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Seems like lots of groups are targeting Aurora kinase. Off the top of my head there is Merck/Vertex, MLNM, RIGL, AZN (?), and I rememeber that IMCL had a paper with early stage research on Aurora kinase inhibitors (from Imclone's small molecule division-now closed down). From the papers that I have seen there is a debate about how to best target Aurora kinase--> target the A or B isoform or target both.
biophud
Corky--What are your expectations for Crystal? Do you think it will put some distance between us and AMGN?
biophud
Corky,
IMO, a strong CMO and CSO are must haves for a company like Imclone. I thought that Frost and Rowinsky were great hires, and I think that they add value to Imclone as a stand alone company (or in the event that Imclone is bought out). Consequently, I do not understand why Frost resigned. Any idea if Rowinsky will stay or go?
biophud
Clinical trial results will provide the ultimate answer. I consider it positive that the NCI is running such a trial. NCI sponsorship means little/no cost for Imclone, and also suggests a strong scientific rational for the combo.
Two Points
1. I would expect combined Erbitux + Tarceva to have bad skin/rash side effects.
2. With combo targeted therapies (like Erbitux and Tarceva) it may be possible to limit or eliminate chemotherapy, and all of its bad side effects.
Have a good weekend,
biophud
I understand your concerns. However, there are basic science reports that the combined used of Erbitux and and small molecule EGFR-kinase inhibitors (see link below) produce additive effects.
One rational that has been put forward is that small molecule kinase inhibition increases cell surface expression of EGFR, thus making more EGFR available for attack by an anti-EGFR antibody.
The questions that I have are-->How much more efficacy do you get from the combo? Does the combo have any added toxicities? Will payers be willing to pay for combined treatment?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
biophud
New Clinical Trials. Erbitux + Tarceva In Lung. Erbitux + everything else in panc cancer.
http://www.clinicaltrials.gov/ct/show/NCT00408499?order=1
http://www.clinicaltrials.gov/ct/show/NCT00408564?order=3
Dew-Any comments on Lexicon Genetics?
biophud
Erbitux and Avastin for Head and Neck--Phase II Trial.
http://www.clinicaltrials.gov/ct/show/NCT00407810?order=1
Lexicon Genetics--my impressions
A former high flyer at a relative low price with a low market cap. It has revenues. In my opinion, knockout mice can serve as a good model of disease. Candidates beginning to start clinical trials:
LX6171 for cognitive disorders (Phase 1 clinical trials)
LX1031 for irritable bowel syndrome (IND announced today)
LX2931 for autoimmune disease (Preclinical development)
Several good partners. Appears to have a strong patent portfolio.
For a biotech without a profit it has a lot of employees, and I would suspect high operating expenses (Please correct me if I am wrong).
Not a particularly strong cash position.
Potential risk of dilution.
The exact targets of their clinical candidates are not disclosed. Difficult to evaluate scientifically and fully handicap.
No phase II or phase III drugs in trials. I think that this largely explains the low market cap.
Drugs that treat cognitive disorders are more in the realm of large pharma rather than small biotechs.
IMO, the stock appears reasonably priced but significant appreciation would be contingent on positive phase II efficacy studies (several years away).
Any opinions would be appreciated,
Biophud
Jbog, when I saw this post, I remembered the collaberation that Imclone has with Neurome. FWIW
http://www.neurome.com/news/press092304.htm
biophud
It look like many of the early stage biotechs with CV-related drugs are moving up on the heels of PFE's bad news.
biophud
Thanks, Dew.
biophud
Re: Torcetrapib's Demise. Is this the demise of Torcetrapid only? Or is it a demise of this class of inhibitors. I seem to recall that Avant (AVAN) was using a vaccine to target the same enzyme. Please correct me if I am wrong.
Regardless, the demise of Torcetrapib would appear to be very good news for Merck's phase III drugs (MK-0524 A and B). Any comments.
biophud
Very interesting article jbog. I will have to read the article in more detail.
