Indications
Our goal is to advance Photodynamic Therapy (PDT) as an effective, toxicity-free alternative to chemotherapy and radiotherapy. Our revolutionary DigiLum™ PDT platform promises to reinvigorate this proven therapy to extend its use to new sites and indications. We currently have two indications under clinical evaluation see clinical studies that target gaps in the standard of care for treating patients with advanced lung and colorectal cancers- the leading causes of cancer related deaths.
Patients with NSCLC with pleural spread or Other malignant pleural disease
The DigiLum™ PDT System and Gleolan™ combination is intended for use in PDT in patients with late-stage NSCLC with pleural spread or other malignant pleural disease, followed by an anti-PD1 agent with or without chemotherapy.
The current standard of care for first-line advanced stage NSCLC without actionable molecular biomarkers is immunotherapy with an immune checkpoint inhibitor (ICI), with most approved agents targeting the PD-1/PD-L1 axis, either alone or in combination with chemotherapy. Patients that respond to such immunotherapy realize remarkable survival benefit, unfortunately only a small minority (<20%) of these patients respond to PD-1/PD-L1 checkpoint blockade therapy, most likely due to the lack of immunogenicity and low expression of PD-L1 in tumors, as it is believed that high expression of PD-L1 is required on tumors and pre-existing tumor-infiltrating activated CD8+ T cells expressing PD-1. Multimodal treatments combining ICI with other therapies, including PDT, may enhance treatment efficacy. PDT initiated tumor cell death results in increased damage-associated molecular patterns and release of tumor associated antigens and inflammatory cytokines such as IL8 and IL6. This promotes the recruitment of immune cells such as neutrophils, which then modulate the subsequent immune system response - dendritic cell maturation and T cell activation, that can promote antitumor immunity, and augment the innate immune response through various pathways (e.g. accumulation and maturation of antigen presenting cells) and favorably alter susceptibility of the tumor microenvironment to immune checkpoint therapy.
Well-designed preclinical studies have shown PDT working in synergy with ICI to invoke anti-tumor immunity, increase PD-L1 expression, promote T cell activation, increase proportion and reinvigoration of CD8+ T cells, and induce immune memory effects. Lumeda's preclinical studies on the sequence of PDT and anti-PD1 agents in Lewis lung carcinoma models- refractory to anti-PD1 immunotherapy, have shown improved tumor control as a monotherapy and in combination with anti-PD1 agent over anti-PD1 alone, and the combination PDT + anti-PD1 agent therapy exhibiting best tumor control along with a significant increase in proliferating CD8+ T cells. The correlated studies in study ID# NCT04836429 will be the first to evaluate these effects in patients with pleural disease treated with PDT followed by an anti-PD1 agent with results expected in 2024.
PDT is administered to these patients intraoperatively using the DigiLum™ system during standard of care procedures in treating patients with pleural disease including thoracentesis, medical thoracoscopy, and pleurodesis, followed by an anti-PD1 agent.
PATIENTS WITH ADVANCED COLORECTAL CANCER THAT ARE CANDIDATES FOR SURGICAL RESECTION
Gleolan™ is intended for use as an optical imaging agent as an adjunct for the visualization of malignant tissue in patients with advanced colorectal cancer with recurrent or T4 tumors undergoing surgical resection. The DigiLum™ PDT System and Gleolan™ combination is intended for use in PDT administered intraoperatively immediately following tumor resection in these patients.
Patients with locally advanced or recurrent colorectal cancer have been shown to have increased surgical complexity and recurrence. Surgical resection is the primary treatment for curative intent followed by adjuvant chemotherapy and/or intraoperative radiation therapy. Despite current efforts, recurrence rates are still problematic, reducing overall survival, and are associated with a significant burden due to symptoms such as chronic pain, neuropathy, obstruction, and pelvic floor and sexual dysfunction. Fluorescence-guided resection with 5-aminolevulinic acid (5-ALA) has been approved to assist surgery in the treatment of malignant gliomas which has led to a significant improvement in patients having a complete tumor resection.
Our intended use of fluorescence-guided resection with 5-ALA (Gleolan™) will likewise visualize and detect residual disease to impart the same benefit in patients with colorectal cancer undergoing surgical resection. In addition to reducing the incidence of positive surgical margins through 5-ALA fluorescence-guided resection, multiple clinical studies have reported that intraoperative PDT is associated with improved clinical outcomes and overall survival. By illuminating the entire surgical bed post-resection, PDT can effectively treat positive surgical margins as well as microscopic residual disease that is difficult to detect. The broad area exposure capability of the DigiLum™ system is uniquely well-suited in this application.
Such bimodal approach of 5-ALA mediated fluorescence visualization followed by therapeutic PDT promises to reduce incidence of disease recurrence especially in the target population where achieving complete surgical resections is difficult and high risk where the tumor has invaded in proximity to nerves, vascular structures, and other organs. Study ID# NCT06307548 will be the first to evaluate the bimodal photodynamic detection and follow-on intraoperative photodynamic therapy (PDD + PDT) in patients with loco-regionally advanced colorectal cancer with recurrent or T4 tumors undergoing surgical resection. The study will test the sensitivity of image-guided fluorescence to detect residual disease using 5-ALA (Gleolan™) and determine the safety and potential efficacy of 5-ALA mediated intraoperative PDT using the DigiLum™ system.
