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Ascenta-->an interesting private biotech (IMO) with products in Phase 1/2 trials. I wonder what Ascenta's strategy is IPO or sell-out?
http://www.ascenta.com/pages/about.htm
Starting my research on Keryx Biopharmaceuticals. I'm trying to understand what expectations are baked into its current price? Comments from the board?
biophud
A few comments/questions.
1. With MEDI 's potential buy-out value of 10B+, how does this affect valuations of other similar biotechs? If MEDI is worth 10B+ in a buyout, then BIIB would appear undervalued (IMO).
2. Any possibility of a large cap bio (like AMGN) being a bidder for MEDI.
3. Any ideas on how a MEDI buy-out would be structured (cash, stock, both)? I would think it would be an all cash deal.
biophud
Repeat question--> Who would/could buy MEDI?
Dew-Not suprised at the results but I am surspised that the results moved the stock so much. Any comments.
biophud
Thanks Dew. I should have thought of that.
biophud
New biotech ETFs. IMCL is in the cancer ETF.
http://www.healthsharesinc.com/product/holdings/2835
biophud
NEW biotech ETFs (at least to me). I came across this today reading the BIIB news. I'm not sure why BIIB was in the ophthalmology ETF. I'm not sure how accurate the titles are (e.g. MEDX in the Pulm fund). Nevertheless, looks like a good way to diversify risk in the biotech sector while gaining exposure to small/mid cap biotechs.
http://www.healthsharesinc.com/
biophud
FYI--New AMGN clinical trial for head and neck.
http://clinicaltrials.gov/ct/show/NCT00454779?order=1
biophud
My understanding of this patent was to conjugate B12 to recombinant proteins like EPO, G-CSF, GH, etc. in order to make these proteins orally available.
Regards,
biophud
Dew--Which company(s) has the best technology for oral peptides? If anyone can come up with a solution, there would be a large market.
Here is a patent from AMGN that I though was interesting-->conjugate vitamin B12 to the peptide/protein and it will bind to intrinsic factor and be absorbed. This sounds like a great idea. Will it work in the real world?
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPT...
biophud
It was a very convincing April Fool's Joke.
Just read Biotech Values MB and I understand why this flew below my radar screen. Should have remembered today's date. Nevertheless, comments/questions on points #1 and #3 are still valid.
biophud
Corky and Biowatch—Thanks for the articles. I’m surprised that this partnership flew below my radar screen. A couple of quick comments/questions?
1. How does the recent Vectibix data alter potential partnerships/M&A?
2. An AMGN/BMY partnership strikes me as unusual. Both are major organizations that could develop a VEGFR peptide antagonist on their own (or in collaboration with a small biotech). The benefit of two major firms teaming-up is unclear to me. For example, AMGN recently purchased Avidia, and could use this technology to develop such an antagonist.
3. I think it is telling that companies with small molecule VEGFR-kinase inhibitors are pursing protein-based extracellular antagonists of VEGFR. IMO, this is the best strategy.
biophud
Biowatch--Thanks for the info. The BMY presentation was the first time that I have heard of adnectins. A few points.
1. IMO, I would rather use a full length MAB with ADCC and a long half life.
2. Aside from the one company with the adnectin technology, there are little to no peer-reviewed papers in the literature.
3. The primary benefit of adnectins seems to be ease of production and avoiding MAB patents.
4. The fact that BMY is targeting EGFR, VEGFR, and IGFR with adnectins further validates these oncology targets.
5. There has been talk on this MB about IMCL making nice with BMY.
6. With the adnectin program-->Is BMY making nice with IMCL?
Regards,
biophud
New Paper-->Circulating VEGF reduction, response and outcome in advanced colorectal cancer patients treated with cetuximab plus irinotecan
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Congrats to DNDN longs. One question that I wanted to ask--> What are the most credible MAB therapies being developed for prostate cancer? Several companies have had anti-PSMA ABs in development (MLNM MEDX). If I were DNDN, I would see an anti-prostate cancer MAB as a competitive threat.
biophud
Question for the MB-with the setback/failure of Vectibix, will AMGN seek to partner another anti-EGFR AB (e.g. from Genmab or YMI)?
biophud
Thanks,
biophud
In BMY's presentation, they talk about adnectins (it is the first time that I have heard of this class of proteins). My understanding is that that are a modified protein structure with antibody-like specificity. It looks like BMY is targeting adnectins to EGFR, VEGFR, and IGFR. Comments appreciated.
biophud
BMY Oncology presentation (3/28). Lots of focus on Erbitux.
http://investor.bms.com/phoenix.zhtml?c=106664&p=irol-presentations
Cypher Stents (?)
