Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
RBC 2015 Biotech Preview - Summary - Top-four longs are CELG, BMRN, VRTX, REGN:
Biotech for 2015: More mixed than prior years, just be stock
selective…
After four straight years of significant outperformance when essentially every mid- and
large-cap stock went up, we still recommend owning the biotech sector but just have more
tempered expectations on absolute returns and need to be particularly more stock selective
this year (CELG, VRTX, BMRN) than in prior years.
On the positive side, biotech secular fundamentals are still solid, innovative pipelines are
exciting (immno-oncology and targeted cancer therapy, Alzheimer’s, orphan drugs, etc.),
volume and pricing intact, earnings growth at 15-20%+ in 2015 would still far outpace the
S&P500, and valuations are not expensive, i.e., P/E multiples at the 17-22x range are not that
far off the pharma group (15-17x) or the broader market—all are good reasons to own
biotech. On the other hand, we see fewer big clinical trial catalysts in 2015 versus prior
years, the big biotech launches that drove so much upside have passed years one and two
now (Hep C, Tecfidera, etc.), and we see fewer relative upward consensus earnings revisions
than we saw in 2013-14 that made biotech easier to recommend.
Four key investor themes that investors will be focused on for 2015: 1) Dynamics of GILD in
Hep C as ABBV launches in January and Merck Phase III data coming, 2) three big clinical trial
readouts for BIIB make it the biggest risk/reward (volatile) stock in biotech: P2 LINGO data in
January, P1 Alzheimer’s data presentation in March, and P3 Tysabri SPMS data in the fall, 3)
FDA panel and potential PCSK-9 approvals and “launch” for AMGN/REGN in H2:15, 4) CELG
court begins against ACT around summer 2015 and whether it ends up settling, meanwhile
EU polymorph patent opposition case ongoing through spring 2015;
Top-four longs are CELG, BMRN, VRTX, REGN: 1) Buy CELG because it could trade at its
current 20-22x multiple on 2016 potentially getting it to $125-150; we raised PT to $135; we
predict a self-fulfilling market prophecy that a “settlement” with ACT could theoretically
happen after spring 2015, when legal discovery ends and before Court could begin around
mid-2015, and bears cannot short if a settlement happens, which would be big upward move
(we are not saying it is inevitable by then, but we acknowledge that the potential exists and
could happen even after Court begins); plus investors should start giving more credit to
pipeline—GED-301 going into Phase III, and now Agios’ drugs are becoming interesting, and
CELG owns half, 2) Buy BMRN for five pipeline readouts for 2015, especially Phase II
achondroplasia data in Q2, which should work, and a new DMD drug, which has a good
chance of FDA approval by YE:15 and is not yet in consensus estimates, 3) Buy VRTX into
early 2015 Phase II VX-661 three-month homozygous data, which should look better than
first-gen ‘809 combo. We want to own into likely ‘809 strong pricing and strong US
launch/demand for mid-2015. Separately, we also raised price targets on others as we adjust
them based on forward 2016 earnings now (see inside table). 4) Buy REGN as Eylea franchise
has no near-term competitive threats and franchise can be extended with combination
products, plus three new blockbuster potential drugs could be approved in 2015-2017.
Top small caps for 2015: 1) XNPT should keep climbing into Q3 Phase II fumarate psoriasis
data, 2) DYAX for Phase I Hereditary Angioedema (HAE) data H1:15 and LINGO derivative
play (2.5% royalty). 3) AERI – A new mechanism of action targeting glaucoma with two
separate Phase III programs, one reading out around mid-2015 and the other in 2016, could
lead to a best-in-class or best anti-glaucoma product. 4) APTO – A new mechanism of action
potentially targeting the underlying mechanism of AML with Phase I updates and activity in
In a research report published this morning, Needham analyst Alan Carr maintained a Buy rating on Acadia (NASDAQ:ACAD) and raised his price target to $40 (from $26), which implies an upside of 22% from current levels.
Carr observed, “We expect Acadia to submit a Nuplazid NDA in Parkinson’s Disease Psychosis (PDP) in 1Q15. Given the drug was designated a Breakthrough Therapy in Sept 2014, we believe a Priority Review is likely and we expect Nuplazid to be approved in the U.S. in 4Q15. As a reminder, positive results from a Phase 3 trial in PDP were announced in 2012. Per discussions with the FDA and EMA, mgmt believes only one successful Phase 3 trial is needed for approval. Nuplazid may have utility across several psychosis indications, given prior success as adjunctive therapy in schizophrenia. Results from a Phase 2 trial in Alzheimer’s Disease Psychosis are expected in 4Q15 and Acadia plans to initiate a Phase 2 trial in schizophrenia as maintenance monotherapy in 2H15.”
news on marketwatch
http://www.marketwatch.com/story/sphere-3d-enters-multi-year-oem-embedded-agreement-with-microsoft-2014-12-22?reflink=MW_news_stmp
http://money.cnn.com/news/newsfeeds/articles/marketwire/1166319.htm
Press Release
Sphere 3D Enters Multi-Year OEM Embedded Agreement With Microsoft
By
Published: Dec 22, 2014 8:01 a.m. ET
Share
SAN JOSE, CA and MISSISSAUGA, ON, Dec 22, 2014 (Marketwired via COMTEX) -- Sphere 3D Corporation ANY, +2.69% a virtualization technology and data management solutions provider, today announced that it has entered into a multi-year, global OEM Embedded Agreement with Microsoft Corporation that allows for the pre-installation of Microsoft Windows Embedded Server software in appliances that utilize Glassware 2.0(R) application virtualization technology.
Through this agreement with Microsoft, Sphere 3D will be able to offer customers Glassware 2.0 application virtualization appliances with Windows Embedded Server preinstalled. Windows Embedded Server is a proven, robust, highly reliable operating system that is binary identical to general purpose Windows Server and provides high-performance, hybrid cloud-service capabilities and innovative storage options for building robust, industry-class server appliances.
"This agreement positions Sphere 3D to further simplify the deployment and management of purpose-built appliances for virtualization to customers," said Eric Kelly, Chairman and CEO of Sphere 3D Corporation. "Under the embedded licensing program with Microsoft, we are able to deliver turnkey solutions for Windows Embedded Server workloads to organizations ranging from small businesses to large enterprises."
About Glassware 2.0 Glassware 2.0 utilizes proprietary technology to achieve application virtualization without the requirement to virtualize the desktop. The Glassware 2.0 family of technologies is comprised of the Glassware 2.0 protocol, microvisor, containers, management, and clustering. Glassware 2.0 utilizes containers to run multiple instances of the same application on a Glassware 2.0-enabled server or appliance, and the ability to share binaries, libraries or the Glassware 2.0 Microvisor. Within these containers, Sphere 3D allows access to only the necessary elements of the operating system an application requires to run. This can include applications that utilize a wide array of Windows-based operating systems, such as Windows XP, Windows 7, Windows 8, etc.
About Sphere 3D Sphere 3D Corporation ANY, +2.69% is a virtualization technology and data management solutions provider with a portfolio of products that address the complete data continuum from active data to data at rest. Dedicated to continue to lead through innovation, Sphere 3D enables the integration of virtual applications, virtual desktops, and storage into workflow, and allows organizations to deploy a combination of public, private or hybrid cloud strategies. Sphere 3D's Glassware 2.0 platform delivers virtualization of some of the most demanding applications in the marketplace today, making it easy to move applications from a physical PC or workstation to a virtual environment. Sphere 3D's V3 converged infrastructure solutions include one of the industry's first purpose-built appliances for virtualization and the Desktop Cloud Orchestrator(TM) management software for VDI. Overland Storage and Tandberg Data, wholly-owned subsidiaries of Sphere 3D, provide an integrated range of technologies and services for primary, nearline, offline, and archival data storage through their data storage, data management and data backup brands, SnapServer(R), SnapScale(R), SnapSan(R), NEO(R) and RDX(R), that make it easy and cost-effective to manage different tiers of information over the data lifecycle. For additional information, visit www.sphere3d.com, www.overlandstorage.com, and www.tandbergdata.com.
Overland Storage, SnapServer, SnapScale, SnapSan and NEO are trademarks of Overland Storage, Inc., and Tandberg Data and RDX are trademarks of Tandberg Data Holdings, S.a r.l. that may be registered in some jurisdictions. All other trademarks are the property of their respective owners.
Media Contact:
Pattie Adams
Director, Global Corporate Communications
+1 408/283-4779
padams@overlandstorage.com
SOURCE: Sphere 3D Corporation
(C) 2014 Marketwire L.P. All rights reserved.
The MarketWatch News Department was not involved in the creation of the content.Stock
References
ANY
+0.14 +2.69% ANY
+0.14 +2.69% More News from
MarketWatch
yes it true i posted the news release now
@ProTradersNews: $ANY: Sphere 3D Enters Multi-Year OEM Embedded Agreement With ... http://t.co/Ff5Zp7LpYL http://t.co/vDXXbcMCWd
Sphere 3D Enters Multi-Year OEM Embedded Agreement With Microsoft
December 22, 2014: 08:00 AM ET
Sphere 3D Corporation (NASDAQ: ANY), a virtualization technology and data management solutions provider, today announced that it has entered into a multi-year, global OEM Embedded Agreement with Microsoft Corporation that allows for the pre-installation of Microsoft Windows Embedded Server software in appliances that utilize Glassware 2.0® application virtualization technology.
Through this agreement with Microsoft, Sphere 3D will be able to offer customers Glassware 2.0 application virtualization appliances with Windows Embedded Server preinstalled. Windows Embedded Server is a proven, robust, highly reliable operating system that is binary identical to general purpose Windows Server and provides high-performance, hybrid cloud-service capabilities and innovative storage options for building robust, industry-class server appliances.
"This agreement positions Sphere 3D to further simplify the deployment and management of purpose-built appliances for virtualization to customers," said Eric Kelly, Chairman and CEO of Sphere 3D Corporation. "Under the embedded licensing program with Microsoft, we are able to deliver turnkey solutions for Windows Embedded Server workloads to organizations ranging from small businesses to large enterprises."
About Glassware 2.0 Glassware 2.0 utilizes proprietary technology to achieve application virtualization without the requirement to virtualize the desktop. The Glassware 2.0 family of technologies is comprised of the Glassware 2.0 protocol, microvisor, containers, management, and clustering. Glassware 2.0 utilizes containers to run multiple instances of the same application on a Glassware 2.0-enabled server or appliance, and the ability to share binaries, libraries or the Glassware 2.0 Microvisor. Within these containers, Sphere 3D allows access to only the necessary elements of the operating system an application requires to run. This can include applications that utilize a wide array of Windows-based operating systems, such as Windows XP, Windows 7, Windows 8, etc.
About Sphere 3D Sphere 3D Corporation (NASDAQ: ANY) is a virtualization technology and data management solutions provider with a portfolio of products that address the complete data continuum from active data to data at rest. Dedicated to continue to lead through innovation, Sphere 3D enables the integration of virtual applications, virtual desktops, and storage into workflow, and allows organizations to deploy a combination of public, private or hybrid cloud strategies. Sphere 3D's Glassware 2.0 platform delivers virtualization of some of the most demanding applications in the marketplace today, making it easy to move applications from a physical PC or workstation to a virtual environment. Sphere 3D's V3 converged infrastructure solutions include one of the industry's first purpose-built appliances for virtualization and the Desktop Cloud Orchestrator™ management software for VDI. Overland Storage and Tandberg Data, wholly-owned subsidiaries of Sphere 3D, provide an integrated range of technologies and services for primary, nearline, offline, and archival data storage through their data storage, data management and data backup brands, SnapServer®, SnapScale®, SnapSan®, NEO® and RDX®, that make it easy and cost-effective to manage different tiers of information over the data lifecycle. For additional information, visit www.sphere3d.com, www.overlandstorage.com, and www.tandbergdata.com.
Overland Storage, SnapServer, SnapScale, SnapSan and NEO are trademarks of Overland Storage, Inc., and Tandberg Data and RDX are trademarks of Tandberg Data Holdings, S.à r.l. that may be registered in some jurisdictions. All other trademarks are the property of their respective owners.
On twitter MSFT news. @Benzinga: Sphere 3D Enters Multi-Year OEM Embedded Agreement With Microsoft $MSFT $ANY
JPMorgan on $ABBV This afternoon, FDA announced that it has approved Viekira Pak, AbbVie’s
HCV combo (ABT-450/267/333). The Viekira Pak label is consistent with our
expectations with 12-week dosing recommended for the majority of patients
and 24-week dosing recommended for some GT1a cirrhotics. In our view, the
label enables AbbVie to be competitive in the market. We continue to expect
AbbVie to take at least 20% market share in what is likely a $15bn+ market,
which translates to our 2015 sales estimate of ~$3bn, with room for upside.
We remain OW ABBV shares.
? Viekira Pak is indicated for 12-week dosing for a majority of patients.
As expected, Viekira Pak is indicated for 12-week dosing for a majority of
patients, including all GT1b patients and all non-cirrhotic GT1a patients.
Ribavirin is recommended for GT1a patients and GT1b cirrhotic patients. In
our view, the Viekira Pak label enables AbbVie to be competitive in the
market.
