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Amgen, Inc. (AMGN) Message Board

rob_cos 72 posts  |  Last Activity: 10 hours ago Member since: Dec 31, 1997
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  • Leerink Swann

    November 20, 2014

    OUTPERFORM

    Reason for report:

    COMPANY UPDATE



    Price Target: $124.00 from $90.00



    AGIOS PHARMACEUTICALS, INC



    .AG-120 Data Strengthen Proof of Principle; Remains an Interesting Name for 2015



    • Bottom Line: At the 2014 EORTC-NCI-AACR (ENA) meeting, AGIO presented initial data from AG-120 (IDH1 inhibitor) in acute myeloid leukemia (AML). The initial robust activity was comparable to the efficacy from more mature data for AG-221 (IDH2 inhibitor). We believe the consistency between AG-120 and AG-221 data strengthens the proof of principle data for both agents and the approach of targeting IDH mutants pioneered by AGIO. Although we are mindful of the high valuation after the recent rally, we believe AGIO remains a highly interesting name for 2015 with solid tumor data on AG-120 and potentially Phase II patient data on AG-348 (for pyruvate kinase deficiency) beyond ASH data on AG-221 and AG-348. We increase our valuation for AGIO from $90 to $124 based on a revised model of AG-221 and AG-120 and a higher probability of success for AG-120.



    • Comparable, if not better, efficacy for AG-120 vs. AG-221 (see page 2); early signs of durability encouraging. Although this was an initial report from a Phase I trial, efficacy data appeared more meaningful with a somewhat larger number of evaluable patients than we imagined (14). Similar to AG-221, activity for AG-120 was seen across all 4 dose cohorts. Although overall response rate (ORR) was slightly lower (50% vs. 56% for AG-221), both complete response (CR) rate and compiled complete and incomplete CR rates were better than AG-221. Treatment duration reached ~6 months for 1 CR patient and overall treatment duration appears good since no patients relapse after achieving an ORR. At the ENA presentation, AGIO management continued to state that there has been no known mechanism of resistance identified.



    • Plasma 2HG biomarker reduced to normal range across all dose levels. While there was a clear dose-related drug exposure, plasma 2HG was reduced across all doses at a similar level (up to 98% inhibition). Consistent with preclinical data, IDH1 inhibition led to 2HG lowering, which further validated drug effect



    • Overall good safety profile. Although there was one limiting toxicity (QT-prolongation), maximum tolerate dose (MTD) still hasn’t been reached and dose escalation continues. Additionally, QT-prolongation was resolved when dose was reduced from 800mg QD to 500mg QD and the patient remains on study with Grade 1 QTc prolongation but achieving a CR. All 6 deaths occurred after 28 days of dosing and were considered not related to the drug.



    • AG-120 expansion cohorts to be initiated in 1H:15, solid tumor data expected in 2015. While dose escalation still continues, expansion cohorts are expected in 2015 in AML, MDS and MPD. Similar to the AG-221 program, AG-120 could have a rapid path to commercialization.

    Please refer to pages 6 - 9 for Important Disclosures, Price Charts and Analyst Certification.

    INVESTMENT THESIS

    AGIO’s strong platform in cellular metabolism has resulted in seminal discoveries which the company has been able to capitalize and translate into a full array of early clinical or late preclinical pipeline agents targeting cancer and ultra-orphan indications of inborn errors of metabolism (IEMs). AGIO is a clear leader in the discipline of cancer metabolism, a potentially

    fruitful area of exploration for new cancer therapeutics. AGIO’s most advanced candidates, AG- 221 and AG-120, target mutations in the enzymes isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2). Both targets are genetically validated and mutations have been identified in acute myeloid leukemia, brain cancer, sarcoma, and biliary tract cancers. Third candidate AG-348 targets the ultra-orphan blood disorder of pyruvate kinase deficiency which is an IEM manifested by severe hemolysis. Although we are clearly mindful that AGIO’s pipeline is very early, there is very strong genetic validation for the lead candidates. The observations of single mutation in IDH1 and IDH2 (isocitrate dehydrogenase) on a single allele being associated with cancer point to gain of function alterations that are well suited for drug therapeutics. As AGIO pioneered the field, there does not appear to be visible competition. AGIO’s strong partnership with CELG (OP) not only funds the programs but also leaves good upside including full US rights for 1 in 3 compounds. These terms, based purely on the cancer metabolism platform with compounds still on the drawing board, are impressive and in our view provide clear validation for AGIO. Additionally, AGIO is leveraging its metabolism platform to target rare IEMs that we believe could provide a rapid path to market. Its lead IEM compound AG-348 appears to be able to accomplish the difficult task of activating multiple defective forms of pyruvate kinase-R and potentially provides a therapy for pyruvate kinase deficiency (PKD), a rare blood disorder.



    AG-120 and AG-221 Data Comparison

    Source: Company reports and Leerink Partners LLC



    Positive read through to data readout in solid tumors, a much larger market potential.



    While solid tumors and hematologic malignancies are very different tumors, two independent positive studies have validated the underlying science and supported anti-IDH cancer therapeutics. Incidence of IDH1 mutations is higher in solid tumors (e.g. ~71% in low grade and secondary glioblastoma, 40% of chondrosarcoma and 1-3% in several solid tumors including colon, melanoma, lung and prostate), which in aggregate could represent 60k patients or multibillion market potential.



    AG-120 AG-221

    Evaluable pts # 14 25

    ORR 50% 56%

    CR 29% 24%

    CR+CRi+CRp 43% 36%





    Compound Timing Event



    8-Dec-14 ASH investor event



    AG-221 (IDH2)



    4Q:14 Initiate Phase I in advanced solid tumors with IDH2



    ASH 2014 (Dec 6-9) Update from Phase I dose escalation study in hematologic malignancies with IDH2 mutations



    AG-120 (IDH1) 1H:15 Initiate expansion cohorts



    AG-348 (PKR activator) ASH 2014 (Dec 6-9) Phase I dose escalation data in healthy volunteers



    By early '15 Initiating Phase II in PKR pts



    Medical conferences in 2015



    Initial data from natural history study



    Drug Status Note

    AG-221 (IDH2 inhibitor) Phase I

    Phase I dose escalation study in IDH2m

    hematologic malignancies initiated in 3Q:13.



    AG-120 (IDH1 inhibitor) Phase I

    Phase I trials in solid tumor and hematologic

    malignancies initiated in 1Q:14



    AG-348 (PKR activator) Phase I

    Phase I trial in healthy volunteer initiated in

    2Q:14



    VALUATION

    We are increasing our valuation from $90 to $124 for AGIO to reflect increased probability of success for AG-120. Our $124 price target is based on DCF and sum-of-the-parts methodology. Our assumed probability-of-success is 70% for AG-221 (IDH2) in AML and MDS, 70% (from prior 55%) for AG-120 (IDH1) in AML and MDS, and 30% for AG-348 as well as AG -221 and AG-120 in solid tumors and $150k per patient pricing (vs. $100k previously). We use a 10% discount rate and believe it is appropriate given probability-weighted sales projections. Our royalty assumption is 10-13% for IDH2 w/w sales and IDH1 Ex-US sales. We include $500M valuation for the platform and other pipeline and an estimated $260M cash

  • Another all time high $111.97 and all time closing high $111.07 for CELG with Crohn's data & ASH soon - 160 data presentations at ASH and GED-031 Crohn's data in a "MAJOR MEDICAL JOURNAL VERY VERY SOON"

  • rob_cos rob_cos Nov 24, 2014 3:18 PM Flag

    High confidence from management in potential share gains with NDMM label expansion.
    CELG was particularly enthusiastic on the potential for significant share and duration gains for Revlimid
    over time once the label is potentially expanded to incorporate front-line MM patients. They pointed out that
    in the EU, front-line market share is

  • Much better than the usual Wells CELG report - packed with positive info. ISI is meeting with CELG in Summit right now - hope we get a similar update from them tomorrow. They might wait until there next Friday Video webcast but not sure they will have one this Friday.

    November 23, 2014
    Equity Research
    CELG: Highlights From Meeting With Management

    Summary: We had the opportunity to host a meeting with CELG’s senior
    management on 11/20. Coming out of our meeting, we are even more confident
    CELG is favorably set up for the near term (with continued commercial
    execution), medium term (with major gains possible by Revlimid, pomalidomide,
    and Abraxane), and long term (with proprietary pipeline candidates such as ‘301
    and partnered programs potentially driving considerable value). We remain
    bullish on shares and continue to see significant opportunity for stock
    appreciation. CELG is on the Wells Fargo Priority Stock List.