New antibody patent application from DNA
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...
Thanks Dew and dewophile for your opinions. I share your optimism for GTC.
Just to play devil's advocate. If GTC's production method is superior, then why haven't we seen the large biotechs (AMGN, DNA, BIIB, MEDI) switch from cell culture production methods to transgenic goats.
IMO, adoption of GTC's production methods by large cap biotechs would be a major positive for GTC's stock price.
biophud
Question for Dew: Re GTC/Abgenix anti-IL-8. I assume that this program is dead (?) However, I think that the gist of my questions applies to other MAB companies as well.
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/05-02-2000/0001206528&...
I thought an advantage making ABs in transgenic mice was to generate an antibody cell-line (without need of additional engineering) that could be grown in large-scale tissue culture for production.
I have wondered why ABGX wanted to use GTC’s goats. Engineering producing goats takes time and money? Are the goats such good protein producers that it is more economical than production via tissue culture? Will the goats replace large-scale tissue culture production methods?
biophud
New paper-->ADCC-enhanced Herceptin.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Also, research that may help to identify pts who will respond to anti-EGFR therapy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
biophud
Thanks Dew.
biophud
In a previous post, I raised the question of biotechs and emerging markets. Glenmarkparma came to my attention because of its recent deal with DYAX. Looks like Glenmark is targeting emerging markets and is pursuing biologics. Does anyone here know anything about Glenmark or any of its programs?
Comments appreciated,
biophud
http://www.glenmarkpharma.com/
rfj1862-->Thanks for your opinion. I think that your analysis is correct. NKTR's stock price could stagnate for a number of years (at current prices I see limited downside risk). In a post biotech bubble world, there are a number of stock holders who sell into strength thus limiting price appreciation.
Regards,
biophud
New patent from HGSI regarding anti-APRIL antibodies. From my quick read of the patent it looks like it would cover BLYS/APRIL heterodimers. Based on my understanding, this agent would be similar to ZGEN's TACI-Fc (in terms of the cytokines that it would neutralize).
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPT...
Comments appreciated,
biophud
New research from IMCL on carbohydrate modification of Erbitux. I'm glad IMCL is looking at this. Carbohydrate composition appears to modulate/enhance ADCC.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Dew--with the recent market downturn are there any biotechs that you think have been unfairly hit and are good values?
One company that I think fits into this category is NKTR. Diversified partnerships. Platform can be applied to multiple second generation pharmaceuticals and biologicals. I like the idea of PEG-irinotecan (beginning phase I trials)-->appears to be a lower risk strategy of product development.
Have a good weekend,
biophud
FYI--> AACR Abstract from Xencor. Xencor also has another abstract at AACR using an ADCC-enhanced anti-CD19.
Abstract Number: 4791
John O. Richards. Xencor, Monrovia, CA
It is now well-established that Fc gamma receptor (F?R) -mediated effector functions play an important role in the anti-tumor capacity of some monoclonal antibodies. These receptors are present on a wide variety of effector cell populations, including natural killer (NK) cells, dendritic cells (DC), neutrophils, and macrophages. We have previously engineered the Fc domains of antibodies to enhance their affinity for Fc?R, leading to dramatic enhancements in NK cell-mediated ADCC. NK cell-mediated lysis occurs predominantly through a single activating receptor Fc?RIIIa. Activation of antigen presenting cells such as DC and macrophage, which has potential to induce adaptive immunity against the tumor target, can also be influenced by the activating receptor Fc?RIIa and inhibitory receptor Fc?RIIb. We have engineered a panel of anti-EpCAM antibody variants with a variety of unique Fc?R affinities and specificities, including selective engagement of Fc?RIIIa and Fc?RIIa over Fc?RIIb. Results indicate that NK cell-mediated killing of LS180 target cells is correlated strongly with Fc?RIIIa affinity, with enhancements in antibody-dependent cytotoxic potency ranging from 3-fold to 10-fold and up to a 20% increase in maximal ADCC against LS180 target cells. Phagocytosis by macrophages is dependent on binding to both Fc?RIIa and Fc?RIIIa, with enhancements in phagocytic potency ranging from 3-fold to 30-fold. Surprisingly, our data show that absolute Fc?RIIb affinity does not negatively impact phagocytosis. Overall these variants have the potential to improve anti-cancer therapy by increasing not only innate effector functions, but also by enhancing adaptive anti-tumor responses, a novel feature of engineered therapeutic antibodies.
