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Patent stocks rally after Supreme Court's Teva ruling • 2:15 PM
Eric Jhonsa, SA News Editor
Worlds (OTCQB:WDDD +11.9%), Spherix (SPEX +6.5%), Wi-LAN (WILN +7.2%), ParkerVision (PRKR +4.3%), and Finjan (FNJN +2.2%) have joined Vringo (previous) in rallying after the Supreme Court ruled (by a 7-2 margin) in Teva Pharmaceuticals' favor in a patent suit against generic drugmakers, reversing a federal appeals court ruling invalidating a Teva patent and sending it back for further review.
SA author Patent Plays thinks the ruling has big implications."The Supreme Court just eliminated a key power the US Court of Appeals has been frequently using in such cases as Vringo (VRNG), VirnetX, and many others. The ability to cast aside substantial evidence findings over the District Courts rule is effectively over ... This win cascades with ramifications to multiple PAE's (Patent Assertion Entities) with litigation pending and in force."
The S.C. decision follows a string of 2014 setbacks for patent licensing firms.
.18 in premarket with volume hummm?????????
@michael_keen: First post up on the @Sphere3D site: Your Application Portfolio is Out of Control!! http://t.co/TzF5dU248a #application #APM ##CxO
Great news for BMY and patients
http://m.news.bms.com/press-release/checkmate-017-phase-3-study-opdivo-nivolumab-compared-docetaxel-patients-second-line-s
@lasonyacobbs: @EdTxAnn We had a meeting with @Sphere3d to pilot the @Istationed curriculum on the #Chromebooks with our students. It works! #GoogleLPJ
questions from JPM for there conference
With the recent announcement of the dose-ranging trial for Iclusig, can you review
the design of this study and expected timelines?
? With Iclusig already capturing ~50% of the on-label market, can you comment on
your plans to grow within the current label and opportunities for label expansion?
? Can you provide an update on EU commercialization and country roll-out for
Iclusig? Are you still on track to launch in the 16 major EU markets in 2H15? On a
commercial front, what type of infrastructure would you need to launch there and
how should we think about that on an expense basis going forward?
? How quickly can you build sales in the US? In the EU?
? Can you review how you plan to resolve the current pricing discrepancy with the
30mg bottle?
? What impact on compliance/continuation of therapy have you seen so far this year
with pts on lower doses? How does this compare to last year?
? What percentage of pts are chronic phase? Do you still expect this to steadily grow?
? What percent of patients qualify for free drug through the patient assistance
program? How do you expect this percentage to change this year/over the longer
term?
? What is the breakdown of patients who have already received Iclusig vs. new
patients? Distribution of patients across lines of therapy?
? What is the average duration of therapy and how does that compare to last year? Can
you comment on your plans to shift the patient mix towards longer duration patients?
? How is the awareness campaign of the REMS program progressing?
? You mentioned plans to pursue earlier lines of therapy for Iclusig; what is your latest
thinking with regard to the clinical plan?
? For GIST, what would you consider to be a meaningful outcome in order to progress
to a pivotal study?
? Can you review the market opportunity in Japan for Iclusig?
AP26113
? Can you comment on the AP26113 pivotal Phase 2 trial design? When do you
expect to reach full enrollment?
? What does breakthrough designation do for development/regulatory timelines for
AP26113?
? What are your thoughts on the market size and competition for AP26113 in ALK+
NSCLC? How is AP26113 differentiated?
? Can you review in detail your next development candidate nominated late in 2014?
? Can you discuss your agreement with Bellicum Pharmaceuticals?
pepsi
from this post and after 2 hours on the phone very interesting indeed. you work for scottrade???????lol
So that throws the naked theory out 100%. Leads us back to them buying and selling to Themselves. In what looks like an unlimited supply of stock to those who think new money is buying up the supply.
cannot confirm etrade but i can tell you what i have been told by higher ups at scott. they have a policy that if they see crossing of shares or what they percieve as manulpation they will restrict the stock
not for sure what they saw, but 100 percent confident they SAW SOMETHING TO RESTRICT THE STOCK.....
asked how often this happens says it does from time to time. they most likely see it in premarket which makes ANY unusual imho
very important imho ---- regarding scottrade or etrade
imho after talking with scottrade agian.
Really fill the Restriction was due to a house that was trading shares between themselves giving a false appearance? which house they would not say?
the brokers scottrade and Etrade saw the MANULIPATION AND FELT it was in the best interest of there clients to Restrict the stock.
by doing this even the shorts that may used those houses have to call in there trade and will not be allowed to do such trades
house to house. makes sense to me.
by doing this it very much may slowed down the shorts???
thoughts???
lambert you can buy you just have to call your broker to do so
same rate
pepsi
i am working man like you
i dont have time to get online to place order and then find out i call a stupid broker to do it.
thats my frustration this is the USA and trading stocks should be easy.
what the shorts have caused is CRAP.
my frustration to Scottrade was to FIX it
hopefully they will
nice day in ANY by the way
Dough
if nothing else i am more CONVINCED THEN EVER that eyes are watching the trading of ANY
and after my discussion today hopefully even more eyes will be watching.
no way you can tell me that the SHORTS or least some or not filling a little PRESSURE today.
tick tick
dough
believe me i gave them a ear full
this mgr knows more about ANY then he ever wanted to.
will give them a day or two and i phone back.
like i said bottomline is he said there has been signs of stock manulipation or unusual trading
why the restriction
sure makes you go hummmmmmmmm???????????
eagle
i did mention about leaving thats when he said that both etrade and scottrade has noticed manupilation in trading in ANY.
he told me they are watching it and its being reported to where it needs to
i asked FINRA he would not say.
bottomline something fishy is for sure going on.
i just read your post eagle
Well HTFBSN indicated today that FINRA was investigating
well how bout that. could be a blessing as etrade and scottrade or on it. could be the spark that lights the fire on the shorts
told me it could take 30 days???
unreal what i just heard. really is.
would luv to hear what etrade says???
very interesting appears scottrade and etrade have noticed MANULIPTION AND THEY HAVE PLACED THE RESTRICTION FOR NOW.
yes you heard me they have noticed unusual trades he used word manulipation, supicious trading activity?? his words not mine.
they are actively reviewing it. encourage others to voice the concerns also.
getting to the bottom of this with scottrade
been on the phone for hour now escalating the concern up the chain of command.
not getting off til i have answer.
will report later
doug
agree i have complained also to scottrade for 3 days now
also filing a complaint as i speak.
its a hassel but a trade can be placed at the good rate just a pain to do
Not true on scottrade
You just have to call it in and they place at Internet rate 7 bucks
Hopefully soon will be lifted
Jess goodluck my friend. Latest from mike king JMP
ET OUTPERFORM | Price: $6.53 | Target Price: $8.00 INVESTMENT HIGHLIGHTS
Ariad Pharmaceuticals plans to initiate Phase II trial in chronic phase CML patients; reiterate our Market Outperform rating and $8 price target derived from our DCF and SOTP methodologies. The company announced that it will initiate Phase II studies in patients with refractory chronic-phase chronic myeloid leukemia (CP-CML) in mid-2015 after concluding discussions with the FDA and EU regulators. The planned trial will inform the optimal use of Iclusig in 450 patients. In light of the impressive efficacy results in the population in previous Phase II trials, we have confidence that this trial will inform the safe and effective use of Iclusig in this patient population.