    Regulatory discussions ongoing for GED-0301 (mongersen) for
    Crohn’s disease, with some hints at a phase II/III strategy that could
    assess the drug’s maintenance prospects and still enable approval by
    the ~2019 timeframe. CELG remains in an ongoing dialogue with regulators
    on pivotal trial design, which we believe centers around areas like how to assess
    ‘301 maintenance and the role of endoscopy as an endpoint, not surprisingly. Our
    sense is CELG hopes to begin a ph.IIb study (which would be part of a
    registrational package) before year-end, assessing the usual 14-day induction, but
    closely tracking durability of effects, with potential for retreatment. Clinical
    response and endoscopy data rolling out of this study, in conjunction with
    additional analyses of the prior phase II results, would guide potential
    incorporation of a retreatment protocol (if needed) into a phase III, planned to
    start H1 2015 and run in parallel. The company expects studies in the pivotal
    program could accrue very rapidly. Management remains very confident in the
    conduct of the prior phase II and that the response seen in trial subjects will be
    representative of response in a real-world Crohn’s population, also noting
    “striking” improvements in physician perceptions of the drug coming out of the
    UEGW data presentation in their quantitative poll.

    Revlimid NDMM regulatory discussions appear on track. Though the
    company did not provide specifics on the exact nature of their ongoing
    discussions with EMA and FDA on label expansion into newly-diagnosed multiple
    myeloma patients, they noted no changes from their prior assumptions in terms
    of likelihood and timing of approvals. We see this as a positive sign reducing
    potential risk, especially as we would expect increasing focus on the NDMM
    regulatory processes as potential 2015 approvals approach. The company will use
    a collection of studies, led by ‘020, which they remain confident will
    overwhelmingly support approval. Potential nuances in the expanded label could
    include recommendations on age (+/-75), number of cycles, etc.

    High confidence from management in potential share gains with NDMM label expansion.
    CELG was particularly enthusiastic on the potential for significant share and duration gains for Revlimid
    over time once the label is potentially expanded to incorporate front-line MM patients. They pointed out that
    in the EU, front-line market share is

  • JMP on KPTI - Outperform & $57 target - KPTI: - ENA2014 conference contained pre-clinical data that provided a fuller picture of KPTI anti-cancer mechanisms


    November 24, 2014
    Biotechnology - Company Update

    Karyopharm Therapeutics Inc. (KPTI)
    ENA2014 Wrap-Up: Selinexor Pre-Clinical Studies; Early Glimpse of PAK4 Inhibitor Activity

    MARKET OUTPERFORM | Price: $41.21 | Target Price: $57.00
    INVESTMENT HIGHLIGHTS

    Presentations at last week’s ENA2014 conference contained pre-clinical data
    that provided a fuller picture of Karyopharm Therapeutics' selinexor anti-cancer
    mechanisms; PAK4 inhibitor profile begins to take shape; reiterate Market
    Outperform rating and $57 price target, based on our DCF, CAGR, and SOTP
    methodologies. Multiple data presentations were provided at ENA2014, both by KPTI
    and outside investigators. Two pre-clinical presentations further elucidated selinexor's
    anti-tumor properties, while a discussion by outside investigators spoke to the drug’s
    ability to synergistically or additively combine with other anti-neoplastic agents.
    Additionally, the next asset in the company’s pipeline (PAK4 inhibitor) is demonstrating
    intriguing activity.

    Selinexor blocks the expression of DNA damage repair genes, and sensitizes
    both solid and hematologic cell lines to DNA damage, inducing agents. In a poster
    presented by scientists from KPTI, selinexor, although not a DNA damaging agent, was
    shown to disrupt the expression of DNA repair proteins, including Rad51 and CHK1.
    Experiments showed that treatment of AML cells with selinexor after their exposure to
    doxorubicin and idarubicin inhibited the repair mechanism of DNA damage, and resulted
    in apoptosis as measured by PARP and caspase-3 cleavage. In a separate experiment,
    effects of single-agent selinexor, radiation, or the combination in lung tumor xenografts,
    showed a reduction in tumor size of 15%, 43%, and 96%, suggesting synergy between
    selinexor and radiation. Selinexor also provided additional cell killing when added to
    CHK1 inhibitors in a cervical adenocarcinoma cell line. Our interpretation of these
    data is that combination therapies, including selinexor, along with other chemotherapy
    agents and radiation, are likely to provide even more impressive clinical benefit than
    has been seen with single-agent selinexor. We have already seen a strong hint of
    combination therapy with selinexor in the myeloma results wherein the drug is combined
    with dexamethasone (albeit not a cytotoxic agent).


    Is selinexor on its way to becoming the partner of choice for a wide variety
    of anti-cancer agents? In a discussion by Dr. Daniel Sullivan of the Moffitt
    Cancer Center in Tampa, FL, selinexor was seen to be additive or synergistic
    with, and can restore sensitivity to, a wide variety of anti-cancer agents. While
    these experiments were all conducted in cell lines, much of the early pre-clinical
    work examining selinexor in cells has been recapitulated in humans. In
    combination with doxorubicin, selinexor was shown to sensitize drug-resistant
    cells to destruction, as well as to increase the number of double-strand breaks in
    DNA. Dr. Sullivan repeated his results with bortezomib (Velcade) and carfilzomib
    (Kyprolis), but also showed that these combinations did not increase toxicity to
    peripheral blood cells (PBMCs). Finally, in series of experiments wherein the
    sequence order of agents was varied (carfilzomib followed by selinexor, and then
    vice-versa), Dr. Sullivan once again confirmed the synergy with the
    aforementioned agents as well as with melphalan, a commonly used agent for
    the treatment of myeloma (particularly in Europe). Recall, this combination is the
    subject of an abstract to be presented at ASH. Oddly, Dr. Sullivan stated that his
    experiments showed no synergy with dexamethasone, a steroid commonly used
    in myeloma patients. We were surprised but not concerned about this finding;
    recall at EHA in June, the company showed robust synergy between selinexor
    and dexamethasone in a highly refractory myeloma patient population. Updated
    findings that confirm these results are also the subject of an oral presentation at
    ASH.

    PAK4 inhibitor packs a wallop against cancer. At the Friday morning poster
    session, KPTI presented pre-clinical data on KPT-7523, an orally available,
    potent and specific small molecule inhibitor of PAK4, also known as p21
    activated kinase. The PAK family of proteins regulates cell survival, cell division,
    and apoptosis (cell death). PAK4 is up-regulated or mutated in many tumor
    types. It is also downstream of the KRAS oncogene and mediates cell
    movement, division and survival by binding to certain essential cell proteins.
    KPTI investigators presented data to show that another PAK4 inhibitor, KPT-
    8752, inhibited 91 different tumor cell lines with an IC50

  • rob_cos rob_cos Nov 24, 2014 12:08 AM Flag

    Of the 4 large-cap biotechs, we believe CELG will probably perform the best for 2015 because 1) we think they should be able to grow EPS over 20%+ next year and in 2016, so if its current reasonable, in our view, GARP 20x multiple on '15E rolls over to '16E, that should get the stock towards $125+, 2) we note there could be a self-fulfilling prophecy of expectations that a "settlement" with ACT is closer to happening, perhaps even after February '15 when legal discovery ends and before Court could begin in mid-15 (we're not saying it's inevitable by then, but acknowledge that the potential exists; otherwise that could also happen even after Court begins), and, 3) we believe investors are going to start giving more credit to the pipeline – already they have gotten excited on GED-301 going into Phase III....and now seem to be highly rewarding partner AGIO with two drugs – AG-221 (CELG has rights) and new AG-120 (CELG has OUS rights) – both as hemonc drugs but could be expanding to solid. Nevertheless, CELG stock hasn't really moved on the AGIO drugs, likely because they are early stage...this could matter in 2015-16...

    For GILD: We continue to watch scripts carefully and clearly acknowledge that analysts are probably "over-modeling" Q4 HCV around $2.7B+ USA, but this is still "achievable" and potentially higher with inventory stocking. But we think the Street may be nervous about Q4 holiday impacts, ABBV launch in Dec, ABBV pricing, and 2015 estimates...so stock might be more choppy until clarity likely emerges in Q1 on the above mentioned.

