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Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca2+ channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established. In the present study, we directly manipulated Cav1.3 channels in Cav1.2 dihydropyridine insensitive mutant mice and found that ventral tegmental area (VTA) Cav1.3 channels mediate cocaine-related and depressive-like behavior through a common nucleus accumbens (NAc) shell calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) mechanism that requires GluA1 phosphorylation at S831. Selective activation of VTA Cav1.3 with (±)-BayK-8644 (BayK) enhanced cocaine conditioned place preference and cocaine psychomotor activity while inducing depressive-like behavior, an effect not observed in S831A phospho-mutant mice. Infusion of the CP-AMPAR-specific blocker Naspm into the NAc shell reversed the cocaine and depressive-like phenotypes. In addition, activation of VTA Cav1.3 channels resulted in social behavioral deficits. In contrast to the cocaine- and depression-related phenotypes, GluA1/A2 AMPARs in the NAc core mediated social deficits, independent of S831-GluA1 phosphorylation. Using a candidate gene analysis approach, we also identified single-nucleotide polymorphisms in the CACNA1D gene associated with cocaine dependence in human subjects. Together, our findings reveal novel, overlapping mechanisms through which VTA Cav1.3 mediates cocaine-related, depressive-like and social phenotypes, suggesting that Cav1.3 may serve as a target for the treatment of neuropsychiatric symptoms.Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.9. © 2017 Macmillan Publishers Limited, part of Springer Nature.


A single transplant of microbes contained in the stool of a healthy donor is a safe and effective way to increase diversity of good bacteria in the guts of patients with ulcerative colitis, according to new research from Weill Cornell Medicine and NewYork-Presbyterian. The findings suggest that fecal microbiota transplantation (FMT) might be an effective treatment for the disease, which causes inflammation and ulcers in the digestive tract. Fecal microbiota transplantation is a procedure in which fecal matter -- which is full of bacteria from the gut -- is collected from a healthy donor, strained and placed in the colon of a patient with inflammatory bowel disease. "The idea is that you can change someone's microbiome, the organisms that colonize the gut," said Dr. Randy Longman, an assistant professor of medicine at Weill Cornell Medicine and a gastroenterologist at NewYork-Presbyterian/Weill Cornell Medical Center. "We introduce good bacteria into the intestines of someone with the disease and hope that it encourages healing." FMT has been proven effective for patients with Clostridium difficile, a serious bacterial infection of the intestines, but questions remain about its effectiveness as a treatment for other diseases. In a study published April 26 in Inflammatory Bowel Disease, a team of gastroenterologists and researchers from Weill Cornell Medicine and NewYork-Presbyterian led by Drs. Vinita Jacob, Carl Crawford and Longman present data suggesting that FMT is safe and increases the diversity of microbes in patients with active ulcerative colitis. "Patients with ulcerative colitis typically have a lower diversity of microbes in their guts," said Dr. Longman, who is also a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease and a clinician in the Jill Roberts Center for Inflammatory Bowel Disease at NewYork-Presbyterian/Weill Cornell and Weill Cornell Medicine. "We know that a more diverse microbiota is correlated with better health, so increasing that diversity may be a key factor in the therapeutic efficacy of FMT for ulcerative colitis." The researchers used a fecal microbiota preparation (FMP) consisting of stool from two different healthy donors that had been screened and purified. This two-donor preparation was used in order to maximize the diversity of bacteria in the transplant. They then used a colonoscopy to transplant the FMP into the colons of 20 ulcerative colitis patients. After four weeks, the investigators collected fecal samples from the patients and performed rectal biopsies in order to measure the fecal microbiome and immune response after treatment. The researchers found that after four weeks, the bacterial populations in the intestines of the patients more closely resembled those of the healthy donors than the patients' original microbiomes. In addition, the treatment also resulted in a reduction in the inflammatory response that drives ulcerative colitis. Overall, 35 percent of patients showed a clinical improvement in their symptoms and 15 percent of patients achieved clinical remission (complete lack of symptoms) by the end of the four-week study. "We still want to know why this treatment helps some patients and not others so that we can find a safer and more reproducible treatment option for a greater majority of patients suffering from ulcerative colitis," said Dr. Crawford, an assistant professor of clinical medicine. Further studies are necessary to determine how long these positive effects may last in ulcerative colitis patients, the exact bacteria that might be most effective for FMP and the most effective delivery method. This study provides promising results for the emerging role for FMT in ulcerative, Dr. Longman said. "We saw clear positive effects, both in terms of increased bacterial population and in clinical response. This points to FMT as an exciting possible therapy for people with ulcerative colitis."


