How can you feel as comfortable speaking to 50, 100, or even 500 people as you do with speaking to 1 or 2? You do it by speaking to the audience 1 or 2 people at a time.
When you speak, pick out a person in the audience and speak directly to him or her for a few seconds. That person might be a friend, a colleague, or some other friendly face. Then, pick out a person at another part of the audience and speak to him or her for a second or two. Do this throughout the speech.
Not only does this make you feel more comfortable with the audience, it enables the audience to build rapport with you. The audience feels like you’re speaking directly to them (not just the people you pick out, but also the people surrounding them.) You’ll be communicating with the audience instead of just talking to them.