Press release - Oslo, Norway, 28 February 2022: Photocure ASA (OSE: PHO), the
Bladder Cancer Company, announces the publication of new results from its
exploratory research program in the journal Biomedicines, entitled "Antitumor
Effect and Induced Immune Response Following Exposure of Hexaminolevulinate
(HAL) and Blue Light in an Orthotopic Model of Rat Bladder Cancer". These
results support initial pre-clinical data on the potential anti-tumor effect of
HAL, which were presented at the BLADDR 2019 congress
[https://photocure.com/news/photocure-new-data-from-hexvixr-trials-presented-at
-the-bladdr-2019-congress-3457632].

The study objective was based on the hypothesis that the positive impact on long
-term outcomes in NMIBC patients who had undergone Blue Light Cystoscopy (BLC)
prior to cystectomy could be caused by a direct anti-tumor effect and/or
activation of the immune system indicating an additional effect of Blue Light
with HAL beyond pure detection. Therefore, as an exploratory preclinical study,
the authors investigated whether intravesical administration of HAL followed by
a diagnostic blue-light illumination-regime, aiming to mimic the one used
currently in Photodynamic Diagnosis (PDD), could have anti-tumor and/or immune
modulating effects as seen with Photodynamic therapy (PDT). In addition, it was
explored if co-administration of a checkpoint inhibitor would increase the
susceptibility to the PD-1/PD-L1 pathway inhibition thus increasing the anti
-tumor effect. Over the years, Photocure has conducted a number of experiments
on "mechanisms of actions" effects of HAL, as well as to see if there
potentially are similar anti-tumor and immune modulating effects of PDD with
blue light as reported with PDT. For this study, rats were treated with HAL and
blue light in an orthotopic model of bladder cancer, and then subjected to
histopathological analysis of the bladder samples and additional assessment of
immune markers. Co-administration of HAL and blue light with a checkpoint
inhibitor was further evaluated in this model aiming to assess for potentiation
of anti-tumor effects when combined with an immunotherapy.

Results of the study demonstrated an anti-tumor effect of HAL and blue light
when aiming to mimic the dosing regimen of a photodynamic diagnostic procedure
(PDD) in an orthotopic bladder cancer model in rats.

The authors conclude "The anti-tumor effect is most probably pertaining to
stimulation of the immune system as evident by tumor infiltration of CD3+ and
CD8+ T-cells. These results support our hypothesis that the positive impact on
patient outcomes observed in patients who had undergone BLC prior to cystectomy
could be explained by systemic immune activation induced by HAL and blue light.
Combination of HAL and blue light with intravesical anti-PD-L1 resulted in
increased anti-tumor effects. Further studies are warranted to explore the long
-term effects of HAL and blue light alone or in combination with checkpoint
inhibitors which should extend to investigate any systemic (abscopal) effects.
Intriguingly is also the idea that local treatment with HAL and blue light can
prime an immune response with potential additional effect of checkpoint
inhibitors."

"The intriguing results from this pre-clinical study are encouraging and might
explain an effect of HAL+BL beyond pure detection. The results motivate further
research to evaluate the potential of HAL as a photodynamic therapy (PDT), which
may be an innovative technique for treatment of non-muscle invasive bladder
cancer.", said Anders Neijber, Vice President, Global Medical Affairs and
Clinical Development at Photocure.

Read the full article here: https://www.mdpi.com/2227-9059/10/3/548

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About Bladder Cancer
Bladder cancer ranks as the seventh most common cancer worldwide, with 1 720 000
prevalent cases (5-year prevalence rate)[1a], 573 000 new cases and more than
200 000 deaths annually in 2020.[1b]

Approx. 75% of all bladder cancer cases occur in men.[1] It has a high
recurrence rate, with an average of 61% in year one and 78% over five years.[2]
Bladder cancer has the highest lifetime treatment costs per patient of all
cancers.[3]

Bladder cancer is a costly, potentially progressive disease for which patients
have to undergo multiple cystoscopies due to the high risk of recurrence. There
is an urgent need to improve both the diagnosis and the management of bladder
cancer for the benefit of patients and healthcare systems alike.

Bladder cancer is classified into two types, non-muscle invasive bladder cancer
(NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of
invasion in the bladder wall. NMIBC remains in the inner layer of cells lining
the bladder. These cancers are the most common (75%) of all cases and include
the subtypes Ta, carcinoma in situ (CIS), and T1 lesions. In MIBC, the cancer
has grown into deeper layers of the bladder wall. These cancers, including
subtypes T2, T3, and T4, are more likely to spread and are harder to treat.[4]
[1] Globocan. a) 5-year prevalence / b) incidence/mortality by population.
Available at: https://gco.iarc.fr/today, accessed [January 2022].
[2] Babjuk M, et al. Eur Urol. 2019