From 2006 to 2012, there were approximately 51,000 emergency department visits per year for patients injured by law enforcement in the United States, with this number stable over this time period, according to a study published by JAMA Surgery. Deaths of civilians in contact with police have recently gained national public and policy attention. While journalists track police-involved deaths, epidemiologic data are incomplete, and trends in nonfatal injuries, which far outnumber deaths, are poorly understood. Elinore J. Kaufman, M.D., M.S.H.P., of New York-Presbyterian Hospital Weill Cornell Medicine, New York, and colleagues used the Nationwide Emergency Department Sample, a nationally representative sample of emergency department (ED) visits, to determine whether the incidence of ED visits for injures by law enforcement increased relative to total ED visits from 2006 to 2012. During this time period, there were 355,677 ED visits for injuries by law enforcement, and frequencies did not increase over time. Of these visits, 0.3 percent (n = 1,202) resulted in death. More than 80 percent of patients were men, and the average age of patients was 32 years. Most lived in zip codes with median household income less than the national average, and 81 percent lived in urban areas. Injuries by law enforcement were more common in the South and West and less common in the Northeast and Midwest. Most injuries by law enforcement resulted from being struck, with gunshot and stab wounds accounting for fewer than seven percent. Most injuries were minor. Medically identified substance abuse was common in patients injured by police, as was mental illness. "While public attention has surged in recent years, we found these frequencies [approximately 51,000 ED visits per year] to be stable over 7 years, indicating that this has been a longer-term phenomenon," the authors write. "While it is impossible to classify how many of these injuries are avoidable, these data can serve as a baseline to evaluate the outcomes of national and regional efforts to reduce law enforcement-related injury." Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.


News Article | April 20, 2017
Site: www.sciencemag.org

The abrupt dismissal of the head of a Utah cancer center is causing backlash from its faculty—and its major philanthropic funder—in a struggle over the center’s autonomy from the University of Utah in Salt Lake City. And nearly 2000 researchers have signed a petition calling on the university to reverse its decision. For 11 years, prominent cell biologist Mary Beckerle has headed the Huntsman Cancer Institute (HCI), which is based at the university but receives its funding largely from philanthropic donations, revenue from its cancer hospital, state funding, and grants from the National institutes of Health. In an email to some clinical staff on Monday, university President David Pershing and Vivian Lee, senior vice president for health sciences, announced that Beckerle would step down “effective today,” but would “remain on faculty as a distinguished professor in biology.” Beckerle, who has not responded to ’s request for comment, told that she had learned of her dismissal in an email less than an hour earlier. Details have been scant from the university, which also did not respond to a comment request. But Beckerle’s colleagues contend that the move amounts to a hostile takeover by the university aimed at capturing the cancer clinic’s revenue, and other prominent scientists are rallying unquestioningly around her. “I find it unimaginable that this would happen,” says cancer biologist Harold Varmus of Weill Cornell Medicine in New York City and former director of the National Cancer Institute, which funds HCI as one of its designated cancer centers. “If you think about great cancer directors around the country, her name comes to mind immediately.” Beckerle’s dismissal is “a real insult to the whole academic establishment that we all have been working to build up, and … an insult to American scientific leadership,” says University of California, San Francisco, biochemist Bruce Alberts (former president of the National Academy of Sciences and former editor-in-chief of ). Alberts served with Beckerle on the leadership board of the American Society for Cell Biologists, based in Bethesda, Maryland. Alberts is among more than 1800 signers of a petition on the website change.org calling for Beckerle’s reinstatement, which was delivered to Pershing’s office after a protest march from HCI yesterday. Billionaire industrialist Jon Huntsman, the Utah philanthropist whose funding helped build the center and has supported it since 1995, was apparently blindsided by the move, which came amidst negotiations for a new $120 million donation. He described Beckerle’s dismissal as a power grab by Lee, and promised to fight to reverse the decision. “I can't imagine anything worse than the University of Utah treating a donor the way they treated us,” Huntsman told the . "Until Vivian Lee is replaced and removed and fired … we have other buildings on the drawing board, other plans for expansion,” he said. (Huntsman is also a major benefactor of the university; its environmental research center, school of business, and indoor sports arena all bear his name.) University officials haven’t clearly explained their reasoning, says HCI molecular biologist Bruce Edgar, but “the general belief is that it has to do with resource allocation and control … [and] that the medical school would like to roll the cancer center into the health sciences center, including the revenue from the cancer hospital.” He adds that many faculty members are resistant to becoming an arm of the university’s health sciences center. “I think part of [Beckerle’s] dedication to the HCI has been to do negotiations on the part of HCI, to retain some autonomy,” he says. A press release published yesterday afternoon by University of Utah Health defending the decision says that “closer collaboration between HCI and the rest of the University will … enable us to apply the combined talent and resources of the University’s entire health system … to our mission of finding improved treatments and ultimately a cure for cancer.” Colleagues who credit Beckerle’s reputation and leadership with pulling the center from obscurity see the change as an existential threat to HCI. “As soon it’s gotten put on the map, they wanted to do a hostile takeover,” says Jody Rosenblatt, a cancer cell biologist at the institute. “If [Jon Huntsman is] not part of it, if Mary’s not the head of it, if we just have this coup and somebody takes over, people like me and lots of others of my colleagues that are constantly getting offers to take jobs in other places, we’re going to go,” she says. “It’s going to be the end of the Huntsman Cancer Institute.”


