The Small-Cap Biotech Watchlist 2015 Unwrapped: Who Are These Guys? And Why Are They Here?

The panelists asked to select the 2015 Small-Cap Biotech Watchlist included George Zavoico of MLV & Co., Joe Pantginis of ROTH Capital Partners, Bert Hazlett of Ladenburg Thalmann & Co., Reni Benjamin of H.C. Wainwright & Co., and moderator Mara Goldstein of Cantor Fitzgerald. Each selected two to three names for the 2015 list, and described the compounds, platforms and catalysts that made them attractive investments.

The Watchlist Selections

MLV & Co.'s George Zavoico selected Peregrine Pharmaceuticals Inc. (PPHM:NASDAQ), with a market cap of about $242 million ($242M), Synta Pharmaceuticals Corp. (SNTA:NASDAQ), with a market cap of about $278M and Threshold Pharmaceuticals Inc. (THLD:NASDAQ), with a market cap of about $235M. The theme? "They're all oncology companies," Zavoico said. "Synta and Threshold have small molecule drugs, and Peregrine has an antibody. These drugs have been in development for a while, and have all reached Phase 3. Considering the market caps and the phase of development, as well as the evidence of safety and efficacy to date, I see all three of these companies as being undervalued."

Peregrine's Phase 3 candidate is bavituximab, a phosphatidylserine-targeting antibody in a Phase 3 clinical trial as a second-line therapy in non-small cell lung cancer (in combination with docetaxel). Bavituximab has shown, in preclinical studies, that it "acts like an immune checkpoint inhibitor upstream from PD-1 and PD-L1 (programmed cell death 1 and programmed cell death ligand 1) and upstream from CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)," Zavoico said.

Recognizing that bavituximab could be leveraged into "what seems to be moving the whole immune checkpoint space," meaning the reversal of immune tolerance in solid and liquid cancers, Peregrine is involved in a number of Phase 1 and Phase 2 trials in different cancers and drug combinations with the compound, Zavoico noted. But the principal catalyst is the SUNRISE Phase 3 trial, which is "guided to full enrollment by the end of 2015, with topline results by the end of 2016."

Synta Pharmaceuticals "has a small molecule heat shock protein 90 (Hsp90) inhibitor called ganetespib," Zavoico said. Ganetespib is in a Phase 3 trial called GALAXY-2, as second-line therapy in non-small cell lung cancer with docetaxel. The drug candidate's unique structure means it doesn't have the toxicities associated with other Hsp90 candidates, Zavoico noted, adding that ganetespib has "emerged as the leading Hsp90 inhibitor."

Ganetespib, in combination with other drugs, is also being evaluated in a number of investigator-sponsored trials for breast cancer, rectal carcinoma, recurring ovarian cancer and mesothelioma. "These are all Phase 1 and Phase 2 trials," Zavoico said. "Many of these trials will play out with topline data and results in 2015, going into 2016. I expect considerable news flow from Synta, culminating with topline GALAXY-2 results by the end of 2015 or early 2016."

Threshold Pharmaceuticals' lead compound is TH-302, a hypoxia-activated prodrug. "The payload is an analog of ifosfamide, a DNA alkylating agent that has been an effective anticancer drug for decades," Zavoico said. "TH-302 has an efficient hypoxia trigger such that the drug circulates benignly, without causing issues elsewhere in the body. It penetrates hypoxia regions of a tumor, where the hypoxia microenvironment releases the ifosfamide analog, concentrating it where it can kill tumor cells that might otherwise evade most other therapeutic agents."

The company is in two Phase 3 trials, "one in soft tissue sarcoma (STS) with doxorubicin, and the other in pancreatic cancer with gemcitabine. The STS trial is likely to play out with topline results by Q3/15 or Q4/15, and the pancreatic cancer trial by Q1/16," Zavoico said. The company is also conducting trials in renal cell carcinoma, hepatocellular carcinoma, advanced leukemias and other cancers, mostly in combination with gemcitabine and Abraxane (paclitaxel; Celgene Corp. [CELG:NASDAQ]), which is the emerging standard of care.

In conclusion, Zavoico noted, "As a theme, all three of these companies are trying to leverage their compounds, which are unique, in multiple cancer types and typically in combination with other agents, and all of them have advanced into a Phase 3 trial. Based on the evidence of efficacy and safety, I think each one of these is worth a look and perhaps an opportunity for investment, since topline results are expected within about a year."

