Achillion Pharmaceuticals HCV pipeline suddenly looking attractive...

Posted 8/29/12 on Business Week.com. Achillion Pharmaceuticals, once regarded as an also ran by Big Pharma suddenly looks sexy again as clinical holds and pipeline failures stymie drug development with Idenix and BMS. Rumors of a takeover has made Achillion stock surge in the past couple of days. The HCV drug development space continues to be one of the most dynamic in pharma, there is definitely no shortage of spills and thrills. 

Achillion Deal Looming as Hepatitis Drugs Fail: Real M&A

By Ryan Flinn and Will Robinson on August 29, 2012

Achillion Pharmaceuticals Inc. (ACHN), the developer of hepatitis C treatments that was passed over by potential acquirers in the last year, is poised to draw renewed interest after setbacks by rival drugmakers.

Bristol-Myers Squibb Co. (BMY) last week said it was abandoning an experimental hepatitis C pill it obtained through its February purchase of Inhibitex Inc. after one patient died and others were hospitalized while taking the drug in a study. This week, Idenix Pharmaceuticals Inc. said U.S. regulators halted its study of a similar therapy, marking the second hold on clinical trials for the company this month.

With the market for new hepatitis C treatments projected to reach $20 billion by 2020 and Achillion facing no delays in two drugs under development, Piper Jaffray Cos. and William Blair & Co. say the $481 million company could gain fresh attention as a takeover candidate for Merck & Co. (MRK), Roche (ROG) Holding AG and Vertex Pharmaceuticals Inc. (VRTX) A suitor could pay a premium of as much as 79 percent to Achillion’s stock price and still acquire the New Haven, Connecticut-based company for less than its peak market value earlier this year, when takeovers and merger speculation spurred a surge in hepatitis C drugmakers’ shares.

“The frenzy has been taken out of the space, but I still think Achillion is very attractive” because its therapies have the potential to be the best of their type, Ted Tenthoff, a New York-based analyst for Piper Jaffray, said in a telephone interview. “We expect the wave of consolidation to continue. Achillion is clearly a target.”

Drug Development
Joe Truitt, Achillion’s chief commercial officer, said it wasn’t appropriate to comment on the company’s development plans, including the possibility of a takeover.

“We’ll make the best strategic options as they come to us, but for right now, we’re developing our drugs and getting them into combinations and making them available to patients,” Truitt said in a phone interview.

Today, shares of Achillion rose 3.5 percent to $6.86 at 9:45 a.m. in New York, the second-biggest gain among 116 stocks in the Nasdaq Biotechnology Index.

Hepatitis C is a viral infection that can cause liver damage and is estimated to affect 180 million people worldwide, according to the National Institutes of Health. Rising deaths among so-called baby boomers from the infection prompted U.S. health officials to declare in May that all of those born from 1946 to 1964 are at risk and should be tested.

Achillion is among several companies racing to develop hepatitis C cures that would replace the standard year-long injectable treatment that can cause flu-like symptoms.

Four Classes
There are four new classes of drugs under development to cure hepatitis C. Each work in different ways to stop the virus from replicating, and can be effective against one or several subtypes of the disease.

Drugmakers such as Abbott Laboratories (ABT), Achillion, Bristol- Myers, Gilead Sciences Inc. (GILD), Merck and Vertex have been testing these therapies, either alone or together, with varying degrees of success. The promise of a market that Achillion Chief Executive Officer Michael Kishbauch estimates will grow to $20 billion by 2020 spurred at least three acquisitions since October.

The biggest deal was Gilead’s $10.8 billion acquisition of Pharmasset Inc., announced in November, which came a month after Roche agreed to buy Anadys Pharmaceuticals Inc. for about $230 million. Bristol-Myers followed in January by announcing its $2.5 billion purchase of Inhibitex.

Fresh Look
Achillion’s Kishbauch said in November that the company was in “advanced discussions” with potential partners or acquirers. Its shares then reached a five-year high of $12.38 in February on takeover speculation before falling (ACHN) 46 percent since then as no deal materialized.

Now, with Bristol-Myers stopping development of the drug it bought from Inhibitex, and Idenix (IDIX) halting testing of a similar therapy, Achillion could attract a fresh look from companies seeking hepatitis treatments to use on their own or in combination with their existing therapies, said Liisa Bayko, a Chicago-based analyst with JMP Securities LLC.

Achillion is testing two types of drugs. By combining several classes of these new hepatitis C drugs, doctors may be able to limit the virus’ ability to infect, mimicking the strategy that a decade earlier helped turn HIV from a killer disease to a controlled one.

During the first quarter, Achillion will be reporting on how effective its two therapies work in combination. Good data could entice competitors to bid, Bayko said.

‘Well-Positioned’
“By the first quarter of next year, we could be a very different company,” Achillion’s Truitt said. “If that combination data comes through, then we really have a commercially viable, competitive combination that will put everybody on notice.”

“We’re pretty optimistic for Achillion,” Bayko said in a phone interview. “They’ll be well-positioned to be a candidate to be taken out, because right now, there are very few options if you want to get involved in hep C, in terms of combinations that are more advanced that are still in clinical development.”

Bayko said that while she expects a suitor to wait for the data on the drugs before making an offer, Achillion still could fetch as much as $10 a share if a company bid for it now, 51 percent more than its closing price yesterday.

Piper Jaffray’s Tenthoff said Achillion could lure suitors such as Merck, Roche and Vertex as they seek to compete against Gilead, which is seen by analysts as having the most promising hepatitis C drug. Gilead is poised to start testing two of its therapies together in a single pill this year, putting it on track to request U.S. regulatory approval for the drug in 2014.

