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Thanks for the info!
biophud
A quick question for the board re Genmab and Morphosys.
I am considering taking a position in Genmab and/or Morphosys. At its current price, Genmab appears to be a good value (IMO).
I was wondering if anyone here has traded these securities.
I was planning on buying the ADRs that trade on the pink sheets (GNMSF and MPSYF) in order to avoid currency exchanges.
I was looking for the conversion ratios of these ADRs (i.e. how many shares/fractional shares does each represent), but I could not find it. If anyone here knows where I could find this info, please let me know.
Thanks in advance!
biophud
Happy 4th of July to all!
Any updates on the LLY/Imclone integration? The article below got me thinking about what LLY is doing. Have there been any major changes (hirings, firings, etc.)? In addition to the current clinical pipeline, I think that there is an opportunity for LLY to provide IMCL with new targets so that IMCL can use its core competency in developing antagonists antibodies to RTKs and other cell surface receptors. I hope that such a cross-talk and expansion of research projects is happening and I hope that LLY is not cutting the IMCL R&D staff. From what I hear, the J&J purchase of Centocor (sp?) worked well, J&J left Centocor alone, and if spun off today Centocor would be much more than J&J's original purchace price.
http://finance.yahoo.com/news/Level-3-expands-services-to-apf-1047705565.html?x=0&.v=1
Interesting paper from Genentech. Sounds like a new and potentially better way to do bispecifics.
http://www.ncbi.nlm.nih.gov/pubmed/19299620?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Dew,
I have not looked at the data closely and I am not sure how much better Motavizumab is compared to Synagis. My feeing is that it is analogous to EPO/Aranesp. I think that MEDI's RSV vaccine has a better chance of being a game changer.
With regards to RSV, what is your read of ALNY's RNAi compound? The quantitative knock down of viral levels seems encouraging. Plus the compound is designed to treat active infection rather than be preventative.
Regards,
biophud
Dew--My current plan is to reinvest a large portion back into LLY. Other than LLY there are a lot of companies that I am considering depending on price.
I want to invest in/add to positions a in European large pharmas--NVS, GSK, and AZN. Currently I only own GSK
I may also add to my Takeda position
The remainder I plan to reinvest in biotechs.
BIIB and possibly GENZ if the price were to come down further
MEDX and Genmab keeping with my antibody theme
Micromet and Ablynx are two earlier stage companies that I am considering
I would not mind adding to my position in ALNY at the right price
Regards,
biophud
My thoughts on LLY purchase:
In general I am satisfied ($70/share is great given these market conditions) and I think that the purchase validates the drug and technology.
At the time of the previous BMY tender, I did not tender any of my shares-in retrospect I realize that this was the wrong decision. However, at that time I justified my decision because I thought that Erbitux would be approved and achieve significant sales. Also, I thought that IMCL would develop other targeted anti-RTK molecules (second generation Erbitux, anti-angiogenesis compounds, etc). Erbitux sales are over 1B and growing and the pipeline has advanced. In fact the depth of IMCL's developmental pipeline has exceeded my expectations. Despite these successes, the final buyout price is that same as the 2001 tender because from 2001-present, there have been multiple events that have inhibited IMCL's share appreciation.
1. RTF/Martha Stewart delayed approval of the drug and tarnished IMCL's name. IMO, the media coverage of IMCL has been consistently negative and bias against IMCL. The IMCL name is tarnished--I wonder what kind of valuation IMCL would get if LLY spun it off (a la DNA/Roche) in a good market under a new name?
2. Avastin->The delay in Erbitux approval enabled Avastin to take a significant portion of the targeted-therapy oncology space; however, with current studies, Erbitux is fighting back and may be superior to Avastin in many instances.
3. AMGN/ABGX molecule-->This was one of my biggest concerns which proved to be unfounded. IMCL has the better molecule (IgG1) and a second generation molecule which it owns completely in Europe and in the US (?).
4. Current financial crisis/market conditions.
I think that I understand IMCL's valuation at $70/share. However as a long term holder since 1999, I had hoped for more--specifically an IMNX-type valuation. Oh well, IMCL holders now have the nice problem of reallocating earnings into other investments.
