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B i l l i o n d o l l a r b l o c k b u s t e r s l o o k i n g v u l n e r a b l e The Barnes Report · No. 3 · March 22, 2007 1
THE BARNES REPORT
IN THIS ISSUE
ARTICLE SUMMARIES
What has clinicians at the Farber so excited? Astra-
DNA, ELN, GPCB, ENDP, JNJ, MDCO, MYGN, NOVC, Zeneca’s Recentin, which has the potential to be first in
class anti-angiogenic drug
Recentin, the most exciting drug in AstraZeneca plc’s (AZN)
Apotex (priv), Virium (priv) pipeline, is causing enthusiasm that is almost palpable around the Farber and I’ve never met a harder group of physicians to get worked Genentech, Inc.’s (DNA) $1.8B
golden child, Avastin, is looking at its first real rival… The fall of a giant; Plavix takes a beating and newcomer Cangrelor just adds insult
to injury
The anti-platelet drug Plavix (by Bristol-Myers Squibb Co. (BMY) and Sanofi-Aventis (SNY)) was
the second highest revenue-producing drug in the world in 2005 behind Pfizer, Inc.’s (PFE) Lipitor.
Worldwide sales were reportedly $5.5-5.9B in 2005. Entry of a generic version of Plavix by a private Canadian company, Apotex, Inc., recently prompted a patent-infringement lawsuit and dented 2006
sales which were listed as $3.2B. While the courts sort out that mess, the makers of Plavix are in for another big hit in the acute care market.continued on page 3 Elan’s real diamond in the rough for Alzheimer’s Disease is not AAB-001
Ask an analyst which Alzheimer’s drug they think looks the brightest, and you’ll probably hear Corp. plc’s (ELN) AAB-001. But ELN has another candidate which just might change their mind
…
Two sides of the same coin? What to make of the latest Satraplatin clinical data

Is it the latest data from Spectrum and GPC’s Satraplatin really positive? Sometimes it is hard to make
heads or tails of press releases. Here’s a closer look at the most recent clinical findings… continued on
page 5
Access and Somanta Pharmaceuticals, a good fit and an impressive pipeline
Access Pharmaceuticals, Inc.’s (ACCP) Prolindac is eyeing the €1.7B monster Oxaliplatin and
Somanta Pharmaceuticals’ (SMPM) Prodrax is looking to clean up the scattered anthracycline
market. Although non-binding at this point, recent talk of a merger would be a great strategic move for
both companies. Here’s a look at what each brings to the table… continued on page 5
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The two year old son of a U.S. soldier deployed to Iraq contracted a rare, severe adverse reaction after touching his father’s smallpox
vaccination site, Reuters reported Friday March 16th. The illness, called ‘eczema vaccinatum’, is potentially fatal and requires
immediate and intensive care. The boy became critically ill with hemorrhagic lesions, respiratory failure and shock. The CDC
mediated a discussion between SIGA Technologies, Inc. (SIGA) and the FDA which allowed the treatment of the boy with SIGA’s
smallpox drug, SIGA-246, under an Emergency IND. SIGA announced a second Phase 1 study of SIGA-246 in February. The drug, a
cysteine protease inhibitor, is orally administered and specific for poxviruses including monkeypox and normal and engineered human
smallpox. Most other smallpox drugs are nucleoside analogs with poor bioavailability and renal toxicity issues. Because there have
been no natural occurrences of smallpox since the late 1970s, human testing of SIGA-246 has been limited to Phase I safety trials to
find adverse reactions and validate that therapeutic levels are achievable in humans. Nonhuman primate data has been very positive,
but this chance to treat an infected human is an extremely rare opportunity. The infected boy’s condition is said to be improving, and
SIGA’s stock rose 15% in response on Monday.