Previous studies support the potential for class defining efficacy. Iclusig clinical activity as a second- and third-line CML agent has been thoroughly substantiated by the results of the Phase II PACE (Ponatinib Ph+ ALL and CML Evaluation) trial presented at ASCO and ASH in 2012. PACE was designed as a pivotal Phase II study to evaluate the safety and clinical activity of Iclusig (given at 45mg QD) in ~450 patients who were resistant or intolerant to either Tasigna or Sprycel, or were positive for T315I mutation following treatment with at least Gleevec. The trial was primarily comprised of patients with CP-CML (N=270), but also included patients with accelerated phase (AP)- CML (N=85) and blast phase (BP)-CML/Ph+ ALL (N=94). The primary and secondary endpoints for the trial included MCyR and MMR, respectively, for patients with CP-CML and major hematological response (MaHR) and MMR for patients with AP-/BP-CML/ Ph+ ALL.
Responses in PACE were striking given the extent to which this patient group had seen multiple prior therapies. Among patients with chronic phase CML, the rate of MCyR (the primary endpoint of the trial) was 56%, while the rate of MMR was 34% (Figure 1). Responses were greater among patients positive for the T315I resistance mutation (70% MCyR vs. 51%) among patients resistant or intolerant to either Tasigna or Sprycel and continued to improve with time on therapy. The rapidity and magnitude of the MCyR rates are also noteworthy in that they exceed the reported second-line response rates of Tasigna and Sprycel, in a patient population exposed to a greater number of prior therapies. The results among patients with T315I mutation alone would seem to put Iclusig in a class of its own with activity beyond the reach of its competitors.
Trial design reflective of previous studies. Maintaining control of CML in the chronic phase and prevention of progression to the accelerated and blast phase is crucial, and as mentioned, Iclusig has shown substantial cytogenetic benefit in this respect. This Phase II trial will largely reflect the trial design of the previous Phase II trial, and will focus on optimizing the risk-benefit ratio of Iclusig. Enrollment is targeted at 450 patients, randomized to receive once-daily 45, 30, or 15 mg Iclusig with a reduction to 15 mg
Jess. Well I don't own aria anymore and have not for over year
Still look at time to time but for now IMHO thought there was better values elsewhere
Goodluck as we all need that
Dough
struftpete. Awesome post. Thanks for putting some numbers to it
From OVRL filings you can figure out that in 2014 the RDX revenue was about $35 million and now that S3D has upgraded the RDX package I would expect a continuous growth of +- 50% for RDX + sales of V3 technology and GW
Only the extra RDX revenue for 2015 could easily be $20 Million and then you can add the other extras
RICK
Here is Jp Morgan report. I try also and post mike king later
To all my buddies
Ariad Pharmaceuticals – ARIA (N, $8 PT)
Waiting on a material re-acceleration of Iclusig sales
What happened in 2014: In 2014, ARIA shares declined 2% vs. the NBI +30% and +13% for the S&P. The key event in the year was the relaunch of Iclusig (for CML) with a more limited label following a relatively quick resolution of the safety-related marketing suspension in the US in late 2013.
2015 Outlook & Thesis: We believe progress with the relaunch of Iclusig in the US will continue to be a key focus in 2015. Overall, we are encouraged by ARIA’s progress so far, but with ~50% (steady for both 2Q and 3Q) of the on-label US market captured (that equates to <$20M/Q in revenue), it’s clear that label expansion (i.e., growing the denominator) will be key going forward. While quarterly sales of Iclusig will be important to monitor in 2015, we believe questions around dosing/efficacy and ultimate market opportunity remain, and these are critical to understanding the longer-term potential of Iclusig. In our view, the design and resulting efficacy/safety data of the pending dosing trial (expected to begin in 2015) will be important in gaining confidence with Iclusig’s outlook.
In the EU, ARIA expects to have reimbursement negotiations complete in essentially all of the key EU countries by mid-15 now that the PRAC review is done. A full EU launch is expected in 2H15 in all 16 EU targeted countries.
Beyond Iclusig, the pivotal Phase 2 ALTA trial of ARIA’s ALK/EGFR inhibitor for lung cancer (ALK+NSCLC pts resistant to crizotinib), AP26113, is expected to complete patient enrollment in 2015. Additionally, following the nomination of a new oncology drug candidate at the end of 2014, we expect to gain insight on the development plan early in 2015, potentially at the J.P. Morgan HC Conference.
Key 2015 Catalysts: The dose-ranging trial for Iclusig is expected to begin in 2015. In the EU, the co thinks the majority of remaining pricing approvals will occur by mid-2015. The co also plans to file in Japan in mid-2015 with a potential approval in mid-2016. Following the nomination of a new oncology drug candidate at the end of 2014, we expect to hear development details at the J.P. Morgan HC Conference in Jan. On ‘113, full patient enrollment of the pivotal Phase 2 ALTA trial is expected in 2015.
Key Product Sales... JPMe vs. consensus: We project 2015 Iclusig WW revenues of $186M, which is above consensus of $133M.
Balance Sheet: ARIA ended 3Q with $274M in cash after raising $177M in a convertible senior note offering in 2Q. ARIA now expects cash at YE14 will be $250-$255M (vs. $230-235M prvsly), sufficient to fund operations into ~2H16.
Valuation and Key Risks: Our Dec-15 price target of $8 per share is based on a blended average of our proprietary probability-adjusted scenario analysis (50%) and a risk-adjusted NPV model (50%). Downside risks to our thesis/price target include slow sales growth for Iclusig, negative data from ongoing Iclusig trials and strong data from competitor drugs. Any clinical setbacks with AP26113 would also negatively impact the value of ARIA’s pipeline. Upside risks include faster than expected uptake of Iclusig and better than expected results from ongoing Iclusig trials.
