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An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options. An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options, according to results from a clinical trial led by Queen Mary University of London. The phase 3 clinical trial, led by Professor Peter Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options. Mick's journey with mesothelioma: "I have five grandchildren and two great-grandchildren now -- I wouldn't want to miss all that." The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment -- which combines a new drug, ADI-PEG20, with traditional chemotherapy -- increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy. The findings are significant, as MPM has one of the lowest 5-year survival rates of any solid cancer of around 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets cancer's metabolism developed for this disease in 20 years. MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with exposure to asbestos. It's usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease. The premise behind this new drug treatment is elegant in its simplicity -- starving the tumour by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that can't manufacture their arginine due to a missing enzyme, this means their growth is thwarted. The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary's Barts Cancer Institute that began with Professor Szlosarek's discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM. Professor Szlosarek said: "It's truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma. I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy." Dr Tayyaba Jiwani, Science Engagement Manager at Cancer Research UK, said: "This study shows the power of discovery research which allows us to dig deep into the biology of mesothelioma to uncover vulnerabilities that we can now target with ADI-PEG20. "Cancer Research UK is delighted to have funded the early stages of this research, including a preliminary clinical trial which established the safety and effectiveness of this drug." There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme (a type of brain tumour) and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may be of benefit in the treatment of multiple other types of cancer.  Mick's journey with mesothelioma Mick worked in a factory boiler room in the 1970s, where he was exposed to asbestos. In 2018, he visited his doctor after he began to feel unwell and had lost three stone in weight. He became anaemic and was eventually diagnosed with mesothelioma. "It was a bit of a shock: I was given four months to live," Mick explains. His doctor referred him to Professor Szlosarek, who enrolled him in the ATOMIC-meso trial. "I always believed in Peter. I said: 'I'm in it to win it -- you're not getting rid of me.' And here I am five years later." For two years, Mick visited St Bartholomew's Hospital every week, accompanied by his wife, Jackie, or one of his children or grandchildren. "I'd have two injections of the new treatment -- one in each arm. I didn't have any serious side effects," Mick explains. "I met many of the other people on the trial. Over time, some of them disappeared. But I kept going." Mick was awarded compensation from his former employer responsible for the asbestos exposure that ultimately led to his mesothelioma. Around 80% of mesothelioma cases are caused by workplace exposure. Two and a half years after Mick enrolled on the ATOMIC-meso trial, his mesothelioma returned and he received a second course of treatment, this time immunotherapy. He experienced more side effects with this therapy, including encephalitis. But his cancer remains under control, and recently he was able to celebrate his 80th birthday. Professor Szlosarek and his team plan to study why certain patients, such as Mick, benefit so greatly from ADI-PEG20, in the hope of discovering how to extend this benefit to more people. Mick says: "This trial has changed the lives of people with mesothelioma, allowing us to live longer. I have five grandchildren and two great-grandchildren now -- I wouldn't want to miss all that."

The annual meeting of the American Society of Gene & Cell Therapy (ASGCT) was held in Washington, DC this week, with literally hundreds of abstracts and presentations. Here’s a look at some of the highlights. The annual meeting of the American Society of Gene & Cell Therapy (ASGCT) was held in Washington, DC this week, with literally hundreds of abstracts and presentations. Here’s a look at some of the highlights. Children with X-linked MTM Breathe on Their Own after Gene Therapy Researchers with Audentes Therapeutics , Hopital Armand Trousseau in Paris, UCLA Medical Center , Children’s Hospital of Chicago and several other institutions, presented data from a Phase I/II clinical trial of gene therapy in X-linked Myotubular Myopathy (XLMTM). XLMTM is a rare monogenic disease caused by mutations in the MTM1 gene, which codes for myotubularin, which is a protein needed for development and function of skeletal muscle. The disease results in extreme muscle weakness, respiratory failure and early death. Of the nine boys who received the gene therapy, all have improved neuromuscular function, most can sit on their own and four can now breathe on their own without ventilators. Principal investigator Perry Shieh, a neurologist at UCLA, said the boys “have gone from nothing to something. Time will tell how much that something will be.” The gene therapy is AT132, which delivers functional copies of the MTM1 gene to skeletal muscle cells. MaxCyte Presented Data on CARMA Trial in Cancer Gaithersburg, Md.-based MaxCyte presented data on its CARMA drug candidate, MCY-M11, a mesothelin-targeting chimeric antigen receptor (CAR), which is in a Phase I clinical trial in mesothelin-expression solid tumors at the National Cancer Institute (NCI) and Washington University in St. Louis. The CARMA platform is noted for its rapid manufacturing and delivery capabilities without a viral component, which was also a significant aspect of the presentation. “The advancement of our first CARMA clinical trial, which is consistently showing the feasibility of our rapid manufacturing process, is significant for MaxCyte and the application of our technology,” stated Claudio Dansky Ullmann, MaxCyte’s chief medical officer. “Development of a cell therapy with application in solid tumors is impactful for patients with unmet needs in a variety of cancers and we look forward to further advancing this program.” Moderna Presented Research from 7 mRNA-based Therapies, and 5 Oral Presentations Moderna always has a lot of irons in the fire and they presented research on many of them at the meeting. The data included preclinical research in ornithine transcarbamylase deficiency (OTC) in collaboration with the Perelman School of Medicine at the University of Pennsylvania; maple syrup urine disease (MSUD), also