Marker Therapeutics Reports MT-401 Non-Clinical Data in AML Cells after Hypomethylating Agent Administration

On June 26, 2023 Marker Therapeutics, Inc. (Nasdaq: MRKR) (Marker or the Company), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported non-clinical data on its lead multi-tumor-associated antigen (multiTAA)-specific T cell product candidate, MT-401, which showed increased anti-tumor activity against an acute myeloid leukemia (AML) cell line after treatment with hypomethylating agents (HMA) (Press release, Marker Therapeutics, JUN 26, 2023, View Source [SID1234632899]). Marker further announces that the Company has been awarded a $2 million grant from the National Institutes of Health (NIH) Small Business Innovation Research (SBIR) program to support the development of MT-401 for the treatment of patients with AML after hematopoietic stem cell transplant (HSCT).

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The multiTAA-specific T cell technology from Marker uses a novel non-genetically modified T cell therapy approach that recognizes multiple antigens expressed on tumor cells, thereby designed to minimize tumor escape. MT-401 was designed to specifically target four different antigens (Survivin, PRAME, WT-1 and NY-ESO-1), which are upregulated in AML but have limited expression on normal cells.

In March 2023, Marker reported clinical updates from the Company sponsored ARTEMIS clinical trial (clinicaltrials.gov identifier: NCT04511130) highlighting the potential benefit of MT-401 in patients with AML who have measurable residual disease (MRD+) after HSCT. Given the promising responses in patients who are MRD+, Marker has been investigating clinical opportunities to further improve AML patient outcomes.

One such opportunity is to combine multiTAA-specific T cell therapy with agents that make cancer cells more visible to cancer killing cells. This opportunity has practical merit because HMAs that do this, such as 5’-Azacytidine and Decitabine, are commonly used as therapies for AML. It also has scientific merit because these agents inhibit DNA methylation, a process which regulates gene expression. By reducing DNA methylation, HMAs can restore physiological gene expression patterns, including the upregulation of tumor suppressor genes, and the inhibition of oncogenes. HMAs have also been found to upregulate the expression of tumor antigens, including MT-401-specific tumor antigens, previously silenced by DNA methylation (Wong et al, Front Oncol, 2021).

Due to this mechanism of action, Laura S. Angelo, Ph.D., and her team at Marker investigated in a set of in vitro experiments, the capacity of MT-401 to inhibit or kill THP-1 cells, an aggressive treatment-resistant AML cell line, after the cells were exposed to HMA. The results of this non-clinical study have been posted on the Investor Relations section of the Marker website, and highlights are briefly summarized below:

· In this in vitro model of treatment resistant AML, tumor cells exposed to HMA for 72 hours upregulated tumor-associated antigen targets of MT-401, including Survivin.

· The THP-1 cell line was bioluminescent modified to allow real-time long-term assessment of cancer cell growth.

· THP-1 cells continued to grow both in the absence and presence of DMSO, the vehicle used to dissolve 5’-Azacytidine.

· The growth of THP-1 cells was reduced in the presence of 5’-Azacytidine (after exposure to the drug for 72 hours).

· The growth of THP-1 cells was also reduced in the presence of MT-401 (manufactured from donors that were partially HLA-matched to THP-1 cells).

· THP-1 cell growth, however, was significantly decreased when MT-401 was added after exposure to 5’-Azacytidine compared to MT-401 or 5’-Azacytidine administration alone, suggesting a synergistic effect between the two agents.

· These in vitro data demonstrate that administration of MT-401 following HMA infusion enhanced AML cell killing and could offer a new therapeutic option for AML patients post-HSCT.

"These non-clinical findings highlight that the potential for treatment of AML cells with HMA to upregulate expression of specific tumor antigens and increase tumor inhibition and killing. These benefits could therefore significantly enhance the potential clinical outcome of our multiTAA-specific T cell product," said Juan F. Vera, M.D., President and Chief Executive Officer of Marker Therapeutics. "In light of these encouraging results we are planning to incorporate these findings into our current AML clinical study to improve and empower our multiTAA-specific T cell outcomes. Details about the revised clinical study design will be announced in Q3 of 2023."