? Not surprisingly, 24-week dosing is recommended for GT1a patients
with cirrhosis. The FDA is recommending a 24-week treatment duration for
GT1a cirrhotics. We note that the label also states that a 12-week treatment
duration may be considered for some GT1a cirrhotics based on prior
treatment history. As a reminder, phase III TURQUOISE-II data showed a
modest SVR12 rate improvement with 24-week dosing in
treatment-experienced GT1a cirrhotics, while treatment-naïve patients had
similar SVR12 rates with both 12-week and 24-week treatments. Along
these lines, we continue to see most GT1a cirrhotic patients on 12-weeks of
treatment.
? Viekira Pak pricing in line with our expectations. Viekira Pak has a list
price of $83,319 for a 12-week treatment, a 12% discount to a list price for a
12-week treatment of Harvoni ($94,500), but a premium to 8-wk Harvoni
($63,000). We continue to expect fairly rational discounting between
AbbVie and Gilead, and we would not be surprised to see AbbVie offer
select rebates in exchange for enhanced formulary access.
? We continue to forecast $3bn in HCV sales for AbbVie in 2015. AbbVie
is well-positioned to capture share in certain difficult patient populations
(i.e. cirrhotics), in our view, and we see AbbVie also capturing additional
share in select accounts with favorable formulary access. We continue to
expect AbbVie to capture ~20% share in a $15+ billion market, which
translates to $3 billion in 2015 HCV sales (with room for upside) and overall
ABBV EPS of $4.40. We would note that with launch spend already
factored into estimates and high gross margins, we would expect much of
any sales upside to fall to the bottom line. We estimate that an additional
$200 million in 2015 HCV sales would translate to roughly $0.09 of EPS
upside.
In a research report issued today, Cantor analyst Mara Goldstein maintained a Buy rating on shares of Celldex Therapeutics (NASDAQ:CLDX) with a $33 price target, following data presentations at the San Antonio Breast Cancer Symposium (SABCS), which took place in San Antonio last week.
Goldstein noted, “Our takeaway view from the conference is that Celldex’s CDX-011, in development for triple negative breast cancer (TNBC), is still very much a contender amongst a number of agents in development for this breast cancer population. We base this on data generated thus far for agents such as Merck’s Keytruda, Roche’s MPDL3280A, and Medivation/Astella’s Xtandi.”
The analyst added, “We like shares of Celldex because of the depth and breadth of candidates in numerous clinical trials and view the opportunities for updates from a number of trials in the near term as potentially accretive to the shares.”
RBC CELG Long-overdue front-line myeloma indication gets positive recommendation - increasing visibility on long-term growth...
First impression
The EU CHMP board issued a positive recommendation for approval for Revlimid for front-line myeloma use (in transplant ineligible pts) based on the MM-020 study, etc. This is 1) a fundamental positive and consistent with our bullish CELG thesis because Revlimid now has a new $1B+ indication to go after and had zero front-line sales in EU but is doing $1B in US already...this helps the 2017+ growth trajectory and beyond; 2) recommendation seems a bit early and should get formal "approval" in a couple months which is earlier than spring 2015 which most had thought/guided to; 3) removes some near-term uncertainty that it was only downside risk and not much upside for the stock but now the recommendation is formal...
We note some investors may point to fact that recommendation was for transplant "ineligible" pts and not "full" front-line including transplant eligible. However the indication they got addresses 65-70% of the front-line market and was at least the base case and we are clear that very few investors would think they'd get the full label. The rest of the 30%+ of the market can be addressed through other Phase III studies we are waiting on longer-term follow-up on OS (CALGB study, and IFM study that are not mature yet...).
We like CELG here for 2015+ based on potential settlement on Revlimid patents and down the line...2020 guidance that gives even more visible growth to investors and pipeline coming into play which has not been the thesis on CELG for the last few years.
WF
Summary. We are initiating coverage of FMI with an Outperform rating, a 12-month, DCF-derived valuation range of $30-32, and 2014/2015 EPS estimates of -$1.92/-$1.85. We believe the company has a first-mover advantage in a high-growth market segment addressing an unmet medical need for comprehensive, actionable, and personalized genetic information matching patients with metastatic tumors to treatment options. We believe the company’s competitive moat is underappreciated--the complexities of next-generation sequencing create technical barriers to entry, while the company’s success engaging physicians via its Interactive Cancer Explore portal locks in a sticky customer base. Meanwhile, the company’s biopharmaceutical customer base provides a reliable (and growing) source of revenue, although the opportunity is not nearly as large as the clinical market, in our view. While reimbursement creates an ever-present risk, we believe the stock presents a favorable risk/reward profile at current levels.
First-mover advantage in high-growth market segment. Foundation Medicine offers comprehensive gene sequencing panels for solid and hematological tumors. The test results offer patients and physicians information about potentially effective therapies--either marketed or in clinical trials. We believe comprehensive cancer panels are one of the highest growth market segments in the molecular diagnostics sector due to significant unmet need for effective treatment of metastatic cancer. At current test prices, we think the market currently addressed by Foundation’s selling efforts is about $3 billion, with current penetration in the very low single digits. Foundation Medicine has a first-mover advantage in this market, with no other commercial competitor and a limited number of cancer centers able to offer an assay capable of identifying all four classes of genomic variation (substitutions, insertions/deletions, copy number alterations, and rearrangements). We believe the company’s first-mover status gives it an opportunity to garner physician mind share--which tends to be sticky once physicians get comfortable with a certain product.
Competitive moat is underappreciated. Next generation sequencing (NGS) is a complicated process, even with the significant improvements in nearly every aspect of the workflow over the past few years. Transforming NGS data into a clinically actionable report is perhaps even more complicated, and Foundation Medicine’s report is strikingly clear and easy to interpret. In effect, Foundation Medicine has made an incredibly complex process seem relatively simple and straightforward--not an easy feat, in our view.
Moreover, Foundation has successfully engaged with physicians via its Interactive Cancer Explorer (ICE), which encourages the sharing of genomic and treatment data, creating a network effect, which we think helps lock in the physician customer base. Since launching the test in 2012, well over 2,100 physicians in over 25 countries have ordered FoundationOne. The company believes approximately 50% of ordering physicians may have placed orders without first being visited by a sales representative.
So far, we believe the only test comparable to FoundationOne (i.e., able to detect all four classes of genomic alterations) is the MSK-IMPACT test available from Memorial Sloan Kettering (MSK). MSK has partnered with Foundation Medicine on FoundationOne Heme but not on FoundationOne. Other academic medical centers may ultimately produce NGS-based tests seeking to compete with FoundationOne in terms of the number of genes interrogated; however, we believe these tests may have limitations in sensitivity, specificity, scalability, minimum sample volume or quality, turnaround time, and reporting. We believe Foundation Medicine also maintains an advantage by curating a database of the latest research and clinical trial data, which requires significant investment. It is the combination of these factors that we believe creates a strong competitive moat for Foundation.
Biopharmaceutical market is strong, but size is limited. Foundation Medicine also sells its tests to biopharmaceutical customers for use in the development of targeted therapeutics. This business generated about half of the company’s revenue in 2013 and is not subject to the same kind of reimbursement risks faced by the clinical market. The biopharma business is growing solidly (68% in 2014 and 34% in 2015 by our estimates), but has already been eclipsed by the clinical business as the opportunity is more limited. However, we believe the biopharma business offers a predictable source of revenue.
Favorable risk/reward profile. Foundation Medicine cannot escape the realities of reimbursement risk faced by the entire molecular diagnostics sector (especially those companies offering high-priced tests). However, we believe several data points suggest Foundation may make more rapid progress on the reimbursement front than the market generally anticipates. The company recently won its first commercial payer coverage decision (Priority Health) and several large corporations (including Google) have decided to make the test available to emplo
Morgan Stanley $IMGN $3 full note: Negative MARIANNE news likely to push IMGN toward our bear case of $3/shr. We see greater risk for Kadcyla in the adjuvant setting.
Neither Kadcyla arm was superior to Herceptin alone: Recall that
MARIANNE investigated three arms: Herceptin alone, Kadcyla alone and
Kadcyla plus Perjeta. This morning Roche (covered by Vincent Meunier)
reported that while both Kadcyla containing arms were non-inferior to
Herceptin, neither arm was superior. Immunogen receives low-to-mid single
digit royalties from Roche on Kadcyla.
Worst outcome possible: We have previously discussed a few scenarios and
set the bar for this study as the Kadcyla plus Perjeta arm being 4+ months
ahead of the Herceptin plus Perjeta PFS delta over Herceptin alone in
CLEOPATRA. This clearly did not occur and in our view suggests that use of
Kadcyla in 1st line mBC is unlikely to be significant. Further, we believe that
today's results highlight the increasing risk of a positive Kadcyla outcome in
the adjuvant study due in 2018 - adjuvant represents the bulk of our Kadcyla
royalty valuation.
Expect sig. downside in IMGN: Given this negative outcome we would
expect the market to be concerned about the durability of the Kadcyla royalties
and their ability to fund the underlying proprietary pipeline. If we only value
the 2nd line and beyond mBC opportunity for Kadcyla our royalty valuation
falls to ~$3/shr. While we would expect some hope to remain on the adjuvant
opportunity given that we have yet to see the PFS curves and if Herceptin
alone outperformed its prior historic PFS. Nonetheless, we believe IMGN is
likely to trade closer to our bear case (~$3/shr) on the news.
@HansKraaijeveld: Getting ready to do a V3 workshop at @TandbergData in Dortmund. @Sphere3D @ClientICTGroep #excited! http://t.co/3vtWa5ZUhS
http://www.healthcareglobal.com/top10/1716/TOP-10:-Research-Companies-on-the-Forefront-of-HIVAIDS-Eradication
1. Calimmune
Founded in 2007, Calimmune has been at the forefront of developing innovative cell-based therapies for HIV/AIDS. The company formed around stem cell technology discovered in the labs of Nobel Laureate, Dr. David Baltimore (Caltech) and Dr. Irvin Chen (UCLA AIDS Institute) in early 2000.
Calimmune announced groundbreaking news earlier this year when they reported that encouraging results from the first group of participants in an HIV stem cell gene modification study were leading to a second cohort in a clinical trial involving the use of Cal-1, an innovative gene-based stem cell therapy to help protect individuals infected with HIV from progressing to AIDS.
In the first phase of this study, four HIV-positive participants were infused with their own blood stem cells as well as mature T cells that had been modified to carry a gene that blocks production of CCR5. The hope is that those stem cells will then create a new blood system that is resistant to HIV. To guard against the virus forming resistance, the team has used a second mechanism to prevent the virus from fusing with the patient’s cells.
The second group of 3-4 participants will not only get Cal-1 but will also get a preconditioning regimen with the aim of making the therapy more effective.
“With more than one million Americans living with HIV, there is clearly an urgent need for a therapy that does more than just hold the virus at bay,” says Jonathan Thomas, Ph.D., J.D., Chair of the stem cell agency’s governing Board. “Current medications are effective, but come with a big cost both in terms of dollars and side effects. Our goal is to find an approach that effectively cures people with HIV/AIDS.”
Dew
Calimmune is using Benitec's ddRNAi technology BNIKF. All I know.
$ACHN JMP Hoping for an early gift from Achillion Pharmaceuticals, we take a deep dive into
expectations for nuc data; we reiterate our Market Outperform rating and place
our price target under review as the stock is trading above our prior $13 target.
Investors are eagerly awaiting the first look at the efficacy of Achillion’s HCV nucleoside
inhibitor (nuc), which we believe is imminent. Based on our analysis of the available
data, we feel that an ~4.5 log viral load reduction would set ACHN’s nuc on par with lead
nuc inhibitor GILD’s sofosbuvir, and when combined with Achillion’s best-in-class NS5a,
it could pave the way to a shorter regimen (which sofosbuvir never quite achieved) and
likely entice an acquirer. Given the strength of the NS5a and the availability of a third
agent, a protease inhibitor, we think there may be some tolerance for slightly lower
activity, down to 4.0 log on the low end. In addition, the upcoming 6-week data, using
sofosbuvir as a placeholder for Achillion's own nuc, while not likely a viable duration on
its own, could highlight the power of the NS5a. We spent time with management earlier
this week and detected a sense of optimism and calm and we look forward to a nearterm
unveiling of the data.
Investors are eagerly awaiting the first look at the efficacy of Achillion’s HCV nucleoside inhibitor (nuc)
that the company has promised “this fall”, which ends December 20. To help investor’s understand
what will constitute “good” data, we analyzed data from other nuc programs. The goal of HCV therapy
is to cure patients and, unfortunately, the only data we have correlating early anti-viral activity to cure
(SVR) is from Gilead’s sofosbuvir and Vertex’s VX-135, which is a relevant comparator for our
purposes even though it was discontinued for safety reasons. As we look forward, Merck is bringing
forward MK-3682, so we include this as a potential part of the future landscape, although we have little
data on this program given its early stage of development.
FIGURE 1. Nucleoside Inhibitors Top-Line Data
Company GILD MRK
Compound sofosbuvir IDIX-437/MK-3682
Dose 400mg 100mg 200mg 300mg
Viral reduction at 7 days 4.7 3.9 4.5 4.3
SVR in combo with NS5a, 12-wk regimen 96% [1] 73% [2] 83% [3] NA
Status approved Phase 1/2
[1] combo of sofosbuvir + ledipasvir in ION studies
[2] combo of VX-135 + daclatasvir
[3] 1 patient discontinued after first dose; SVR is 91% in patients who completed 12 weeks
VRTX
VX-135
suspended
Source: Company reports
Quick background on ACHN’s study
ACHN is conducting a proof-of-concept, 7-day monotherapy study of its nucleoside inhibitor, ACH-
3422, in genotype 1 HCV patients in Australia and New Zealand. The study includes four doseescalating
cohorts starting at 50mg, the highest dose has not been disclosed. We believe the highest
dose could be up to 150mg, as management noted that doses up to 150mg evaluated for 14 days were
well-tolerated in healthy volunteers. We expect top-line antiviral results by the end of December.
