Posts Tagged ‘LCAT’

Curator: Aviva Lev-Ari, PhD, RN


UPDATED on 7/29/2018


HDL-C: Is It Time to Stop Calling It the ‘Good’ Cholesterol? – Medscape – Jul 27, 2018.


In Eli Lilly’s Pipeline: DISCONTINUING Evacetrapib, a CETP inhibitor that’s meant to boost HDL

Reporter: Aviva Lev-Ari, PhD, RN


On April 3, 2012 we published

Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore

ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme.

LCAT, an enzyme in the bloodstream, is a key component in the reverse cholesterol transport (RCT) system, which is thought to play a major role in driving the removal of cholesterol from the body and may be critical in the management of high-density lipoprotein (HDL) cholesterol levels.  The LCAT enzyme could also play a role in a rare, hereditary disorder called familial LCAT deficiency (FLD) in which the LCAT enzyme is absent.

On April 4, 2013, the next day, a new study was published on a novel class of compounds, cholesteryl ester transfer protein (CETP) inhibitors, has demonstrated many potentially beneficial lipid-modifying effects was published on Anacetrapib, a compound that causes near-complete CETP inhibition, has among its effects, robust reductions in LDL-C and lipoprotein(a) as well as dramatic increases in HDL-C. The ability of anacetrapib to reduce coronary disease events is being tested in the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial (NCT01252953).

Writer’s VIEWS:

    • AstraZeneca acquisition of AlphaCore represents its market entry into the CETP inhibitor segment via an acquisition where the company did not have presence or inhouse research. The results of the second study will position Merck at a superior position upon completion of Phase III Clinical Trials for Anacetrapib
    • If Biologics will help increase HDL in wide market penetration, the market share of Statins will be negatively impacted. Patent expiration and generic market availability of Statin erode future profits
    • Anacetrapib in in Phase III clinical Trial, if successfully completed — will be the FIRST biologics to use CETP inhibition biology of lipid metabolism in the quest to fight atherosclerosis by improving CVD outcomes
    • A connection between this two events and cites in Disclosure, AstraZeneca, Merck, supporting the research of Christopher P Cannon on the study on Anacetrapib.
    • Full Article PDF file was published in Research Reports in Clinical Cardiology, one of the Journals on Beall’s list publisher, where scientists pay to have the article been published, Dove Press, on its Web site says, “There are no limits on the number or size of the papers we can publish.” See reference for Beall’s list publishers

Study Goals:

  • testing the hypothesis that CETP inhibition may reduce atherosclerotic outcomes. 
  • answer important questions regarding the role of CETP in the biology of lipid metabolism and atherosclerosis.

Research Reports in Clinical Cardiology, 4 April 2013 Volume 2013:4 Pages 39 – 53

Dylan L Steen,1 Amit V Khera,2 Christopher P Cannon1

1TIMI Study Group, Cardiovascular Division, 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA


Dr Cannon is a member of the advisory boards of and has received grant support from Alnylam, Bristol-Myers Squibb, Pfizer, and CSL Behring; has received grant support from Accumetrics, AstraZeneca, Essentialis, GlaxoSmithKline, Merck, Regeneron, Sanofi, and Takeda; and is a clinical advisor to Automated Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper.

Abstract: Despite major advances in cardiovascular care in recent decades, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Statins have been shown to reduce cardiovascular events by 25%–40% in a dose-dependent fashion; yet additional therapies are needed to reduce vascular disease progression and acute thrombotic events. In addition to low-density lipoprotein cholesterol (LDL-C) reduction, other lipid risk factors, such as low high-density lipoprotein cholesterol (HDL-C), have created interest as therapeutic targets to lower cardiovascular risk. However, the absence of compelling data for incremental benefit of non-LDL-centric therapies in the statin era has limited their clinical use. A novel class of compounds, cholesteryl ester transfer protein (CETP) inhibitors, has demonstrated many potentially beneficial lipid-modifying effects. While in vitro and animal data for CETP inhibition have been encouraging, the initial enthusiasm for the class has been tempered by the failure of two CETP inhibitors (torcetrapib and dalcetrapib) in Phase III trials to reduce cardiovascular outcomes. Anacetrapib, a compound that causes near-complete CETP inhibition, has among its effects, robust reductions in LDL-C and lipoprotein(a) as well as dramatic increases in HDL-C. The ability of anacetrapib to reduce coronary disease events is being tested in the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial (NCT01252953).

