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An interesting news release on a Sunday evening--New funds for Lexicon (LXRX). Any comments on the deal?
biophud
Biowatch, I have a posted on the IMCL board regarding MEDX (msg# 3937). I would be interested to hear your comments.
Regards,
biophud
Thanks Dew!
Happy Fathers Day to all of the dads. IMCL M&A possibilities—Just wanted throw out my opinions on a couple of M&A possibilities. Full disclosure--I’m long IMCL, MEDX, and DYAX.
Because of the complexities and uncertainties of antibody patents, I would not mind seeing IMCL buy its own method of generating antibodies (see my previous post). IMO DYAX would be a good choice. DYAX has a low market cap and the majority of IMCL’s preclinical antibodies were generated using DYAX's phage-display.
Another possibility would be MEDX. The positives would be geographic proximity, both companies have a relationship with BMY (not sure if this is a positive), and if BMY wanted to take-out either IMCL or MEDX, such a merger could be a defensive move (protecting both companies from BMY—similar to the Biogen/Idec merger) and resulting in a dominant antibody-focused biotech company.
One key difference--IMCL has the size/cash to buy DYAX. I’m not sure how an IMCL/MEDX could be structured. If MEDX has significant price appreciation (most likely due to advancement of its anti-CTLA4 AB), it would not be inconceivable that MEDX could have a market cap on par with IMCL.
Comments appreciated,
biophud
Dew—a few more questions that reflect my ignorance on patent law.
How do two groups “fence in” the same patent? I thought that a patent gives ONE holder exclusivity on the invention.
If two groups fence in the same idea and one group generates a product based-on the invention, how are the profits split?
Hypothetically, in the case of IMCL/PDLI, if IMCL were to put a humanized AB on the market (I don’t think that this is going to happen), could PDLI demand a high percentage of the sales (as opposed to the 3-5% royalty rate that if receives now on ABs that use its technology)? In this hypothetical, I am talking about a humanized CDR-grafted anti-EGFR. I am not talking about IMCL’s fully-human phage-display antibody.
Couldn’t IMCL pursue an exclusive license with PDLI?
Regards,
biophud
Anti VE-cadherin research article (abstract only)
http://www.genesdev.org/cgi/content/abstract/21/12/1546
Dew-thanks for your comments. I understand the need to be defensive in order to prevent others from developing competing products. However, I would have thought that a patent coving a specific antigen would be broad enough to cover multiple antibody production methods (phage-display, CDR-grafted, transgenic animals, ribosome display, etc.). My view is that antibody-generation technologies are different roads to the same end. I'm not sure what the courts have allowed or will allow, but IMO using an alternative method to generate an antibody to a known antigen does not seem like an especially novel invention. Also, the humanized CDR-grafted approach that IMCL mentions in the patent would seem to be covered by PDLI's patents.
biophud
New patent application for humanized version of C225.
Why is IMCL patenting a humanized version of C225, when it has a fully human (phage-display-derived antibody) in clinical trials (phase II/III)? If anyone has any insight on this please let me know.
biophud
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FP...
Corky--Do the numbers include or exclude resected patients? Thanks in advance.
biophud
Re; Biowatch--Continuation of GTCB/MEDX post. Thanks for the info. I agree that anti-EGFR, anti-RANKL, and manufacturing capacity were the driving forces in the ABGX acquisition. AMGN emphasized anti-EGFR in its press releases. However, IMO the anti-RANKL royalties were a critical part of the deal. ABGX also had an anti-PTH antibody program. I do not see any mention of this program in AMGN’s current pipeline. Anti-PTH addresses secondary hyperparathyroidism commonly seen in chronic renal disease so it would seem to be a key strategic fit with AMGN. AMGN also has Sensipar for secondary hyperparathyroidism (not sure if AMGN wants/needs two products treating this indication). So I was wondering if the anti-PTH program was still active at AMGN. If anyone knows please let me know. Below, I’ve cut and pasted info on ABX-PTH from a press release.