Gilead Bid
Ronald Rogers, a spokesman for Merck, said the company doesn’t comment on speculation when asked whether the Whitehouse Station, New Jersey-based drugmaker was interested in Achillion, while an e-mail to Basel, Switzerland-based Roche’s media relations office wasn’t returned. Megan Pace, a spokeswoman for Cambridge, Massachusetts-based Vertex, declined to comment.

Even Gilead could seek to acquire Achillion as a way to remove a potential competitor and bolster its position, said Peter Kolchinsky, co-founder and general partner at RA Capital Management LLC, which oversees $300 million, including Achillion shares.

“Gilead could solidify its supremacy if it had Achillion’s drugs, each best in its respective class based on what we know so far,” Kolchinsky said in an interview. “Acquiring Achillion would also be a wise defensive move for Gilead, keeping it from falling into a competitor’s hands or from becoming an independent low-cost competitor.”

Safety Concerns
Cara Miller, a spokeswoman for Foster City, California- based Gilead, said the company (GILD) doesn’t comment on market speculation.

Brian Skorney, an analyst with Brean Murray Carret & Co. in New York, says Achillion won’t be a takeover target soon because it has “a lot more to prove” with clinical data next year. Other companies that developed hepatitis C treatments like Pharmasset and Inhibitex proved their drugs were effective before they were bought, and the only remaining question about their products was safety, he said.

The safety problems that challenged the drug Bristol-Myers bought from Inhibitex and the regulatory holds that Idenix faces show how much risk is still left in the market for hepatitis C treatments, said Les Funtleyder, a fund manager focused on the health-care industry at New York-based Poliwogg.

“What’s that phrase, ‘Once burned, twice shy?’” Funtleyder said in a phone call. “If someone was to repeat what happened to Bristol, shareholders would start to ask questions about management’s judgment.”

Cheaper Now
Still, after the drop in Achillion’s stock this year, a buyer would be taking on the risk of the therapies potentially failing at a lower price tag.

During the past 12 months, acquirers that announced deals for biomedical companies paid 65 percent more than the target’s average 20-day stock price in transactions greater than $500 million, according to data compiled by Bloomberg. A bidder for Achillion could offer a premium of as much 79 percent to yesterday’s stock price and still get the drugmaker for less than its record market value of $863 million in February.

The market for treating the viral infection is too big to be dominated by Gilead alone, so large drugmakers may have the appetite to acquire a company such as Idenix or Achillion once they produce sufficient data on the safety and effectiveness of their drugs, said Y. Katherine Xu, a New York-based analyst at William Blair. Kelly Barry, a spokeswoman for Cambridge, Massachusetts-based Idenix, didn’t return a voicemail message and e-mail sent after business hours about whether the company has been approached by suitors.

“Both Idenix and Achillion, their strategy is to sell themselves,” Xu said. “Timeline-wise, these two used to be similar, but now Achillion may be a little bit ahead.”

To contact the reporters on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net; Will Robinson in New York at wrobinson11@bloomberg.net.

To contact the editors responsible for this story: Sarah Rabil at srabil@bloomberg.net; Reg Gale at rgale5@bloomberg.net.

Idenix suffers another FDA-mandated clinical hold...

Posted 8/27/12 on Fierce Biotech.com. Idenix suffers another setback as the FDA puts its NS5B inhibitor, IDX19368 on clinical hold as the fallout from the AE's from BMS-094 continue. Both IDX184 and IDX19368 are in the same class of nucs as the ill-fated BMS-094 and share the same active metabolite. Idenix CEO Ron Renaud feels there is enough differentiation between BMS-094 and the Idenix compounds to put safety concerns to rest, but the company is doing its due diligence in terms of ensuring the safety of the patients enrolled in its trials. The clinical holds certainly slow down the development of Idenix's nucs, but hopefully Mr. Renaud is right and the Idenix compounds still hold market potential. 

Idenix plunges after FDA puts another hep C treatment on hold

August 27, 2012 | By John Carroll

Idenix already faces a partial clinical hold on its top hepatitis C program. Now the FDA has stepped in to add a clinical hold on its preclinical therapy IDX19368, another nucleotide polymerase inhibitor, or "nuc," in the pipeline. The biotech ($IDIX) also spelled out some added safety checks for its lead hep C treatment, which the company says can be completed in a matter of weeks. But its shares swiftly plunged on the fresh round of troubling news.

"Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Idenix CEO Ron Renaud. "Both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094. However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094."

Idenix's FDA woes were triggered by the abrupt failure of BMS-094, a once sizzling-hot hep C treatment which raised alarms after one patient died and 8 others in a study were hospitalized, just 8 months after Bristol-Myers Squibb paid $2.5 billion to acquire Inhibitex. Bristol ($BMY) announced on Thursday that it was writing off $1.8 billion and scrapping the drug entirely. Idenix added today that BMS is lending a hand in resolving the holds.

Idenix also reported that it has lined up ethocardiograms for 50 patients enrolled in its IDX184 study. A few done so far have not revealed any safety concerns and the developer says that it should be able to complete this process in a few weeks.

A lingering concern for Idenix, though, is whether the company can regain the glow that had enveloped it after some big deals in the hepatitis C space made the company a prime takeover target, with analysts speculating about the prospect for a big premium. The Cambridge, MA-based company has been among the leaders in the mad scramble to advance new "nucs" and NS5A inhibitors that can be combined with ribavirin into an all-oral regimen with megamarket potential.

