INTASYL compounds are chemically modified siRNA’s, combined with antisense technology to provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity targeting a broad range of cell types and tissues.
INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. INTASYL demonstrated preclinical efficacy in both Direct-to-Tumor and Adoptive Cell Therapy (ACT) applications.
In comparison to biologics and cell and gene therapies, INTASYL has a favorable non-clinical toxicity and safety profile, and a streamlined chemical synthesis that reduces costs and offers substantial convenience to the prescriber and patient.
INTASYL is the only self-delivering RNA interference (RNAi) technology focused on immuno-oncology therapeutics.
Adoptive Cell Therapy Products
INTASYL™ Pipeline for Adoptive Cell Therapy Applications
- PH-762 reduces the expression of the immunosuppressive protein PD-1 in T-cells used for ACT, enabling them to overcome tumor resistance mechanisms and thus improving their ability to destroy the tumor cells.
- Preclinical studies have shown how PH-762 can activate human T-cells grown for ACT and how it can increase their tumor cell-killing ability. The tumor-killing potency of these PH-762 T-cells against the tumor cells of the same patient was increased by about 2 fold as compared to untreated T-cells. As a result, the use of PH-762-treated ACT is expected to enhance therapeutic responses in cancer.
- Data, completed in partnership with the Karolinska Institutet in Sweden, demonstrated that the application of PH-894 can silence BRD4 in human T-cells while being grown for ACT.
- It was also shown that T-cells treated with PH-894 have increased antitumor activity.
- PH-804 provides powerful dose-dependent silencing of TIGIT that can be seen in both T-cells and NK cells.
- In addition, PH-804 has demonstrated induced silencing of TIGIT in NK cells and T-cells, which can overcome their “off switch” with the cells becoming weaponized to kill cancer cells.
INTASYL™ Pipeline for Direct-to-Tumor Applications
- Through local administration of PH-762, we can reprogram the tumor microenvironment (TME) and achieve local activation of immune cells.
- The potential of such direct therapeutic use of PH-762 has been demonstrated in animal studies. Administration of PH-762 through intratumoral injection resulted in potent antitumoral effects, whereby the treated animals showed a complete and statistically significant inhibition of tumor growth. In contrast, placebo-treated animals displayed exponential tumor growth.
- Direct injection of INTASYL™ therapeutics can successfully penetrate solid tumors and impact the TME by activating the immune response in animal models of solid tumors, resulting in reduced tumor growth. Based on our positive preclinical data, we are preparing for a clinical study with PH-762 using intratumoral administration for patients with advanced melanoma.
- Data published by Phio showed the use of PH-894 in a validated mouse model of hepatocellular carcinoma. In this study, local administration of PH-894 through intratumoral injection resulted in potent and statistically significant antitumoral effects.
- PH-894 shows the power of INTASYL™ to modulate expression of intracellular and/or commonly considered ‘undruggable’ targets, a limitation for small-molecule and antibody therapies.
PH-762 is an INTASYL™ compound that reduces the expression of PD-1, a protein that inhibits T cells’ ability to kill cancer cells. By suppressing PD-1, the T cells are re-activated to kill cancer cells. PH-762 is being developed as a standalone drug therapy (Direct-to-Tumor) and also in combination with ACT. The Phase 1b study is currently being conducted at the Gustave Roussy Institute, one of the largest cancer centers in Europe. It is evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of PH-762 in a neoadjuvant setting in subjects with advanced melanoma.
PH-894 is an INTASYL™ compound that silences BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well as the tumor. What sets this compound apart is its dual mechanism: INTASYL PH-894 suppression of BRD4 in T cells results in T cell activation; additionally, suppression of BRD4 in tumor cells results in tumors becoming more sensitive to T-cell killing.
PH-804 silences the suppressive immune receptor T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), which is a checkpoint protein present on immune cells, such as T-cells and NK cells. TIGIT is one of the most recent immune checkpoints to be investigated as an immunotherapeutic target. Similar to PD-1, cancer cells can suppress the activity of these immune cells by activating TIGIT. This triggers an “off switch”, resulting in tumor immune evasion, which can be prevented by blocking or silencing TIGIT.