December 6, 2010

University of Maryland School of Pharmacy researchers have developed a mathematical model for choosing an appropriate dosage of the hepatitis medications for individual patients. The work helps explain why African American patients tend to not respond as well to the drugs as other patients.

For the work, student researcher Runyan Jin, MD, PhD, won the best student research award and a $1,000 prize for her work at the 2010 American College of Clinical Pharmacology (ACCP) scientific meeting. Her project involved analyzing 900 blood samples from 400 patients enrolled in a multi-center trial to determine why hepatitis therapy works for some patients, but not others.

Hepatitis C is a serious liver disease caused by the hepatitis C virus and if not treated can lead to liver cancer and death. African Americans have a higher incidence and death from liver cancer.

The therapy, consisting of the anti-virus drug ribavirin, along with injections of the protective protein interferon, cures hepatitis C in some patients within six months due to a sustained viral response [SVR], suppressing the virus to undetectable levels for an extended period of time.

"Our question was why some patients in the large trial did not get this SVR cure. The response rate of African American patients was about half that of non-African Americans," says Thomas Dowling PharmD, PhD, associate professor in the School of Pharmacy's Clinical Pharmacology Unit. [Jin and Dowling are pictured above.]

Jin, who is Dowling's post-doctorate student and is already a pediatrician, reported that blood from the African American patients contained lower levels of the ribavirin drug than blood from non-African American patients on the same therapy. Especially in early stages of the therapy, the ribavirin was not getting into the blood system as efficiently in African Americans as in Caucasians. The mathematical model showed that the African Americans had a pharmacodynamic difference somehow in the distributional volume, which means the space where the drug moves, says Dowling.

The different response by African Americans to ribavirin is not the first time medical science has seen such a drug response difference between races.

"We are trying to model how to change the dosage not just change dose recommendations now. ýEventually personalized therapy will mean proper doses for each patient's genotype."

Pediatrician Jin hopes that her pharmacy work on anti-virus mediations and how they work in different people, pharmacodynamics, will also be useful in treating children. "This is especially important in children to get the correct dosages for safe and effective treatments." ý

"I was very lucky," says Jin. "When I was a second year [PhD]) student, I was looking for a research project in pharmacodynamics." She applied a mathematical method called Bayesian statistics to simplify the pharmacodynamic relationship between the drug and the 400 patients in the 2006 study, a method taught to her by Michael Fossler, PharmD, PhD, an alum of the School of Pharmacy now with drug maker GlaxoSmithKline.

"Runyan pulled a very nice story together with direct clinical applications. What we are faced with now [in drug development] is studies that are now so very expensive, says Fossler. "Bayesian methodology helps us cut our losses saves some patients from taking drugs that don't work sometimes."

Jin's research poster, "Population Pharmacodynamic Model in Patients with Chronic Hepatitis C Virus Genotype 1," won the 2010 Wayne A. Colburn Memorial Award at the annual ACCP. She has accepted a position at the U.S. Food and Drug Administration. ýIn her new career, she says, "I want to be an expert in this area of quantitative clinical pharmacology."

Posting Date: 12/06/2010
Contact Name: Steve Berberich
Contact Phone: 410-706-0023
Contact Email:


New HCV Drugs at AASLD


from Jules: below are links to key data reports on the many new oral HCV drugs at various stages of development and there are numerous drugs in development from the various new classes which include protease inhibitors, polymerase inhibitors (nucleosides, nucletides, various types of NNRTIs), NS5A inhibitors, and if pegIFN must be used there is peg-lambda IFN. Of course Vertex & Merck presented phase 3 data results at AASLD but also there were many data updates from the other drugs in earlier stages of development. Response-Gulded Therapy (RGT) will be the new mantra in HCV therapy once the 1st oral drugs hit the market and this means patients & clinicians must bring in patients at time-checks early after starting therapy to see if viral load is undetectable or not; these time-point checks to decide if a patient should continue or stop therapy, and I see this concept continuing to be refined over time, we will move towards 16 week or even 12 week total therapy as we improve regimens to include 3 or 4 orals with or without peg/rbv.