Idenix shares plunged 40% on news of the partial hold 11 days ago. This morning the stock plunged another 16% in premarket trading. Both of these programs are unpartnered, which leaves Idenix holding the bag now for any long-term loss in value.

Novartis restructures HCV licensing deal with Idenix...

Posted on 8/1/2012 on PharmaTimes.com. It seems like subtle change is afoot in the HCV drug development field. Gilead announced that it would co-formulate GS-5855 and GS-7977 into one pill with an expected launch date of 2014 and Vertex posted earnings well below expectations of Wall Street on lower-than-anticipated sales of Incivek. Now, Novartis announces it is restructuring it's licensing deal with Idenix, giving the latter company back it's development rights for it's HCV pipeline. We can only speculate on why the rights were handed back to Idenix, but I'm sure Gilead's bold announcement and the post-EASL dampening of the current marketplace and it's chilling effect on the life cycles of the first generation of anti-HCV drugs didn't offer any remedy for cold feet.


Idenix gets rights back to pipeline from Novartis
WORLD NEWS | AUGUST 01, 2012

KEVIN GROGAN

Idenix Pharmaceuticals has regained the rights to hepatitis C compounds that were partnered with Novartis and announced plans to raise $150 million.

The US firm and the Swiss major first teamed up in May 2003 when the latter purchased a 54% stake in Idenix and licensed the hepatitis B treatment Tyzeka/Sebivo (telbivudine). Under the original agreement, Novartis had the option to license any of Idenix' candidates after proof-of-concept, so long as it maintained at least a 30% stake.

Novartis currently has a 31% holding but the pact has now been restructured. The option to license Idenix's development-stage drug candidates in any therapeutic area has been terminated and Novartis will be entitled to royalties on future hepatitis C virus drugs.

Novartis will have a non-exclusive option to conduct trials evaluating a combination of any of its and Idenix' HCV drug candidates, and the latter firm will no longer receive royalty or milestone payments from Tyzeka/Sebivo sales. The Basel-headquartered group will retain the right to designate one member to Idenix's board, reduced from two, as long as it continues to own at least a 15% stake.

Ron Renaud, Idenix chief executive, said the new agreement gives the firm "increased flexibility to optimise the value of our pipeline". By regaining the worldwide rights to all its drug candidates, "we believe Idenix will be well-positioned to develop pan-genotypic all-oral direct-acting antiviral combination treatments with potential collaborators," he added.

As the restructured deal was being announced, Idenix noted that it has commenced an underwritten registered public offering of $150 million of its common stock.

The proceeds will be used to develop combination Phase IIb trials of its HCV drugs IDX184 and IDX719, and Phase IIa studies with IDX19368 in combination with ribavirin. The funds may also be used to "potential acquisitions of new businesses, technologies or products that Idenix believes complements or expands its business".

Idenix hepatitis C drug IDX719 gets FDA fast track designation...

Posted on 7-25-12 on businessweek.com. IDX719, Idenix's HCV NS5A inhibitor gets fast track designation from the FDA. 


July 25, 2012

CAMBRIDGE, Mass. (AP) — Shares of biotech drugmaker Idenix Pharmaceuticals Inc. rose Wednesday after the company said its experimental treatment for hepatitis C will be reviewed under the Food and Drug Administration's fast track program.



Drugs that receive fast track status at the FDA receive extra meetings and correspondence with regulators throughout the review process. The program is designed to speed up the approval of drugs that treat life-threatening diseases for which there are few other therapies.

Idenix has studied the safety and effectiveness of its drug, known as IDX719, in several small studies lasting up to seven days.

"We are pleased and encouraged by the receipt of fast track designation from the FDA for IDX719 as we believe this reflects the critical need for new treatment regimens to address HCV infection," said Idenix President and CEO Ron Renaud in a statement.

Shares of Idenix rose 24 cents, or 2.4 percent, to $10.31 in midday trading.

The Street.com: Bristol-Myers Missing Hep C Data Raises Red Flags, May Boost Gilead, Idenix

Posted on 5/7/12 on The Street.com. The Street.com's Nathan Sadeghi-Nejad is picking up some signals that BMS might be having trouble with his polymerase inhibitor INX-189 (now BMS-094) acquisition from Inhibitex. Namely, Sadeghi-Nejad points to a chemical called 1-naphthol that is a byproduct of in the metalbolization of  BMS-094 that is toxic to hepatocytes. Details below. 

Bristol-Myers Missing Hep C Data Raises Red Flags, May Boost Gilead, Idenix

Nathan Sadeghi-Nejad
05/07/12 - 07:00 AM EDT

NEW YORK (TheStreet) -- Since my return from the European Association for the Study of the Liver (EASL) conference two weeks ago, I have been unable to get over the strange behavior of executives at Bristol-Myers Squibb(BMY). As I discussed in my EASL wrap-up, investors should view with suspicion Bristol-Myers' complaints about Gilead Sciences'(GILD) refusing to collaborate on a late-stage study of the hepatitis C drugs GS-7977 and daclatasvir partnership. Then there's Bristol-Myers' odd and prolonged silence about INX-189 -- the nucleoside polymerase inhibitor, or "nuc," acquired in the $2.5 billion Inhibitex deal.

I suspect something is wrong with Bristol-Myers' INX-189, which has since been renamed by the company as BMS-094. The red flags are popping up everywhere. If I'm right about Bristol-Myers being in trouble, Gilead's lead in the race to develop all oral therapies for hepatitis C will expand and Idenix Pharmaceuticals'(IDIX) hepatitis C drugs become more attractive.