Nice mention http://storageswiss.com/2015/01/05/sphere-3d-and-overland-storage-merger/
Home › Blog › Briefing Note: Sphere 3D and Overland Storage complete merger, introduce new VDI Appliance
Briefing Note: Sphere 3D and Overland Storage complete merger, introduce new VDI Appliance
Posted on January 5, 2015 by Eric Slack — Leave a comment
On December 2nd 2014, Sphere 3D, manufacturer of the Glassware 2.0 application virtualization platform, completed the merger announced in May with longtime storage vendor Overland Storage, makers of the SnapServer NAS products, NEO tape libraries and RDX portable disk drives. Sphere 3D also added the V50 to their V3 line of “desktop cloud computing” solutions, designed to provide a turnkey environment for up to 50 Windows virtual desktops. The already-available V100 and V200 can support 100 and 200 desktops respectively.
Desktop Cloud Computing
Sphere 3D uses this term to describe their turnkey VDI environment that provides the flexibility of a traditional ‘cloud’ in a self-contained, local infrastructure. By combining storage, compute and networking (a hyper-converged architecture), these 2U appliances support existing shared storage or eliminate the need for a SAN completely, providing more consistent VDI performance and more cost-effective scalability with its distributed architecture. According to the company, V3 appliances are guaranteed to run 2x-8x faster than physical desktops and can be set up and running in an hour or less.
While these appliances are designed as turnkey solutions for the mid-market, according to the company, the V3 solution can linearly scale to 1000s of desktops, effectively serving the needs of larger enterprises as well. According to the company, they’re also being used for managed service provider deployments, where the appliance is offered as a desktop-as-a-service solution.
Overland Storage
Overland Storage has a long history in the tape, backup and disk storage industry. They pioneered the expandable, modular tape library design over a decade ago and have built a business in the NAS market after acquiring the SnapServer technology from Quantum. Most recently Overland merged with Tandberg, which brought the RDX removable disk drive and InfiniVault archive products. Throughout its history, Overland Storage has always enjoyed a strong VAR and reseller channel, domestically and internationally.
VDI is a technology that should be attractive for smaller companies but, according to Sphere 3D, hasn’t really caught on in the SME space. Part of the challenge has been complexity. Implementing a VDI solution has typically involved an integration project with servers, networked storage and a VDI platform. The V3 appliances were designed to address this challenge by providing all the needed components integrated into a turnkey solution.
Another issue has been the channel. Smaller companies rely on VARs, reseller and MSPs to implement more complex solutions, like VDI, for which they lack the time and expertise. This is where the Overland Storage merger comes in. For Sphere 3D, Overland brings an array of established data protection and storage products, plus, a roster of channel partners that are currently selling them. For Overland Storage Sphere 3D’s V3 product could be an ideal point of entry to the VDI marketplace.
StorageSwiss Take
The term “hyper-converged” in the enterprise storage space usually means server virtualization and typically, larger users. In the Sphere 3D context, it refers to a purpose-built turnkey solution for desktop virtualization. But semantics aside, the key to this application of the hyper-converged architecture is the simplicity it brings to a relatively complex solution, making VDI a better fit for companies well below the enterprise level.
While it can scale out to much larger capacities, the V3 solution is primarily designed for small to mid-sized companies, the kind that Overland Storage’s VARs, resellers and MPs have traditionally served. With this merger, Sphere 3D can leverage Overland’s channel to make desktop virtualization fit in the SMB and mid-market space.
About Eric Slack
Eric is an Analyst with Storage Switzerland and has over 25 years experience in high-technology industries. He’s held technical, management and marketing positions in the computer storage, instrumentation, digital imaging and test equipment fields. He has spent the past 15 years in the data storage field, with storage hardware manufacturers and as a national storage integrator, designing and implementing open systems storage solutions for companies in the Western United States. Eric earned degrees in electrical/computer engineering from the University of Colorado and marketing from California State University, Humboldt. He and his wife live in Colorado and have twins in college.
Dew. January 13, 2015 Calimmune presenting
W. David Hardy, MD
A Gene-modified Stem Cell and CD4+ T Cells Approach to Curing HIV/AIDS -the Calimmune Perspective
http://cfar.ucsf.edu/cfar?page=symposia-15-home
Anybody following this HBV play for 2015
. (TLOG) - Pharmaceuticals Corp. (TLOG) - Buy, PT $16.00
HBV Program Update at AASLD; Reiterate Buy Rating
Company Update
INVESTMENT HIGHLIGHTS: This morning at the American Association for the Study of Liver Disease (AASLD) meeting, TetraLogic presented new preclinical data supporting the development of birinapant in hepatitis B (HBV). The company announced the initiation of a Phase Ib/IIa study in chronically infected HBV patients. We expect data mid next year. Given the demonstrated safety profile of birinapant and the strong preclinical data and rationale for treating HBV, we are optimistic that we could see not only viral load reductions but also reduction in surface antigen and even seroconversion which is not achievable with direct antivirals.
Update on Birinapant in Infectious Disease. TetraLogic hosted an investor forum with Dr. Marc Pellegrini of the Walter & Eliza Hall Institute in Australia who has conducted preclinical efficacy and mechanism of actions studies of birinapant vs entecavir in mouse models of HBV infection. Dr. Pellegrini reported significant reduction in viral load in infected mice treated with 10 and 30 mg/kg of birinapant along with decreases in surface antigen. While viral load reduction was seen with entecavir, surface antigen reduction was not seen. As a reminder, the surface antigen decreases are significant because they represent reductions in the latent reservoirs of the disease which are not reduced by current antivirals such as entecavir. Additionally, viral load reduction was more effective in models that received birinapant and entecavir. The most encouraging data was that the mice seroconverted by developed antigens to HBV in as little as 2 weeks, while sparing healthy liver cells. We believe that this preclinical data is exciting and presents a new mechanism of treating HBV. TetraLogic initiated a placebo-controlled, dose-escalating Phase Ib/IIa study in 48 chronically infected HBV patients in Australia and New Zealand already being treated with tenofovir or entecavir today. The study will look for reductions in surface antigen in patients out to 85 days, safety and tolerability, and PK. Patients will be assigned to 1 of 6 dosing cohorts, and those assigned to a birinapant dose will be given a dose weekly for 4 weeks. Topline data is expected to be released mid-‘15.iterate Buy Rating
Company Update
INVESTMENT HIGHLIGHTS: This morning at the American Association for the Study of Liver Disease (AASLD) meeting, TetraLogic presented new preclinical data supporting the development of birinapant in hepatitis B (HBV). The company announced the initiation of a Phase Ib/IIa study in chronically infected HBV patients. We expect data mid next year. Given the demonstrated safety profile of birinapant and the strong preclinical data and rationale for treating HBV, we are optimistic that we could see not only viral load reductions but also reduction in surface antigen and even seroconversion which is not achievable with direct antivirals.
