Thursday, December 30, 2010

CytRx is an Up and Coming Biopharma Company with 3 Promising Candidates.

CytRx Corporation (NASDAQ: CYTR) is a biopharma R&D company that specializes in oncology therapeutics.  The pipeline has 3 drug candidates for various cancers, which have caught my attention.  I think that CYTR is an interesting company and their products have the potential to be widely used for treatment of cancers.  What is more impressive is that the company's 3 candidates have different mechanisms of actions and are being studied for a wide range of cancers unlike a lot of small cap companies that put all their eggs in one basket.  It will still be a few years before the candidates will hit the market.  Here's a brief overview:
  • Initiation of Phase 2b clinical trials of its drug candidate bafetinib in patients with high-risk B-cell chronic lymphocytic leukemia and advanced prostate cancer, and a pharmacokinetic clinical trial in patients with brain cancer. 
  • Phase 2 trials with its oncology candidate INNO-206 for soft tissue sarcomas and pancreatic cancer.
  • Tamibarotene for non-small-cell lung cancer (Phase 2b), and acute promyelocytic leukemia (APL).  
  • Seeking a potential partnership of molecular chaperone technology.  
  • 17% equity interest in RXi Pharmaceuticals Corporation, or RXi (NASDAQ: RXII).  There has been speculation for a long time about RXII being acquired by a big pharma.  Nothing has come to fruition.
CYTR is currently trading at $1.00 after sliding from a high of $1.11 from just a couple of weeks ago.   The price began falling after a site reported that a uptrend was spotted for CYTR.  Guess they got to the party when it was already over.  I began following the stock when it was trading at $0.74 during the summer.  I have studied papers of each of their candidates and think the company is onto something.  The market cap is $109 million, which is lower than similar biotech/pharma companies.  Perhaps the company is undervalued.    If you did not pounce on the stock during the uptrend, this is the perhaps the best time to join in on the action.  When CYTR begins Phase 3 trials, the price is surely to go up.  Phase 3 trials may begin in mid to late 2011 if everything goes as planned. 

I would like to just briefly explain the specifics of INNO-206 and its potential as it is similar to a project that I have worked on and many researchers around the world have studied. 

INNO-206 (formerly DOXO-EMCH) is a pro-drug of doxorubicin., a very commonly used drug in oncology.  Doxorubicin is used for a wide variety of cancers and has a liposomal nanotechnology formulation called Doxil, which has effectively replaced doxorubicin.  CYTR has the worldwide rights to INNO-206.  The design of the drug is similar to another nanotechnology formulated drug called Abraxane by Abarix Bioscience.  Whereas Abraxane is manufactured with paclitaxel attached to a blood protein called albumin, INNO-206 is doxorubicin modified with a chemical linker that binds with albumin when injected.  The linker breaks down when it enters the tumor environment which is acidic.  Abraxane and Doxil have been spectacular in reducing adverse effects of the original drugs.  I believe that INNO-206 can do better than these.  Doxil is the main competition for INNO-206; it would be interesting to see Phase 3 trials comparing the two formulations.

There are several issues that INNO-206 must address for wide acceptance by oncologists and pharmacists:
  1. Doxorubicin has a cumulative lifetime dose maximum.  This means a person can only receive a certain amount of it throughout their life.  It is unknown if this also applies to Doxil. 
  2. This relates to the previous issue.  Doxorubicin is known to be cardiotoxic and that is why it has a limit.  CYTR must demonstrate that there is no toxicity issues with the heart if they want a blockbuster oncology drug.  
  3. This relates to the previous two posts.  Patients with heart problems such as heart failure are exempt from taking doxorubicin.  By demonstrating that INNO-206 has no toxic effects on the heart, a greater number of patients can qualify for therapy.
  4. Doxil has a side effect known as Hand-Foot Syndrome.  This is another issue that INNO-206 must overcome.
  5. Doxorubicin can cause serious damage to the skin and blood vessels when being given to the patients.  By avoiding this, INNO-206 will gain favor with patients.
  6. The technology used in INNO-206 needs to demonstrate higher accumulation in the tumors.  
  7. CYTR must also evaluate if cancer develops resistance to INNO-206.  Resistance is a big drawback to effective doxorubicin treatment.
  8. Doxorubicin is used for many types of cancer.  Can INNO-206 be applied to these cancers?  Is CYTR willing to test 5+ types of cancer? Probably not off the back.
This may seem like an overwhelming list but this is what companies have to consider when bringing new drugs to the market.