Let's examine the details:

1. New BMS-094 data should have been available by EASL. In mid-January, Bristol-Myers completed enrollment in a Phase II trial of BMS-094 in genotype 2/3 patients, an easier-to-treat subpopulation of hepatitis C. By the time the hepatitis C world gathered in Barcelona for EASL in April, Bristol-Myers likely had four-week and 12-week on-treatment viral response data from this study. These results will provide an important first look at BMS-094's efficacy and safety, yet Bristol-Myers said nothing about the data at EASL.

2. Bristol-Myers passed on a second chance to provide insight on BMS-094 during the company's first-quarter earnings conference call. At least 16 weeks have now passed since the study completed enrollment. By now, Bristol-Myers should have four-week sustained virologic response (SVR4) data, an early indication of cure.

Yet on its April 26 conference call, Bristol-Myers executives once again declined to provide a meaningful clinical update on BMS-094. Instead, Chief Scientific Officer Elliot Sigal spoke in generalities about the drug.

"We feel that there are multiple doses that are safe for human testing from 50 to 200 [mg]," said Sigal , referring to BMS-094. "We will be getting more experience with 200 [mg] throughout this year. We will have safety data on a range of doses of 50 to 100 [mg], which we will at least have internally and hopefully talk about towards the end of the year." [Emphasis mine.]

3. BMS-094 produces a toxic metabolite. At a scientific conference in 2010, Inhibitex presented preclinical data on the metabolic pathway for BMS-094, then known as INX-189. The first step in this metabolic pathway yields a byproduct called 1-naphthol, a chemical that is toxic to hepatocytes, or liver cells. (My source for the background data is a 1984 paper published in Biochemical Pharmacology.) To be fair, the clinical importance of 1-naphthol at BMS-094's potential clinical doses remains unclear. However, two other nucs in clinical development -- Gilead's GS-7977 and Idenix' IDX-184 -- do not produce 1-naphthol. As an investor, the presence of this toxic byproduct should be a big concern until proven otherwise.

4. BMS-094 has shown potential toxicity across multiple organ systems. Data presented in 2009 indicate that BMS-094 (again, known then as INX-189) has a relatively low CC50, a measure of cytotoxicity, across lymphoid, bone marrow, kidney, and liver cells. Bulls will, reasonably, counter by citing the drug's potency and resulting therapeutic index, an indicator of drug safety equivalent to the ratio of the drug's in vitro efficacy measured via the EC50 relative to CC50. For BMS-094, the
therapeutic index is widest in lymphoid tissue and narrowest in the bone marrow, with liver in the middle. Again, this single data point isn't a smoking gun, but it does raise another red flag.

5. BMS-094 appears far less effective at lower doses than Gilead's GS-7977. After three days of dosing at 200 mg once daily, BMS-094 reduces median viral load by roughly 3.0 log. That's less than the 3.7 log viral load reduction seen with a 400 mg once-daily dose of Gilead's GS-7977 after three days, although in the same ballpark and therefore comparable and competitive.

At a 100 mg once-daily dose, however, BMS-094's impact is far less impressive, with a 1.15 log reduction in viral load. This brings BMS-094's effect size closer to Idenix's nuc IDX-184, which gets criticized for lackluster efficacy. [I think the jury is still out on the Idenix nuc. Management claims the drug's effect size will improve over time. That's possible, since BMS-094 gains some efficacy with an additional few days of dosing.]

If Bristol-Myers can't dose BMS-094 safely at 200 mg, the drug may not be competitive with Gilead's GS-7977. (Gilead's GS-7977 studies use a 400 mg once daily dose.) Importantly, none of Bristol-Myers' ongoing or publicly listed BMS-094 studies use the 200 mg once-daily dose. Not a good sign.

6. Bristol-Myers had limited safety data for BMS-094 when it purchased Inhibitex. Investors frequently cite a partnership or acquisition as validation of the smaller company's technology. I often disagree with the validation hypothesis, and that's true in this case. It seems very unlikely that Bristol-Myers had meaningful non-public safety data for BMS-094 prior to the company's January purchase of Inhibitex for $2.5 billion. This limited visibility might not raise a red flag, but I think it makes the validation defense less compelling.

Bristol-Myers is a big company so the investment impact of potential trouble in its hepatitis C drug pipeline is unclear. Most analyst models don't yet include forecasts for significant sales from the company's experimental hepatitis C drugs. The anticoagulant Eliquis, which has an FDA approval decision date in late June, is by far Bristol-Myers' most important near-term driver. [I expect Eliquis to receive approval, and consensus earnings estimates look achievable but not necessarily low.]

Nonetheless, failure of a high-profile program like BMS-094 would certainly knock the shine off Bristol-Myers' 17-timesearnings multiple, which exceeds most of the company's peer group. I think it's worth considering Bristol-Myers as a short, butI wouldn't make it a big position.

Failure or problems with Bristol-Myers' nuc would likely have a more significant impact on Gilead and, potentially, Idenix. Bothcompanies stand to benefit should BMS-094 stumble. Idenix would have a more attractive asset in IDX-184. I think it's worth taking a small long position in Idenix at current prices.

I think Gilead has more to gain from possible Bristol-Myers problems. Gilead would expand its lead in the race to develop an all oral regimen for HCV, and would gain significant negotiating leverage in any development partnership discussions. Given the potential for multiple positive catalysts over the next year -- including likely FDA approval of the Quad HIV pill this summer -- I am inclined to be long Gilead. I would not be an aggressive buyer of the stock until or unless it dips meaningfully below
$50 per share.