AZN’s Recentin has potential to be first in class anti-angiogenic on’t overlook Recentin as ‘just another small molecule 3. Avastin is specific for VEGF isoform A, one of four VEGF inhibitor’; it is good enough to give Avastin a serious proteins which activate the three VEGFRs. Recentin inhibits run for its money. AstraZeneca plc’s (AZN) Recentin
all three VEGFRs, two targeting blood vessels and one (AZD2171) is an extremely potent small molecule inhibitor (SMI) of all three VEGF receptors (VEGFR1-3), c-Kit, and PDGF receptor beta (PDGFRB). Activation of VEGFRs in 4. Avastin’s half-life in the blood stream is about 20 days. cells is blocked with sub-nM concentrations and in Recentin’s half-life is about 20 hours, so unwanted effects can biochemical assays with <5nM concentrations of the drug. So be easily managed by dose interruption. If a patient needs how does that compare with the potency of some drugs you surgery, Recentin is cleared very quickly compared to the long may have heard of? Sorafenib (Nexavar, by Bayer
time it takes to clear Avastin from the blood stream. Pharmaceuticals Corp. (BAY) and Onyx Pharmaceuticals,
Inc. (ONXX)) and sunitinib (Sutent, by Pfizer, Inc. (PFE))
5. Every preclinical model tested shows a response to inhibit their targets at concentrations between 20-100nM, so Recentin at doses that are well tolerated in mice. The wide Recentin is 4-20 times more potent than those drugs. range of tumor susceptibility, along with the drug’s potency, has prompted AZN’s Clinical VP of Oncology to characterize As expected with such anti-VEGF efficacy, in vivo the drug is Recentin as “better than anything our discovery group had a very potent angiogenesis inhibitor. Angiogenesis inhibitors are already making an impact in the clinic and on pharmaceutical profits. Avastin, Genentech, Inc.’s (DNA)
6. Recentin has already been tested in over 700 patients and anti-VEGF monoclonal antibody is the gold standard for this the side effect profile is well characterized as manageable, class of drug. It generated $1.8B in total revenues in 2006 for with high blood pressure topping the list. the company and prolongs survival in colorectal, breast and lung cancer. To date, no serious competitor has emerged to So the short answer to whether Recentin can compete is: challenge Avastin’s dominance. That is about to change as absolutely yes; and it has a very good prospect of moving Recentin begins its late stage clinical development. AZN is straight to the top of the list. AZN’s development plan for coming out swinging and looks to be holding a very large bat. Recentin is designed to “establish the clinical activity rapidly and robustly, to combine the agent with chemotherapy in Can Recentin compete with Avastin and the other VEGF multiple tumors and undertake carefully risk-managed Phase inhibitors on the market? Well, let’s get down to detail: 2/3 studies in lung and colorectal cancer”. They have stayed true to that plan. Recentin is currently engaged in 32 separate 1. Avastin requires I.V. administration in the clinic once every clinical trials for over 20 different types of cancers. It is going 2-3 weeks. Recentin is an orally administered pill taken once a head-to-head with Avastin in first and second line combination therapy for Metastatic Colorectal Cancer, and head-to-head studies in Avastin’s other big market (Lung 2. Avastin is a humanized monoclonal antibody which carries Cancer) are in the works. It is a very bold development a risk of allergic reaction. Recentin is a SMI which does not strategy, but that just goes to show how confident AZN is that they can exceed the clinical benefit of Avastin in its For more information on receiving this publication or contacting the authors herein, please email [email protected] B i l l i o n d o l l a r b l o c k b u s t e r s l o o k i n g v u l n e r a b l e The Barnes Report · No. 3 · March 22, 2007 3
But that is a review of preclinical, pharmacokinetic, and A Phase 2 trial at Mass General Hospital (MGH) followed pharmacodynamic stuff, and that rarely has any affect on the patients who were treated with Recentin when their tumors mood of an oncologist. So why are people at the Farber recurred after surgery and XRT. Overall, the tumors shrank by at least 25% in three-quarters of the study participants and by 50% or more in half of the patients. A significant decrease of I’ll focus on one study that was just completed in my area of intracranial edema (swelling in the brain), which is a very expertise, a brain tumor called Glioblastoma multiforme devastating symptom of GBM, was seen almost immediately (GBM). A bit of