Regards,
biophud
IMCL is the first and only message board on which I have posted. From what I have seen, the collective intelligence of the board is very high. I appreciate the insights that I have read and consider many of the posters friends.
EORTC link--Multiple IMCL abstracts presented. An impressive and diverse collection of pipeline molecules.
http://www.ecco-org.eu/Conferences-and-Events/EORTC-NCI-AACR-2008/page.aspx/268
Also of note-->data from AMGN on their anti ErbB-3 antibody (developed with ABGX and U3). Interesting because the study looks at combination therapy with c225.
Fully human anti-HER3 mAb U3-1287 (AMG 888) demonstrates unique in vitro and in vivo activities versus other HER family inhibitors in NSCLC models M. Treder1, S. Ogbagabriel2, R. Moor1, U. Schulze-Horsel1, T. Hettmann1, M. Rothe1, R. Radinsky2, D. Freeman2. 1U3 Pharma, Research, Munich, Germany; 2Amgen Inc, Oncology Research, Thousand Oaks, CA, USA
Background: HER3 is a member of the Human Epidermal Growth Factor Receptor (HER) family and is an important component of HER family driven tumorigenesis. Though HER3 lacks intrinsic kinase activity, it is a scaffold for PI3K/AKT signaling for the HER family via heterodimeric interactions. HER3 signaling may be a resistance mechanism for EGFR and HER2 inhibitors. We report unique in vitro and in vivo activities of U3-1287 (AMG 888), the first fully human Anti-HER3 mAb vs. current HER family inhibitors in NSCLC models. Combinations with EGFR inhibitors are also explored. Methods: To determine the inhibition of HER3 oncogenic signaling, A549, Calu-3 and H1975 NSCLC cells were treated with up to 10 mg/ml of U3-1287 (AMG 888), C225 (Anti-EGFR), c2C4 (Anti-HER2) or control mAbs 1 hour prior to heregulin-beta (HRG) or vehicle stimulation. Since HER3 is a heterodimerization partner for HER family members, U3-1287 (AMG 888) was combined with EGFR inhibitors in vitro. To determine in vivo efficacy, mice bearing ~200mm3 A549 NSCLC xenografts were treated 2×/week with anti-HER or control Abs. A549 xenograft tumors were analyzed for the inhibition of pHER3 by Western blotting. The anti-tumor effects of U3-1287 (AMG 888) with an EGFR inhibitor was tested in the Calu-3 and H1975 NSCLC xenograft models. Results: Treatment with U3-1287 (AMG 888) resulted in an inhibition of ligand-induced pHER3, basal pHER3 and pAkt in A549, Calu-3 and H1975 NSCLC cell lines, respectively. In NCI-H1975 cells, combining U3-1287 (AMG 888) with the anti-EGFR mAb C225 resulted in greater pHER3 and pAkt inhibition in vitro than with either single agent alone. Administration of U3-1287 (AMG 888) resulted in tumor stasis in the (EGFR TKI resistant) A549 NSCLC xenograft model vs control and other HER mAbs and tumor inhibition in Calu-3 and NCI-H1975 xenografts compared to IgG treated mice (p < 0.05). Combinations with the anti-EGFR mAb C225 resulted in tumor growth inhibition that was greater than either single agent alone in CaLu-3 (p < 0.001) and NCI-H1975 (p < 0.001) xenografts. Conclusions: U3-1287 (AMG 888) inhibits basal and ligand-induced HER3 oncogenic signaling in NSCLC cell lines in vitro and basal pHER3 in vivo. NSCLC xenografts are sensitive to U3-1287 (AMG 888) treatment as single agent or in combination with an anti-EGFR mAb, including an EGFR TKI resistant model. These data provide preclinical evidence for the potential clinical application of U3-1287 (AMG 888) in NSCLC.