Gilead’s sofosbuvir (SOF) achieved viral load reduction of 4.7 log at day 7, with half of the patients (4/8)
reaching undetectable at day 7. VX-135 200mg came close with a 4.5 log reduction, followed by MK-
3682 monotherapy at 4.2 log and VX-135 100mg dose at 3.95 log. SOF and VX-135 200mg appear to
have more rapid viral kinetics as demonstrated by the day 3 viral drop of 3.9 log vs. ~2.2-2.4log for MK-
3682 and 2.6 log for VX-135 100mg. To make the correlation to the ultimate goal SVR, we only have
data for SOF and VX-135. For these two examples, we can say that higher is better, where SOF came
in at 96% for 12 weeks for its combination with ledipasvir NS5a, versus 91% (excluding patient who
discontinued after one dose) for VX-135 200mg in combination with BMY’s daclatasvir NS5a and 73%
with VX-135 100mg with daclatasvir. More powerful early anti-viral activity seems to drive higher cure
rates, based on our analysis of the data.
For Achillion, a viral reduction of 4.5 log with ACH-3422 will give us comfort that ACH-3422 can achieve
competitive SVR when combined with its NS5a inhibitor ACH-3102. However, ACH-3102 appears to be
more potent than other NS5a inhibitors, so perhaps this could boost the efficacy even further or make
up for a slightly less impressive early anti-viral activity of the nuc in the 4.0 range. If the monotherapy
activity falls below 4 log, we believe Achillion would have to introduce a third drug (protease inhibitor)
into the cocktail to develop a competitive regimen.
We hosted several investor meetings with management this week where we learned that the company
has set 3.5 log as a go/no-go threshold on ACH-3422 based on scientific rationale. In Achillion’s view,
activity of 4 log or greater puts the 8-week dual regimen on the table.
We emphasize that long-term safety is required to de-risk this program.
TAKING IT TO THE NEXT LEVEL – SHORTENING THERAPY
The next opportunity for innovation is to shorten therapy to two or even one month, the latter would
represent a significant advancement given the need for a single month-long prescription. However, key
opinion leaders and regulators are not willing to sacrifice any efficacy for shorter duration, so this
remains a lofty goal. Can Achillion get there? We feel that with SOF-like activity and a better NS5a, 8-
week duration is possible; however, much will depend upon the strength of the nuc ACH-3422.
6-week “PROXY” data – 6-wk blue-sky scenario but important to validate 8-wk regimen. ACHN is
set to report 6-week data for its NS5a inhibitor, ACH-3102, in combination with Gilead’s sofosbuvir
(SOF) by the end of December. The study serves as a proxy for ACHN’s own combo regimen of NS5a
inhibitor ACH-3102 and nuc ACH-3422. Achillion’s NS5a appears to be fairly potent and thus far, we
view it as best in class. We believe this data serves several purposes: 1) to show the power of the
NS5a; 2) to potentially show that a 6-week regimen is possible; and 3) at a minimum, it shores up the
8-week regimen.
Assuming that ACHN’s upcoming nuc ACH-3422 antiviral data are on par with that reported for SOF,
we expect:
? ACHN is unlikely to shorten duration of treatment to 6 weeks with two direct antivirals, and we
believe a third DAA would be required in the cocktail to achieve this goal. A 100% SVR rate
would put the 6-week regimen on the table, but it is a blue sky scenario, in our view. Beyond,
SVR, relapse rates will be critical to evaluate.
? SVR of >85% for the 6-week regimen would give us comfort that ACHN could shorten the
duration of treatment to 8-weeks. Anything less than this threshold might introduce uncertainty to
the viability of the 8-week regimen with a dual regimen.
Achillion’s NS5a appears to be best in class. The antiviral activity for ACHN-3102 appears to be
better than GILD’s GS-5816 and ledipasvir, as monotherapy (Figures 3-6). Specifically, ACH-3102
achieved a 3.8 log viral load reduction with a single dose. GS-5816 achieved a comparable 3.6 log
reduction with three doses and the viral curve for GS-5816 shows a slower viral HCV RNA decline.
Ledipasvir appears to have nearly maxed its viral clearance after a single dose, although we note a
slightly lower 3.3 log HCV RNA reduction compared to 3.8 log with ACH-3102. This data might explain
why ACHN achieved a 100% SVR rate with ‘3102 on the background of SOF, which GILD’s NS5a
inhibitors have not quite hit, with a caveat of cross-trial comparisons and small samples in Phase 2
studies.
An 8-week regimen is possible for ACHN if other things line up
ACHN-3102/SOF is the only dual regimen that produced a 100% SVR rate with 8-week treatment
duration (Figure 7). The data are particularly impressive because 9 out of 12 patients had high viral
load at baseline, suggesting more difficult-to-treat patients in the ACHN study (Figure 7). We are also
encouraged by the potentially better antiviral activity of ACH-3102 as monotherapy, compared to
GILD’s NS5a inhibitors, which could bridge ACHN into 8-week duration that GILD’s Harvoni has not
quite achieved, assuming that ACHN’s nuc looks similar to SOF. Given the small size of the 8-week
ACHN dataset, we would like to see this data validated in additional studies, including the 6-week trial
discussed below. The data point that gives us a pause on 8-week duration is the viral kinetics at 2 and
4 weeks on treatment with ACH-3102/SOF, as reviewed below.
Speed of viral clearance leaves 8-week duration with dual regimen on the fence. ACHN reported
that 83% of patients achieved viral load below the lower limit of quantification (LLOQ, <25IU/mL, virus
can be detected but not quantified) at 2 weeks and 100% at 4 weeks. At the same threshold of
<25IU/mL, these data are comparable to Harvoni (Figure 8). However, at the lower threshold of
<10IU/mL where virus cannot be detected, ACHN’s data looks slightly worse than MRK’s data at
<15IU/mL, particularly given that MRK’s 8-week data were generated in difficult-to-treat cirrhotics.
While not a strictly direct comparison, the speed of viral clearance with ACHN’s regimen appears
comparable to that of GILD’s (8-week not achieved for all patients) and it might be slightly slower than
MRK’s regimen (8-week duration might be viable based on Phase 2 data). The speed of viral clearance
is important to prevent relapse after treatment.
6-weeks has been an elusive goal so far
We reviewed the available data for various MRK and GILD combinations, all on the background of SOF
evaluating 4- to 8-week treatment durations. The only regimen that looks good at 8 weeks is the triple
combination of MRK’s NS5a, protease inhibitor, with SOF, which is not commercially viable and so
MRK will repeat the study, switching out its nuc, MK-3682, for SOF hoping to drive an 8-week regimen.
To date, we have not seen any data suggesting that 6 weeks is viable. We do not view ACHN’s ACH-
3102-based regimen as significantly better than others reviewed below to gain confidence in a 6-week
regimen, but we think an 8-week regimen may be possible, depending upon the strength of the nuc.
? MRK’s 6-week regimen ok but not good enough, going forward with 8-week regimen.
MRK’s triple regimen (NS5a/PI/nuc), while producing a 95% SVR rate with 8 weeks, fell short on
the 6-week duration with 87% SVR and an even lower 39% SVR with 4 weeks. The viral
kinetics curves for ACH-3102/SOF does not appear better than with the MRK regimens (Figure
8), suggesting that it might be difficult for ACH-3102/SOF to achieve significantly higher SVR
rates with a 6-week regimen than MRK. We believe MRK will advance the 8-week duration, but
that it might make an attempt at a 6-week regimen with its newly acquired nuc and novel NS5a.
? Gilead’s sofosbuvir combo (Harvoni) not good enough. GILD’s Harvoni (ledipasvir/SOF)
resulted in high SVR rates in just 8 weeks (94% SVR rate in the Phase 3 ION-3 and 95% in
Lonestar). However, it was approved for 12 weeks as the 8-week regimens produced an
unacceptably high 10% relapse rate in patients with high viral load. When the duration of
treatment was shortened to 6 weeks in one of the Phase 2 studies, the SVR rate dropped to
68%, even on the background of RBV. The week 2 and 4 on treatment data for Harvoni and
ACH-3102/SOF are comparable, suggesting that a 6-week duration may be a long shot for
ACHN.
? Novel dual pan-GT GS-5816/SOF failed the 8-week duration, going forward with a 12-week
duration. GILD’s dual pan-genotypic regimen GS-5816/SOF resulted in a 90% SVR rate when
evaluated at 8 weeks. No data are available for this regimen at 6 weeks, but we note that GILD
is evaluating a 12-week duration in ongoing Phase 3 studies, implying that 12 weeks is needed.
? GILD’s triplets produced viable SVRs at 6 weeks. The only viable SVR rates at 6 weeks were
produced by GILD’s triple regimens that included a non-nuc and protease inhibitor. However,
Gilead has said that it will not pursue protease inhibitors given potential safety concerns and
thus, we think these are off the table.
Dew you really need to buy the stocks you pic
Awesome job FIRST place
http://www.siliconinvestor.com/readmsg.aspx?msgid=29849298
CELG: Additional Color From Abraxane Neoadjuvant Therapy SABC Supports Potential For Meaningfully Expanded Use
From WF
Sector Rating: Biotechnology, Market Weight
**Following the presentation on the Abraxne neoadjuvant breast cancer ph.III data, we had a chance to further review the slides. Several additional takeaways:
**Rates of pathological CR (pCR) look strong across all subgroups tested, reaffirming Abraxane's benefits. In particular, data appeared robust in triplenegatives (pCR 48%, vs. 26% standard paclitaxel, odds ratio 2.69), who represent 15% of the population with a high unmet needrecall TNBC is a difficult breast cancer subtype to treat, since most chemotherapies target receptors, such that triplenegative cancers often require combination treatments with greater tolerability/toxicity profiles. U.S./EU adoption solely in this subgroup, assuming 3 cycles at current pricing, would provide an opportunity of >$700M.
**Data was consistent across multiple definitions of pCR, including those delineated by FDA, which should help potential regulatory case.
**Efficacy does come at cost of some side effects. Abraxane treatment was associated with higher rates of certain hematological toxicities, including anemia of any grade (92.4% versus 88.3%, p=0.019), and neutropenia of any grade (87.3% versus 81.5%, p=0.007); gd.3/4 hematologic tox was not statistically worse though it trended greater for Abraxane. Nonheme tox was also notably higher for Abraxane, including sensory neuropathy and handfoot syndrome, as well as rash, fatigue, and diarrhea. This benefit/risk equation, as well as confirming whether the trial is registration quality (we note lead PI consulted to FDA on approvability guidelines, a positive sign), would likely go into FDA's assessment of whether Abraxane's pCR advantage in light of its added side effects would likely confer ultimate PFS/OS benefits to support accelerated approval on this surrogate. The lower discontinuations due to disease progression for Abraxane patients (1.7%, vs. 5%) is another directionally favorable sign.
**BOTTOM LINE: Though efficacy comes at some side effect costs, totality of data suggests accelerated approval for a neo adjuvant label is very possible, as is offlabel use of Abraxane in this setting, potentially significantly expanding Abraxane sales and augmenting CELG's topline growth. Reiterate Outperform.
CS on TGTX
TG Therapeutics (TGTX)
TGR-1202 is a delta specific inhibitor most similar to GILD's idelalisib. It is being developed in combination with TGTX's proprietary anti-CD20 antibody. Alone, these assets would be less interesting but because TGTX has global rights (excluding India) to drugs in two validated and combinable drug classes for NHL and CLL, TGTX is an attractive strategic acquisition target for a hem/onc company such as PCYC, CELG, or JNJ that have complementary programs (e.g. BTK inhibitors). The assessment of the risk of TGR-1202 to INFI will largely depend on whether TGTX is acquired or partners and who the acquirer/partner is
TGTX: Oh What an ASH; Now What? Target
Upped to $33; Reiterate Focus Pick
We believe TG had a very strong ASH and these are our two key takeaways: 1)multiple positive KOL views on the data strength and especially the safety profiles of TG’s drugs relative to the competition and 2) we think Pharmacyclics (PCYC-Buy) just takes it out. Reiterate Focus Pick and increasing price target to $33 from $25.
Event
In an oral presentation at ASH, data were presented from the combination study of TG's two lead drugs, TG-1101 and TGR-1202. Additionally, a third cohort was added by adding Pharmacyclics' (PCYC-Buy) Imbruvica for a "triplet" therapy. 100% of CLL/SLL patients (9/9) saw nodal reductions (6/9 with PRs with 3/9 on study showing nodal reductions ranging from 15-45%). 83% response rate in 5/6 NHL patients (3/3 DLBCL and 2/3 FL) who responded at highest dose treated, including two CRs in DLBCL (GDB subtype representing dire unmet medical need). These CRs were independently confirmed. Early data from the triplet therapy including Imbruvica showed that five patients could be treated safely in heavily pre-treated NHL, CLL and Richter's transformation patients. No dose limiting toxicities or Grade 3/4 adverse events were seen. 2 of 3 evaluable patients have shown responses including a follicular lymphoma (FL) patient who was refractory to both Imbruvica and Ritux00 delivering a pivotal stage company.