Regards,
biophud
ABX-PTH
The following three abstracts for ABX10241 (also known as ABX-PTH), the company's fully human monoclonal antibody that targets and neutralizes the action of parathyroid hormone (PTH), will be presented at the 26th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) in Seattle, Wash., Oct. 1 - 5, 2004:
"Generation and Therapeutic Potential of ABX10241, A Fully Human Neutralizing Monoclonal Antibody to Human Parathyroid Hormone," (Oral Presentation #1201, Tue., Oct. 5)
"Treatment of Parathyroid Carcinoma with ABX10241, a Monoclonal Antibody to Parathyroid
Hormone," (Poster Presentation #SA498, Sat., Oct. 2)
"A Phase 1, Single-Dose Study of ABX10241, A Fully Human Monoclonal Antibody to Parathyroid Hormone Secondary Hyperparathyroidism (SHPT) Patients," (Poster Presentation #SU530, Sun., Oct. 3)
The following two abstracts for ABX-PTH will be presented at the American Society of Nephrology (ASN) 37th Annual Meeting & Scientific Exposition in St. Louis, Mo., Oct. 29 - Nov. 1, 2004:
"Results of a Double-Blind, Single Dose, Dose Escalation Study of a Fully Human Monoclonal Antibody to PTH (ABX10241) in Patients with Secondary Hyperparathyroidism (SHPT)," (Oral Presentation, Room 260, Sat., Oct. 30)
"Treatment of Severe Hyperparathyroidism Secondary to Parathyroid Cancer with ABX10241, a Fully Human Monoclonal Antibody Directed Against Parathyroid Hormone," (Poster Presentation #F-PO981, Fri., Oct. 29)
Biowatch,
<I forget what Fc type(s) MEDX chose. Do you recall if they picked more than one? Are all the antibodies the MEDX mice produce capable of inducing ADCC?>
As I recall most/all(?) of the MEDX ABs that I have seen reported in the literature are IgG1. However, my understanding is that MEDX’s mice are capable of producing all isotypes. Here is some info from the MEDX site.
http://www.medarex.com/Development/UltiMAb.htm
HuMab-Mouse“Our HuMAb--Mouse transgenic strains contain key gene sequences from unrearranged human antibody genes that code for both the heavy and light chains of human antibodies.”
Kirin TC Mouse--“Through an exclusive partnership with the pharmaceutical division of Kirin Brewery Co., Ltd., we have access to the Kirin TC Mouse. Kirin has developed mice that contain complete sets of the variable and constant genes found in the corresponding natural human immunoglobulin loci. These mice are "transchromosomic," meaning that the mouse genes for creating antibodies have been inactivated and have been replaced by the human chromosomes containing all of the human antibody genes, including all heavy chain classes that encode all isotypes (IgG1-4, IgA1-2, IgD, IgM and IgE). The TC Mouse also has the ability to make fully human monoclonal antibodies. We have entered into a collaboration and license agreement, which provides for us to exchange with Kirin certain cross-licenses for each other's technology for the development and commercialization of human antibody products.”
KM-Mouse --“Together with our partner, Kirin, we have developed the KM-Mouse, a crossbred mouse that combines the characteristics of our HuMAb-Mouse with Kirin's TC Mouse that retains the capability to produce all human antibody isotypes with an immune response we believe previously unseen in any human antibody producing mouse system.
HuMab-Mouse?It is unclear to me what isotypes these mice produce.
Kirin-TC?Looks like it makes all immunoglobulin isotypes.
KM-Mouse?A cross of the two mice. The benefits of this strain are unclear to me.
<Are all the antibodies the MEDX mice produce capable of inducing ADCC?>
My understanding (as a nonimmunologist)?Immunoglobulin activation of ADCC varies with isotype. IgG1 is the most potent activator of ADCC. IgG2 and IgG4 are weaker activators of ADCC (unsure of the exact numbers). IgG3 can activate ADCC. I have seen patents from DNA/BIIB that have looked at IgG3 variants of Rituxin.
What it looks like is that MEDX mice can make all IgG isotypes. However, the most frequent isotype that MEDX and its partners have chosen to use is IgG1?I would presume due to it ability to activate ADCC, potentially an advantage in oncology settings. In non-oncology indications, activation of ADCC may not be necessary. For example, Tysabri is an IgG4. Also, HGSI has worked on IgG4 antibodies that antagonize CCR5.
<What do you think of MEDX in general?>
I own (and like) MEDX. Here are some positives.
1. Diverse reality stream on multiple antibody products with multiple high quality partners (PFE, J&J, AMGN, etc.).
2. Anti-CTLA-4. I think that anti-CTLA-4 has a good chance at approval. I’m not sure who will be first (or best) MEDX/BMY or PFE.
3. J&J phase III trials (CNTO148 and CNTO1275).
4. Genmab equity interest (recently reduced) and product royalties.
Couple of questions for you.
What does IIRC stand for?
<AMGN dumped most of Abgenix's research programs>?What is your source on this?
Regards,
biophud
Thanks Dew!
biophud
Significance of the BIIB Tender offer?--Is there a reason that BIIB is using a tender offer as opposed to a stock buyback on the open market? When boards approve buybacks on the open market frequently only a small% of the approved amount is ever bought back by the company (please correct me if I am wrong). Is a tender offer then a more serious stock buyback program? Another question--> what is motivating the buyback? a stock purchase of another company? IMO the amout being offered is not compelling for an owner of BIIB who has a long term horizon.