    For BIIB: Street is nervous about Tecfidera scripts which have been flattish for 2 months...Q4 should be achievable but we believe it's about whether Q1 might be too high if TRx are flattish and consensus models solid growth in 2015...we think the stock is a long going into LINGO data in January here at low end of $300 range, but data may need to be strong in order to keep interest high afterwards if Tecfidera scripts are under scrutiny...

    In mid-caps we like BMRN and VRTX for 2015. In sticking with our theme of growing interest in biotech, we would want to be long BMRN into the Dec 10th analyst event and 5 pipeline readouts for '15, especially Phase II achondroplasia data in Q2 which should work regardless: it could be stat sig, but even if not, it can dose higher and there should be (+) trends that seem likely. VRTX should be a long into early '15 Phase II VX-661 3-month homozygous data which should look better than first-gen '809 combo. We want to own into '809 strong pricing and USA launch for mid-15...

  • RBC bios into yr-end & 2015 "Of 4 lrg caps, "CELG will perform best in 2015 with 1) 20% EPS growth 2) ACT settlement 3) Pipeline incl 2 AGIO drugs and GED-031"...

    What we're saying into holiday year-end and going into 2015
    Maintain CELG, BMRN, VRTX as top ideas into 2015

    November 23, 2014

    RBC Capital Markets, LLC
    Michael J. Yee (Analyst)

    Thanksgiving biotech thoughts

    After lots of recent marketing meetings across regions, sentiment for biotech remains positive but importantly, a few themes seem to be prevalent across discussions: 1) fund managers are already asking on themes and ideas for '15 and do think the group can work for 2015 but are not expecting as much outperformance as 2014, 2) thus if biotech continues to work for 2015, then we think midcaps should continue to work which we believe would be good for names like BMRN and VRTX. If fund managers are going to buy biotech, why buy AMGN for 10%+ potential when BMRN or VRTX might see 25% or more over next 12 months?...but, importantly, 3) investors have been watching performance of GILD and BIIB as two big-cap growth biotechs that have been choppy for the last few months and wonder that if they continue to lag whether that will impact generalist interest in biotech...

    Of the 4 large-cap biotechs, we believe CELG will probably perform the best for 2015 because 1) we think they should be able to grow EPS over 20%+ next year and in 2016, so if its current reasonable, in our view, GARP 20x multiple on '15E rolls over to '16E, that should get the stock towards $125+, 2) we note there could be a self-fulfilling prophecy of expectations that a "settlement" with ACT is closer to happening, perhaps even after February '15 when legal discovery ends and before Court could begin in mid-15 (we're not saying it's inevitable by then, but acknowledge that the potential exists; otherwise that could also happen even after Court begins), and, 3) we believe investors are going to start giving more credit to the pipeline –

  • I just posted the CELG chart on Investorvillage CELG message board.. unfortunately it wont paste here but go there and see it.One of the better charts on CELG I have seen in awhile - about to breakout here imo on GED-031 data publication in major medical journal.....

    Constructive Chart - Should explode once we break above that 109.17 area and then above all time intraday high 109.25. Should happen next week on GED-031 data publication (Thanksgiving week usually a good one for market as well)

    Yes - CELG is about to explode through all time highs to the upside on publication of GED-031 chrohns data next week,, ASH in 2 wks. with 160 presentations at the biggest hematology conference in the world and of the yr and then with 2020 and a few surprises at JPM healthcare conf in early January

  • Reply to

    Now that money managers are high fiving

    by chrisnh689 Nov 22, 2014 1:53 AM
    rob_cos rob_cos Nov 22, 2014 9:25 AM Flag

    CELG is about to explode through all time highs to the upside on publication of GED-031 chrohns data next week,, ASH in 2 wks. with 160 presentations at the biggest hematology conference in the world and of the yr and then with 2020 and a few surprises at JPM healthcare conf in early January

  • + Otezla CHMP opinion de-risks approval; Expected label a little more specific

    Celgene received positive opinions from CHMP on Otezla for psoriasis (PsO) and psoriatic arthritis (PsA) (see link http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003746/WC500177621.pdf). It appears the EU label will have the same indications as the US label, but with more specifics on prior treatment experience. For PsO, the CHMP suggests patients failed to respond to or, who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA). For PsA, Otezla is for patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy. In contrast, the US label does not specify the patient characteristics for PsA, and addresses PsO patients who are candidates for phototherapy or systemic therapy. Given the fact that the specified populations are the main targets of Otezla, we don't consider the differences to be commercially important. The timing is in line, and supports our 2015 forecast of $43m in EU sales. Given the long duration and positioning in the treatment paradigm of Otezla, we believe there is real upside to 2015-17 consensus.

    + Two-year data of Otezla at ACR may support the use before biologics

    The long term data in PsA were presented earlier this week at the ACR meeting, which showed Otezla continues to be efficacious and safe after 2yrs on drug. The new data strengthen our belief that more coverage plans may require patients fail Otezla before getting biologics (seehttps://neo.ubs.com/shared/d1jaAadfbKVAqow and https://neo.ubs.com/shared/d1T0IDx60v). We are aware this is already happening in some plans, but we think the lack of serious side effects supports an expansion of the policy.

    + Recent inflection in Rx trend suggests upside to 2015

    An upward inflection in Otezla scripts was seen following the approval in PsO in late Sept., and the growth trend has been linear since then, with a steady increase of 6-9% w/w. If the current trend continues, Otezla would track towards US sales of $43m for 4Q ex-inventory (Street/UBSe: $44m), and $488m for 2015 (vs. Street WW $344m; UBSe: US: $471m; WW $515m).

    + Valuation: Buy, $112 PT based on 21x 2015e EPS

    We still think Otezla can surprise to the upside and drive upward revisions.

  • Celgene Receives Positive CHMP Opinion for OTEZLA® (apremilast), the First Oral PDE4 Inhibitor for the Treatment of Patients with Psoriasis and Psoriatic Arthritis
    Celgene International Sàrl (CELG), a wholly-owned subsidiary of Celgene Corporation, today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for OTEZLA® (apremilast), the Company’s oral selective inhibitor of phosphodiesterase 4 (PDE4), in two therapeutic indications: 1

    For the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or, who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA).
    Alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.
    Psoriasis is an immune mediated skin condition characterised by raised scaly lesions on the skin. It affects approximately 14 million people across Europe2 and about 125 million people worldwide.3 Plaque psoriasis, also called psoriasis vulgaris, is the most common form of the disease, representing about 80 percent of cases.4 Up to 30 percent of people with psoriasis may develop psoriatic arthritis, which involves pain and swelling in jointsand other manifestations and may lead to significant disability.5

    “This CHMP positive opinion is an important step forward for people with psoriasis and psoriatic arthritis in Europe. These immune mediated diseases are frequently debilitating and cause severe physical and emotional pain to the individual,” stated Tuomo Pätsi, President, Celgene Europe, the Middle East and Africa (EMEA). “We are proud to have moved one step closer to offering patients OTEZLA®, a new, oral treatment approach that could significantly help control their symptoms and make a considerable difference to their quality of life.”

    In the ESTEEM studies, which form the basis of CHMP’s positive opinion for apremilast in psoriasis, treatment resulted in significant and clinically meaningful improvements in plaque psoriasis as measured by PASI-75 (a 75 percent improvement in the Psoriasis Area Severity Index) scores at week 16, the primary endpoint.6,7 Patients on apremilast also benefited from significant improvements in difficult to treat areas, such as nail and scalp, and itch, known to have a marked impact on patients’ quality of life and perception of disease severity.8,9,10

    In the PALACE program, which forms the basis for CHMP’s positive opinion for apremilast in psoriatic arthritis, treatment resulted in significant and clinically meaningful improvements in the signs and symptoms of psoriatic arthritis, as measured by the modified ACR-20 (a 20 percent improvement in the American College of Rheumatology disease activity criteria) response at 16 weeks, the primary endpoint. 7,11 Patients on apremilast showed improvement across multiple disease manifestations specific to psoriatic arthritis, such as swollen and tender joints, as well as dactylitis, enthesitis and overall physical function.12,13,14

    In the two Phase III programs, PALACE and ESTEEM, the clinical response of OTEZLA was maintained through week 52 across multiple endpoints. 15,16

    Across these phase III clinical studies, the most commonly reported adverse reactions were consistently diarrhoea, nausea, upper respiratory tract infection, tension headache and headache.6,11 These adverse reactions were mostly mild to moderate in severity. Gastrointestinal adverse reactions generally occurred within the first two weeks of treatment and usually resolved within four weeks.6,11 During the placebo-controlled phase of the clinical trials, the rate of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, was comparable between placebo and apremilast groups.6,11

    OTEZLA® was approved on March 21, 2014 by the U.S. Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis and on September 23, 2014 for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In Canada, OTEZLA was approved for the treatment of moderate-to-severe plaque psoriasis in November 2014. A New Drug Submission (NDS) for psoriatic arthritis was submitted to Canadian Health Authorities in the second quarter of 2013. Marketing authorisation applications are ongoing in other countries, including Australia and Switzerland.

