Periodic Reporting for period 1 - IMPACT (Immune Photo-Activated Cancer Therapy for the Treatment of Upper Tract Urothelial Cancer (UTUC) and other solid tumours)
Okres sprawozdawczy: 2024-12-01 do 2025-11-30
Upper Tract Urothelial Carcinoma (UTUC) accounts for approximately 5–10% of urothelial cancers and develops in the renal pelvis or ureter. These tumours respond poorly to systemic chemotherapy and often recur, making radical nephroureterectomy or partial bladder resection the current standard of care. However, surgery is frequently not feasible or can severely reduce patient quality of life due to complications. UTUC patients are typically older, with an average age of 73 at diagnosis, and often have co-morbidities that compound health risks. Up to 50% of patients already have impaired renal function, and surgery can worsen this, limiting future use of cisplatin-based chemotherapy for metastatic disease. Currently, there are few effective systemic treatments for UTUC, leaving clinicians unable to treat patients who are ineligible for surgery or for whom surgery would be excessively harmful. Even when treatment options exist, morbidity and toxicity remain high, leading to complications, reduced quality of life, and diminished future treatment possibilities due to renal failure.
In 2019, EU inpatient care spending represented about 3.1% of GDP (€432.52 billion), while overall health spending was 7% (€983 billion). Current UTUC treatment protocols often require multiple hospitalizations. A retrospective study reported excess costs of $252,272 (~€220,840) per patient over five years, largely due to the high incidence of end-stage renal failure following surgery. Most low-grade UTUC patients undergo radical nephroureterectomy within a year of diagnosis, underscoring the need for alternatives.
Padeliporfin VTP (Vascular Targeted Photodynamic Therapy) offers a novel, minimally invasive oncology platform for treating solid tumours. It combines an intravenous drug, Padeliporfin-dipotassium, with a proprietary laser and fibre device for localized, non-thermal light delivery. Padeliporfin is derived from bacteriochlorophyll and remains inactive until illuminated. After administration, it binds to serum albumin and circulates for a short time before elimination. When activated by laser light, it reacts with oxygen to produce radicals that block tumour blood vessels, causing tumour necrosis within hours. This process triggers immunogenic cell death and immune activation, enhancing efficacy while sparing healthy tissue. The treatment is repeatable in the same area, preserves the organ, and minimizes side effects. The innovation consists of two elements: the drug and the device enabling precise photoactivation. The therapy eliminates tumours efficiently, preserves renal function, and avoids surgical morbidity. It also activates the immune system, improving outcomes beyond local control. The technology has reached TRL7 and has been validated in operational settings, including EMA approval for low-grade prostate cancer and a Ph1 trial for low-grade UTUC. Current efforts focus on qualifying and validating drug efficacy in a Phase 3 pivotal study under the EIC framework, preparing for market entry after trial completion and regulatory approval.
In 2019, EU inpatient care spending represented about 3.1% of GDP (€432.52 billion), while overall health spending was 7% (€983 billion). Current UTUC treatment protocols often require multiple hospitalizations. A retrospective study reported excess costs of $252,272 (~€220,840) per patient over five years, largely due to the high incidence of end-stage renal failure following surgery. Most low-grade UTUC patients undergo radical nephroureterectomy within a year of diagnosis, underscoring the need for alternatives.
Padeliporfin VTP (Vascular Targeted Photodynamic Therapy) offers a novel, minimally invasive oncology platform for treating solid tumours. It combines an intravenous drug, Padeliporfin-dipotassium, with a proprietary laser and fibre device for localized, non-thermal light delivery. Padeliporfin is derived from bacteriochlorophyll and remains inactive until illuminated. After administration, it binds to serum albumin and circulates for a short time before elimination. When activated by laser light, it reacts with oxygen to produce radicals that block tumour blood vessels, causing tumour necrosis within hours. This process triggers immunogenic cell death and immune activation, enhancing efficacy while sparing healthy tissue. The treatment is repeatable in the same area, preserves the organ, and minimizes side effects. The innovation consists of two elements: the drug and the device enabling precise photoactivation. The therapy eliminates tumours efficiently, preserves renal function, and avoids surgical morbidity. It also activates the immune system, improving outcomes beyond local control. The technology has reached TRL7 and has been validated in operational settings, including EMA approval for low-grade prostate cancer and a Ph1 trial for low-grade UTUC. Current efforts focus on qualifying and validating drug efficacy in a Phase 3 pivotal study under the EIC framework, preparing for market entry after trial completion and regulatory approval.
