Damora Therapeutics 3rd Annual Healthcare Innovation Conference

Sure. Thanks, Rosie, for having us here today. Hi, everyone. Before I get started, we're going to be making some forward-looking statements, so refer everyone to our latest SEC filings for risk factors and other information. My name is Sherwin Sattarzadeh. I'm the Chief Operating Officer at Damora. Becker Hewes, Chief Medical Officer. We worked together at Blueprint Medicines before this, working on bringing an important medicine to market in the hematology space. Damora is in the MPN space. We are advancing a portfolio of potential best-in-class antibodies for the treatment of essential thrombocythemia and myelofibrosis, both of which are severely debilitating diseases. I think many people know about myelofibrosis, which causes the bone marrow fibrosis leading to reduced overall survival, and ET is a very serious disease that comes with the risk of thrombosis and hemorrhage, and the risk of progression to myelofibrosis.

DMR-001 is our lead asset and is an Fc-null antibody that is a pan-mutant inhibitor with a long-lasting half-life that compares favorably against the lead competitor molecule in the space at the moment that has completely or significantly de-risked the biology, and we are looking to advance our program forward in those two indications. MPNs are a very large market opportunity with over a $5 billion U.S. opportunity alone. We'll talk a little bit about the prevalence of the different mutCALR mutations, but this is about a 45,000-patient population in the U.S. that currently does not have any symptom, any disease-modifying therapies, and really the therapies right now are just symptomatic improvement agents. We've recently started our phase I study. It's called CLARITY-101. It'll be a global study.

It's in the U.S. and Australia already, and we'll be rolling out more broadly beyond that, and we're looking to very rapidly move this DMR-001 through dose escalation and into expansion to bring it to patients with both Type 1 and non-Type one patients that are waiting for this therapy. Lastly, I'll just say we have $530 million in cash and have built a team of highly experienced hematology oncology drug developers, and we'll be moving the program quickly towards phase III, which we anticipate starting in mid-2028.

Yeah. Myelofibrosis therapies have been around for some time, about 10, 15 years now, and generate billions of dollars worldwide. These are primarily JAK-directed therapies, and there have not been disease-modifying therapies for mutCALR patients. After JAK, mutCALR makes up the next largest group of patients, with about 25% of ET patients having a CALR mutation and about 35% of MF patients, amounting to about 45,000 patients worldwide. The current therapy, our lead competitor, Incyte 989, has really de-risked the biology in the space and has demonstrated that an Fc-null targeting agent in looking at mutCALR is a viable path to treating these patients. Unfortunately, the activity of that agent right now is really in the Type 1 patients and less so in the non-Type one patients, as well as its limitations on its PK profile, its high dose, and frequent volume of route of administration.

We're looking to bring forward DMR-001 with an every four-week subq administration, pan-mutant activity, as we've recently talked about and we'll be talking about more as ASH data is presented, for the broader patient population.

I think what has been shown thus far is that the targeting of mutCALR with the Incyte molecule has clearly demonstrated that you can gain good activity for both ET and MF patients, and yet there is about 50% of the population who have the non-Type one mutations that really are not seeing the same level of benefit as what DMR-001 can bring. What we have also done is improve the PK profile relative to what they have been able to show to have a much longer-lasting antibody that can be dosed far less frequently than 989 can.

I mean, I think the preclinical data that 989 demonstrated is really playing out in the clinic as was originally expected. Their shorter half-life, their potency primarily on the Type 1 molecule really gives us confidence that our preclinical profile will be able to address those limitations as we move it forward. What we want to see is particularly in the early part of the study is to see that translation of our PK profile, of our preclinical profile into the clinic. We will be looking at that activity across mutations. We will be looking for that validation of the PK half-life in humans, to really lend proof to the differentiation of this molecule.

Yeah, I can start on that.