Scholar Rock Holding Corporation Common Stock Canaccord Genuity's 46th Annual Growth Conference

Thanks for being here. Well, thanks, Gary, and it's wonderful to be with all of your clients here at the conference.

As I was noting, it's always fun when it's a home game for us, just across town from Cambridge to Boston. As Gary noted, we will be celebrating our 15th anniversary as a company this year. This is my 10th year as board chairman and second as CEO, and we certainly are excited to again be on the clock with the FDA, with a PDUFA date of September 30th to usher in the next era of innovation in treating children and adults living with SMA, and that would be the world's first muscle-targeted therapy to be potentially approved by the FDA. Not that anyone is counting, but it is 49 days and counting. Anytime between now and September 30th, we're ready to go.

Gary, you raise a really important point, and that is that myostatin is not a new target. It was discovered at Johns Hopkins about 30 years ago, in 1997, as a growth factor that is released from muscle, and it is the body's natural negative regulator of growing muscle. Since that very exciting discovery, nearly all pharmaceutical companies have actually developed a strategy or a product candidate to develop to try to inhibit myostatin. In fact, Wyeth was the first company to put a myostatin inhibitor into the clinic. That was way back in 2004, before the acquisition by Pfizer. Since then, there has been somewhere between 10 to 15 approaches, as I said, from many household names in the pharmaceutical industry, and they have all failed.

We thought when we started Scholar Rock, we knew the reason why they failed, and that is that myostatin, both the mature form of the growth factor of the protein as well as the receptor, resembles other TGF-β superfamily growth factors. If you develop either a trap or an antibody to target myostatin or the receptor, you are likely to have really unwanted off-target effects that could impact either safety or efficacy. We, as a company, had determined that when myostatin is released from the muscle, it is actually so potent that it has actually got a protective chemical cage. It is the latent form of myostatin. The interesting thing is, when the body needs it, the cage opens up and the mature myostatin is released.

We said, "Boy, there is nothing in the body that chemically resembles the propeptide or latent form of the disease, so let us develop an antibody to the latent form of myostatin." We have exquisite selectivity to that and are able to completely inhibit myostatin in patients. This was a product we brought into clinical development, healthy volunteers in 2018, brought into clinical development in SMA in 2019. It has been a rigorous, long development program, and I am really proud to say now, seven, eight years later, apitegromab is the first and only myostatin inhibitor to ever have been proven to be successful- in a phase III registration trial in any disease.

In this case, we specifically chose SMA, spinal muscular atrophy.