We believe TG had a very strong ASH and these are our two key takeaways: 1)multiple KOL positive views on the data strength and especially the safety profiles of TG’s drugs relative to the competition and 2) we think Pharmacyclics (PCYC-Buy) just takes it out. We are likely days away from the start of the first Phase III study with TG-1101 and PCYC’s Imbruvica. The Phase II update from this combination was quite positive, in our belief, and we believe is a very strong proxy for the success of the Phase III. Looking forward for the shares, we believe TG is in its relative infancy with regard to its true Street visibility based on both early skeptics and the data which have quickly evolved into
We reiterate our Buy rating, Focus Pick and are raising our price target to $33 from $25. We believe that TG is positioning itself strongly with its lead candidate drugs, with the potential to be integrated in the evolving standard of care for B-cell malignancies.
Intraday price: $13.89 at 10:04am ET, 12/10/14
CS - CELG a top pick for 2015 - raising target from $125 to $145..Domain Dominance-3 blockbusters, pipeline and patent settlement will provide additional upside...
Key picks from our 46 stock coverage universe: Large Cap – Biogen (TP400) – three high-reward catalysts; CELG (TP$145) – continued "domain domination" premium and patent settlement upside. Smid Cap – OVAS (TP $60) – potential paradigm shift in IVF, ATLN (TP SFr135) – Longer term Uptravi potential, CLDN (TP $20) – high risk/higher reward catalyst due in Q1, IRWD (TP $18) – Linzness ramp + pipeline appreciation, PCTC (TP $66) DMD leader + growing pipeline, ESPR (TP $41) – Catalyst rich 2015.
¦ Target price and recommendation changes: We are making the following key changes to our coverage universe: We are downgrading UTHR to Underperform (from Neutral) while increasing our TP to $120 (from $100). We are also making several target price changes as follows: AMGN $180 (from $160), CELG $145 (from $125), ALXN $200 (from $184), VRTX $130 (from $94) BMRN $95 (from $75), ENTA $55 (from $44), IRWD $18 (from $16), XNPT $10 (from $7), ACHN $12 (from $10), SCMP $10 (from $8) and MVIR'B-SK SEK125 (from SEK115).
Celgene – Outperform, TP $145 (from $125 previously): We are increasing our TP for CELG to $145 (from $125 previously) and retaining our Outperform recommendation. Our positive outlook for CELG is driven by a combination of strong growth from CELG's current base business combined with its "Domain Domination" and concomitant pipeline. We expect Celgene to continue to post strong growth driven by the recent launch of three blockbuster drugs – Pomalyst, Abraxane and Otezla with a patent settlement for Revlimid providing further potential upside. We also view Celgene as a company that is furthest along the track to achieving domain domination especially in the areas of dominating the science and translating it into efficacious research, deep knowledge of the regulatory pathways and dominating marketing of products. On CELG’s pipeline, we believe that GED-301 in Crohn’s disease could be a potential blockbuster with the potential to change the entire disease paradigm. Our TP of $145 implies a multiple of ~22.5x on our '16 EPS estimate of $6.44, representing a 50% premium to the '16 PE multiple of the S&P500. We believe this premium is warranted due to the >20% top- and bottom-line growth that CELG appears set to deliver from 2014 to 2017.
Nomura - Abraxane better- Substantial opportunity in neoadjuvant early high risk breast cancer.Impressive Ph 3 ready pipe (AGIO,XLRN,etc), RLI triple combos & lymphoma..Upward revisions to guidance coming Jan 2015...$136 tgt....
Nomura
RatingBuy
Target price USD $136.00
Positive Neoadjuvant BC Data For Abraxane
Positive results for Abraxane as neoadjuvant chemotherapy in early high risk breast cancer were presented by the German Breast Group at the 2014 San Antonio Breast Cancer Symposium. We believe the neoadjuvant setting represents $500mn-$1bn in incremental Abraxane sales, potentially providing a boost to long-term Abraxane projections when new guidance is given early next year. CELG remains our top large-cap pick heading into 2015, with approval expected for Revlimid front-line/maintenance MM therapy in Europe (1H15) and the US (Feb 22, 2015 PDUFA), and emerging data in lymphoma to open up a $3-4bn opportunity. We believe recent ASH data pointed to triple combos that firmly establish Revlimid as a backbone in myeloma, combined with an impressive Phase III ready pipeline (Agios, Acceleron, etc.) that could lead to new 5-year guidance and upward revisions to Street estimates in Jan. 2015.
? Abraxane better than paclitaxel in neoadjuvant BC. The Phase III
results showed 38% of Abraxane patients achieved pCR (pathological
complete response), a significant improvement over paclitaxel’s 29%
(p<0.001). Patients reaching pCR after neoadjuvant treatment have shown
to have longer term benefit. The FDA has accepted pCR as a surrogate
marker for accelerated approval in high risk breast cancer.
? Abraxane dosing was lowered after interim safety analysis. The final
dose used was 125mg/m2, about half of the recommended dose for
refractory breast cancer (260mg/m2). The initial higher dose was reduced
as toxicities caused higher dropouts (17% vs 6%), but Abraxane lead to
lower incidences of local disease (1.7% vs 5%). Analysis of toxicities for
the lower dose is planned.
? Substantial opportunity in neoadjuvant early high risk breast cancer.
We believe early treatment for high risk breast cancer is growing. High risk
markers like HER-2 are estimated to be about 20% of breast cancer. We
estimate an incremental $500mn to $1bn in peak sales of Abraxane in
neoadjuvant early high risk breast cancer
Jmp on kpti
Karyopharm Therapeutics shares have declined approximately 23% over the past five days after what we believe to have been an outstanding showing at ASH; reiterating our Market Outperform rating and $57 price target based on DCF, CAGR and SOTP methodologies. KPTI shares have declined sharply since the conclusion of ASH and what we felt was a strong investor event on the evening of Monday, December 8. While we would expect some weakness in many of our ASH names once their specific data catalysts are removed, we believe the recent sell-off in the stock is overdone, and we urge investors to take advantage of the current weakness to accumulate the shares.
Investor concerns over multiple myeloma strategy misplaced. During the recent investor meeting held at ASH 2014, the selinexor clinical development strategy and timeline was outlined for all of the company's hematologic cancer indications, including AML, Richter’s syndrome, DLBCL, and multiple myeloma. Regarding myeloma, the company believes that based on its recent Phase I results it can quickly move into single-arm, registration-directed multiple myeloma trials and receive approval before the advent of the novel monoclonal antibodies, including elotuzumab and the anti-CD38- based combinations. Additionally, KPTI’s combination development strategy will allow it to gain full FDA approval with existing standard of care therapies including proteasome inhibitors (Kyrpolis/Velcade) and iMiD’s (Pomalyst, Revlimid).
Initiating third selinexor registrational trial in DLBCL. The company today announced the initiation of a Phase II trial for the treatment of patients with relapsed/ refractory diffuse large B-cell lymphoma (R/R DLBCL) termed SADAL (Selinexor and Dexamethasone in Aggressive Lymphoma). This study represents the third registration- directed trial of selinexor, and complements the other two trials of selinexor for the treatment of R/R AML (SOPRA) and for the treatment of Richter’s transformation (SIRRT). This open-label Phase 2b study will evaluate the safety and efficacy of high-dose (100 mg) versus mid-dose (60 mg) Selinexor in combination with low-dose dexamethasone. This announcement follows the recent preliminary results from the ongoing Phase I trial in patients with heavily treated R/R non-Hodgkin’s Lymphoma (NHL), which demonstrated a 40% ORR in patients treated with high-dose selinexor and a 37% ORR in patients treated with mid-dose. Importantly, this study had enrolled four patients with double-hit DLBCL, a recently established predictor of highly refractory disease after conventional therapy. All four patients had responses with one patient in remission at over one year. The FDA has stipulated that at least half the patients in SADAL be of the germinal center B-cell (GCB) subtype, a particularly recalcitrant form of the disease. In our view, a response rate of 30% with meaningful durability would qualify selinexor for approval.
CS aria Changes to our valuation
We are decreasing our TP to $6 from $8 and we highlight the changes we made to our valuation below.
¦ We have reduced our outlook for Iclusig in the earlier lines of therapy based on re-launch metrics: We think Iclusig is largely reserved for the sicker patients that typically stay on therapy for a limited period. On the Q3:14 call, ARIA disclosed that about 50% of the CML patients were in chronic phase, implying that 50% were in accelerated or blast phase which typically have much shorter treatment duration. Approximately 20% of the CML patients were second line, but the "majority" (we assume a large majority) of second line CML patients were T315I patients.
¦ Changed our pricing assumptions to account for "flat pricing": We have increased our blended price for Iclusig over our prior assumptions for Q4:14 and 2015. We also assume that ARIA will increase the overall price point once it moves to the true flat pricing following the introduction of the 30mg pill in H2:15.
¦ Lowered AP26113 projections: We decreased the penetration into the front line and relapsed/refractory lines of therapy given that AP26113 is likely to be the third or fourth ALK inhibitor to market.
¦ Removed premium for a takeout as a debt offering suggests it unlikely near- term: The recent debt offering suggests that ARIA is more likely to pursue a go alone strategy rather than a near-term acquisition. We model the next capital raise in H1:16.
Changes to our valuation
We are decreasing our TP to $6 from $8 and we highlight the changes we made to our valuation below.
¦ We have reduced our outlook for Iclusig in the earlier lines of therapy based on re-launch metrics: We think Iclusig is largely reserved for the sicker patients that typically stay on therapy for a limited period. On the Q3:14 call, ARIA disclosed that about 50% of the CML patients were in chronic phase, implying that 50% were in accelerated or blast phase which typically have much shorter treatment duration. Approximately 20% of the CML patients were second line, but the "majority" (we assume a large majority) of second line CML patients were T315I patients.
¦ Changed our pricing assumptions to account for "flat pricing": We have increased our blended price for Iclusig over our prior assumptions for Q4:14 and 2015. We also assume that ARIA will increase the overall price point once it moves to the true flat pricing following the introduction of the 30mg pill in H2:15.
¦ Lowered AP26113 projections: We decreased the penetration into the front line and relapsed/refractory lines of therapy given that AP26113 is likely to be the third or fourth ALK inhibitor to market.
¦ Removed premium for a takeout as a debt offering suggests it unlikely near- term: The recent debt offering suggests that ARIA is more likely to pursue a go alone strategy rather than a near-term acquisition. We model the next capital raise in H1:16.
Someone asked me to post CS
Downgrading to Underperform: Launch Metrics Still Weak & Price Benefit Likely Temporary
We believe that Iclusig will likely remain the last option for CML patients who have specific resistant mutations or fail other therapies. Neat-term US sales will benefit from the implementation of the new pricing strategy that doubled the 30 mg price. However, we think this will likely be short-lived and sales will face a drop in H2:15 when ARIA moves to true flat pricing. We are downgrading to Underperform and reducing our TP to $6 from $8. Model changes increase our 2015 EPS estimates and decrease our 2016 EPS estimate.
¦ Launches still tepid in US and EU: Metrics for the re-launch suggest Iclusig is reserved for the sicker patients and this trend is not likely to change until ARIA provides new clinical data, which could be at least 18-24 months away. ARIA estimates half of CML patients receiving Iclusig are chronic phase patients. We think the large majority of second line CML patients are T315I patients, indicating that doctors are reluctant to use Iclusig ahead of other approved TKIs in patients without resistant mutations.
¦ Hangover from new pricing likely in H2:15: ARIA doubled the price of the 30mg dose by replacing its 60-count 15mg bottle with an equivalently priced 30-count 15mg bottle on Sep 8th (Figure 1 and 2 on page 2). This move increased the average price per patient by 57% to ~$175,000 from ~$111,000 (assuming same dose distribution as Q3). While this will markedly increase sales in Q4:14 and H1:15, we believe there could be a hangover once ARIA goes to true flat pricing (likely H2:15). That said, this might be the first step to ARIA moving to "orphan drug pricing" in the CML setting, which could cause a backlash with payors and/or physicia
Thanks Wes. In my 25 years investing exp
IMHO. Once money is raised. NEWS usually is not far behind
JPMorgan $BLUE Updating Model Post #ASH14 Target to $103 Following BLUE’s update at ASH earlier this week, the co held a call Wednesday morning to review the data presented for its gene therapy,
LentiGlobin. Not much new came out of the call; however, the co not only reinforced
LentiGlobin’s compelling potential in Beta-Thalassemia (B-Thal), but also reiterated
their excitement about the sickle cell disease (SCD) opportunity. Indeed, we are
incrementally more positive on the prospects in SCD (a substantially larger
opportunity than B-Thal) coming out of ASH, which was further reaffirmed
Wednesday as the co provided a rationale of why results seen in B-Thal could have
positive read-through to SCD. With additional updates on B-Thal, our first look at
sickle cell data, and the potential emergence of the co’s CAR-T program partnered
with CELG, all expected next year, 2015 is shaping up as a another banner year for
BLUE. We are reiterating our OW rating—BLUE remains a top small cap pick and
on the J.P. Morgan Focus List—and increasing our YE15 PT to $103 from $53.