Wednesday, December 29, 2010

Mucus Producing Proteins: The Key to Curing Cancer? Minerva Biotech Bets on It.

Over the past fours years, I have done research on designing nanotechnology based drug delivery systems to target and kill cancer cells.  I have decided to target a particular protein that it over-expressed on many cancer cells.  While there are thousands of labs targeting receptors like epithelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEFGR), which control growth and blood vasculature. I went another direction and targeted mucus producing proteins called mucin, specifically MUC-1.  One study I read stated that over 90% of late stage ovarian cancer cells over-expressed the mucin receptor.  Another stated that nearly 75% of epithelial cancers over-express mucin proteins.  What does a mucus producing protein have to do with cancer? And why aren't more companies interested in exploiting mucins?

Studies have discerned functions of the mucin proteins ranging from controlling the environment surrounding the cells, preventing drugs from entering the cells, participating in metastasis and growth, intracellular signalling, and recent studies showed that it may interact with EGFR.  All these steps are important to the initiation, growth, and metastasis of cancer.  Mucin appears to be the untapped gold mine for cancer research.  I believe that many big pharma companies are working on mucins but not substantially investing in it because of the relative recent studies.  They're probably waiting for more research to come out before pouring money into projects.  Of course investing millions of dollars into research of mucins is filled with risk, but the reward is immense. It is also noteworthy that the current accepted test for monitoring ovarian cancer is the CA-125, which is a mucin protein.

There is a private biotech company in Waltham, MA named Minerva Biotechnologies.  They have produced some amazing results concerning the functions of mucins and how to exploit them for treating cancers.  They discovered that the mucin proteins are not only overexpressed on cancer cells, they are expressed as a different form.  The scientists at Minerva discovered that in cancer cells, a large chunk of the mucin protein breaks off and thus initiates the processes involved in cancer progression.  While there are a lot of academic researchers targeting mucins, based on Minerva's findings, they are targeting the chunk of the receptor that breaks off.  This broken off piece does play a role in cancer, acting like a ligand and activating the mucin receptor.  Minerva has worked on targeting the piece of the receptor that remains on the cell, the piece on the outside is about 45 amino acids in length.

Minerva Biotechnologies is perhaps the leader of targeting mucin receptors and has the possibility of changing the landscape in cancer treatment.  Investors cannot benefit form the results because Minerva Biotech is currently a private company.  I will be very interested when Minerva IPO is available and believe that investors will greatly benefit by investing into the company.       

Tuesday, December 28, 2010

Can a Monoclonal Antibody Take Over Cheaper Drugs?

Amgen's (AMGN) denosumab (Xgeva/ Prolia) is a fully human monoclonal antibody that is FDA approved for the treatment of osteoporosis and prevention of skeletal-related events in patients with bone metastasis (a fancy way of saying that it helps to prevent cancer cells from spreading into bones and prevent fractures and pain caused by cancer cells).

A drug class called bisphophonates are typically used to treat these conditions. An example is Boniva, which had Sally Fields as a spokeswomen.  Compared to denosumab, these drugs are much cheaper , but have some serious adverse effects such as degradation of the jaw bone (osteonecrosis of the jaw).

