Wes Kaupinen, Founder and CEO of Palvella (SOURCE: Palvella)

Palvella’s Phase II Qtorin Data Lay Foundation for A Late-Stage Trial

By Mark Terry
March 15, 2023

Palvella Therapeutics, headquartered in Wayne, Pa., announced positive topline data from its Phase II trial of Qtorin rapamycin in Microcystic Lymphatic Malformations, or Mycrocystic LM. The proof-of-concept study evaluated 12 people with Microcystic LMs who received the drug once a day for 12 weeks, with all showing improvement.

Wes Kaupinen, Founder and CEO of Palvella, told BioBuzz, “For people living with microcystic lymphatic malformations (LMs), there is a significant disease burden and tremendous unmet need without an FDA-approved therapy.”

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Microcystic LM is a rare, chronically debilitating genetic disorder. It is caused by dysregulation of the PI3K/mTOR pathway and is marked by localized masses of malformed lymphatic vessels. These masses stick up through the skin and leak lymph fluid and bleed. It often causes recurrent serious infections and cellulitis. Currently, there are no FDA-approved treatments. In the U.S., about 30,000 people have been diagnosed with Microcystic LM.

Kaupinen said, “If approved, QTORIN™ rapamycin has the potential to become the first therapy and standard of care for the estimated more than 30,000 individuals currently suffering from microcystic LMs in the U.S. We plan to advance to Phase 3, pending additional regulatory interactions, supported by the positive topline results of the Phase 2 study in which all 12 participants study demonstrated improvement on the Clinician Global Impression of Change scale, with all rated as either ‘Much Improved’ or ‘Very Much Improved’ by clinicians after twelve weeks of treatment with QTORIN™ rapamycin.”

The 12 people in the study received Qtorin rapamycin once a day for 12 weeks. The trial involved multiple efficacy evaluations, including clinician and patient global impression assessments in addition to assessments of individual clinical symptoms, such as lesion height, leaking, bleeding, erythema, and crusting/hyperkeratosis.

The drug was generally well-tolerated. The most common side effects were application site pain and pruritus (itching). No serious adverse events were observed. Also, rapamycin was not detected in any of the participants’ systemic circulation anywhere during the study, which is a major goal of the company’s Qtorin technology platform.

Qtorin rapamycin is a 3.9% rapamycin anhydrous gel. In addition to Microcystic LM, it is being developed for Pachyonychia Congenita (PC) and the prevention of Basal Cell Carcinomas (BCCs) in Gorlin Syndrome (GS).

PC is a very rare genetic disease affecting the skin and nails. It is caused by mutations affecting keratins, proteins that provide structural support to cells. It is classified into five types depending upon which keratin gene is affected.

Gorlin Syndrome is another rare, inherited disease affecting many organs and tissues. People with GS have a very high risk of basal cell skin cancer during adolescence or early adulthood and are also at risk of developing a type of brain cancer, medulloblastoma, and other types of cancer.

All three clinical disorders have similarities in underlying disease pathology in the mTOR pathway that can be targeted by rapamycin. The mTOR pathway is overactivated, causing disease.

The company’s Qtorin platform focuses on the challenges related to topical delivery for a range of drugs, including rapamycin. Those challenges include high molecular weight, chemical and physical instability, acceptable drug concentrations and targeting skin penetration to limit systemic absorption. The platform handles those challenges and is compatible with a range of therapeutic cargoes for targeted delivery.

The drug has been granted FDA Fast Track Designation for PC, Microcystic LM, and for the prevention of BCCs in GS.

Kaupinen told BioBuzz, “We completed an End of Phase 2 meeting with the FDA in February 2023, and pending additional regulatory interactions, we plan to initiate a pivotal Phase 3 study in the second half of 2023. The FDA has granted Orphan Drug and Fast Track Designations to QTORIN™ rapamycin for the treatment of microcystic LMs – support that can help expedite the review process of the drug to meet an unfilled need. We’re also very pleased that Jim Treat, MD, from Children’s Hospital of Philadelphia, an investigator in our Phase 2 study, and our other clinician collaborators are highly supportive of advancing QTORIN™ rapamycin to a pivotal Phase 3 study.”

Earlier this year, in January, Palvella closed on a Series D financing round worth $37.7 million. The round was led by Petrichor and included new investor Gore Range Capital. Existing investors Samsara BioCapital, BVF Partners, Agent Capital, Nolan Capital, and BioAdvance also participated.

As part of the financing, Tadd Wessel, Founder and Managing Partner of Petrichor joined Palvella’s board of directors.

The proceeds from the raise will be used to advance Qtorin rapamycin for PC, Microcystic LM, and BCCs in GS.

The company is expecting a topline data readout from the Phase IIb trial of Qtorin rapamycin in GS in the first half of this year, and topline data from the Phase III trial in PC mid-year.

In addition to its Qtorin technology platform, Palvella’s business model revolves around partnering with patient advocacy groups and their patient registries to design accelerated development programs. The idea is to speed the introduction of targeted therapies to patients with unmet medical needs.

Kaupinen said, “We founded Palvella to bring life-changing therapies to people who suffer from overlooked, serious, genetic diseases like microcystic LMs that don’t have an FDA-approved therapy. The Phase 2 results signal positive progress toward achieving that goal.”