This article brings of an off-topic question for you and the board. Regarding anti-obesity drugs, what level of efficacy is needed to have a marketable injectable drug?
The data that I have seen for Leptin and Regeneron's drug have been modest (IMHO).
biophud
The trials that I post are new trials that I find on clinicaltrials.gov
Many of these trials are early stage trials. Many are sponsored by groups other than Imclone (University Investigators, NCI, etc.) In general, I consider it positive that a number of investigators, independent of Imclone, are pursuing clinical trials of Erbitux.
I agree with you that it would be nice to have more follow up of clinical trial results. Admittedy, there are a number of clinical trials which end up going nowhere for whatever reason-->side effects, small indication, enrollment, etc.
In terms of reporting clinical trial results, it would be nice to have a database of completed trial results (both good and bad)--I seem to recall that some Big Pharma companies are starting to do this? If trial results are positive, then there is good incentive to report/publish. If they are negative then the results can also be reported/published. In terms of reporting negative results, I'm not sure what the ethical/moral/legal standard(s) are in terms of reporting. As long as a trial is well done, negative results can be useful, and advance future studies.
From an investing perspective, successful phase III trials (and in some cases phase II trials) are the most important clinical trials (IMHO). For example, I expect the upcoming Crystal trial to have a major material impact on Imclone-->significantly more than the early stage trials that I post. Hope this helps.
Two new clinical trials for Erbitux.
http://www.clinicaltrials.gov/ct/show/NCT00403052?order=1
http://www.clinicaltrials.gov/ct/show/NCT00402545?order=2
Use of Erbitux for treatment of metastatic and chemorefractory thymoma.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Bispecific AB paper from Imclone.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Question(s) to board. I came across these Imclone patent appications--all of which are stem cell-related (see link below). As I recall, several years ago I saw a microarray paper from Princeton (sponsored by Imclone) in which they defined a stem cell expression profile.
My questions-->Why hasn't Imclone mentioned/emphasized their stem-cell research. As I recall, the stem-cell work is not mentioned in the annual report at all.
Where are the patents/patent appications on the early stage products (e.g. RON, FGFR, etc.)? In contrast to the stem-cell research, the Imclone annual report does emphasize these early programs.
Any insight on this apparent disconnect will be appreciated.
biophud
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...
Thanks Dew for your opinions on DYAX.
I was not aware of either Jerini of Pharming. Seems like a fair amount of competition for a small indication.
How do you trade foreign biotechs not listed in the US? I've looked into this, and called several brokers, but it seems like more trouble than it is worth.
Happy Thanksgiving,
biophud
Dew, Thanks for your opinions on DNDN on the IMCL board.
I would like opinions on DYAX as an investment. My Pros and Cons are listed below.
Pro’s:
My bet is that DX-88 will be approved. HAE is a small indication, but it may be enough to be material to DYAX.
DX-88-->Strong partner with Genzyme.
A fully human phage-antibody company with a small market cap.
One of the cheapest fully human phage-antibody companies by market cap (to the best of my knowledge).
Possibility of royalties on future antibody sales-->Many of Imclone’s phage-antibodies were generated using DYAX phage display.
DX-88 for CABG(?)
Stock is at a relative low.
Con’s:
Could DYAX survive a delay or demise of DX-88?
Basically a one-product company.
Other than DX-88, a limited near-term pipeline.
Any opinions would be appreciated.
biophud
New review article on flt-1.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Dew-How do you handicap the success of DNDN's sipuleucel-T?
My impression is that the treatment would be logistically difficult to administer, and a very high level of efficacy will be needed in order for it to be a commercial success. Correct me if I am wrong. Thanks in advance.
biophud
Jbog-- If the cardiovascular side effects are, in fact, due to targeting Flt-1, then what can we expect from IMC-18F1. What will be the impact of specifically targeting Flt-1? Any thoughts would be appreciated.
biophud
Peregrine Pharmaceuticals with early stage antibody to VEGFR-2.
http://www.peregrineinc.com/content.php?mi=NzM=
New BMY patent for combination EGFR and VEGFR inhibition.
