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ACAD piper CONCLUSION
ACADIA reported 3Q results yesterday after the close, ending the quarter with $338M, which may be sufficient to profitability based on our model. Management pushed the timeline for pimavanserin's (Nuplazid) NDA filing for Parkinson's disease psychosis (PDP) to 1Q15 (from YE14) and expects to file the MAA 6-9 months after. According to management, the delay is purely to ensure solid applications and not due to interactions with the agencies or changes to the clinical outlook for Nuplazid. We projected minimal sales in 2015 in the U.S., so there is no impact to our $46 price target. We reiterate our Overweight rating on expectations for establishment of Nuplazid as a pipeline in a pill, initially by market success in PDP and clinical validation in ADP and possibly schizophrenia and other indications.
• Commercial-prep progress for Nuplazid. ACADIA successfully completed the drug- drug interaction and stability studies for Nuplazid. We expect the NDA and MAA filings are intact, however procedural timelines of some sort were possibly underestimated. Commercialization efforts are well underway. Nuplazid will be given QD as 2 20mg pills if approved. Market studies have been conducted by ACADIA including >800 PDP treating neurologists, psychs, and LTC physicians. These studies have given the company a sense of the PDP market, suggesting ~11k PDP treating physicians in the U.S. and ACADIA plans to employ 135 sales reps to reach those doctors. The company estimates ~400k PDP patients, and about 50% with "disruptive" symptoms, which we believe is in-line with our model's projections.
• Other programs advancing apace. The Alzheimer's disease psychosis (ADP) study of ~200 patients continues to enroll and we expect data in 2H15. A study to treat sleep disturbance in Parkinson's patients is expected to start in 1H15 and a monotherapy Phase II study for the maintenance treatment of schizophrenia is expected to start in 2H15. We think pima' has a good shot at improving on the atypical antipsychotics for the same reasons it appears to do so in PDP: efficacy with a cleaner safety profile due to more targeted activity.
Sent from my iPhonegigaom.com/2014/11/10/whats-the-best-selling-device-in-k-12-markets-this-year-google-says-chromebooks
https://gigaom.com/2014/11/10/whats-the-best-selling-device-in-k-12-markets-this-year-google-says-chromebooks/
@michael_keen: Chromebooks. One example where @Sphere3D is seeing great success w/ Glassware tech #microcontainer #appvirtualization http://t.co/iz3TZq4dHk
ISI on Merck
3. MRK is not the only one studying shorter duration of therapy with GILD’s Sovaldi... GILD has previously presented data from the NIH-led study of the triplet combo of Harvoni (Sovaldi + ledipasvir) and either its PI GS-9451 or non-nuc GS-9669 given for 6 wks with SVR rates of ~95- 100%. And BMY also has an ongoing ph2 study. (GILD has not provided updated data and no results for shorter-duration regimens are expected from GILD or BMY at this AASLD). Why MRK’s 6-wk data appears inferior to GILD’s data from the NIH study is unclear.
4. Going forward... MRK has announced plans to start add’l ph2 trials called C-CREST in Q1’15 that study the combo of its acquired nuc from IDIX (IDX21437 or MK-3682) with its PI MK-5172 and NS5a MK-8742 for 8 wks. MRK will also study its nuc MK-3682 and PI MK-5172 in combination with its next-generation NS5a MK 8408 for 8 wks and will continue to pursue 6 wk duration of therapy depending on the new 8 wk data. (The 7-day dosing data for MK-3682 in HCV patients and preclinical data for MK-8408 are expected later this week at AASLD.)
We believe the stock reaction to the data will likely be modest given expectations going into AASLD (MRK made what we interpreted and what we believe investors interpreted as bearish comments regarding the data on the 3Q’14 call). That said, in part due to the points made above, GILD could move modestly up and MRK modestly down on the data.
Dndn BANKRUPT What was!
What could have been?
Now nothing
9.77 on ask so thin so thin
have a good weekend all
dough
days like today is when you wish the market stayed open a few hours later
love the action
dough
ovrl 4 bucks
Bmo abbv Impact & Analysis
When we made AbbVie our top pick following the 2014 EASL conference, we were convinced that the Street was underestimating the potential for the company’s Hep-C franchise. At the time, 2015 Hep-C consensus was roughly $1Bn. However, the Street’s expectations are much higher now, and we believe the stock price (up ~35% since mid-April) reflects that. Now Hep-C consensus for 2015 is $2.7Bn (vs. our $2.1Bn forecast) with some estimates going as high as $3Bn and $3.6Bn. Although this kind of performance is certainly possible, here we argue that it is unlikely because we see AbbVie primarily competing in 15-25% of GT1 patients (Rx experienced with cirrhosis). We also see serious Hep-C competition in the not so distant future that may cast uncertainty over the longer term prospects of this franchise (e.g., MRK C-SWIFT data at AASLD). In short, we believe Hep-C is the most important driver for ABBV in 2015, and we think expectations may now be too high. We also expect increased Humira biosimilar concerns in 2015 as the Remicade biosimilar is expected to enter new European markets, and Humira biosimilar developers get closer to completing their programs. Incrementally positive updates from ABT-199, Elagolix and Elotuzumab are for the most part expected in 2015, and not enough to offset the headwinds above, in our view.
Valuation & Recommendation
Our price target is now $65 based on DCF supported by 15x our 2015 EPS of $4.35. We have low
MAXIM 11/7 tkmr
Tekmira Pharmaceuticals Corp Buy
Ebola Patients in US Treated with TKM-EBOLA
Summary
• Tekmira reported 3Q14 with $4M in revenues, $11M in expenses, and $120M
in cash on the balance sheet.
• DoD has exercised a $7M option to manufacture TKM-EBOLA-Guinea and the
supply of the product (500 doses), which should be available in December
2014. Several Ebola-infected patients (primarily in the US) have been treated
as part of emergency use granted by the FDA, though success or failure was
not disclosed, and any success would not constitute a clinical trial. We expect
TKM-EBOLA to be in clinical trials in 2015.
• TKM-HBV preclinical data showed rapid reduction in HBV surface antigen
(HBsAg) across multiple genotypes, likely due to the promotion of
seroconversion via attacking viral mRNA and preventing surplus viral proteins
from dampening immune responses. TKM-HBV will go into clinical trials in
2015.
• The phase I/II TKM-PLK1 trial in gastointestinal neuroendocrine tumors (GINET)
or adrenocortical carcinoma (ACC) tumors has completed enrollment,
and, in the phase I/II in hepatocellular carcinoma (HCC), the first patients have
been dosed.
Details
Tekmira joins an international Ebola consortium. TKM-EBOLA-Guinea may be
selected for clinical trials at Ebola treatment centers, as it has been prioritized
as an investigational therapeutic. This is good news, as, on September 22, the
FDA authorized the emergency use of TKM-EBOLA in patients with confirmed or
suspected Ebola virus infections, an authorization that would not preclude the need
for controlled clinical trials to gain drug approval. However, joining a consortium could
give Tekmira an opportunity to seek approval based on trials in Africa.