Disclosure: Sadeghi has no positions in any of the stocks mentioned in this article

JMP Securites upgrades Idenix stock on HCV pipeline...

Posted on 4/30/12 on CBSNews.com. JMP Securities analyst Lisa Bayko doesn't think much of Idenix's nucleotide inhibitor IDX 184 (recently given the green light from the FDA after a clinical hold) but has higher hopes for compounds deeper in the Idenix pipeline. Specifically, she mentions NS5A inhibitor IDX 719 which Idenix currently retains ownership of.  

April 30, 2012 3:15 PM

Idenix Pharmaceuticals rises on analyst upgrade

NEW YORK — Shares of Idenix Pharmaceuticals Inc. rose Monday after a JMP Securities analyst upgraded the stock, saying it should trade higher as Idenix reports new data on its experimental hepatitis C drugs.

THE SPARK: Analyst Liisa Bayko upgraded the shares to "Market Perform" from "Market Underperform." Bayko said she doesn't think the company's most advanced drug candidate is effective enough to be the basis of a new treatment for the virus, but had a more optimistic view of some of Idenix's other drug candidates.

"We expect a steady flow of news from Idenix's hepatitis C pipeline in the second half of 2012 to generate increased interest in the stock," she wrote.

THE BIG PICTURE: Idenix is paid royalties on sales of the hepatitis B drug Tyzeka, which is marketed by Swiss drugmaker and Idenix shareholder Novartis AG. Idenix's most advanced drug candidate is designated IDX184. That drug is currently in mid-stage clinical testing. In January, the company started an early-stage trials of a drug candidate called IDX719.

Novartis has an option to license IDX719, but Bayko said she thinks Novartis will decline. That would give Idenix full control of the drug, and it would be able to combine IDX719 with other experimental drugs and look for another development partner.

SHARE ACTION: Idenix stock rose 29 cents, or 3.4 percent, to $8.84 in afternoon trading, after peaking at $9.21 during the session. The shares are down 44 percent from their 52-week high of $15.25, which they set Jan 19.

Barclays analyst on GILEAD and IDENIX....

Original article posted on StreetInsider.com 2/10/12 - This is an article a good friend pointed out to me earlier today. If a combo of one nucleoside inhibitor and ribavirin can become a dominant therapy type for HCV - a virus notorious for excessively high, error-prone replication and an uncanny ability to evade the host immune system - then I'm in.  To my mind however, that's either excessively positive thinking or a typo.


Barclays on U.S. Pharma: A New Era for Hep C Therapy - Starts Coverage on GILD & IDIX

Analyst, C. Anthony Butler, said, "The race towards developing the second-generation of direct antivirals (DAAs) may be a dead-heat. By the end of this decade, we believe two dominant therapy types will emerge for hepatitis C (HCV) patients: 1) a combination of a nucleotide polymerase inhibitor (Nuc) and ribavirin; and 2) a cocktail of a nucleotide polymerase inhibitor and one or two DAAs of other mechanisms."

"GILD has leapfrogged competitors through the bold acquisition of Pharmasset, and its stock move (+32.7% YTD vs NASDAQ +11.8%) reflects the market sentiment that GILD is leading the HCV race. We estimate that GILD could capture ~40% of the US HCV market by 2020 and US sales would peak at $2.8B in 2017."

"IDIX needs to find a home for its Nuc IDX184 in order to remain a contender."

Currently, shares of IDIX are trading down 1.25% and shares of GILD are flat on the session.

Idenix seeks a partner for IDX184...

From Bloomberg News:  Idenix CEO Ron Renaud announces they need a protease inhibitor or NS5A inhibitor-weilding partner for their HCV nuc, IDX184. Analysts speculate that Tibotec or Merck may be attractive partners.

Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says

By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.

“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”

The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.

The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”

Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.

Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.

Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.

On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.

“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.

While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.

Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.

To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net

The Motley Fool - Investors flee Inhibitex and Idenix stock on Pharmasset PSI-938 news...

Idenix Shares Plunged: What You Need to Know
By Evan Niu, The Motley Fool
Posted 3:59PM 12/16/11 Investing

Although we don't believe in timing the market or panicking over market movements, we do like to keep an eye on big changes -- just in case they're material to our investing thesis.

What: Shares of Idenix (NAS: IDIX) are plunging today, down by 16% at the low, after competitor Pharmasset (NAS: VRUS) discontinued use of one of its experimental drugs due to safety concerns.

So what: Pharmasset's experimental hepatitis C drug PSI-938 reported complications with liver function, although the developments aren't expected to interfere with Gilead Sciences' (NAS: GILD) planned acquisition of the company. Idenix also has a hepatitis C drug in its pipeline, which is the company's current focus.

Now what: The news is causing concern among some hepatitis C drugmakers, including Inhibitex (NAS: INHX) , which is also seeing downside today. Interestingly, rival Vertex Pharmaceuticals (NAS: VRTX) is seeing healthy gains, with setbacks for PSI-938 considered positive for Vertex. Idenix's and Inhibitex's hepatitis C drugs are more similar to Pharmassets, which is causing investors to flee for cover.

The San Francisco Chronicle on the Gilead/Pharmasset deal...