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...
EGFR/IGFR heterodimerization.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
New review article on side effects of vegf inhibitors. I have not read it in detail but it may be useful to the current discussion.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
ASH Abstract [1152] A Putative Role for VEGFR-1 (FLT-1) in B Cell Commitment and Differentiation. Session Type: Poster Session, Board #280-I??Rita Fragoso, Catia Igreja, Claudia Appleton, Alexandra Henriques, Nuno Clode, Yan Wu, Zhenping Zhu, Sergio Dias Angiogenesis Laboratory, Instituto Portugus de Oncologia, Lisboa, Portugal; Instituto Gulbenkian Cincia, Oeiras, Portugal; Hospital de Santa Maria, Lisboa, Portugal; ImClone Systems, New York, USA??VEGF and its receptors are expressed in the hematopoietic system. A role for FLT-1 in particular was described in monocyte-macrophage migration and lineage differentiation (Sawano A et al, 2001), megakaryocytes maturation (Casella I et al, 2003) and dendritic cell differentiation (Dikov M et al, 2005). Given that the expression of this receptor in the lymphoid lineage is not known, we to studied FLT-1 expression and a putative function in normal lymphoid progenitors. To address this question we induced in vitro CD34+ cells differentiation into the B cell lineage using a well established assay (on S17 stromal cells). With this approach, we observed that FLT-1 is expressed throughout B cell differentiation increasing along the differentiation process, and reaching its highest at the immature B cell stage. We also neutralized FLT-1 during B cell differentiation in vitro. Surprisingly, in the presence of the FLT-1 neutralizing antibody (6.12 monoclonal Ab, from ImClone systems), at the end of the assays (4 different experiments) a significantly higher number of CD19+ cells (mainly immature B cells) were detected. Analyzing some of the transcription factors known to be involved in the commitment and differentiation of lymphoid B cells, we observed that the expression of PU.1, Pax5 and E47 was up-regulated by FLT-1 neutralization. Next, given that FLT-1 function was mainly associated with cell migration, and since it is expressed in B cells that are ready to exit the bone marrow into secondary lymphoid organs, we reasoned that FLT-1 might have a role in B cells exit from the bone marrow. For this purpose, we treated mice with the FLT-1 neutralizing Ab for 3 days and analyzed B cells levels in bone marrow and peripheral blood. FLT-1 neutralization led to a significant decrease (p<0.05) in B cells in the bone marrow and peripheral blood. Taken together, our data supports a clear role for FLT-1 in B cell commitment. To understand if VEGF/PlGF signalling through FLT-1 promotes myeloid differentiation, suppresses B cell differentiation or simply regulates the quiescent state of hematopoietic stem cells, we differentiated in vitro CD34+/FLT-1- cells and CD34+/FLT-1+ cells (10% of CD34+ cells) using the assay described above. Interestingly, CD34+/FLT-1- differentiation in vitro largely promoted B cell differentiation, while CD34+/FLT-1+ cells originated mostly myeloid cell differentiation. We are currently exploiting the molecular basis whereby FLT-1 signalling may impair B cells commitment and possibly promotes myeloid differentiation.?Abstract #1152 appears in Blood, Volume 108, issue 11, November 16, 2006?Keywords: B cell development|VEGFR|Cord blood CD34+ Cells??Saturday, December 9, 2006 9:00 AM??Poster Session: Hematopoiesis: Cytokines and Signal Transduction I (9:00 AM-7:30 PM)
New paper regarding Erbitux and ADCC
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
New clinical trial-->Erlotinib and Cetuximab
http://www.clinicaltrials.gov/ct/show/NCT00397384?order=1
Unable to find this news on TNOX. Do you have a link?
Thanks,
biophud
BMY patent--> Synergy of EGFR blockers + taxanes
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPT...
Research on IGF signaling.
http://www.eurekalert.org/pub_releases/2006-11/chop-gfs110906.php
New publication--Efficacy of pregabalin in the management of cetuximab-related itch.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
New paper on anti-flt-1 from Imclone.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...