What differentiates TKM-HBV. The answer is where in the viral replication cycle
TKM-HBV targets the mRNA. HBV’s DNA genome can remain in the nucleus of
a hepatocyte for years, either active (making mRNA), or inactive and waiting to
reactivate. The mRNA will be translated into viral proteins and eventually new DNA
to make new virions. Nucleotide analogues block the replication of the DNA during
the replication process but cannot prevent the mRNA synthesis and translation of
viral protein products. The viral protein products (i.e., HBsAg and HBsE antigens)
get into the blood and prevent seroconversion. In other words, they complex with any
anti-HBV antibodies to prevent the immune system from beating back the infection,
which, over time, can lead to cirrhosis, liver cancer, and death. TKM-HBV uses
interfering RNA to destroy HBV mRNA, thus, potentially allowing the patient to
seroconvert and fight infection.
TKM-HBV could be combined with SOC. The mode of action of TKM-HBV
complements standard-of-care nucleoside/nucleotide (NUC) therapy, and lack of
drug antagonism has been demonstrated with entecavir, lamivudine, and tenofovir
on infected primary human hepatocytes. The drug mechanism of action is well
understood, and RNAi-mediated site-specific cleavage of viral mRNA by TKM-HBV
has been confirmed using RLM-RACE sequence analysis.
Valuation. We use a risk factor of 15% based on Tekmira’s partner progress and
clinical evidence of the viability of LNP-enabled siRNAs. Our other assumptions are
that TKM-Ebola moves forward and receives a US government supplier contract by
2016. Along with our assumptions on ALN-TTR02, Marqibo, and Ebola, this drives
a $31.00 target
Tgtx In a research report published today, Brean Capital analyst Jonathan Aschoff reaffirmed a Buy rating on TG Therapeutics (NASDAQ:TGTX) with a $22 price target, as updated data from the company’s TG-1101 plus ibrutinib trial, the TG-1101 plus TGR-1202 trial, as well as the TG-1202 single agent trial became available.
Aschoff observed, “The addition of TG-1101 generates earlier clinical responses than historically seen with ibrutinib monotherapy. The ORR was 94% in all CLL patients and was 100% in high risk CLL patients having both 17p and 11q del, with responses attained rapidly (median time was 8 weeks to response). Among the 8 high risk CLL patients, there were 1 CR and 7 PRs. The ORR was 83% in MCL patients, which was achieved at first efficacy assessment (prior to cycle 3), and further improved by the second efficacy assessment (prior to cycle 6). TG-1101 appears to control ibrutinib related lymphocytosis with more than half of the patients within the normal range for ALC by first efficacy assessment. As of August, 21 patients were enrolled with efficacy data in 15 (5 CLL and 10 NHL) and safety data in all 21 (8 CLL and 13 NHL) available. We expect TG to present data in at least 30 CLL and NHL patients on this regimen at ASH. ORR in CLL and NHL remained the same as what was presented in July. Four of the 5 CLL/SLL patients and 2 of the 10 NHL patients achieved a PR, and 80% of all 15 had reduced tumor burden at first assessment. No new DLTs and no events of TGR-1202 related hepatotoxicity were reported.”
TGTX Burris Reviews Two Promising New Agents in CLL Pipeline - See more at: http://www.targetedonc.com/conference/chemo-2014/Burris-Reviews-Two-Promising-New-Agents-in-CLL-Pipeline#sthash.vNKD18KA.dpuf
As the targeted therapy era in chronic lymphocytic leukemia (CLL) continues to unfold, two next-generation agents are generating responses with improved safety profiles as single agents and in combination regimens, according to Howard A. "Skip" Burris III, MD.
TGR-1202 is a PI3K-delta inhibitor administered in once-daily oral dosing while ublituximab (TG-1101) is a glycoengineered anti-CD20 monoclonal antibody, explained Burris during the hematologic malignancies session as the 2014 Chemotherapy Foundation Symposium opened Wednesday.
Notably, ublituximab will be evaluated in combination with ibrutinib (Imbruvica) in patients with previously treated high-risk CLL in a phase III trial expected to be launched this year. The trial aims to enroll approximately 330 patients who harbor 17p or 11q chromosomal deletions, or TP53 mutations.
The new regimens are being developed as part of an emerging therapeutic landscape in CLL in which it is “not unrealistic to talk about, if not a cure for patients, certainly [patients] living long enough to die of other causes and from natural means,” said Burris.
Burris specializes in early-phase clinical trials at the Sarah Cannon Research Institute in Nashville, Tennessee, where he is chief medical officer and executive director of the Drug Development Program. He was honored earlier this year with a Giants of Cancer Care™ award, a program that the Intellisphere Oncology Specialty Group launched to recognize oncology specialists who have made significant contributions to cancer care.
The structures of both TGR-1202 and ublituximab offer potential advantages, Burris noted.
He said TG-1202’s structure “contributes to a favorable pharmacokinetic profile which enables once-daily dosing and a differentiated safety profile” from other PI3K-delta inhibitors such as the recently approved idelalisib (Zydelig) and IPI-145 still in development. He said hepatic toxicities have been “noticeably absent,” and that there have not been colitis events.
Ublituximab binds to a unique epitope on the CD20 antigen and is glycoengineered for enhanced affinity for Fc?RIIIa receptors, resulting in enhanced antibody-dependent cell-mediated cytotoxicity, said Burris.
“Both TGR-1202 and ublituximab have displayed single-agent activity in a variety of relapsed/refractory hematologic malignancies,” said Burris.
The favorable safety profile that each drug has demonstrated as monotherapy has also been evident when the two novel agents were combined in a phase I involving 21 patients with CLL, diffuse large B-cell lymphoma, Richter, and follicular lymphoma. Overall, 14 of 15 evaluable patients achieved stable disease =12 weeks with manageable neutropenia and infusion-related reactions as thre most frequently reported adverse events, according to results presented at the Pan Pacific Lymphoma Conference held in Hawaii in July (Lunning et al).
In his symposium abstract, Burris presented findings for evaluable patients with CLL who received the drugs across all studies, which he said constituted the largest patient population whose experiences could be analyzed (Table).
In the most advanced regimen under study, investigators will seek to determine whether the addition of ublituximab improves upon outcomes delivered by ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor that the FDA approved this year in combination with chlorambucil for patients with previously untreated CLL and as monotherapy for patients with 17p deletions. -
In a phase II trial, all of the 20 patients who were among the first group enrolled in the study responded to the combination, said Burris. Findings were presented at the 19th Congress European Hematology Association held in Italy in May (Sharman et al).
The phase III study involving ublituximab and ibrutinib was designed under a special protocol agreement (SPA) between the FDA and TG Therapeutics, which is developing both TGR-1202 and ublituximab. Burris said patients will be stratified by prior lines of therapy and then randomized to receive either ublituximab and ibrutinib in combination or ibrutinib alone.
The overall response rates for the first 200 patients to be treated will be analyzed as the basis for an accelerated approval for ublituximab. Progression-free survival will be evaluated for all 330 participants in the trial as the primary endpoint for a full approval, said Burris.
“It’s certainly a novel way to approach this,” Burris said.
@pbookman: Wow! 950 + 1827 and growing number of applications running on #dell VRTX with #glassware from @Sphere3D http://t.co/Nm0szl24tW
Achn. 5-6 reports. Thanks to captain sequence on twitter
Ma$†¡N®
Achieved4now
23 hours ago
martyc likes this. Quote
Deutsche Bank:
Winter is coming & so is the 3422
data this Q. DB take on weakness
We have gotten many questions about Achillion weakness this morning. They issued their quarterly numbers with corp updates. We think today’s reaction is an over-reaction.
? The key focus here is the nuke 3422. The language from the note was “we expect top-line results from our ongoing Ph1 trial of ACH-3422 later this quarter”
? Based on our call volume, we have gotten questions as to whether this is a delay or not.
