SQZ Biotechnologies Announces FDA Clearance of Investigational New Drug (IND) Application for SQZ-eAPC-HPV, a Novel mRNA-based Cell Therapy for the Treatment of HPV16 Positive Solid Tumors
WATERTOWN, Mass.–(BUSINESS WIRE)– SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today announced that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for SQZ-eAPC-HPV, authorizing the company to proceed with initiating a Phase 1/2 clinical trial of the novel cell therapy candidate. The company plans to initiate its COMMANDER-001 Phase 1/2 clinical trial of SQZ-eAPC-HPV in patients who have HPV16+ solid tumors, including head and neck, cervical, and anal cancers, and have progressed following standard therapies.
SQZ-eAPC-HPV is created by delivering five different mRNAs into a patient’s monocytes, B cells, T cells, and NK cells – engineering four cell types with five functions in a single step. In preclinical models, SQZ® eAPCs have been shown to generate robust CD8 T cell responses against multiple antigens, including HPV16 proteins, through simultaneous expression of antigens, CD86, membrane bound IL-2, and membrane bound IL-12.
“We believe SQZ eAPCs represent a major advance in cell therapy with the largest number of multiplexed components ever advanced into clinical testing. We are incredibly excited to explore its potential for patient impact,” said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. “SQZ eAPCs build upon the promising preliminary monotherapy clinical activity shown by our first SQZ APC platform. Through multiplexed engineering of a patient’s monocytes, B cells, T cells, and NK cells, we are able to integrate antigen presentation and enhanced immunological functions into a single clinical candidate that could become a powerful weapon against solid tumors.”
By focusing on engineering physiological mechanisms, SQZ cell therapies do not require patient pre-conditioning and have thus far been well tolerated in clinical study. Similar to our other clinical programs, SQZ eAPCs can be manufactured in under 24 hours and have the potential for future implementation on our point-of-care platform.
The SQZ eAPC trial is the third FDA IND clearance for a clinical candidate based on the company’s Cell Squeeze® technology.
SQZ® Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane bound IL-2 and IL-12. The company presented preclinical findings in November 2021 at the Society for Immunotherapy of Cancer (SITC) showing that SQZ eAPCs generated robust T cell responses in human in-vitro models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broad HPV16+ patient populations.
COMMANDER-001 Trial Design
SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response in less treatment-experienced patient populations.
About Human Papillomavirus Positive Cancers
Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.