In the Vertex large phase 3 ADVANCE Study of the HCV protease inhibitor telaprevir, which included over 1000 genotype 1 treatment-naïve patients presented at AASLD, study patients who received telaprevir plus Pegasys/rbv had a significantly higher SVR (Sustained Viral Response, cure): 75% vs 44% of patients who received just Pegasys/rbv. These numbers included patients who had either 24 or 48 weeks total therapy. Patients, both blacks and whites, who had undetectable viral load at the early time-checkpoints, weeks 4 and 12, about 90% achieved SVR. In the Merck SPRINT-2 phase 3 Study of boceprevir presented at AASLD, over 1000 genotype 1 treatment-naïve patients participated, patients received either boceprevir plus Pegintron/rbv or just Pegintron/rbv, with 67-71% of non-Blacks achieving a SVR (cure) vs 40% for study patients who received Pegintron/rbv, and 42-53% of Blacks achieving cure vs 23% who received only Pegintron/rbv, these results were for patients who had a total duration of therapy of 24 or 48 weeks. An undetectable viral load at the early time-check-points in this study, weeks 8 and 24, also achieved high rates of SVR, cure.

How much affect on outcome (SVR) will IL28B and the genotype 1a vs 1b have once oral therapy are added to peg/RBV remains to be seen, but certainly as you add more than 1 oral to peg/rbv their impact will diminish & eventually be minimal or disappear altogether. BMS presented the early data, the 1st data in null-responders receiving 2 orals only or 2 orals plus peg/rbv, the results from this study were highly anticipated and begin to give us important information on treatment without peg/rbv but also in treating null-responders, as all 10 null-responders had undetectable viral load after 12 weeks with all 4 drugs. After initial monotherapy ABT-450 looked very potent, perhaps a 6-log drug. The nucleoside polymerase R7128 shows good 12 week data underscoring the importance that this drug or class appears not be associated with resistance developing easily & early, and this is important. Pharmasset presented data on 2 nucleotides with potency & also the possibility of not be associated with resistance developing. The BMS NS5A is potent. Some drugs are administered once daily, some three times daily, the side effects profiles differ between the drugs, and success with therapy will require management of side effects, like anemia. The data from both Vertex & Merck show that African-Americans can have response rates as high as whites if they have early RGT results, that is if the viral load is undetectable at the early-time-points the cure or SVR rates are equally high for blacks, latinos and whites.

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Mon, Nov 29, 2010

A new study has demonstrated that irreversible covalent inhibition can increase selectivity, potency and duration of action, broadens applications for targeted covalent drugs to the protease gene family.

Avila Therapeutics Inc., a biotechnology company developing novel targeted covalent drugs, has demonstrated the first-ever selective irreversible inhibition of a viral protease using a targeted covalent drug.

Avila has used its proprietary Avilomics platform to design covalent irreversible protease inhibitors that are highly selective, potent and with superior duration of action as compared to conventional protease inhibitors.

The research has demonstrated that covalent drugs can be designed and targeted to irreversibly and covalently bond to molecular domains specific to proteases.

"This research elevates covalent drug design to a fundamentally new level. By creating extremely selective protease inhibitors with their platform, Avila is showing the remarkable therapeutic potential of irreversible covalent drugs to address a broad spectrum of drug targets," said Simon Campbell , a renowned scientist.

"This approach can make a difference to patients living with HCV infection, and we expect to make an impact in other important areas such as cancer and inflammatory disease," said said Juswinder Singh, co-author of the paper.

In order to maximize selectivity and minimize off-target effects, the irreversible covalent inhibitors of HCV protease were designed to covalently target a unique structure in the HCV protease not found in human proteases. Key findings include:

A representative irreversible covalent inhibitor designed, by Avila, was shown to inhibit the HCV protease (also known as "NS3") in cells at a concentration of 6 nM.

Specific covalent bond formation between the drug and target protease was demonstrated through use of mass spectrometry and also x-ray crystallography.

The findings were published in the journal Nature Chemical Biology. (ANI)


Avila Presents New Data on its Novel, Orally-Available Targeted Covalent Drug, AVL-192

Covalent Inhibition Achieves Superior Potency Against Drug-Resistant HCV Mutants

BOSTON and WALTHAM, MA - November 2, 2010 - Avila TherapeuticsTM, Inc., a biotechnology company developing novel targeted covalent drugs, presented results today of preclinical studies that demonstrate its orally-available targeted covalent drug candidate, AVL-192, achieves superior potency against drug-resistant mutations of the Hepatitis C Virus (HCV). These new data were presented today at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) international meeting in Boston, Massachusetts.

