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The Life Sciences Report Watchlist 2013


2/1/2013 11:58:48 AM

The Life Sciences Report Watchlist 2013

The Life Sciences Report Watchlist 2013

Source: George S. Mack of The Life Sciences Report (2/1/13)

http://www.thelifesciencesreport.com/pub/na/14958

Which biotech companies will take off in 2013? To zero in on possible winners, The Life Sciences Report teamed up with Sagient Research to crunch the numbers for companies with potential catalysts on the calendar. The results were sent to experts who, based on their experience in the space, could determine which companies have the best chances for upward stock price movement. The result is the groundbreaking Life Sciences Report Watchlist 2013. In this exclusive article, you can follow the thought process that went into generating the short list, and learn more about the potential winners and what they are poised to accomplish in the next 12 months.

There is a noticeable urgency in the air, as evidenced by the U.S. Food and Drug Administration's (FDA) approval of eight new drugs in December 2012. Legislation passed in 2012 has spurred FDA to cut through red tape, enabling more drugs to clear regulatory hurdles and ramping up the drug approval process. (For more on the FDA approval process and related catalysts, click here.)

"The FDA has canceled Advisory Committee (AdCom) panel meetings recently," says John McCamant, editor of the Medical Technology Stock Letter. For instance, the AdCom for Celgene Corp.'s (CELG:NASDAQ) multiple myeloma candidate pomalidomide was canceled. "It shows you that the FDA is not going to waste time," he says. "It makes me feel better about the FDA going forward, because I know [it is] trying to do a better job to work with companies and not waste taxpayer dollars."

New drug approvals are now apt to emerge like surprise packages. For example, in mid-December, Ariad Pharmaceuticals Inc.'s (ARIA:NASDAQ) Iclusig (ponatinib) was approved for chronic myelogenous leukemia (CML), a full three months ahead of its scheduled Prescription Drug User Fee Act (PDUFA) meeting date, on the strength of its ability to target the tyrosine kinase BCR-ABL and its mutants, which confer resistant immunity to tumor cells. The need was there, and the FDA responded without the previously endemic bureaucratic mire.

Catalysts and Stock Volatility

Given that the FDA normally follows AdCom panel recommendations, AdCom events are probably the most defining of all regulatory steps. It follows that share price volatility would be at least, if not more, volatile for AdCom recommendations than for the PDUFA date decision (see tables: Advisory Committee Volatility and Price Movements on PDUFA Dates 2012). By the time the panel meets, drugs under consideration have come through trials and the sponsor companies presumably feel good about their prospects. On the other hand, two days before the panel meeting the FDA disseminates a set of briefing documents to the public and to the committee. Sometimes these briefing docs, which contain background, safety and efficacy data, look like an indictment. Concerns about the potential dangers of a n ew drug are a major component of these reports. Recommendations are presented at the end of the report, and they may include the need for additional studies and warning labels.

The two- or three-day span between briefing document presentation and the AdCom panel vote can be very volatile for a company's stock (see table: Advisory Committee Volatility). "What's interesting here," says Sagient Research Systems Inc. Vice President Michael Hay, "is that people are unable to read the tea leaves from the briefs." Hay, who manages the BioMedTracker analyst team at Sagient, adds, "We've analyzed a lot of briefs before the AdCom meetings, and over the last three years we have found it rather difficult to predict the outcome of the panel vote from the briefs. A lot of ti mes stocks move the opposite way from what you think, and the AdCom has overall become just as volatile as phase 3 data."

The PDUFA date is the last step in the approval process. One might casually think that a drug approval would result in big buying of shares. But stocks sometimes selloff because the good news has been baked in from the results of the AdCom—or even from pivotal phase 3 data—and investors may not envision any more near-term catalysts. Other issues, such as the FDA placing an unexpected restriction, or perhaps a "black box" warning, on the drug label, can also cause a stock to sell off. This happened when Ariad's Iclusig was approved on Dec. 14; its black box warning resulted in a 20% sell-off. Some analysts and observers expect lower volatility in the future because there will be more predictability; this is due in part to provisions of PDUFA IV, a 2007 renewal of legislation that improved the FDA's authority and expanded its resources appreciably—which is hopefully now part of FDA's culture and regular way of doing business.

Looking for Ideas with Upside

While certain disease indications seem to wax and wane over time, oncology is always near to or at the top of company pipelines and the FDA's list of potential approvals. The volume of phase 2 and 3 clinical trial data in the cancer arena consistently outweighs other categories dramatically. According to data gathered and crunched by San Diego-based Sagient Research's BioMedTracker, the oncology category will comprise nearly 28% of phase 2 and 3 events with large impact potential in 2013 (see table: Where the Focus Will Be in 2013). In 2012, phase 2 and 3 oncology trial data moved stocks up approximately 9% and down by 15.1%, depending on the news and what was expected. However, for all disease categories in 2012, stocks were up 11.4%, versus 14.75% on the downside, when trial data were reported (see table: Ups and Downs on Trial Data in 2012).

