Barclays Plc ownership in IONS / Ionis Pharmaceuticals, Inc.

The Security and Class in the table below are shown exactly as filed by the investor. We do our best to track continuity of investments through acquisitions, and this will be reflected in the table as changes in names. In addition to descriptive data, performance of the investment is shown over time. To calculate quarterly performance, we first calculate cost basis of the shares purchased during the quarter, then use that to calculate gross profit. Quarterly return is Gross Profit / Starting Portfolio value.

Note that cost basis is calculated and stored in thousands, so small quarterly changes in shares frequently result in a cost basis of zero.

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In addition to reporting standard equity and debt issues, institutions with more than 100MM assets under management must also disclose their put and call option holdings. Since put options generally indicate negative sentiment, and call options indicate positive sentiment, we can get a sense of the overall institutional sentiment by plotting the ratio of puts to calls. The chart to the right plots the historical put/call ratio for this instrument.

Using Put/Call Ratio as an indicator of investor sentiment overcomes one of the key deficiencies of using total institutional ownership, which is that a significant amount of assets under management are invested passively to track indices. Passively-managed funds do not typically buy options, so the put/call ratio indicator more closely tracks the sentiment of actively-managed funds.