    The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within two to three months. If approval is granted, detailed conditions for the use of this product will be described in the Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).

  • Jeffries - More Positive On Otezla And Baricitinib Prospects After ACR Feedback

    Biotechnology
    More Positive On Otezla And Baricitinib
    Prospects After ACR Feedback

    EQUITY RESEARCH AMERICAS

    Key Takeaway
    At the American College of Rheumatology (ACR) meeting in Boston, we spoke with 27 physicians about Celgene’s Otezla and Incyte’s baricitinib. Feedback on both drugs was generally positive and we would highlight the preponderance of feedback on earlier positioning of Otezla, including a number of physicians who would choose Otezla as a first-line agent over methotrexate, price notwithstanding, and interest in using Otezla with a biologic for severe patients.

    Favorable Opinions On Earlier Use Of Otezla. We spoke to 18 physicians at ACR about Celgene’s (CELG, Buy) Otezla (apremilast), which has been approved in the U.S. for the treatment of psoriasis and psoriatic arthritis (PsA). Of the twelve rheumatologists who opined on when to use Otezla in the treatment of PsA, the majority favored use before biologics with six advocating second-line use (following methotrexate [MTX]), four favoring first-line use assuming reimbursement (before MTX), and just two advocating third-line use (following MTX and biologic failure). One of the more vocal first-line Otezla advocates was
    from the U.S., noting that half of his nearly fifty Otezla patients were treatment-naïve and that he used it as a better MTX. We note that three of the advocates of first-line use were from countries where Otezla is not currently approved for PsA (2 Canada, 1 UK), stipulating their preference would depend on government reimbursement. Second-line Otezla use was more common, with five U.S. physicians and one UK doctor who suggested he would use it over TNFs in his moderate patients if the cost is acceptable. This was a common refrain for physicians, with three of the five U.S. physicians noting that they would favor second-line usage primarily among mild to moderate patients, but prefer use biologics in the most severe patients. Of the two U.S. physicians who advocated third-line Otezla use, both voiced a familiarity with existing therapies, suggesting they would really only use second line Otezla in patients who were contraindicated against biologics or had a strong preference for oral therapies.
    Potential For New Otezla Uses. In addition incorporating Otezla into the PsA treatment paradigm, six physicians discussed their views on using Otezla in combination with other biologics for their more severe patients. This is not a setting where any data has been generated yet, but speaks to the emerging positioning of Otezla as a “better MTX.” Two U.S. physicians noted that they were currently treating two of their most severe PsA patients with both Otezla and a biologic. One physician noted that he was not worried about Otezla combination safety, but noted that immunogenicity remained to be seen (one of methotrexate’s potential advantages is to suppress any potential immunogenicity reaction to a biologic). That said, we do not believe that this will be much of an issue with human or humanized biologics. He also noted that reimbursement of the combination remains a challenge, but he is currently pursuing creative solutions to the reimbursement dilemma to enable other severe patients to receive the combination. The other physician noted that he planned to use Otezla to accelerate the patient’s clinical response a biologic, but also cited insurance as a challenge. Two physicians on the fence about a combination therapy noted they expected to see data from combination studies next year, with one having a preference for MTX and biologics until more data is available. Combination use could enhance our Otezla outlook as it would likely increase both penetration and duration of therapy in the third-line setting. Separately, we spoke to a Turkish physician about the use of Otezla in Behcet’s disease. Although she did not have access to Otezla yet, she mentioned that she would use it off-label in refractory Behcet’s patients rather than a biologic, except in severe disease. She noted that the cost difference between Otezla and colchicine may make it difficult to adopt as a first-line Behcet’s therapy. She further mentioned that she knew U.S. physicians were using Otezla off-label in Behcet’s, including a doctor in Oregon who has had two patients on the drug without a problem. Although not a large indication in the U.S., we believe Behcet’s could be a source of upside to our Otezla estimates

    Learning From PFE’s Mistakes: Pricing Likely To Be A Factor For Baricitinib
    Adoption. We spoke to seven doctors at ACR about their opinions on Jak inhibitors for the treatment of rheumatoid arthritis (RA), including the Phase 3 compound baricitinib under development by Incyte (INCY, Buy) and partner Eli Lilly (LLY, Hold), and Pfizer’s (PFE, Buy) approved Xeljanz, which has had a disappointing initial launch. The majority of commentary on Jaks and the limited use of Xeljanz despite oral convenience focused on
    its limited efficacy at the approved dose in comparison to similarly priced biologics. We note Pfizer priced Xeljanz similar to biologics at launch, although the annual cost has increased more slowly (currently $28k for Xeljanz v. $38k for Enbrel and Humira). One physician speculated that a Jak that shows success in biologic failures would be able to
    justify a premium. Another physician seconded the importance of a clean safety profile for a follow-on Jak to be competitive, and highlighted a bad PFE sales efforts and poor pricing decision likely contributed to the failure of the Xeljanz launch. This was further by a rural U.S. prescriber who complained that, with its perceived inferior efficacy, Xeljanz should have been priced at half its current cost, calling both the pricing and marketing effort “arrogant.” A VA physician noted that he has only been able to recently start his first patient on Xeljanz given the cost and continuing VA preference for injectable biologics. Two ex-U.S. physicians noted that they may use Xeljanz as an easier option in biologic failures with a Canadian doctor noting that there would likely need to be significant discounting. As we await further data from the four ongoing Phase 3 trials of baricitinib later this year and throughout 2015, we remain optimistic as we believe it offers the potential for both better safety and efficacy relative to Xeljanz and we believe LLY will have the benefit of PFE’s launch mistakes. We continue to believe that investors have prematurely dismissed the potential for upside to baricitinib royalties in the current INCY valuation.

  • Griffiin-ZIOP poised to expand clinical development-Controlled CAR T for proper efficacy/safety balance...will pique interest in XON/ZIOP stocks...IND's soon..underpin negotiations with multinational & regional pharma co's.....$12 target


    Griffin Securities

    Stock Symbol NYSE: ZIOP
    Current Price $3.65
    12 mos. Target Price $12.00

    Ziopharm BUY
    Company Update : Biotechnology

    New Immunotherapy Presentations Announced

    Ziopharm seems poised to expand its clinical development
    program. The Company and its partner, Intrexon Corporation,
    have four poster presentations at a meeting called Tumor
    Immunology and Immunotherapeutics: A New Chapter, which will
    be held on December 1 – 4. The meeting, which is sponsored by
    the American Association for Cancer Research, will provide an
    insight into the collaborators’ efforts to defeat cancer with powerful
    immunotherapies. Only the titles of the presentations are available
    presently, but the following are our impressions of the research
    until the abstracts become available:

    o Ziopharm will provide an update on the clinical results from
    its two Phase 2 trials of an interleukin- 12 gene therapy.
    The studies involved injecting directly into tumors the DNAbased
    medicine, which is controlled by Intrexon’s proprietary
    RheoSwitch® and an activator ligand. The studies were the first
    to demonstrate controlled expression of the powerful anticancer
    cytokine in vivo.

    O Intrexon has created a chimeric antigen receptor (CAR)
    targeting a biomarker of hematological malignancies,
    CD- 19. Importantly, expression of the CAR is regulated via the
    RheoSwitch, which means that activation of CAR T- cells may
    be controlled to achieve the proper balance between efficacy
    and patient safety.

    o A high- throughput assay permits the identification of
    targeting molecules for immunotherapeutics. This test
    should enable Intrexon to quickly evaluate huge numbers of
    potential synthetic receptors for CAR T- cells and other types of
    immune- activating cells.

    o Intrexon has created a stem cell to facilitate immunological
    targeting of malignant tissue. This novel approach uses the
    natural proclivity of stem cells to home into tumors by sensing
    the inflamed microenvironment of malignant growths. There,
    bispecific antibodies on the stem cells “show” the cancer to the
    immune system for destruction.