? We have always used Achillion’s timelines as guidance and not assumed data at AASLD
The guidance has been data during the fall. Fall ends Dec 20 and it began Sept 21. That is technically later this quarter. We don’t see this as a delay
? We spoke to mgmt this morning and they said the program remains on track. This remains consistent with what we have been hearing from mgmt before this press release this morning
Here is how we have been thinking about the timelines for this study:
? Typically cohorts take 5-6 weeks to complete. We assume patient enrollment of 12 healthy pts and 8 HCV infected. The healthy study takes 14 days. The infected HCV pts then have to be enrolled and treated for 7 days. We then assume a week for viral loads and data analysis. This is about 5-6 weeks.
? Our sense was the company was likely in healthies at 150mg in early Aug. So that would mean by our math 150mg ended mid Sept. If they started 300mg late Sept, then assuming 5-6 weeks, that would mean late Oct/early Nov. If they were dosing up, the next cohort maybe will start Nov. That would imply it would end in early to mid Dec. This has not been confirmed by the company but is our sense on where the co may be since we get a lot of questions.
? Lastly, it is possible that the company does not read any data until the full dose escalation is done.
? Interesting side bar, the co identified a novel complement related platform for oral inhibitors of complement Factor 2. There will be some early data in vitro & in vivo at ASH this year.
Ma$†¡N®
Achieved4now
23 hours ago
martyc likes this. Quote
Wells Fargo:
ACHN: Buying Opportunity Presents Itself, Ahead Of Nuc Data
Brian Abrahams, M.D., Senior Analyst (212) 2148060
Sector Rating: Biotechnology, Market Weight
**This morning ACHN shares are down substantially (18%,
vs. BTK +0.03%) we believe because of the fact that '3422 nuc
data were not reported today concurrent with the company's earnings press release.
**We had the opportunity to speak with the company today and we remain confident that the trial is proceeding on track and
that the data will look good.
**Though the company had insinuated previously that data could potentially be available by endOctober,
based on our
discussion we believe this timeline may have assumed all would have gone perfectly smoothly from a logistics standpoint,
and that given the sequential cohort design any minor prolongations in conductsuch
as one or two patients coming to the
clinic a week later than expected to start dosing would
push everything back.
**While the design of the study allows ACHN to dose escalate to achieve the desired 4 log VL reductions, our understanding
is that ACHN would likely have announced if there was an amendment to explore higher doses beyond 500mg; as such, we
do not believe the delay reflects ACHN needing to explore higher doses due to insufficient efficacy.
**We continue to believe based on the preclinical potency, characteristics, and chemical structure that fundamentally, this
agent has a high probability of achieving competitive ~4 log viral load declines at the higher doses currently being studied.
**BOTTOM LINE: Given all this, we believe today's weakness is an overreaction and provides an excellent buying
Ma$†¡N®
Achieved4now
22 hours ago
martyc likes this. Quote
UBS:
3Q14 Update: Clarifying Timelines on Data
Conclusion: ACH-3422 timing reiterated, read-through is limited
While 3Q financial results were largely in-line with our estimates, the key update on the
quarter was on timing of the ACH-3422 read-out as well as additional clarity on the
strategic path forward once data are available. Importantly, the company has clarified
the previous guidance and expect data later this quarter (vs. "fall" previously). We
spoke with the company and do not see this as a meaningful change on timing.
Notably, while specific timing remains ambiguous the only implication is on pricing of
Nov. options, which remains tricky (but based on this update we can't exclude it will
come prior to Nov. expiry). Importantly, we do not see any read-through from the
revised language, and continue to expect a positive read-out. Further, while the
company indicated plans to start a triple combination study in 2015 (likely in reaction to
MRKs push into shorter treatment durations), management confirmed the ph2 trial will
enroll several cohorts (incl. '3422/rbv) and should have a protocol initiated by year-end.
Overall we see the 3Q update as in-line, with the ph1 ACH-3422 the key catalyst.
Highlights from the quarter
[1] ACH-3422 data are expected by year-end (vs. fall previously). The updated language
is to help clarify timing as the narrow focus on the start/end of fall was generating too
much confusion. [2] Once data are available, the strategic focus will likely move to triple
combinations (likely as a reaction to MRK/C-SWIFT). The goal remains to start the ph2
protocol by year-end (with the triplet cohorts likely to enroll in 2015). [3] The
complement Factor D program is interesting and diversifies ACHN beyond HCV. A 2015
IND would be an upside surprise and given the mechanism could see proof-of-concept
data relatively quickly. Preclinical data are expected at ASH.
In-line results suggest minimal impact to our model: focus on the data
We expect minimal investor focus on quarterly results and see the near-term ACH-3422
data as the key driver of investor (and strategic) interest.
Ma$†¡N®
Achieved4now
20 hours ago
martyc likes this. Quote
COWEN:
The Cowen Insight
Investor focus is on the ability of nuc candidate ACH-3422 to achieve a 4 log drop
in HCV RNA over 7 days. Based on its strong preclinical data, and following our
conversation with management today, we remain hopeful that 3422 will be sufficiently
potent. We believe there is a positive risk-reward into the Q4 data release and remain
at Outperform.
ACH-3422 Antiviral Data Next Major Catalyst. We Remain Optimistic.
The next major milestone for Achillion is the release of proof-of-concept data from
its uridine nuc candidate ACH-3422 later this quarter. ACH-3422 has produced
intriguing preclinical data including PK data supportive of 1x/day dosing and a lower
(better) EC50 for the HCV polymerase that Gilead’s sofosbuvir, with no apparent
effect on human polymerases. Achillion initiated a first-in-human trial and a proof
of concept ex-U.S. Phase I in Q2:14. The trial is a dose-escalating study testing 4
doses of ACH-3422 (According to the ANZCTR website the doses being tested are
50mg, 150mg, 300mg, and 500mg). At each dose level healthy volunteers were first
given single doses in the fed, and then single doses in the fasted, state. Healthy
volunteers were then dosed for 14 days at that dose, followed by dosing of HCV
patients for 7 days at the same dose. Following analysis of the data, the next, higher
dose was tested in a serial design. Achillion expects to announce the first anti-viral data from the trial later this quarter. ACHN's stock is down today as investors
seem to be interpreting the fact that data from the trial are not out yet as a sign that
'3422's profile may be disappointing. We think this is an over interpretation. Today we
discussed the conduct of the trial with ACHN management. Management said that
it typically takes 6 weeks (or perhaps a bit more) to cycle through each dose, from
the initial single dose in healthy volunteers through final analysis of the antiviral data.
According to ACHN's press release, patient dosing in the trial began around June 10.
If one assumes each dose cohort takes 6 weeks, results would be expected around
November 25. Therefore a data release in late November or early December seems
likely, consistent with ACHN's original guidance for data disclosure "this fall." During
our conversation management said that the doses being tested are within the range
disclosed on the ANZCTR website (500mg or less). Management did note that the trial
design is adaptive, suggesting that the doses may not be exactly the same as those
on the website. Nonetheless, ACHN has previously disclosed preliminary safety data
from the first two cohorts, saying that '3422 had a good safety profile following 14
days of exposure with 50 mg and 150 mg in healthy subjects. Management further
indicated in our conversation that thus far there have been no safety issues in the trial.
Therefore it seems to us that there have been no major changes to the trial design
due to safety or efficacy issues, and that data will come in late November or early
December simply because it takes 24-26 weeks to complete a large Phase I study like
this.