HCV protease (also known as NS3) is a promising target of intervention for the treatment of hepatitis C infection. However, medicines currently in late stages of clinical development are vulnerable to drug- resistant mutations. AVL-192 is a novel, orally available compound that can rapidly and completely silence the HCV protease through highly selective, irreversible covalent bonding to the target protein. Preclinical data have demonstrated that AVL-192 achieves very high potency and selectivity for NS3 and also potently and effectively inhibits the drug-resistant mutations observed clinically.

Avila's covalent approach to silencing the NS3 protein has resulted in a product candidate with a potential best-in-class profile due to the ability to retain potency against clinically-arising resistance mutations, and potential breadth of activity across HCV genotypes with anticipated once-per-day dosing.

In a poster presentation at the meeting, entitled, "Second Generation of Covalent Irreversible Inhibitors Have Superior Potency Across Genotypes and Drug Resistant Mutants," data were presented from preclinical studies that evaluated the efficacy of AVL-192 in biochemical and cell culture studies. Highlights of the data demonstrate:

· AVL-192 has a time-dependent mode of action that delivers potent and rapid inhibition of WT NS3/4A and retains high potency against drug-resistant mutant NS3/4A proteases;
· AVL-192 is able to inhibit the protease long after the compound is removed, offering the benefit of less frequent dosing;
· AVL-192 as monotherapy can be curative in the replicon clearance assay;
· AVL-192 is highly selective and spares host proteases; and
· AVL-192 has high plasma exposure following oral administration in rats and dogs.

"These new data reinforce our belief that our targeted covalent drug candidate AVL-192 has the potential to be a best-in-class, pan-genotype HCV therapeutic due to its unique mechanism of action," said Juswinder Singh, Ph.D., Avila's Founder and Chief Scientific Officer.

About Avila TherapeuticsTM, Inc.

Avila focuses on design and development of targeted covalent drugs to achieve best-in-class outcomes that cannot be achieved through traditional chemistries. This approach is called "protein silencing". The company's product pipeline has been built using its proprietary AvilomicsTM platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners. For additional information, please visit


Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine

Brief Communication
Nature Chemical Biology, 28 November 2010

Margit Hagel, Deqiang Niu, Thia St Martin, Michael P Sheets, Lixin Qiao, Hugues Bernard, Russell M Karp, Zhendong Zhu, Matthew T Labenski, Prasoon Chaturvedi, Mariana Nacht, William F Westlin, Russell C Petter & Juswinder Singh 1Avila Therapeutics, Inc., Waltham, Massachusetts, USA. 2Millenium: The Takeda Oncology Company, Cambridge, Massachusetts, USA. *e-mail:

Designing selective inhibitors of proteases has proven problematic, in part because pharmacophores that confer potency exploit the conserved catalytic apparatus. We developed a fundamentally different approach by designing irreversible inhibitors that target noncatalytic cysteines that are structurally unique to a target in a protein family. We have successfully applied this approach to the important therapeutic target HCV protease, which has broad implications for the design of other selective protease inhibitors.

The fundamental challenge in designing protease inhibitors is to achieve potency without sacrificing selectivity. This problem arises frequently because the typical protease inhibitor achieves potency through covalent interactions with the catalytic apparatus, yet such pharmacophores also confer affinity for other proteases in the same mechanistic family1. This is a significant challenge for protease drug design, because over 500 proteases exist in the human genome. Achieving selectivity while targeting the catalytic machinery is thus particularly difficult2.

Covalent irreversible drugs that form persistent, nonlabile covalent bonds yield unique therapeutic benefits including rapid onset of inhibition, greater potency, longer duration of drug action and potent and persistent activity against mutations that would otherwise lead to drug resistance3. There are many examples of drugs that work through irreversible covalent bonding that have proven to be safe and successful therapies for a wide variety of indications4. Despite their prevalence, to date covalent drugs have largely been discovered serendipitously, and general methods to facilitate their deliberate discovery and design have yet to be described.

