Biotech looks set to close out 2015 as its worst performing year since 2008. That may sound bad, but despite this, the iShares Biotechnology Index ETF (NASDAQ: IBB) is still up over 11% year to date. Not bad for a relatively bad year.

Can we expect a better 2016 for this exciting sector? It has gotten some negative focus lately due to the buy-and-raise antics surrounding a certain controversial biotech CEO named Martin Shkreli who, to add insult to injury, just happened to get himself arrested on charges of securities fraud. Overall though, there are too many exciting late-stage trials going on for biotechs large and small that could materially change the sector for the better.

Here are four biotech picks for 2016 that present a balance of both risk and stability for the new year.

Roche

Roche, which is traded over the counter, is s staple of any diversified biotech portfolio. At $229 billion in market cap, its stability and dominance are as rock solid as you can get in the sector. What makes Roche an especially interesting choice for 2016 though is the new technology it got access to via a partnership with private firm SQZ Biotech for $500 million.

The technology is quite simple conceptually. It’s called CellSqueeze, and what it does is force blood though a capillary so tiny that it squeezes the cell membranes so they become porous. While in the capillary tube they can absorb any other molecule put in there together with it. What Roche and SQZ are trying to do is get immune cells in the blood to absorb certain cancer markers that will enable them to recognize tumors and destroy them. Preclinical studies show that this method is much more effective than any other known method of opening up cell membranes, in terms of the number of cells it can implant and that survive the process.

This is normally the kind of risky innovation you’d find with a trial stage biotech, so the opportunity to invest in what could be a disruptive technology through a large cap like Roche is not very common.

Amgen

This biotech staple may not inspire too many oohs and ahhs in terms of original stock picks, but there is something going on behind the Amgen Inc. (NASDAQ: AMGN) curtain that makes it a little bit more than a bland large cap allocation for 2016. That is, its focus on biosimilars. Biosimilars are biologics that seek to replace an existing therapy by proving no meaningful clinical difference in efficacy. They are cheaper to develop and already have proven markets.

Amgen has three late stage biosimilars in its pipeline, all in Phase 3 or having already completed it. Two of them seek to compete with Roche blockbusters. One is a biosimilar of Avastin, which sold $6.6 billion last year, and the second looks to replace Herceptin, both cancer treatments. The third, APB 501, already has been filed for approval, having met its Phase 3 endpoints for biosimilarity to Humira. This, combined with Humira’s imminent patent expiration, means Amgen could capitalize well on APB 501 in 2016.

Valeant

After getting crushed following alleged accounting fraud, Valeant Pharmaceuticals International Inc. (NYSE: VRX) is now 62% off its lows, but still more than 57% off its highs. The fact that it fell so badly may have been catalyzed by the buy-and-raise regulatory fiasco that Valeant is heavily involved in, but the meat of the decline was more likely due to allegations of double counting revenues.

Those allegations seem to be blowing over for now and investors look to be forgetting about them, meaning Valeant is likely to continue slowly floating back up to a more familiar price in the upper hundreds as 2016 progresses. It was trading at $112 as of December 17.

Bluebird Bio

A more speculative pick than the other three, Bluebird Bio Inc. (NASDAQ: BLUE) is one of the leaders of the CAR-T space, or chimeric antigen receptor T-cells. The basic concept of this technology is sticking on an artificial, or “chimeric” antigen receptor onto an immune cell to recognize cancer, similar to what Roche is doing with SQZ, just with a different method.

The CAR-T space generated waves of investor enthusiasm this year, but a look at a chart of Bluebird Bio will show that enthusiasm has died down. Nothing has changed with the prospects or the science though, and Bluebird Bio is knocking up against support. So if you’re looking to get into the CAR-T market and you were hitting yourself over the head for not buying when these stocks were showing triple-digit gains, 2016 may be the time to buy low.

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