Keywords: anacetrapib, cholesteryl ester transfer protein, cholesteryl ester transfer protein inhibitor, atherosclerosis

  • Niacin, which augments HDL-C by 20%–25%, recently failed to lower atherosclerotic events in both the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH)6 and Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials.7,8
  • Lp(a) lowering has not yet been evaluated in randomized controlled trials, but observational and genetic (including Mendelian randomization) analyses have demonstrated an independent association of increased Lp(a) levels with increased CV events, suggesting Lp(a) lowering may confer benefit.9
  • surprising failure of the first two CETP inhibitors (torcetrapib and dalcetrapib) in Phase III outcomes trials has somewhat tempered this initial excitement and forced a re-evaluation of the complex effects of CETP inhibition on lipid metabolism and vascular biology.
  • Anacetrapib results in near-complete CETP inhibition with more pronounced lipid effects than its predecessors and is currently in a Phase III study for secondary prevention of coronary events. If successful it is likely that anacetrapib will also be considered for statin-intolerant patients and for primary prevention in patients who require LDL-C lowering beyond statin monotherapy
  • Human CETP is a 476-residue, 74 kDa, hydrophobic glycoprotein primarily secreted by the liver and adipose tissue.13 CETP was first cloned in 1987.14 The structure of CETP allows formation of a tunnel with the opening on one end interacting with HDL and the other with a very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), or LDL particle. The hydrophobic central cavity of this tunnel is large enough to allow transfer of neutral lipids (eg, cholesteryl esters [CEs], triglycerides [TGs]) from donor to acceptor particles, but conformational changes may occur to accommodate larger lipoprotein particles. The concave surface of CETP matches the curvature of the HDL particles to which it is primarily bound in the bloodstream.15,16
  • The overall effect of CETP is a net transfer of CE from HDL to these apolipoprotein B (apoB)-containing particles and TG to HDL and LDL
  • An important driver of the transfer of CE from HDL to apoB-containing particles is the production of CE from free cholesterol within HDL by lecithin acetyltransferase (LCAT).17

    The role of CETP in reverse cholesterol transport.

    Beginning in the peripheral tissues, free cholesterol is predominantly taken up by small “immature” HDL particles (eg, pre-β-HDL) via the ABCA1 transporter. Alternatively, it can be taken up by larger “mature” HDL particles (eg, HDL2) via the ABCG1 transporter. LCAT converts free cholesterol into cholesteryl ester, which is then shuttled to apoB-lipoproteins (eg, LDL, VLDL) in exchange for triglycerides. Only a minority of cholesteryl ester is delivered directly to the liver by HDL via the SR-BI; the majority is delivered indirectly to the liver by apoB-lipoproteins via the LDL recepter.

    Abbreviations: CETP, cholesteryl ester transfer protein; HDL, high-density lipoprotein; ABCA1, ATP-binding cassette transporter A1; ABCG1, ATP-binding cassette transporter G1; LCAT, lecithin acetyltransferase; apoB, apolipoprotein B; LDL, low-density lipoprotein; VLDL, very low density lipoprotein; SR-BI, scavenger receptor-BI; FC, free cholesterol; CE, cholesteryl ester.

  • One of the interesting questions in CETP deficiency is whether the HDL particles produced by potent CETP inhibition are functional. Regardless of whether reverse cholesterol transport is increased, the initial steps of cholesterol efflux from foam cells may be one of the key anti-atherogenic functions of HDL.5
  • This increased efflux is related to the very high content of LCAT and apoE in these large HDL particles, presumably driving net cholesterol efflux by promoting cholesterol esterification.36
  • effect of CETP deficiency on liver uptake of cholesteryl ester, an important downstream step in a reverse cholesterol transport. These studies suggest that there may be increased CE uptake via SR-BI as well as through a high affinity of large apoE-rich HDL for LDL receptors.20
  • meta-analysis established that three CETP genotypes were not only associated with decreased CETP activity and increased HDL but also with a lower risk of myocardial infarction (MI). For example, for each allele inherited, individuals with the TaqIB polymorphism had lower mean CETP activity (−8.6%), higher mean HDL-C (4.5%), higher mean apoA-I (2.4%), and an odds ratio for coronary disease of 0.95 (95% confidence intervals [CI], 0.92, 0.99). Similar associations were found for the other two CETP genotypes.40
  • Subsequent studies have confirmed that genetic variants leading to reduced CETP activity and its corresponding anti-atherogenic lipid profile are associated with reduced atherosclerotic outcomes.41–43
  • In ILLUSTRATE, an inverse association between HDL-C achieved and the primary endpoint of atheroma volume (r = −0.17, P , 0.001) was found. In addition, the highest quartile of HDL-C achieved (.86 mg/dL) demonstrated atheroma regression, suggesting that there may be a “threshold effect” to HDL-C elevation.68
  • Other CETP inhibitors:

was developed by Hoffmann–La Roche until May 2012. It did not raise blood pressure and did raise HDL, but it showed no clinically meaningful efficacy.


is under development by Eli Lilly & Company.
was developed by Pfizer until December 2006 but caused unacceptable increases in blood pressure and had net cardiovascular detriment.
Anacetrapib At the 16th International Symposium on Drugs Affecting Lipid Metabolism (New York, Oct 4-7, 2007), Merck reported on a Phase IIb study. The eight week study reported dosage correlated reduction in LDL-C and increases in HDL-C levels with no corresponding increases in blood pressure in any cohort. The increase in HDL was particularly significant, averaging 44 percent, 86 percent, 139 percent and 133 percent at doses of 10 mg, 40 mg, 150 mg and 300 mg. Merck performed a dose-ranging study of anacetrapib, with the results presented in 2009.


Anacetrapib is a 3,5-bis-trifluoromethyl-benzene derivative with similar binding properties to CETP as torcetrapib. The compound was developed when it was found that a substitution modification of the oxazolidinone ring increased its potency for CETP inhibition in a transgenic mouse model.85 In terms of its pharmacokinetics and pharmacodynamics, anacetrapib is rapidly absorbed with a time-to-peak plasma concentration of about 4 hours. The oral bioavailability of anacetrapib is poor, with only about 20% being absorbed; however at this exposure, LDL-C is reduced up to 40% and HDL-C increased up to 140%. It is recommended that anacetrapib be taken with food (ie, low-fat diet) to increase drug exposure (and efficacy) as well as compliance.86

Anacetrapib is highly protein bound (eg, CETP) in the plasma (.99.5%). It is cleared by oxidative metabolism via Cytochrome P450 3A4 (CYP3A4) with excretion of the metabolites via the biliary/fecal route. Only a trace amount is eliminated by urinary excretion.87 Importantly, while anacetrapib is a sensitive CYP3A4 substrate, anacetrapib neither inhibits nor induces CYP3A4 activity. No meaningful interactions have been found between anacetrapib and simvastatin, digoxin, or warfarin.86 Anacetrapib in part to its redistribution to adipose tissue has a long terminal half-life.88

In terms of safety endpoints, anacetrapib demonstrated no increase in side effects (including myalgia), drug-related adverse effects, adverse events leading to drug discontinuation, or other important safety endpoints, such as BP, electrolyte, aldosterone, creatinine kinase, or transaminase levels. A very small increase in C-reactive protein of undetermined significance was seen with anacetrapib, which notably was also reported with torcetrapib and dalcetrapib in their Phase III studies. It is unknown whether this is a class effect as the small sample size in the evacetrapib Phase II study limits evaluation of small C-reactive protein changes.

It is expected that the REVEAL (the Phase III) population will also have lower starting LDL-C levels, both because statin-intolerant subjects will not be enrolled and because of more stringent lipid entry criteria. The final major difference is that the primary endpoint in REVEAL is focused on coronary events, while ACCELERATE has a broader primary endpoint. A broader primary endpoint along with a slightly higher risk population will allow for a shorter follow-up duration and much smaller sample size in ACCELERATE.