Ma$†¡N®
Achieved4now
19 hours ago
Quote
FBR Capital:
Speculation about Nuc and Diversification beyond
HCV Gives Post-Halloween Spook
Summary and Recommendation
Today, Achillion Pharmaceuticals (ACHN) reported financial results for 3Q14 and
updated investors on the timing of its HCV development platform. Investors reacted
negatively to the perceived uncertainty surrounding the timing of key data from
the development-stage nuc, ACH-3422, the main value driver for ACHN shares,
increasing volatility. The company changed the wording for ACH-3422 data release
from prior guidance for the “fall” to “later this quarter,” which led to speculation
that the trial had been expanded to accommodate higher dosing because of lack
of efficacy or lower dosing because of safety. Importantly, we confirmed with
management that the altered wording of the guidance was not intended to be a
deviation from prior guidance and that it still was on track to meet prior guidance.
Additionally, the company indicated that the sample size of the trial had not been
increased beyond the planned 112 patients. The uncertainty about the nuc data
was magnified by the company’s announcement of diversification outside HCV, with
early data from a complement platform at the upcoming ASH meeting. We also
note that Achillion will present SVR12 data from its combination of ACH-3102 and
Gilead’s Sovaldi for patients receiving eight weeks of treatment on November 10 at
the annual Liver Meeting (AASLD). We continue to view Achillion’s HCV program as
compelling and on track, and think that the volatility, while understandable given the
speculative nature of the company, is overblown. We see Achillion, with a wholly-owned, potentially best-in-class NS5A/nuc combination, as an ideal candidate for
larger HCV players including AbbVie, Bristol-Myers, Roche, and even Gilead. Our
updated revenue model and income statement can be found at the end of this
report.
Key Points
¦ HCV guidance unchanged/trial size not expanded. Achillion confirmed that it
had not intended to change the prior guidance for the timing of nuc efficacy
and safety data. Importantly, the trial size has not increased to accommodate
additional cohorts of patients, which should ease concerns that efficacy and
safety results were less than compelling, necessitating expanding the sample.
We do note that the trial is adaptive design, which allows for adjusting doses
and exposures within the cohorts.
¦ Nuc remains primary value driver. Management reaffirmed its commitment to
the HCV franchise despite diversification. We maintain that the upcoming data
for ACH-3422 is the prime value driver for ACHN shares and have not changed
our probability of success or timing.
¦ ACHN takeout thesis intact. We continue to see ACHN as an ideal takeout target
for any of the HCV-focused companies given the potential for a pan-genotypic
NS5B nuc and potentially best-in-class NS5A inhibitor. This includes AbbVie,
Bristol-Myers, Roche, or Gilead.
Quote
Leerink:
Possible Dose Escalation Pushes ACH-3422 Data to Later this
Quarter
• Bottom line:ACHN reported 3Q:14 earnings yesterday and announced
that the Phase Ib proof-of-concept top-line data for its uridine-analog
nuc ACH-3422 would be available “later this quarter.” While the data
timeline remains in the fall (which is technically through Dec 21) as
previously guided, it appears to be somewhat later than many investors
were anticipating. Although ACHN noted the trial’s adaptive design allows
for increasing or decreasing dose cohorts, it seemed possible that the
company has moved to higher doses to further explore efficacy. The
publicly disclosed trial design appears to indicate doses similar to other
nucs. We look forward to additional updates on ACH-3422, along with
SVR12 data from a Phase II trial of the NS5A inhibitor ACH-3102 in
combination with GILD’s (OP) Sovaldi (sofosbuvir), at AASLD.
• Adaptive trial design allows additional dose cohorts in the Phase
I ACH-3422 study. According to ANZCTR (the Australian New Zealand
Clinical Trial Registry), the trial is divided into the three parts. In the first
two parts, healthy volunteers receive one of several doses (50, 150, 300,
and 500 mg) of ACH-3422 or placebo for four single doses (Part 1) and
once a day for 14 days (Part 2). In 2Q:14, the company announced it
had completed the 50 mg and 150 mg healthy volunteer cohorts and
had observed a good safety profile at that point. Part 3 of the study, as
described in ANZCTR, investigates these four doses of ACH-3422 in
HCV patients once daily for 7 days. However, the company has stated the
trial has an adaptive design which allows for the doses to be escalated
even further (to 700 mg per day and higher) or reduced at any point
based on the results of the previous cohort. We believe that exploration
of a higher dose can be viewed as a positive from a safety standpoint.
Previous nucs, including Sovaldi, MRK’s (MP) IDX21437, and VRTX’s
(OP) VX-135 (see table on page 3.) showed potent viral reduction at a
dose in the range of 200-400 mg.
• Dosing has been completed for the 6-week cohort in the Phase
II ACH-3102+Sovaldi trial. While SVR4 data is not yet mature from
this cohort, SVR12 results from the 8-week cohort will be presented at
AASLD. The late-breaking abstract (LB-23) reported an SVR8 of 100%
and stated that all 12 patients had viral loads below the lower limit of
quantification (LLOQ) by week 3 and below the lower limit of detection
(LLOD) by week 5. We attempted to compare these viral kinetics data to
those seen with Sovaldi+ledipasvir+GS-9669, which was able to achieve
a 95% SVR12 rate after 6 weeks of therapy in the SYNERGY trial.
Unfortunately the data were not presented in exactly the same format,
although it would appear to us that ACH-3102 / Sovaldi data may be in a
generally similar range with regards to the speed of viral decline despite a
high baseline viral load.
Ma$†¡N®
Achieved4now
about an hour ago
Quote
Baird:
No change to view following 3Q14 results. Achillion's press release yesterday,
that did not include ACH-3422 results, led to a sell-off without a fundamental
rationale but one that we find difficult to defend against nonetheless. We still view
the risk/reward into ACH-3422 data as attractive at these levels but can't help but
feel that we wouldn't have seen yesterday's press release if the profile of 3422 was
clearly matching sofosbuvir, the nuc that all nucs will be compared to.
n Where's the 3422 data? Clearly the question the market was asking yesterday
amidst a 15.6% decline in the stock. While it is hard to point to anything
specifically within the press release as a negative, the absence of 3422 data
ahead of the AASLD conference this weekend, the timing of this release (they
PR'd quarterly results a week later last year), a slight timing delay for
Read more: http://bridgetunnelinvestor.freeforums.net/thread/500/achn-deutsche-bank?page=1&scrollTo=2250#ixzz3ICxfWA2N
Achn Deutsche Bank:
Winter is coming & so is the 3422
data this Q. DB take on weakness
We have gotten many questions about Achillion weakness this morning. They issued their quarterly numbers with corp updates. We think today’s reaction is an over-reaction.
? The key focus here is the nuke 3422. The language from the note was “we expect top-line results from our ongoing Ph1 trial of ACH-3422 later this quarter”
? Based on our call volume, we have gotten questions as to whether this is a delay or not.
? We have always used Achillion’s timelines as guidance and not assumed data at AASLD
The guidance has been data during the fall. Fall ends Dec 20 and it began Sept 21. That is technically later this quarter. We don’t see this as a delay
? We spoke to mgmt this morning and they said the program remains on track. This remains consistent with what we have been hearing from mgmt before this press release this morning
Here is how we have been thinking about the timelines for this study:
? Typically cohorts take 5-6 weeks to complete. We assume patient enrollment of 12 healthy pts and 8 HCV infected. The healthy study takes 14 days. The infected HCV pts then have to be enrolled and treated for 7 days. We then assume a week for viral loads and data analysis. This is about 5-6 weeks.