    We think the new data on the Ziopharm-Intrexon immunotherapy program will pique investors’ interest in both companies’ stocks and underpin partnering discussions. The program has a solid foundation that includes CARs and antibodies expressed in a controlled manner by T-cells and stem cells, plus IL-12 as a therapy in its own right and as a cytokine that improves engraftment and persistence of cell therapies. ZIOP shares are rated BUY.

    POSTER SESSIONS ON IMMUNOTHERAPIES

    Intrexon and its partner Ziopharm Oncology will have four poster presentations at a conference sponsored by the American Academy of Cancer Research called Tumor Immunology and Immunotherapy: A New Chapter. The meeting is called for December 1 – 4, but the four posters are scheduled for December 3rd from 12:30 – 2:45. The poster number, title and author information is shown below:

    B11 Ad-RTS-hIL-12 + veledimex regulation of IL-12 expression in advanced breast cancer (BC) and melanoma patients. John J Nemunaitis, Gerald P Linette, Haythem Ali, Francois Lebel, John A Barrett,Thomas Reed, Suma Krishnan, Jonathan Lewis.

    B16 Development of a high-throughput imaging screen for the functional assessment of cell-linking moieties using effector and target cells in a cell kill assay. Jeffrey Rosenbloom, Jason Isaacson, Srinivas Rengarajan, Paul Szymanski, Jennifer Buenviaje, Kristi Elliott, Francois Lebel, John A Barrett, Richard Einstein.

    B24 Construction and validation of a RheoSwitch® (RTS®) regulated CD19 chimeric antigen receptor. Dina Schneider, Darong Wu, Paul Szymanski, Nadia Sinitsyna, Jennifer Buenviaje, Srinivas Rengarajan, Gustaf Angelborg, Catherine Tran, John Beaber, Stephen Schauer, Charles Reed, Jonathan Carson, Kristi Elliott, John Barrett, Francois Lebel, Daniel Bednarik.

    B25 Controlled production of a bispecific antibody by a genetically-modified stem cell triggers T cell activation and cytolysis in non-small cell lung carcinoma. Amy Wesa, Yumei Xiong, Tim Chan, Jeff Rosenbloom, Srinivas Rengarajan, Paul Szymanski, John A Barrett, Francois Lebel, Farzad
    Haerizadeh, Richard Einstein.

    The B11 presentation will provide an update on the status of patients with melanoma and breast cancer treated with Intrexon/Ziopharm’s IL-12 therapy Ad-RTS-hIL-12. The B24 title indicates that Intrexon has created a chimeric
    antigen receptor, regulated by the RheoSwitch®, that recognizes a biomarker, CD-19, found on B-cell lymphomas.

    In another (B25), a stem cell that expresses a bispecific antibody in a controlled manner is used to activate cytolytic T cells against non-small cell lung cancer. The use of a stem cell in this manner is exciting because it serves as a homing device for cytotoxic T-cells. Stem cells have the natural tendency to home into tumors, but are not affected by the same signals that malignant cells employ to evade the immune system. Intrexon’s modified stem cells have the ability to identify the tumor and then to effect an immunological attack. Finally, we interpret the title of B16 to mean that Intrexon has created a rapid screen to assess the binding properties of such molecules as synthetic receptors, antibodies, and saccharides. (We note, for instance, that the sugar moiety of the anti-cancer agent
    bleomycin binds to certain cancer cells and that derivatives of the disaccharide have improved binding properties.1,2)

    These presentations indicate that Intrexon has addressed important issues involved in creating safe and effective cell therapies against cancer. Hence, we believe Ziopharm will soon submit INDs on innovative immunotherapeutics and that the data provided in these presentations will underpin negotiations with multinational and regional pharmaceutical companies seeking to participate in this exciting new field of medicine.

  • I have posted links to both NEJM Online First & Lancet Online First publications on Investorvillage CELG board (yahoo does not allow links) - GED-031 Crohn's Disease Trial Full data set should hit any day now (9 days ago mgt said "We should immediately see publication in major medical journal coming very,very soon")...

    ISI said this publication would cause a "crescendo" in Celgene share price - has to be soon soon soon.

    NEJM online first

    NEJM Gastroenterology Specialty Site

    Lancet online first

    see investorvillage celgene board for links

    CELG at CS Healthcare conference November 11th:

    We are quite excited and you’ve heard us speak about this a lot lately. You saw data earlier on the GED-0301 late stage product that we acquired earlier this year. And you will hear us speak more about the plans for taking that through to Phase 3 and then approval as we move through our regulatory discussions and can give you some more details on that soon.

    But the data and the potential for transforming the treatment of Crohn’s with this product is quite striking. We are very excited about it and are anxious to add it into the franchise alongside OTEZLA and treat unmet medical needs in Crohns’s.

    SO WE HEAR A LOT MORE ABOUT THAT. WE SHOULD IMMEDIATELY SEE THE PUBLICATION OF THE PHASE 2 RESULTS FOR THIS COMPOUND IN A MAJOR MEDICAL JOURNAL. SO IT SHOULD BE COMING VERY, VERY SOON AND YOU WILL HEAR MORE ABOUT OUR DEVELOPMENT PLANS FOR THE PRODUCT OVER THE COMING WEEKS AND MONTHS

    Sentiment: Strong Buy

  • Must read MS analysis of CELG partners/drugs.CELG has $0 in current stock price for this "stealth pipeline" & I believe CELG will get $3 to $5 billion a yr INCREMENTAL revenue from these partnerships....

    ...they also own equity in some of these companies (for instance the 14% of AGIO CELG owns has increased $50 million in value yesterday and over $100 million the past 2 months)
    Here is a nicely detailed list of the main partners by MS after their Bus Tour to visit CELG and their partners....some of the charts don't past so I will send to my distribution list. There is also a slide deck by company I will be posting one by one over the next day or so...There is ZERO dollars in current CELG stock price for all of the drugs controlled by CELG under those deals and also the EQUITY STAKES. Remember CELG owns 14% of AGIO (stake worth $50 million+ more on yesterdays AGIO increase/ +$100 million in past 2 months), 10% Acetylon, 14% XLRN, 11% EPZM, 3% Morphosys. 14% NantBioScience &5% of Sutro as of Sept 30th
    I personally believe the 25+ partnerships will ultimately result in CELG incremental sales of at least $3 to $5 billion a yr...AGIO's -120 & AG- 221, Morphosys' MOR202, XLRN's sotatercept (ACE-011) & lupatercept (ACE-536). , OMED's demcizumab (and perhaps OMP-305B83 & OMP-131R10 someday) & Concert's CTP-730 are particularly exciting imo. Time will tell.