Interesting abstract from 2007 AACR Differences in activity between matuzumab and cetuximab in A431 cells may rely on MAPK cascade inhibition
Debora D. Meira, Isabel Nobrega, Janio S. Moror?, Vitor Hugo Almeida, Lucia H. Bardella, Everardo D. Saad, Ricardo Silva, Rodolpho M. Albano, Carlos G. Ferreira. Brazilian Nacional Cancer Institute, Rio de Janeiro, Brazil, Dendrix, Ltda, S?o Paulo, Brazil, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
Objectives: Preclinical studies have shown potential antitumor efficacy of some monoclonal antibodies (MAbs) directed to the Epidermal Growth Factor receptor (EGFr) in combination with chemo and/or radiotherapy (RxT). However, there is a lack of information on the preclinical data with matuzumab or EMD 72000 (EMD) in combination with chemo and RxT in cancer cell lines. The present study was undertaken to examine the growth inhibitory effects of EMD or cetuximab (C225) alone or in combination with cisplatin (CDDP) and RxT in the human cell line A431 and the influence of these MAbs on EGF receptor phosphorylation and downstream signaling pathways.
Methods: Cytotoxicity was assessed by MTT and clonogenic assays (CA). A431 cell line was treated with EMD or C225 alone or in combination with CDDP (IC 30, 50, 80) or RxT, or with both, at different conditions. Western Blotting (WB) analysis was performed with antibodies against: EGFr (Tyr 845, 992, 1045 and 1068), AKT, HER2, SRC and MAPK (total and phosphorylated).
Results: No significant difference in short- or long-term citotoxicity (MTT and CA) was observed when EMD was combined with RxT, CDDP, or both (regardless of the combination schedule). In contrast, C225 plus RxT led to a stronger inhibition (n=3, P<0.05) of A431 cell proliferation than each treatment alone (MTT). This was confirmed in clonogenic assays, in which a survival inhibition occurred following the addition of C225 to RxT or RxT/CDDP (P<0.05). As an effort to explain the differences between EMD and C225, we performed WB analysis to detect phosphorylated EGFr residues (Tyr 845, 992, 1045 and 1068) in cells that were treated with EMD or C225 (100 ug/mL, both) in the presence or absence of EGF (10 ng/mL). Under these conditions, no difference in the phosphorylation of these residues was found for any of the treatments. Furthermore, there were no changes in the amount of total or phosphorylated HER2, SRC and AKT proteins. In contrast, ERK 1/2 (Thr202, Tyr204) protein phosphorylation was strongly inhibited by cetuximab but, surprisingly, not by matuzumab.
Conclusions: These data suggest that there is no additive effect when EMD is combined with RxT, CDDP, or both. In contrast, we observed at least an additive effect of C225 treatment plus CDDP or CDDP/RxT in decreasing A431 cell viability and survival. This difference between the MAbs activity is not correlated with differences in EGFr, AKT, HER2 and SRC phosphorylation status, but may be explained by a marked inhibition of the MAPK cascade by C225, which is not observed with EMD treatment.
Question for the board. Assuming regulatory sucess, which MS pts will BIIB/PDLI target with Daclizumab?
With 3 products for MS (Interferon, Tysabri, Daclizumab) is there a risk that BIIB will cannabilize sales of the other two drugs? Comments appreciated.
biophud
Dew--Regarding ADCC, Xencor is an interesting private biotech. They have put out some good papers that look at Fc modifications. In my opinion, it looks like a company that could be a target for larger players in the MAB space (e.g. Medimmune, Genetech, etc.). BioWa and MEDX also have an agreement on ADCC. I think that you are correct, and second generation products will be optimized ABs with enhanced ADCC.
Another way to enhance ADCC is with co-administration of cytokine therapies. Chir/NVS have looked at IL-2 given with Rituxin. Also, ZGEN is looking at IL-21(?) given with monoclonal ABs.
Thinking long term, with multiple ABs on the market, a cytokine that enhanced ADCC could be a major blockbuster.
I will have to study up on GTC's research in this area.
Regards,
biophud
I'm not sure the best way to play an increase in transfusions. Chiron (now NVS) was involved in testing (hep HIV) with Genprobe. With regards to NVS, I would quess that blood testing is a small percentage of its total revenues. Genprobe was a a very high priced stock (the last time I checked).
What percentage of EPO sales (high dose EPO, off label use , etc.) is affected by the recent news? I'm trying to get a sense of how significant this is for AMGN. With its recent price decline, it looks like AMGN is nearing a good entry point for long term biotech investors who want a large-cap/conservative biotech.
biophud
Did anything significant come out of the JPMS pancreatic cancer research conf call?
biophud