Denosumab (Prolia) for Treatment of Osteoporosis
Cummings SR, Martin JS, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361:756-65.
  • Compared to placebo, denosumab reduced the risk of vertebral fracture (2.3% denosumab, 7.2% placebo)
  • Denosumab reduced the risk of hip fracture (0.7% denosumab, 1.2% placebo)
  • Reduced non-vertebral fracture in denosumab group (6.5% denosumab, 8.0% placebo)
  • No increased risk of cancer, infection, heart disease, slow fracture healing, injection site reactions, and no reports of osteonecrosis.
  • Patients typically develop immune reactions to monoclonal antibodies (auto-antibodies) and the treatment becomes ineffective.  There have been no such reports in osteoporosis trials of denosumab, which is a good sign.
    • It should be kept in mind that the trials were only a couple of years in duration and osteoporosis treatment would be lifelong.  This increases chances of immune tolerance.
  • Bisphosphonates are taken usually taken weekly or monthly (Reclast is taken once a year).  the side effects are intolerable and the patient has to stand or sit up for 30-60 min after taking the dose.  Denosumab is taken twice a year.  This is a convenience factor and patients prefer the most convenient form.
  • Further studies are needed comparing denosumab to bisphosphonates.  Denosumab acts through a different mechanism to prevent bone loss and may be more effective than bisphosphonates.
  • Denosumab costs around $1,650 yearly.  This price should decrease as it will continue to compete with bisphosphonates.  I believe that Reclast, the once yearly bisphosphonate cost about the same.  However, Reclast requires an infusion, given over a hour or more, and Prolia is a subcutaneous injection like an insulin injection.  The cost of treatment for Prolia end up being less than Reclast.  Compound that with ease of administration and less injection reactions, expect Prolia to become the favorites  among physicians and patients.
Denosumab (XGEVA) for Treatment and Prevention of Bone Metastasis  
  • Denosumab and Zometa were studied in castrate-refractory prostate cancer.
  • Bone metastases occur in 1.5 million patients with cancer worldwide.  Most of these patients are debilitated by skeletal issues such as fractures and pain.
  • Patients with bone metastases have higher medical costs.  Treating these skeletal issues can significantly reduce costs.
  • The most common cancers associated with bone metastases  are those of the prostate, lung, and breast.
  • Patients receiving XGEVA developed bone metastases about 8 months later than those taking Zometa
  • Adverse effects, jaw bone degradation (osteonecrosis), overall survival, and cancer progression were similar in both groups.
  • The fact that treating skeletal issues drastically reduces costs means that hospitals are acively seeking ways to treat the issue and lower their costs.
  • To compete with Zometa cost wise, Amgen has begun the XGEVA FIRST STEP Coupon Program, the 1st of its kind for onocology commercial co-pay program and it does not have any income eligibility requirement.
    • Patients will not have to pay out of pocket for the initial injection and only $25 for subsequent injections.
    • XGEVA may become the preferred treatment for prevention of bone metastasis for similar reasons as those for osteoporosis.
Is Denosumab a Game Changer

  • Denosumab is a novel way to treat osteoporosis and prevent bone metastases
  • The costs are competitive vs. bisphosphonates
  • Denosumab has a slightly better adverse effect profile and may be preferred by patients and physicians
  • Denosumab has a high probability of being a game changer and becoming the standard of care for the approved conditions
  • Further studies will need to examine adverse effects and immune tolerance
  • Amgen has been trading in the $52-58 range over the past 6 months.  This can really give a boost to the stagnant stock price.

Monday, December 27, 2010

Otsuka Holdings Outlook

Otsuka Holdings recently held its IPO on the Tokyo Stock Market priced at $2.4 billion, the largest IPO in Japanese history.  Otsuka was offered at the lower end of its range because there are concerns about future drug products that it will be a successor after Abilify (aripiprazole) is off patent in 2015.  The company is based on two business segments: pharmaceuticals and consumer products similar structure to Pfizer.     

Otsuka has several drugs in their pipelines which include drug candidates for depression, schizophrenia, ADHD, low blood sodium, cancer, tuberculosis, Crohn's disease, dry eyes, and COPD.  These agents range from Phase I to Phase III.  Otsuka does have one other drug on the market that has the potential to alter treatment standard: tolvaptan.

The drug Samsca (tolvaptan) is a FDA approved oral agent for the treatment of hyponatremia (low sodium in the blood).  The main competitor is Vaprisol (conivaptan) marketed by Astellas.  It's not fully clear which is the the superior drug, but theere probably are ongoing clinical trials evaluating them.  Other therapeutic options for low blood sodium are sodium rich fluids, fluid restriction, and treating the cause of the low sodium (this is usually not clear).  These are quite ineffective and the need for new options was great; leading to the disocveries of conivaptan and tolvaptan.

The SALT-1 and SALT-2 Phase III trials evaluated tolvaptan in patients with low sodium.  Patients receiving tolvaptan reached normal sodium levels and maintain these levels while on tolvaptan.  Unfortunately, the sodium levels dropped upon discontinuation of therapy.  

Tolvaptan would have been a gem if positive results were obtained in the EVEREST trial.  Tolvaptan showed modest improvement in difficulty of breathing, but no significant improvement in improving morbidity and mortality in patients with heart failure.