The idea is to not get caught in last year's trailing trend. Hepatitis C (HCV) was the rage in 2010 and up until the beginning of 2012, but then Gilead Sciences Inc. (GILD:NASDAQ) made the big buy, acquiring Pharmasset Inc. and its nucleotide GS-7977 (sofosbuvir), which will be tested in many different combinations.

"Hepatitis C just doesn't do a lot for me right now," says McCamant. "It got bought out and played out, and you just don't have the pure players left." But McCamant does want to talk about gene therapy.

"Researchers started out way too aggressive and tried to bite off more than they could chew," McCamant says of the gene therapy sector. But "we're finally seeing gene therapy come to fruition." He's talking about Sangamo BioSciences Inc. (SGMO:NASDAQ), which is currently in a phase 2 study with a potential "functional cure" for HIV. The idea is to edit or modify the gene that encodes for the protein CCR5, employed by HIV to infect T-cells. If the cells don't express CCR5, then they are infected at a lower rate when exposed to the virus. Sangamo's market valuation more than doubled to $325M in 2012, but McCamant thinks it can go much higher. "There will be some phase 2 data this year," he says. "This is getting closer to a cure for HIV."

McCamant also sees market-moving data coming from Pharmacyclics Inc.'s (PCYC:NASDAQ) drug ibrutinib (PCI-32765), a small-molecule Bruton's tyrosine kinase (BTK) inhibitor. Ibrutinib is close to entering phase 3 for chronic lymphocytic leukemia (CLL), and is being tested in mantle cell lymphoma and diffuse large B-cell lymphoma. "At the American Society of Hematology (ASH) meeting in December, the phase 1b/2 and phase 2 data in CLL just blew people away," says McCamant.

"You don't get cancer drugs that are this effective," he says. "This is the best drug candidate I've ever seen. The drug is going to be the monotherapy and combination therapy of choice." Senior Analyst and Managing Director Michael King of JMP Securities is also very interested in Pharmacyclics, and he knows that investors' ears are tuned into any new data. He refers to ibrutinib and its target BTK as a "very seminal discovery" in medicine. "We think ibrutinib is going to be a big winner over time. It's certainly changing the paradigm for CLL treatment."

Raghuram "Ram" Selvaraju is managing director and head of healthcare equity research at Aegis Capital Corp. in New York City. He believes there is untapped value in companies that have launched new products. In this case the catalysts are product sales, which, after all, are what all the years of drug development time and expense have been leading up to. He likes Amarin Corp. (AMRN:NASDAQ) for its hypertriglyceridemia drug Vascepa (icosapent ethyl). He believes sales will surprise investors. It's the same story with Medivation Inc.'s (MDVN:NASDAQ) Xtandi (enzalutamide) for prostate cancer and with Ariad's Iclusig.

He is positive on the outlook for Synergy Pharmaceuticals Inc. (SGYP:NASDAQ) following the release of favorable phase 2/3 data with the company's lead drug candidate, plecanatide (SP-304) in chronic idiopathic constipation. Plecanatide is considered a risk-mitigated asset at this juncture, because it shares a mechanism of action with the recently launched drug Linzess (linaclotide), which is being marketed in the U.S. by Ironwood Pharmaceuticals Inc. (IRWD:NASDAQ) and Forest Laboratories Inc. (FRX:NYSE).

Selvaraju has some interest in the infectious disease space, and particularly in antibiotics, where it has been particularly difficult to get new drugs approved in recent years. He refers to Trius Therapeutics Inc.'s (TSRX:NASDAQ) product TR-701 (tedizolid phosphate) as "the best of the bunch." Phase 3 data for skin and skin structure infections are expected in Q1/13. "The results from this trial are likely to be positive based on findings from the first pivotal trial," Selvaraju says. "But it is unlikely to show numerical superiority to Pfizer Inc.'s (PFE:NYSE) Zyvox (linezolid) on a clinical cure rate." Given the FDA's concerns over development of new resistant strains of bacteria and the ensuing need for new bactericidal and bacteriostatic agents, non-inferiority in an antibiotic could be a satisfactory endpoint, all other factors being equal. Regulators worldwide, including the FDA and the Centers for Disease Control, are keen to have new antibiotics in the wings for patients whose infections are resistant to older products, not to mention having the insurance that new agents might provide against potential pandemics.

