SIRPant Immunotherapeutics
Delivering Novel Cancer Immunotherapy

Cancer Immunotherapy has revolutionized the cancer treatment landscape in the past few years. Its success, however, has been limited to the liquid tumor space—despite pouring billions of dollars into research aimed at pushing this boundary.

Solid tumor elimination is still an unsolved riddle for the healthcare industry. Immunosuppressive tumor microenvironments (TME), inefficient trafficking into tumors, and heterogeneity of tumor antigens are primary reasons for this quandary. High intra-tumoral pressure of solid tumors also serves as a barrier to successful treatment delivery.

To achieve greater consistent success in the journey of care for patients with advanced solid tumors, we need to go beyond existing norms and challenge the status quo.

A company that has taken a significant leap in this direction is SIRPant Immunotherapeutics.

SIRPant Immunotherapeutics aims to revolutionize the treatment of solid tumors with a focus on the cell biology of the immune response. As an early-stage company, it discovers, develops, and implements transformative cell-based therapies for the treatment of cancer and lifealtering immunopathology.

“Most of our pre-clinical work utilized syngeneic solid tumor models involving some of the most difficult to treat cancer cell lines, such as MC38 colorectal carcinoma, KPC pancreatic ductal adenocarcinoma, and LLC non-small cell lung carcinoma,” says Robert J. Towarnicki Sr., the President and CEO of SIRPant Immunotherapeutics.

Empowering the Immune System

SIRPant Immunotherapeutics recognizes that the solution to a problem is sometimes found not by staring at the problem itself but by getting at its underlying cause. Cancer is fundamentally a cell biological problem that can be solved by harnessing the body’s own immune cells and re-educating them to elicit a response against cancer.

Cancerous cells arise in any given individual about once per day, but the average human being has full-blown tumors once or twice in life (typically late in life). The immune system plays a key role in this; it regularly detects and destroys new cancerous cells. So, cancer can only establish and grow by evading the immune response.

To this end, SIRPant Immunotherapeutics has developed cellular immunotherapy against cancer— SIRPant-M™—that promotes a polyclonal anti-tumor immune response and endures both in time (resulting in immune memory that prevents recurrence) and in space (resulting in clearance of metastases) to eliminate cancerous cells throughout the body.

“Our technology reverses the immunosuppressive environment of tumors to empower the immune system to do what it does best—clearing both primary tumors and metastases,” says Towarnicki.

SIRPant Immunotherapeutics’ solution harnesses the body’s own immune cells and re-educates them to elicit a response against cancer.

SIRPant-M™ employs a proprietary macrophage activation solution—PhagoAct™—to license immune cells for recognizing and eliminating cancer. Much like a vaccine, it mobilizes both the cellular and humoral arms of the immune system to spot and kill cancer cells throughout the body, resulting in long-lasting immune memory against cancer.

Leading the Cellular Immunotherapy Space

SIRPant-M™ is cancer agnostic. It requires no genetic modification to target cancer-associated markers such as HER-2. This approach mobilizes an immune response that targets a broad array of cancer neo-antigens, first by the macrophage’s demonstrated ability to phagocytize cancer cells, as exemplified in testing against the NCI- 60 cancer cell line panel, which includes carcinomas, lymphomas, leukemias, glioblastomas, and melanomas. SIRPant-M™ macrophages leverage numerous endogenous effector immune cells which have been screened through the process of thymic selection to eliminate self-reactive cells from a patient’s immune system. This creates a safe treatment regimen.

“Over several years of research, we have employed SIRPant-M™ in more than ten pre-clinical models. The company has not observed any adverse effects in the clearance of the established cancers,” says Towarnicki.

Utilizing in vivo syngeneic murine cancer models (comprising colon, lung, melanoma, pancreatic, breast, and lymphoma cancers), SIRPant-M™ was successful in eliminating tumors from animals and boosting immunity. Once the cancer was removed, researchers at SIRPant Immunotherapeutics tried to re-establish the same cancer up to 3 times over approximately 15 months. The bolus of cancerous cells failed to establish, however, due to the creation of memory T-cells and antibodies to cancer neoantigens. The company finds this especially exciting in a neo-adjuvant setting where SIRPant-M™ could be utilized to prime the immune system, preventing recurrence or relapse post-surgical excision.

“Head and neck cancers and NSCLC found early enough for surgical intervention still have a high probability of recurrence. SIRPant-M™ can change the paradigm,” says Towarnicki.

SIRPant-M™ captures many of the best attributes in other notable cancer therapies such as CD47-SIRPα blockade, tumorinfiltrating lymphocyte (TIL) therapy, and macrophage-centric therapies. SIRPant-M™ is poised to target and eliminate any type of cancer by effectively engaging a patient’s immune system.

Spearheading Progress in Immunotherapy

“Most of the existing therapies aim to treat cancer by inciting inflammation or diminishing anti-inflammatory mechanisms to foster a tumor microenvironment that favors elimination of the cancerous cells,” says Towarnicki.

SIRPant-M™ mounts a pro-inflammatory response and curtails the resolution of inflammation that would otherwise enable cancerous cells to stifle productive anti-cancer immune responses. “We’ve seen several promising immunotherapies in recent years—from checkpoint inhibitors, to CAR-T and CAR-NK,” notes Towarnicki. “We take a step back from this mechanistically—rather than using the effector cells and molecules of the immune system, we use the cells that drive those responses. We believe that the macrophages we engineer are uniquely suited to drive robust and durable polyclonal responses that attack both primary tumors and metastases from multiple angles.”

SIRPant Immunotherapeutics has always focused its research on SIRP-α and the role it plays in immune modulation. SIRP-α, the macrophage receptor for CD47 (the “don’t eat me signal”) plays a significant role in immune evasion by cancer, among other disease conditions that are caused by immune dysfunction. By targeting cancer, the company has demonstrated the therapeutic efficacy of downregulation of SIRP-α. Today, its work is focused on the creation of macrophages with therapeutically relevant downregulation of SIRP-α activity and expression. SIRPant Immunotherapeutics expects to file an IND in Q4 of this year and initiate clinical trials early in 2023.

Utilizing its proprietary technology and insights in modulating SIRP-α, SIRPant Immunotherapeutics anticipates additional products and potential therapies for cancer as well as conditions of immune hypoactivation (e.g. infectious diseases) and immune hyperactivation (e.g. autoimmunity) where modulation of SIRP-α expression may play a greater role.