I’m still trying to digest all of the recent news. I’m confused by the recent talk of splitting up IMCL. The questions that I have are the following:
1. Does splitting IMCL mean splitting Erbitux from 11F8 with BMY buying Erbitux and IMCL developing 11F8 and the rest of the pipeline?-->Negatives potential antagonistic situation between IMCL and BMY; up-side for IMCL if 11F8 can out compete Erbitux.
or
2. Does Splitting IMCL mean BMY buying both Erbitux and 11F8 with the remainder of IMCL being spun off as a new equity?-->Advantage preserves the anti-EGFR franchise under one entity with both cash and equity to IMCL shareholders (granted such an equity would have more intrinsic risk once the only approved drug has been divested).
In my opinion it does not make sense to split Erbitux from 11F8--The same company (or companies) that develop Erbitux should develop the second-generation molecule (IMO). I would think that having established sales and distribution channels with Erbitux would facilitate introduction of the second-generation molecule.
We will see what happens.
Comments appreciated,
biophud
FYI--The link below is the patent that I was looking for-->IMCL's patent for 11F8, human anti-EGFR generated using DYAX's phage display. I found it on WIPO (I did not see it listed on USPTO).
http://www.wipo.int/pctdb/en/fetch.jsp?SEARCH_IA=US2005009583&DBSELECT=PCT&C=10&TOTAL=56&IDB=0&TYPE_FIELD=256&SERVER_TYPE=19-10&QUERY=%2811F8%29+&ELEMENT_SET=B&START=51&SORT=41231877-KEY&RESULT=52&DISP=25&FORM=SEP-0%2FHITNUM%2CB-ENG%2CDP%2CMC%2CAN%2CPA%2CABSUM-ENG&IDOC=1305267&IA=US2005009583&LANG=ENG&DISPLAY=STATUS
biophud
I recall that Ichan wanted BIIB to share material information with potential buyers. I wonder if today's news about PML cases was part of this material information.
IMO it is very important what other immunotherapy regimens these patients were on. If these patients were receiving monotheray, the news is much more significant.
biophud
<The prominent discussion of 11F8 on the recent CC and BMY’s buyout offer are not unrelated>. I tend to agree. However, I am still puzzled by the Adnexus purchase where BMY bought a competing technology to generate extracellular protein antagonists to receptor tyrosine kinases (the same RTKs that IMCL is working on). Given this purchase, do you think that there are any regulatory barriers/anti-trust issues in the BMY purchase of IMCL?
Regards,
biophud
Thanks for your opinion. 11F8 is an EGFR-drug, specifically a phage derived human anti-EGFR. Strictly speaking 11F8 is NOT a humanized/CDR-grafted antibody. I'm not sure how this will be treated from a legal standpoint.
The question that I have is the following: does 11F8 have any meaurable efficacy advantage over Erbitux?
We will see what happens in a couple of months.
Regards,
biophud
Significance of the BMY/Adnexus purchase. I reread the restriction on competing products that corky posted on the yahoo board (see below) and I have a few thoughts. Based on the BMY purchase of Adnexus it would appear that they are pursing adnectin-based technology as a strategy to block the extracellular domains of receptor tyrosine kinases. I cannot find the link but I recall a presentation in which BMY/Adnexus were investigating antagonists of VEGFR, EGFR, IGFR, as well as dual targeted agents. If BMY is pursuing an adnectin-based EGFR antagonist, this would appear to violate the restriction on competing products--Could this be the reason that IMCL has 100% right to 11F8?. It would seem that after buying Adnexus, it would be redundant for BMY to partner the IMCL pipeline. As I recall, the Adnexus purchase went for ~400 million, significantly less than it would cost to purchase IMCL. Comments appreciated.
biophud
RESTRICTION ON COMPETING PRODUCTS. During the period from the date of the Commercial Agreement until September 19, 2008, the parties have agreed not to, directly or indirectly, develop or commercialize a competing product (defined as a product which has as its only mechanism of action an antagonism of the EGF receptor) in any country in the Territory. In the event that any party proposes to commercialize a competing product or purchases or otherwise takes control of a third party which has developed or commercialized a competing product, then such party must either divest the competing product within 12 months or offer the other party the right to participate in the commercialization and development of the competing product on a 50/50 basis (provided that if the
Dew--I'm not sure, but my understanding is that companies like IMCL licence phage display technology from DYAX and use the technology themselves to isolate antibodies directed toward specific targets.