HCV NS3/4A viral protease (HCVP) activity is essential for viral replication5 and has been recently validated as a clinical target6, 7, 8, 9, 10, 11, 12, 13, 14, 15. Protease inhibitors such as telaprevir exemplify the challenges of covalent targeting of the catalytic binding site; upon binding to HCVP, the α-ketoamide forms a reversible covalent linkage with the catalytic serine that is conserved within proteases6, 10. Indeed, telaprevir inhibits some host serine proteases at concentrations that may be achieved in a therapeutic setting14, 16.

The aim of this study was to achieve potent inhibition of viral proteases through covalent bond formation without compromising selectivity of the inhibitors. Our new design strategy used structural bioinformatics to create a structural alignment between viral proteases and host proteases to identify nucleophilic amino acids in the binding site that were unique to the viral proteases. Our structural alignment revealed that current covalent inhibitors such as telaprevir target a catalytic residue that is common across the protease family and therefore susceptible to selectivity issues. In contrast, we identified a nucleophilic amino acid, cysteine 159 (Cys159), in the substrate-binding site that could be targeted for covalent bonding. Importantly, Cys159 is strictly conserved across all 919 HCV NS3 sequences in a database of all known HCVP sequences, including all HCVP subtypes and genotypes sequenced to date (Supplementary Fig. 1), allowing design of a pan-genotype HCVP inhibitor. Although HCVP shows structural similarity with host proteases, Cys159 is structurally unique to HCVP and therefore was an ideal target for achieving selectivity between HCVP and host proteases.

Structure-based drug design was used to create a peptidomimetic inhibitor (1) (Fig. 1a), designed to form canonical reversible interactions with the S2-S1-S1' pockets of HCVP similar to those observed with other reversible peptidomimetic inhibitors12, 17, 18. Further molecular modeling was used to evaluate structures that positioned a low-reactivity Michael acceptor close enough to Cys159 to form a covalent bond (2) (Fig. 1a). 2 was prepared by installation of an acrylamide using a simple glycine linker. Linking the electrophilic acrylamide via a D-alanine linker provides the more conformationally constrained inhibitor 3 (see Supplementary Methods). Our expectation was that propanamide 4, the reversible congener of 3, would bind weakly to the HCVP, as potent inhibitors reported to date typically possess functionality that forms extensive nonbonding interactions with the S3 and S4 pockets.

As predicted, 1 and 4 showed weak inhibition of the wild-type HCVP (half-maximal inhibitory concentration (IC50) of 1 = 2,458 nM, 4 IC50 = 1,147 nM) whereas 2 and 3 were very potent inhibitors (2 IC50 = 4 nM, 3 IC50 = 2 nM) (Supplementary Table 1). To further support the importance of covalency in conferring activity of 3, we tested the activity of 3 against a mutant NS3 protein in which the target cysteine is changed to a serine (C159S). The C159S protease is comparable in enzymatic activity to wild-type protease (Supplementary Fig. 2); however, mutation of the amino acid required for bond formation results in a sharp decrease in potency of the covalent inhibitor (IC50 = 1,782 nM; Supplementary Table 1). In further support of the mechanism, 3 shifted the mass of HCVP by 685 Da, consistent with the formation of a covalent complex between 3 and the protease, but was unable to covalently bond to HCVP with the C159S mutation (Supplementary Fig. 3). We also confirmed with X-ray crystallography that 3 was covalently linked to the side chain of Cys159 (Fig. 1b, Supplementary Fig. 4 and Supplementary Table 2).

The selectivity of 3 was further demonstrated using a panel of host proteases. As expected, 3 showed no notable inhibition of host proteases, whereas telaprevir inhibited multiple host proteases, when each inhibitor was tested at 10 µM (Fig. 2a). Moreover, 3 showed no significant nonspecific reactivity toward glutathione (Supplementary Fig. 5). These data highlight the value of covalent bonding to a noncatalytic residue as a means of achieving HCVP selectivity while minimizing the potential for nonspecific reactivity with other thiols such as glutathione.

