I cant wait till ASH. It will be amazing for CELG and many other companies that will be presenting there. I always use that to make my shopping list for companies I think could be the next CELG. Not that I would ever sell CELG but I usually keep it and one other as a great prospect in my portfolio.
It will post here if you take out the "dot' and insert the word "dot"
Couldn't agree more. Love the chart. Yes breakout will occur without the GED-031 data and then explode when it hits. Stock hits $200 next year as it becomes a big momo play, and analyst keep upping estimates for the next 3 years out.
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
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
Today's news on Otezla supports your statemeny
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.
Since 2017 is still two years off, lots more can happen to the entire CELG pipeline.
Rob, been following your lead for a few years. Most of the time I don't really have a clue what your saying however I do get the vibes and feelings.....Once again (probably the 50th time) in the last 10 years I purchased a load of celgene ( 50.86 and again for 88.40)-
I appreciate your information.
+ 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
More Positive On Otezla And Baricitinib
Prospects After ACR Feedback
EQUITY RESEARCH AMERICAS
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.
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 )
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
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.
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.
(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.
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.
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.
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.
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.
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.
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).
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.
I forgot, they really haven't come up with new estimates. Even though it is from a recent event they indicated that numbers will be updated. So eventually we will see a whole new estimate along with new Earnings per share.
No one ever saw that one coming. Apparently Bionor Pharma said that their Vacc+4x in combination with Revlimid increased CD4 levels in HIV patients to by 30% vs 17% in Vacc+4 alone.
The play in the numbers depends on new indications. Revlimid has 2 new indications in 2015, Abraxane has 1 and Otezla has 2. That is why there is variables.