    MORGAN STANLEY & CO. LLC
    Celgene Corp ( CELG.O , CELG US )
    Celgene Corp
    Sorting Through The Partnered Pipeline
    Celgene has 20+ partnerships with early-stage biotechs. We provide high-level takeaways and a comprehensive list of all the partnered assets.
    26 disclosed partnerships offer potential: 5 are in inflammation and 21 in
    hematology/oncology (hem/onc), of which three are multiple myeloma (MM)
    add-ons. 10 partnerships have clinical-stage assets. We provide key takeaways
    on the clinical assets inside (Exhibit 1). Please see our companion slide deck
    for details on all the partnerships.
    38% of partners have clinical-stage assets with 12% in PhII: Acceleron's
    ACE-011/ACE-536 (TGF-beta ligand traps), VentiRx's VTX-2337 (TLR8) and
    OncoMed's demcizumab (NSCLC) are in PhII studies. Acetylon's HDACs are in
    PhI, Agios' IDH-1/2 compounds are in PhI (though offer a fast path to market),
    Concert's CTP-730 recently entered a healthy volunteer study, Epizyme's
    DOT1L remains in PhI, InhibRx's CD47 appears IND ready, MorphoSys'
    MOR202 (antiCD38) is in PhI and Triphase's marizomib (GMB) is in PhI. We
    believe AG-221 in AML and ACE-011/536 in Beta Thalassemia have enough
    data to suggest they have greater than a 50% chance of making it to market.
    We believe MOR202 offers the highest potential value as the mechanism is derisked
    (J&J and Sanofi have CD38 clinical data) and peak sales could be multibillion
    as it is a Revlimid add-on. We await initial data in 2015.
    62% of partnerships are preclinical: Many of the preclinical partnerships are
    researched-based without any disclosed targets. Of the preclinical assets with
    disclosed targets, Bluebird is working on CAR-T cells (2015 clinical candidate),
    AnaptysBio is working on novel antibody inflammation targets (it has an
    unpartnered IL-33, but Celgene targets are undisclosed), NantBio has two
    targets - a chemotherapeutic agent NTB-011 and an HSP90 inhibitor NTB-010,
    Presage Biosciences has developed a novel injection system to increase the
    throughput of combination testing in preclinical models and Sutro Biopharma
    is developing novel ADCs and bispecific antibodies.
    Pipeline helps the multiple, but sig. visibility is far away for the
    majority of deals: The positive side of this development strategy is that it
    offers mgt. a wide array of targets, novel science and potentially better R&D
    productivity than an in-house only R&D engine. The negative is that the PhII
    pipeline is of limited scope and many of the assets are for niche targets. Of the
    clinical candidates, only a few appear to have $1B+ potential. Further, with
    development times of at least 5 years from IND to approval, only those assets
    in the clinic now are likely to offer diversification at the time when Revlimid
    goes generic. Thus, while the effort is broad, given that the majority of the
    deals have yet to make it into the clinic we believe we have to wait before
    these deals could cause sig. multiple expansion.
    Clinical Stage Assets
    Acceleron
    Assets: Celgene has licenced sotatercept (ACE-011) and lupatercept (ACE-536). Both compounds target red blood cells via the TGF-beta superfamily of ligands. Both molecules are in Phase II testing for beta thalassemia and myelodysplastic syndromes (MDS). Sotatercept is also being studied for chronic Kidney Disease (CKD).
    Celgene Deal: Celgene has licenced both molecules and owes royalties and milestones on development and commercial sales. For development there are $320M of remaining milestones and Celgene pays all clinical costs.
    For commercialization there are $230M of remaining milestones, Celgene will pay a tiered royalty of low-to-mid 20% to Acceleron and fund an Acceleron sales force.
    Current Data: Acceleron will be presenting Phase II data of ACE-011 (abstract #3251) and ACE-536 (abstract #533 & 411) in patients with beta-thalessemia and myelodysplastic syndrome (MDS) on December 7-8th at ASH. The most recent data on both compounds was presented at EHA. Data in β-thal suggests a durable dose dependent hemoglobin response (430 days follow-up). Given sotatercept’s impact on bone, mgt. is pursuing the CKD/dialysis market with this antibody. ACE-536 has the same mechanism as sotatercept, but contains the extracellular domain of activin receptor type IIB instead of IIA. Data in β-thal are very similar to sotatercept with~3g/dL max Hb changes. In MDS, similar effects were observed with 6/16 transfusion dependent pts able to reduce their RBC units by ≥ 50% and 2/3 non-transfusion dependent pts able to incr. their Hb by ≥1.5g/dL (at the highest-dose).
    Our take: On sotatercept, we see the see the pursuit of CKD/dialysis as a much harder market given the need for long-term safety, entrenched EPO and the long drug half-life (13 days). That said, mgt. believes that morphology changes, incl. bone and vascular calcification could differentiate sotatercept. On ACE-536, we see MDS as the most direct path to market, though note that β-thal incl. 40k pts globally (Italy, Greece, Turkey, etc). β-thal likely needs less long-term follow-up and thus could be more relevant from a valuation prospective. We believe a β-thal Phase III study is likely to start in 2015 while Celgene assess the path forward in MDS.
    Acetylon
    Assets: Celgene has an exclusive option to acquire Acetylon for its portfolio of HDAC inhibitors, including its lead asset ACY-1215. ACY-1215 is HDAC 6 selective inhibitor that potentially is additive to Velcade or Revlimid. It is currently in Phase I/II trials. Acetylon is also developing ACY-738, an HDAC 1/2 inhibitor, for neurological diseases.
    Celgene Deal: In July 2013 Acetylon and Celgene entered into an exclusive strategic collaboration for an $100M upfront payment to advance Acetylon’s clinical and pipeline programs, including the ongoing combination clinical trial of ACY-1215 with Celgene’s Revlimid + dexamethasone in multiple myeloma, and combinations of ACY-1215 with other anti-cancer agents. The agreement includes an exclusive option for the potential acquisition of Acetylon by Celgene. If Celgene exercises its right to acquire Acetylon, in addition to the purchase price based upon independent company valuations to be paid at the time of the acquisition, Acetylon shareholders will be eligible to receive up to $250M for regulatory milestones and $850M for sales milestones for an aggregate amount of $1.1B. Celgene had previously made a $15M strategic equity investment in Acetylon in February 2012.
    Current Data: Acetylon will be presenting Phase Ib data of AYC-1215 in combination with Revlimid + dexamethasone (abstract #4764) and ACY-1215 in combination with Velcade + dexamethasone (abstract #4772) in patients with R/R multiple myeloma on December 6-8th at ASH. The company last reported data from the studies at EHA in June stating all 22 evaluable patients receiving ACY-1215 in combination with Revlimid demonstrated stable disease or better, with 64% having partial response or better, including 1 complete response, 5 very good partial responses, 8 partial responses, and 3 minor responses; 10 of the evaluable patients were previously refractory to Revlimid. In combination with Velcade, patients demonstrated an overall response rate 53% in 19 evaluable patients, or 36% of the intention-to-treat population; 10 patients were previously refractory to Velcade (See Acetylon Press Release.)
    Our take: HDAC inhibitors clearly have a mechanistic rationale in myeloma. Clearly, Novartis' panobinostat suggest solid activity; hwr, the safety profile (and the dropouts it causes) have created issues in its ability to be approved. Given the current limited data, the more selective HDAC 6 compound from Acetylon appears to be better tolerated. We await a broader dataset to more completely judge the safety. We would expect this combination to be pursued in combination with Pomylast for the refractory population.
    Agios
    (Rob note: this was authored BEFORE the stunningly positive AG-120 data Weds)
    Assets: Celgene has licensed AG-221, an IDH2 inhibitor, and secured ex-U.S. option rights to Agio's IDH1 inhibitor AG-120. Both compounds are currently being studied in hematologic malignancies and solid tumors. AG-221 has received orphan drug designation for AML and fast track designation for patients with IDH2-mutant AML. In addition, a Phase I/II of AG-221 in patients with advanced solid tumors with an IDH2 mutation recently initiated in October 2014.
    Celgene Deal: Celgene exercised its option to ex-US rights for AG-120 in February 2014 and AG-221 in June 2014 as a part of the global strategic collaboration entered between the companies in 2010. Agios is eligible for up to $120M in milestone payments and tiered royalty on any net sales of AG-221. For AG-120, Agios is eligible for up to $120M in milestones, keeps US rights while Celgene has exUS rights and each party pays a cross royalty on sales in their territories. Under the agreement, Celgene is responsible for all development costs of AG-221 and the parties share the costs for Ag-120.
    Current Data: Agios will be presenting new safety, PK/PD, and efficacy data from the Phase I study of AG-221 in advanced hematologic malignancies on December 7th at ASH (abstract #115). Initial results from the abstract indicate AG-221 is well tolerated and patient responses have been durable. Most AEs have been grade 1 or 2; however, there has been 9 deaths, 8 of which occurred within the first 28 days of receiving AG-221, with one of the deaths reported as possibly related to AG-221. In the last full dataset at EHA, data included 35 patients up from 10 at AACR. EHA responses (ORR) were 44% (14/32, 19% CR with 3 patients not yet at day 28) down from 60% (6/10, 30% CR) at AACR. Patients with CRs achieved 2.5+ months of duration. On AG-120, Phase I data in patients with hematologic malignancies will be presented at EORTC-NCI-AACR on November 19th (abstract code 1LBA).
    Our take: AG-221 is clearly active. However, given that IDH2m is a favorable marker that confers longer PFS, we believe the larger sample size at EHA more closely represents its true activity than the data at AACR. That said the path to market appears clear and we would not be surprised to see break-through therapy designation given the target and responses. Commercially, AML is a small indication with ~2,500-5,000 US patients. Thus, AG-221’s potential value to Celgene comes from expanding into other cancers with IDH2m (MDS, NHL). We await the initial data for AG-120.
    Concert