The unifying theme for the selections of Joe Pantginis of ROTH Capital Partners is also oncology, focusing on immunotherapy and what he calls the "hot targets area" for cancer. He put three names on the list: Lion Biotechnologies (LBIO:OTCBB; for immunotherapy), TG Therapeutics Inc. (TGTX:NASDAQ, "hot targets") and MEI Pharma Inc. (MEIP:NASDAQ; "hot targets").

Despite "the blowup of Dendreon Corp. (DNDN:NASDAQ)," Pantginis expressed enthusiasm about the prospects of companies developing cancer immunotherapies. "What's been keeping the name immunotherapy alive has been the checkpoint inhibitors, the anti-PD-1s and also the chimeric antigen receptor (CAR) T-cells."

"Right now, Lion is just beginning to scratch the surface with regard to investor visibility," Pantginis said. "We view Lion as essentially a pure play on T-cells. The company's technology was developed in the Rosenberg Laboratory at the National Cancer Institute, basically one of the grandfathers of immunotherapy." Lion has licensed tumor-infiltrating lymphocytes (TILs) for the treatment of metastatic melanoma.

"We could talk about mechanism and science all day, but it always comes down to clinical data," Pantginis said. In Lion's case, four different centers have run independent Phase 2 studies on TILs, and "in metastatic melanoma, each Phase 2 has independently shown a 50% response rate in patients, including those who have failed Yervoy (ipilimumab; Bristol-Myers Squibb Co. [BMY:NYSE]) and anti-PD-1." Pantginis expects Lion, which just filed an investigational new drug application, to run its own Phase 2 trial with the Rosenberg technology. The company is also looking to enhance its manufacturing abilities since the technology is autologous.

"If this Phase 2 is positive—if it even approaches the types of response rates that were seen in four independent Phase 2 studies—Lion could, in our belief, see a potential accelerated path or even potential breakthrough designation," Pantginis said. In addition, the technology could be applicable to other tumor types, which would bolster the long-term potential for the company. "We think this is going to be a good breakout year."

Pantginis highlighted two TG Therapeutics drugs. TG-1101 (ublituximab) targets blood cancers; the analyst likened it to "a next-generation Rituxan (rituximab; Genentech/Roche Holding AG [RHHBY:OTCQX])."

Once again, he pointed to the data: "When the company combines Imbruvica (ibrutinib; Pharmacyclics Inc. [PCYC:NASDAQ]) with TG-1101, we now are approaching 100% response rates in chronic lymphocytic leukemia patients." TG Therapeutics will start a Phase 3 study with ibrutinib later in 2015, and is looking at additional combinations. To give a sense of the potential, Pantginis shared the story of a patient who'd failed four previous Rituxan regimens and was about to be admitted to hospice. When put on TG-1101, she "converted to a complete response and hasn't looked back yet. And that was as a monotherapy. So very, very promising."

TG Therapeutics' second product, TGR-1202, is a PI3K kinase inhibitor, "again, a very hot target," Pantginis said. The drug candidate is showing "very good response rates in lymphoma patients. What's interesting is that this is a once-per-day drug, compared to twice-a-day with other drugs and, importantly, has not shown any of the liver toxicities seen with other PI3K inhibitors." He also noted that TG, with a $689M market cap, was a top-performing stock last year in biotech and is the Focus Pick of his firm. "We think the stock has room to grow here. . .these hot targets are literally just scratching the surface from TG."

With regard to MEI Pharma, Pantginis said, "This is another company, in our belief, which is starting to come into its own. Its lead product, pracinostat, is a potentially differentiated histone deacetylase (HDAC) inhibitor, and is currently being delivered for acute myeloid leukemia (AML) and myelodysplastic syndrome patients. At the American Society of Hematology conference in 2014, the company announced positive Phase 2 data in an AML study, and will be entering Phase 3 in 2015. We think one of the intriguing characteristics of pracinostat is that the clinical responses seen in the study got better over time."

Bert Hazlett of Ladenburg Thalmann shifted gears, moving out of oncology and into antibiotics. "That's a sector that has turned around dramatically over the past 36 months [because of] the pressing need for new antibiotics due to resistance," Hazlett said. "The bugs always win. That sense of urgency has been communicated by the community to our regulatory agencies and to the legislators, and has led to material changes in the sector."

Among those changes: the GAIN (Generating Antibiotics Incentives Now) Act, which has "led to rational clinical trial designs [and] improved intellectual property (IP) protection in the sector. . .then, on top of that, it's provided funding for the Biomedical Advanced Research and Development Authority (BARDA). . .As a result, we've seen multiple recent approvals. We've had multiple mergers and acquisitions (M&A) transactions. Durata Therapeutics Inc. was purchased by Actavis Plc (ACT:NYSE). Most recently, Merck & Co. Inc. (MRK:NYSE) purchased Cubist Pharmaceuticals Inc., and I think that got the attention of many in the investment community because that's big pharma."