Here is a patent for anti-FGFR antibodies generated by IMCL using DYAX phage technology. Note that IMCL is the only assignee listed on the the patent.
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=45&f=G&l=50&co1=AND&d=PG01&s1=dyax&OS=dyax&RS=dyax
My understanding is that DYAX will collect milestones payments and royalities on future sales if a product comes to market.
Regards,
biophud
Comments regarding recent Yahoo postings on 11F8 and humanized c225. Corky mentioned that 11F8 and humanized C225 are not the same thing. I think that this is an important point that raises several questions. Specifically how are these two molecules treated in terms of intellectual property? and how are these two entities treated in terms of IMCL's contractual agrements?
IMCL has a patent on a CDR-grafted humanized c225. See below.
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=2&f=G&l=50&co1=AND&d=PTXT&s1=imclone.ASNM.&OS=AN/imclone&RS=AN/imclone
As far as I know IMCL does not have a clinical trial with a CDR-grafted humanized c225 antibody
11F8 is a fully human phage-derived antibody derived from DYAX's phage library technology.
As far as I know IMCL does not have a patent on a fully human phage-derived anti EGFR-antibody.
Comments appreciated,
biophud
Dew--do you think that there is any chance of stock deal in lieu of cash? All of the recent biotech buyouts that I can think of have all been for cash. As a shareholder of DNA I would not mind receiving Roche stock.
Thanks in advance,
biophud
FYI--IMCL patent application for psoriasis.
biophud
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PG01&s1=IMCLONE.AS.&OS=AN/IMCLONE&RS=AN/IMCLONE
Dew--I wonder how this deal will affect DYAX? The stock has been under pressure lately.
Regards,
biophud
Question for the board. Any opinions on Silence Therapeutics?
I have a position in ALNY as I think that it is the most dominant company in the RNAi space. I recently learned about Silence Therapeutics and was impressed by the number of major pharma/biotech partners as well as by the number of drugs in clinical trials. I also noticed its relative price weakness over the past 1 year in contrast to ALNY. When I look at price actions of the stocks I cannot understand why there would be such a disconnect in price action without material news. Opinions appreciated.
biophud
Happy 4th of July to all!
biophud
Thanks Dew
biophud
Dew thanks for the info on Takeda. Here is a link with info on TKPHY and other ADRs.
http://www.adr.com/adr?page=search&dir=yes&name=T
TKPHY does respresent half a share; however, TKPHF appears to represent one full share as it is trading at twice the price of TKPHY. Correct me if I am wrong.
These issues aside what is your investment opinion of Takeda.
biophud
Jbog--Thanks for your opinion. I reinvested some of my MLNM profits into Takeda (TKPHY). I like the fact that they are investing in US biotechs. While they may have overpaid for MLNM (I'm not complaining), I think that the move will pay off in the long term.
Also there is a connection to IMCL/anti-EGFR. The link below shows that Takeda USA is developing EMD72000--I did not realize that Takeda had rights to this compound? I thought that Merck KGA has discontinued its development?
I think that it is interesting that EMD72000 binds to a different epitope than c225 and there are preclinical data that suggest that it may be beneficial to target both epitopes. A combined product (two separate antibodies or a bispecific antibody targeting both epitopes) would be interesting.
