• Objective responses observed in patients’ refractory to programmed death receptor-1 (PD-1) inhibitors and BRAF-targeted therapy
• Responses in both injected and noninjected tumors suggest systemic anticancer immune activation
• Evidence of rekindled antitumor activity was seen among patients failing immune checkpoint inhibitors

DURHAM, NC, April 21, 2021 – Istari Oncology, Inc., a clinical-stage biotechnology company, today announced the publication of “A phase 1 trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma” in the Journal for ImmunoTherapy of Cancer. The results of this study suggest that PVSRIPO holds promise for patients with advanced melanoma refractory to both PD-1 inhibitors and BRAF-targeted therapy.<super>1<super>

Twelve patients received 1, 2, or 3 intratumoral injections of PVSRIPO at 21-day intervals. Four of six patients (67%) who received 3 injections had an objective response, 3 of whom received anti-PD-1 therapy within 30 days prior, suggesting that PVSRIPO was able to initiate or rekindle immune responses in patients who have failed anti–PD-1 therapy. Responses were observed in both injected and noninjected tumors, suggestive of an abscopal response. These results are consistent with the findings from mechanistic studies that PVSRIPO generates a functional antitumor CD8+ T cell response capable of mediating effective, systemic antitumor immunity.<super>2,3<super>

Following study completion, 11/12 patients (92%) re-initiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up duration of 18 months. The antitumor responses observed suggest that PVSRIPO, either alone or in combination with anti–PD-1, may be an effective treatment in anti–PD-1 refractory melanoma.<super>1<super>

“The responses observed in patients with advanced disease, including in noninjected tumors in patients with significant in transit metastases, is potentially good news for the growing population of patients with unresectable melanoma who are refractory to anti–PD-1 and BRAF-targeted therapies,” said Georgia Beasley, MD, Principal Investigator of the phase 1 study at Duke University. “These responses were observed without serious or dose-limiting toxicities.”

“The responses seen in both injected and noninjected in-transit tumors with PVSRIPO are an important finding,” noted Yana Najjar, MD, Assistant Professor of Medicine at the UPMC Hillman Cancer Center and Principal Investigator of the LUMINOS-102 phase 2 multicenter study (NCT04577807), which is investigating PVSRIPO alone and in combination with anti–PD-1 therapy and is now open to enrollment across the United States. “LUMINOS-102 will build on these data and further evaluate the ability of PVSRIPO to generate a systemic immune response that fights cancer in both injected and noninjected tumors and suppresses cancer growth over time in patients with unresectable anti–PD-1 refractory melanoma.”

“The findings of this study are important further evidence of the therapeutic potential of PVSRIPO,” said W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. “PVSRIPO appears uniquely capable of engaging both innate and adaptive immune responses to generate antitumor immunity.”

For more information about Istari Oncology and their ongoing clinical trials and research on PVSRIPO, visit istarioncology.com.

About PVSRIPO

PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has a distinct point of entry (the poliovirus receptor, CD155), which is expressed on virtually all solid tumors and antigen-presenting cells. Upon entry into the cell, PVSRIPO targets tumors via two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) generating innate and adaptive antitumor immune responses via nonlethal infection of antigen presenting cells in the tumor, which stimulates a specific signaling pathway resulting in a sustained, robust type-I/III interferon-dominant response, with minimal release of unwanted cytokines. Its effects are potentiated by prior vaccination against poliovirus. 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.

About Istari Oncology

Istari Oncology, Inc., headquartered in Research Triangle Park, North Carolina, is a privately held clinical-stage biotechnology company focused on novel immuno-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors. The company was founded by Darell Bigner, MD, PhD and Matthias Gromeier, MD, of Duke University Medical Center in 2016. Istari licensed a broad range of patents and patent applications from Duke University and has access to additional intellectual property to continue clinical and commercial development of these technologies. The company’s primary platform currently in clinical development is PVSRIPO. For more information, please visit istarioncology.com.

References

1. Beasley GM, Nair SK, Farrow NE, et al. A phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer. 2021 https://jitc.bmj.com/content/9/4/e002203
2. Brown MC, Holl EK, Boczkowski D, et al. Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs. Sci Transl Med. 2017;20;9(408):eaan4220. doi: 10.1126/scitranslmed.aan4220
3. Brown MC, Mosaheb MM, Mohme M, et al. Viral infection of cells within the tumor microenvironment mediates antitumor immunity via selective TBK1-IRF3 signaling. Nat Commun. 2021 [in press].

Disclosures

Yana Najjar, MD previously served on an advisory board for Array BioPharma and has research funding from Bristol Myers Squibb, Pfizer, Merck & Co.; no disclosures w/Istari Oncology, Inc.

Istari Oncology Medical Affairs Contact:
Email: MedicalAffairs@istarioncology.com

Investor Contact:
Stern Investor Relations
Christina Tartaglia
Email: Christina.tartaglia@sternir.com

Media Contact:
FleishmanHillard
Leigh Fountain
Email: leigh.fountain@fleishman.com

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