Update on Birinapant in Infectious Disease. TetraLogic hosted an investor forum with Dr. Marc Pellegrini of the Walter & Eliza Hall Institute in Australia who has conducted preclinical efficacy and mechanism of actions studies of birinapant vs entecavir in mouse models of HBV infection. Dr. Pellegrini reported significant reduction in viral load in infected mice treated with 10 and 30 mg/kg of birinapant along with decreases in surface antigen. While viral load reduction was seen with entecavir, surface antigen reduction was not seen. As a reminder, the surface antigen decreases are significant because they represent reductions in the latent reservoirs of the disease which are not reduced by current antivirals such as entecavir. Additionally, viral load reduction was more effective in models that received birinapant and entecavir. The most encouraging data was that the mice seroconverted by developed antigens to HBV in as little as 2 weeks, while sparing healthy liver cells. We believe that this preclinical data is exciting and presents a new mechanism of treating HBV. TetraLogic initiated a placebo-controlled, dose-escalating Phase Ib/IIa study in 48 chronically infected HBV patients in Australia and New Zealand already being treated with tenofovir or entecavir today. The study will look for reductions in surface antigen in patients out to 85 days, safety and tolerability, and PK. Patients will be assigned to 1 of 6 dosing cohorts, and those assigned to a birinapant dose will be given a dose weekly for 4 weeks. Topline data is expected to be released mid-‘15.
Great discussion on twitter tonight.
Read all the tweets under this one
@pbookman: Check out the latest @Sphere3D video explaining the Glassware Microvisor. Another component explained. http://t.co/0hfKkVKHZ5 via
@pbookman: @ahagelthrope @Sphere3D Online usage statistics tell of why the Windows license is so important :) Check it out! http://t.co/1WFQiAdwfY
@pbookman: @ahagelthrope @Sphere3D More can be found here. Its where I got it. I also have the report, but cannot reshare. http://t.co/uvK2uc7J32
OT but interesting how big these companies are
2014 was an eventful year for internet stocks with many highs and many lows. How will internet stocks fare in 2015? With the New Year right around the corner, RBC Capital analyst Mark Mahaney compiled a list of internet stock “surprises” that could occur in 2015. Mahaney describes a ‘surprise’ as “an event which the average Internet investor thinks is highly improbable, but has a reasonable chance (30%+) of occurring.”
Google:
Google (NASDAQ: GOOGL) has not had the best year, having fallen short on earnings expectations for 4 consecutive quarters in a row. Despite this, Mahaney currently has an outperform rating on the stock, believing that Google could begin returning cash to shareholders in 2015.
He noted, “At the current rate, Google could end up having over $80B in cash & marketable securities by the end of 2015. That’s not too far off from the level ($100Bish) when Apple announced that it would begin paying a dividend. And we believe that Google management does pay particular attention to Apple’s activities. So perhaps, Google will begin to return cash. By the way, we believe that such a move would be perceived positively by the markets and plausibly lead to a sustained re-rating of Google shares.”
Mahaney has rated Google 32 other times since June 2009, earning a 73% success rate recommending the stock and an impressive +34.0% average return per recommendation.
Facebook:
Facebook (NASDAQ: FB) saw a large growth in mobile use and revenue in 2014 partly due to the acquisition of messaging application WhatsApp for $19 billion that took place earlier this year and the increase in Instagram users, a photo sharing app Facebook acquired in 2012. Mahaney currently has an outperform rating on Facebook, speculating that the social media website could grow its expense base by about 70% in 2015.
The analyst stated, “FB announced on its Q3 EPS call that it would look to increase its expense base by 50%-70% in 2015. As far as we can tell… nobody believes them. For one, that would imply a material acceleration in its costs growth, which are expected to rise 35% in ’14. And second, the company has previously guided to aggressive opex growth and then trimmed those expectations down over the following quarters. So the Street reaction is that FB is largely being conservative. But given the company’s long-term investment orientation and the inclusion of the WhatsApp and Oculus Rift acquisitions, perhaps the market shouldn’t be so dismissive of the 70% scenario.”
Mahaney has rated Facebook 17 other times since June 2012, earning a 100% success rate recommending the stock and a +59.4% average return per recommendation.
Amazon:
Amazon (NASDAQ: AMZN) has continuously seen a decrease in profit since 2011, recently reporting its biggest loss in more than a decade during its third quarter earnings report. The loss was bigger than expected due to a surge in spending on R&D and product development for items like the Amazon Fire phone, which ended up being a big flop. Mahaney still has an Outperform rating on the stock, stating that he still sees potential in Amazon’s margins to recover and its revenue growth to reaccelerate.
Mahaney continued, “Given AMZN’s current close-to-trough P/S multiple and its +20% 2014 correction, sentiment is clearly negative. In large part, because after four years of investments we haven’t seen operating margins or revenue growth stabilize. But we believe there are a variety of factors that could drive this surprise – the demand-driving impact of faster shipping times, ongoing expansion into the CPG and Fashion & Apparel verticals, the full-year impact of the Prime price increase, easing comps, etc… And we believe that this surprise would be met with a material appreciation in AMZN shares.”
Mahaney has rated Amazon 27 other times since April 2009, earning a 68% success rate recommending the stock and a +18.4% average return per recommendation.
Pandora:
Pandora (NYSE: P) has come a long way in 2014 to improve their profits, such as testing Sponsored Listening, a format that allows users to gain access to an hour of commercial-free music, and the launch of Pandora Artists Marketing Platform, a free service that allows artists and music executives to view a detailed overview of their audience. Mahaney has an Outperform rating on the stock, assuming that Pandora can make a deal with music labels that will allow the company to pay reasonable rates for songs before the end of 2015.