background on this disease: The prognosis in most participants and continued for at least 28 days, with for this type of cancer is particularly dismal. GBMs are very some benefits persisting up to four months. While the study is aggressive, disseminate throughout the brain extensively and too preliminary to assess whether the overall survival of the can be very advanced before any symptoms arise. Over the patients significantly improves, many oncologists are very past 20 years, while advances for other types of cancers have optimistic. It is nearly unheard of to get good anti-tumor made an impact on the overall survival of those patients, very activity with a single agent in GBM, and the results from this little has changed for patients with GBM. Rarely do patients study are in line with the buzz about the performance of who are diagnosed with this tumor live longer than one year and most succumb within six months. Treatment usually includes neurosurgery to remove as much of the tumor mass This is my favorite late-stage oncology drug and I expect it as possible, followed by radiation and temozolomide will have an extremely bright future. AZN reports that an (Temodar by Schering-Plough Corp. (SGP)) treatment
Cangrelor touted to become standard of care in ACS ach year over four million people are admitted to the only choice. A fast acting P2Y12 platelet receptor antagonist hospital with Acute Coronary Syndrome (ACS). with a very short half-life would significantly change the game. Currently patients with ACS are given a very well defined set of medications while they wait to go to the cardiac In response to this pharmaceutical gap, two companies have catheterization lab. Depending on the degree of blood vessel shorter acting P2Y12 antagonists in late phase clinical occlusion, either placement of a stent at the time of the development. AZN’s AZD6140 is an oral prodrug that needs angiogram or cardiac bypass surgery, are the two possible to be metabolized by the liver for activity. It is still relatively endpoints. At the time the ACS medications are started, the long acting, with a two hour onset of action and a 12 hour physician must hedge his bets on the likelihood of which half-life. AZD6140 is currently in Phase 3 testing and if endpoint the patient falls into and ask himself “do I also add successful an NDA is expected in late 2009. While the kinetics Plavix to the medications this patient is receiving, or not?” are better than Plavix, they are still too slow to fill this niche. The Medicines Company’s (MDCO) Cangrelor is a direct
Clinical data clearly show that Plavix (by Bristol-Myers
acting P2Y12 antagonist in Phase 3 clinical trials. MDCO Squibb Co. (BMY) and Sanofi-Aventis (SNY)), a P2Y12
licensed the exclusive worldwide rights to this drug from AZN receptor antagonist that blocks platelet activation, given 15 in 2003. Cangrelor is an I.V. drug which does not need to be hours prior to the placement of a stent, has established long metabolized by the liver for activity. Maximal inhibition is term mortality benefits. Further, the combination of the found within 15min and its half-life is 2-3min. Upon platelet aggregation inhibitor Integrilin by SGP (which is withdrawal of the drug, blood levels drop rapidly and are already one of the medications a patient with ACS is given) undetectable in 20-50 min. Cangrelor’s pharmacokinetics are a and Plavix synergize to provide an even greater benefit. So far, perfect match for use in the acute intervention scenario so good. However, if the patient ends up requiring bypass surgery there is a high risk of bleeding and in most cases, patients who received Plavix have to wait five days for bypass So how would Cangrelor alter the current management of surgery. The risk is enough to make even the best and most A patient with ACS is prescribed the normal set of drugs plus Why five days? Plavix irreversibly binds the platelet and is Cangrelor when he is admitted to the hospital. The patient therefore in the bloodstream for the lifespan of the platelet ~5- goes to the cath lab and is found to require bypass surgery. 7 days, which in this case is a major disadvantage. The long Cangrelor can be withdrawn and clear of the system, length of time it takes to clear the bloodstream makes Plavix a eliminating the risk of bleeding complications, by the time that poor choice for acute interventions, but at this time it is the the patient is brought to the operating room, so no delay of For more information on receiving this publication or contacting the authors herein, please email [email protected] B i l l i o n d o l l a r b l o c k b u s t e r s l o o k i n g v u l n e r a b l e The Barnes Report · No. 3 · March 22, 2007 4
