READ THE FULL SQZ RESEARCH REPORT
Since Our Last Update
Since our last update, SQZ Biotechnologies Company (NYSE:SQZ) has made progress on the regulatory front with an investigational new drug (IND) clearance, the addition of strategic advisor John Maraganore, Ph.D. and the publication of preclinical research on SQZ APCs.
Highlights since our last update:
➢ John Maraganore, Ph.D. joins as Strategic Advisor - January 2022
➢ FDA clears IND for SQZ-eAPC-HPV in HPV16+ tumors - January 2022
➢ Publication of preclinical research on SQZ APC T cell activation - February 2022
Upcoming Milestones
➢ Enhanced APC trial launch - 1H:22
➢ AAC HPV data presentation - 2022
➢ Enhanced APC (eAPC) data presentation - 2H:22
➢ IND for immune tolerance in celiac disease - 3Q:22
➢ eAPC IND filing in HBV - 2H:22
➢ AAC or eAPC IND for KRAS mutant solid tumors - 2H:22
John Maraganore, Ph.D. Joins as Strategic Advisor
On January 6, 2022, SQZ announced that John Maraganore, Ph.D. joined SQZ as a Strategic Advisor. Dr. Maraganore served as the founding CEO and a Director of Alnylam, an RNA interference (RNAi)-focused company, from 2002 to 2021, where he built and led the company from early platform research on RNA interference through global approval and commercialization of the first three RNAi medicines. Prior to Alnylam, he served as an officer and a member of the management team for Millennium Pharmaceuticals and was responsible for the company's product franchises in oncology, and cardiovascular, inflammatory, and metabolic diseases. Before Millennium, he served as Director of Molecular Biology and Director of Market and Business Development at Biogen where he invented and led the discovery and development of ANGIOMAX (bivalirudin) for injection. Prior to Biogen, Dr. Maraganore was a scientist at ZymoGenetics, Inc. and the Upjohn Company. Dr. Maraganore received his Master of Science and Ph.D. in biochemistry and molecular biology at the University of Chicago. He is a Venture Partner at ARCH Venture Partners and a member of the board of directors of Agios Pharmaceuticals, Beam Therapeutics and the Biotechnology Industry Organization.
FDA Clears IND for SQZ-eAPC-HPV
On January 24, 2022, SQZ announced that the FDA had cleared its IND for SQZ-eAPC-HPV in HPV16+ solid tumors. SQZ' eAPCs are derived from patient peripheral blood mononuclear cells squeezed with target antigens and are enhanced with an mRNA payload that provide additional stimulatory signals to CD8 T cells, enabling more potent CD8 T cell responses. SQZ-eAPC-HPV is engineered with five different mRNA, encoding for multiple target antigens and immuno-stimulatory signals. The IND clearance will allow SQZ to proceed with its COMMANDER-001 Phase I/II clinical trial in HPV16+ solid tumor progressors. In preclinical models, SQZ eAPCs have been shown to generate robust CD8 T cell response against multiple antigens. COMMANDER-001 is evaluating SQZ-eAPC-HPV both as a monotherapy and in combination with pembrolizumab. The study consists of two parts. The first part will assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients following monotherapy dose escalation, and dose de-escalation for the combination with pembrolizumab. The second will assess clinical response in less treatment-experienced patient populations.
Publication of Preclinical Research in SQZ APC
On February 1st, 2022, SQZ announced a publication entitled "Microfluidic Squeezing Enables MHC Class I Antigen Presentation by Diverse Immune Cells to Elicit CD8+ T Cell Responses with Antitumor Activity" in the February 15th Edition of Journal of Immunology, featuring comprehensive preclinical research on SQZ' ability to engineer a broader variety of immune cell types, namely T cells; B cells; NK cells; and monocytes, to drive MHC-I antigen presentation and subsequent CD8 T cell response across multiple antigens. CD8 T cells play a critical role in the immune response; however, a major hurdle for CD8 T cell activation has been presenting the desired antigen(s) to these T cells through the MHC-I pathway. In the publication, SQZ scientists and collaborators describe how this challenge is overcome through the delivery of antigens directly into the cytosol via microfluidic squeezing. In multiple in vivo studies, engineered B cells, T cells, or mixed peripheral blood mononuclear cells (PBMCs) were all capable of activating the immune response across multiple antigens, and the immune responses had prophylactic effect, were able to drive tumor regression, and formed long-term memory against future tumor challenge. The protection correlated with infiltration of antigen-specific CD8 T cells. Finally, scalability of Cell Squeeze was confirmed, comparing research- and manufacturing-scale viability and delivery of various PBMCs.
SQZ Clinical Strategy
SQZ is pursuing HPV+ cancer based on the unmet need in this global disease. This indication also serves as a useful first target as HPV has been well-studied, providing standardized markers of success for the company's work. HPV+ tumors in patients that are HLA-A*02+ have been extensively researched and there are many known biomarkers that can be leveraged to assess therapeutic activity and monitor patient metrics. Demonstrating efficacy in HPV serves as excellent proof of concept for this novel technology and has applications in multiple solid tumor types. The SQZ-APC-HPV candidate is being evaluated in a Phase I study and has licensed certain commercialization rights to Roche. The cells are engineered, autologous PBMCs squeezed with HPV+ solid tumor specific antigens. Squeezing, in contrast to other delivery methods, enables robust MHC-I presentation of the target and drives activation of the patient's endogenous CD8+ T cells against the HPV+ tumor cells.
The SQZ-AAC-HPV program is also in Phase I with monotherapy cohorts started in 2021 and data expected in 2022. The trial is an open-label, multicenter study of the safety and tolerability, immunogenic effects, antitumor activity, and pharmacodynamics of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with recurrent, locally advanced or metastatic HPV16+ solid tumors.
Summary
Since our last update, SQZ has made progress on several fronts, receiving IND clearance for the eAPC-HPV study, adding John Maraganore, Ph.D. as a strategic advisor and publishing preclinical research on SQZ APCs. In 2022, SQZ anticipates enrollment and readout of its eAPC trial, reporting of data from its AAC monotherapy Phase I trial, potential submission of further INDs and expansion of the highest dose cohort in the AAC program. SQZ' portfolio offers treatments for multiple indications using a simple approach to engage the body's immune response. Results from SQZ' lead program provide further evidence that the APC platform stimulates an immune response in patients that have failed other lines of therapy.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR.
DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.
________________________
2. ESMO, December 2021. PowerPoint Presentation
3. ESMO, December 2021. PowerPoint Presentation