Tolvaptan can have a huge impact of saving on hospital budgets. Boscoe et al. estimated that direct cost of treating low sodium to be $1.6-3.6 billion annually.(Boscoe A, Paramore c, Verbalis JG. Cost of illness of hyponatremia in the United States. Cost Effectiveness and Resource Allocation. 2006;4:10 doi: 10.1186/1478-7547-4-10).  Another study showed that low sodium accounts for a 47.1% increase in treatment cost at 1 year (Shea AM, Hammill BG, Curtis LH, Szczech LA, Schulman KA. Medical costs of abnormal serum sodium levels. J Am Soc Nephrol. 2008;19:764-770). 


1.MacDonald E. New drug bulletin: Tolvaptan (Samsca- Otsuka America). University of Utah Hospitals & Clinics. Sept. 2009.

Dosage forms
Dosage Regimen
AWP cost per day
20 mg/mL in D5W
20 mg LD, then 20 mg/d IV
15 mg or 30 mg blister pack of 10 tab
15 mg/d po –
30 mg/d po

  • Tolvaptan is less costly than conivaptan and this will be a deciding factor for hospital's to choose tolvaptan over conivaptan unless conivaptan is proven to be far superior
  • Tolvaptan is an oral agent.  It is preferred by patients, easy to administer, and  much cheaper to administer.  
  • Patients do not have to be in the hospital to take tolvaptan: additional costs savings. 
  • Tolvaptan should become the standard treatment for low blood sodium
  • Otsuke expects profits to grow 18% by March 2011 (
  • IPO offering at the low range means there is more room for Otsuka to grow and investors to cash in.
  • The stagnant Japanese economy is not encouraging.
  • Otsuka trades at about 15 times future earnings compared to Takeda which trades at about 13 times future earnings.
  • 56.7 million shares will be traded outside of Japan
  • Although analysts may worry about Otsuka after 2015, I believe that it will be a good position which tolvaptan having a large clinical role and other candidates will reach the market if successful.  The consumer market should increase if the Japanese economy grows and Otsuka begins more heavy marketing of consumer products overseas.

King Pharma Re-submits NDA for Remoxy

King Pharma (NYSE: KG) is resubmitting its NDA for Remoxy to the FDA.  The NDA was submitted berfore, but the FDA wanted more information about the deterrence technology used in Remoxy and its effectiveness.  If Remoxy is approved, it's main competitor will by OxyContin manufactured by Purdue Pharma.  Because the high abuse of Oxycontin, it may be given that a drug with abuse deterrence will trump the use of one without such technology.  King Pharma has taken a leading role in developing drug deterrence technology and may get a large market share in narcotic medications.

Remoxy is a novel formulation of the pain killer oxycodone, which has high addictive and abuse potential.  Purdue's OxyContin is a delay-release formulation, which means that the drug is slowly release and the patient does not get the "high" feeling.  However, drug abusers have found ways to extract the oxycodone from the formulation for recreational use.  Remoxy is a high viscosity (think thick) liquid in a hard gelatin capsule (physical barrier).  Freezing, dissolving in ethanol, and manipulation are made difficult.  The fraction of oxycodone released is a fraction compared to OxyContin.    

There are two other formulations that fall in the same cateogry as Remoxy: Embeda by Alpharma which was bought by King Pharma and Acurox by Acura Pharma and King Pharma.  Embeda has been approved by the FDA while Acurox was rejected in April.

Both technologies are great in fighting against abuse of narcotics.  Personally, I believe Embeda's drug deterrence technology is better than Remoxy.  Embeda is a combination of morphine and naltrexone, which opposes the effects of morphine.  When swallowed, naltrexone is digested by the stomach and has no counter-effect.  When injected, naltrexone is active and prevents effects of morphine.  Separating naltrexone from the formulation is difficult without degrading morphine.  Remoxy's deterrence technology may be easier to "hack."  There might be higher prescribing of Embeda than Remoxy but  it may be too early to tell.

Since both formulations are under license of King Pharma, it is a win-win situation potentially (not to mention Acurox is also developed by King Pharma).  It will be interesting to see if KG stock price increases in response to submission of the Remoxy NDA.  The price may simply increase because of FDA approval.  The sales figures from the two drugs are difficult to predict and the fact that they may compete against each other may cancel any great benefit for investors.  Both drugs are used for moderate-to-severe pain.  Think of GM when it had numerous brands and each brand had models that competed against each other.  Embeda is restricted to use in opioid-tolerant patients; those who no longer respond to lower potency drugs.  KG may decide to try to market them in different ways to increase prescribing.  It would be wise of King Pharma to promote Remoxy and if the patient becomes tolerant (unresponsive) to it, the patient could be placed on Embeda.  