? Why LentiGlobin could work in SCD. BLUE provided rationale as to why it is
optimistic about the potential of LentiGlobin in sickle cell disease. In SCD, pts with
the trait but a normal B-globin gene (60-70% of total Hb and 30-40% sickle globin)
are asymptomatic, suggesting if corrected globin could reach 60-70% in SCD pts, a
functional cure could ensue. Additionally, pts with elevated levels of hemoglobin F
(~30%) have a “dramatic attenuation” of SCD. Furthermore, the co pointed to use
of hydroxyurea (only approved drug for SCD) which works, in part, by raising HbF
levels and even with modest elevations (~15-20%) a clinical benefit is observed.
Lastly, there is some evidence from allogenic transplant literature showing a partial
engraftment of normal donor cells that make up no more than 15-20% of the total
hematopoietic cells leads to an effective clinical cure. For reference, the proportion
of vector derived Hb seen in B-Thal pts so far ranges from 40%+ to 70%+.
? Model update; increasing our Dec 15 PT to $103 from $53. We have added SCD
revenue into our model assuming a still modest 25% prob of success, and we have
also slightly increased the POS we assign to B-thal (to 55%). The net effect of our
changes is an increase in our Dec15 price target to $103 from $53.
? Upcoming events. Additional updates from the Phase 1/2 studies for LentiGlobin in
B-Thal major (from the HGB-205 and Northstar trials) are expected in 2015;
enrollment in both studies is expected to be completed in 2015. In addition, the first
clinical outcomes for SCD pts treated with LentiGlobin should be available in 1H15
(from the HGB-206 US trial). CAR-T could also enter the clinic in 2015.
DEW you appreciate this on tgtx
What the KOLS are saying on 1101 and 1202 from roth report
Msg 193147 of 193158 at 12/10/2014 6:14:01 PM by
dougheuring
OT TGTX what the KOLS are saying about 1101 and 1202
Summary of Physician Commentary
Dr. Jeff Sharman - U.S. Oncology
Dr. Sharman is the principal investigator (PI) on the ongoing Phase II TG-1101/Imbruvica combo study and will be the PI on the GENUINE Phase III study, which is expected to begin imminently. Regarding the data update at ASH showing 95% ORR in high risk CLL (targeted population for the Phase III), Dr. Sharman indicated that the responses seen in the study were rapid and attributed it to 1) the change in "compartment" from lymphocytosis from Imbruvica and 2) rapid "clearing" of those cells by TG-1101. He mentioned that Imbruvican is not a "perfectly easy drug" based on the arthralgias and diarrhea seen. However, in discussion TG-1101, he has seen a low rate of infusion reactions and has conducted a lot of work with Gazyva, which has led to rapid and intense infusion reactions (not the case for TG-1101). Regarding the CLL population in the study and for the Phase III, do expect good lymph node responses but with the concomitant lymphocytosis and the addition of TG-1101 has provided an exciting path forward. When you look at Imbruvica alone, the lymphocytosis is well known, however it leaves a "disease burden" following treatment with a BTK or other TKI inhibitors, which does not necessarily help the prognosis for the patients. With the addition of TG-1101 the data suggest more clonal eradication at earlier timepoints (i.e. fewer cells left behind to confer resistance).
When asked about having duration data from the combo study, the audience was reminded that the Phase II was designed as a 6-month study, so patients were taken off of TG-1101, so was not set up to answer that question (though patients could stay on Imbruvica). Also he importantly indicated that he did not see performance/efficacy differences in patients who were either Rituxan-refractory or sensitive.
Regarding the upcoming GENUINE Phase III study, he reminded us that the expected monotherapy ORR with Imbruvica is in the 60-65% range and the combo study is powered to show a 15-20% difference.
Dr. Owen O'Connor - Columbia
Dr. O'Connor gave an updated from his work with TG-1101 as a monotherapy and provided a brief update from the Phase I/II study. Emphasis was placed again on the lack of observed Grade 3 or 4 infusion reactions with '1101. Recall that data presented at ASCO/EHA 2014 showed a 43% ORR in patients relapsed/refractory to patients and a MZL patient we previously highlighted just crossed the two year mark of her complete response. Recall that this MZL patient was going to be sent to hospice after failing four prior Rituxan regimens and when she went on TG-1101, converted to a complete response. 11 of 30 patients on the Phase I/II study are >1 year and two patients are >2 years on study.
Dr. Manish Patel - Florida Cancer Specialists - Sarah Cannon
Dr. Patel's focus was is participation in other PI3K-delta inhibitor studies and points to the TGR-1202 monotherapy's adverse event profile, especially the very low frequency of Grade 3/4 events. For TGR-1202, no colitis has been seen, no hospitalization has been required for diarrhea and no pneumonitis has been seen with all AEs being <10% in frequency. Only two patients came off of the '1202 study, one with Legionaires pneumonia (unrelated) and with pneumonia (possibly related). Dr. Patel also indicated the intriguing nature of how the nodal responses improve with time.
Dr. Nathan Fowler - MD Anderson
As discussed above, Dr. Fowler was impressed about the TG-1101/TGR-1202 combo study being accepted for oral presentation at ASH despite small patient numbers at the time of submission. This study also added a dosing cohort that included Imbruvica so we are excited to see not only the doublet combination but also what the incremental improvement in responses may be from the triplet. Safety was the focus again as there has been a significant lack of transaminitis.
More focused commentary on safety
It was asked whether colitis could still emerge as an AE with '1202. Dr. Patel indicated that with all PI3K inhibitors he has worked with (irrespective of class) colitis comes out late. In the '1202 study the median time on drug is ~6 months with many patients on 1.5+ years and believes would have seen colitis by now if were to be a treatment emergent adverse event.
When asked about '1202 vs. other inhibitors such as IPI-145 or idelalisib, the docs can tell who is on what drug based on the AE profile and dose adjustments seen. With the other drugs, recall physicians have seen up to 20% transaminitis and up to 50% of patients seeing dose reductions.
Dr. Fowler has worked on almost all Phase I studies with BTKs and PI3Ks. For the '1202 data, while the numbers are relatively small, the data are holding. In mentioning a competitive product, one PI3K patient has severe colitis and severe diarrhea requiring hospitalization and vasopressor treatment for hypotension. TGR-1202 is "just not the same."
Dr. O'Connor has just recently started using idelalisib and he has seen AE differences right off the top with diarrhea, LFTs and maybe colitis.
When Dr. Fowler was asked about impressions about ABT-199, he indicated that he is continuing to work through the tox profile (including fatal tumor lysis syndrome) and is more difficult since he focuses on patients with low grade disease.
Lastly an Imbruvica anecdote was given regarding MCL patients. Once patients start to progress following Imbruvica, the tumor is very aggressive and it was suggested that Imbruvican should not be stopped before transition to other drugs or a combination.
Bernstein comments CELG PCYC INFI And TGTX. TGTX finally being recognized by
Others From IV ROB CO big thanks
Bernstein "Celgene's Revlimid plus Rituxan Finally and Decisively Better Than Rituxan Alone in Front Line Follicular Lymphoma"
December 10, 2014
CELG, PCYC: Final ASH Session Offers Insights into Potential, and Problems, of Novel Orals in Follicular Lymphoma Coverage Initiation
o The final day of this year's ASH meeting was quieter than the frenzy of oral presentations, poster sessions, company events, expert consultations and one on one meetings that had marked the first few days. Investors seem to be coming back to earth after the explosive stock price moves earlier in the week, and already our attention is shifting to the back to back San Antonio Breast Cancer meeting.
o The most important insights we gained from the last day's presentations came from a series of phase I and phase II trial results for Celgene's Revlimid, PCYC's Imbruvica, Infinity's duvelisib (IPI-145) and TG Therapeutics novel CD20 antibody and PI3K inhibitor in follicular, or indolent Non Hodgkins Lymphoma (NHL). None of these drugs are approved for this indication today, but they are attempting to catch up with Gilead's Zydelig (idelalisib) in this indication, and to either improve on that drug's efficacy, or reduce its toxicity and tolerability issues. While every company still insists that they have significant commercial opportunities in this disease, it is becoming clear that not all of these drugs will have major roles. PCYC's Imbruvica has disappointing single agent activity in this disease, whereas single agent PI3kinase inhibitors do seem to have significant single agent activity. We also saw the first data for the three drug combination of a CD20 antibody, a PI3K delta kinase inhibitor and a BTK
inhibitor (Imbruvica) which has so far acceptable tolerability.
o Celgene's Revlimid plus Rituxan Finally and Decisively Better Than Rituxan Alone in Front Line Follicular Lymphoma. While it seems as though we have been talking about the Revlimid-Rituxan combination in NHL for nearly a decade, one of the presentations yesterday provided strong evidence that the ongoing phase III trials of this combination should be strongly positive at least for efficacy and should provide a platform for Revlimid to expand its indications from Myeloma and MDS. In the presentation yesterday, European investigators showed the results from a randomized phase II trial of Rituxan alone or with Revlimid in treatment naïve follicular lymphoma patients. The patients were relatively healthy, but had clinically significant disease necessitating early treatment and almost half were high risk. The treatment schedule was continuous dosing with a reduced dose (15mg) of Revlimid for 18 weeks, and four weekly Rituxan infusions from weeks 1 to 4, and then again from weeks 12 through 16.
154 patients were enrolled and randomized 1:1 to either Rituxan or the R2 combination. From the Rituxan alone arm, 21 patients discontinued treatment, mostly from stable or progressive disease at the first week 10 evaluation. From the combination arm, only 3 patients discontinued for stable or progressive disease. 12 patients discontinued from Revlimid alone mostly due to unacceptable toxicity. On an ITT basis, at week 10 the response rate increased from 45% to 75% with the addition of Revlimid,
and at week 23 the response rate was 61% to Rituxan alone, compared to 82% for the combination. The complete response rate increased from 25% to 36% and this difference wa statistically significant. The addition of Revlimid did increase the rate of grade 4 neutropenia and thrombocytopenia, and also added significant rash and hypertension to Rituxan alone. This study is still immature, and requires further follow up for PFS and OS, but it adds to the evidence that R2 really is a viable regimen in this indication, although it also confirms that Revlimid is hardly a benign drug when used in combination with other widely used medicines in these diseases. This is at the heart of the challenges (and delays) Celgene has
faced in trying to bring Revlimid to the B cell malignancies – the drug is active, and boosts the responses to other agents, but it also adds tolerability and toxicity liabilities, and it requires care in figuring out the
correct dose, and dose schedule, to maximize the drug's risk-benefit trade off. We remain hopeful about the drug's potential in follicular NHL, and to an extent also in ABC DLBCL; it has little activity in GCB DLBCL, and still seems likely to be left at the altar in CLL, with too many other more active drugs jumping into increasingly complex multi-drug regimens.
Here’s summary and then some PCYC and TGTX comments (moved up summary with CELG comments)
o PCYC's Imbruvica (ibrutinib) Shows Disappointing Single Agent Activity in Relapsed Follicular NHL.
Investigators presented phase II results for single agent ibrutinib in patients with relapsed/refractory follicular NHL. In an earlier phase I trial the response rate was 44% overall and at higher doses was
55%, with a median duration of response of 13.4 months. The trial presented yesterday enrolled 41 patients with relapsed and refractory FL. Patients were quite heavily pre-treated, with a median of 3 prior
therapies; 45% were Rituxan-refractory and 35% were refractory to their most recent treatment. The response rate in this trial was a disappointing 28%, with only 5% (2) complete responses. There was a
striking difference in the response rate between patients who were Rituxan-naïve (67%), Rituxansensitive
(but experienced) (42%) and Rituxan-refractory (6%) suggesting once again that there is some
sort of fundamental overlap between the activity of the two drugs and raising questions again about the
utility of Imbruvica-CD20 antibody combinations, at least compared to other combinations with less
mechanistic "overlap". 72% of patients had some reduction in tumor volume, but many of these
reductions were relatively modest (30% or less). For those patients who responded, the median response
duration was not reached, but surprisingly some patients progressed relatively quickly (at 3 and 5
months). The one year PFS was 50%, which is consistent with relatively unimpressive activity. The
Imbruvica adverse events and tolerability were consistent with prior studies, although 35% of patients
had at least one grade 3 or grade 4 adverse events including a single fatal bleed. While PCYC and JNJ are
proceeding actively with phase II/III trials in follicular and diffuse large B cell lymphoma, this study
suggests that at least in FL the drug's opportunity, with or without Rituxan, might be limited. Other
combinations may offer more promise, including those with checkpoint antibodies, other CD20
antibodies, Revlimid and other kinase inhibitors.
S TG Therapeutics Advances Novel CD20 Antibody/Novel PI3Kinase Inhibitor Combination. TG
Therapeutics (TGTX – not covered) are advancing their proprietary CD20 antibody ublituximab to
potentially compete with Roche's Rituxan and Gazyvo, in combination with their own PI3Kinase
inhibitor TGR1202. Their antibody reportedly binds to a different sequence on the CD20 target to
existing antibodies, and is designed to enhance antibody dependent cytotoxicity which appears to be a
key component of Rituxan's activity. The drug has previously shown some activity in patients who have
progressed on Rituxan, and is being developed for use in Rituxan's known B cell malignancy indications.
The company's PI3k is a small molecule kinase inhibitor suitable for once daily dosing with a tolerability
profile (so far) that seems to be free of the more serious adverse events associated with Gilead's Zydelig
(and Infinity's duvelisib). The trial presented yesterday was dose ranging for both the antibody and the
small molecule up to 900mg per monthly cycle of ublituximab and 800mg/day of the kinase inhibitor.