In addition to his interest in Pharmacyclics, JMP's King is watching Ariad's launch of Iclusig. "A lot of people are looking to see how well it does," he says. He's also got his eye on Navidea Biopharmaceuticals Inc. (NAVB:NYSE), a smaller name. Its imaging agent Lymphoseek (technetium Tc 99m tilmanocept) was developed for use during surgery to spot disseminated disease in lymphatic tissues with a gamma detector. "It will hopefully get approved in the early part of this year and then have a good launch," he says.

"To see The Life Sciences Report Watchlist 2013, click here."

King thinks Celsion Corp. (CLSN:NASDAQ) will move on the strength of data from the company's pivotal phase 3 HEAT trial for its chemotherapy agent ThermoDox (encapsulated doxorubicin) in hepatocellular carcinoma (liver cancer). Doxorubicin is a long-approved and commonly used chemotherapy agent. Licensed from Duke University, Celsion's new technology involves the use of doxorubicin-containing liposomes that are triggered to release their cytotoxic payload in diseased tissue when the temperature is raised just slightly above body temperature. More chemo can be delivered to tumors with less overall circulating toxicity to the patient. The primary endpoint of the study is progression-free survival, with a secondary endpoint of overall survival. Data are expected at any time.

King believes there is tremendous upside in Onyx Pharmaceuticals Inc.'S (ONXX:NASDAQ) Kyprolis (carfilzomib), which was approved in July for multiple myeloma. The product's launch will surprise investors, he says, noting that compared to Takeda Pharmaceutical Co. Ltd. (TKPYY:OTCPK) franchise drug Velcade (bortezomib), "Kyprolis is an all-around better drug." He believes the bigger competitor to Velcade will ultimately be Celgene's pomalidomide, which is now in phase 3 for both multiple myeloma and myelofibrosis. But Kyprolis' performance has been excellent in phase 2, according to data from the American Society of Hematology (ASH) annual meeting. "In the newly diagnosed myeloma patient population, it is getting remarkable results—100% response rates in some cases," King says.

Attacking at the Gene Level

Excluding surgery and other physical interventions, the first 6,000 years of scientific medicine have produced two modalities of therapy that are in use today: the small molecule and the biologic, the latter of which encompasses the monoclonal antibody revolution of the last two decades. Both the small molecule and the antibody target or inhibit proteins.

Now a newer technology, referred to as antisense, which includes RNA interference, uses oligonucleotides to prevent or modify protein synthesis right at the gene level. Investors are generally familiar with antisense pioneers Alnylam Pharmaceuticals Inc. (ALNY:NASDAQ) and Isis Pharmaceuticals Inc. (ISIS:NASDAQ), both of which have advanced clinical-stage assets, huge pipelines and big pharma partners. Sangamo BioSciences fits the genetic modification profile as well. Referring to the antisense industry in general, JMP's King says, "I like to say we're in an RNA world these days, and these oligo companies are the antibody companies of two decades ago."

Sarepta Therapeutics (SRPT:NASDAQ) has entered the clinic with its dramatic morpholino exon-skipping technology, which has made broadcast and newsprint headlines on the basis of a small clinical trial. The aim of Sarepta's eteplirsen is to skip exon 51 in the dystrophin gene, enabling it to synthesize a serviceable form of dystrophin that supports muscle strength. The absence of dystrophin is the causal factor in Duchenne muscular dystrophy (DMD), which occurs in about one in 3,500 males, the majority of whom lose the ability to walk early in life. The disease is ultimately fatal.

"Eteplirsen has proven to be active and quite exciting in DMD," says King. However, he notes that there is no lack of competition in this rare disease indication. Prosensa (private) is developing PRO051, another proposed exon-51 skipping therapy that is in a phase 3 trial, and there are others as well. As for upcoming catalysts, there was some thought that Sarepta would file eteplirsen early in hopes of accelerated approval, but given that the product would be a chronic therapy given early in childhood and presumably through to life's end, the FDA is apt to be cautious. "We do think the data look promising," says King's colleague Heather Behanna, associate analyst at JMP. "But we think it's highly unlikely, with this small sample size, that the FDA is going to give eteplirsen accelerated approval. Obviously, there is huge upside if it did, but we don't see it as likely."

King is curious about any interesting company he can find. He's watching Hyperion Therapeutics Inc. (HPTX:NASDAQ), which he does not currently follow. The company is developing HPN-100 (glycerol phenylbutyrate) for urea cycle disorders (UCDs), which he refers to as "ultra-orphan" indications. UCDs result from a protein or enzyme deficiency in the urea cycle. Ammonia is produced during protein metabolism, and if allowed to accumulate instead of being excreted in urine, it acts as a powerful neurotoxin and the buildup can result in irreversible brain damage, coma and death. King points out that Hyperion's HPN-100 is in a phase 3 trial; data should emerge this year and will tell the story.