Huh-7 wild-type (1b) replicon cells were used to demonstrate that 3 can potently inhibit HCVP activity in cells, leading to decreased replication of viral RNA. Luciferase activity was greatly reduced in cells treated with 3 (half-maximal effective concentration (EC50) = 6 nM) (Fig. 2b and Supplementary Table 1). In contrast, the reversible congener, 4, did not inhibit luciferase activity (EC50 > 3000 nM), demonstrating that covalent bonding greatly enhances potency for this class of compounds. Importantly, 3 does not inhibit proliferation of Huh-7 wild-type replicon cells, nor does it affect growth of other cell lines tested (Supplementary Table 3), strongly suggesting that replicon inhibition is because of specific viral protease inhibition. 3 was inactive in the C159S mutant replicon cells (EC50 > 3,000 nM) and, as expected, the activity of 4 and telaprevir were unchanged by the C159S mutation, as they are not dependent on the cysteine for their mechanism of action (EC50 > 3,000 nM, EC50 = 623nM, respectively) (Fig. 2b and Supplementary Table 1). Of note, the C159S mutant replicon cells showed fitness similar to that of wild-type replicon cells (Supplementary Fig. 6).

Numerous NS3 mutations have been reported that render HCVP resistant to the current protease inhibitors. Thus, activity against drug-resistant clinical mutations is important for effective antiviral therapeutics19. 3 was able to inhibit and bond to HCVP proteins of clinically relevant NS3 variants (Supplementary Table 1 and Supplementary Fig. 7). Furthermore, the selectivity conferred by Cys159 also allows for binding and inhibition of HCVP from multiple genotypes (Supplementary Table 1 and Supplementary Fig. 8), suggesting that this approach will lead to potent and selective pan-genotype HCVP inhibitors.

To demonstrate direct inhibition of HCVP activity using our irreversible covalent drug, we developed an assay using the internal self-cleavage activity of HCVP20 (Supplementary Fig. 9). We confirmed the necessity of HCVP activity in the proteolytic cleavage of NS3/4A by expressing wild-type HCVP or a protease-dead mutant, NS3/4A-S139A (Supplementary Fig. 10). This autoproteolytic cleavage activity was used to directly measure HCVP activity in replicon cells in the presence and absence of the covalent inhibitor. When HCVP activity is inhibited, self-cleavage is abolished, leaving only the full-length holoenzyme. 3 demonstrated inhibition of HCVP internal self-cleavage activity, and the inhibition was sustained for 8-24 h after compound removal. In contrast, HCVP self-cleavage activity had completely returned by 30 min after removal of telaprevir (Supplementary Fig. 11a,b).

A unique advantage of an irreversible covalent molecule is that it allows the investigation of target occupancy in a time- and dose-dependent manner. We designed a biotinylated irreversible covalent probe that bonds to NS3/4A protease (Supplementary Scheme 4), enabling the quantitative analysis of NS3 occupancy with 3, and found that inhibitory activity and NS3-occupancy closely correlate (Fig. 3a,b). Following treatment with 3, there is little or no free NS3 available to bind to the biotinylated probe for at least 8 h after 3 has been removed (Fig. 3b). This indicates that essentially all of the NS3 protein was bound by 3, and newly synthesized protein is being detected at 8-24 h. Return of self-cleavage activity is concomitant with the detection of newly synthesized protease. The biotinylated covalent probe compound is also an indicator of the selectivity of 3, as the two compounds share structural similarities and electrophiles. Only the full-length NS3 protein and NS3/4A cleavage products were detected as having been labeled by the biotinylated probe, indicating that it is specific for NS3/4A under these conditions (Fig. 3c).

A targeted covalent design approach21 has been applied to kinases, several of which are currently in clinical testing with encouraging evidence of efficacy and safety22. This study describes the first successful example of applying targeted covalent inhibition to the protease family. Our data indicate that the electrophile on 3 must be brought into close proximity to a nucleophilic thiol via specific affinity-driven binding to enable covalent bond formation between the small molecule and the targeted HCVP . This strategy enables us to selectively inhibit HCVP and minimize the potential for toxicity through reactivity with off-target proteins. 3 is an excellent prototype HCVP inhibitor but has a number of important limitations as a drug candidate; these properties have been optimized in our current development compounds, AVL-181 and AVL-192, which have excellent pharmacokinetics and bind potently to wild-type HCVP as well as to multiple other genotypes and mutant forms of HCVP, including C159S, but only covalently modify when Cys159 is present23. The successful design of a highly selective targeted covalent inhibitor of HCVP suggests that this approach can be broadly applied to other protease family members and indeed to a wide range of protein families.