Comments appreciated,
biophud
Interesting NVS clinical trial-->Erbitux + NVS's mTOR inhibitor. Rowinsky has several publications regarding mTOR. Also, as I recall WYE has a more advanced mTOR inhibitor in development.
biophud
http://clinicaltrials.gov/ct/show/NCT00478634?order=2
ADCC(?)
Patent for Erbitux (and other MABs) in drug coated stents.
http://www.wipo.int/pctdb/en/fetch.jsp?LANG=ENG&DBSELECT=PCT&SERVER_TYPE=19&SORT=1202620...
DEW-I would appreciate any comments you have regarding my post#3742 on the IMCL board. TIA
biophud
Legal/Intellectual Property Question—I have used the search engines (WIPO and USPTO) listed below to research potential biotech investments.
Imclone has a number of interesting patents that can be found by searching the WIPO site.
Question? What is the significance of a patent being listed @WIPO? @USPTO?
World Intellectual Property Organization
http://www.wipo.int/patentscope/en/
US patent and trademark Office
http://www.uspto.gov/patft/
New paper in Lancet oncology (title only)--Circulating VEGF predicts response to Erbitux
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
Dew-as a MEDX shareholder, I have considered MEDX's equity position in Genmab as a positive (although not a primary reason to own MEDX). Consequently, I did not like to see MEDX reduce its holdings even though it reduces the need to raise additional cash and dilute the stock. Any comments/opinions.
biophud
Re MEDX's price/volume action today. Is today's high volume/price increase due to pre-ASCO buzz? Any other news that could explain the volume/price?
biophud
New research on ADCC
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
A case report (title only)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
biophud
Dew—I agree with you that biogenerics are a risk to large cap biotechs. However, based on AMGN’s current valuation, the market seems to be valuing AMGN as a pharmaceutical company rather than a high PE biotech. Like big pharma, AMGN will be subject to generic competition, and it would seem that the market is already taking this risk into account (I know what you think about the efficient market hypothesis-LOL).
Regards,
biophud
Jbog--I agree this is an interesting study. Thanks for the info. I have read the Yahoo MB since ~1999, and I appreciate the opinions and insights that you have contributed.
biophud
Jbog--Thanks for the info. IMO it is a good sign when multiple independent groups come to the same conclusion--further validating IGFR-1 as a good therapeutic target. I was not aware that Pfizer's AB is an IgG2. Not sure why Pfizer decided to go with an IgG2 AB.
Any insights on how IMCL plans to develop its pipeline. Combination trials with Erbitux (?) Trials on patients who have failed Erbitux (?) Frontlineline trials in combination chemo/radiation?
I do not think that Xenomouse ABs from ABGX are all IgG2. My understanding is that the Xenomouse platform can produce all isotypes (Chir-12.12 is an example of an IgG1 AB from the Xenomouse platform).
Regards,
biophud
Biogen's site now shows that they have an anti-IGFR antibody in preclinical development.
http://www.idecpharm.com/site/025.html
biophud
Questions for board--ALNY's experimental infection model
http://biz.yahoo.com/bw/070507/20070507005609.html?.v=1
1. Is this type of experimental infection model common in infectious disease trials?
2. Does this experimetal infection model speed up clinical development of ALNY's drug? Are they looking for in vivo efficacy of RNAi prior to starting large scale trials in naturally infected patients?
3. Since ALNY already has Phase I saftey data, can't they go directly to treating patients infected with RSV?
4. Did MEDI do similar trials with Synagis?
5. Is ALNY being cautious, prior to starting trials on kids?
Comments appreciated.
biophud
Thanks for your comments. Looks like you have a good basket of biotech stocks. Also looks like you believe in RNAI stocks (RNAI, ALNY, ROSG). I hold ALNY (short term I think that it may be overvalued) and I am considering a position in ROSG. It is very early for ROSG, but its diagnostic technology is very promising, and in principle, could be used to identify patients who will respond to targeted therapies.
Regards,
biophud
New IMCL research on anti-PDGFR-beta
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...
biophud
Jbog--Re Where are the Bio Funds Going Post on the Yahoo board.
I think you raise an interesting point. From my perspective I have owned CHIR (purchased by NVS) and MEDI (purchased by AZN). When I look to invest cash from the MEDI purchase into a comparable biotech, I see very little available (maybe BIIB or GENZ?).