Prana Biotechnology Ltd. (PBT:ASX) is taking on serious neurodegenerative diseases that disrupt the lives of patients and their families. The company has a miniscule $70M market cap, and shares should move dramatically on positive data. Results of phase 2b studies of the company's orally bio-available PBT2 small molecule for the treatment of Huntington's disease should be forthcoming in H2/13, and from an Alzheimer's disease trial by the end of Q4/13. "This represents one of the biggest risk/reward opportunities of 2013," says Senior Biotechnology Analyst George Zavoico of MLV & Co. "We are awaiting proof of concept and if it pans out, it should position Prana for a major partnership deal."

Peregrine Pharmaceuticals Inc. (PPHM:NASDAQ) has been on a roller-coaster ride in 2012. Equivocal results from a frontline non-small cell lung cancer (NSCLC) phase 2b trial of its phosphatidylserine-targeting antibody, bavituximab (in combination with carboplatin and paclitaxel) undermined its stock in March. This was followed by positive results of a second-line NSCLC phase 2b trial of bavituximab (in combination with docetaxel), which caused the stock to skyrocket in May—only to be torpedoed by the discovery that there was a coding error in that trial in September. "This was an incredible stroke of bad luck," says Zavoico. "Peregrine has been investigating the error for more than three months, and on Jan. 7 reported that it expects to salvage the trial results, providing justification to move forward to an end-of-phase 2 meeting with the FDA and a pivotal phase 3 trial that c ould start by midyear." With the positive results confirmed, a partnership deal could also be forthcoming, Zavoico added.

Attacking with Vaccines

Observers and investors have been focused on Celldex Therapeutics (CLDX:NASDAQ) mostly for its peptide-based therapeutic vaccine rindopepimut, which targets EGFRvIII-expressing brain tumors. A phase 3 trial is under way but news flow will be limited to enrollment updates for a while. However, the company's pipeline is rich beyond rindopepimut, and valuation expansion could be driven by the development path for CDX-011, an antibody-drug conjugate targeting glycoprotein NMB, a protein expressed by tumors in several cancers including melanoma and breast cancer. Data for CDX-011 was highlighted at the San Antonio Breast Cancer Symposium on Dec. 8, 2012. "The company has been in discussions with the FDA regarding the development path for CDX-011, and we believe the outcome could add incremental value to the shares," says Cantor Fitzgerald Senior Biotechnology Analyst Mara Goldstein, who follows Celldex.

"The company will know what the scope of its phase 3 program will be like after this meeting," she continues. "It is important because it speaks to whether or not Celldex can undertake the program alone or whether it would need further funding and/or a partner to undertake a registrational program. The outcome of the meeting should produce guidance regarding size of the phase 3 trial, such as 150 patients versus a much larger program. This directly affects cost and time, both of which are critical to investors."

Small-cap Galena Biopharma Inc.'s (GALE:NASDAQ) lead program is NeuVax (nelipepimut or E75), a vaccine being tested in early-stage breast cancer patients whose tumors express low levels of HER2 (HER2 1+ and HER2 2+), who have been treated conventionally via surgical resection/chemotherapy/radiation, and who are determined to be disease-free upon completion of treatment. The idea is to prevent recurrence of disease due to micrometastases through immunization against HER2 expression in women deemed at risk after treatment with standard of care.

The company presented updated results from its phase 1/2 study of NeuVax in women with early-stage breast cancer at the San Antonio Breast Cancer Symposium. "The data continue to show consistency of results supporting the rationale for a larger phase 3 study," says Goldstein. The company could update enrollment during H1/13 on a 700-patient trial called PRESENT. Patients will receive an intradermal injection once each month for six months, followed by a single booster every six months, until either the trial ends (36 months) or there is disease progression. The endpoint for PRESENT is disease-free survival after three years. Galena is now in the process of enrolling sites and patients.

"This is a pretty aggressive target in terms of enrollment, with that number of patients in more than 100 sites in the U.S., Europe and Asia. We think it is achievable, considering that there is such a large, motivated base of patients who want to prevent recurrence of disease," she says. "The NeuVax PRESENT trial will account for the largest component of the company's future valuation, and this is what we are focused on right now. Any update will help investors gauge the development time horizon, and that's important because this is a company with a current modest valuation, even though it has a late-stage asset."