surgery is necessary. Essentially, the benefits of combining of care for the treatment of ACS. With over four million Integrilin and Plavix are retained, but the risk of surgical people per year coming into the Emergency Room with ACS and no similar short acting drug in late clinical trials, Cangrelor’s market is huge. One last ‘detail’: patent protection Current clinical trials are assessing Cangrelor for the same mortality benefit as Plavix. If these studies show a similar protective effect, Cangrelor stands to be added to the standard Preclinical data highlight potential of Elan’s other Alzheimer’s Drug he Alzheimer’s Disease (AD) treatment market was $4B Wyeth (WYE), AAB-001 is a humanized antibody to βA, that
in 2005 and has been estimated to be $5.75B by 2010. when administered is thought to bind to βA and promote its Presently, there are four drugs approved by the FDA for clearance from cells. This drug is currently in Phase 2 clinical AD, with mild effects on disease. Three of the four drugs are Acetylcholinesterase Inhbibitors (ACE inhibitors) approved for mild to moderate AD, with the market highly dominated Elan has previously taken the immunotherapy approach to AD by PFE’s Aricept. The other two drugs, Razadyne by Ortho-
treatment, looking at AN-1792, a βA peptide used as a vaccine, McNeil Neurologics Inc., a subsidiary of Johnson &
as a way to promote the body’s own clearance of βA. Johnson (JNJ), and Exelon by Novartis AG (NVS), will
Development of this drug was halted after Phase 2a studies continue to fade due to patent expirations in 2008 and 2007, due to a higher incidence of encephalitis. While AAB-001 has generated the most excitement for AD The most recent drug approved for AD is a NMDA receptor therapies, it also comes with significant risk. Data presented at antagonist which has avoided direct competition with the ACE the 9th International Symposium on Advances in Alzheimer inhibitors by gaining approval in moderate to severe AD. The Therapy in April of 2006, showed some patients developed issue here remains that there is no approved drug for AD normal MRI signals. The penetration of the antibody into the which can actually stop underlying pathologic brain damage brain is low at best, and as a humanized antibody the risk of or prevent or reverse the progression of the disease. The allergic and immunological reactions is a consideration. Alzheimer’s Association estimates that delaying the onset of AD by five years could lead to a $50B yearly savings in In my opinion, AAB-001 is not the most exciting AD prospect healthcare related costs. Needless to say, insurance companies in Elan’s pipeline. A collaboration between Transition
would be happy to front the $6B in treatment costs to save Therapeutics (TTHPF.PK) and Elan has spawned the
roughly $44B in AD healthcare related costs. development of AZD-103. This is the best drug in Elan’s AD landscape; currently in Phase 1 trials, this drug has all the To fill this demand, several companies have drugs in late stage attributes of a blockbuster. AZD-103 is a small molecule, a trials which are directed at the three major therapeutic naturally occurring stereoisomer of inositol, called scyllo- underpinnings of AD: the beta-amyloid (βA) protein and its inositol. Preclinical data has just been published on AZD-103, associated plaques, neurofibrillary tangles comprised mainly released ahead of print by the Journal of Molecular Medicine of Tau protein and neuro-inflammation. Drugs targeting βA are considered the most exciting and as having the highest therapeutic value. Let’s take a look at three late stage Myo-inositol, is the most common stereoisomer of inositol and is a critical component of all mammalian cells. Because myo- and scyllo-inositol are so highly related, preclinical studies
Alzhemed (by Neurochem Inc. (NRMX)) is a small, orally-
were undertaken to evaluate whether administration of AZD- administered βA antagonist. This drug is being tested in 103 would disrupt the normal function of myo-inositol. Long patients with mild to moderate AD, and may help provide stabilization of the disease. Top line Phase 3 results are due in AZD-103 was tested in a mouse model of AD called the TgCRND8 mouse. This mouse accumulates βA similar to the
Flurizan (by Myriad Genetics, Inc. (MYGN)), a nonsteroidal
