11 January 2021 - - The he US Food and Drug Administration has granted orphan drug designation for PVSRIPO for the treatment of advanced melanoma (stage IIB-IV), US-based biotechnology company Istari Oncology, Inc said.

PVSRIPO is a novel viral immunotherapy, based on the Sabin type 1 polio vaccine, that activates a patient's innate and adaptive immune system to facilitate an anti-tumor response and establish long-term immunologic memory to help prevent the cancer's return.

Currently, Istari is recruiting for LUMINOS-102, a Phase 2 open-label, randomized trial (clinicaltrials.gov NCT04577807) in patients with advanced, unresectable melanoma who previously failed anti-PD1 therapy.

This study will characterize the safety, tolerability, and initial efficacy of PVSRIPO intratumoral injection alone and in combination with a PD-1 inhibitor.

The first patient is expected to be dosed this quarter.

LUMINOS-102 follows a successful Phase 1 monotherapy study of PVSRIPO in anti-PD1 refractory advanced melanoma in which patients who received 3 injections had an overall response rate of 67%.

Melanoma is the deadliest type of skin cancer TODAY with approximately 7,000 deaths in the US each year.

Treatment-resistant, advanced melanoma patients have very poor survival rates, with less than 28% of metastatic melanoma patients surviving five years.

PVSRIPO aims to address the significant unmet need in advanced melanoma, since most patients are treated with checkpoint inhibitors, and many do not respond or later become resistant and require other options, which are limited.

Orphan drug designation is granted by the FDA Office of Orphan Products Development to drugs or biological products intended for the treatment of rare diseases or conditions that impact fewer than 200,000 people in the US.

This designation acts as a stimulus for the development of drugs for rare diseases through several incentives, including eligibility for federal grants, research and development tax credits, waiver of filing fees, and the potential for a seven-year marketing exclusivity period after FDA approval.

The granting of an orphan drug designation does not alter the standard regulatory requirements and process for obtaining marketing approval. More information about orphan drug designation can be found on the OOPD website.

PVSRIPO is a virus based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. Unlike other viral immunotherapies,

PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors.

Via CD155, PVSRIPO targets tumors with two primary mechanisms: direct damage to and killing of cancerous cells; and engaging innate and adaptive antitumor immune responses via sublethal infection of antigen presenting cells in the tumor, which unleashes an inflammatory cascade resulting in sustained systemic antitumor immunity.

PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.