I think that the megacaps AMGN and DNA are good companies, but their size limits their growth prospects. The market caps of both GILD and CELG have always seemed high to me. While both GILD and CELG are very good companies, I think of them more as pharmaceutical companies developing small molecule drugs rather than protein/antibody type drugs.
Of the top 10 biotechs that you listed, IMCL has the best prospects for substantial and sustainable price appreciation (IMO). IMCL has a product, a profit, a large and underappreciated pipeline, and a comparatively low market cap relative to the other biotech on the top 10 list.
Regards,
biophud
Can anyone here comment on HGSI's intellectual property position on anti-TRAILR antibodies? In my opinion anti-TRAILR antibodies are a promising strategy for cancer. Both AMGN and DNA have anti-TRAILR antibodies in clinical trials (in addition to a recombinant TRAIL protein--I think the antibody approach is better). In addition, academic researchers @UAB have identified the TRA-8 antibody (anti-DR5). IMO multiple groups coming to the same conclusions further validates the anti-TRAILR approach. HGSI has the most advanced clinical development. Based on my readings, HGSI looks like they have a strong/dominant IP position on anti-TRAILR antibodies. Is HGSI's IP position strong enough to prevent other anti-TRAILR antibodies from coming to market?
Comments appreciated,
biophud
11:55AM Human Genome reports growing evidence that tts TRAIL Receptor Antibodies have significant potential in the treatment of a broad range of cancers (HGSI) 11.29 +0.00 : Co reported that clinical and preclinical evidence continues to emerge demonstrating that its TRAIL receptor antibodies, HGS-ETR1 (mapatumumab) and HGS-ETR2 (lexatumumab), have significant potential for use in the treatment of a broad range of cancers. "We believe that HGS-ETR1 and HGS-ETR2 could offer novel, highly targeted therapeutic options that may prove useful in the treatment of a number of cancers," said Gilles Gallant, B. Pharm., Ph.D., Vice President, Clinical Research - Oncology, HGSI. "We note with pride that the Journal of Clinical Oncology, one of the field's most prestigious peer-reviewed publications, chose to publish the first human study of HGS-ETR1 earlier this month with an accompanying editorial - and, last week at AACR 2007, approximately 1500 cancer scientists and researchers attended our oral presentation of research results to date."
Comments/Questions on MEDI.
1. Suprised by the price and that it was an all cash deal.
2. Looking to reallocate cash from the MEDI Deal; I cannot find a similar biotech in terms of disease focus, market cap, etc. Any suggestions?
3. Both CHIR and MEDI are biotechs that make vaccines and have an infectious disease focus. Both were bought out for cash by European large pharma. Any significance to this?
biophud
Thanks Dew!-I get it now.
Regards,
biophud
Thanks Dew for the distinction. Based on the press release, my understanding was that the ALNY's drug contains two separate RNAi nucleotides-one targeting VEGF and the other targeting KSP (two separate active ingredients). Consequently, I was suprised that they were not running mono trials first.
New question re ALNY’s new trial.
http://biz.yahoo.com/bw/070417/20070417006082.html?.v=1
1. ALNY is starting development with a combination product.
2. My understanding is that antisense drugs (and RNAi drugs) are treated as chemical entities rather than biologics, and file NDAs rather than BLAs? Please correct me if I am wrong.
3. Several biotechs are researching bispecific antibodies. The papers that I have read state that bispecifics would have a regulatory advantage over combination mono-specific antibodies (i.e. one set of clinical trials rather than two).
4. It looks like the rules are different for chemical entities and biologics? Companies can start combination trials of novel chemical entities but not combinations of novel biologics (?) Please correct me if I am wrong.
5. If my understanding is correct, it would seem that development of combination therapy using antisense/RNAi compounds would be superior to development of combination biologic therapy (from a pure regulatory perspective).
Comments appreciated
biophud
Post# 3526 has a link to a BMY Onc Presentation 3/28. The presentation has a slide showing a bispecific adnectin targeting IGFR and EGFR. I only looked at the slides; I'm not sure what was said during the presentation.
Regards,
biophud
BMY developing an anti EGFR adnectin made me look at the original BMY agreement.
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
parties cannot reach agreement with respect to such an arrangement, the
competing product must be divested within 12 months).
A few qustions-->Why the 2008 deadline? What is the legal definition of "indirectly, develop or commercialize a competing product"? By developing an anti-EGFR adnectin, could BMY be in breech of the agreement? Comments?
FYI-Link between immune system and lipids. I think Biogen has a soluble receptor targeting this pathway.
http://www.eurekalert.org/pub_releases/2007-04/uocm-lfb040907.php