    Assets: Celgene has worldwide rights to CTP-730, a deuterated compound being investigated for the treatment of inflammatory diseases. Concert announced the initiation of a randomized, double-blind, single ascending dose Phase I study in CTP-730 in September 2014.
    Celgene Deal: In May 2013 Concert entered into a strategic collaboration with Celgene which initially focuses on one program, but has the potential to encompass multiple targets. Concert received a $35M upfront payment from Celgene and is eligible to receive greater than $300M in development, regulatory, and sales milestone payments for each program selected for development by Celgene. The next milestone payment under the initial program is $8M upon completion of Phase I clinical trials of CTP-730. Concert will also receive tiered royalties ranging from mid-single digits to low double digits below 20% on any product sales for each of the programs advanced.
    Current Data: None available.
    Epizyme
    Assets: Celgene has an exclusive ex-U.S. license to Epizyme's DOT1L program which includes EPZ-5676, a small molecular inhibitor of DOT1L currently in Phase I clinical trials for the treatment of two types of genetically defined acute leukemias: MLL-r and MLL-PTD. In addition, Celgene has the option to license ex-US rights of other histone methyltransferases (HMT) programs not covered by existing collaborations.
    Celgene Deal: In April 2012, Epizyme received a $90M upfront fee and equity payment in a collaboration and license agreement with Celgene to develop compounds that inhibit HMT. Epizyme is responsible for development costs of Phase I clinical trials for EPZ-5676 after which Celgene and Epizyme will equally co-fund global development. Each company will fund development costs specific for its territory. Celgene will also pay royalties ranging from the mid-single digits to the mid-teens on net product sales outside of the U.S. for each target selected.
    Current Data: Epizyme will be presenting preliminary data from the dose escalation and expansion stages of the EPZ-5676 Phase I study on December 8th at ASH (abstract #387 & 2187). The abstract indicated that of the 36 patients evaluable for safety across six dosing cohorts (12, 24, 36, 54, 80 and 90 mg/m2/day), EPZ-5676 was safe and well-tolerated, with predominantly Grade 1 or Grade 2 AEs and only two patients who discontinued treatment due to possible drug-related AEs. Of the 28 patients evaluable for efficacy, 2 MLL-r patients in the 54 mg/m2 dosing cohort achieved complete responses.
    Our take: We believe the efficacy of this compound is uncertain. There does not appear to be a linear doser esponse curve, suggesting that the signal seen at 54mg could be noise (there were no more responses at higher doses). We await a larger dataset.
    GlobeImmune
    Assets: Celgene has licensed the GI-6300 program, including GI-6301,a Tarmogen targeting the brachyury protein. GI-6301 is currently in Phase I clinical trials in patients with late-stage cancers known to express the brachyury protein including chordoma. Celgene also has the option for GI-6207 a Tarmogen targeting carcinoembryonic antigen, which is being developed for the treatment of medullary thyroid cancer, currently in Phase II clinical trials.
    Celgene Deal: In May 2009, GlobeImmune entered into a worldwide strategic collaboration and option agreement with Celgene for product candidates for the treatment of cancer. Upon the achievement of certain development, regulatory and commercial milestones, the company would be eligible to receive milestone payments and tiered royalties based on net sales of each licensed product. Under this agreement, in July 2013 Celgene exercised its option for a worldwide, exclusive license to the GI-6300 program.
    Current Data: In October 2014 GlobeImmune reported results to date from the 11 chordoma patients in the Phase I study. Of the 11 patients, 8 (73%) have stable disease at day 85 restaging (2 had stable disease at study entry) and 1 patient had a confirmed partial response (9%) that has continued past one year. GI-6301 was generally well tolerated with mild/moderate injection site reactions as the most common AEs. A Phase II study design for GI-6301 is now in progress (see GlobeImmune Press Release).
    Our take: While the brachyury protein is expressed on lung, breast, colon, bladder, kidney, ovary, uterus and prostate cancers, the only data to date is in the rare bone cancer chordomas. Thus, it is very difficult to judge the relevance of this therapeutic in the more prevalent (and thus more relevant to valuation) cancers. Both MTC and chordomas are too small to significantly impact Celgene.
    MorphoSys
    Assets: Celgene has licensed MOR202, a fully human monoclonal HuCAL antibody directed against CD38. MOR202 is currently being tested in a Phase I/IIa trial in patients with relapsed/refractory multiple myeloma.
    Celgene Deal: In June 2013 Celgene entered a strategic alliance with MorphoSys for a $92M upfront license fee to jointly develop MOR202 (anti-CD38) globally and to co-promote MOR202 in Europe. MorphoSys could receive up to EUR 511 million (US $664.5M) in development, regulatory and sales milestones and tiered royalties on net sales of MOR202 outside the co-promotion territory. In the co-promotion territory, MorphoSys retains a 50/50 profit sharing right on MOR202 in exchange for paying one third of the MOR202 development costs. Should MorphoSys choose to opt out of its co-promotion rights, MorphoSys would receive tiered royalties on net sales of MOR202 globally.
    Current Data: MorphoSys last reported pre-clinical data of MOR202 at ASH in 2012 demonstrating MOR202 mediated antibody-dependent cell-mediated cytotoxicity in multiple myeloma cells derived from patients invitro.
    Our take: CD38 is clearly a validated target with daratumumab from Genmab/J&J and SAR650984 from Sanofi. Given that Revlimid will likely be a backbone in this combination therapy, MOR202 has the potential to be one of the more relevant collaboration agreements. We await initial clinical data on the compound in 2015.
    OncoMed
    Assets: Celgene has the option to obtain, demcizumab, an anti-DLL4 monocolonal antibody that is designed to block the Notch signaling pathway in cancer stem cells, currently in Phase II trials. Celgene also has the option for OMP-305B83, an anti-DLL4/anti-VEGF antibody with an IND filing planned in 2014, and OMP-131R10, an anti-RSPO3 antibody with an IND filing planned in early 2015.
    Celgene Deal: In December 2013 Celgene entered a collaboration agreement with OncoMed for a $155M upfront payment to jointly develop/commercialize up to six anti-cancer stem cell (CSC) product candidates from OncoMed’s pipeline. OncoMed will control and conduct initial clinical studies. Celgene also has R&D and commercialization rights to small molecule compounds in another cancer stem cell pathway, with ncoMed eligible to receive milestones and royalties on any resulting products. The collaboration also includes up to five preclinical or discovery-stage biologics programs.
    Current Data: OncoMed most recently presented clinical data on demcizumab at ESMO in September. In the Phase Ib clinical study of demcizumab in combination with gemcitabine plus Abraxane in patients with first-line metatstatic pancreatic cancer 9 of 22 patients (41%) achieved partial responses and 10 (45%) had stable disease, resulting in an overall clinical benefit rate of 86% (see demcizumab poster). Additionally, in the Phase Ib study of demcizumab in combination with pemetrexed and carboplatin in non-small cell lung cancer (NSCLC) patients, of 33 patients evaluable for efficacy, 1 (3%) had a complete response, 15 (45%) had a partial response and 13 (39%) had stable disease. The overall clinical benefit rate was 88% (see demcizumab poster).
    Our take: The efficacy in pancreatic cancer appears interesting, esp. given the poor standard of care. That said, demcizumab has had sig. safety problems, with DLL4 upregulating VEGF and thereby causing cardiac toxicity. While management believes it has found the right schedule to ameliorate these safety signals, we await data in a larger cohort before getting comfortable with the safety profile.
    Triphase
    Assets: Marizomib is a protease inhibitor derived from a novel marine-obligate actinomycete and is being evaluated for the treatment of multiple myeloma and glioblastoma (GBM). An intravenous formulation has been evaluated in 240 patients across four Phase 1 studies, and now Triphase is developing an oral formulation of marizomib.
    Celgene Deal: In October 2014, Triphase expanded its strategic collaboration with Celgene adding a Phase I development program that will explore IV formulation of marizomib with bevacizumab in glioblastoma.
    Triphase will receive additional development funds through a cost sharing agreement with Celgene (payment undisclosed) and Triphase will control product development and retain all commercial rights to marizomib unless Celgene exercises its option to acquire the product from Triphase for an undisclosed payment at which time Triphase would be eligible to receive regulatory and sales milestone payments.
    Current Data: Triphase presented preclinical data of marizomib + Pomalyst in multiple myeloma in June 2014 at ASCO. The results demonstrated a significant decrease in viability of all cell lines in response to treatment with combined marizomib and Pomalyst compared with either agent alone (see marizomib poster).
    VentiRx
    Assets: VTX-2337/Motolimod is a monoclonal antibody that binds to the TLR8 receptor inside myeloid-derived dendritic cells (mDCs) currently being investigated in Phase II clinical studies.
    Celgene Deal: In October 2012, Celgene paid $35M upfront to fund further research and development of VTX- 2337 through pre-defined clinical endpoints. During the option period, VentiRx will be eligible to receive additional funding, including a potential equity investment by Celgene.
    Current Data: In November 2014 VentiRx presented data of VTX-2337 in combination cetuximab + chemotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (see VTX- 2337 Poster). 12 patients were enrolled in the study and 10 were evaluated for disease response. The best overall responses were partial response in 2 patients (16.7%) and stable disease in 4 patients (33%), with an overall disease control rate of 50%.
    Our Take: TLR7/8s are well known to have anti-cancer effects. Imiquimod (a topical TLR) has demonstrated an impact on many skin cancers. Thus, from a mechanistic stand-point, the TLR8 pathway is interesting. However, given the limited amount of data thus far, we prefer to wait for the larger Phase II studies.

