initial term of the collaboration is three years. Medigene will contribute its proprietary TCR discovery platform for the development of TCRs against multiple solid tumor targets nominated by BioNTech. Medigene’s automated, high throughput TCR discovery platform is designed to bypass central tolerance to yield high affinity TCRs. T cell therapy has become a disruptive medical innovation in the treatment of patients with cancer. Engineered TCR-modified T cells (TCR-T cells) are reprogrammed to express a TCR that can recognize specific antigens only present on tumor cells, thereby enabling a precise and potent immune response to attack a patient’s tumor. “This collaboration with Medigene expands our cell therapy portfolio and TCR discovery capabilities, and further strengthens our ability to be a leader in the rapidly emerging field of engineered cell therapies. We look forward to working closely with Medigene to develop new treatments which address solid tumors with high unmet medical need.” Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: “Medigene is at the forefront of the development of TCR-T therapies for oncology. The sale and licensing deal with BioNTech is an important validation from a global leading biotech company of our proprietary technologies to discover and characterize highly specific TCRs and empower resulting TCR-T cells to fight solid tumors. This partnership provides Medigene with meaningful financial resources to fuel our next generation development programs targeting potentially novel tumor-specific “dark matter” antigens, further tools to enhance T-cell-based immunotherapies, as well as additional potential strategic deals with future milestone payments and royalties.” BioNTech will acquire Medigene’s next generation preclinical TCR program, which combines TCR-4 of Medigene’s MDG10XX program targeting PRAME with Medigene’s proprietary PD1-41BB switch receptor technology. BioNTech will also obtain the exclusive option to acquire additional existing TCRs in Medigene’s discovery pipeline and will receive licenses to the company’s PD1-41BB switch receptor and precision pairing library. This has the potential to augment TCR cell therapy efficacy and can be applied to all BioNTech cell therapy programs. Under the terms of the agreement, Medigene will receive EUR 26 million upfront, as well as research funding for the period of the collaboration. BioNTech will be responsible for global development and hold exclusive worldwide commercialization rights on all TCR therapies resulting from this research collaboration. Medigene will be eligible to receive development, regulatory and commercial milestone payments up to a triple digit million EUR amount per program in addition to tiered deferred option payments on global net sales for products based on TCRs arising from the collaboration and royalties on products utilizing at least one of the licensed technologies. About BioNTech Biopharmaceutical New Technologies is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bi-specific checkpoint immuno-modulators, targeted cancer antibodies and small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Genmab, Sanofi, Bayer Animal Health, Genentech, a member of the Roche Group, Regeneron, Genevant, Fosun Pharma and Pfizer. About Medigene Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard) is a publicly listed biotechnology company headquartered in Planegg/Martinsried near Munich, Germany. With its scientific expertise, Medigene is working on the development of innovative immunotherapies to enhance T cell activity against solid cancers in fields of high unmet medical need. Medigene’s pipeline includes preclinical as well as clinical programs in development. Medigene’s strategy is to develop its own therapies towards clinical proof-of-concept. In addition, the Company offers selected partners the opportunity to discover and develop therapies on the basis of its proprietary technology platforms. In return for such partnerships, Medigene expects to receive upfront and milestone payments as well as research and development funding and royalties on future product sales. About Medigene’s TCR-T cells T cells are at the center of Medigene’s therapeutic approaches. With the aid of Medigene’s immunotherapies the patient’s own defense mechanisms are activated, and T cells harnessed in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs). The resulting TCR-T cells should thereby be able to detect and efficiently kill cancer cells. About Medigene’s PD1-41BB switch receptor Checkpoint inhibition via PD1-PDL1 pathway: Solid tumor cells are known to be sensitive to killing by activated T cells. Tumor cells can escape this killing activity by expressing inhibitory molecules, so-called ‘checkpoint proteins’, such as Programmed Death Ligand 1 (PD-L1) on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 by tumors represents an adaptive immune resistance mechanism that can lead to tumor survival and growth. About Medigene’s precision pairing library T cell receptors (TCRs) consist of an alpha and a beta chain, which together act as a receptor on the cell surface of T cells. Medigene's therapies aim to equip the patient's own T cells with tumor-specific TCRs. The resulting TCR-T cells should thereby be able to detect and efficiently kill cancer cells. The precision pairing library allows selection of specific modifications in each chain of a TCR so that the alpha and beta chains preferentially pair with each other, with the result that improved TCR surface expression and/or functionality is achieved.

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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. Lower levels of cGMP are found in people with sickle cell disease (SCD) and beta-thalassemia and are associated with reduced blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide mediated vasodilation. Blocking PDE9 acts to increase cGMP levels, which is associated with several benefits including the potential reactivation of fetal hemoglobin (HbF), a natural hemoglobin produced during fetal development. Increased levels of HbF in RBCs have been demonstrated to improve symptomology and substantially lower disease burden in both patients with SCD and patients with beta-thalassemia. About Sickle Cell Disease Sickle cell disease (SCD), a hemoglobinopathy, is a rare inherited red blood cell disorder. The disease causes structural abnormalities in hemoglobin that cause red blood cells to become inflexible and elongated, ultimately blocking blood flow to organs, which can lead to vaso-occlusive crises (VOCs). 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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