Researchers identify two groups of neurons related to Leigh Syndrome

Medical News | September 18, 2019

Leigh Syndrome affects one in every 40,000 newborns and is produced by deficits in the mitochondria, which are in charge of providing the energy needed for cells to function correctly. Thus, cells with a high energy demand such as the brain and muscles are most affected. Recently, the Mitochondrial Neuropathology laboratory at the UAB Institute of Neuroscience, directed by Albert Quintana, published an article in eLife describing the neurons responsible for the different affectations produced by this disorder. The generation of two new mouse models of this disease has allowed researchers to understand better the causes and opens the door to new studies which could find a treatment. In order to establish which neurons were responsible for the different disease symptoms, researchers "deactivated" the Ndufs4 gene, a key piece of the mitochondria in three types of neurons: the glutamatergic neurons, which activate other cells; the GABAergic neurons, which inhibit other cells; and the cholinergic neurons, which carry information from the brain to the organs. The mice with modified cholinergic neurons did not present any manifestation of the disease, whereas the others did: in both cases, the mice had very low body weight and died prematurely. Therefore, this is the first time that evidence has been found that the neurons releasing glutamat and GABA are related to Leigh Syndrome, while this is not the case in the cholinergic neurons.

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Spotlight

The Octet platform is helping researchers characterize the binding interactions of biomolecules to better understand their safety and efficacy. Useful through discovery and development, the real-time measures of binding affinity can help elucidate mechanisms of action and identify off-target interactions. In contrast to other label-free platforms, Octet users are up, running, and getting data in just a few hours.
Using a fluidics-free design, the Octet systems offer increased throughput and reduced operating costs. Its selection of disposable Dip and Read™ biosensors also enable faster and more flexible assay development options.

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MEDTECH

Pfizer to Acquire Trillium Therapeutics Inc.