News Article | April 17, 2017
Site: www.eurekalert.org

Detecting red blood cells in the urine of asymptomatic patients who don't see blood when they urinate (asymptomatic microscopic hematuria) is common but it can signal cancer in the genitourinary system. Routine urinalysis for screening of genitourinary cancer isn't recommended by any major health group but patients who undergo urinalysis for a variety of other reasons are often found to have microscopic hematuria, which prompts further evaluation. A new article published by JAMA Internal Medicine explores the cost-effectiveness of four initial diagnostic protocols for these patients. Joshua A. Halpern, M.D., M.S., of Weill Cornell Medicine, New York, and his coauthors analyzed the cost-effectiveness of: computed tomography (CT) alone, cystoscopy (using a scope to examine the urinary tract) alone, CT and cystoscopy combined, and renal (kidney) ultrasound and cystoscopy combined. The combination of cystoscopy and renal ultrasound was the most cost-effective with an incremental cost of $53,810 per cancer detected, according to the results. "The use of ultrasound in lieu of CT as the first-line diagnostic strategy will reduce the cost, morbidity and national expenditures associated with evaluation of AMH [asymptomatic microscopic hematuria]. Clinicians and policy makers should consider changing future guidelines in accordance with this finding," the article concludes. To read the full study, please visit the For The Media website. Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Related material: The commentary, "Asymptomatic Microscopic Hematuria - Rethinking the Diagnostic Algorithm," by Leslee L. Subak, M.D., and Deborah Grady, M.D., M.P.H., of the University of California, San Francisco, also is available on the For The Media website. Related audio material: An interview with the authors is available for preview on the For The Media website. The podcast will be live when the embargo lifts on the JAMA Internal Medicine website. To place an electronic embedded link in your story: Links will be live at the embargo time: http://jamanetwork.


NEW YORK, NY (May 6, 2017) -- Leading pediatric experts from Weill Cornell Medicine and NewYork-Presbyterian will be presenting at the Pediatric Academic Societies 2017 Meeting in San Francisco, CA from May 6 - 9. Below is a list of Weill Cornell Medicine and NewYork-Presbyterian's noteworthy presentations and experts available for comment on research being presented at this year's meeting. Workshop Title: 1262: Pediatricians and Child Poverty Revisiting the APA's Childhood Poverty Curriculum Author: Dr. Susan Bostwick Session Date & Time: May 6, 2017, 8:30 AM - 11:30AM Location: Sierra Suite K (Marriott Marquis) Poster Title: 1507: What Predicts Whether Perceived Responsibility of Pediatric Trainees Leads to Practices in Caring for Mental Health Problems? Author: Dr. Cori Green Session Date & Time: May 6, 2017, 1:00PM - 04:00PM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 1535: Is The Long Standing Maternal Antibiotic Regimen for Expectant Management of Preterm Premature Rupture of Membranes the Most Appropriate Choice for Preterm Neonates? Author: Drs. Lauren Blatt, Ericalyn Kasdorf, Rebecca Baergen, Shari Gelber and Jeffrey Perlman Session Date & Time: May 6, 2017, 1:00PM - 04:00PM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 2710: Role of Echocardiography in the Evaluation and Management of Pediatric Stroke Patients Authors: Drs. Sonia Voleti, Elizabeth Herrup, Sheila Carroll and Jeffrey D. Dayton Session Date & Time: May 7, 2017, 4:15PM - 7:30PM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 2730: Dietary Iron Supplementation Leads To Cortical Bone Loss in Juvenile Mice With Adenine-Induced Chronic Kidney Disease Authors: Drs. Oleh Akchurin, Edwin Patino, Angara Sureshbabu, Vidhi Dalal, Divya Bhatia, Stefano Rivella, Adele Boskey and Mary E. Choi Session Date & Time: May 7, 2017, 4:15PM - 7:30PM Location: Poster & Exhibit Hall (Moscone Center West) Invited Science Session Title: 3515 - Safe and Sound and Homeward Bound: Optimizing Hospital - to - Home Transitions Author: Dr. Snezana Nena Osorio Session Date & Time: May 8, 2017, 1:00PM - 3:00PM Location: SFC-3006 (Moscone Center West) Poster Title: 3489 - Paroxysmal Depolarizing Shift (PDS) - A Potential Marker of Intracellular Seizure (Sz) Activity and Precursor to Sleep Wake Cycles (SWC) in Term Infants undergoing Selective Head Cooling (SHC) Authors: Drs. Jeffrey Perlman and Murray Engle Session Date & Time: May 8, 2017, 4:15PM - 7:30PM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 3814 - Red Blood Cell Transfusion Associated Delirium in Children Authors: Drs. Sevini Shahbaz, Marianne Nellis and Chani Traube Session Date & Time: May 8, 2017, 4:15PM - 7:30PM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 4148 - Radiation Exposure to PEM Providers while Providing Procedural Sedation for Fluoroscopic-Guided Fracture Reduction in Children Authors: Drs. Jason Chan, Sunday Clark, Mary J. Ward and Shari Platt Session Date & Time: May 9, 2017, 7:00AM - 10:00AM Location: Poster & Exhibit Hall (Moscone Center West) Poster Title: 4131 - Behavioral (BEH) Problems (P) in Very Low Birthweight Infants (VLBWI) Are Associated with Cerebellar (CBL) Vermis Hypoplasia and Thinning of the Corpus Callosum (TCC) Authors: Drs. Vargabi Ghei, Linda Heier, Gail Ross, Jeffrey Perlman, Vivien Yap, Session Date & Time: May 9, 2017, 7:00AM - 10:00AM Location: Poster & Exhibit Hall (Moscone Center West)


News Article | May 4, 2017
Site: www.marketwired.com