He explained, “Pandora and the Music Labels via SoundExchange are currently going through an arbitration process that is not scheduled to conclude until December 2015. Uncertainty over the rates that will emanate from the arbitration process has been a major overhang on P shares, we believe. Thus, a negotiated conclusion on seemingly “reasonable” terms could be a positive catalyst for Pandora’s stock.”
Mahaney has rated Pandora 12 other times since July 2011, but has not seen a lot of success, earning only a 20% success rate recommending the stock and a -7.8% average return per recommendation.
Twitter:
Twitter (NYSE: TWTR) has had a rough year, hitting its lowest price in May and continuing to report slowing growth rates throughout 2014. Most recently, rumors have been swirling around that Twitter CEO Dick Costolo will be stepping down after he sold all of his Twitter shares from his family trust. Mahaney currently has a Perform rating on the stock with hopes that the company’s monthly average users will reaccelerate, Dick Costolo will remain CEO, and they will gain material traction with advisers.
The analyst noted, “Our thought here is that the market assigns a low probability to all three of these events. And yes, they are linked. But we have seen UI (user interface) improvements drive greater usage at other Internet companies, and it turns out that advertising dollars really do follow eyeballs (e.g. Google). So perhaps the market is being overly negative here.”
Mahaney has rated Twitter 11 other times since November 2013, earning a 63% success rate recommending the stock and a +6.2% average return per recommendation.
Netflix:
Netflix (NASDAQ: NFLX) has had quite an eventful year, producing a slew of original new content and rapidly expanding all over the globe. There is no question that Netflix is on its way to becoming a network in its own right. Mahaney has an Outperform rating on the stock with hopes that Netflix will experience a big increase in U.S. Net Sub Adds in 2015.
Mahaney stated that Netflix has “a relatively large series of Original Content launches slated for 2015, and they could combine to keep U.S. Net Sub Adds north of 5MM in 2015, which we believe would be a positive surprise for NFLX shares…”
The analyst has rated Netflix 28 other times since June 2009, earning a 57% success rate recommending the stock and a +60.7% average return per recommendation.
@DortchOnIT: Got or getting #bigdata? You're gonna need big, secure storage...
http://t.co/Yg1Iw3rPzR
ROTH full $BLUE note: BLUE: A potential Cure for SCD May Not be
Far Fetched, Target to $120 - With a potential cure for ß-thalassemia within reach, attention has now
gravitated towards the impending readout from Sickle Cell Disease (SCD). In
the ß-thalassemia studies, patients achieving transfusion independence with
high levels of ßA-T87Q-globin in peripheral blood. SCD is not a homogenous
disease and patients with high fetal hemoglobin (HgF) and HbA-expression
have a milder phenotype. Hence, increasing ßA-T87Q-globin could translate
to reduction in disease burden and transform severe SCD into a milder
phenotype.
SCD is a collection of genetic disorders characterized by the Hb-S variant
of the ß-globin gene. Individuals with sickle cell anemia have two copies
(homozygous) of the variant (Hb SS), and the primary hemoglobin present in
their red blood cells is sickle hemoglobin. Homozygous individuals are most
severely affected. Other SCD patients are heterozygous and possess one
copy of the Hb-S variant plus one copy of another (ß-globin gene variant, like
Hb-C or Hb-ß-thalassemia). These individuals produce a mixture of variant
hemoglobin’s and individuals with Hb-SC and Hb-S/ß-thalassemia tend to
have a more benign form of the disease.
Patients with severe SCD have 1% to 5% HbA: Compared to this, patients
with moderate and milder forms of SCD have between 6% to 16% and 16%
to 30% HbA, respectively. Additionally, patients with the mildest form of the
disease have greater than 30% fetal hemoglobin.
Robust NorthStar and HGB-205 studies bodes well for HGB-206: Betathalassemia
patients achieving transfusion independence had ßA-T87Qglobin
proportion in peripheral blood in excess of 70%. If similar outcomes are
achieved in SCD anemia patients then the sickle hemoglobin content could be
diluted out transforming the patients to a milder phenotype.
Data from the first SCD patient expected during 1Q15: The patient
was transplanted in October 2014, without serious adverse events and had
neutrophil engraftment on day 37. The current standard-of-care is not curative
(excluding stem cell therapy, which is only available to <20% of the patients),
and is associated with significant mortality, morbidity, and economic burden as
lifetime treatment costs exceed $500K.
Lentivirus safety profile will be the key for regulators: The fact that in the
natural history of HIV no T-cell oncogenic events have been reported, coupled
with the absence of any reports from lentivirus-based clinical studies provide
reasonable assurances that this approach could be safe.
Target $120: Risk-adjusted NPV is as follows: (1) Lenti-D to $3/share, (2)
ß-Thalassemia $74/share, (3) SCD $26/share, (4) CART collaboration with
Celgene (CELG-NC) at $3/share and (5) estimated cash $14/share.
CLDN from CS in October
Summary
We are initiating coverage of Celladon Corporation with an Outperform rating and $20 target price. Founded in 2004, Celladon is a biopharmaceutical company based in San Diego, California. Celladon specializes in the research and development of agents targeting sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) enzymes. Celladon's lead pipeline asset is Mydicar, a genetic enzyme replacement therapy for correcting SERCA2a enzyme deficiency, that is being developed as a potential treatment of systolic heart failure. Mydicar received Breakthrough Therapy Designation from the FDA in April 2014. Celladon is currently evaluating Mydicar in systolic heart failure in the CUPID 2 PIIb trial. This trial was fully enrolled as of February 2014. Topline CUPID PIIb data is expected in April 2015.
Mydicar replaces SERCA2a enzyme via gene transfer. Mydicar utilizes a recombinant adeno-associated viral vector 1 (AAV1) serotype to deliver the gene for SERCA2a enzyme. Deficiency of SERCA2a enzyme has been implicated as a central cause of heart failure. Patients with advanced heart failure have unusually low levels of SERCA2a enzyme. SERCA2a enzyme controls the pumping action of the heart by regulating calcium ion levels. During a contraction of the heart, calcium ions are released from the sarcoplasmic reticulum, activating myofilaments resulting in muscle contraction. During a relaxation of the heart, SERCA2a enzyme via the protein phospholamban brings the majority of the calcium ions back into the sarcoplasmic reticulum. Dysregulation of calcium ion levels affects systolic (i.e. contractile) as well as diastolic (i.e. relaxative) function.