  • There is NOTHING in CELG current stock price for ANY of the drugs they control from the 25 top tier small bio partnerships. NOTHING from AGIO 2 drugs, XLRN, BLUE, OMED, MPSYY, EPZM, CNCE, etc CELG owns equity in many of these companies like AGIO, EPZM, XLRN, etc and controls drugs from almost all of them,.

  • Bionor Pharma Announces That the Combination of Vacc-4x + Revlimid(R) Is Safe and Increases CD4 Counts in People Living With HIV



    OSLO, NORWAY--(Marketwired - Nov 17, 2014) - Bionor Pharma ASA (OSLO: BIONOR)
    • Treatment with Vacc-4x + Revlimid (lenalidomide) was safe and well tolerated
    • Increase in CD4 count in both treatment groups notably in Vacc-4x + Revlimid group
    • Qualitative immune response analyses support the quantitative findings
    Bionor Pharma ASA (OSLO: BIONOR) announces the results from the Vacc-4x + Revlimid (lenalidomide) study also known as the "Boost & Kill" study. The Phase II trial was an exploratory double-blind placebo controlled immunogenicity study of Vacc-4x + Revlimid versus Vacc-4x in HIV subjects on ART (HIV standard of care treatment).
    Bionor Pharma CEO Dr. Anker Lundemose commented, "We are encouraged by today's results with data demonstrating that the effects of Vacc-4x can be boosted by lenalidomide. This gives the option to add the 'Boost & Kill' to our current 'Kick & Kill' development strategy towards achieving a functional cure for HIV."
    The study's principal objective was to assess the combination of Vacc-4x + Revlimid in people living with HIV on ART but who have not regained a healthy CD4 level. Twenty four patients were randomized into two groups where one group received Vacc-4x + placebo and one group received Vacc-4x + Revlimid. Patients received six cycles of Vacc-4x vaccination with Revlimid or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end).
    CD4 counts, the key primary efficacy endpoint, increased in both groups. The largest increase was in the Vacc-4x + Revlimid group where CD4 count increased by 30% (p=0.009) from baseline. In the Vacc-4x + placebo group the CD4 count increased with 17% (p=0.10). However, this was an exploratory study, with a limited number of patients and no statistical difference was observed between the two groups.
    The three other primary endpoints investigating immune response were T-cell response to Vacc-4x, antibody titer to Vacc-4x peptides and p24, and assessment of antibody titers to a commonly used tetanus toxoid. These immune markers supported the quantitative findings of the CD4 cells.
    Only one serious adverse event was observed and deemed unrelated to treatment and overall both Vacc-4x and the combination treatment of Vacc-4x + Revlimid were safe and well tolerated.
    "Study results announced today point to a novel step in the clinical research of a functional cure for HIV infection and these findings deserve to be further studied and confirmed as a part of a larger clinical trial," said Prof. Dr. Jan Van Lunzen University of Hamburg, Principal Investigator of the study.
    "This trial demonstrated that Revlimid combined with Vacc-4x in people living with HIV is well tolerated. The results of this trial confirm our hypothesis that Revlimid may enhance the effects of Vacc-4x," said Jerome B. Zeldis MD, PhD, CMO Celgene Inc, CEO Celgene Global Health and Bionor Pharma ASA Board member.
    Full data analysis is ongoing and will be submitted to a future major HIV medical conference. Furthermore the results will be discussed with FDA and EMA. The study is a collaboration between Celgene Corp (NASDAQ: CELG) and Bionor Pharma. Bionor Pharma has been the study sponsor and Celgene has co-funded the trial and supplied lenalidomide. This study, an important outcome of this collaboration, will be further discussed and analysed by the companies.
    About the Trial
    The Phase I/II trial was an exploratory double-blind placebo controlled immunogenicity study of Vacc-4x + Revlimid (lenalidomide) versus Vacc-4x with an initial open label dose escalation assessment of lenalidomide in HIV infected subjects on antiretroviral therapy, ART (SOC HIV treatment). Part A, the Phase I part of the trial, was an open label dose escalation assessment of lenalidomide, showed that all three doses tested were well tolerated, and the highest dose has been chosen for Part B of the study. Part B was a double-blinded placebo controlled parallel design, multicenter study. Both parts were in HIV infected subjects who are on ART but have not fully regained a healthy CD4 level (CD4 counts 200x106/mL and 6/mL. The trial was conducted in four centers in Germany.
    The primary objective of this study is in Part A to establish the maximum tolerated dose of lenalidomide and in Part B to evaluate the immunomodulatory effect of lenalidomide under immunization with Vacc-4x (Vacc-4x + lenalidomide versus Vacc-4x + placebo) on CD4 counts, T-cell response to Vacc-4x and assessment of antibody titer to Vacc-4x peptides and p24, and four vaccine peptides to a non-HIV vaccine antigen (tetanus toxoid antibody titer) as measured from week 21 to week 26.
    Study period for part B, Phase II of the trial, was 26 weeks (13 weeks immunization period + 13 weeks follow-up). Twenty four patients were randomized into two groups where one group received Vacc-4x + placebo and one group received Vacc-4x + Revlimid. Patients received six cycles of Vacc-4x vaccination with Revlimid or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end).
    During treatment period all patients remained on ART and received six immunizations (four primary immunizations and two booster immunizations) at weeks 1, 2, 3 and 4 and booster immunizations at weeks 12 and 13 with either Vacc-4x +lenalidomide or placebo over a 13 week period. Key endpoints were observed at week 13 and at week 26 (study end). The patients received lenalidomide or placebo two days prior and on each day of vaccination.
    One serious adverse event reported (SAE) in this study was a case of subcutaneous abscess that appeared 45 days after the patient was vaccinated. The SAE was evaluated and classified as unrelated by study investigators. The overall clinical and laboratory tolerance profile was satisfactory.
    About the Bionor Pharma
    Bionor Pharma is a leading biotechnology company, searching for breakthrough products for the treatment and prevention of life-threatening viral diseases. The Company is listed on the Oslo Stock Exchange, and is developing vaccines for viral infections. The vaccines are based on a proprietary technology platform developed following more than two decades of research into peptides, and they are designed to safely stimulate the immune system to combat viral diseases.

  • AGIO/CELG late breaker title VERY positive-full abstract out tomorrow. "Clinical safety/activity in AG-120,a 1st in class,selective,potent IDH1-mutant protein inhibitor,in patients with IDH1 mutant positive advanced hema malignancies

    VERY positive titlle...Stock hits 90s after this then ASH 2 more drugs new data in 2 wks

    The FULL abstract will be out tomorrow (Tues) the latest. Presentation Weds..title is VERY positive imo.
    LATE BREAKING ABSTRACT: Clinical safety and activity in a phase I trial of AG-120, a first in class, selective, potent inhibitor of the IDH1-mutant protein, in patients with IDH1 mutant positive advanced hematologic malignancies
    Speaker: D. Pollyea (USA)

    Oral and abstracts where authors did not consent to have their abstract available 2 weeks prior to the meeting, will become available the first day of the meeting. Late Breaking and media selected abstracts will become available on the day of presentation.

  • Reply to

    Time to take Profits?

    by redtr4 Nov 17, 2014 8:49 AM
    rob_cos rob_cos Nov 17, 2014 10:45 AM Flag

    Take near 100 after Weds and ASH - 3 presentations

AMGN
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