? Our sense was the company was likely in healthies at 150mg in early Aug. So that would mean by our math 150mg ended mid Sept. If they started 300mg late Sept, then assuming 5-6 weeks, that would mean late Oct/early Nov. If they were dosing up, the next cohort maybe will start Nov. That would imply it would end in early to mid Dec. This has not been confirmed by the company but is our sense on where the co may be since we get a lot of questions.
? Lastly, it is possible that the company does not read any data until the full dose escalation is done.
? Interesting side bar, the co identified a novel complement related platform for oral inhibitors of complement Factor 2. There will be some early data in vitro & in vivo at ASH this year.
biotech jim or others
sny a buy here??? longterm
@Sphere3D: @pbookman Great cameo and special thanks to @SimonBramfitt for contributing ;)
I am behind?? Did not know Simon was on sphere research
Team??
From twitter. @Sphere3D: Much more coming, but been holding on to this one since VMWorld. Glassware containerizes Windows... http://t.co/qHEA8CXX1E
Dew. Thoughts on this??
Separately we have had a pre-NDA meeting with the FDA to discuss our odanacatib results. We have agreed together upon a plan to characterize more completely the adjudicated adverse event reporting in this study which will mean that our filing will be delayed until 2015. The data that we presented at the ASBMR meeting in September demonstrate that odanacatib could provide a meaningful therapeutic option to reduce the frequency of osteoporotic fractures in women at high risk for these events.
Take-home points
? In our opinion, both TG-1101 and TGR-1202 demonstrate solid evidence of efficacy and durability, both as a monotherapy, and in particular, in combination with marketed products. However, we maintain that efficacy alone cannot get both products across the finish line. As highlighted above, a key differentiator for these two products is the side- effect profile. Given the lower SAE’s demonstrated, we are confident that trials evaluating combinations maybe be able to push already established dosing limits and potentially increase efficacy rates.
? We believe either one or both lead therapeutic candidates are acquisition targets within the next 24 months. We believe that the Pharma powerhouses that are leaders in hematology/oncology will strive to acquire and have in-house their own checkpoint inhibitor program which could then be used to combine monoclonal antibodies or other target therapies. Given that TG Therapeutics represents one of the few stand-alone companies with world-wide rights to two of the most sought after targets in biotech, we believe the company could squarely move into the acquisition cross-hairs of marquee companies such as Pharmacyclics and Celgene (CELG; not rated) as the data from ongoing clinical trials mature.
HCW Two Blockbuster Therapies in One Company; Initiating with Buy Rating
e of TG Therapeutics with a Buy rating and a target price of $17, based on a discounted revenues and earnings per share valuation methodology. TG Therapeutics’ core franchise is comprised of a glycoengineered anti- CD20 monoclonal antibody and a novel PI3Kd inhibitor targeting B- cell lymphomas. The company has multiple Phase 1 and 2 clinical studies ongoing with the potential to report updated data over the next 12 months. In addition, with a SPA in place, the company is poised to begin a registration study in combination with ibrutinib in 4Q14. With two de-risked lead assets ready to target multi-billion dollar therapeutic areas, news flow to generate shareholder value, and a cash position of $43 MM (pro forma), expected to fund operations until 2H15, we believe TG Therapeutics represents an undervalued player with significant upside for the long-term investor.
TG-1101/TGR-1202: A blockbuster in tandem or separately. Phase 1 and 2 clinical studies of lead therapeutic candidates TG-1101 and TGR-1202 have demonstrated excellent safety and a comparable or better efficacy relative to other marketed products. Preliminary data evaluating TG-1101 with ibrutinib demonstrated a superior 100% overall response rate in relapsed CLL as compared to 43% for ibrutinib alone and equivalent to ibrutinib in combination with Rituxan. Similarly, TGR-1202 has shown significantly lower liver toxicities when compared to Gilead’s (GILD; not rated) Zydelig which suggests to us that potential combination therapies may be better tolerated with TGR-1202. Despite a growing competitive landscape, we believe multiple opportunities exist for assets displaying efficacy and better side effect profiles to gain market share versus existing therapies.
Licensing and takeout potential. We believe the recent AbbVie (ABBV; not rated) mega-deal with Infinity (INFI; not rated) for the world-wide rights to IPI-145 ($275 MM upfront and $530 MM in milestones) underscores the upside potential at TG Therapeutics. While we believe that Pharmacyclics (PCYC; not rated) represents the ideal suitor given the myriad of studies currently underway combining ibrutinib with CD20-targeting monoclonal antibodies and PI3Kd inhibitors, we cannot rule out the possibility of separate partnership/licensing opportunities for each asset.
Data drives value. In our opinion, TG’s pipeline currently boasts two strong therapeutic candidates with excellent safety profiles. If successfully initiated, the Phase 3 study evaluating TG-1101 and ibrutinib could report results as early as 2016, representing a fundamental inflection point for investors. In the meantime, ongoing Phase 1 and 2 studies in CLL and NHL have the potential to report updated results at the American Society of Hematology Meeting in 4Q14, representing near-term drivers for investors.
Valuation. We value TG Therapeutics using a discounted earnings per share and revenue multiple analysis. Applying an 8x multiple to our risk (50%) adjusted 2023 revenues of approximately $1.01 billion and a 28x multiple to our 2023 earnings per share of approximately $4.63, we obtain a 12-month price target of $17.25, wh
FBR on gild
Strong 3Q Script Trends: Gilead Positioned to Beat Revenue Expectations across Portfolio
Summary and Recommendation
Based on Symphony Health Solutions and IMS Health prescription data, we believe Gilead is positioned to beat 3Q consensus revenue expectations for U.S. sales across the entire drug portfolio, with the exception of recently launched Zydelig. Zydelig was approved for three blood cancers (CLL, FL, and SLL) on July 23, with two months of sales. Zydelig stocking may offset the weak script trends, and it is unclear how well Zydelig is represented in the audit databases as a specialty oncology product. Notably, Sovaldi, Atripla, and Truvada are tracking 4%, 5%, and 4%, respectively, above worldwide consensus expectations. Accordingly, we are raising our forecasts for the quarter and our net annual product sales to $24.1B for 2014, above the consensus mean of $23.9B and prior guidance of $21B to $23B. For 3Q14, we expect net revenue of $6.37B and EPS of $1.97. Qualitatively, investors are likely to focus on hepatitis C payor dynamics and the recent Harvoni and Zydelig launches. Color on the European launch is also likely to be important, given the lack of script data to gauge expectations. Investors will also be looking for additional color around Gilead’s use of Irish tax strategies. Gilead reports on Tuesday, October 28 after market close. Risks to our raised revenue forecasts include weaker-than-anticipated European sales, for which we have little visibility given the lack of audit data availability.