way humans do, showing cognitive deficits at 3-6 months of anti-inflammatory (NSAID) drug, has been shown to lower βA, age comparable to that of advanced stage AD in humans, and but does not have a direct effect on the protein itself. Also in by seven months the animals have a βA burden roughly Phase 3 trials for mild AD, interim data is expected in 2H2007. equivalent to human end stage AD. AZD-103 was tested for the ability to prevent the appearance of the disease and its AAB-001 (bapineuzumab) is, perhaps, the most widely ability to reverse the disease after symptoms had fully anticipated drug in advanced AD clinical trials. Developed developed. AZD-103 performed very well, and the estimated through a collaboration between Elan Corp., plc (ELN) and
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therapeutic dose range (IC50 ~1µM) was well below the range The mechanistic data indicate AZD-103 doesn’t depolymerize the βA clusters, but it binds and neutralizes them. This results Inositol as a drug therapy has been around for over 20 years. in the blockade of plaque formation and significant restoration Myo-inositol has been used successfully in many psychiatric of cognitive function in animal models. The drug is in Phase 1 diseases without negative effects on organ function. The AZD- trials, and Elan has set a goal of moving this to Phase 2 by the 103 preclinical data are quite impressive, more so than that for end of the year. If so, this drug will quickly upstage AAB-001, AAB-001. The drug is orally available, is able to pass through as its properties are so much more attractive and much more the blood brain barrier and gain entry to the neurons and likely to have a big impact on mild, moderate, and advanced supportive cells affected by AD, and the safety profile for the n 2005, prostate cancer was the second leading cause of respectively). The mortality data on the study are still pending. cancer death in men in the US. When it is confined locally, prostate cancer is curable. However, advanced disease is How do you put the data into meaningful perspective? not considered curable. Although androgen-deprivation therapy (ADT) may control advanced prostate cancer for We first have to realize that this is a palliative treatment. The many years, patients eventually develop hormone-refractory drug treatment will not cure the disease. There is no set prostate cancer (HRPC). Taking docetaxel every three weeks standard of care for second-line treatment, so we are not with prednisone, recently obtained approval from the FDA as comparing the performance of Satraplatin against another drug. a standard, first-line chemotherapy regimen for patients with Therefore, the question becomes: does the drug offer a benefit HRPC. The median survival benefit in docetaxel registration to a patient with end-stage disease and is this benefit worth trials was between two and three months, and survival remained disappointingly short. After failure of first-line chemotherapy with docetaxel and prednisone, there is no To this end, the overall survival data will be very important. second-line regimen that is considered a standard of care. The PFS data, while statistically significant, represents only a Clearly, opportunities exist to improve the outcome of patients small benefit. If no overall survival benefit is found, I think with HRPC who receive treatment with docetaxel-based SPPI will have a hard time getting approval in this indication. If we look to the data from a small (50 patient) European study of Satraplatin in HRPC, the mortality benefit ended up Spectrum Pharmaceuticals, Inc.’s (SPPI) Satraplatin, a
as 14.9 months with treatment versus 11.9 months with Phase 3 oral, anti-cancer drug is being co-developed with placebo; a three month difference was found. While this may GPC Biotech AG (GPCB) for its initial indication: second-
seem small compared to a front-line trial of non-advanced line chemotherapy for HRPC. Updated data on Satraplatin’s disease, three months is reasonably good for this situation. The registration trial (called ‘the SPARC trial’) was reported at the FDA found that in patients with advanced, end-stage lung or ASCO Prostate Cancer Symposium in February and has been pancreatic cancer, the addition of a few months was clinically reviewed in two very different manners. At first glance the beneficial. The same is likely in this case. If the mortality take away messages from the interim analysis sound great, benefit is more than 1-2 months, the drug is likely to find a with highly significant improvement in progression-free niche in HRPC. As for the increase in mortality in the survival (PFS) in patients regardless of prior exposure to a Satraplatin arm of the study, it is too early to tell whether that taxane drug. But a closer look at the data raises some is a really meaningful risk or just a