Sirnaomics, Inc., a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announced today that the company’s IND application for a systemic siRNA (small interfering RNA) drug candidate, STP707, received the U.S. Food and Drug Administration (FDA) acknowledgment “Study May Proceed” in patients with advanced solid tumors.
This “Phase 1 Multicenter, Open-Label, Dose Escalation Study and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of STP707 Administered Intravenously in Subjects with Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy” is expected to begin enrolling in coming months.
Sirnaomics’ lead product candidate, STP707, is an anti-cancer siRNA (small interfering RNA) therapeutic. It takes advantage of a dual-targeted inhibitory property and a proprietary polypeptide nanoparticle (PNP)-enhanced targeted delivery to solid tumors and metastatic tumors via systemic administration. Initial preclinical study has demonstrated that knocking down TGF-β1 and COX-2 gene expression simultaneously in tumor microenvironment increases active T cell infiltration. A further combination study demonstrated a synergistic antitumor activity between STP707 and PD-L1 antibody using a mouse orthotopic liver cancer model.
“The IND green light from the U.S. FDA for Sirnaomics’ first IV oncology drug, STP707, represents another major milestone for the company’s mission in discovery and development of novel siRNA therapeutics for unmet clinical needs. Sirnaomics’ drug target selection and tumor targeting delivery should support a high rate of success for novel anticancer siRNA therapeutics, which have been verified in our clinical and preclinical studies,” said Patrick Lu, Ph.D., founder, President and CEO of Sirnaomics. “Sirnaomics is currently in a strong position to lead the RNAi community in the development of novel oncology therapeutics.”
“This IND approval represents a very important moment for the company as we can now expand our therapeutic reach in IV administration. This will allow more opportunities to target critical diseases with high unmet clinical need,” stated Michael Molyneaux M.D., Chief Medical Officer at Sirnaomics. “We expect that our rigorous oncology basket clinical study design will enable us to gain great insights into the impact of STP707 on multiple solid tumor types. Our IND enabling non-clinical studies with STP707 demonstrated an excellent safety profile as well as very good efficacy in multiple tumor types.”
STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics’ STP705 product. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs, and combining the two siRNA’s produces a synergistic effect that diminishes pro-inflammatory factors. The drug substances in STP707 are two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively. Over-expressions of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, intravenous (IV) delivery resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver and lung. In addition, in preclinical models STP707 had antitumor activity in various solid tumor types.