There is a significant need for more efficacious therapies to treat heart failure. The current first-line treatment involves a combination of angiotensin-converting-enzyme (ACE) inhibitors and ß-Blockers. Other drugs including aldosterone antagonists, diuretics, and digoxin are used as well. As the disease progresses to the end stage, medical devices including implantable cardioverter-debrillators (ICDs) and left ventricular assist devices (LVADs) are used. Inevitably, a heart transplant will ultimately be required. Mortality is still high: (1) ~50% of patients diagnosed with heart failure will die within 5 years. (2) ~50% of Medicare patients with heart failure die within 3 years following a hospitalization due to this disease. It is estimated that the prevalence of heart failure is ~5.2M in the US and ~12.4M in the EU. The number of patients diagnosed with heart failure is expected to increase, driven by an aging population and rising obesity rates. The direct costs to the healthcare system is also substantial. It is projected that the total medical costs for heart failure in the US is expected to increase 2.5-fold from ~$21B in 2012 to ~$53B in 2030. The majority (~80%) of these costs are attributed to hospitalizations.
Mydicar will be used on top of current pharmacological standard-of-care in heart failure. Mydicar is expected to complement drugs that are currently used to treat systolic heart failure. Mydicar involves a one-time outpatient cardiac catherization, in which a catheter is put into a blood vessel in the arm, upper thigh, or neck and threaded to the heart. The SERCA2a gene is then infused into the coronary arteries and makes contact with cardiac muscle cells. A non-pathologic adeno-associated virus (AAV) delivers the SERCA2a gene to the cell nucleus.
Mydicar has shown promising efficacy in treating systolic heart failure in CUPID 1.
CUPID 1 was a 39-patient PIIa trial evaluating 3 doses of Mydicar (6×1011 , 3×1012, and 1×1013 DNase Resistant Particles (DRP)) and placebo in patients with NYHA Class III/IV systolic heart failure. Mydicar High-Dose (1×1013 DRP) showed a reduction in frequency as well as delay in the onset of recurrent clinical events relative to placebo. Specifically, Mydicar High-Dose showed a statistically significant reduction in recurrent (non-terminal) cardiovascular events relative to placebo through 1 year (88% risk reduction, HR=0.12, p=0.003). These differences were sustained through 3 years (82% risk reduction, HR=0.18, p=0.048). There appears to be a slight trend in survival improvement that favors Mydicar High-Dose. Mydicar High-Dose also stabilized or improved various clinical parameters relative to placebo. There were some imbalances in baseline patient characteristics across
the treatment arms in CUPID 1. In particular, there was a higher percentage of healthier patients in Mydicar arms relative to placebo arms. Post-hoc sensitivity analyses though suggested that the differences in baseline patient characteristics could not completely explain the clinical outcomes observed in CUPID 1.
The key valuation inflection point is the readout of CUPID 2. CUPID 2 is a 250-patient PIIB trial evaluating Mydicar High-Dose (1×1013 DRP) in patients with NYHA Class II/III/IV systolic heart failure. The primary endpoint is time to recurrent hospitalization in the presence a terminal event (all-cause death, heart transplant, LVAD implant). This trial has 83% power to detect at least a 45% reduction in risk (HR=0.55) with a p-value of 0.05. The trial was fully enrolled as of February 2014. Topline CUPID 2 PIIb data is expected in April 2015.
There are few other genetic therapies in clinical development for heart failure. Other clinical-stage genetic therapies include: (1) JVS100 (Juventas) uses a non-viral plasmid encoding stromal cell-derived factor. JVS100 is being evaluated in a PII trial. (2) Ad.HAC6 (Renova) uses an adenovirus serotype 5 encoding human adenyl cyclas type 6. Ad.HAC6 is being examined in a PI/II trial. Preclinical-stage genetic therapies include BB-R12 (Beat Biotherapeutics), Carfostin (NanoCor), and VN-100 (VentiNova).
Mydicar is projected to reach worldwide peak sales of ~$1.5B by 2025. Our sales estimates for Mydicar are based on the following assumptions: (1) Mydicar is approved as a treatment for systolic heart failure in the US and EU. (2) The addressable population in the US and EU is ~350K. (3) Mydicar achieves a penetration of 35% in the US and 25% penetration in the EU after 8 years from initial launch. (4) Celladon sells Mydicar directly in the US and EU. (5) The net price per (one-time) infusion for Mydicar is ~$36K in the US and ~$23K in the EU. (6) The timing of peak sales for Mydicar though will depend on the outcome of CUPID 2 as well as the FDA's and EMA's acceptance of CUPID 2 as a registrational trial. Our modeling assumes that a PIII program will be required and Mydicar will be launched in late 2019 / early 2020. If CUPID 2 hits the primary endpoint and is accepted as a registrational trial by FDA and EMA, then Mydicar could be launched in 2018. Otherwise, assuming the requirement of a PIII trial, Mydicar could reach the market in late 2019 / early 2020. (7) Mydicar is protected from biosimilar competition until 2030.
The rest of the pipeline could drive further upside. Celladon is currently exploring additional indications for Mydicar that are currently not included in our valuation. Celladon is currently enrolling a PI/II trial examining Mydicar in patients with advanced heart failure with LVAD. Celladon plans to start a PIIa trial evaluating Mydicar in arteriovenous fistula maturation failure soon as well. Topline data from this study is expected in 2015. Celladon is also evaluating the potential of Mydicar in diastolic heart failure in preclinical studies. In addition to Mydicar, Celladon has 2 preclinical-stage compounds – SERCA2b small molecule and Stem Cell Factor.
William Blair’s Top BioPharmaceutical Stock Picks for Q1 2015
2014 has been an eventful year on Wall Street. Now that the year is coming to an end, what stocks should investors be on the lookout for in the first quarter of the New Year? To answer this question, William Blair analyst Y. Katherine Xu named 5 Biotechnology stocks to watch in the first quarter of 2015.
Medivation:
Medivation (NASDAQ: MDVN) is best known for developing therapies to treat serious diseases. Earlier this year, the biopharmaceutical company received FDA approval to expand the use of Xtandi, a prescription medicine used to treat men with prostate cancer. Since the expansion of the drug was approved, Medivation’s stock has increased about 60% and they raked in $200 million in revenue in their most recent quarter. In the first quarter of 2015, Medivation is poised to report data collected from the TERRAIN study, which evaluated Xtandi in comparison to Casodex, a direct competitor of the treatment, in metastatic prostate cancer.
Xu gave Medivation an Outperform rating and a $116 price target, reasoning that data from the TERRAIN study “could push Xtandi to eventually replace Casodex, becoming the biggest prostate cancer drug.” The analyst believes “Positive TERRAIN data will further push urology adoption,” which is the “key for Xtandi’s next leg of growth.”