The healthcare provider is the first among its peers in New York City to offer paid leave for new parents and comprehensive services for families NEW YORK, NY--(Marketwired - May 04, 2017) - NewYork-Presbyterian Hospital has announced that it will roll out paid parental leave for its employees who are new parents. The new policy is the most comprehensive of its kind among New York City hospitals and healthcare systems, offering new parents two to six weeks of paid time off, extended leave for six months and continuation of benefits, in addition to flex time currently available for new parents. The new paid parental leave policy covers women and men welcoming a child through birth, adoption and surrogacy. NewYork-Presbyterian Hospital will offer primary caregivers six weeks of paid leave and secondary caregivers two weeks of paid leave. In addition, birthing mothers will be eligible to receive paid, medically necessary leave related to the birth of their child, which is generally up to an additional six to eight weeks. "Our employees are the lifeblood of our organization," said Dr. Steven J. Corwin, president and CEO of NewYork-Presbyterian Hospital. "This new policy represents an investment in them and their families, but more than that, it's simply the right thing to do." "Welcoming a child is a special occasion for any family, and it's important that our employees have the peace of mind and resources to truly enjoy this time," said Dr. Laura Forese, executive vice president and chief operating officer of NewYork-Presbyterian Hospital. "Ultimately, the goal of this new policy is to assist our employees to have a work/life balance that works for them." In addition to the new paid parental leave benefit, NewYork-Presbyterian Hospital is also providing a variety of additional support programs for new and working parents: The policy will apply to employees at the six-campus academic medical center, NewYork-Presbyterian Hospital who have welcomed new children on or after April 1, 2017. The benefit will then be extended to employees at NewYork-Presbyterian's Regional Hospitals over the next year. "NewYork-Presbyterian is proud to provide our employees with a comprehensive and competitive benefits package," said Shaun Smith, senior vice president and chief human resources officer, NewYork-Presbyterian Hospital. "We're setting a new standard for healthcare employers in New York City." NewYork-Presbyterian is one of the nation's most comprehensive, integrated academic healthcare delivery systems, whose organizations are dedicated to providing the highest quality, most compassionate care and service to patients in the New York metropolitan area, nationally, and throughout the globe. In collaboration with two renowned medical schools, Weill Cornell Medicine and Columbia University Medical Center, NewYork-Presbyterian is consistently recognized as a leader in medical education, groundbreaking research and innovative, patient-centered clinical care. For more information, visit www.nyp.org and find us on Facebook, Twitter and YouTube.


- Clinical Trial Shows Weight Loss Trends of Up to One Pound Per Week and an Early Favorable Safety and Tolerability Profile - - Improvements in Metabolic Parameters and Trends for Weight Loss Supportive of Drug Effect - - Results Support Advancement to Phase 2 Clinical Trial in Patients with Type 2 Diabetes in the Second Half of This Year - BOSTON, May 04, 2017 (GLOBE NEWSWIRE) -- Zafgen, Inc. (Nasdaq:ZFGN) today announced positive topline data from its Phase 1 clinical trial of ZGN-1061, the Company’s second generation MetAP2 inhibitor. ZGN-1061 demonstrated rapid drug absorption and clearance in line with pre-specified criteria established for the molecule, and was well-tolerated and safe, with no evidence of prothrombotic effects. Patients in the clinical trial experienced mean weight loss of up to approximately one pound per week. “The results from this clinical trial mark an important first step in the clinical development of ZGN-1061, which has been optimized to improve glycemic control and body weight, with a favorable safety profile,” said Thomas Hughes, Ph.D., President and Chief Executive Officer of Zafgen. “The safety data and the early efficacy signals support the further development of this compound, and we plan to advance ZGN-1061 into a Phase 2 clinical trial in the second half of this year in patients with type 2 diabetes who are overweight or obese.” The Phase 1 clinical trial included a single ascending dose (SAD) phase, which enrolled healthy volunteers, and a multiple ascending dose (MAD) phase, which evaluated twice-weekly administration of ZGN-1061 in overweight or obese patients over four weeks. The SAD phase was comprised of six dosing cohorts ranging from 0.2 mg to 4.8 mg and the MAD phase was comprised of three dosing cohorts of 0.2 mg, 0.6 mg and 1.8 mg. The SAD phase included 39 volunteers (ZGN-1061 N=28, placebo N=11), 90% male and average body mass index (BMI) of 26 kg/m2; and the MAD phase included 29 patients (ZGN-1061 N=22, placebo N=7), 76% male and average BMI of 33 kg/m2. Patients in the MAD phase were domiciled while receiving treatment and were subjected to inpatient safety monitoring for most of the clinical trial’s 28-day duration. ZGN-1061 was safe and well-tolerated, with no serious adverse events (SAEs), and no severe adverse events (AEs). There were no AEs leading to early withdrawal from the clinical trial. All AEs were of mild intensity in the MAD phase except one (toothache). The most common side effects were mild gastrointestinal issues, which were comparable between the ZGN-1061 and placebo groups, headache and procedural related irritation. There was no prothrombotic effect observed with ZGN-1061. No treatment emergent venous thromboembolisms (VTEs), no clinically meaningful D-dimer elevations indicative of thrombosis and no elevations in mean D-dimer levels were observed in the dosing groups compared to baseline or placebo.  