coincidence. important questions. I will review the data and try to give some perspective by comparing to other end-stage diseases, Interestingly, some new data are suggesting that this type of like advanced lung and pancreatic cancers. treatment (platinum-based drugs) may be particularly effective in tumors which show neuroendocrine differentiation (NE). The SPARC trial enrolled 950 patients with HRPC; 635 HRPC sometimes shows this clinical feature and may well be received Satraplatin and 315 got placebo. Overall PFS was part of the reason Satraplatin is having an effect. It would be significantly increased by Satraplatin, but the benefit is small. interesting and informative to evaluate the patients enrolled in The significance really boils down to a difference of about 10 the trial for the presence of NE characteristics. Correlation of NE features and response to Satraplatin would certainly help classify which HRPC patients might benefit most from the The endpoint of PFS was a composite of several measures, treatment. The bottom line here is while the PFS data appear including: systemic progression, tumor progression by MRI, to be statistically powerful, the final mortality numbers are CT, or X-Ray and increase of pain. The study found more going to be critical in helping Satraplatin secure approval as deaths in the Satraplatin group versus placebo (9.1 vs 4.7%, the first treatment for second line therapy in HRPC. For more information on receiving this publication or contacting the authors herein, please email [email protected] B i l l i o n d o l l a r b l o c k b u s t e r s l o o k i n g v u l n e r a b l e The Barnes Report · No. 3 · March 22, 2007 6
Merger will form impressive pipeline of next generation chemotherapeutic drugs
n late February, Access Pharmaceuticals, Inc. (ACCP)
tumor. Accumulation in normal tissues is significantly lower announced plans to acquire a small oncology focused and avoids neurotoxicity, which is common for platinum- company, Somanta Pharmaceuticals (SMPM). Although
based drugs. Prolindac is in single agent Phase 2 studies in these are two small and relatively unknown companies, the Europe for relapsed ovarian cancer and in the U.S. as an merger would establish a pipeline that could seriously investigator sponsored study in head and neck cancer. challenge the widely used platinum- and anthracycline-based Prolindac is also in a Phase 1-2 study in combination with chemotherapeutic markets. The platinum market is dominated Florouracil/Leucovorin in colorectal cancer. by oxaliplatin, which grossed €1.7B for SNY in 2006. The anthracycline market is a bit more fragmented, with no clear PB is an HDAC inhibitor currently in Phase 2 trials for standout between doxorubicin, daunorubicin, epirubicin and recurrent glioblastoma and prostate cancer. PB is being co- mitoxantrone. The anthracycline-based drugs are among the developed by SMPM and Virium Pharmaceuticals. This may
most widely used chemotherapeutic drug classes. pan out as a nice compliment to Prolindac. The drug has been shown in preclinical models to synergize when administered SMPM CEO, Agamemnon Epenetos, characterized the with cytotoxic drugs, even in chemoresistant tumors. proposed acquisition as ‘highly synergistic’. And although Concomitant Prolindac and PB may yield better results than those are strong words, the proof is in the pudding, so to speak. the either drug alone, not to mention extension of patent The combined pipeline at first glance is broad and focused on anti-cancer drugs with minimal redundancy. But, upon closer examination we find additional significant potential for Alchemix is a novel drug in the anthraquinone (AQ) family combining at least two of SMPM’s drugs with ACCP’s which includes daunorubicin, doxorubicin and mitoxantrone. Prolindac. So in addition to having value as single agents, Alchemix has shown efficacy at nM concentrations. The concomitant use of their drugs holds its own promise. problems with current AQ-based drugs include cardiotoxicity, resistance, normal tissue damage, and difficulty in delivering But these are not just any old anti-cancer drugs. ACCP and and maintaining sufficiently high levels in tumors. Some very SMPM make use of advanced chemistry and specialized inventive chemistry, prompted by these limitations, lead to the delivery mechanisms to improve tumor penetration and reduce discovery of Alchemix and Prodrax. Although similar, the two systemic toxicity. Both of these companies hold the next are being developed for different indications. Alchemix is generation of ‘selective’ chemotherapeutic drugs which being looked at for