Bmo on bmy
Better than our positive expectations. We were impressed with the performance of Yervoy, Orencia, and Sprycel. Eliquis should continue on a good trajectory with its new indications and good access. Early signs of Hep-C launch in Japan are encouraging. We forecast that Bristol will likely exceed its 2014 guidance. Looking ahead, we increased our forecasts for the key products to reflect the strong performance in 3Q. Our estimates remain significantly above the Street for 2015 and 2016 because of higher expectations for Nivo in lung cancer, and higher Sustiva and Hep-C forecasts. We expect Street estimates to rise after 3Q14 and probably before 1Q15 to reflect the longer exclusivity with Sustiva and Nivo’s potential in lung cancer. We expect positive results from the upcoming Nivo 063 trial in advanced squamous NSCLC patients. Based on the 003 Study, we expect Nivo 3mg/Kg to show ORR of ~20-25%, median Overall Survival (OS) of ~9-10 months, and 1-year OS Rate of ~45-55%. Given the narrow efficacy band seen with current options (i.e., ORR < 10%, median OS of 6-8 months, 1 year OS of 25-30%), our expected results from this single-arm trial should be sufficient for Nivo approval in NSCLC by mid-2015. Moreover, based on the Nivo 003 and 012 studies, we believe that both Nivo phase-3 second-line NSCLC trials (017 and 057) have a high probability of success, which could get reflected in the stock after the 063 results on October 31.
Lots of twitter action today. Ole my
BoAML GED- 0301 Shows Durable Response to 12 Weeks CELG
Clinical remission rate of 65% for high dose reliable
We attended the United European Gastroenterology Week (UEGW) conference,
where phase 2 GED-0301 results in Crohn’s disease were presented. As reported
yesterday, 65.1% of patients in the high-dose group (160 mg/day) met the primary
endpoint and achieved clinical remission, compared to placebo (9.5%, p<0.0001).
The primary endpoint is clinical remission at day 15 (one day after the 2-week
dosing period) and maintained for at least 2 weeks. Given that patients must be in
remission at both time points, we view this endpoint as highly stringent, which
translates to more reliable results. There were slight differences between the study
cohorts in duration of disease (lower in 40mg and 160mg doses), CDAI scores at
baseline (slightly lower in GED cohorts vs. placebo), % of patients refractory to
steroids (lower for 40mg group) and patients currently on immunomodulators (lower
for 10mg group).
12-week results demonstrate durable response
We view the 12-week remission rates as highly encouraging. Remission rates for
the high 160mg dose were 67.4% at day 15, 72.1% at day 28, and 67.4% at day 84
(all p<0.0001 vs. placebo). Remission rates for the 40mg dose were 57.5% at day
15, 70.0% at day 28, and 62.5% at day 84 (p<0.0001 for day 15, 28 and p<0.0008
at day 84). Only a few patients lost remission at 12 weeks, with only 2 weeks of
treatment with GED-0301. Both response and remission rates were higher than
those observed with anti-TNFs Humira and Remicade in Ph2 trials (refer to pg.2).
However, of note, the patients in the Humira and Remicade trials had higher
baseline CDAI scores.
Clinical efficacy corroborated by inflammation biomarker
Approximately 61.4% of patients enrolled in the study had elevated c-reactive
protein (CRP), an inflammation biomarker, at baseline. In the 160mg dose, 67.9% of
the patients had high baseline CRP, but were able to achieve clinical remission at
day 15 and 28 (p<0.0001). Roughly 20% of these patients had normal CRP at day
15. Approximately 45.5% of patients with high baseline CRP in the 40mg dose
cohort were also able to achieve remission at day 15 and 28 (p=0.01). No
colonoscopy was performed, so no data on mucosal healing is available.
Safety appears benign, with no strictures at week 12
No adverse events related to stricture development were reported. There were 9
serious adverse events in 6 patients (3 were in the low-dose 10mg/day group and
one in each of the 40mg/day and 160mg/day groups) and these were mostly related
to CD-associated complications and symptoms. The one SAE in the 160mg dose
was thermal burn (burn sensation during evacuation). There were no
discontinuations in the 40mg and 160mg dose cohorts. Adverse events that
occurred in 5%+ of patients included abdominal pain, worsening of Crohn’s,
increase in CRP, pyrexia, abdominal mass and diarrhea, amongst others
DB on arwr. I took a hit on this one today
We see higher risk but do not think program is dead. New TP $20
We don't think the program is dead, but we see timeline risks. New TP is $20
The viral reductions w/ ARC-520 were lower (0.2 and 0.3 log) than expected but we do not think the program is dead. We are disappointed the management handling of expectations around the Ph 2a trial. Given the results we see risk from 1) longer timelines,2 ) potential competitors & 3) risk of using higher doses. However, this abstract was selected as a late breaker which underlines the importance of data to Hep-B community. Given the Stock is trading close to cash ($3/sh), the risk reward may be favorable into the AASLD. However, we are reducing the TP to $20 from $45 previous to account for the increased risk. Maintain Buy.
meaningful for the space.
New Target Price $20; Maintain Buy. Risks
We are lowering our TP to $20 from $45 before as we reduce the probability of success of ARC-520 to 25% from 40% previous and increase the discount rate to 14% from 12% previous to account for increased risk. Our $20 TP for Arrowhead is based on DCF (14% discount rate to account for the risk associated with development and 2% terminal growth rate to account for the platform technology). Downside risks include: 1) lack of efficacy for lead asset ARC-520 or future product catalysts, 2) safety signal on ARC-520 or future product candidates, 3) smaller-than-projected market opportunity in HBV, 4) competition and smaller than expected future asset opportunities
We are doing an on the fly conf call at 1:30PM ET today to talk about our thoughts on ARC-520 data. Dial in: 800 309 8606. Conf id: 18386755
We spoke to mgmt – Key questions and answers
Why did the response differ at days 43 and days 85? Mgmt says this is due to small numbers and variability around that. At day 43, the knockdown did show a dose dependent relationship. They are surprised by the duration of response which is better than they thought.
Do we think ARC-520 is dead? We think higher doses will show a greater dose dependent relationship. Mgmt says that they can start ph2b within their expected timelines. There will be multiple doses and that 50pct KD is a reasonable low dose. We think that higher doses than 2mg will certainly be needed, so we await data on 3mg. Mgmt reiterates at 2mg is right at onset of effect. We think expectations at the high end were around .5 logs.
What is status on 3mg and 4mg? As of a couple weeks ago, the co said that they had 2 pts left on the 3mg. We would assume it’s close to done now. The 4mg healthy is complete. Mgmt says timelines for 3mg at AASLD will be very tight. Gating step for 4mg is they need to get approval, protocol amend, and present 3mg safety to dsmb.
What to expect at AASLD? Mgmt suggests there will be further data presented at AASLD during the late breaker. We will be looking for curves at these 2 doses, any more detail on safety to make sure the high doses are safe. We do think AASLD has a high std for data presented as LB so these data are
@michael_keen: RT @EarthLink: We need to start thinking of contextual & mailable apps 4 sec & user engagement & exp. http://t.co/cWhLZKVWXd CC: @Sphere3D
@michael_keen: @MobilePhillip for now, but watch what @Sphere3D is doing in this micro-container space for legacy Windows apps. Very cool #containers #EUCA
DB on Merck/idix
? Merck/Idenix: We saw full Phase 1 data for Idenix nuke which Merck recently acquired. Viral load reductions at 300mg QD were ~4.23log in GT1 and 4.27log in GT2/3. These reductions are similar to previously communicated by the companies. This is the first time we have seen the full data.
? Alios/JNJ: Preclinical data for 2 nukes are in two abstracts. One of these nukes is Guanosine while other one is Uridine. Most of the Guanosines have failed in clinical development. We do not see a lot of incremental info in these abstracts and note that these assets are very early stage assets. The co said that they can take a nuke into the clinic in 4Q14. We note that Alios wasn acquired by JNJ yesterday.
