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Dew and jbog,
Thanks for the info that you sent on bispecific antibodies. As far as I can tell all of these methods use recombinant methods to generate bispecific antibodies.
I was wondering if anyone is working on generating bispecific by chemical-linking methods.
Regards,
biophud
I know IMCL and others are working on bispecific antibodies. Does anyone know of any companies/groups that are working on covalently linking two therapeutic monoclonal antibodies so that two distinct antibodies can be linked. put in one bottle, and treated as one drug from a regulatory perspective. Comments appreciated.
biophud
New paper in Cancer Cell regarding Matuzumab binding to EGFR.
Some points that I picked up base on my quick read:
1. Cetuximab and Matuzumab bind to distinct and non-overlapping binding sites.
2. Matuzumab does not directly block access of the ligand to the domain III ligand-binding site.
3. Matuzumab blocks the local conformational changes in domain II that are critical high affinity ligand binding and dimerization. The inhibition is non-competitive and the ligand binding site on domain III is not blocked (In contrast to Cetuximab which is a competitive inhibitor that blocks the ligand binding site on domain III).
4. Cetuximab and Matuzumab can bind EGFR simultaneously.
5. The authors of the paper raise the possibilities of a potential synergy if Cetuximab and Matuzumab are administered together.
Comments appreciated,
biophud
PS I wonder if we will ever see this type of structural data from the AMGN/ABGX antibody?
Biowatch--Thanks for your comments. Argot is indeed an interesting name. It seems like the people forming this consulting firm are getting maximal benefit from a bad situation. Someday, I hope that longstanding IMCL shareholders will benefit from their investment.
biophud
Argot Partners-->Consulting firm with IMCL alumni.
http://images.google.com/imgres?imgurl=http://www.argotpartners.com/images/andrea.jpg&imgrefurl=http://www.argotpartners.com/page.php%3Fpage%3Dbio_andrea&h=150&w=150&sz=13&hl=en&start=1&um=1&tbnid=ikX_hvHbmcsc0M:&tbnh=96&tbnw=96&prev=/images%3Fq%3Dandrea%2Brabney%26um%3D1%26hl%3Den%26safe%3Doff%26client%3Dsafari%26rls%3Den%26sa%3DG
biophud
New publication from IMCL on an anti-TYRP antibody (using MEDX's mouse).
http://www.ncbi.nlm.nih.gov/pubmed/18334748?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
biophud
FYI-Tax incentives for IMCL to bring jobs to NJ.
http://www.nj.com/news/index.ssf/2008/03/nj_offers_imclone_28m_in_tax_b.html
biophud
New IMCL patent. Can someone on this board explain this patent to me (what is it and why does IMCL want to protect it?). Thanks in advance.
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
biophud
Jbog--Thanks for your insights. Clearly, there is a lot cooking in the pipeline, and I look forward to watching the pipeline develop. IMO, the pipeline is still underappreciated. In the near term the investment community seems most focused on ASCO and FLEX data rather than on the pipeline.
Regards,
biophud
PS Thanks for the investment report that you sent via private communication. Lately I have not been doing well enough in my biotech investments for the premium iHUB subscription :)
Dew, one is RespiGam--Respiratory Syncytial Virus Immune Globulin (RSV-IGIV). I'm not sure about the third.
biophud
Jbog--IMCL has an impressive pipeline. Given the number of clinical trials it seems to me that IMCL will need help in development/clinical trials. How do you think IMCL will proceed with development (go it alone vs collaborations). I know IMCL has mentioned potential collaborations for non-oncology indications. What molecule(s) does it make sense for IMCL to develop without a partner? The questions I have are when will IMCL partner, at what stage phase of development, and with whom. I would think that the anti-IGFR antibody would be a good candidate to partner due to the multiple competing molecules in development. On the other hand IMCL has NCI support in the development of this molecule.
Comments appreciated,
biophud
New papers rearding anti-EGFR therapy: dosing of Erbitux every two weeks, resistance to anti-EGFR therapy by ErbB-3 activation, and correlation of miRNA levels with response to small molecule EGFR inhibitors.
http://www.ncbi.nlm.nih.gov/pubmed/18305055?dopt=AbstractPlus
http://www.ncbi.nlm.nih.gov/pubmed/18297114?dopt=AbstractPlus
http://www.ncbi.nlm.nih.gov/pubmed/18304967?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Regards,
biophud
Dew--thanks for your comments on ALNY.
Regarding point#5--"RSV vaccines are available commercially."
Is this a reference to Synagis? Synagis is an ant-RSV MAB that produces passive immunological protection? Synagis is not a vaccine.
My understanding is that MEDI (now AZN) is/was working on a RSV vaccine.
Regards,
biophud
Tumor resensitization to erlotinib following brief substitution of cetuximab.
http://www.ncbi.nlm.nih.gov/pubmed/18283460?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
biophud
Thanks Dew. Appreciate your comments.
biophud
Crystal structure of IMCL's fully human anti-EGFR antibody.
Interesting line--> "Fab11F8 interacts with a remarkably similar epitope, but through a completely different set of interactions"
I will have to read the article.
http://www.ncbi.nlm.nih.gov/pubmed/18275813?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Question for the board. The approval of recombinant Thrombin makes me wonder if there are any other examples of low-hanging fruit (blood derived products that could be replaced with recombinant counterparts). Specific examples that I think could be replaced are RhoGAM and IVIG. Would it be profitable to develop recombinant fully human versions of RhoGam and IVIG? Are any companies working on this. Comments appreciated.
biophud
IMCL board member David Sidransky, M.D named to the Medical Advisory Board of
Rosetta Genomics.
http://biz.yahoo.com/prnews/080204/ukm035.html?.v=14
Also an interesting excerpt from a Rosetta press release regarding miRNA testing that they are developing (Dec 11, 2007).