Xu has rated Medivation twice since February 2011, earning an overwhelming +143.5% average return per recommendation.
Dynavax:
Dynavax (NASDAQ: DVAX) is known for developing products to prevent and treat infectious and inflammatory diseases and cancer. Three total interim data safety monitoring board reviews have been scheduled for Dynavax’s HBV-23 treatment, the company’s adult hepatitis B vaccine candidate, with the first review recently completed in October of this year. The second review is set to happen in February 2015.
Xu gave Dynavix an Outperform rating with a $40 price target, noting “the focus of HBV-23 is on the safety side; therefor, each positive DSMB review should further de-risk the study.”
Xu has rated Dynavax 6 times since May 2010, earning a 67% success rate recommending the stock.
Tokai Pharmaceuticals:
Tokai Pharmaceuticals (NASDAQ: TKAI) focuses on developing proprietary therapies for prostate cancer and other hormonally-driven diseases. Tokai has plans to begin enrollment in its Phase III ARMOR3-SV study in the first half of 2015. The company’s Phase III study is meant to target men with prostate cancer who have shown resistance to Johnson & Johnson’s (NYSE: JNJ) Zytiga and Medivation’s (NASDAQ: MDVN) Xtandi.
Xu gave Takai an Outperform rating and a $44 price target. Xu acknowledged that “the development of a companion diagnostic to identify AR-V7 expression for the study enrollment, as well as FDA approval for this diagnostic, is a prerequisite to beginning this Phase III trial.” Thus, “finalizing and validating the assay is the next major milestone to be achieved in the development program,” in her opinion. This is the first time Xu has given a recommendation for Tokai.
Vertex:
Vertex (NASDAQ: VRTX) develops new medicines for people with serious diseases. The final readout of Vertex’s 12-week Phase II study data of its cystic fibrosis treatment, Kalydeco, with VX-661, a placebo, in homozygous patients is expected during the first quarter of 2015. The data will be benchmarked with two different studies titled TRAFFIC and TRANSPORT. The company is getting ready to start a Phase III trial in early 2015 in patients 12 years and older with cystic fibrosis.
Xu gave Vertex an Outperform rating with a $115 price target with the expectation that the data from the company’s Phase II study of Kalydeco with VX-661 “to be better than that observed with TRAFFIC and TRANSPORT.”
Xu last rated Vertex in January 2010, earning a +13.8% return.
Chimerix:
Chimerix (NASDAQ: CMRX) develops oral antiviral treatments in areas of high unmet medical need. The company plans to initiate a Phase III study of CMV and BKV, which will “determine the effectiveness of brincidofonier in the prevention of cytomegalovirus (CMV) and BK Virus (BKV) infection in kidney and kidney-pancreas transplant recipients,” according to Xu’s research note.
Xu gave Chimerix an Outperform rating and a $46 price target, noting “The study initiation in the renal transplant setting will be followed by top-line data releases from two earlier Phase III programs during 2015- SUPRESS study data in the third quarter 2-15 and AdVise study data around the end of 2015.”
Xu last rated Chimerix in October of this year, earning a +15.4% return on the stock.
These 5 biopharmaceutical companies have a lot to look forward to in 2015 with Y. Katherine Xu remaining bullish on all of them.
PIPER $ACHN Price Weakness Offers Buying Opportunity; Reiterate Overweight
Shares of ACHN traded down $3.65 or 23.6% yesterday due to a competitor downgrade
and fueled by year-end profit taking. We believe this sell-off is overblown and are buyers
on weakness. Earlier this weak, new Phase I data showed that Achillion's nuc ACH-3422
was safe and achieved an impressive 4.8 log viral load reduction at 700mg after 14 days of
monotherapy. Achillion also reported interim Phase II data showing that NS5A inhibitor
ACH-3102 + Gilead's Sovaldi achieved 100% SVR4 after only 6 weeks of therapy. Based
on these data, we view Achillion's HCV pipeline as further de-risked and look for
additional Phase II validation in 2015. Achillion ended 3Q:14 with cash of $127 million.
We reiterate our Overweight rating and $22.50 price target.
• ACH-3422 Nuc Safe and Potent. The Phase I placebo-controlled trial randomized
treatment-naïve HCV genotype 1 patients to escalating doses of 50mg, 150mg and
300mg ACH-3422 for 7 days and 500mg and 700mg ACH-3422 for 14 days of
monotherapy. Importantly, all doses were well-tolerated with no discontinuations due
to AEs, significant laboratory or ECG findings or treatment-related SAEs. The 700mg
ACH-3422 cohort showed an impressive mean max viral load reduction of 4.8 log IU/
ml with 3/6 (50%) patients at undetectable levels of HCV RNA (<10 IU/mL). We view
this as validating data that Achillion has a safe and potent nuc.
• ACH-3102 Combo Accelerates Cure. Achillion also announced interim results from
a Phase II combo study of NS5A inhibitor ACH-3102 + Gilead's nuc Sovaldi. The
combo achieved 100% (12/12) SVR4 after only 6 weeks of treatment. The reduction
was achieved independent of viral load, which was high in this cohort with 7 patients
displaying baseline HCV RNA >6 million IU/ml. The combo was well tolerated with
no discontinuations, significant lab or ECG abnormalities or SAEs. SVR12 data is
expected in 1H:15. We believe Achillion's best-in-class NS5A inhibitor ACH-3102 with
a nuc could further shorten treatment duration and cut cost vs. Gilead's HARVONI.
• Future HCV Development Plans. Based on the efficacy shown by ACH-3422 and
ACH-3102, Achillion plans to conduct the Phase II SPARTA trials in 2015 that will
feature doublets of ACH-3422 and ACH-3102, as well as triple combinations with
Achillion's protease inhibitor sovaprevir.
Piper C L U S I O N
End of year is always a useful time to reflect on what new themes could emerge in the year
ahead, and also consider what 'surprises' may lurk around the corner that could have
meaningful impact on the broader market or specific stocks. In this report we identify
15 events that haven't reached a high level of visibility or consideration but which could
prove transformative in 2015. While not all are "high probability events," there is still
value in considering the 'fat tails', i.e., lower probability events that are off radar screens
but could be potentially impactful ones. Among the list, perhaps not surprisingly, gene
therapy is well represented as we believe the field is positioned to delivery multiple proof of-
concept readouts.
