Redefining cancer therapy with photoimmunotherapy

Aspyrian Therapeutics’ photoimmunotherapy destroys tumors and activates anticancer immunological response. With its first drug candidate RM-1929, Aspyrian is expected to enter phase 3 multinational trials in early 2018.

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Clinical trials are under way for a new antibody-based anticancer platform called photoimmuno­therapy (PIT), which has shown promise in selectively destroying tumors and activating anticancer immune responses by depleting intratumoral immunosup­pressive cells. PIT was discovered at the US National Cancer Institute1, and Aspyrian Therapeutics has secured an exclusive license from the institute to develop and commercialize PIT therapeutics.

PIT uses antibody conjugates with a nontoxic payload (IRDye 700DX) that can be activated at the tumor site with 690-nm red light. The cell-bound, light-activated antibody conjugates can induce tumor-specific cancer cell destruction without dam­aging normal surrounding tissues. The PIT platform can be applied to deplete tumor-infiltrating regula­tory T cells, leading to robust and sustained tumor destruction.

In May 2015, Aspyrian initiated a phase 1 clinical trial of its first PIT drug product, RM-1929, to evalu­ate its safety and anticancer activity in second-line recurrent head and neck cancer. The phase 1 study included a single treatment with RM-1929. Promising results from the study led to the submission of an amended protocol in April 2016 to study the safety and efficacy of repeated treatment cycles with the intent to achieve complete responses or sustained disease control, and to evaluate the drug’s effect on disease progression and overall survival. This trial is currently ongoing at six clinical centers in the United States, and enrollment is expected to be complete by mid-2017.

Two different modalities

PIT destroys locoregional cancers by directly target­ing cancer cells. PIT-induced cell killing causes rapid tumor necrosis and induces immunogenic cell death, triggering the release of proinflammatory intracel­lular molecules. This process leads to the activa­tion and recruitment of both innate and adaptive immune cells. PIT treatments can then be used to treat locoregional disease and, in combination with immune-modulatory approaches, metastatic dis­seminated disease (Fig. 1).

In addition, PIT can also be used as a new modality to directly target cancer-promoting immunosup­pressive cells in the tumor. An example is using PIT to selectively kill regulatory T cells within the tumor with minimal effects on the periphery2. Preclinical studies demonstrate that a single locoregional CD25–IR700 PIT treatment leads to substantial CD8+ T cell–dependent anticancer activity that destroys both locoregional and metastatic tumors.

Figure 1: Photoimmunotherapy can be used to kill cancer cells directly or to activate an anticancer immune response by eliminating intratumoral immune-suppressive or tumor-promoting cells.

PIT for initial targeting of EGFR with RM-1929

RM-1929 targets epidermal growth factor receptor (EGFR), a cancer antigen expressed on multiple types of solid tumors, including head and neck squamous cell carcinomas (HNSCCs). Aspyrian completed dose escalation studies of RM-1929 in patients with recur­rent HNSCC for whom existing treatments, including platinum-based therapies, had failed, and who were not suitable candidates for surgical resection or radia­tion therapy. Some had also failed on treatment with Erbitux (cetuximab) or immune-checkpoint modula­tors such as anti-PD-1.

The phase 1 study evaluated the safety and anticancer activity of a single treatment cycle and defined the optimal RM-1929 and light-activation doses. Light, applied with lasers and fiber optics, could be delivered to treat large (multi-centime­ter) tumors at any location of the head and neck. RM-1929 has since progressed to a new clinical study, which is evaluating the long-term safety and efficacy of repeated treatment cycles in patients with recurrent HNSCC. On April 27th 2017, Aspyrian presented clinical data from patients treated at Thomas Jefferson University (TJU). The team at TJU described high response rates and good safety in second-line head and neck cancer in patients that had failed all existing therapies. Evidence of tumor necrosis post treatment was also observed in all patients treated. The presentation received the American Head & Neck Society Poster of Distinction Award in the category of clinical trials/immunother­apy. Based on the promising results of the ongoing trial, Aspyrian aims to initiate phase 3 multinational trials in early 2018.

In 2018, Aspyrian also plans to conduct additional studies combining RM-1929–PIT treatments with immune-checkpoint inhibitors such as anti-PD-1. These studies will evaluate the safety and synergistic effects on sustained anticancer immune responses. The long-term objective is for PIT therapies to achieve optimal control of locoregional disease and activate a durable immuno-oncological response, thereby leading to complete remission or prevention of metastatic cancer.

  1. Mitsunaga, M. et al. Nat. Med. 17, 1685–1691 (2011).
  2. Sato, K. et al. Sci. Transl. Med. 8, 352ra110 (2016). 


Miguel Garcia-Guzman,
President and CEO
Aspyrian Therapeutics Inc.
San Diego, California, USA
Tel: +1-858-925-5621

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Aspyrian Therapeutics

Aspyrian Therapeutics is a clinical stage oncology company developing novel precision-targeted therapies based on the photoimmunotherapy technology (PIT) platform. PIT utilizes antibody conjugates that accumulate at the tumor after systemic infusion and can be activated with light to induce rapid, specific, and robust tumor destruction. PIT causes immunogenic cell death of the cancer cells and can lead to activation of innate and adaptive anti-cancer immune responses. In addition, PIT conjugates can be designed to target and destroy tumor immunosuppressive cells located at the tumor microenvironment resulting in activation of cytotoxic NK and T-cells that destroy the localized and disseminated tumors. Aspyrian’s first PIT drug product, RM-1929, is currently in Phase 1/2 clinical trials to treat terminal head and neck cancer patients that have failed all existing therapies. Aspyrian intends to develop RM-1929 as a monotherapy and in combination with immune modulators.

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