There were no clinically significant changes in coagulation laboratory parameters or other key biomarkers of interest, including von Willebrand factor, soluble thrombomodulin and plasminogen activator inhibitor-1. On average, patients treated with ZGN-1061 for four weeks lost weight relative to placebo-treated patients (-4.6 lbs, -2.2 lbs, and -3.8 lbs for 0.2 mg, 0.6 mg, and 1.8 mg, respectively vs. -0.51 lbs for placebo), with trends for improvements observed in waist circumference, food intake, low density lipoprotein-cholesterol, C-reactive protein, adiponectin and leptin. ZGN-1061 demonstrated rapid drug exposure and clearance for all dose levels, in line with prospectively established criteria. Effective concentrations of drug were reached in circulation based on measurements of drug binding to the MetAP2 target enzyme. “The data from this clinical trial provide a first view of the therapeutic potential of ZGN-1061 and its early favorable tolerability and safety profile,” stated Dr. Louis Aronne, the Sanford I. Weill Professor of Metabolic Research and a professor of clinical medicine at Weill Cornell Medicine.[i] “These early data provide a strong rationale for continued development of this promising molecule for the twin public health concerns of type 2 diabetes and obesity.” “The compound showed a promising efficacy signal on weight loss and improvement in metabolic parameters, which is consistent with what we would expect to see with MetAP2 inhibition,” said Dennis Kim, M.D., Chief Medical Officer of Zafgen. “In addition, ZGN-1061 demonstrated more favorable pharmacokinetic and safety attributes compared to first generation MetAP2 inhibitors, with no clinically meaningful impact on sleep and no evidence of elevated thrombotic risk in this small clinical trial.” Zafgen will host an investor conference call today, May 4, 2017 at 4:30 p.m., Eastern Time, to discuss the Phase 1 clinical trial data and provide a financial update. This call will replace the Company's usual quarterly earnings call. Investors and other interested parties may participate by dialing (844) 824-7428 in the United States or (973) 500-2177 outside the United States and referencing conference ID number 13508906. The call will also be webcast live on the Company's website at http://ir.zafgen.com/events.cfm. A replay of this conference call will be available beginning at 11:30 p.m. ET on May 4, 2017 through May 11, 2017 by dialing (855) 859-2056 in the United States or (404) 537-3406 outside the United States. To access the replay please provide Conference ID number 13508906. ZGN-1061 is a fumagillin-class, injectable small molecule second generation MetAP2 inhibitor that was advanced into development due to its unique properties that maximize impact on metabolic parameters relevant to the treatment of type 2 diabetes and other related metabolic disorders. In pre-clinical studies, ZGN-1061 has demonstrated promising efficacy in animal models of type 2 diabetes and obesity, with an improved pharmacokinetic profile and safety margin relative to previous molecules in the MetAP2 class. As demonstrated clinically for MetAP2 inhibitors, ZGN-1061 is anticipated to improve glycemic control while also helping to restore balance to fat metabolism, enabling calories to once again be used as a productive energy source, leading to improved metabolic control and long-term weight loss. Zafgen recently completed its first Phase 1 clinical trial of ZGN-1061, and is planning to advance the compound to Phase 2 clinical testing in patients with type 2 diabetes who are overweight or obese. Zafgen holds exclusive worldwide rights for the development and commercialization of ZGN-1061. Zafgen (Nasdaq:ZFGN) is a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by metabolic diseases including type 2 diabetes and obesity. Zafgen is focused on developing novel therapeutics that treat the underlying biological mechanisms of metabolic diseases through the MetAP2 pathway. Zafgen has pioneered the study of MetAP2 inhibitors in both common and rare forms of obesity, and in patients affected by type 2 diabetes. Zafgen's lead product candidate is ZGN-1061, which is a novel, first-in-class, subcutaneous injection. Zafgen aspires to improve the lives of patients through targeted treatments and has assembled a team accomplished in bringing therapies to patients affected by metabolic diseases. Various statements in this release concerning Zafgen's future expectations, plans and prospects, including without limitation, Zafgen's expectations regarding the use of ZGN-1061 and other MetAP2 inhibitors as treatments for metabolic diseases including type 2 diabetes and obesity, ZGN-1061’s improved safety margin, including as it relates to pro-thrombotic characteristics compared to first generation MetAP2 inhibitors, such as beloranib, and Zafgen's expectations with respect to the timing and success of its pre-clinical studies and clinical trials of ZGN-1061 and its other product candidates may constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Zafgen's ability to successfully demonstrate the efficacy and safety of ZGN-1061 and its other product candidates and to differentiate ZGN-1061 and its other product candidates from first generation MetAP2 inhibitors, such as beloranib, the pre-clinical and clinical results for ZGN-1061 and its other product candidates, which may not support further development and marketing approval, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Zafgen's ability to obtain, maintain and protect its intellectual property, Zafgen's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, competition from others developing products for similar uses, Zafgen's ability to manage operating expenses, Zafgen's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives when needed, Zafgen's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Zafgen's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Zafgen's subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Zafgen's views only as of today and should not be relied upon as representing its views as of any subsequent date. Zafgen explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. ___________________________ [i] Dr. Aronne is a Zafgen stockholder and member of the Company’s Clinical Advisory Board.