The study enrolled a mixture of different B cell malignancy patients, including 9 CLL, 9 FL, 7 DLBCL
(mostly GCB subtype) and 1 Richter's. The patients had a median of 3 prior therapies, and two thirds had
more than 2 prior Rituxan-chemo regimens. The main adverse events observed included neutropenia and
fever, infusion reactions and some nausea and diarrhea. No hepatic toxicity was observed through the
treatment duration so far. In CLL 6 of 9 (67%) responded, and all 9 patients remain on study; it is
possible that the response rate will increase with further treatment. The combination also showed
significant activity in FL and GCB DLBCL. Of the 9 FL patients enrolled, all had a reduction in tumor
burden, and one had a CR and another reached PR; 7 of 9 patients with FL remain on treatment. 3 of 7
(43%) patients with GCB DLBCL responded, including 2 PR's. This data is consistent with the results
seen with Gilead's Zydelig in combination with Rituxan in refractory FL, and the question remains
whether the tolerabilityof these two drugs will really be better than the existing agents with prolonged
treatment duration. TG also presented very early data for this same combination with Imbruvica in a
handful of refractory patients with NHL and CLL. Initially at least this "triplet combination" seems to be
quite well tolerated, with no early grade 3 AE's and no required dose reductions. Among the three
patients given this combination there was an interesting partial response in a patient with FL who had 4
prior treatments and was refractory to those treatments, and had also failed prior Imbruvica. The
company also reported a CR in a patient with mantle cell lymphoma, although this patients had not failed
prior Imbruvica and could well have achieved the CR with any one of the agents alone. The third patient
with Richter's transformed 17p CLL did not respond to the triplet. Overall this combination seems viable
from a safety and tolerability standpoint, and TG seem to be quite aggressive about exploring other
combinations early in their development, thus potentially catching up with incumbents and competitors.
S Infinity's Duvelisib (IPI-145) Shows Single Agent Activity in Follicular NHL but is it Differentiated
from Zydelig? Infinity's duvelisib is the most advanced competitor PI3K inhibitor to Gilead's Zydelig,
and is in an array of phase II and phase III trials in a variety of B cell malignancies. Infinity recently
announced a collaboration with AbbVie to jointly develop and commercialize duvelisib, and many
investors and observers assume that the drug will now be studied and developed in combination with
AbbVie's ABT-199. This study reported yesterday at ASH expanded on the dose of 25mg BID/day in
patients with indolent NHL (mainly FL). Patients enrolled were quite advanced, with a median of 3 prior
therapies and 37-43% stage IV. The median time on treatment was 12 months at the 25 mg dose being
advanced into pivotal trials, and 26% remain on treatment beyond 24 months. Three quarters of patients
at the 25mg dose have now discontinued, mostly due to adverse events (37%) or progression (21%). The
response rate at the 25 mg dose was 72%, with 33% (6) patients having complete responses and 33%
having PR's. An additional 22% had stable disease. The response rate in FL was 69%, with 38% CR's
and relatively rapid responses. 69% of patients were progression-free at 24 months at the 25mg BID dose
and the overall survival was 89% at 2 years. It appears that duvelisib is likely to produce a response rate
of about 65-70% in this disease, and the expected treatment duration seems likely to be in the 18 month
range. The main adverse events seen at any dose were liver enzyme changes (47-53%), rash (37-53%),
diarrhea and GI effects (32-50%), neutropenia (21-31%) and pneumonia and related lung disorders (21-
28%). We understand that there were some opportunistic infections in other parts of this trial, and it
appears to us that the tolerability of the product is not materially better than Zydelig, and duvelisib may
still carry its own additional liabilities. The company selected the 25mg dose for further development
based on the higher rates of GI and rash adverse events at the higher doses of the drug studied in this
trial. Duvelisib is clearly a drug with sufficient activity in this disease to justify further development
alone and in combination, although it is still hard to see what the compound's advantage is over Zydelig.
S Overall we conclude that FL remains up for grabs, at least in earlier lines of disease. These oral medicines all seem to offer additive efficacy on top of Rituxan, but all come at a price as well in terms of additional adverse events and tolerability issues. Of the group, Revlimid seems to be the most advanced in terms of potentially moving to front line, ibrutinib seems to have the most uncertain future, and duvelisib has clear and impressive single agent activity, but a profile that seems to have at least as many, if not more, adverse event liabilities compared to Gilead's incumbent Zydelig. Reassuringly, TG's data suggests that we don't yet have the ultimate combination, and more and more triple or quadruple
regimens are likely to be explored as more of these breakthrough drugs come to market in their first indications. The data from Europe suggest that durable responses can be achieved in this disease without capitulating to the "permanent treatment" paradigm, and thus shorter regimens, with more mechanisms included, might be a feature of further development efforts in FL.
HCW on TGTX
1) Physicians highlight tolerability in combination therapies with TGR-1202 and/or TG-1101:
Building on the results we already discussed in the days 1&2 highlights report, TG Therapeutics presented updated data from ongoing trials involving TGR-1202 and TG-1101 (ublituximab), which attracted considerable attention from conference attendees. In a poster presentation, TG provided data for 52 patients in an ongoing Phase 2 trial examining the combination of TGR-1101 with the BTK inhibitor ibrutinib in the treatment of R/R CLL and MCL patients. As expected, the combination was well-tolerated with grade 3 IRR occurring in only 3 patients, none of which required a dose reduction. More importantly, the combination yielded an ORR of 96% in high-risk CLL patients. In our opinion, the impressive response rate to date far out-paces those historically seen with ibrutinib alone (55.9% in R/R CLL with del17p) and could be a key asset to watch as it moves into its planned Phase 3 GENUINE trial, expected to initiate within weeks.
In an oral presentation, the company disclosed preliminary efficacy and safety data from an its ongoing Phase 1/2 dose escalation study of TG-1101 in combination with TGR-1202 in patients with heavily pre-treated R/R B-cell malignancies. In total, the “doublet” combo results included 26 patients with the majority (67%) harboring 17p and/or 11q deletions. Impressively, the doublet therapy generated an ORR of 67% amongst CLL/SLL patients, and halted disease progression in 78% of FL patients. In DLBCL, the combination yielded a 43% ORR, with two confirmed CRs. Critically, the combination continues to demonstrate a favorable safety profile, with no hepatic toxicity observed in any patients treated to date.
Highlighting the benign safety profile of TG-1101 and TGR-1202, early data was presented for a “triplet” combination including TG-1101, TGR-1202, and ibrutinib. A small cohort of five patients was treated with the triplet therapy with no dose reductions or delays necessary in patients for more than four months thus far. Although the data is very preliminary, we are encouraged by the tolerability of the triplet therapy, which has already generated a CR in a MCL patient and a PR in one of two FL patients. In our view, the triplet combination represents a safe and effective alternative to similar combinations targeting both CD20 and PI3K-delta, without exacerbating the unpleasant and potentially dangerous side effects that can come along with ibrutinib, and further dispels concerns of potential antagonism between anti-CD20 antibodies and BTK inhibitors.
News December 09, 2014 19:53 ET
Cyrus Group of Funds Acquires Common Shares of Sphere 3D Corporation
TORONTO, ONTARIO--(Marketwired - Dec. 9, 2014) - Cyrus Capital Partners, L.P. ("CCP") today announced that it has acquired indirect control over an aggregate of 5,915,807 common shares ("Common Shares") of Sphere 3D Corporation ("Sphere 3D") (NASDAQ:ANY), which Common Shares were acquired by FBC Holdings Sàrl ("FBC"), Cyrus Opportunities Master Fund II, Ltd. ("CMF II"), CRS Master Fund LP ("CRS"), Crescent 1 LP ("CRES"), and Cyrus Select Opportunities Master Fund Ltd. ("CSOM", and together with CMF II, CRS, and CRES, the "Funds") pursuant to a series of transactions in connection with the merger of Sphere 3D with Overland Storage, Inc. (the "Sphere-Overland Merger"), as described in greater detail in the "early warning" report required to be filed in accordance with applicable Canadian securities laws. In addition, CCP has acquired indirect control over 135,975 common share purchase warrants of Sphere 3D ("Warrants") and US$19,500,000 in aggregate principal amount of convertible debentures ("New Debentures") entitling CCP, FBC, and the Funds to acquire, directly or indirectly, control over and/or beneficial ownership of, an aggregate 2,586,955 additional Common Shares upon the exercise of such Warrants and the conversion of such New Debentures. CCP is the investment manager of each of the Funds and FBC, and exercises sole discretion over all investment decisions made by each of them.
Following the acquisition of Common Shares, but without giving effect to the issue of the 135,975 Common Shares issuable upon the exercise of the 135,975 Warrants, or the issue of the 2,450,980 Common Shares issuable upon the conversion in full of the New Debentures, CCP now exercises indirect control over an aggregate of 5,915,807 Common Shares, or approximately 16.86% of the issued and outstanding Common Shares. Ownership of the 5,915,807 Common Shares over which CCP exercises indirect control is collectively held by FBC and the Funds.
Following the acquisition of the Common Shares, and assuming the exercise of the 135,975 Warrants for 135,975 Common Shares, and the issue of the 2,450,980 Common Shares issuable upon the conversion in full of the US$19,500,000 aggregate principal amount outstanding under the New Debentures, CCP exercises indirect control over an aggregate of 8,502,762 Common Shares, or approximately 22.58% of the issued and outstanding Common Shares on a partially diluted basis. The following table sets forth the number and percentage amount of outstanding Common Shares owned by FBC and each of the Funds on the date hereof, on a partially diluted basis, after giving effect to the acquisition of the Common Shares, including the exercise of all Warrants and the full conversion of the New Debentures.
Fund Number of Common Shares Held (on a partially diluted basis) Percentage of Common Shares Held (on a partially diluted basis)
CMF II 1,105,355
2.94 %
CRS 339,340 0.90 %
CRES 383,865 1.02 %
CSOM 164,368 0.44 %
FBC 6,509,834 17.29 %
Total 8,502,762 22.58 %
Neither the holder of the New Debentures nor Sphere 3D may convert any portion of the principal amount of such debentures or accrued interest thereon to the extent that the exercise of the conversion right will result in the holder of the New Debentures either (i) becoming a "Control Person" (as that term is defined in Policy 1.1 of the TSX Venture Exchange's Corporate Finance Manual), if applicable, unless the exchange has granted its approval for the creation of a new "Control Person", or (ii) being in violation of any other applicable listing requirement of the exchange on which the Common Shares are then listed or any other regulatory requirement.
For purposes of calculating the percentages of Common Shares owned by FBC and the Funds and indirectly controlled by CCP, CCP has assumed that there were 35,069,410 Common Shares outstanding at December 1, 2014, after giving effect to the Sphere-Overland Merger, as disclosed by Sphere 3D to CCP.
Other Information
CCP acquired indirect control over, and FBC and the Funds acquired ownership of, the Common Shares that are the subject of this news release for investment purposes.
In connection with the investment by FBC and the Funds in the Common Shares, CCP may engage in communications with members of management and the board of directors of Sphere 3D, other current or prospective shareholders, industry analysts, existing or potential strategic partners or competitors, investment and financing professionals, sources of credit and other investors with respect to Sphere 3D. CCP intends to review FBC's and the Funds' investment in Sphere 3D on a continuing basis. Depending on various factors including, without limitation, Sphere 3D's financial position, the price levels of the Common Shares, conditions in the securities markets and general economic and industry conditions, CCP's, FBC's or the Funds' business or financial condition and other factors and conditions CCP deems appropriate, FBC and/or the Funds may in the future take such actions with respect to their investment in Sphere 3D as CCP deems appropriate including, without limitation, seeking additional board representation, making proposals to Sphere 3D concerning changes to the capitalization, ownership structure or operations of Sphere 3D, acquiring additional Common Shares, and/or selling or otherwise disposing of some or all of their Common Shares. In addition, CCP may formulate other purposes, plans or proposals regarding Sphere 3D or any of its securities to the extent deemed advisable in light of general investment and trading policies, market conditions or other factors or may change its intention with respect to any and all matters referred to in this new release.
In connection with the Sphere-Overland Merger, Daniel Bordessa, an employee of CCP, was appointed to the Sphere 3D board of directors on December 1, 2014.
Neither the issuance of this news release in connection with the matters disclosed herein nor the anticipated filing by CCP of the corresponding "early warning" report required to be filed in accordance with applicable Canadian securities laws is an admission that an entity named or otherwise referred to in this news release owns or controls any described securities or is a joint actor with another entity named or otherwise referred to in this news release.
CCP's address and other contact information is set forth below. For further information, including to obtain a copy, once filed, of the "early warning" report required to be filed in accordance with applicable Canadian securities laws, contact CCP at the address specified below.
CONTACT INFORMATION
Cyrus Capital Partners, L.P.
Thomas Stamatelos
Chief Financial Officer/Co-Chief Operating Officer
(212) 380-5800
Cyrus Capital Partners, L.P.
399 Park Avenue, 39th Floor
New York, NY 10022
United States of America
Leveraging Data for Storage Solutions and Innovation
Nilesh Patel
Vice President-Overland Storage
Tuesday, December 2, 2014
Print
Forward
inShare
The software defined IT is the latest trend driving transformation in technology. In terms of how business in future would deliver applications, data and services to their internal and external customers. In addition, there are four major technological trends in regard to Software-Defined IT that can assist in delivering efficiency, agility and scalability in technology. These trends include Cloud-ready IT, Mobile-ready IT, Scalable IT and Distributed IT.