Posted on: Mon, 06 Dec 2010 09:15:00 EST

HOUSTON, Dec 06, 2010 (BUSINESS WIRE) --

Emerging Healthcare Solutions, Inc. (PinkSheets: EHSI
PowerRating) announced today that its newly acquired biotechnology division Celulas Genetica seeks to contract a Chinese firm to test a new stem-cell treatment for liver disease.

Last week, Celulas Genetica purchased a license to develop and market the revolutionary Rutherford Procedure, a groundbreaking organ regeneration treatment intended to utilize proton-beam technology to destroy diseased organ tissue for regeneration using adult stem cells. Celulas Genetica licensed the procedure from a Chinese firm, BBFITCL, and views the emerging Asian superpower as the ideal locale to test and develop its potential new treatment for liver disease.

"China has pushed hard for years to become a world leader in the fields of stem cell research and regenerative medicine," said EHSI President and CEO Cindy Morrissey. "The scientific and medical resources needed to test the Rutherford Procedure are both abundant and affordable in China, and Celulas Genetica is currently exploring the possibility of working with a proton therapy facility there to develop this new treatment for liver disease."

Morrissey said she plans to travel to China soon to meet with Chinese stem-cell researchers and potentially help open a Celulas Genetica business office there. Extending its reach into the R&D hotbed of China would build on EHSI's rapidly expanding global footprint--Celulas Genetica is headquartered in Panama, and Morrissey opened EHSI business offices in Poland and Germany last month.

"Liver disease is a truly global affliction," Morrissey said. "It requires a global solution. Working together with scientists and doctors in Panama, China and elsewhere, we believe we can develop the Rutherford Procedure into an effective, minimally invasive treatment for liver disease that will not require transplants."

Last week, EHSI announced its acquisition of a Rotary Cell Culture System, or bioreactor, developed using revolutionary NASA research in the field of microgravity. Cell cultures, including stem cells, grown inside the bioreactor look and function much closer to human cells grown within the body than cell cultures grown in Petri dishes. During the Rutherford Procedure, proton therapy will be used to destroy scar-tissue cells in the liver using high-energy proton beams, a non-invasive treatment proven to minimize damage to healthy tissues and to eliminate the side effects (including nausea) of traditional radiation therapy.

As the scar tissue is systematically destroyed by the proton therapy, a catheter will deliver the patient's own cultured stem cells directly to his or her liver through the bloodstream. As more and more diseased tissue is destroyed, these cultured stem cells could help regenerate the patient's damaged, cirrhotic liver into a healthy, functioning organ once more.

EHSI invests in technology developed to compete in the stem-cell research industry alongside Dendreon Corp. (NASDAQ: DNDN), Gilead Sciences (NASDAQ: GILD), Celgene Corp. (NASDAQ: CELG) and Biogen Idec Inc. (NASDAQ: BIIB).

About Emerging Healthcare Solutions, Inc.

Emerging Healthcare Solutions, Inc. invests in and participates in the profits of emerging breakthrough medical technologies. The Company believes the secret of leveraging future value for its shareholders is the proper timing of its investment in promising new medical technologies. EHSI aims to capture future profits of promising new medical technologies by investing in these technologies at the inflection point of product development. We believe this model will deliver long-term positive results for our investors.

For more information, please visit

Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This news release contains forward-looking information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements that include the words "believes," "expects," "anticipate" or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of the company to differ materially from those expressed or implied by such forward-looking statements. In addition, description of anyone's past success, either financial or strategic, is no guarantee of future success. This news release speaks as of the date first set forth above and the company assumes no responsibility to update the information included herein for events occurring after the date hereof.

SOURCE: Emerging Healthcare Solutions, Inc.

Emerging Healthcare Solutions, Inc.
Cindy Morrissey, 713-821-1486
President and CEO

NEW HAVEN, Conn., Dec. 6, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that data from the Company's ongoing clinical studies of ACH-1625 has been accepted for presentation at the 21st Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL 2011) to be held February 17-21, 2011 in Bangkok, Thailand.

ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.