News Article | April 28, 2017
Site: www.businesswire.com

NEW YORK--(BUSINESS WIRE)--Weill Cornell Medicine today announced a gift made by WorldQuant, LLC (“WorldQuant”) and Igor Tulchinsky that will further realize the promise of precision medicine. The $5 million gift establishes a new initiative that will use predictive tools to enhance Weill Cornell Medicine’s capability to diagnose and treat a variety of illnesses, with the goal of improving outcomes for patients. The WorldQuant Initiative for Quantitative Prediction brings together financial and medical experts whose collaboration strives to enhance biomedical research. Weill Cornell Medicine’s scientists, working closely with researchers and technologists from WorldQuant, will deploy predictive tools and quantitative methods to deepen the understanding of genetic factors that drive disease in individual patients. Using sophisticated algorithms, the new initiative will enable the research team to analyze genomic data to identify patterns and trends that may predict patients’ future risk of developing disease, as well as potential outcomes. These insights may be used to improve the diagnosis and treatment of a variety of illnesses, including cancer, neurological disorders, cardiovascular diseases and infections. Weill Cornell Medicine researchers Dr. Christopher Mason, the WorldQuant Research Scholar, and Dr. Olivier Elemento, the Walter B. Wriston Research Scholar, will lead the initiative, which will involve joint work with physician-scientists at the Caryl and Israel Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “This outstanding gift will accelerate and expand Weill Cornell Medicine’s approach to precision medicine, providing new predictive tools that will lead to even better outcomes for patients,” said Jessica Bibliowicz, chairman of the Weill Cornell Medicine Board of Overseers. “We are very grateful to Igor Tulchinsky and WorldQuant, LLC for making this initiative possible.” “The use of quantitative prediction for patients represents an important new tool at Weill Cornell Medicine,” said Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean at Weill Cornell Medicine. “We appreciate Mr. Tulchinsky’s generosity, which will help us achieve new goals in the rapidly evolving field of precision medicine.” For WorldQuant, an international quantitative investment management firm founded by Mr. Tulchinsky, who is chairman and CEO, applying predictive algorithms to medical research is a natural progression. “There is a great opportunity to leverage the technology and proprietary algorithms we’ve developed for use outside of the financial markets, particularly around predictive medicine and cancer research, where the stakes are so high,” said Mr. Tulchinsky, a member of the Board of Overseers at Weill Cornell Medicine. “This initiative has tremendous possibilities, and I am proud to help drive advances in the field.” Drs. Mason and Elemento, as co-directors of the initiative, will leverage new technologies to analyze clinical samples and visualize various diseased tissues at single-cell resolution. These methods will be combined with a supercomputing infrastructure, which includes developing new software to crunch data using advanced pattern-recognition algorithms to model disease progression. One of the initiative’s ultimate goals is to give researchers the ability to examine a blood draw or urine sample from one patient and predict his or her future risk for developing a specific type of cancer. The same technology could also give researchers the ability to rapidly diagnose patients and predict which treatments might work, which treatments may encounter resistance and how the disease is likely to progress. In the future, this framework may enable investigators to analyze single cells and molecules from blood, tumor biopsies, saliva or other clinical samples collected from patients seeking care at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, and then use analytical algorithms to create personalized predictive models based on findings from longitudinal healthcare data collected from thousands of patients. To accomplish this, Drs. Mason and Elemento will work closely with WorldQuant’s research team and intend to recruit software engineers and experts in artificial intelligence who can develop innovative quantitative prediction tools and analyze findings. They will continue to provide advanced training in quantitative biology and modeling to Weill Cornell Medicine’s physician-scientists to support this effort. “We are looking forward to using the tools and methods that will result from this philanthropic investment to tease apart disease cells’ secrets and create predictive models of health for patients,” said Dr. Mason, who is also an associate professor of physiology and biophysics, an associate professor of computational genomics at the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine, and an associate professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. “Not only does this gift enable new science and predictive models in medicine, it also creates an unprecedented collaboration between two big-data groups at Weill Cornell Medicine and WorldQuant.” “This incredibly generous gift will likely spur a whole new generation of biomedical discoveries by helping bring predictive disease analytics to precision medicine,” said Dr. Elemento, who is also associate director of the Institute for Computational Biomedicine and an associate professor of physiology and biophysics at Weill Cornell