The San Francisco Chronicle speculates that Gilead's acquisition of Pharmasset...at a premium... may start a trend of other companies vested heavily in the antiviral arena buying similar, smaller companies with potentially commercially viable molecules in development. I don't know if we'll see this large a premium paid for a company again in the near future, but the article does name Inhibitex, Achillion and Idenix Pharmaceuticals as possible takeover targets by antiviral behemoths like J&J, BMS and Roche.

Gilead's Pharmasset buy may spur similar deals

Meg Tirrell,Tara Lachapelle, Bloomberg News

Tuesday, November 22, 2011

Gilead Sciences' acquisition of Pharmasset at the highest valuation on record for a drug takeover is turning makers of hepatitis C therapies from Inhibitex to Achillion Pharmaceuticals into the next targets.

Gilead agreed Monday to buy Pharmasset for $10.8 billion, valuing the developer of an experimental, oral treatment at 70 times its net assets, the most ever for a medical drug acquisition greater than $500 million, according to data compiled by Bloomberg. The price is 94 percent higher than Pharmasset's 20-day average, also the industry's richest on record. Applying that premium, Inhibitex would cost $1.1 billion, Achillion $791 million, and Idenix Pharmaceuticals $1.3 billion, the data show.

With the market for the next generation of hepatitis C therapies potentially worth $20 billion by 2020, Inhibitex, Achillion and Idenix may be bought within a year, William Blair & Co. said. While Gilead suffered its steepest stock drop in a year and a half Monday, and none of these unprofitable biotechnology companies have a hepatitis C drug for sale yet, the other targets would require no more than a fifth of the price for Pharmasset even with the same premium, the data show.

Waves of deals

"These deals tend to happen in waves," said Dan Veru, who oversees $3.4 billion including Pharmasset shares as chief investment officer of Palisade Capital Management LLC. "It's amazing to me that Gilead's willing to gamble $11 billion. It is a statement on the future opportunity to the market. Hepatitis C is an enormous business target."

Foster City's Gilead, the world's largest maker of HIV medicines, is paying $137 a share in cash for Pharmasset to gain an oral drug in development for a virus that is now largely treated with injections. The price tag is 70 times its book value, or the value of its assets minus liabilities, topping the industry's previous record of 60 times when Barr Laboratories Inc. bought Duramed Pharmaceuticals Inc. in 2001, according to data compiled by Bloomberg.

Pharmasset reported earlier this month that 40 patients who received its experimental hepatitis C treatment, PSI-7977, were responsive after 12 weeks. About half the patients had been followed up to 24 weeks and were all cured with no significant adverse events. The drug was tested in combination with ribavirin, a medication currently used in treating the disease, in patients with hepatitis C genotypes 2 and 3. Genotype 1 is most common and hardest to treat.

Hepatitis C is a viral infection that can lead to swelling of the liver. As many as 170 million people globally carry the virus, which is transmitted through exposure to infected blood, and more than 350,000 die from related illnesses each year, according to the World Health Organization.

"Hepatitis C is very prevalent in the population," said Andrew Berens, a senior health care analyst with Bloomberg Industries. "A lot of the market opportunity is going to expand if you have an all-oral regimen. We're going to see a land grab to try and get companies that are developing them."

Shares tripled

Even after Pharmasset's shares more than tripled this year before the deal was announced, the price is still 94 percent higher than its 20-day average of $70.65. That's a record for a takeover greater than $500 million in the drug industry, which has fetched an average premium of only 25 percent, according to data compiled by Bloomberg.

"Usually we associate these kinds of premiums with biotech bull markets, but it also can be a function of other possible bidders, scarcity and stage of assets," said Les Funtleyder, a health strategist and portfolio manager at Miller Tabak & Co., which owns Pharmasset shares. "If anybody was thinking about doing something in hepatitis C, they would be thinking a lot harder today than they would be yesterday."

Pharmaceutical companies that may look to expand in the market for hepatitis C treatments include Roche Holding AG, Merck & Co., Bristol-Myers Squibb Co. and Johnson & Johnson, according to Funtleyder and Brian Skorney, an analyst at Brean Murray Carret & Co.

These companies are "all heavily invested in the antiviral arena," Skorney said. "Worldwide this is a huge, huge market opportunity."

Market data provided by Bloomberg News


Read more: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2011/11/22/BUBM1M2KS9.DTL#ixzz1eV5AwfCx

Wedbush analyst Duane Nash talks, people listen... Idenix stock rises.

(I wish I had that kind of power. Wedbush analyst Duane Nash recommends Idenix stock. He feels that Idenix's nucleotide inhibitor IDX184 is currently ripe for partnership and cites Pharmasset's partnership with BMS and J&J with PSI-7977 as a prime example of small pharma partnering with Big Pharma to leverage economies of scale on the development and commercialization front.)

Idenix rises as analyst looks to partnerships

NEW YORK

Shares of Idenix Pharmaceuticals Inc. rose Tuesday after an analyst upgraded the stock, saying the company's experimental hepatitis C drug may become a hot commodity in 2012.

THE SPARK: Wedbush analyst Duane Nash raised his rating on Idenix shares to "Outperform" from "Neutral." Nash said big drugmakers will be interested in the heptatitis drug, now called IDX184. After Idenix reports more data on the drug candidate, he said, it could find a marketing partner or a company interested in acquiring the drug outright. He raised his price target on Idenix shares to $11 from $6.

The company plans to report early results from a mid-stage trial of IDX184 during the first quarter of 2012.