A cloud-ready IT infrastructure is a key trend that can transform static and traditional enterprise IT infrastructure to be more agile and service-oriented. In addition, this IT enabled businesses to convert their CAPEX to OPEX, thus driving significant financial advantage. On the other hand, in terms of Mobile-ready IT, today's mobile employees require on-the-go flexibility in order to be productive. They are functioning 24/7 on a number of mobile devices, in various locations around the globe. Thus, corporate IT needs to be responsive to these dynamic forces, and securely deliver the applications and data required by mobile personnel in any place, any time and on any device or platform.
In the sphere of Scalable IT, today's corporate command efficiency and agility from their IT infrastructure to meet the prospective growth requirement. This is driving the requisite for small, scalable building block solutions, which are purpose-built and optimized for specific use-case needs that can be added or re-provisioned as required. Alternatively, Distributed IT is leveraging on the availability of a variety of skills and resources that are dispersed anywhere in the world and could be a competitive advantage for businesses. Therefore, capitalizing on accessibility and availability of these global resources has become a key requirement for IT departments.
Provisioning the Need of IT
Over a decade ago, server virtualization was a transformative trend. It was mainly intended for driving efficiency by increasing utilization of application servers, and was an uncomplicated technique to support multiple workloads in a single server. However, virtualization technology has developed over the years, and it has acquired many levels of complexities. Accordingly, conventional virtualization solutions are promoted further in the new era of mobility and cloud. In this new technological era, the IT buyers demanded decentralization of infrastructure and small, scalable building blocks that are inherently secured. They wanted apps, data and desktops to be protected, managed and delivered anywhere, in any place and on any device, without any restrictions and devoid of an inflated infrastructure.
Key Issues Facing By Global Business Leaders
From a CXO's perspective, the vital issues encountered by today's business leaders, mainly centers on building agility and to be responsive to the altering needs of business. It is also vital to leverage and optimize resource productivity within the organization or wherever the resources are located, including working with our partners as one team.
Technological Advances
The conventional method to perceive technology is to have the best-of-breed technology; however, the focus is to deliver best-of-breed customer value by focusing on a complete end-to-end solution as opposed to only part of the solution. For instance, Overland Storage, along with Sphere3D, brings breakthrough containerized software technology that is delivered via purpose-built, drop-in-ready hyper-converged appliances for desktops and apps supplied on private, public and hybrid clouds. Moreover, incorporated with a scalable, software-defined storage infrastructure, customers could build an end-to-end solution from apps and desktops that are securely delivered to any place and on any device to data storage solutions, which are inherently protected and scalable to meet the most stringent of IT requirements. Accordingly, our capability to deliver this apps and virtualization technology makes our solution cloud-ready, mobile-ready, highly-scalable and deployable anywhere, anytime and on any device.
Keeping up with Technological Challenges
In this competitive world, it is critical to stay updated with technology and other transformative trends that shape tomorrow's businesses and customer needs. With respect to this, maintaining simplicity of products and solutions, overall customer experience, as well as simplicity of engagement within the company, its partners and external customers, is a constant challenge. Moreover, it is a matter of survival for innovation-led businesses like ours to be able to consistently convert technology innovations into realizable value and benefits to customers ahead of the competition. Another challenge as a CXO is being able to consistently deliver the best value to customers is not only a challenge, but a key motivation for us.
To overcome these challenges posed by the industry, we always keep the customer value proposition in mind, focus on simplicity, and drive that value into everything from solution definition to customer adoption of solutions. Another significant aspect is leveraging and functioning with the partner ecosystem, including channel partners as well as the technology and solution partners. (As told to Shahina Islam)
dew imho TGTX data is early but very encouraging Safety as the KOLS keep talking about is excellent.
with tgtx owning 100percent of these assests going forward.
Clinical Activity -- Triple Therapy: TG-1101 + TGR-1202 + Ibrutinib
Of the 5 patients enrolled to date on the triple combination of TG-1101, TGR-1202, and ibrutinib, 3 were evaluable for efficacy (1 FL, 1 MCL, and 1 patient with Richter's Transformation) and 2 were too early to evaluate. Of the 3 evaluable patients, 2 responded (MCL and FL). The MCL patient was diagnosed as Stage IV, and had previously progressed within one year of an autologous stem cell transplant, and achieved a PET negative CR at the first response assessment (day 60). The FL patient had also been diagnosed as Stage IV, was refractory to both rituximab and ibrutinib, and achieved a PR at the first response assessment (day 60) with a 74% nodal reduction. Enrollment into the triple combination cohort continues, with TGR-1202 currently dosed at 600 mg, with additional dose escalations planned.
TGTX excellent data with SAFETY
Preliminary Data From Ongoing Phase I/II Dose Escalation Study of TG-1101 (Ublituximab) in Combination With TGR-1202 in Heavily Pre-treated Relapsed/Refractory B-Cell Malignancies Demonstrates Encouraging Clinical Activity and Safety.TG Therapeutics, Inc.
2 minutes ago
GlobeNewswire ????.????...Content preferences ....Done ..
....•100% of evaluable CLL/SLL patients (9/9) had nodal reductions, with 6 of 9 patients achieving a PR with the remaining 3 patients on study with nodal reductions ranging from 15% to 45% and a peripheral response (normalization or >50% decrease in ALC) pending additional assessments
•83% (5/6) of patients with Non-Hodgkin's Lymphoma; 3/3 DLBCL and 2/3 Follicular Lymphoma (FL) responded to the combination at the highest dose tested, including 2 CR's in patients with DLBCL confirmed by independent review
•Collectively, 87 patients have been treated with TGR-1202, alone or in combination with TG-1101, without the observance of drug-related hepatic toxicity
•Dose escalation continues with TGR-1202 at 800mg micronized
•The combination of TG-1101, TGR-1202, and ibrutinib ("Triple Therapy") was safely administered to 5 patients with heavily pre-treated NHL, CLL, and Richter's transformation with no dose limiting toxicities observed, and no Grade 3 or 4 events observed to date
•2 of the first 3 evaluable patients responded to the Triple Therapy, including an ibrutinib-refractory, rituximab-refractory patient with Follicular Lymphoma
SAN FRANCISCO, Dec. 9, 2014 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (TGTX), an innovative, clinical-stage biopharmaceutical company today announced clinical results from its Phase 1/2 clinical study of TG-1101 (ublituximab), the Company's novel glycoengineered anti-CD20 monoclonal antibody, in combination with TGR-1202, the Company's novel once per day PI3K delta inhibitor. These data are being presented today in an oral presentation by Dr. Matthew Lunning from the University of Nebraska Medical Center at the 56th Annual American Society of Hematology (ASH) meeting being held in San Francisco, CA.
"We continue to be very impressed with the safety profile and activity observed to date in a heavily pre-treated population of patients with the combination of ublituximab and TGR-1202," said Dr. Matthew Lunning. "The activity seen to date has been impressive across all disease types, but of particular interest is the high level of activity seen in DLBCL, specifically the GCB subtype, a population of patients in dire need of effective therapies in the relapsed / refractory setting. We were also very excited to introduce a cohort into the study that explored the triple combination of ublituximab, TGR-1202, and ibrutinib, and have been very pleased with the early safety and activity profile of this combination."
Michael S. Weiss, the Company's Executive Chairman and Interim CEO commented on the data, "We remain focused on developing the most efficacious, least toxic treatment options for patients with B-cell malignancies, and believe the data presented today by Dr. Lunning is a major step in that direction. We are very pleased with the early safety and activity profile of our proprietary combination, and look forward to additional follow-up and to seeing the effects of higher doses. Based on the safety and efficacy profile, we believe the combination has the potential to be the leading backbone for incremental combination therapy, as illustrated by the early triple combination data presented today." Mr. Weiss added, "We look forward to further dose escalations in this study while at the same time evaluating designs for our first registration trial for this proprietary combination, ideally to be announced in the first half of 2015."
OVERVIEW OF THE DATA:
The presentation includes data from 27 patients on the combination of TG-1101 and TGR-1202 with relapsed and/or refractory B-cell malignancies, with a median 3 prior lines of therapy, 65% of patients having seen 2 or more prior lines of rituximab, and 41% of patients refractory to prior therapy. The study has explored doses of 600mg and 900mg of TG-1101, and escalating doses of TGR-1202 beginning at 800mg (initial formulation) and escalating to 600mg of the micronized formulation. Five additional patients were treated in the triple combination cohort evaluating the combination of TG-1101, TGR-1202, and ibrutinib in which ibrutinib was dosed per its label in combination with TG-1101 at 900mg and TGR-1202 at 400mg and 600mg micronized. Based on recently reported safety and exposure-response relationship data for TGR-1202 as a single agent, the Company intends to continue dose escalation in this trial to 1200mg micronized with the potential for higher dose levels.
Safety and Tolerability -- All Patients
The combination of TG-1101 and TGR-1202 was well tolerated in the 27 patients evaluable for safety, with day 1 infusion related reactions (IRR) being the most frequently reported adverse event. All IRR events were manageable without dose reductions, and all but one event was Grade 1 or 2 in severity. Other adverse events included neutropenia, nausea, and diarrhea, with neutropenia being the only Grade 3/4 adverse event reported in > 10% of patients (33%). Consistent with the data observed to date in the ongoing TGR-1202 single agent Phase 1 study, no drug-related events of hepatic toxicity (ALT/AST elevations) were observed among the 27 patients treated to date with the combination of TG-1101 and TGR-1202. Additionally, no events of hepatic toxicity were observed amongst the 5 patients treated with the triple combination of TG-1101, TGR-1202, and ibrutinib. Collectively, with the results from the Phase 1 single agent study of TGR-1202, 87 patients have been treated with TGR-1202, alone or in combination with TG-1101, without the observance of drug-related hepatic toxicity. Additionally, in those 87 patients, there have been no events of colitis observed to date, with patients on the combination of TG-1101 and TGR-1202 for up to 9 months, and patients on single agent TGR-1202 upwards of 19+ months.
The triple combination of TG-1101, TGR-1202, and ibrutinib was well tolerated in the 5 patients evaluable for safety. No DLTs were observed and no Grade 3/4 events have been reported, with IRR, nausea, fatigue, and diarrhea being the most commonly reported Grade 1/2 adverse events. No dose reductions or dose delays have occurred.
Clinical Activity of TG-1101 + TGR-1202 in Chronic Lymphocytic Leukemia (CLL)
Of the 11 CLL/SLL patients enrolled to date, 9 were evaluable for efficacy. One patient was found to be ineligible prior to first efficacy assessment and one CLL patient is on the triple therapy and too early to evaluate. Patients in this group were heavily pre-treated with 67% (6/9) harboring a 17p del and/or 11q del.
A summary of the CLL/SLL data reported is as follows:
•All 9 evaluable patients exhibited nodal reductions with 6 of 9 achieving a Partial Response by the iwCLL (Hallek 2008) or Cheson criteria
•The remaining 3 patients achieved nodal reductions ranging from ~15% to 45% accompanied by either a normalization of ALC or a greater than 50% reduction of ALC, sometimes referred to as a "peripheral response"
•All evaluable CLL patients remain on study (durations of 3+ to 9+ months) pending further efficacy assessments and intra-patient dose escalation, which is permitted per protocol
The lymphocytosis generally observed in CLL patients treated with TGR-1202, similar to other PI3K delta and BTK inhibitors, appears to be mitigated by the addition of TG-1101.
Similar to the trend observed in the single agent study of TGR-1202, responses to the combination of TG-1101 and TGR-1202 have been shown to improve overtime and dose escalation continues now at 800mg micronized and up to 1200mg micronized, with the possibility of dosing higher.
Clinical Activity of TG-1101 + TGR-1202 in Hodgkin's Lymphoma (NHL) / Richter's Syndrome
Of the 17 NHL or Richter's patients enrolled to date, all were evaluable for efficacy (7 DLBCL, 9 FL and 1 Richter's). Patients in this group were heavily pre-treated, with 53% refractory to their prior treatment regimen. In the DLBCL group, patients had a median of 3 prior lines therapy and 5 of the 7 patients had the GCB subtype, with one patient classified as "triple-hit" (overexpression of BCL2, BCL6, and MYC rearrangements). In the Follicular Lymphoma group, patients had a median of 5 prior lines of therapy, with 56% being deemed rituximab refractory.
Among patients with Non-Hodgkin's Lymphoma treated at the highest doses tested, 83% (5/6) of the patients (3/3 of DLBCL and 2/3 of FL) responded to the combination. Of particular note was the potential signal in DLBCL, where an ORR of 43% (3/7) was observed with 2 patients (29%) achieving a Complete Response (CR), both of which were confirmed by independent radiologic review. Two of the three DLBCL responders were GCB subtype, which has historically been less responsive to BCR targeted agents. The 3 DLBCL patients who achieved a response remain on study, progression-free for greater than 7 months.
Additionally, despite the advanced disease and multiple lines of rituximab-based therapy, all of the FL patients treated to date with the combination were stable at first assessment and exhibited a reduction in tumor mass. Consistent with the exposure-response data recently reported in the single agent dose escalation trial of TGR-1202, 2 of 3 patients with FL treated at the highest dose of TGR-1202, 600mg micronized, responded at the first assessment (day 60). The remaining patient had a nodal reduction and remains on study pending further efficacy assessments. Dose escalation of the combination continues with TGR-1202 now at 800mg micronized and up to 1200mg micronized, with the possibility of dosing higher.