  • CETP remains a valid target and that the lipid changes resulting from its inhibition may be protective. The biology of CETP inhibition is complex, and questions remain regarding which lipid changes (eg, reductions in LDL and Lp(a), increases in HDL) are most likely to be important and whether there are still unknown effects that may negate any overall clinical benefit.
  • if potent CETP inhibition is found to be beneficial, it is still unclear whether this effect will be homogeneous or vary based on individual metabolism.
  • anacetrapib-induced HDL (especially the apoE-rich HDL2 particles) may have an enhanced ability for reverse cholesterol transport without any known adverse effects. Importantly, if a threshold effect for HDL-C augmentation exists, the vast majority of patients taking anacetrapib would be expected to cross it.
  • Despite a difficult beginning for the class of CETP inhibitors, anacetrapib and evacetrapib hold promise as future therapies for patients with atherosclerosis

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submit your manuscript | Dovepress Dovepress 51 Anacetrapib for coronary heart disease Research Reports in Clinical Cardiology 2013:4

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Curator: Aviva Lev-Ari, PhD, RN

If Biologics will help increase HDL in wide market penetration, the market share of Statins will be negatively impacted.

The biologics was developed by NIH funding, as reported on 2/14/2012, see last section, below.

NHLBI SMARTT Program Awards AlphaCore Pharma Funding to Manufacture Potential Treatment for Familial Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency


In an Interview I had with the VP of Scientific Affairs at AstraZenaca on 3/18/2013, the Executive Dr. D.S., MD, PhD, told me that the Cardiovascular Therapeutic Area at AstraZeneca is at present and in the future, probably the most important one of all of its businesses to date, thus, the position he is interviewing for, Director of Scientific Affairs Cardiovascular, will be the most powerful one within the Scientific Affairs Office.

Per my discussion of BRILINTA (ticagrelor), referring the VP to my post on this topic on 12/28/2012,

PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack

VP said, “the position will be beyond BRILINTA, or Cardiovascular.” A candidate not found yet. AZ keeps on calling, Keeps searching.

AstraZeneca – The Biggest R&D Spenders In Biopharma

Company: AstraZeneca

2011 spending: $5.5 billion
2010 spending: $5.3 billion
Change: +3.6%
Percentage of revenue: 16.3%

Like several other top 10 pharma companies, AstraZeneca ($AZN) saw its R&D expenses climb somewhat in 2011. But this year, as CEO David Brennan unveiled the annual results for 2011, he started with a new restructuring plan. And R&D is intended to bear some of the biggest cuts.

Hit with sliding profits and eviscerated by analysts for one of the weakest late-stage pipelines in the Big Pharma business, Brennan had to do something significant. Of more than 7,000 pink slips being readied, 2,200 were being reserved for R&D as the company moved to shutter R&D facilities in Soedertaelje in Sweden and Montreal. Neuroscience, once a key feature in the pipeline, is being scaled way back, with plans to field a “virtual” team in key hubs.

AstraZeneca became the poster child for the R&D quagmire when Forbes‘ Matthew Herper concluded that AstraZeneca had the worst ratio of R&D costs to approvals in the industry. For a company that went 6 years without a drug approval ahead of the 2009 OK for Onglyza, accumulated setbacks have reached a breaking point.

AstraZeneca, though, can’t cut its way to a turnaround in R&D. That’s going to take new programs and new technologies. It only began to address the issue with a licensing pact for a slate of Amgen antibodies. Research chief Martin Mackay was quick to follow up by telling Reuters‘ Ben Hirschler that more deals were coming. And indeed just weeks later, AstraZeneca acquired a late-stage gout drug with the $1.26 billion buyout of Ardea. The fact that AstraZeneca didn’t bother to stick with its disease strategy, and quickly indicated that it wouldn’t in the future, underscored just how crucial it is to move fast.

Nevertheless, AstraZeneca will find it hard to shake its legacy of failures. Just weeks ago the company was forced to wash its hands of a billion-dollar deal with Targacept ($TRGT) for a prospective depression drug that failed 4 out of 4 late-stage studies. And as criticism mounted, Brennan has been forced to adopt a defensive posture.

“I read and hear and see lots of things, but we’re here trying to change policy, make good decisions and execute our strategy,” the CEO told Bloomberg, vowing to stick to the game plan. “Maybe somebody sees something different, but spending more money does not have a linear increase in the number of returns you get from a research and development perspective.”