in collaboration with Penn; arginase-1 (ARG1) deficiency in collaboration with the University of California, Los Angeles Department of Surgery and Department of Molecular and Medical Pharmacology; Factor VIII deficiency (hemophilia A), in collaboration with Seattle Children’s Research Institute; and several other programs. “mRNA medicines have the potential to treat the underlying cause of many metabolic diseases, and may offer important advantages over conventional gene and enzyme replacement therapies for eligible patients,” stated James M. Wilson, director of the Gene Therapy Program at Penn. “This includes the potential to develop controlled, dose-dependent and transient treatments that may benefit infants and children with these disorders and patients with diseases that are not addressable with current viral-based approaches.” Translate Bio Presented mRNA Therapies in Metabolic Disorders Translate Bio presented “Treatment of Metabolic Disorders Using Lipid Nanoparticle (LNP)-Encapsulated Messenger RNA Therapeutics (MRT).” The presentation summarized data from research in three mouse models of metabolic disorders including ornithine transcarbamylase (OTC) deficiency, arginosuccinate synthetase (ASS1) deficiency (citrullinemia) and methylmalonic acidemia (MMA). “We have engineered our mRNA therapeutic (MRT) platform to deliver mRNA that codes for the missing enzymes in several metabolic disorders,” stated Frank DeRosa, Translate Bio’s senior vice president of research and process development. “These data demonstrate the potential broad applicability of the MRT platform to treat various genetic disorders using our proprietary liver delivery technology.” Homology Medicines Discusses Gene Therapy Platform Homology Medicines discussed its manufacturing platform, including serum-free suspension transfection, which is both scalable and optimized to manufacture its adeno-associated virus vectors (AAVHSCs). Specifically, its AAVHSC15 vector showed an 18-fold decrease in phenylalanine compared to an AAV5 vector carrying the identical DNA construct in the phenylketonuria (PKU) murine model. “We have a great sense of urgency to advance our gene therapy and gene editing programs with the goal of bringing transformative treatments and potential cures to patients with rare genetic diseases,” stated Albert Seymour, Homology’s chief scientific officer. “We are pleased to share the progress that we have made across our PKU and MLD development programs, as well as demonstrate the scalability, quality and superiority of our manufacturing process for our human-derived AAVHSCs. We are carrying this momentum forward in our IND-enabling studies in MLD and in our gene editing program for PKU and look forward to starting our Phase I/II pheNIX trial in adults with PKU and reporting initial clinical data this year.”

Pegzilarginase Monotherapy Demonstrates Anti-Tumor Activity AUSTIN, Texas, Oct. 22, 2018 (GLOBE NEWSWIRE) --  Aeglea BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage biotechnology company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer, today announced that it presented positive clinical data for pegzilarginase in melanoma patients at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany. The poster, titled “Initial cohort expansion results of sustained arginine depletion with Pegzilarginase in melanoma patients in a phase 1 advanced solid tumor trial,” was presented on October 21. Clinical data from the Company’s ongoing Phase 1 clinical trial investigating pegzilarginase as a single agent includes expansion cohorts for cutaneous melanoma and uveal melanoma.  “This ongoing clinical study of pegzilarginase demonstrated single agent anti-tumor activity in what is a difficult-to-treat population of heavily pre-treated melanoma patients,” said James Wooldridge, M.D., chief medical officer of Aeglea. “These findings are in line with expectations from our single agent preclinical studies. Given the significant synergies we observed in preclinical studies with immune checkpoint inhibitors, we look forward to data readouts from the Phase 1/2 combination clinical trial.” Data highlights from ESMO 2018: Pegzilarginase demonstrated single agent anti-tumor activity in patients with advanced melanoma--Of the 28 patients included in the two cohorts, there was one confirmed partial response (PR) and eight patients with stable disease (SD). Six patients remained on treatment at the time of the data cutoff.--Anti-tumor activity appeared greater in patients with tumors that lack ASS1 (argininosuccinate synthetase 1) expression, which is consistent with preclinical studies that suggest tumors lacking ASS1 expression are dependent on extracellular arginine for survival.Pegzilarginase rapidly and sustainably depleted plasma arginine with a manageable safety profile, treatment related adverse events were grade three or lower              About Pegzilarginase in CancerPegzilarginase is an enhanced human arginase that enzymatically degrades the amino acid arginine. In some cancers, tumor cells stop producing specific amino acids and must acquire them from the blood, making the tumor cells susceptible to starvation through depletion of those amino acids. Aeglea is developing pegzilarginase to exploit vulnerabilities in some cancers that lead to an increased dependency on extracellular arginine. Pegzilarginase targets these arginine dependent cancers by depleting blood arginine levels to below the normal range. Preclinical data demonstrated that the resulting arginine starvation inhibits proliferation, induces cell death, increases turnover of cell components and promotes anti-tumor immune responses. The Company’s Phase 1 data in advanced solid tumors demonstrated that pegzilarginase was well tolerated at doses that produced marked and sustained reductions in blood arginine levels below the normal range. About Aeglea BioTherapeutics Aeglea is a clinical-stage biotechnology company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer. The Company is developing pegzilarginase, its lead investigational therapy, for the treatment of Arginase 1 Deficiency, as monotherapy in arginine-dependent cancers and in combination with an immune checkpoint inhibitor for small cell lung cancer. In addition, Aeglea has an active research pipeline of other human enzyme-based approaches in both therapeutic areas. For more information, please visit http://aegleabio.com. Safe Harbor / Forward Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, the potential therapeutic benefits and economic value of our lead product candidate or other product. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 filed with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.              Media Contact: David CalusdianSharon Merrill Associates617.542.5300AGLE@investorrelations.com Investor Contact: Joey Perrone Director, Finance & Investor RelationsAeglea BioTherapeutics investors@aegleabio.com