Clinical Activity -- Triple Therapy: TG-1101 + TGR-1202 + Ibrutinib
Of the 5 patients enrolled to date on the triple combination of TG-1101, TGR-1202, and ibrutinib, 3 were evaluable for efficacy (1 FL, 1 MCL, and 1 patient with Richter's Transformation) and 2 were too early to evaluate. Of the 3 evaluable patients, 2 responded (MCL and FL). The MCL patient was diagnosed as Stage IV, and had previously progressed within one year of an autologous stem cell transplant, and achieved a PET negative CR at the first response assessment (day 60). The FL patient had also been diagnosed as Stage IV, was refractory to both rituximab and ibrutinib, and achieved a PR at the first response assessment (day 60) with a 74% nodal reduction. Enrollment into the triple combination cohort continues, with TGR-1202 currently dosed at 600 mg, with additional dose escalations planned.
Presentation Details
The presentation, titled "Ublituximab, a Novel Glycoengineered Anti-CD20 mAb, in Combination with TGR-1202, a Next Generation Once Daily PI3K Delta Inhibitor, Demonstrates Activity in Heavily Pre-Treated and High Risk Chronic Lymphocytic Leukemia and B-Cell Lymphoma" was presented today, Tuesday, December 9, during the session titled "Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Indolent B-cell NHL and T-cell NHL", from 8:00 to 9:30am Pacific Time. The presentation is available on the Events page, located within the Investors & Media section of the Company's website at www.tgtherapeutics.com.
ABOUT TG THERAPEUTICS, INC.
TG Therapeutics is a biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. Currently, the company is developing two therapies targeting hematological malignancies. TG-1101 (ublituximab) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TG Therapeutics is also developing TGR-1202, an orally available PI3K delta inhibitor. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-lymphocytes. Both TG-1101 and TGR-1202 are in clinical development for patients with hematologic malignancies. The Company also has a pre-clinical program to develop IRAK4 inhibitors, also for B-cell malignancies and autoimmune diseases. TG Therapeutics is headquartered in New York City.
CAUTIONARY STATEMENT
$TGTX ROTH TGTX: #KOL #Event; Great Data with Major
Emphasis on Safety; Reiterate Focus Pick
TG hosted a KOL event yesterday to discuss the strength of clinical data
presented at ASH. Importantly, we believe a key takeaway is the dominant
focus on the favorable safety profiles of TG-1101 and TGR-1202 relative to
other drugs in their respective classes. The KOLs certainly highlighted this
differentiation as a key driver to their future treatment decisions. Reiterate Buy
and Focus Pick.
Event
To wrap up ASH, TG hosted a KOL event to discuss the ongoing and planned
studies at the company. Participating in the event was Dr. Jeff Sharman from
U.S. Oncology (PI of the '1101/Imbruvica Phase II and PI of the upcoming
GENUINE Phase III), Dr. Nathan Fowler from MD Anderson (main involvement
in '1101/'1202 study to be released later this morning, Dr. Owen O'Connor from
Columbia (has led efforts with '1101) and Dr. Manish Patel from Florida Cancer
Specialists-Sarah Cannon.
Key Takeaway - Safety, Safety, Safety
The views on the strength of the clinical data from the 1) '1101/Imbruvica
Phase II, 2) '1101 Phase I/II update and 3) the '1202 monotherapy study
quickly changed to having the safety differentiation of these drugs dominate
the discussion. We summarize the KOL commentary below. Later this morning
(11am ET) the company will present an oral presentation of the TG-1101/
TGR-1202 combination study and Dr. Fowler made special comment about
why it was impressive to be accepted for an oral presentation at ASH based
on small numbers of patients at the time of submission. With all the positive
data in hand, the next important catalyst is the imminent start of the Phase III
GENUINE study based on the strength of TG-1101/Imbruvica Phase II data.
The study will be in previously treated CLL patients (high risk cytogenetics).
This planned randomized study will enroll ~330 patients and compare TG-1101
+/- Imbruvica. The primary endpoint of the study, as per the SPA will be overall
response rate (ORR) which be analyzed following ~two-thirds of patients
receiving treatment. All patients enrolled into the study will then be followed
for progression free survival (PFS), which, should serve as the basis for full
approval.
Action
We reiterate our Buy rating, Focus Pick and $25 price target. We believe that
TG is positioning itself strongly with its lead candidate drugs, with the potential
to be integrated in the evolving standard of care for B-cell malignancies.
Suntrust Robinson: $BLUE LentiGlobin Shines with ASH Data, 2015 Catalyst-Rich, Raising PT from $57 to $115 - What's Incremental
ASH data from BLUE's HgB 204 (U.S.) and 205 (France) Phase I/II studies of
LentiGlobin in beta-thal represent our best case scenario, with 4/4 evaluable
patients in 2 studies being "cured" on key clinical measurements. 2 patients in
the 205 study remain transf. independent at 12 and 9 mos, 2 patients in the
204 trial have reached transf independence, (including a beta-0/beta-0), with
the remaining 3 too early to assess. 2/3 (1 too early) add'l beta-thal patients
and 1 patient with sickle cell disease (205 study) experienced successful
engraftment. There is no clonal dominance seen to date.
2/2 evaluable patients in the 204 (U.S.) study achieved transf.
independence. 5 patients had been transplanted with LentiGlobin product,
including one patient discussed in the abstract that had exhibited increasing
levels of T87Q beta-globin. With a follow up of 6 months, this patient did not
get any additional transfusion units and is now trans. independent. No clonal
dominance emerged, suggestive of minimal to no risk of leukemia.
Importantly, a beta-0/beta-0 patient achieved transf. independence. This
patient saw rapidly increasing T87Q beta-globin levels (4 and 6.8 g/dL, at
mos 2 and 3). We spoke with mgmt, who noted that impressive activity in
this patient could be due to the high VCN (1.5 in this pt.), but also a possible
mechanism for T87Q beta-globin expression in beta-0/beta-0 pts that is
less encumbered by dysfunctional hemoglobin E. 3 add'l patients have
been transplanted (VCN of 0.7, 0.9, and 1), and 2 evaluable experienced
engraftment (within 14-17 days).
Transfusion independence maintained in the 205 study, safety looks
benign. Dr. Marina Cavazzana presented data from the 2 beta-0/beta-e
patients showcased at EHA, who had maintained transf. independence with
9 and 12 months of follow-up. The 2 patients continue to harbor increasing
levels of LentiGlobin induced T87Q beta-globin and stabilization of fetal HgB.
However, total HgB levels now trend towards normal in these patients (13-14
g/dl).
The first sickle cell disease (SCD) patient successfully transplanted,
more mature data in 2015. One SCD patient was treated in the 205 study,
with patient-specific LentiGlobin VCN 1.2/1.0, and 5.6M cells. Notably,
sustained increase in T87Q globin seen (significantly >20-30% of total) in
the beta-thal patients provide a positive read-through to SCD, where KOLs
Raising our price target to $115 from $57 on increased clarity for LentiGlobin's clinical profile
in beta-thal; No SCD in model. Based on these data, we believe that the LentiGlobin program in
beta-thalassemia is incrementally de-risked, and we assign a probability of success (PoS) of 90%
from our previous 50%, and our discount rate is reduced from 12% to 11%. Based on our sum-ofthe-
parts DCF analysis, our price target is increased from $57 to $115. We continue to exclude any
potential impact from SCD to BLUE's valuation.
A flurry of catalysts in 2015 will include additional study read-outs, new program
announcements. We anticipate additional clinical data from beta-thalassemia and SCD programs,
as well as first analyses from the likely pivotal CCALD trial. BLUE could also announce the target
and/or timeline details on the design of their CAR T program (CELG collaboration).
Scottrade has been 75percent for months
ROTH $TGTX '1202 Profile Keeps Getting Better; We Think Differentiation Clear
At #ASH14 yesterday, TG announced a strong update to the ongoing Phase I dose
escalation study for TGR-1202. The positive efficacy is also bolstered by what
continues to be a differentiated safety profile. Later today we look forward to the
the TG-1101/Imbruvica combo update and on Tuesday the oral presentation
for the TG-1101/TGR-1202 combo study. Reiterate Buy and Focus Pick.
Event
TG announced a strong update to the ongoing Phase I TGR-1202 dose
escalation study in relapsed/refractory lymphoma patients at ASH yesterday.
Positive responses were seen across multiple lymphoma types with the
primary focus on CLL patients. A 93% (13/14) response rate was seen in CLL
patients. >50% of patients saw nodal responses and 50% of patients achieved
PRs per iwCLL criteria. As dose escalation continues, two key takeaways
beyond the strong efficacy seen are that 1) no changes in the adverse event
profile has been seen as dose escalation continues (including no drug related
hepatotoxicity or colitis) and 2) no MTD has been established yet.Later this
morning, we expect to receive a strong update from the TG-1101/ Imbruvica
Phase II combo study in CLL patients, which we anticipate will act as a proxy
for the Phase III which is about to begin. This evening, we expect to receive
updated KOL views from the ongoing studies. On Tuesday, the company will
be presenting an oral presentation from the TG-1101/TGR-1202 combination
study in r/r CLL and NHL patients. Importantly, recall that this study includes
those patients refractory to prior PI3K and BTK therapy.
Impact
We continue to be very impressed by '1202's efficacy and differentiated toxicity
profile and our confidence in the drug continues to grow. Recall the company
recently announced a combination study with TGR-1202 and Imbruvica in CLL
and MCL patients. We believe this study could drive one of the several pivotal
studies TG has planned for 2015 going forward. The main focus right now is
the imminent start of the TG-1101 / Imbruvica Phase III combination study in
CLL patient. The company is within weeks of starting its first Phase III study
combining TG-1101 and Pharmacyclics' (PCYC-Buy) Imbruvica.
Action
We reiterate our Buy rating, Focus Pick and $25 price target. We believe that
TG is positioning itself strongly with its lead candidate drugs, with the potential
to be integrated in the evolving standard of care for B-cell malignancies.
NOMURA: LIVE@ #ASH14 Investors Focused on $AGIO and $KITE -
$CELG & $INCY Biggest Winners in our Universe
We are attending the 2014 American Society of Hematology Conference
where investor focus remained on emergence of novel treatments for AML
(Agios) and ALL (Kite Pharma). We believe biggest winners in our coverage
universe were CELG and INCY as data at ASH firmly established Revlimid as
the backbone of myeloma while physician feedback on Jakafi suggested a
faster ramp in PV following Dec 4th approval. We believe the conference also
provided further confirmation of Imbruvica’s expected dominance in CLL, while
Gilead’s Zydelig continues to look to have a role in relapse NHL, despite
potential safety concerns given boxed warning. We believe Amgen’s ASPIRE
data will support initial second line MM use but competitive data and
expansion into first line setting remains key to upside.
? CELG: Revlimid Firmly Established as Backbone in Myeloma, Pipeline
Keeps Getting Better. CELG is our top large cap pick given proximity to
Revlimid approval for front line/maintenance therapy in US and Europe and
triple combo data that both establishes Revlimid as a backbone in myeloma
and points to longer treatment duration. This is on top of emerging data that
could open up a $3-$4bn opportunity in lymphoma. This combined with an
impressive late-stage pipeline sets the stage for potential upward revision to
Street estimates when new 5-year guidance is introduced in Jan. 2015.
? AMGN: ASPIRE to support second expansion but upside dependent
on front line use. We believe Kyprolis’ long-term trajectory and Street’s
$4bn peak sales estimate remain contingent on positive data from the head
to head versus Velcade ENDEAVOR and CLARION trials, expected to read
out 1Q15 and 1Q16 respectively. These trials are needed to support label
expansion into 1st line and would support a potential best-in-class profile.
? PCYC: Imbruvica preferred 2nd line CLL regimen; 1st line key to upside.
We believe physicians are using Imbruvica in CLL in-line with our March
2014 physician survey that saw Imbruvica as a preferred second-line
therapy, supporting our $900mn peak sales in the relapse setting. We
expect additional upside to come from expansion into front-line CLL and
relapsed/refractory FL, with both pivotal Phase III (RESONATE-2) and
Phase II (DAWN) data expected in 2H15.
? INCY: PV Oppt’y Could be Larger than Our and Street estimates. We
believe physician enthusiasm for PV treatment is already high as evident by
informal audience poll at an educational symposium we attended. We
believe this enthusiasm points to upside to our $700mn peak sales estimate.
? GILD: Confirming Zydelig’s role in NHL, but Imbruvica still CLL leader.
Results of an informal survey at an educational symposium confirmed our
expectation for physician enthusiasm for Zydelig in R/R NHL. This
enthusiasm will be key to supporting our $850mn NHL peak sales estimate.
We are more cautious on the CLL opportunity where we expect Imbruvica to
dominate, placing our peak CLL sales estimate of ~$750mn at risk.
TLOG: Focusing on MDS and HBV to drive upside. Update to
birinapant Phase Ib/IIa dose escalation and expansion study in
combination with Vidaza showed 4 patients (out of 16 pts) with significant
reduction in bone marrow blast count (previously 3 out of 9 patients).
However we remain focused on the interim Phase II data for MDS (basis
of our valuation), as well as Phase I/II data in HBV (upside to our model),
both expected mid-2015.