The presentation, entitled "Viral Kinetics Modeling of Short-term Monotherapy Data of ACH-1625, an HCV Protease Inhibitor," will be presented by Dr. Atul Agarwal, Senior Director of Computational Chemistry of Achillion. (Abstract A-315-0024-00792.) The presentation describes a mathematical analysis of HCV RNA data collected after oral administration of ACH-1625 in HCV genotype 1 infected subjects. This analysis shows rapid and near complete hepatitis C virus clearance following ACH-1625 administration at all dose levels tested. In addition, mathematical modeling of HCV viral kinetics provided information that allowed for subsequent dose selection for Phase II clinical development of ACH-1625.

"These data support and further demonstrate ACH-1625's robust antiviral activity," said Dr. Agarwal. "With clinical data that demonstrated reductions in viral RNA between 3-4.25 log10, these mathematical data quantitatively show the percentage of total virus cleared after five days of ACH-1625 monotherapy. This data also identifies specific patient population characteristics."

"We are pleased to continue to put forward a large body of scientific and clinical data on ACH-1625," commented Michael D. Kishbauch, Chief Executive Officer of Achillion. "We look forward to completing the current Phase II clinical trial of ACH-1625 to further support its profile as a potential best-in-class protease inhibitor for the treatment of HCV."

About ACH-1625

ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once daily dosing. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50~1nM.

In clinical studies, HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.07 log10 to 4.25 log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 1log10 from baseline through day 12, the last day of viral load measurement in the study.
About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease -hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit or call 1-203-624-7000.

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the potency, safety and other characteristics of ACH-1625, which may not be duplicated in future cohorts at different doses or in future clinical studies of longer duration, as well as Achillion's expectations regarding timing and duration of other clinical trials. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2009.


Research Fuels Hope for Hard-To-Treat Hepatitis C Patients

Released: 12/6/2010 12:00 PM EST
Source: Saint Louis University Medical Center

Newswise — The outlook for patients with hepatitis C continues to improve as results from a clinical trial led by a Saint Louis University researcher found that the drug boceprevir helped cure hard-to-treat patients. The findings were reported at the 61st annual meeting of the American Association for the Study of Liver Disease’s earlier in November.

Bruce R. Bacon, M.D., professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor, boceprevir, and found that it significantly increased the number of patients whose blood had undetectable levels of the virus.

“These findings are especially significant for patients who don’t respond to initial treatment,” said Bacon. “When the hepatitis C virus is not eliminated, debilitating fatigue and more serious problems can follow.”

Hepatitis C is caused by a virus that is transmitted by contact with blood. The infection may initially be asymptomatic, but for patients who develop chronic hepatitis C infection, inflammation of the liver may develop, leading to fibrosis and cirrhosis (scarring of the liver), as well as other complications including liver cancer and death.

The prognosis varies for patients with chronic hepatitis C. With the current standard therapy, about half fully recover after an initial course of peginterferon and ribavirin anti-viral therapy that may last from six months to a year.

The remaining patients, known as non-responders, may improve with initial treatment but the virus is not eliminated, or may not respond to treatment at all.

For this group, the only current option is to retreat patients with the same or similar drugs, which increases the likelihood of severe treatment side-effects. In addition, researchers have found that the success of treatment depends on the major strain, or genotype, of hepatitis C that a patient has.

The HCV RESPOND-2 study looked at 403 patients with chronic hepatitis C infections with genotype one, the most difficult strain of the virus to treat, who still had significant levels of the virus after being treated with peginterferon and ribavirin, the standard hepatitis C treatment.

"These results are very exciting," Bacon said. “In this study, boceprevir helped cure significantly more patients in 24 weeks of therapy than did treatment with peginterferon and ribavirin alone."

A second study, HCV SPRINT-2, examined patients with hepatitis C with genotype one who had not yet been treated with the standard treatment. They, too, responded well to the drug.

Bacon calls the progress made in treating hepatitis C remarkable.

“We’ve gone from the discovery of the virus in 1989 to where we are now, 22 years later, when we have the ability to cure a large majority of those with hepatitis C,” Bacon said. “It’s a true success story.”

“Drugs like boceprevir are going to revolutionize care of those with hepatitis C.”

The clinical trial was funded by Merck, which expects to begin seeking FDA approval this year.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.