Medicine. “We’re profoundly thankful to Igor for his support, and grateful to have WorldQuant as a partner in pioneering new approaches to understanding cancer, infections and neurological diseases.” Weill Cornell Medicine is committed to excellence in patient care, scientific discovery and the education of future physicians in New York City and around the world. The doctors and scientists of Weill Cornell Medicine — faculty from Weill Cornell Medical College, Weill Cornell Graduate School of Medical Sciences, and Weill Cornell Physician Organization — are engaged in world-class clinical care and cutting-edge research that connect patients to the latest treatment innovations and prevention strategies. Located in the heart of the Upper East Side's scientific corridor, Weill Cornell Medicine's powerful network of collaborators extends to its parent university Cornell University; to Qatar, where an international campus offers a U.S. medical degree; and to programs in Tanzania, Haiti, Brazil, Austria and Turkey. Weill Cornell Medicine faculty provide comprehensive patient care at NewYork-Presbyterian Weill Cornell Medical Center, NewYork-Presbyterian Lower Manhattan Hospital and NewYork-Presbyterian Queens. Weill Cornell Medicine is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu. WorldQuant, LLC is a global quantitative investment firm that was founded in 2007 by Igor Tulchinsky and now has more than $5 billion in assets under management. The firm has more than 20 offices in 15 countries and over 600 employees and 500 consultants. WorldQuant develops and deploys systematic investment strategies across a variety of asset classes in global markets, utilizing a proprietary research platform and investment process. For more information on WorldQuant’s culture and philosophy, please visit www.WeAreWorldQuant.com.


- Clinical Trial Shows Weight Loss Trends of Up to One Pound Per Week and an Early Favorable Safety and Tolerability Profile - - Improvements in Metabolic Parameters and Trends for Weight Loss Supportive of Drug Effect - - Results Support Advancement to Phase 2 Clinical Trial in Patients with Type 2 Diabetes in the Second Half of This Year - BOSTON, May 04, 2017 (GLOBE NEWSWIRE) -- Zafgen, Inc. (Nasdaq:ZFGN) today announced positive topline data from its Phase 1 clinical trial of ZGN-1061, the Company’s second generation MetAP2 inhibitor. ZGN-1061 demonstrated rapid drug absorption and clearance in line with pre-specified criteria established for the molecule, and was well-tolerated and safe, with no evidence of prothrombotic effects. Patients in the clinical trial experienced mean weight loss of up to approximately one pound per week. “The results from this clinical trial mark an important first step in the clinical development of ZGN-1061, which has been optimized to improve glycemic control and body weight, with a favorable safety profile,” said Thomas Hughes, Ph.D., President and Chief Executive Officer of Zafgen. “The safety data and the early efficacy signals support the further development of this compound, and we plan to advance ZGN-1061 into a Phase 2 clinical trial in the second half of this year in patients with type 2 diabetes who are overweight or obese.” The Phase 1 clinical trial included a single ascending dose (SAD) phase, which enrolled healthy volunteers, and a multiple ascending dose (MAD) phase, which evaluated twice-weekly administration of ZGN-1061 in overweight or obese patients over four weeks. The SAD phase was comprised of six dosing cohorts ranging from 0.2 mg to 4.8 mg and the MAD phase was comprised of three dosing cohorts of 0.2 mg, 0.6 mg and 1.8 mg. The SAD phase included 39 volunteers (ZGN-1061 N=28, placebo N=11), 90% male and average body mass index (BMI) of 26 kg/m2; and the MAD phase included 29 patients (ZGN-1061 N=22, placebo N=7), 76% male and average BMI of 33 kg/m2. Patients in the MAD phase were domiciled while receiving treatment and were subjected to inpatient safety monitoring for most of the clinical trial’s 28-day duration. ZGN-1061 was safe and well-tolerated, with no serious adverse events (SAEs), and no severe adverse events (AEs). There were no AEs leading to early withdrawal from the clinical trial. All AEs were of mild intensity in the MAD phase except one (toothache). The most common side effects were mild gastrointestinal issues, which were comparable between the ZGN-1061 and placebo groups, headache and procedural related irritation. There was no prothrombotic effect observed with ZGN-1061. No treatment emergent venous thromboembolisms (VTEs), no clinically meaningful D-dimer elevations indicative of thrombosis and no elevations in mean D-dimer levels were observed in the dosing groups compared to baseline or placebo.  There were no clinically significant changes in coagulation laboratory parameters or other key biomarkers of interest, including von Willebrand factor, soluble thrombomodulin and plasminogen activator inhibitor-1. On average, patients treated with ZGN-1061 for four weeks lost weight relative to placebo-treated patients (-4.6 lbs, -2.2 lbs, and -3.8 lbs for 0.2 mg, 0.6 mg, and 1.8 mg, respectively vs. -0.51 lbs for placebo), with trends for improvements observed in waist circumference, food intake, low density lipoprotein-cholesterol, C-reactive protein, adiponectin and leptin. ZGN-1061 demonstrated rapid drug exposure and clearance for all dose levels, in line with prospectively established criteria. Effective concentrations of drug were reached in circulation based on measurements of drug binding to the MetAP2 target enzyme. “The data from this clinical trial provide a first view of the therapeutic potential of ZGN-1061 and its early favorable tolerability and safety profile,” stated Dr. Louis Aronne, the Sanford I. Weill Professor of Metabolic Research and a professor of clinical medicine at Weill Cornell Medicine.