These aren't the best of times for Juno Therapeutics (NASDAQ:JUNO) and Alnylam Pharmaceuticals (NASDAQ:ALNY). Both have experienced major clinical setbacks this year. Both biotechs have also lost over half of their market cap since then beginning of 2016. Which of these two stocks is the better pick for investors now? Here's how Juno and Alnylam stack up.

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The case for Juno

Just a month ago, the path for Juno's success seemed straightforward. A clinical hold placed by the FDA on CAR T candidate JCAR015 had been lifted. Enrollment in the phase 2 study for the experimental treatment of relapsed or refractory B cell acute lymphoblastic leukemia was rolling along. Juno just needed to have that study go well for a possible U.S. approval as early as mid-2018.

That path appears to be much less navigable now. On Nov. 23, Juno announced that one patient in the phase 2 study had died and another wasn't expected to recover. Two patients had died earlier in the year also, but Juno thought that the issue stemmed from the combination of JCAR015 with fludarabine and was allowed to resume the trial without the added chemotherapy.

Is there still an investing case for Juno? Yes, although it's obviously not as strong now. The odds that the biotech will be able to move forward with JCAR015 are low. Juno does have other pipeline candidates, though, most notably JCAR014 and JCAR017.

Like JCAR015, both of these experimental drugs are CD19-directed CAR T cell therapies. That doesn't necessarily mean that JCAR014 and JCAR017 will encounter safety issues similar to JCAR015, however. Both of the candidates use a 1:1 ratio of helper and killer CAR T cells, a composition that could decrease toxic side effects.

In December, Juno announced encouraging results from a phase 1 study of JCAR014 in treating patients with chronic lymphocytic leukemia (CLL) who failed treatment with Imbruvica. Based on this study, Juno plans to initiate a study of JCAR014 in combination with Imbruvica in early 2017 and potentially move forward with a study of JCAR017 in treating CLL. 

Juno has a long road ahead of it, though. With JCAR015 sidelined, the biotech's most advanced pipeline candidates are still in early stage development.  

The case for Alnylam

As with Juno, there would have been a much stronger investing thesis for Alnylam earlier in 2016. However, Alnylam announced on Oct. 5 that it was throwing in the towel for once-promising revusiran. Safety issues arose in a late-stage study of the experimental drug in treating hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM).

With revusiran out of the picture, Alnylam's hopes now rest largely on another hereditary ATTR amyloidosis drug: patisiran. The discontinuation of revusiran didn't impact the phase 3 study under way evaluating patisiran in treating hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN).

Is there reason for investors to be concerned about safety issues with patisiran? Like revusiran, the experimental drug uses RNA interference, which attempts to silence specific messenger RNA and prevent proteins that cause hATTR from being made. However, there are differences in how the two drugs are administered and how RNA interference in the liver is achieved. Alnylam's review of clinical data hasn't turned up any serious safety problems for patisiran.

Alnylam has a couple of phase 2 programs with hemophilia candidate fitusiran and hypercholesterolemia candidate ALN-PCSsc. The biotech's pipeline also includes two early stage candidates targeting genetic disorders.

Better buy

I would recommend caution with buying either of these two biotech stocks. Both Juno and Alnylam face a lot of uncertainty. However, if I had to pick one right now, my choice would be Alnylam.

Juno could eventually enjoy tremendous wins with its CD19 program. However, Alnylam simply has the higher probability of success in its favor with several products that have already advanced past early stage studies. Of course, as we saw with revusiran, anything can happen. Alnylam gets the nod over Juno for now, but significant risks remain.