Time to Buy InterMune (ITMN)?

Gilead Sciences Inc. (Nasdaq: GILD) just announced that it is halting it's Phase III clinical trial of ambrisentan dubbed ARTEMIS-IPF.   Ambrisentan was a drug candidate for the treatment of idiopathic pulmonary fibrosis (IPF).  GILD cited lack of efficacy as the reason for stopping the trial. 

IPF is a condition that results in thickening and scarring of lung tissue.  There is actually a change in the type of tissue of the lung.  This causes less oxygen and gases to be transferred within the lungs.  Therefore, the body receives less oxygen, especially the brain.  The cause of IPF is unknown (idiopathic means that the cause is unknown).  IPF affects nearly 200,000 patients in the US.  Currently, there are no drugs that effectively treat or cure IPF.  Physicians prescribe drugs that treat the symptoms or stabilize the disease. Source: Pulmonary Fibrosis Foundation

The FDA recently approved InterMune's (Nasdaq: ITMN) Esbriet (pirfenidone) for the treatment of IPF. The drug was also approved in the EU.  This is the first drug that effectively treats IPF.  It is likely that pirfenidone will become the standard of care for IPF as other treatment options are not ideal.   ITMN recently surged on news of positive results and should get another boost on the bad news from GILD as this eliminates some serious competition. 

Sunday, December 26, 2010

Hyperthermia, Radiofrequency, and Microwaves: The Future of Cancer Therapeutics

Recently I heard about a forward thinking biotech company called BSD Medical (BSDM).  The company designs systems that deliver radiofrequency or microwave energy to precise targets within the body, primarily tumors located near the surface of the skin.  They also have systems to reach deeper tumors.  I was excited researching this company as I have worked on some projects involving hyperthermia therapy for cancer treatment.  Unlike BSDM, I worked with superoxide  iron nanoparticles and carbon nanotubes.  Our plan was to use MRI or some other form of external rotating magnet field to help target and then heat up and destroy cancer cells.  We hypothesized that we could heat and destroy tumors while leaving normal surrounding tissue unharmed.

The BSDM  website explains that their hyperthermia technology treat cancer with heat and boost the efficacy of radiation therapy.  BSDM's website explains that the immediate environment surrounding tumors (acidic and low amount of oxygen) causes radiation to be ineffective while microwave therapy is enhanced in this environment.  Since cancer patients are usually treated with multiple forms of therapy: drugs (chemotherapy), surgery, and radiation, BSDM's system can easily be added onto standard treatment protocols to increase effectiveness.  The microwave therapy is utilized in tumor ablation therapies in which soft tissue is vaporized.

Reasons that I AM excited about BSDM:
  1. Novel form of therapy.  Expect BSD Medical to maintain a large share of the market for several years.
  2. The technology can be combined with other conventional forms.  As briefly mentioned before, cancer patients are routinely treated with different forms of treatment.  Microwave technology can be used as a primary form of treatment, used before surgery to reduce the size of the tumor so surgeons can more easily remove it, or it can be used after surgery to kill any remaining cancer cells.
  3. Drug resistance is a ever-present concern when treating cancer.  There is less concern of resistance to microwave and radiofrequency therapies, but this must be kept in mind.
  4. BSDM is also beginning to supply its systems for worldwide distribution.  This is very exciting because physicians and healthcare practitioners overseas tend to be more welcoming to novel forms of cancer therapy than their counterparts in the USA.  An example is the I-SPY clinical trials for breast cancer therapies.  It was a novel way of performing clinical trials and has a novel paradigm of treating breast cancer.  It was only recently started in the USA. 
Reasons that I AM NOT excited about BSDM:
  1. The adoption of therapy may be slow.  Physicians, especially older ones, are reluctant to try new agents let alone novel forms of therapy.  When dealing with cancer, you can bet that a new form of therapy will be met with some resistance.  BSDM does hold training events and their success will be do in part to educating physicians about their technology.
  2. The technology is new and it will take several years to better understand the mechanisms.  In addition, we do not know of all side effects and long term detrimental effects.  
  3. In addition to convincing physicians to use their technology, BSDM will need to convince patients to use microwave or radiofrequency treatments.  Patients are now involved more in their treatments than ever before.  BSDM will need to focus on patient education.  The website does a decent job providing patient information.
  4. Insurance companies will need to cover the expense of treatment.  They are the more difficult to convince.

