Preheat the oven to 350 degrees F. Move a rack to the middle of the oven. Coat a 9-by-13-inch baking dish with nonstick cooking spray.
In a large pot set over high heat bring 1 gallon of water with 2 tablespoons kosher salt to a boil. Add the penne and cook 2 minutes less than the package directions, stirring occasionally. The pasta will be slightly underdone. Use a measuring cup or ladle to remove 1/3 cup pasta water and set aside. Drain the pasta into a colander. Return the pasta to the pot and set aside.
Melt 4 tablespoons of the butter in a large skillet set over medium heat. Add the flour and cook for 3 to 4 minutes, whisking constantly. Pour in the milk, whisking constantly until the mixture starts to thicken like heavy cream and then becomes almost pudding-like, 2 to 3 minutes. Add the shredded cheese and whisk until smooth, the sauce will be very thick. Add the nutmeg and season with some salt and pepper.
Combine the asparagus, pasta, reserved 1/3 cup pasta water and cheese sauce and toss well. Season with salt and pepper, then transfer to the prepared baking dish and top with a layer of the cheese slices. Cut the remaining 2 tablespoons butter into 1-inch cubes. Sprinkle the panko over the cheese slices, and top with the butter cubes. Bake until the top is golden brown and crisp, 20 to 25 minutes. Remove from the oven and cool for 10 minutes before serving.
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