Pfizer Inc | August 24, 2021

Pfizer Inc. and Trillium Therapeutics Inc. today announced that the companies have entered into a definitive agreement under which Pfizer will acquire Trillium, a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer. Under the terms of the agreement, Pfizer will acquire all outstanding shares of Trillium not already owned by Pfizer for an implied equity value of $2.26 billion, or $18.50 per share, in cash. This represents a 118% premium to the 60-day weighted average price for Trillium. Trillium’s portfolio includes biologics that are designed to enhance the ability of patients’ innate immune system to detect and destroy cancer cells. Its two lead molecules, TTI-622 and TTI-621, block the signal-regulatory protein α (SIRPα)–CD47 axis, which is emerging as a key immune checkpoint in hematological malignancies. TTI-622 and TTI-621 are novel, potentially best-in-class SIRPα-Fc fusion proteins that are currently in Phase 1b/2 development across several indications, with a focus on hematological malignancies. “Today’s announcement reinforces our commitment to pursue scientific breakthroughs with the addition of potentially best-in-class molecules to our innovative pipeline,” said Andy Schmeltz, Global President & General Manager, Pfizer Oncology. “The proposed acquisition of Trillium builds on our strong track record of leadership in Oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our deep experience in understanding the science of blood cancers, along with the diverse knowledge base we have developed across our growing hematology portfolio of eight approved and investigational therapies, provide us with a foundation to advance these important potential medicines to patients who need them.” Hematological malignancies are cancers that affect the blood, bone marrow, and lymph nodes. This classification includes various types of leukemia, multiple myeloma, and lymphoma. More than 1 million people worldwide were diagnosed with a blood cancer in 2020, representing almost 6% of all cancer diagnoses globally. In 2020, more than 700,000 people worldwide died from a form of blood cancer. “We’re delighted to announce Pfizer’s proposed acquisition of Trillium. Today’s announcement reflects Trillium’s potentially best in class SIRPα–CD47 status and contribution to immuno-oncology,” said Dr. Jan Skvarka, Chief Executive Officer of Trillium. “Trillium has the only known SIRPα–CD47 targeting molecules with clinically meaningful monotherapy responses as well as a strong basis for combination therapies, which is supported by preclinical evidence with a diverse set of therapeutic agents. With Pfizer’s global reach and deep capabilities, we believe our programs will advance more quickly to the patients we’ve always aspired to serve. We believe this is a good outcome for patients and our shareholders.” In clinical studies to-date, TTI-622 and TTI-621 have demonstrated activity as monotherapy in relapsed or refractory lymphoid malignancies, including Diffuse Large B-cell Lymphoma (DLBCL), Peripheral T-cell lymphoma (PTCL), Follicular Lymphoma (FL), and other lymphoid malignancies. As of July 26, 2021, Phase 1 data for TTI-622 in 30 response-evaluable patients have shown deep and durable responses in heavily pretreated patients, including two complete responses (CRs), one lasting over 114 weeks, with responses ongoing. TTI-622 and TTI-621 are currently the only known CD47-targeted molecules that have demonstrated meaningful single agent activity and CRs in multiple hematological malignancies. Thus far, adverse events (AEs) reported with TTI-622 and TTI-621 have been manageable. Related Grade 3 and 4 AEs with TTI-622 were rare and limited to transient cytopenias. In particular, the molecules demonstrate minimal red blood cell binding and few reported cases of anemia, an observed risk with other CD47-targeted approaches. Further data are expected to be shared at a forthcoming medical conference. “We are encouraged by the early clinical data for TTI-622 and TTI-621 monotherapy for patients with heavily pretreated lymphoid malignancies and early encouraging activity for TTI-622 in patients with multiple myeloma. Just as PD-1 and PD-L1 blockers have proven to be effective immuno-therapeutics for many solid tumors, the SIRPα-CD47 interaction defines a second key immune checkpoint for which disrupting agents are expected to become another important backbone immunotherapy for multiple types of cancer, especially hematological cancers,” said Chris Boshoff, MD, PhD, Chief Development Officer, Oncology, Pfizer Global Product Development. “Utilizing Pfizer’s leading research and global development capabilities, we plan to accelerate the clinical development of SIRPα fusion proteins as a potential new scientific breakthrough and explore combinations within our own portfolio and with innovative next-generation medicines for hematological malignancies.” In September 2020, as part of the Pfizer Breakthrough Growth Initiative (PBGI), Pfizer invested $25 million in Trillium and Jeff Settleman, Senior Vice President and Chief Scientific Officer of Pfizer’s Oncology Research & Development Group, was named to Trillium’s Scientific Advisory Board. Established in June 2020, PBGI’s goal is to provide funding for scientific research as well as access to Pfizer’s experts to ensure the continuity of clinical programs that could be of potential strategic interest for Pfizer. Pfizer has committed to providing up to $500 million in total funding to the PBGI. Additional Transaction Details The proposed acquisition of Trillium is to be completed by way of a statutory plan of arrangement under the Business Corporations Act (British Columbia) and subject to customary closing conditions, including approval of 66⅔% of the votes cast by Trillium shareholders, voting together as one class, at a special meeting of Trillium and approval of 66⅔% of the votes cast by Trillium shareholders and warrant holders, voting together as one class, at a special meeting of Trillium. Completion of the acquisition is also subject to court and regulatory approval, as well as certain other closing conditions customary for transactions of this nature. Pfizer’s financial advisors for the transaction are BofA Securities, Inc., with Ropes & Gray LLP and Norton Rose Fulbright Canada LLP acting as its legal advisors. Centerview Partners LLC served as Trillium’s financial advisor, while Goodwin Procter LLP and Baker McKenzie LLP (Canada) served as its legal advisors. About SIRPα/CD47 Accumulating data suggest that the SIRPα–CD47 axis is a key immune checkpoint in hematologic malignancies, similar to the PD-L1 / PD-1 checkpoint for solid tumors. CD47 is a protein that is overexpressed in numerous cancer cells, and in general, high CD47 expression correlates with more aggressive disease and poorer clinical outcomes. SIRPα is an inhibitory receptor expressed on myeloid cells that binds to CD47, preventing the immune system from destroying cancer cells. Disruption of the CD47-SIRPα interaction has been proven to elicit tumor destruction through triggering of an innate immune response. About Pfizer Oncology At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma. About Pfizer: At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. About Trillium Therapeutics Trillium is an immuno-oncology company developing innovative therapies for the treatment of cancer. The company’s two clinical programs, TTI-622 and TTI-621, target CD47, a “don’t eat me” signal that cancer cells frequently use to evade the immune system.