recurrent CNS, colon, ovarian and renal preferentially accumulate in cancerous tissue but not in normal tissue. ACCP has focused its effort on two main products: MuGard and Prolindac. SMPM brings four main drug Prodrax is an AQ with advanced chemistry, which in short, candidates to the table: PB (phenylbutyrate/VP101), Alchemix, eliminates most of the toxic side effects common with AQ’s. It is preferentially activated by the hypoxic environment of a tumor and shows markedly reduced normal tissue toxicity in MuGard received FDA marketing clearance in December of vivo. Prodrax is related to AQ4N, a drug being developed by 2006 for the treatment and prevention of oral mucositis (OM). Novacea, Inc. (NOVC). AQ4N, in addition to having single
OM is a serious, often painful, and frequent dose-limiting agent anti-tumor activity, acts as a radiation sensitizer and also toxicity associated with chemotherapy and radiation therapy potentiates the anti-tumor activity of cisplatin. So this also is a for cancer. It frequently leads to the interruption of radiation good candidate to use in combination with Prolindac. Given or chemotherapeutic treatment which predictably results in that Prodrax is a more advanced compound, it is engineered to decreased efficacy. MuGard is a thick liquid that coats the soft improve upon AQ4N’s performance. Prodrax is in tissue in the mouth and protects it from damage. OM is a development for recurrent lung, breast, ovarian, pancreatic and particularly serious problem for approximately 400,000 esophageal cancers. SMPM acquired the rights to patients (~40% of cancer patients undergoing treatment in the commercially develop Alchemix, Prodrax, and other potential novel anti-tumor compounds through a collaborative chemotherapy for solid tumors. It is estimated that the size of agreement with the University of Bradford, in the U.K. Angiolix is the last drug in development at SMPM and is kind Prolindac is a platinum-based drug designed to limit of a stand alone. It is a humanized antibody to lactadherin, accumulation and toxicity in normal tissue while concentrating important in tumor angiogenesis. Preclinical data on this drug its cytotoxic action in tumors. The drug makes use of a was presented at the Stem Cells and Cancer conference in delivery mechanism which preferentially concentrates drug early March 2-7. The mechanism of action for Angiolix is (reported as much as 16 times more active drug than reported to be similar to that of Avastin, although it works oxaliplatin at equitoxic doses) in the low pH environment of a through a VEGF-independent mechanism. In addition to this For more information on receiving this publication or contacting the authors herein, please email [email protected] B i l l i o n d o l l a r b l o c k b u s t e r s l o o k i n g v u l n e r a b l e The Barnes Report · No. 3 · March 22, 2007 7
antibody, SMPM holds the rights to any lactadherin-directed SMPM may be his best work. The two companies have similar therapeutic for cancer. This drug is a bit of a bonus for ACCP; goals of targeting special attributes of tumor biology while it is very different from anything they have going on and hits a sparing damage to normal tissues. The lead drugs make big area of interest with cancer stem cell as a touted target. advances on platinum- and anthracycline-based drugs, both of The plan for Angiolix at SMPM was to develop the drug which are widely used and non-competitive with each other. through Phase 2 clinical trials and then partner. The market potential here is very big; several of these compounds could make a big splash on their own, and the While the merger may seem random, it is likely the handiwork prospect of combining them introduces a whole new of Jeff Davis. Mr. Davis has served on the board of directors dimension. The combined pipeline is broad in scope, and with at Virium, SMPM and ACCP. And it may not be the first time their best drug candidates named Prolindac and Prodrax, the Mr. Davis has facilitated a successful collaboration, as SMPM fusion of the two even works esthetically. is developing PB with Virium. The merger of ACCP and
Jessica Barnes is author of The Barnes Report. Jessica received her Ph.D. in Molecular Neuroscience from the University of
Illinois, and is currently a research fellow cross-appointed at Dana-Farber Cancer Institute, Children's Hospital Boston and
Harvard Medical School. She studies the angiogenic basis of brain tumors with Dr. Judah Folkman and investigates experimental
therapeutics and novel molecular imaging modalities with Dr. Mark Kieran.

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