IMHO not much value at all if any being placed
At this point not much. Pima in PD alone IMHO can support
Still a higher price
With that said acad hitting in AD doubles share price
I like those odds and have over the last 6 months been adding
Acad. Great post by Biotech Jim.
On the Topic of the Relationship between PDP and ADP
I have been thinking about this for some time, starting a couple years ago when I first bought the stock (as a trader) and it was clear that the ACAD trial, if successful, could launch ACAD into the big time.
To start, anyone who tells you that they fully or even substantially understand the relationship between these two types of psychoses, refer to my previous post regarding "you cannot bullshit a bullshitter". Ask them how many synapses are involved in the psychosis for each disease, and how they proceed from the established altered neuronal architecture to the final outflow of the psychosis symptoms. Then ask them how many of these synapses contain significant 5HT2a receptors and how that was determined. Then ask them how many inhibitory synapses are present in the relevant neural circuit, and if any of these contain 5HT2a receptors.
Obviously there are significant 5HT2a receptors in the PD patient somewhere along the path of the the lost nigrostriatal dopamine synapses to the outflow of the psychotic symptoms of visual hallucinations. How about for the AD patient that has auditory or another type of psychosis? The pathology in AD is neurofibrillary tangles and Abeta containing plaques. Somehow, these neuroanatomical pathologies lead to the CNS outflow of psychosis. The neuroanatomical substrate is in all liklihood cortical, but what is yet not firmly established is whether 5HT2a synapses are involved. The literature is not convincing to me, and as such since we have a very clean drug it is a good idea to go into man to test the hypothesis obviously. There is some animal AD model work with pimavanserin, that most here are aware ( http://www.ncbi.nlm.nih.gov/pubmed/22750845 ). The problem with the rodent models of AD is that they generate a "quick" phenotype, that may not have all the adaptive changes in the natural disease. Nonetheless, pima prevented DIO-induced head twitches, reversed ampehetamine induced locomotor responses, and normalized prepulse inhibition in b-amyloid treated animals. I should note here that 5HT2a receptors need not be elevated in AD for pima to show efficacy, but only to have a significant involvement in the relevant neuronal circuitry.
There is no way that I know whether visual vs auditory hallucinations involve most of the same ouflow pathway in the CNS. But, if several synapses are involved, the likelihood is that there are close similarities between the two types of psychoses. Note also that AD patients can have auditory hallucinations as well as auditory hallucinations.
My view is that you have a safe drug for psychosis and this alone warrants testing in ADP. Unlike memory-enhancing drug candidates for AD that need to be tested early on during the disease course, agents for psychosis do not necessarily need such early treatment. I give pima a somewhat better than 50% chance of efficacy in ADP.
@lasonyacobbs: @pbookman @newcaneyisd @Sphere3D Yes! We just had our student login to Istation on their @dell Chromebooks. It works perfectly! #glassware
Interesting tweet
@sphere3d #glassware + istation for Chromebooks = amazing solution for @newcaneyisd
— LaSonya Cobbs (@lasonyacobbs) September 29, 2014
Licensing Full TGR-1202 Rights Inclines Us To Raise TP To
$22 From $19. From BREAN
Investment Summary
We are raising our TP to $22 from $19 due to adjustments to our model. We are now modeling TG-1101 and TGR-1202 sales, versus TG-1101 sales alone. This change also reflects the expectation that CLL is the primary market that TG’s drug candidates are targeting, as well as our increased confidence in the prospects for both of them. Earlier this week, TG exclusively acquired the full (excluding India) rights to TGR-1202 from Rhizen Pharmaceuticals, representing an early exercise of its full in-licensing option versus its initially licensed 50% rights. The move was, in our view, clearly due to the similar efficacy seen thus far but with only QD dosing, the lack of hepatotoxicity, and the more benign toxicity profile in general, versus peer PI3K delta inhibitors, as well as the success with the drug's micronization. The drug has been progressing rapidly through the clinic, much like TG-1101 after TG took control of it, and we believe that it too will be eventually awarded an SPA in combination with TG-1101. Last week TG achieved an important SPA with the FDA regarding its first Phase 3 trial for TG-1101 plus ibrutinib. This differentiated SPA dictates a primary endpoint of ORR to support accelerated approval for TG-1101, an endpoint that can be achieved quickly and which is important to have. We look forward to data from more than 30 Phase 2 CLL patients at ASH taking TG-1101 and ibrutinib, as well as data from about 30 patients taking TG-1101 and TGR-1202.
Discussion
We are raising our TP to $22 from $19 due to adjustments to our model. We are now modeling TG-1101 and TGR-1202 sales, versus TG-1101 sales alone. This change also reflects the expectation that CLL is the primary market that TG’s drug candidates are targeting, as well as our increased confidence in the prospects for both of them.
TGR-1202. Earlier this week, TG exclusively acquired the full (excluding India) rights to TGR-1202 from Rhizen Pharmaceuticals, representing an early exercise of its full in-licensing option versus its initially licensed 50% rights. TG will pay $4 million in cash and 370,000 common shares of TG stock to Rhizen upfront, and is obligated to pay milestones of up to $240 million based upon future success (regulatory filing, approval, and sales milestones) and tiered royalties on any net sales of TGR-1202 to Rhizen in the future. The early in-licensing of TGR-1202 was, in our view, clearly due to the similar efficacy seen thus far but with only QD dosing, the lack of hepatotoxicity, and the more benign toxicity profile in general, versus peer PI3K delta inhibitors, as well as the success with the drug's micronization. The revised deal provides TG with greater control and flexibility in the development of TGR-1202, and we believe that it all came inexpensively. The drug has been progressing rapidly through the clinic, much like TG-1101 after TG took control of it, and we believe that it too will be eventually awarded an SPA in combination with TG-1101. We note the high cost of drugs like Imbruvica and Arzerra, and the competitive advantage of potentially being able to deliver a similar potency and greater safety versus peer combination therapies, but at a lower cost due to having control of both drugs.
TG-1101. Last week TG achieved an important SPA with the FDA regarding its first Phase 3 trial for TG-1101 plus ibrutinib for CLL patients with high-risk cytogenetics. A total of about 330 CLL patients will be randomized into the Phase 3 trial to receive TG-1101 plus ibrutinib or ibrutinib alone, and about the first 2/3 of the patients will be assessed for overall response rate (ORR). This differentiated SPA dictates a primary endpoint of ORR to support accelerated approval for TG-1101, an endpoint that can be achieved quickly and which is important to have given the competition in this space. All patients will then be assessed for PFS, which will support a full approval for TG-1101. More details about the SPA will be announced at the launch of the Phase 3 trial by YE14. At the ASH conference in December, we look forward to efficacy and safety data from more than 30 Phase 2 CLL patients taking TG-1101 and ibrutinib. Also at ASH, we note that TG will deliver data from about 30 patients taking TG-1101 and TGR-1202, and that all patients will have enrolled by the end of September and thus a minimum of 2 months of follow up should be available for all. Patients in this trial will be followed up for a maximum of 6 months.