Regards,
biophud
http://www.tpna.com/pipeline.asp
Question for Dew and the board. Regarding Takeda, I noticed that it trades under two symbols TKPHY (an ADR) and TKPHF (common stock). Are there any pros and cons about which share to buy? I favor the ADR because it is easier/cheaper to purchase at my current brokerage? Comments appreciated.
biophud
BLYS antagonists--I have noticed that Biogen and Genentech no longer list the BR3-soluble receptor/BLYS antagonist on their current pipeline list. Also the anti-BR3 antibody is no longer on the Genentech pipeline list. Does anybody have any updates on these programs? Have they been discontinued? or are they running in stealth mode? Comments appreciated.
biophud
T-cells and anti-EGFR therapy
http://www.ncbi.nlm.nih.gov/pubmed/18481381?dopt=AbstractPlus
biophud
EGFR extracellular polymorphism associated with response to Erbitux.
http://www.ncbi.nlm.nih.gov/pubmed/18544172?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
biophud
Thanks Dew--I will check out the 1099.
biophud
Question about PDLI's one time dividend payment. Does anyone know how this transaction is treated from a tax perspective? Is it treated as a dividend or as a capitol gain/loss. I have lost money on PDLI as I purchased the stock in the low $20, and don't want to pay taxes. Comments appreciated. Thanks in advance.
biophud
Thoughts on IGFR antagonists. I'm optimistic about this class of drugs. In general it is a good sign when multiple academic and industry groups come to similar conclusions.
I think the worry about a me-to-mess can be overstated. Multiple statins coexist in the market, and in terms of biologics there are multiple TNF-alpha inhibitors (AMGN, J&J, ABT, and many more in development).
Also, there is the issue that biological are complex molecules that vary by isotype, affinity, and ability to activate ADCC.
Based on the clinical trials that I have read about, I would expect different companies to stake out specific therapeutic areas where they are not in direct competition (at least initially). IMO
biophud
Price predictions post ASCO data.
Identifying the good biotech companies is not the difficult part. The difficult part is trying to guess how the market will react (I recall Jim McCamant making a similar statement on CNBC).
I think this statement applies to IMCL going into ASCO. I’m positive on IMCL on multiple levels (Erbitux data, lung data, K-Ras, and pipeline).
I think that K-Ras data is a long term positive for IMCL; however, this data could also be used to argue that there will be decreasing sales (at least initially).
I’m debating adding to my position in the low 40s. I can envision a 10-20 point increase following the data. I can also imagine a pull back to the low 30s.
biophud
New IMCL patent application on neural progenitor cells.
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=2&f=G&l=50&co1=AND&d=PG01&s1=imclone&OS=imclone&RS=imclone
biophud
New issued patent on IMCL's VE-cadherin antibody.
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=imclone.ASNM.&OS=AN/imclone&RS=AN/imclone
biophud
Pfizer's IGFR patent on their IgG2 antibody. Reduced immunogenicity (sp?). IMHO, if you are targeting cancer with an antibody to a cell surface receptor(s), then you want an IgG1 antibody.
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=5&f=G&l=50&co1=AND&d=PTXT&s1=imclone&OS=imclone&RS=imclone
biophud
Thanks Dew I always appreciate your opinions.
biophud
Interesting new paper.
http://www.ncbi.nlm.nih.gov/pubmed/18424917?dopt=AbstractPlus
Dew-what is your take on the MLNM deal. I know that there is some discontent on some of the message boards for MLNM not entertaining other offers. I would not have expected a deal with a Japanese firm; I thought that JNJ would be the most likely or maybe BIIB. In previous posts I know that you have mentioned Japanese drug firms have not undergone the large scale MandA consolidation of their US and European counterparts--Is the Takeda purchase of MLNM the beginning of such a trend? Do you think that Takeda is a good investment?
Regards,
biophud
Dew--What is your take on the HGSI swap? It would appear that HGSI is very confident in its TRAIL antibodies. HGSI's IP appears to be stronger on the TRAILR-1 antibody and there are no other competing antibodies out there (that I know of). For TRAILR-2, there are competing antibodies in development (AMGN and DNA) and an ongoing IP battle.
I was wondering if it is a possibility for HGSI to strike a deal with either AMGN or DNA to consolidate IP, compare clinical data, and to select the best antibody(s). Otherwise, why would HGSI agree to such a deal?
Full disclosure I own shares in AMGN, DNA, and HGSI. I am interested in this issue because success of TRAILR antibodies would have the most significant effect on HGSI's market cap.
Regards,
biophud