AstraZeneca – The Biggest R&D Spenders In Biopharma – FierceBiotech

On April 3, 2013, FierceBiotech reported that


3 April 2013

AstraZeneca today announced that MedImmune, its global biologics research and development arm, has acquired AlphaCore Pharma, an Ann Arbor, Michigan-based biotechnology company focused on the development of ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme.

LCAT, an enzyme in the bloodstream, is a key component in the reverse cholesterol transport (RCT) system, which is thought to play a major role in driving the removal of cholesterol from the body and may be critical in the management of high-density lipoprotein (HDL) cholesterol levels.  The LCAT enzyme could also play a role in a rare, hereditary disorder called familial LCAT deficiency (FLD) in which the LCAT enzyme is absent.

Cardiovascular and metabolic disease is a core therapy area for AstraZeneca’s small and large molecule research.

“As the science in this area continues to evolve, we are committed to exploring unique pathways that could lead to new combination or standalone therapies for patients living with chronic and acute cardiovascular diseases,” said Dr. Bahija Jallal, Executive Vice President, MedImmune. “Cardiovascular disease is projected to remain the single leading cause of death worldwide over the next decade and beyond. Through novel approaches like LCAT, we hope to shift the treatment paradigms in this area to help prevent and treat these conditions.”

In 2012, results from a Phase I clinical trial of ACP-501 met the primary safety and tolerability endpoints.  No serious adverse events were reported.  ACP-501 also met the study’s secondary endpoints by rapidly and substantially elevating HDL cholesterol.  The data from this study support ongoing clinical development of ACP-501.


 AstraZeneca gambles on cardio therapy in AlphaCore buyout

By Ryan McBride

In another early-stage bet, AstraZeneca’s MedImmune unit acquired the biotech AlphaCore Pharma. The deal comes as AstraZeneca ($AZN) reboots a floundering R&D effort and adds a recombinant LCAT enzyme therapy from AlphaCore that could combat cardiovascular disease.

MedImmune, the biologics division of Astra, faces years of additional development before AlphaCore’s ACP-501 becomes part of the London-based pharma group’s late-stage pipeline, which has many holes yet to be filled. Last year, Ann Arbor, MI-based AlphaCore touted Phase I work on ACP-501, reporting that the enzyme therapy was well-tolerated and quickly boosted levels of HDL or “good” cholesterol in patients.

AZ CEO Pascal Soriot

New AstraZeneca CEO Pascal Soriot has signaled his desire to wager on new science amid an overhaul of R&D announced last month that will cost 1,600 research jobs across the company and after the ouster of former R&D chief Martin Mackay in January. Bahija Jallal, executive vice president of MedImmune, survived the round of cutbacks and plans to pursue new biologics such as ACP-501, which she stated could treat both acute and chronic cardiovascular disease.

“Cardiovascular disease is projected to remain the single leading cause of death worldwide over the next decade and beyond,” Jallal said. “Through novel approaches like LCAT, we hope to shift the treatment paradigms in this area to help prevent and treat these conditions.”

The ACP-501 is an engineered version of the natural LCAT enzyme from the liver that plays a role in ridding the body of cholesterol and keeping up levels of beneficial HDL cholesterol. The candidate could aid millions of patients with cholesterol problems as well as those with a rare inherited disease called familial LCAT deficiency that robs the body of the enzyme.

Bahija Jallal, EVP of MedImmune

The AlphaCore buyout comes on the heels of AstraZeneca’s sizable $240 million upfront payment to Moderna Therapeutics to get in early on the startup’s preclinical programs that use messenger RNA to turn cells in the body into makers of healing proteins. The financial details of the AlphaCore buyout weren’t disclosed.

Still, analysts expect Soriot to pull the trigger on larger deals to bolster the late-stage pipeline or even provide marketed products as AstraZeneca faces the impact of patent expirations on blockbuster cholesterol pill Crestor and the heartburn med Nexium. As Reuters noted, the company has only 6 drugs in late-stage development and aims to double that number by 2016.