THE BIG PICTURE: Throughout this year, companies like Pharmasset Inc. have been reporting strong clinical trial data for new hepatitis C drugs. Some of those drugs, including Pharmasset's PSI-7977 and Idenix's IDX184, are nucleotide drugs designed to prevent the hepatitis C virus from making copies of itself. Vertex Pharmaceuticals Inc.'s new hepatitis C drug Incivek also stops the virus from replicating, but it attacks a different part of the virus' genome and is not a nucleotide drug.

Nash said the data will get large pharmaceutical companies interested in nucleotide drugs. However there are not many of them available: Pharmasset already has development partnerships with Bristol-Myers Squibb Co. and Johnson & Johnson, and several other drug companies have similar partnerships.

Nash said only two companies are running clinical trials of a nucleotide drug that is not already partnered: Idenix and Inhibitex Inc.

"Due to the growing likelihood that (nucleotide drugs) will be essential for interferon-free therapy, and combined with the scarcity value of available nucs, we are increasingly optimistic that IDX184 will be partnered or acquired in 2012," Nash wrote.

Idenix spokeswoman Kelly Barry said the company has "multiple ongoing discussions with potential partners."

SHARE ACTION: Shares of the Cambridge, Mass., company picked up 26 cents, or 3.9 percent, to $7 in afternoon trading. Earlier in the session, the stock reached a three-year high of $7.38.

Idenix compounds put on 'clinical hold' after three serious adverse events...

CAMBRIDGE, Mass., Sept. 7 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that the company received verbal notice on Friday, September 3, 2010 from the U.S. Food and Drug Administration (FDA) that the IDX184 and IDX320 programs have been placed on clinical hold. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. This decision was made after Idenix notified the FDA of three serious adverse events that occurred during a drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers. These observed serious adverse events were elevated liver function tests detected in three subjects during post exposure safety visits. The liver function tests have returned to nearly normal levels in all three subjects during follow-up. All planned studies of IDX184 and IDX320 to date have been completed and there are currently no healthy volunteers or patients receiving IDX184 or IDX320. Idenix will submit full data to the FDA from recently completed preclinical and clinical studies, including 3-month chronic toxicology studies of IDX184, a 14-day study of IDX184 in combination with pegylated interferon/ribavirin (PegIFN/RBV), a 3-day proof-of-concept study of IDX320 in hepatitis C (HCV) infected patients, and the IDX184 and IDX320 drug-drug interaction study in healthy volunteers in order to assess next steps in the development of both compounds.

"We have not yet received a formal letter from the FDA, nor has the Agency had an opportunity to review the safety and efficacy data from recently completed clinical trials with IDX184 and IDX320. Based upon our discussions with the Agency, we are primarily focused on three cases of elevated liver function tests observed during our drug-drug interaction study of the combination of IDX184 and IDX320 in healthy volunteers," said Jean-Pierre Sommadossi, Ph.D., Idenix Chairman and Chief Executive Officer. "Based upon the safety and antiviral activity we observed in the IDX184 14-day study and the IDX320 3-day proof-of-concept study, both in HCV-infected patients, we remain committed to the future potential of these drug candidates. We will work closely with independent experts and our external safety committee to better understand the cause of these serious adverse events in the combination study of IDX184 and IDX320 and to provide the FDA with more information in order to expedite their review and resolve this matter as quickly as possible."
Full data presentations of IDX184, IDX320 and IDX375 studies will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD), which will be held at the end of October in Boston.

Phase I: IDX184/IDX320 Combination
Idenix completed a two-week Phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetic drug-drug interaction between IDX320 and IDX184 in healthy volunteers. Two cohorts were evaluated in the study with 10 subjects in each cohort randomized eight to active drug and two to placebo. Subjects in the first cohort received 400 mg once-daily of IDX320 for the first week, subsequently adding 100 mg once-daily of IDX184 for the second week. Subjects in the second cohort received 100 mg once-daily of IDX184 plus placebo for the first week, subsequently adding 400 mg once-daily of IDX320 for the second week. The combination of IDX184 and IDX320 was generally safe and well tolerated during the 14 days of treatment. Liver function abnormalities deemed to be serious adverse events were detected in three subjects during the post exposure safety visits. Liver function tests in these subjects have returned to nearly normal during follow-up. Pharmacokinetic drug-drug interactions between IDX184 and IDX320 were not considered to be clinically significant. Neither the plasma exposure of IDX184 and its metabolite, 2'-methylguanosine, nor IDX320 plasma exposure explain these three serious adverse events.

Phase IIa: IDX184, a liver-targeted HCV nucleotide prodrug
This 14-day, Phase IIa clinical trial evaluated 50 to 200 mg doses of IDX184 in combination with PegIFN/RBV in treatment-naive HCV genotype 1-infected patients. At Day 14, mean (+/- standard deviation) viral load reductions were 1.5 (+/- 1.3) logs for placebo (n=16), 2.7 (+/- 1.3) logs for 50 mg IDX184 QD (n=16), 4.0 (+/- 1.7) logs for 50 mg IDX184 BID (n=8), 4.2 (+/- 1.9) logs for 100 mg QD (n=8), 4.1 (+/- 1.2), for 150 mg QD (n=15), 4.1 (+/-1.4) logs for 100 mg BID (n=8) and 3.7 (+/- 1.2) logs for 200 mg QD (n=8). In the cohorts of 100 mg, 150 mg, and 200 mg daily doses in combination with PegIFN/RBV, 50%, 40% and 25%, respectively, of patients achieved undetectable virus levels (<15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved with all doses of IDX184. The side effect profile of the three drug combination was consistent with the known side effect profile of PegIFN/RBV alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.
Phase I/II: IDX 320, an HCV protease inhibitor

