GAITHERSBURG, Md. and SUZHOU, China—Sirnaomics Inc. and Innovent Biologics, Inc. have jointly announced a strategic collaboration in which both companies will conduct clinical studies using Sirnaomics’ RNAi drug candidate STP705 (cotsiranib) and Innovent’s antibody drug Tyvyt (sintilimab injection). The companies plan to use the drugs for combination treatment in advanced cancers, such as hepatocellular carcinomas (HCC) and cholangiocarcinoma (CCA), with high unmet need in the U.S.
“This collaborative effort between Sirnaomics and Innovent will be the first example of a combination strategy using an RNAi drug candidate together with an approved immune checkpoint antibody drug for the treatment of liver cancers,” said Patrick Lu, Ph.D., president and chief executive officer of Sirnaomics. “This represents an important clinical approach for combating these deadly diseases where the silencing of gene targets that reduce T-cell access and activity may augment the activity of checkpoint inhibitors in liver cancer.”
Sirnaomics’ STP705 is a small interfering RNA (siRNA) therapeutic which takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the U.S. FDA and the Chinese NMPA, including treatments of cholangiocarcinoma, non-melanoma skin cancer and hypertrophic scarring.
STP705 has also received FDA Orphan Drug designation for treatment of cholangiocarcinoma and primary sclerosing cholangitis. STP705 has demonstrated a dramatic improvement in T-cell penetration into tumors in the liver with single agent action, as well as improvement in the efficacy of an anti-PD-L1 antibody checkpoint inhibitor in an HCC model. This effect may improve other immune checkpoint inhibitor efficacies, in addition to those targeting the PD-1/PD-L1 axis.
“Sirnaomics is very excited to enter into this collaboration agreement with Innovent to potentially bring lifesaving therapies to patients with hepatocellular cancers. It is well known that, despite recent advances in cancer therapies, HCC is still a deadly form of liver cancer with high unmet need,” explained Michael Molyneaux, M.D., chief medical officer of Sirnaomics. “Our preclinical proof of concept oncology data has consistently demonstrated single agent efficacy with STP705 in HCC, and our most recent work on mechanism of action strongly suggests that the use of our lead asset (STP705) in combination with antibody therapies could greatly benefit patients with HCC.”
“Innovent has a very strong track record for innovation and execution in the clinical space, and a shared vision of bringing lifesaving therapies to their patients. We believe that combining Sirnaomics novel siRNA technology with Innovent’s cutting edge antibody therapies has the potential to significantly improve the current treatment landscape for patients with hepatocellular cancer,” added Molyneaux.
Innovent’s Tyvyt is a type of immunoglobulin G4 monoclonal antibody which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-1 Ligand-1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies for sintilimab injection to evaluate its safety and efficacy in a wide variety of cancer indications, including eight registration or pivotal clinical trials. Innovent is also conducting clinical studies of sintilimab injection in the U.S.
“Sintilimab has been granted marketing approval by the NMPA and is the only PD-1 inhibitor included in the NRDL. Sintilimab has gained broad recognition by the market, due to its profiles in safety and efficacy. Through partnership with other companies, we are exploring more sintilimab-based combination therapies and have seen some promising results. Developing a combination therapy, comprised of an antibody drug and a RNAi drug, may provide more comprehensive and effective treatments for patients,” noted Dr. Hui Zhou, vice president and head of Oncology Strategy and Medical Sciences of Innovent. “The potential clinical value of the combination therapy of sintilimab and cotsiranib will be evaluated and we hope more patients will benefit from this potential therapy globally.”