LTX-401 is a novel oncolytic compound designed for the local treatment of solid tumors. In the present study, we have examined the applicability and efficacy of LTX-401 in a rat model JM1 hepatocellular carcinoma, with particular interest in its ability to induce antitumor immunity. LTX-401 induces necrotic cell death followed by the release of immunogenic cell death mediators such as high-mobility group box 1 protein, ATP, and cytochrome c. When injected into subcutaneous and orthotopic JM1 tumors, LTX-401 treatment resulted in a strong antitumoral effect followed by complete tumor regression in the majority of animals. Additionally, LTX-401 could affect the growth of distal tumor deposits simulating metastases, hence indicating immune-mediated abscopal responses. Furthermore, LTX-401 treatment induced tumor-specific immune responses as seen by protection against tumor rechallenge and increased production of interferon-gamma (IFN-γ) by splenic cells in response to stimulation with tumor cells. Taken together, our data demonstrate that the oncolytic compound LTX-401 provides local tumor control followed by protective immune responses and may be exploited as a novel immunotherapeutic agent in hepatocellular carcinoma.

01 Aug 2019·Cell Death & DifferentiationQ1 · BIOLOGY

Recruitment of LC3 to damaged Golgi apparatus

Q1 · BIOLOGY

Article

Author: Jimenez, Ana Joaquina ; Arnaut, Luis G ; Souquere, Sylvie ; Storch, Marko ; Divoux, Séverine ; Kroemer, Guido ; Rekdal, Øystein ; Sauvat, Allan ; Kepp, Oliver ; Sveinbjørnsson, Baldur ; Xie, Wei ; Perez, Franck ; Gomes-da-Silva, Lígia C

LC3 is a protein that can associate with autophagosomes, autolysosomes, and phagosomes. Here, we show that LC3 can also redistribute toward the damaged Golgi apparatus where it clusters with SQSTM1/p62 and lysosomes. This organelle-specific relocation, which did not involve the generation of double-membraned autophagosomes, could be observed after Golgi damage was induced by various strategies, namely (i) laser-induced localized cellular damage, (ii) local expression of peroxidase and exposure to peroxide and diaminobenzidine, (iii) treatment with the Golgi-tropic photosensitizer redaporfin and light, (iv) or exposure to the Golgi-tropic anticancer peptidomimetic LTX-401. Mechanistic exploration led to the conclusion that both reactive oxygen species-dependent and -independent Golgi damage induces a similar phenotype that depended on ATG5 yet did not depend on phosphatidylinositol-3-kinase catalytic subunit type 3 and Beclin-1. Interestingly, knockout of ATG5 sensitized cells to Golgi damage-induced cell death, suggesting that the pathway culminating in the relocation of LC3 to the damaged Golgi may have a cytoprotective function.

03 Jul 2019·OncoImmunologyQ2 · MEDICINE

Tumor lysis with LTX-401 creates anticancer immunity

Q2 · MEDICINE

ArticleOA

Author: Pol, Jonathan ; Yamazaki, Takahiro ; Mauseth, Brynjar ; Kepp, Oliver ; Xie, Wei ; Mondragón, Laura ; Kroemer, Guido ; Zitvogel, Laurence ; Lévesque, Sarah ; Eksteen, Johannes J ; Zhou, Heng ; Wang, Yan ; Rekdal, Øystein ; Sveinbjørnsson, Baldur

Local immunotherapies such as the intratumoral injection of oncolytic compounds aim at reinstating and enhancing systemic anticancer immune responses. LTX-315 is a first-in-class, clinically evaluated oncolytic peptide-based local immunotherapy that meets these criteria. Here, we show that LTX-401, yet another oncolytic compound designed for local immunotherapy, depicts a similar safety profile and that sequential local inoculation of LTX-401 was able to cure immunocompetent host from subcutaneous MCA205 and TC-1 cancers. Cured animals exhibited long-term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors. Nevertheless, the local treatment with LTX-401 alone had only limited abscopal effects on secondary contralateral lesions. Anticancer effects resulting from single as well as sequential injections of LTX-401 were boosted in combination with PD-1 and CTLA-4 immune checkpoint blockade (ICB), and sequential LTX-401 treatment combined with double ICB exhibited strong abscopal antineoplastic effects on contralateral tumors underlining the potency of this combination therapy.