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CELL AND GENE THERAPY

Graphite Bio Enrolls First Patient in Phase 1/2 Clinical Trial of GPH101 for Sickle Cell Disease

Graphite Bio | November 26, 2021

Graphite Bio, Inc. a clinical-stage, next-generation gene editing company focused on therapies that harness targeted gene integration to treat or cure serious diseases, announced that the first patient has been enrolled in the company’s Phase 1/2 clinical trial of GPH101, an investigational gene-edited autologous hematopoietic stem cell therapy designed to directly correct the genetic mutation that causes sickle cell disease. The company expects to treat the first patient with GPH101 in the first half of 2022, with initial proof-of-concept data anticipated by the end of 2022. “GPH101 is the first investigational therapy to enter clinical development that uses our next-generation gene editing platform technology to directly correct the mutation in the beta-globin gene that causes sickle cell disease. Using our gene correction approach, we have demonstrated in preclinical studies an ability to decrease the production of harmful sickle hemoglobin and restore the expression of normal adult hemoglobin. This approach has the potential to restore normal physiology and is viewed as the gold standard for curing sickle cell disease. We are thrilled that our first patient is now enrolled in our CEDAR clinical trial, and we look forward to evaluating GPH101’s potential as we continue to advance its development with urgency in hopes of delivering a curative therapy to the sickle cell community.” Josh Lehrer, M.Phil., M.D., chief executive officer at Graphite Bio The CEDAR trial is an open-label, multi-center Phase 1/2 clinical trial of GPH101 designed to evaluate the safety, engraftment success, gene correction rates, total hemoglobin, as well as other clinical and exploratory endpoints and pharmacodynamics of GPH101 in patients with severe SCD. The trial will enroll approximately 15 adult and adolescent participants at up to five clinical trial sites in the United States. Graphite Bio will present information about the CEDAR trial at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, being held virtually and in Atlanta December 11-14. The company’s poster presentation will take place on Saturday, Dec. 11, at 5:30-7:30 p.m. ET. About Sickle Cell Disease (SCD) SCD is a serious, life-threatening inherited blood disorder that affects approximately 100,000 people in the United States and millions of people around the world, making it the most prevalent monogenic disease worldwide. SCD is caused by a single mutation in the beta-globin gene that leads red blood cells to become misshapen, resulting in anemia, blood flow blockages, intense pain, increased risk of stroke and organ damage, and reduced life span of approximately 20-30 years. Despite advancements in treatment and care, progressive organ damage continues to cause early mortality and severe morbidity, highlighting the need for curative therapies. About GPH101 GPH101 is an investigational next-generation gene-edited autologous hematopoietic stem cell (HSC) therapy designed to directly correct the genetic mutation that causes sickle cell disease (SCD). GPH101 is the first investigational therapy to use a highly differentiated gene correction approach that seeks to efficiently and precisely correct the mutation in the beta-globin gene to decrease sickle hemoglobin (HbS) production and restore normal adult hemoglobin (HbA) expression, thereby potentially curing SCD. Graphite Bio is evaluating GPH101 in the CEDAR trial, an open-label, multi-center Phase 1/2 clinical trial designed to assess the safety, engraftment success, gene correction rates, total hemoglobin, as well as other clinical and exploratory endpoints and pharmacodynamics in patients with severe SCD. About Graphite Bio Graphite Bio is a clinical-stage, next-generation gene editing company harnessing high efficiency targeted gene integration to develop a new class of therapies to potentially cure a wide range of serious and life-threatening diseases. Graphite Bio is pioneering a precision gene editing approach that could enable a variety of applications to transform human health through its potential to achieve one of medicine’s most elusive goals: to precisely “find & replace” any gene in the genome. Graphite Bio’s platform allows it to precisely correct mutations, replace entire disease-causing genes with normal genes or insert new genes into predetermined, safe locations. The company was co-founded by academic pioneers in the fields of gene editing and gene therapy, including Maria Grazia Roncarolo, M.D., and Matthew Porteus, M.D., Ph.D.

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Research Solutions Announces Partnership with BIO Business Solutions to Bring One-Click Scientific Literature Access to the Biotech Industry

Research Solutions | October 12, 2020

Research Solutions/Reprints Desk (NASDAQ: RSSS), a pioneer in providing cloud-based workflow solutions for R&D driven organizations, today announced that it has partnered with BIO Business Solutions to help life sciences companies save time and money on scholarly literature access via its award-winning Article Galaxy research platform. Operated by the Biotechnology Innovation Organization (BIO), BIO Business Solutions is the industry's largest cost savings purchasing program. More than 4,500 member companies worldwide—including biotechnology and biopharmaceutical firms, medical device firms, academic institutions, state biotechnology centers, and related organizations—together save more than $511 million annually through the BIO Business Solutions® program.

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