Palvella Therapeutics, Inc. Common Stock Canaccord Genuity's 46th Annual Growth Conference

Thank you for having me, Whitney.

Sure. Well, thanks so much for having me. This is our second year in a row having the opportunity to present at the Canaccord Conference. Appreciate your coverage. You were one of the first analysts to initiate coverage on Palvella after we went public and appreciate all your support since we have been a public company. I am going to start with the name Palvella, which in Finnish means "to serve." The mission of our company is to serve patients that have serious rare diseases, and we specifically focus on those diseases where there are no approved therapies. The strategy of the company can be summed up in a word, which is first. We want to deliver drugs that are first-approved therapies for these serious rare diseases.

The vision of the company, Whitney, is to build the enduring and leading biopharmaceutical company, addressing rare skin diseases and rare vascular malformations for which there are no FDA-approved therapies. That's obviously rare skin disease is a corridor of the orphan universe that you know well. I would describe rare skin diseases as high unmet need. There's approximately 600 rare skin diseases.

Fewer than 2% have approved therapies, but also very low competitive intensity. Those dynamics really lend itself to building a company in the space. You've referenced our pipeline and our platform. We have both a late-stage pipeline and a platform. Our late-stage pipeline, the flagship product is called QTORIN rapamycin. That is our 3.9% anhydrous formulation of the mTOR inhibitor rapamycin. Earlier this year, we read out a positive phase III study in a disease called microcystic lymphatic malformations. That's a serious, rare genetic and lifelong disease for which there are no approved therapies. There's more than 30,000 of these patients in the United States. We recently had a pre-NDA meeting with the FDA and have initiated, thanks to Jeff Martini and his team, a rolling NDA submission at the agency. Beyond that, we're going to expand the uses of QTORIN rapamycin to other mTOR-driven skin diseases.

Since we went public, we read out a positive phase II study in a disease called cutaneous venous malformations, also a type of vascular malformations, no approved therapies. These patients have this condition at birth. It is a lifelong disease. We also believe this to be driven by the mTOR pathway as well. Our third indication for QTORIN rapamycin listed on the slide here is called angiokeratomas. Thanks to our clinical operations team, we initiated a phase II study here earlier this year. That study will read out in the second half of this year. That is a type of a superficial lymphatic malformation.

More recently thought to be driven by the mTOR pathway. FDA has granted us Fast Track designation in both angiokeratomas, cutaneous venous malformations, and microcystic lymphatic malformations. We have Breakthrough designation, Fast Track designation, as well as Orphan Drug Designation. You mentioned the platform as well. We have a second molecule that we've paired with the platform, and that's called pitavastatin. Our second product candidate is called QTORIN pitavastatin. That will be studied in a serious rare genetic disease called disseminated superficial actinic porokeratosis. We're completing our pre-IND work there, our IND-enabling studies, and we expect to initiate a study there later this year. So four diseases that we're currently in today.

Really excitingly, we are going to announce two more diseases by the end of the year, such that we are going to exit this year developing programs, QTORIN and derived programs, in six rare diseases, each of which we have the opportunity to deliver that first approved therapy.

Sure. Genetics were elucidated about a decade ago. We know that we estimate close to 100% of these are driven by PIK3CA mutations. mTOR is directly downstream of PIK3CA. mTOR is hyperactivated. What does that cause? You can see in the picture here, that causes genetically malformed vessels to protrude out through the skin. The major clinical issues to these patients is that they have discharge of lymphatic fluid onto the skin. That phenomenon is called lymphorrhea. That results in the skin barrier being compromised. Because the skin barrier is compromised, these patients are prone to super infections and oftentimes have infections like acute cellulitis, and they can be hospitalized. They also, as you can see from the picture here, can bleed. So those are two of the major clinical burdens to these patients, oftentimes being in these cycle of infections.

It is proliferative and progressive, so if left untreated, clinically it should predictably get worse. There is an urgency to intervene, and the FDA considers it a serious disease, which is a prerequisite for both Fast Track and Breakthrough designations.

Great. What preceded the phase III was a phase II study. 12 patients we studied in phase II. All 12 patients improved on a clinician change scale, where all 12 patients were rated as much improved or very much improved. That was the basis upon which we designed the phase III study. It was also the basis upon which we applied for Breakthrough Therapy Designation, which was granted. The phase III study was a 51-patient study. This was our pivotal study that read out in Q1 of this year. Our primary endpoint was called the Microcystic Lymphatic Malformation Investigator Global Assessment. It is a seven-point scale where physicians are rating the patient's lesion severity at the end of treatment compared to day zero.