Over the past year, Impact Biotech has advanced its clinical, operational, and regulatory programs supporting the development of Padeliporfin Vascular Targeted Photodynamic Therapy (Padeliporfin VTP) for the treatment of Low-Grade Upper Tract Urothelial Cancer (LG-UTUC). This report summarizes the company’s progress, outlining the status of clinical site activation, patient enrolment and induction-phase completion, interim safety and efficacy observations, and regulatory interactions with the U.S. Food and Drug Administration (FDA). Impact Biotech continues to demonstrate strong progress toward bringing a novel therapeutic option to patients with this underserved, orphan indication.
During the first year of the grant period, Impact Biotech focused on expanding and solidifying its network of clinical sites capable of supporting the pivotal clinical trial for LG-UTUC. As planned, the company initially considered the activation of 30 total clinical sites, a number determined by anticipated patient availability, historic urological patient’s referral patterns, and the distribution of specialty urological clinics managing this rare disease. Throughout the year, the company conducted ongoing, data-driven assessments of its clinical trial operations to ensure optimal allocation of resources. Based on this continuous strategic evaluation, the company determined that a focused network of approximately 20 high-performing clinical sites would most effectively support enrolment and operational efficiency for the pivotal trial.
To date, more than 20 clinical sites have been established to support trial operations. Within the United States, 12 clinical sites are currently active and have initiated patient treatment. In Europe, four clinical sites are active across Germany (1 site), Spain (1 site), and France (2 sites). These locations have played an important role in enabling international patient access and diversifying enrolment sources. All these sites are led by investigators who are at the fore front of the urological therapeutic area, specifically in UTUC.
A principal milestone for the reporting year was the initiation of the induction treatment phase for patients enrolled in the pivotal trial. The FDA aligned with Impact Biotech on the plan requiring the enrolment of 100 patients to achieve 79 evaluable patients for the primary analysis. Over the past year, patient enrolment has progressed steadily at a pace of approximately three to five patients per month.
During the first year of the grant period, Impact Biotech focused on expanding and solidifying its network of clinical sites capable of supporting the pivotal clinical trial for LG-UTUC. As planned, the company initially considered the activation of 30 total clinical sites, a number determined by anticipated patient availability, historic urological patient’s referral patterns, and the distribution of specialty urological clinics managing this rare disease. Throughout the year, the company conducted ongoing, data-driven assessments of its clinical trial operations to ensure optimal allocation of resources. Based on this continuous strategic evaluation, the company determined that a focused network of approximately 20 high-performing clinical sites would most effectively support enrolment and operational efficiency for the pivotal trial.
To date, more than 20 clinical sites have been established to support trial operations. Within the United States, 12 clinical sites are currently active and have initiated patient treatment. In Europe, four clinical sites are active across Germany (1 site), Spain (1 site), and France (2 sites). These locations have played an important role in enabling international patient access and diversifying enrolment sources. All these sites are led by investigators who are at the fore front of the urological therapeutic area, specifically in UTUC.
A principal milestone for the reporting year was the initiation of the induction treatment phase for patients enrolled in the pivotal trial. The FDA aligned with Impact Biotech on the plan requiring the enrolment of 100 patients to achieve 79 evaluable patients for the primary analysis. Over the past year, patient enrolment has progressed steadily at a pace of approximately three to five patients per month.
Among the 60 patients completing the induction phase, 50 patients (83%) demonstrated a response at the time of the Primary Response Evaluation (PRE). Within this group, 40 patients (67%) achieved a Complete Response (CR), and an additional 10 patients (17%) demonstrated a Partial Response. Investigators have characterized these interim efficacy findings as promising and anticipate that outcomes will remain significantly favourable compared with the existing direct competitor, Jelmyto. These data reinforce the therapeutic potential of Padeliporfin VTP and reflect strong alignment with the trial’s clinical objectives.
From a safety perspective, the interim findings reflect a stable and well-tolerated profile, with no treatment-related concerns emerging during the course of the trial to date. No patients have discontinued participation due to treatment-related adverse events, and the adverse events observed to date have been attributable primarily to the underlying urological procedures rather than to Padeliporfin VTP itself. This strong safety profile, also compared (indirectly) with the available approved treatment in the market (Jelmyto), provides a solid foundation for the ongoing development of the therapy and supports its progression toward regulatory submission.
From a safety perspective, the interim findings reflect a stable and well-tolerated profile, with no treatment-related concerns emerging during the course of the trial to date. No patients have discontinued participation due to treatment-related adverse events, and the adverse events observed to date have been attributable primarily to the underlying urological procedures rather than to Padeliporfin VTP itself. This strong safety profile, also compared (indirectly) with the available approved treatment in the market (Jelmyto), provides a solid foundation for the ongoing development of the therapy and supports its progression toward regulatory submission.