News (Medical) associated with LTX-401

17 Nov 2022

·www.prnewswire.com

Lytix Biopharma third quarter 2022 results

OSLO, Norway, Nov. 17, 2022 /PRNewswire/ -- Lytix Biopharma ("Lytix") (Euronext Growth Oslo: LYTIX), a Norwegian immune-oncology company, today releases its third quarter 2022 results. Highlights include regulatory approval received to expand our ATLAS-IT-05 study to three European countries and the appointment of Stephen Worsley as CBO. "We are very pleased to now being able to include patients from Spain, France and Norway in our Phase II study. The expansion of the site network will mitigate recruitment challenges, drive enrollment towards completion and extend the clinical impact field for LTX-315", says CEO and Co-founder of Lytix Biopharma, Øystein Rekdal. Highlights from the third quarter 2022: LTX-315 Regulatory approval received to expand the ATLAS-IT-05 study to three European countries (Norway, France and Spain) Verrica Pharmaceuticals is in good progress with their Phase II study in BCC, and the conclusion of part 1 of three parts is expected in Q1 2023 IND enabling activities required to start a Phase I study with LTX-401 is progressing as planned Stephen Worsley appointed as Chief Business Officer (CBO), and he is already introducing Lytix to KOLs and companies within the industry Post-period events: Compelling data describing how LTX-315 activates dendritic cells and contributes to anti-cancer immune response was presented at the Society for Immunotherapy of Cancer (SITC) Additional study sites opened in Europe to support ATLAS-IT-05 patient recruitment ATLAS-IT-04 Clinical Study Report completed Proof-of-concept achieved, demonstrating the clinical benefits of LTX-315 in combination with Adoptive Cell Therapy (ACT) in heavily pre-treated sarcoma patients Financial: Total operating income for Q3 2022 includes NOK 1.4 million in revenue from our licensing partner Verrica. This revenue is for sale of LTX-315 for use in Verrica's development program. This is the first, and currently only, agreement where Lytix sells LTX-315 to a commercial party. Total operating expenses for the six months that ended September 30 are in line with the same period last year, and as a clinical drug development company, R&D efforts represent the majority of our expenses. A portion of the excess liquidity has been placed in a liquidity fund explaining the increase in short-term financial investments. At the end of the period cash plus short-term financial investments was NOK 172 million. Key figures (unaudited): Government grants recognized in profit and loss, part of Other operating Income, for Q2 2022 was reported at NOK 805 thousand which was NOK 750 thousand lower than actual. The correct amount is NOK 1,555 thousand. The figures in this report are correct, but the YTD figures will therefore not be reconcilable with the H1 report without adjusting for this error. The results will be presented in a webcast with CEO Øystein Rekdal, CDO Graeme Currie and CFO Gjest Breistein today at 14.30 CEST. The presentation and subsequent Q&A session will be held in English and may be viewed live at A recording of the presentation will be made available on after the presentation. For more information, please contact: Gjest Breistein, CFO: [email protected] Ole Peter Nordby, Head of IR & Communication Manager: [email protected] SOURCE Lytix Biopharma AS

Phase 2Phase 1Executive ChangeFinancial StatementImmunotherapy

25 Aug 2022

·www.prnewswire.com

Lytix Biopharma: Second quarter and first half of 2022 results

OSLO, Norway, Aug. 25, 2022 /PRNewswire/ -- Lytix Biopharma, a Norwegian immune-oncology company, today releases its second quarter and first half 2022 results - New encouraging clinical data. "The first six months of 2022 have been fueled by clinical development and clinical data presentations across international conferences alongside seeing our partner Verrica Pharmaceuticals advance its Phase II study evaluating LTX-315 for basal cell carcinoma. For Lytix, the most significant clinical trial development was the completion of the Phase II study evaluating LTX-315 in combination with adoptive therapy (ACT) in soft tissue sarcoma patients. This combination treatment provided meaningful clinical benefit for patients with progressive metastatic soft tissue sarcoma and clearly shows the potential of using LTX-315 in combination with ACT to generate a high number of tumor-specific T cells", says Dr. Øystein Rekdal, CEO of Lytix Biopharma. Highlights from the first quarter 2022: Data from the Phase II ATLAS-IT-04 trial evaluating LTX-315 in sarcoma patients demonstrated proof-of-concept by showing that the compound improved the outcome of adoptive cell transfer treatment by stabilizing the disease in patients with progressive metastatic soft tissue sarcoma. In April, Verrica Pharmaceuticals dosed the first patient in its Phase II study evaluating LTX-315 in basal cell carcinoma (BCC), triggering an initial milestone payment to Lytix. Regulatory process is initiated and ongoing to expand the site network for the ATLAS-IT-05 study to highly recognized sites with intratumoral immunotherapy expertise in three European countries. The preclinical safety testing for LTX-401 has been completed demonstrating a favorable safety profile. Preparations for a Phase I clinical study are progressing according to plan. In April, Lytix received a USD 1 million milestone payment from Verrica following first patient dosed in its Phase II study of LTX-315 for the treatment of basal cell carcinoma. Total operating expenses for the six months ended 30 June 2022 ended at NOK 36.6 million, which is in line with last year's figures of NOK 36.1 million. Key figures (unaudited): The full report and a presentation is linked to this press release (and available at ). The results will be presented in a webcast with CEO Øystein Rekdal, CDO Graeme Currie and CFO Gjest Breistein at 14:30 CEST. The presentation and subsequent Q&A session will be held in English and may be viewed live. Please register for the presentation at Lytix Biopharma Q2 webcast 25.08.22 A recording of the presentation will be made available on after the presentation. For more information, please contact: Ole Peter Nordby [email protected] Lytix Biopharma in brief: Based in Oslo, Norway, Lytix is a clinical stage biotech company developing novel cancer immunotherapies, an area within cancer therapy that is aimed at activating the patient's immune system to fight cancer. The company's technology is based on pioneering research in "host defense peptides" – nature's first line of defense towards foreign pathogens. Lytix Biopharma's lead product, LTX-315, is a first-in-class oncolytic molecule representing a new and superior therapeutic principle to boost anti-cancer immunity, with the potential to be the ideal combination partner with other types of immunotherapies. LTX-315 targets cancer cells and disintegrates their cell membranes, causing immunogenic cell death and release of a patient's tumor specific antigens and potent immunostimulants. This mode of action allows cytotoxic T cells to recognize, infiltrate and attack cancer cells. This information was brought to you by Cision The following files are available for download: SOURCE Lytix Biopharma AS

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Indication	Highest Phase	Country/Location	Organization	Date
Liver Cancer	Preclinical	NO	Lytix Biopharma AS	-

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