This randomized, parallel-arm, double-blind, placebo-controlled proof-of-concept trial evaluated the safety, tolerability, antiviral activity and pharmacokinetics of IDX320 in treatment-naive HCV genotype 1-infected patients. Thirty patients were randomized equally and received placebo, 50, 100, 200 or 400 mg of IDX320 orally once-a-day for three days. One cohort of eight patients was randomized to receive 200 mg IDX320 BID or placebo. At Day 3, mean (+/- standard deviation) viral load reductions were 0.1 (+/- 0.15) logs for placebo (n=5), 2.6 (+/-0.49) logs for 50 mg IDX320 QD (n=5), 3.1 (+/- 0.29) logs for 100 mg QD (n=6), 3.1 (+/- 0.41) logs for 200 mg QD (n=6) and 3.3 (+/- 0.28) logs for 400 mg QD (n=7). At daily doses of placebo, 50, 100, 200, and 400 mg, 0%, 20%, 67%, 67% and 86%, respectively, of patients achieved greater than or equal to 3 log reduction in HCV RNA at the end of treatment. In the 200 mg IDX 320 BID cohort at Day 3, mean (+/- standard deviation) viral load reductions were 3.8 (+/- 0.52) logs and all patients (100%) achieved greater than or equal to 3 log reduction in HCV RNA. In the 3-day proof-of-concept study, IDX320 was generally safe, well tolerated, and demonstrated potent, dose-related HCV antiviral activity.

Phase I: IDX375, an HCV non-nucleoside polymerase inhibitor
Idenix has an ongoing Phase I clinical trial in healthy volunteers evaluating single doses of the free acid form of IDX375 ranging from 200 to 1200 mg per day. Overall, IDX375 achieved pharmacologically relevant drug exposure and was well tolerated for doses up to 1200 mg for one day in healthy subjects. In the fourth quarter of 2010, Idenix plans to initiate a 3-day proof-of-concept trial in treatment-naive genotype 1 HCV-infected patients.

Conference Call Information
Idenix will hold a conference call today at 8:30 a.m. ET. To access the call please dial (800) 471-3635 U.S./Canada or (706) 758-9475 International and enter passcode 99538089. A replay of the conference call and webcast will be available until September 21, 2010. To access the replay, please dial (800) 642-1687 U.S./Canada or (706) 645-9291 International and enter the passcode 99538089.
About HCV

Idenix starts recruiting for drug-drug interaction study evaluating the combination of IDX320 and IDX184 in healthy subjects

Idenix, Inc starts recruiting phase I, double-blind, multiple-dose study to evaluate the pharmacokinetic drug-drug interaction between it's protease inhibitior IDX320 and it's polymerase inhibitor IDX184 in healthy subjects
More info here: http://bit.ly/dlDQdC

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

Idenix Pharmaceuticals Initiates Proof-of-Concept Study for Protease Inhibitor IDX320 in Hepatitis C Patients

PR Newswire US - Jun. 10, 2010

CAMBRIDGE, Mass., June 10 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced that it has initiated a 3-day proof-of-concept study of IDX320, a protease inhibitor for the treatment of hepatitis C virus (HCV) infection, under a Clinical Trial Application (CTA). The study is evaluating IDX320 in treatment-naive hepatitis C genotype 1-infected patients.

"The potent and multi-genotypic activity demonstrated in vitro, as well as the favorable pharmacokinetics observed in healthy volunteers, suggests a promising profile for further development of IDX320," said Jean-Pierre Sommadossi, Ph.D., chief executive officer of Idenix. "The landscape for combination development in HCV is evolving quickly. Assuming favorable results from the IDX320 proof-of-concept study, we plan to discuss with regulatory agencies a direct-acting antiviral combination strategy with IDX320 and IDX184, our HCV nucleotide polymerase inhibitor."

Douglas Mayers, M.D., Idenix's chief medical officer commented, "We are encouraged by the results seen to date with IDX320 and are hopeful that future clinical studies will allow us to continue advancing this program with the ultimate goal of treating a wide range of patients infected with HCV."

The proof-of-concept trial in HCV-infected patients is a Phase I/II randomized, parallel-arm, double-blind, placebo-controlled study evaluating the safety and antiviral activity of IDX320 in treatment-naive adult patients infected with chronic hepatitis C. The study will evaluate four doses of IDX320, ranging from 50 to 400 mg once-per-day, administered for three days. Each cohort of the study will evaluate eight patients randomized six to IDX320 and two to placebo. 

About IDX320

IDX320, a macrocyclic HCV protease inhibitor, is an inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC50 values from 0.8 to 1.9 nM), as well as from genotype 3a (IC50=23 nM). IDX320 did not inhibit nine tested cellular proteases (IC50 > 10 uM) in vitro, suggesting high selectivity. IDX320 bound tightly to the HCV protease enzyme with a long dissociation half-life (> 9 hours). After single 2 mg/kg oral doses of IDX320 in two animal species, favorable bioavailability and a long plasma half-life were observed, with substantial plasma concentrations 24 hours post dose. Comparable drug exposure was confirmed in healthy volunteers (n=6) receiving a single 200 mg oral dose. Further, no significant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients.

About IDX184

IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine monophosphate, which includes Idenix's proprietary liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing. IDX184 in combination with pegylated interferon and ribavirin has demonstrated a generally favorable safety profile and potent antiviral activity in an ongoing Phase IIa study.