February 14, 2012 09:17 AM Eastern Daylight Time

NHLBI SMARTT Program Awards AlphaCore Pharma Funding to Manufacture Potential Treatment for Familial Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency

ANN ARBOR, Mich. & ROCKVILLE, Md.–(BUSINESS WIRE)–AlphaCore Pharma, a biopharmaceutical company, and Advanced Bioscience Laboratories (ABL), a biomedical contract research and manufacturing company, today announce funding from the National Institutes of Health, National Heart, Lung and Blood Institute (NHLBI) “Science Moving towards Research Translation and Therapy” (SMARTT) program, to manufacture recombinant human lecithin-cholesterol acyltransferase (rhLCAT) for the treatment of familial LCAT deficiency.

“This is a significant step towards developing a treatment for familial LCAT deficiency. We are pleased by the strong support from the NHLBI and ABL and look forward to advancing this program.”

Also known as ACP-501, rhLCAT represents a promising new approach in the fight against atherosclerotic cardiovascular disease, and has demonstrated preclinical efficacy in promoting HDL maturation and cholesterol flux, a natural process by which cholesterol is removed from the body. Currently, ACP-501 is in Phase 1 clinical development with the eventual goal of reducing the risk of cardiovascular events in patients presenting with acute coronary syndrome. Manufacturing support from the NHLBI SMARTT program will enable production of additional material that will be used to determine the safety and efficacy of rhLCAT enzyme replacement therapy for patients with familial LCAT deficiency – a potentially life-threatening illness for which there is no FDA-approved treatment.

“This is a significant step towards developing a treatment for familial LCAT deficiency. We are pleased by the strong support from the NHLBI and ABL and look forward to advancing this program.” said AlphaCore President, Bruce Auerbach.

The enzyme, rhLCAT, will be produced by ABL in its Rockville, MD biologics production facility under a contract from the NHLBI SMARTT program. Dr. Thomas VanCott, ABL’s President and Chief Executive Officer stated, “ABL is privileged to be working with AlphaCore Pharma in support of their ACP-501 (rhLCAT) program. Research in rare genetic diseases can encounter funding hurdles, yet through this NHLBI-sponsored manufacturing project we have the potential to advance an urgently needed enzyme replacement therapy. This effort further demonstrates ABL’s expertise of partnering with the NIH to support major development programs and our commitment to deliver the highest quality cGMP biologics to our clients in a cost-effective manner.”

Peter Greenleaf, chief executive of MedImmune. (Jeffrey MacMillan – JEFFREY MACMILLAN)Peter Greenleaf is stepping down down as president of Gaithersburg-based biotechnology giant MedImmune, according to a company spokesman, to take the helm of parent company AstraZeneca’s Latin America business.

He will be replaced by Bahija Jallal, who currently serves as MedImmune’s executive vice president of research and development. Jallal joined the company in 2006 as vice president of translational sciences.

The leadership change comes as MedImmune was formally designated a biologics research and development site for AstraZeneca, meaning Jallal will report directly to AstraZeneca chief executive Pascal Soriot, said company spokesman Mike O’Brien.

He added that MedImmune’s commercial organization will now report into AstraZeneca’s North American business and its manufacturing group will be folded into AstraZeneca’s global operations group.

“There’s no new news on jobs today,” O’Brien said. “The driver for these changes is not cost but even faster decision-making in key areas of the business and a need to reduce complexity.”

O’Brien said Greenleaf will continue to be based in Maryland, where he has become a figure­head of sorts for the life sciences industry.

Greenleaf was an advocate for Democratic Gov. Martin O’Malley’s InvestMaryland initiative, which allocates state money for investment in local upstarts. He serves as chairman of the Maryland Venture Fund Authority, a nine-member board assigned to oversee its implementation.

MedImmune has long been an anchor of Maryland’s biotechnology hub along the Interstate 270 corridor. The company was purchased by AstraZeneca in 2007 for $15.6 billion, a sales price that some industry observers still question.

The Washington Business Journal reported the personnel changes earlier.



Mineo C, Yuhanna IS, Quon MJ, Shaul PW., (2003). HDL-induced eNOS activation is mediated by Akt and MAP kinases. J. Biol. Chem., 278:9142–9149.

Shaul, PW and Mineo, C, (2004). HDL action on the vascular wall: is the answer NO? J Clin Invest., 15; 113(4): 509–513.

Other related articles to this topic on the Open Access Online Scientific Journal include the following:

Aviva Lev-Ari, PhD, RN, 4/7/2013


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