“Differentiating squamous from non squamous lung cancer - As current targeted therapy for lung cancer can cause hemorrhaging in squamous cell lung cancer patients, differentiating between the cancer types is critical. Rosetta Genomics has identified several microRNA biomarkers that may allow for sensitive and specific identification of squamous cell carcinoma.”
Comments appreciated,
biophud
Thanks Dew! I always appreciate your insights.
Regards,
biophud
Dew--a couple of quick questions/comments re marketing drugs in Japan
When I see a headline like this, I wonder why does a large company like AMGN need a Japanese partner to market its drugs? This seems to be a general trend in which large pharmaceutical companies partner with Japanese companies to market in Japan. Is this because of cultural, political, or regulatory reasons? Is there an example of a large US/European drug company that markets its drugs in Japan without a Japanese partner? Are there laws/protectionist policies that prevent foreign companies from marketing in Japan?
To the best of my knowledge there are no megacap Japanese drug companies (compared to US and European drug companies), please correct me if I am wrong.
Comments appreciated,
biophud
FYI--Interesting Motley Fool comment regarding the AMGN purchase of ABGX. The article below states that the elimination of denosumab royalties was the MAIN reason for the AMGN purchase of ABGX. Several posters here have cited this as the reason. However, this is the first time that I have seen this opinion directly stated in the financial press.
http://www.fool.com/investing/high-growth/2008/01/28/a-wing-and-a-prayer-for-amgen.aspx
Correction-Good reference
biophud
Goof reference on antagonism of BLYS and APRIL. It looks like it is unclear/unknown if some of these agents inhibit BLYS/APRIL heterodimers. At this point, I'm not sure what is the ideal inhibition strategy. While inhibition of both BLYS and APRIL may seem more potent, there is data that there is an inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus (see reference below).
http://www.ncbi.nlm.nih.gov/pubmed/15308519?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Comments appreciated,
biophud
New publication on Erbitux's synergy with chemo.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=18094427&itool=pubmed_DocSum
biophud
Thanks corky. I appreciate your opinion and share your optimism on IMCL's future.
Regards,
biophud
Jbog--I agree. I think a sale at this time would be premature. Looking forward to the upcomig trial data.
biophud
Corky--With the Yeda patent issue resolved, do you think that it affects the prospects for deals/M&A activity?
I would think that after the Yeda setlement, it would remove uncertainty, and make it easier to value IMCL.
Regards,
biophud
New IMCL patent application for stem-cell preservation factor. IMCL has several patents/patent applications like this. In addition, IMCL has supported stem-cell genomics research with Princeton. I wonder what IMCL's strategy/goal is with this line of research. Any comments?
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
Thanks Dew. Always appreciate your perspective.
biophud
Dew--With a deal like this, I would think that NVS could have bought all of DYAX and own its human-phage display technology. Any comments?
biophud
New patent application from IMCL--> Anti-FGFR antibodies for obesity.
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
Observation--Very low volume today considering the IMS numbers and the Erbitux-resection paper/press release.
biophud
Interesting new basic research article re Erbitux and activation of EGFR.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=18033688&itool=pubmed_DocSum
biophud
Interesting new research article. Nebulized Erbitux.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18030605&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
biophud
Happy Thanksgiving to all!
biophud
Interesting new NCI clinical trial-->Erbitux + Pertuzumab [an anti-ErbB-2 antibody (not Herceptin) from Genentech].
http://clinicaltrials.gov/ct/show/NCT00551421?order=4
Corky,
I think that this is an interesting article--The fact that computational methods can be used to improve antibody affinity. However, IMO all of the different methods for geneating antibodies (phage-display, transgenetics animals, CDR-grafting, computational methods, etc.) are multiple roads to the same end. I do not believe that any one method is best suited to produce the "perfect" antibody candiate. Regardless of how an AB is generated it must be validated functionally, in vitro and in vivo.
Another point to consider is that higher affinity may not translate into improved therapeutic efficacy (I wonder if this was a problem with the AMGN/ABGX antibody, in addition to it being IgG2). In some of IMCL's papers they have addressed this issue and stated that increased affinity may reduce tumor penetrating ability. In other words the affinity needs to be high enough but further increasees in affinity may reduce efficacy.
IMCL enhanced the affinity of its anti-VEGFR through testing various light-chains with the heavy chain of 2C6. In this case it seemed to work as tumor penetration may not be as critical in anti-angiogenic theray. Based on my reading of the literature, it does not appear that IMCL has pursued such a strategy (testing various light-chains) with its human anti-EGFR AB. It is unclear to me what the exact affinity of IMCL's human anti EGFR AB is? They have stated that it is similar to Erbitux; however, I seem to recall IR stating that the affinity was higher. We will see what the clinical trials show. Do you have any expectations that the IMCL's human anti-EGFR could have enhanced efficacy in addition to reduced side effects?
Regards,
biophud
Thanks Dew!
Dew- to clarify your baseball analogy-Did ALNY show up MRK by signing the Roche deal or did Merck show up ALNY by their purchase of SIRNA?
Regards,
biophud
ALNY's price stength following the break up with Merck? Just curious if anyone on the board had any insights/ideas. Comments appreciated.
biophud