A Large-Cap Option

Larger-cap stocks are normally big-picture stories about execution, downsizing and buybacks, so it's most unusual to hear an analyst talk about a large-cap play based on upcoming events that typically move small-cap shares. "Celgene Corp. kicked off 2013 with positive clinical data for the new drug apremilast (for treatment of psoriasis) and encouraging financial guidance, but there is near-term news flow expected this quarter," says Goldstein. "Data presentation of Abraxane for use in advanced pancreatic cancer was expected at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium (on Jan. 25), and the magnitude of clinical benefit is likely to be a driver of share price movement."

Celgene already has a strong presence in multiple myeloma with Revlimid (lenalidomide), and it now has a new one on the horizon with Pomalyst (pomalidomide), which has a PDUFA date set for Feb. 10. The likelihood of approval is high since pomalidomide not only shows good efficacy, but also gets good response in Revlimid-refractory patients. Revlimid is still a huge product for Celgene, but it is not approved for first-line use in multiple myeloma. A readout of the MM-020 study is scheduled to be completed in Q1/13, and this could pave the way for first-line use of the drug in the U.K. "If MM-020 is received favorably by the European regulators, it would certainly speak to Revlimid's ultimate market size. The trial is examining Revlimid in combination with dexamethasone in newly diagnosed patients," says Goldstein.

Immunotherapy Gets Hot

After a long period of failures and unspectacular successes, immunotherapy has become a hot area for investors who hold hope that some of these newer technologies can work, even in very tough indications like pancreatic cancers. A novel program at NewLink Genetics Corp. (NLNK:NASDAQ.GM) is more than two years into a phase 3 trial, and is being conducted under the FDA's Special Protocol Assessment and Orphan Drug designation. The product is HyperAcute Pancreas (algenpantucel-L), which contains two separate allogeneic (not from the patient, but from another human) pancreatic tumor cell lines that have been genetically engineered to express alpha-Gal (alpha(1,3)galactosyl) on cell surfaces, which is not expressed in native, spontaneously occurring pancreatic cancers. Patients who have had a surgical tumor resection receive up to 18 immunizations of 300 million immunotherapy cells, along with standard-of-care therapy. The investigators' operating theory is that when the product is administered, the patient's immune cells are activated and antibodies form against both the therapeutic and native tumor cells to destroy them both.

"NewLink is a company that I recommend because I feel that the stock price valuation does not adequately reflect the promise of the pipeline," says Goldstein. "There is a significant milestone upcoming, which is the interim review for the phase 3 trial called IMPRESS in surgically resected pancreatic cancer." The primary endpoint is overall survival, and the trial, which began in May 2010, is now more than halfway to its estimated enrollment mark of 722 patients, which will trigger an interim analysis that is expected by mid-year 2013. "The interim analysis will be a significant milestone because it will be the first opportunity to remove futility from the list of possible outcomes," Goldstein says. "We also anticipate that NewLink will begin additional late-stage trials in other cancer indications this year."

A Longer View

A lot of attention has been deservedly heaped onto ImmunoGen Inc. (IMGN:NASDAQ). The company's licensee is expected to get approval for its antibody-drug conjugate T-DM1 (trastuzumab emtansine), for metastatic breast cancer patients whose tumors overexpress HER2, sometime before H2/13. But the problem for the company, which already has a $1.1B market cap, is the low, single-digit royalty rate it will derive from partner Roche Holding AG (RHHBY:OTCQX), which is developing the product.

Although great technology platforms can produce many candidates, and the company has its own pipeline in addition to those being developed by partners, there is limited visibility as to how such an occurrence will change the near-term picture for investors. "Beyond T-DM1, there is a lag in time to another commercial product," says Goldstein. "And that means the company is likely to continue to incur losses for some period of time. We think the broad applicability of the technology is compelling, but the cost of developing a proprietary product is expensive."

"You could see some phase 2 data emerge for IMGN901 (lorvotuzumab mertansine) for small cell lung cancer (SCLC) in late 2013," Goldstein adds. "There has been little advancement in new drugs to treat SCLC in the past 20 years, so a positive phase 2 trial could be an important driver of valuation for the shares."

Sunesis Pharmaceuticals Inc. (SNSS:NASDAQ) has little visibility for market-moving data over the next couple of quarters, but its pivotal drug vosaroxin (formerly voreloxin) for acute myeloid leukemia (AML) will complete a phase 3 trial in the early part of 2014. It's possible that some data could emerge from an ongoing European trial sometime this year, but "the big catalyst will be the unblinding of the vosaroxin VALOR trial data, which is not likely to happen in 2013," says Goldstein.

Click here to see The Life Sciences Report Watchlist 2013.



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