 Recommendation: BSDM is buy-strong buy.  I love where the company is heading.  This is not some biotech company that is focused on treating rare conditions that only effects a thousand or so patients and design drugs that have prohibitive costs and that insurance companies will not even consider covering.  There is a very high ceiling and this is the best time to buy BSDM.       

Saturday, December 25, 2010

Why Not to Become Excited About Diet Pills.

Investors become excited when a biotech or pharmaceutical company completes Phase III trials and are being reviewed by the FDa.  This results in increasing stock prices.  This is likely due to the many investors who become interested in the stock.  I like to believe that this is somewhat of an artificial increase in stock price.  After a couple of days to a week, the price begins to fall.  This is precisely what we see with Arena's stock price.

I would like to concern this post regarding whether it is worth investing with Arena Pharmaceuticals and what recent developments mean for the short term and long term future of the stock.  I introduce some pharmaceutical and medical terminology and will try my best to explain them; however, if the meaning is still unclear, please post a comment and I will clarify the issue.  

The Food and Drug Adminstration (FDA) held a End-of-Review meeting with Arena Pharmaceuticals (ARNA) recently concerning the New Drug Application of lorcaserin, a diet pill.  The FDA has not aproved the agent earlier this year over concerns of safety and efficacy.  To date, there is only one FDA approved  diet pill on the market, orlistat, which is available OTC (Alli) and by prescription (Xenical).  Sibutramine was another diet pill approved by the FDA, but due to heart problems, sibutramine was removed from the US market.  Effects on the heart will always remain a concern with diet pills and any company selling diet pills will be required to perform post-marketing surveillance and pay close attention to heart problems. 

There are other agents currently be studied in clinical trials: Bupropion/naltrexone (Contrave, still in Phase III, but well on its way to approval), phentermine/topiramate (Qnexa), and rimonabant.  Due to the way these agents work, do not expect them to be met with open arms by the medical community.  Physicians prefer diet and exercise rather than prescribing a diet pill.  Earlier this month, the FDA approved expanding the eligibility scope of implementing Allergan's Lap-Band for weight loss.  These are just some of the barriers facing lorcaserin from becoming a blockbuster drug.  

Lorcaserin is the first therapeutics agent that is classified as a selective serotonin 2C receptor agonists, which means that it activates the receptor. According to Arena's website, "The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area involved in the control of appetite and metabolism."  They fail to mention that the receptor is also involved with regulating mood, anxiety, and reproductive function. Although it is exciting that lorcaserin is the first in class, there are two primary concerns.  
  1. Little is known about the adverse or unwarranted effects of the stimulating the serotonin 2C receptors.  There are other agents with effects on the the same receptor.  The majority of these drugs are anti-psychotics (aripiprazole (Abilify)).  Also, anti-depressants such as fluoxetine (Prozac) are known to inhibit or turn off the serotonin 2C receptor.  Since turning off the receptor treats depression, this raises depression as a concern in therapy involving lorcaserin.  
  2. Copy cat agents on well on their way.  Medicinal chemistry seeks to either mimic biological molecules or agents that are already on the market.  Small chemical changes are made to optimize the properties of the drug.  For example, the chemists may want the drug to be eliminated from the body more slowly so the patient can take less drug and achieve the same results.  Another typical issue is to improve the efficacy the drug and reduce side effects.    
In conclusion, there is little hope of the FDA approving lorcaserin for weight loss and management.  If the agent is approved by the FDA, then ARNA is a good short term buy and then sell.  Lorcaserin is Arena's most advanced drug candidate.  ARNA has four other drug candidates (including one with Ortho-McNeil Janssen).  All of them are in Phase I and it is too early to project whether any of them will be a success.  ARNA states that its main interest is designing drugs for G-protein coupled receptors (GPCRs), which are a very common type of receptor.  It should be kept in mind that these receptors are rather complex and difficult to only elicit the desired response because different receptors interact with each other.  Given the current product pipeline and lack of diversification (different ways the drugs work) of these products (think about this like diversifying your stock portfolio), for long term investors, I would recommend not buying or if you own ARNA to sell the stock.