Hazlett mentioned two names in the antibiotics arena. Cempra Inc. (CEMP:NASDAQ), with a valuation approaching $1 billion ($1B), is not a small cap, but "has a promising macrolide antibiotic, solithromycin, which just read out Phase 3. It's for community-acquired pneumonia and other indications." He also likes Paratek Pharmaceuticals Inc. (PRTK:NASDAQ), which went public in H2/14 and has a $352M market cap.

Paratek "focuses on tetracycline antibiotics, next-generation assets in the tetracycline class. It has two primary assets, one of which has more material valuation—omadacycline," Hazlett said. Omadacycline is a once-daily, intravenous and oral formulation with broad-spectrum activity and potency versus key pathogens in multiple indications, including methicillin-resistant Staphylococcus aureus (MRSA), Hazlett explained. "From a tolerability and safety standpoint, it looks very good," he said. Paratek is moving omadacycline into Phase 3 trials for multiple indications, including community-acquired pneumonia, acute bacterial skin and skin structure infections, and urinary tract infections. The drug has a "$1B profile, from what we've seen from data in prior years," he added.

Paratek's second asset, sarecycline, is a "narrow-spectrum tetracycline" targeting acne. Like omadacycline, sarecycline is taken once per day and is "very well tolerated." Partner Actavis has started two 1,000-patient Phase 3 studies, with data readouts expected later in 2015.

Hazlett's second small-cap choice is CTI BioPharma (CTIC:NASDAQ), which focuses on hematologic malignancies. "Its primary asset is a Janus kinase (JAK) 2/FLT3 inhibitor called pacritinib, for myelofibrosis. It's in Phase 3, and it's partnered with Baxter International Inc. [BAX:NYSE]." The first Phase 3 study is due to read out at the end of Q1/15, and the company intends to file for approval with the U.S. Food and Drug Administration (FDA) sometime in H2/15. "We like what we see with CTI. It's a company that's developing some novel assets in hematologic malignancies," Hazlett said.

Reni Benjamin of H.C. Wainwright & Co. added Can-Fite BioPharma Ltd. (CANF:NYSE.MKT), a micro cap with a $30M valuation, to the watchlist. The company's most advanced product is in Phase 2/3 for psoriasis—"not a slouch of a market," Benjamin said. The analyst noted that other companies, including large-cap biotech Celgene Corp., play in this field, but Can-Fite has an oral candidate that "has shown some very, very promising data" in both its Phase 1/2 trial and in an interim data release of Phase 2/3 data.

"If you don't like clinical binary risk, this is not the stock for you," Benjamin qualified. "Maybe you look at Can-Fite after the clinical data come, and then you play the potential for M&A (merger and acquisition) with this company. However, if you can stomach the risk, the positive interim results do suggest a higher probability of success for the final results. It has other trials ongoing in liver cancer and erectile dysfunction. It has $12M in cash, which does not sound like a lot, but it only burns about $1.25–1.5M/quarter. Getting past these key events—the Phase 3 data as well as a potential partnering deal—the company has plenty of cash, so you don't have to worry about a potential dilution in the near term."

Benjamin also likes OncoSec Medical Inc. (ONCS:OTCBB), which has a market cap of about $97M. OncoSec is "supercharging DNA vaccines," which has particular value in light of the current emphasis on checkpoint inhibitors. OncoSec's technology has the potential to boost efficacy of these inhibitors, according to Benjamin.

"OncoSec just started clinical trials looking at its proprietary platform in combination with checkpoint inhibitors in the hopes of improving response rates," Benjamin explained, noting that there is no data yet. But OncoSec "has significant capital, over $34M, to run several trials," as well as collaboration with Merck. "OncoSec is a company investors should keep on the radar. Data are what drive our industry, and OncoSec has data coming out at the major meetings [in 2015]. It's definitely a name to keep in mind."

Benjamin's final name is Oncothyreon Inc. (ONTY:NASDAQ), which is making a comeback despite a cancer vaccine candidate that failed in a Phase 3 clinical trial.

The company, however, now has a HER2 inhibitor targeting breast cancer. Oncothyreon's drug is "very similar to Puma Biotechnology's (PBYI:OTCBB) HER2 inhibitor, neratinib [but] appears to have a better side-effect profile," Benjamin said. The drug may be able to "carve a niche in breast cancer that's metastasized to the brain, which occurs in a significant number of breast cancer patients."