[i] “These early data provide a strong rationale for continued development of this promising molecule for the twin public health concerns of type 2 diabetes and obesity.” “The compound showed a promising efficacy signal on weight loss and improvement in metabolic parameters, which is consistent with what we would expect to see with MetAP2 inhibition,” said Dennis Kim, M.D., Chief Medical Officer of Zafgen. “In addition, ZGN-1061 demonstrated more favorable pharmacokinetic and safety attributes compared to first generation MetAP2 inhibitors, with no clinically meaningful impact on sleep and no evidence of elevated thrombotic risk in this small clinical trial.” Zafgen will host an investor conference call today, May 4, 2017 at 4:30 p.m., Eastern Time, to discuss the Phase 1 clinical trial data and provide a financial update. This call will replace the Company's usual quarterly earnings call. Investors and other interested parties may participate by dialing (844) 824-7428 in the United States or (973) 500-2177 outside the United States and referencing conference ID number 13508906. The call will also be webcast live on the Company's website at http://ir.zafgen.com/events.cfm. A replay of this conference call will be available beginning at 11:30 p.m. ET on May 4, 2017 through May 11, 2017 by dialing (855) 859-2056 in the United States or (404) 537-3406 outside the United States. To access the replay please provide Conference ID number 13508906. ZGN-1061 is a fumagillin-class, injectable small molecule second generation MetAP2 inhibitor that was advanced into development due to its unique properties that maximize impact on metabolic parameters relevant to the treatment of type 2 diabetes and other related metabolic disorders. In pre-clinical studies, ZGN-1061 has demonstrated promising efficacy in animal models of type 2 diabetes and obesity, with an improved pharmacokinetic profile and safety margin relative to previous molecules in the MetAP2 class. As demonstrated clinically for MetAP2 inhibitors, ZGN-1061 is anticipated to improve glycemic control while also helping to restore balance to fat metabolism, enabling calories to once again be used as a productive energy source, leading to improved metabolic control and long-term weight loss. Zafgen recently completed its first Phase 1 clinical trial of ZGN-1061, and is planning to advance the compound to Phase 2 clinical testing in patients with type 2 diabetes who are overweight or obese. Zafgen holds exclusive worldwide rights for the development and commercialization of ZGN-1061. Zafgen (Nasdaq:ZFGN) is a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by metabolic diseases including type 2 diabetes and obesity. Zafgen is focused on developing novel therapeutics that treat the underlying biological mechanisms of metabolic diseases through the MetAP2 pathway. Zafgen has pioneered the study of MetAP2 inhibitors in both common and rare forms of obesity, and in patients affected by type 2 diabetes. Zafgen's lead product candidate is ZGN-1061, which is a novel, first-in-class, subcutaneous injection. Zafgen aspires to improve the lives of patients through targeted treatments and has assembled a team accomplished in bringing therapies to patients affected by metabolic diseases. Various statements in this release concerning Zafgen's future expectations, plans and prospects, including without limitation, Zafgen's expectations regarding the use of ZGN-1061 and other MetAP2 inhibitors as treatments for metabolic diseases including type 2 diabetes and obesity, ZGN-1061’s improved safety margin, including as it relates to pro-thrombotic characteristics compared to first generation MetAP2 inhibitors, such as beloranib, and Zafgen's expectations with respect to the timing and success of its pre-clinical studies and clinical trials of ZGN-1061 and its other product candidates may constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Zafgen's ability to successfully demonstrate the efficacy and safety of ZGN-1061 and its other product candidates and to differentiate ZGN-1061 and its other product candidates from first generation MetAP2 inhibitors, such as beloranib, the pre-clinical and clinical results for ZGN-1061 and its other product candidates, which may not support further development and marketing approval, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Zafgen's ability to obtain, maintain and protect its intellectual property, Zafgen's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, competition from others developing products for similar uses, Zafgen's ability to manage operating expenses, Zafgen's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives when needed, Zafgen's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Zafgen's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Zafgen's subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Zafgen's views only as of today and should not be relied upon as representing its views as of any subsequent date. Zafgen explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. ___________________________ [i] Dr. Aronne is a Zafgen stockholder and member of the Company’s Clinical Advisory Board.

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