Valuation / Target Price
We derive our target price through a DCF analysis, using a 30% discount rate and a 5 multiple of the terminal value for the projected 2022 EBITDA.
pigger from mike king jmp
ESMO update of AP26113 Phase I data in ALK+ NSCLC characterized by steadily
impressive objective response, best-in-class PFS, and tolerability; reiterate our
Market Outperform rating on ARIAD Pharmaceuticals and $7 price target based
on our DCF and SOTP valuation methodologies. We are attending the ESMO 2014
Congress this weekend, where ARIA presented updated Phase I data with AP26113
in patients with ALK+ NSCLC. Briefly, with an additional 15 patients and three months
follow-up since ASCO, the Phase I data continue to impress (72% ORR, eleven months
median DOR, minimal pulmonary symptoms with titrated dosing), particularly against
the backdrop of Zykadia (NVS, NC), which shows signs of worsening tolerability with
longer follow-up. We believe these data will benefit accrual in the registration-directed,
Phase II ALTA trials in crizotinib-resistant patients. However, we see only incrementally
positive impact to the stock given the limited contribution of '113 (~$1.60/share) to our
overall valuation for ARIA.
AP26113 continues to impress on efficacy since ASCO, bearing several hallmarks
of best-in-class ALK inhibitor activity. Specifically, overall objective responses were
steady at 72% as the number of evaluable patients grew from 57 to 72 (69% ORR
(45/65) in crizotinib-experienced patients, 100% (7/7) in crizotinib-naïve patients),
including four CRs (two in each treatment category), compared to only one crizotinibnaïve
CR recorded at ASCO. Also of note, PRs were also observed in 1/3 patients on
study receiving prior treatment with Zykadia. Overall duration of response (DOR) was
~11 months, as was median PFS among crizotinib-experienced patients. Albeit still from
a smaller data set, these responses compare favorably to that of Zykadia, which showed
56% ORR in crizotinib-experienced patients (including three (1.8%) CRs), median DOR
of 8.25 months and PFS of 6.9 months in its ESMO update. Brain activity with ‘113 was
more or less similar to ASCO, with 10/14 patients showing some regression of brain
mets (compared to 9/13 at ASCO), including four CRs (two of which were in crizotinibnaïve
patients and two PRs).
Roth Capital Maintains Buy On Overland Storage Following 4Q14 Results
September 24, 2014 8:18 PM
In a research report issued today, Roth Capital analyst Krishna Shankar maintained a Buy rating on Overland Storage (NASDAQ:OVRL) with a price target of $4.43.
Shankar observed, “OVRL reported 4Q14 revenues/GAAP EPS results of $24.2 million/$(0.42) versus our $24.5 million/$(0.33) estimates. We believe that OVRL’s pending merger with Sphere 3D Corporation (Nasdaq: ANY) may create a leading virtualization, data management/storage platform company . We believe that OVRL and Sphere 3D are making good progress on platforms combining OVRL’s storage products with Sphere 3D’s Glassware cloud/ mobility virtualization platform and V3 desktop virtualization appliance. The deal may close by Oct/Nov 2014 with 65% of OVRL’s shareholders supporting the deal.”
Tgtx roth update. BW your going to be busy
Given the positive clinical readouts to date with TGR-1202 alone and in combination with TG-1101, we believe acquiring the full rights for TGR-1202 is a favorable course of action. We believe that this way, TGTX would have significant leverage if it chose to pursue a partnership. This is particularly emphasized by the recent favorable terms that Infinity (INFI-NC) secured in the deal with AbbVie (ABBV-NC) for its PI3K inhibitor. Recall that the TGR-1202 single agent study showed that 100% of CLL patients treated with = 800mg TGR-1202 exhibited significant nodal reductions and 80% achieving PR or nodal PR. Importantly, TGR-1202 was shown to be safe and well tolerated in patients treated over a year with no hepatotoxicity. The combination study of TG-1101 and TGR-1202 achieved 100% ORR. These data indicate that TGR-1202 is a potential best-in-class PI3K-delta inhibitor as well as very good combinable potential with other drugs and therefore can have potential interest from a partnering standpoint.
TGTX has a very busy rest of the year ahead as the company 1) initiates the Phase III of TG-1101/Imbruvica combo study, 2) will disclose additional Phase III studies by year end, and 3) release additional data readouts at ASH from single agents studies of '1101 and '1202 as well as from the Phase II combination study of '1101 with 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.
WF - CELG: GED-0301--Big Expectations In Crohn's Disease (CELG remains a top pick and on WF's Priority Stock List)
Summary: We are exploring one of biotech's most highly anticipated catalysts of the fall, ph.II results from recently in-licensed pipeline candidate GED-0301 for Crohn’s disease (abstract posting in coming days, medical meeting presentation 10/21). Though CELG had already seen this nonpublic data--which they called compelling--upon in licensing of the product, we believe full details will be important for shaping the Street perceptions about its promise. Based on our analyses, although unknowns remain, we feel comfortable that the data will indeed live up to the high expectations set by CELG, stimulating enthusiasm for ‘301’s potential future revenue contribution to the company and driving appreciation for shares. CELG remains a top pick and is on Wells Fargo’s Priority Stock List.
Expect strong data to emerge, near-term driving upside potential as Street appreciation for the opportunity increases: Beyond CELG’s enthusiasm, our analyses of ‘301's mechanism, prior studies of ‘301 and other drugs, and the ph.II design all suggest to us robust efficacy is likely to be reported; we believe the short treatment duration will unlikely reveal any safety concerns.
Several thing we would focus on in ph.II results: We would primarily look at remission rates--rates of 50-75% (vs. ~20-35% pbo) would look compelling to us and allow for some decrement in larger pivotals, and we would also look at safety (fibrosis signals), dose dependence, durability of treatment effect, and patient baseline characteristics (to contextualize vs. other studies), to help support replicability of treatment and ‘301’s potential place in the future treatment paradigm.
Still some important risks that need to be resolved over time: These risks include theoretical fibrosis risk due to continual TGF-beta upregulation (though potentially addressable with intermittent dosing, assuming high durability, and attributes of pathophysiology could also limit this), high historical Crohn’s failure rates going from ph.II to ph.III (which keeps us at 60% probability of success, though could be addressed by trial design optimization), and the drug's local effect (which could modestly limit the addressable population).
Market opportunity could be meaningful to CELG in out years: Even with relatively conservative penetrations, we believe $1.6B+ sales in TNF-refractory patients could be easily achievable just 5 years into launch, with potential upside if ‘301 moves into earlier lines of therapy (feasible given convenient oral administration) and/or with additional inflammatory disease indications--helping augment CELG's future revenue base.
REPEATING
We believe that OVRL’s pending merger with Sphere 3D Corporation may create a leading virtualization, data management/storage platform company.
We believe that OVRL and Sphere 3D are making good progress on platforms combining OVRL’s storage products with Sphere 3D’s Glassware cloud/mobility virtualization platform and V3 desktop virtualization appliance.
The deal may close by Oct/Nov 2014 with 65% of OVRL’s shareholders supporting the deal.”
Roth Capital Maintains Buy On Overland Storage Ahead Of 4Q14 Results
September 22, 2014 1:37 PM EDT
In a research report issued today, Roth Capital analyst Krishna Shankar maintained a Buy rating on Overland Storage (NASDAQ:OVRL) with a price target of $4.43, ahead of the company’s fourth quarter results.
Shankar said, “We expect OVRL to report 4Q14 revenues/GAAP EPS of $24.5 million/ $(0.33)on Sept 23. We believe that OVRL’s pending merger with Sphere 3D Corporation may create a leading virtualization, data management/storage platform company. We believe that OVRL and Sphere 3D are making good progress on platforms combining OVRL’s storage products with Sphere 3D’s Glassware cloud/mobility virtualization platform and V3 desktop virtualization appliance. The deal may close by Oct/Nov 2014 with 65% of OVRL’s shareholders supporting the deal.”