Oncothyreon also a drug delivery technology in its pipeline. "This product actually has the potential to create CAR T-cells within the body. . .by the end of this year, if that program has moved forward and in vivo models actually show what Oncothyreon hopes they will show, you're looking at potential partnering opportunities."

Mara Goldstein of Cantor Fitzgerald added three small-cap names to the watchlist.

"I cover a small gene therapy-based company called Applied Genetic Technologies Corp. (AGTC:NASDAQ; AGTC), which is working in the field of adeno-associated viral vectors," Goldstein said. "It is developing treatments for eye diseases—principally orphan eye diseases—and it should have some data and news about Phase 1 trials in the new year. We think there's a pretty good opportunity to build value in this name as clinical data begin to accrue."

AGTC also recently announced that it is exploring the field of wet age-related macular degeneration (wet AMD), which Goldstein identified as "a very hot area in the field of gene therapy. We think there's more value that can accrue to this name, and it's one we like on that basis."

With regard to Verastem Inc. (VSTM:NASDAQ), the second Goldstein selection, the analyst said, "We've liked the company's work in the field of cancer stem cells and the clinical trial programs. The most advanced, in mesothelioma, will have an important interim look, expected in Q2/15, when the company will know if resizing on the basis of biomarker information will occur. Other candidates are also moving forward, and we think that they will improve visibility on the company's valuation over the course of this year."

Goldstein's third company, Sunesis Pharmaceuticals Inc. (SNSS:NASDAQ), on the other hand, "had a major inflection point with the readout of the Phase 3 VALOR trial examining Qinprezo (vosaroxin) in AML. The trial missed significance, which appears to be a function of confounding due to transplantations. Using a prestratified grouping, the trial achieved significance," said Goldstein.

"We think there is opportunity for the FDA to accept a new drug application filing from the company given the data generated in the trial and the abysmal clinical trial history of drugs for this disease," Goldstein continued. "This, we believe, will be an opportunity to reset the valuation. Whether the FDA would be willing to approve the drug is a very large question mark, and one where very limited precedent exists to do so. However, based on other clinical scenarios that we have identified, we think there is such an opportunity, and that drives our interest in the shares in spite of the very binary nature of the next inflection point."

Another name that has caught Goldstein's attention is Radius Health Inc. (RDUS:NASDAQ). The company recently released topline Phase 3 data for its drug, abaloparatide, in osteoporosis. "They were positive data," Goldstein noted, adding "The name is an interesting opportunity. It's a nice asset. We think there are limited novel assets in the endocrine/women's health space, so that makes it very compelling. In addition to abaloparatide for severe osteoporosis, the company has a midstage candidate with applications in treating hormone-related breast cancer as well as vasomotor symptoms. . .we think there's an opportunity for Radius Health's portfolio to advance and continue to add to the valuation."

Goldstein also mentioned two companies outside the small-cap realm: Celldex Therapeutics Inc. (CLDX:NASDAQ) and NewLink Genetics Corp. (NLNK:NASDAQ.GM), both of which are in the oncology space in immunotherapy. Both also "have binary endpoints with their lead vaccine products in the next six months or so, but they've also grown their businesses sufficiently that they have other clinical assets that we think are nice offsets," the analyst said.

Celldex has a peptide-based vaccine for glioblastoma that produced "compelling Phase 2 data. . .an overall survival benefit in an immunotherapy trial in glioblastoma in a controlled setting," Goldstein said. The drug, a monoclonal antibody drug conjugate licensed to Seattle Genetics (SGEN:NASDAQ), "has shown higher overall response rates, higher progression-free survival levels," than others in the field, but the company's promise as an investment doesn't rest solely on that product. The company has a number of other assets, including one in a Phase 3 trial for triple-negative breast cancer, that balance the binary risk. Celldex "is doing a study with Opdivo (nivolumab) and also has a variety of other early-stage studies. Investors have a lot of offsets if the rindopepimut Phase 3 trial doesn't read out positively," Goldstein said.

"For similar reasons, we also like NewLink Genetics," Goldstein added. The company's platform cancer vaccine treatment is called HyperAcute, and the first product candidate is in development for pancreatic cancer. "The Phase 3 trial is likely to have an interim look in H1/15, and while there is a final endpoint analysis planned if early stopping does not occur at the interim, we think a lack of early stopping will cause investors to dismiss this trial. While we think there could very well still be opportunity, we like the offset of the company's IDO/TDO inhibitor platform in the field of checkpoint inhibition in cancer. This platform was recently the subject of a development deal with Roche, which lends credibility as well as resources to the development of such candidates," the analyst said.

2015 Small-Cap Biotech Watchlist Portfolio Tracker

The Approval Process in Action Infographic