1. Gene therapy establishes proof of concept in hemophilia
2. Heart failure explodes on the biopharma scene with gene therapy success
3. Biopharma does even better in 2015 than it did in 2014
4. Failed trials get approved, starting with BMRN's drisapersen
5. BLUE cures sickle cell anemia
6. BIIB finishes the year with the best large-cap pipeline and freedom to operate on Tecfidera
7. SNY/MNKD Afrezza launch goes well
8. PD1 antibodies start to look like a thing of the past
9. AMGN blocks REGN/SNY's PCSK9 antibody
10. A biosimilar Soliris enters Phase 3
11. Gene therapy cures blindness
12. Iran gets the nuke; military spending hikes force other budget cuts
13. Two large-cap biotechs get acquired
14. CBD hits the radar screen for autism
15. ProQR transforms the CF landscape
@jkatcher74: Even more reasons coming for 2015...7 reasons Google Chromebooks hit their stride in 2014 http://t.co/qcy5mf9Ocv via @pcworld
MERRY CHRISTMAS everyone. Latest from JMP
Ariad Pharmaceuticals inks agreement for marketing and commercialization of Iclusig in Asia with Otsuka; reiterate our Market Outperform rating and $7 price target based on DCF and SOTP valuation methodologies. ARIA announced that it has partnered with Otsuka to commercialize Iclusig (ponatinib) in Asia including Japan. Details of the agreement include an upfront payment of $77.5MM to ARIA, with Otsuka retaining exclusive rights and funding future clinical development in Asia. We believe the deal will allow ARIA to rapidly capitalize on the Asian market for Iclusig in CML and additional indications while providing non-dilutive funding to ARIA. We estimate the total CML market opportunity in Japan to be about $332MM with estimated peak sales of $74MM in 2022.
Details of the agreement. As mentioned, in exchange for exclusive rights to Japan and nine other Asian territories, Otsuka will pay ARIA a $77.5MM upfront fee, with additional milestone payments upon approval in Japan for resistant and intolerant Philadelphia chromosome positive leukemia and other indications. ARIA will fund the continuing Phase III registrational trials forming the basis of the NDA in Japan, with Otsuka retaining the option to contribute funds to gain access to the data for continued development in these territories.
Changes to our model. We are making changes to our model to reflect the details of the agreement incorporating the $77.4MM in upfront economics and a downstream estimated regulatory milestone payment of $20MM for regulatory approval in Japan, and making changes to later streams of revenue from the Asian territories to reflect their shift from full contribution to an estimated 22% royalty recognition (Figures 2-4, 8). Specific changes to our DCF and SOTP valuations are shown in Figures 6 and 7, with valuations essentially remaining in line with our $7 price target.
We remain buyers of ARIA shares at current levels. We view PRAC’s recommendation as a clear positive for ARIA, alleviating concerns around the EU commercial opportunity and stalled pace of the European commercial launch. Iclusig is approved and selling in seven European countries, with another seven expected to come online in 1H15. We forecast 4Q and FY14 Iclusig sales of $14MM and $54.6MM, respectively.
Maybe someone else can chime in here also. But when ANY traded on CDN exchange
It appeared to me UBSS was the house Doing a majority of the shorting
I was using CDN stock watch
What I Can tell you as truth is almost daily I am getting responses from people
Inquiring about Sphere3D on twitter
Interest is for sure picking up IMHO
UBSS was the short on CDN exchange FYI.
IMHO going to get interesting later today
Leerink $ACHN ups PT to $25.00 - ACH-3422 Data On Par with Sovaldi After 2 Wks; PROXY Data a 1st for 2-DAA Combo
• Bottom Line: ACHN announced highly anticipated Phase I data for
its nucleotide HCV polymerase inhibitor (nuc) ACH-3422, showing a
mean maximal viral log reduction of 4.8 over 14 days with the 700 mg
dose. Although 7-day viral load reduction (appears to be ~3.4 logs) looks
lower than GILD’s (OP) Sovaldi (~4.6 logs) or MRK’s (MP) IDX21437
(4.2 logs), there is continued, steeper viral decline on ACH-3422 in week
2 such that at the end of 2 weeks ACH-3422 looks to have a similar
viral decline compared to data on Sovaldi + ribavirin that we were able
to find (~5 logs). We believe there is more than sufficient activity for
ACH-3422 to be the backbone of a 2- or 3- direct antiviral agent (DAA)
combination. ACHN also reported remarkable data from the 6-week arm
of the PROXY study combining its NS5A inhibitor (NS5Ai) ACH-3102
with Sovaldi, demonstrating for the first time that 6-week treatment could
be feasible for a 2-DAA regimen (100% SVR4 rate in 12 patients) and
ACH-3102 as a differentiated NS5A inhibitor. With what appears to be
a safe and effective nuc, a strong NS5Ai, and a protease inhibitor (PI;
sovaprevir), ACHN is the only remaining small biotech company that has
a clinical stage nuc as well as an internal portfolio to develop its own 3-
DAA regimen and we believe it is in an attractive position. As a result of
these data, we are increasing our price target to $25 from $12 based on
improved outlook for ACHN's compounds.
• Lower exposure, longer half-life lead to slower onset but sustained
viral log reduction for ACH-3422 as compared to Sovaldi. The
company reported that while ACH-3422 took 14 days to achieve the
4.8 log drop, this was due to the fact that it showed sustained antiviral
activity resulting in an additional 1.4 log reduction between days 7
and 14 and, according to management, 1.3-1.4 logs between days 3
and 7. The log drop at day 10 was 4.2. The rate of decline of Sovaldi
appears to decrease after day 3 and appears to decline by less than 1
log between days 3 and 7 (see Figure 2). While we are unaware of any
publicly available viral kinetic data past 7 days for Sovaldi monotherapy,
the declines seen for Sovaldi + ribavirin (RBV) between days 7 and
14 appear to be on the order of ~0.5 logs (see Figure 3), and the total
viral load decline on Sovaldi plus RBV for 2 weeks appears to be
approximately 5 logs. It appears that ACH-3422 starts slow especially
in the first 3 days but catches up with Sovaldi after 2 weeks due to a
steeper slop in the second week in particular. The explanation for a
slower onset of action of ACH-3422 appears to be a lower exposure of
the prodrug (700 mg ACH-3422 producing only 1/5 of the exposure as
Sovaldi), reaching the highest level of triphosphate at 48 hours, which is
considerably later compared to other nucs, as well as a longer half-life of
the triphosphate that may be responsible for a more sustained viral drop.