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Long time readers of my columns know that I take a "shotgun" approach to biotech investing. Due to the volatility and high failure rates of developing new compounds I think it is only wise to take much smaller allocations in a larger array of companies than I would in other sectors.

An investor must also accept that some of their bets are not going to play out and some companies will fail and go bankrupt. Fortunately, when a winner emerges it can easily double or triple in a relatively short amount of time. Two of my best performing recommendations have come from the biotech sector. Novavax (NASDAQ:NVAX) has more than tripled since I profiled it in March of 2012. Pacific Biosciences of California (NASDAQ:PACB) is up more than 150% since I highlighted it this March.

In this article I will update a couple of my previous profiled biotech companies. Here are two more bold speculative biotech plays.

Geron Corporation (NASDAQ:GERN) is a biopharmaceutical company that develops biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, and diabetes. The stock has almost doubled since I wrote a piece on it in late February but still could have upside. GERN did little for six months but has rocketed up in September.

There have been a couple of catalysts behind the stock's stellar rise. In early August, the company reported new details from studies on imetelstat as a treatment for myelofibrosis (a blood disorder), that investors viewed as positive. Piper Jaffray upgraded the stock from "Neutral" to "Overweight" soon thereafter.

This week a speculator took a large bullish call spread position in the shares and must be expecting good news from a Mayo Clinic study on imetelstat. I have sold half my position simply because no one ever went broke taking some profits. I am letting the rest ride as imetelstat could be a game changer if it turns out to be effective.

In addition, the company has $70mm in cash on the balance sheet to get through trials. Insiders are not selling even with the recent run up in the stock which I view as another good sign. If imetelstat continues to generate positive results, it would not surprise me if the company became an acquisition target for a larger player.

Navidea Biopharmaceuticals (NYSEMKT:NAVB) is a biopharmaceutical company, and focuses on the development and commercialization of precision diagnostics and radiopharmaceutical agents. The stock has done little since I highlighted it in March, but I am still positive on the company's prospects.

Navidea is making progress on a variety of fronts. The company recently reached an agreement with the FDA over the design, endpoints and statistical analysis for two Phase III trials of the company's NAV5001 imaging agent in diagnosing Parkinsonian Syndromes from non-Parkinsonian tremor. Navidea also signed with Siemens to manufacture its AV4694 PET imaging agent, which is in Phase II and Phase III trials for evaluating patients with signs of Alzheimers disease and mild cognitive impairment.

The median price target held by the 8 analysts that cover the stock is $5 a share, ~80% above the current stock price. Insiders have been net buyers of the stock this year and revenue is projected to accelerate to $20mm in FY2014 after posting ~$4mm in sales this fiscal year. The company recently raised almost $30mm so funding is there until sales/cash flow increase in the years ahead.

Source: 2 More Bold Speculative Biotech Plays