Based on this non-clinical data, Marker received a $2 million grant from the NIH. The awarded SBIR grant will support a nationwide multi-center Phase 2b clinical trial in AML patients following HSCT to evaluate the effect of MT-401 administered after pre-treatment with HMAs. This proposed Phase 2b study includes evaluation of efficacy and safety of MT-401, as well as immune monitoring of patient samples. AML is considered an orphan indication and in 2020, MT-401 was granted orphan designation by the U.S. Food and Drug Administration for treatment of patients with acute myeloid leukemia (orphan drug designation number DRU-2020-7363).

"We are pleased to receive the SBIR grant from the NIH to support our clinical Phase 2b study in AML patients, a rare disease with limited treatment options after a stem cell transplant," said Dr. Angelo, PI of the study.

"We previously observed promising results in our Phase 2 ARTEMIS trial for patients with AML who are MRD+ post-transplant, suggesting that MT-401 can effectively positively impact this patient population before relapse. The SBIR grant will greatly contribute to further advance our clinical trial and to investigate the benefit of HMA administration before MT-401 therapy in patients after HSCT, and for whom no treatments have been approved," concluded Dr. Vera.

About the NIH SBIR Program

The NIH Small Business Innovation Research (SBIR) Program sets aside more than $1.2 billion from its Research & Development Funding to specifically support early-stage small businesses throughout the United States. Many companies leverage the NIH SBIR funding to attract the partners and investors needed to take an innovation to market. The Small Business program focuses on a variety of high-impact technologies including research tools, diagnostics, digital health, drugs, and medical devices, and can provide the seed funding needed to bring scientific innovations from bench to bedside.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 180 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated, demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect. Unlike other cell therapies which require hospitalization and close monitoring, multiTAA-specific T cells are designed to be administered in an outpatient setting.

Corporate presentation

On June 26, 2023 Lipocine presented its corporate presentation (Presentation, Lipocine, JUN 26, 2023, View Source [SID1234632898]).

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KAZIA CORPORATE UPDATE AND CORPORATE PRESENTATION

On June 26, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported an update on key corporate and clinical initiatives and release a new investor presentation (Press release, Kazia Therapeutics, JUN 26, 2023, View Source [SID1234632897]).

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Key points

Dr John Friend completes transition into the CEO role, including a full portfolio review.


Final data anticipated from GBM AGILE pivotal study of paxalisib in glioblastoma in 2H CY2023.


Interim data from phase II Pacific Pediatric NeuroOncology Consortium study in diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) now expected to be available in July or August 2023.


Phase I expansion cohort is enrolling for brain metastases study sponsored by Memorial Sloan Kettering Cancer Center. Two other preeminent cancer centres have joined the study. Preliminary data from expansion cohort is anticipated by 1Q24.

Following his appointment as CEO on 1 May 2023, Dr John Friend has completed his transition into the role. He commented, "In the weeks since my appointment, I’ve worked with the team to review the full set of assets and clinical trials within the Kazia portfolio and the process has strongly reinforced my conviction in the opportunities ahead of us."

"We believe substantial potential exists across our pipeline and in particular, across three key pillars of development for paxalisib—adult brain cancer, paediatric brain cancer and brain metastases. We are keen to explore paxalisib’s use in patient populations that may have the greatest benefit from a PI3K/AKT/mTOR targeted therapeutic candidate."

"As we move toward the second half of 2023, critical milestones are approaching for both paxalisib and EVT-801. We look forward to keeping investors updated across our progress on these important programs."

Clinical programs update

11 clinical trials are currently in progress or in planning for Kazia’s two assets, paxalisib and EVT-801, and Kazia continues to execute across all programs. Current program highlights are set out in brief below. Refer to the appended corporate presentation for more detail:

Paxalisib

Kazia’s lead program is paxalisib, an investigational brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of brain cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in various brain cancers.

GBM AGILE Pivotal study

Final data are expected from the GBM AGILE pivotal study of paxalisib in glioblastoma in 2H CY2023. Depending on the results of the study, Kazia may use such data to support submission of a new drug application for marketing authorisation to the FDA.

PNOC022 phase II study

Paxalisib is being studied as an investigational drug for the treatment of the paediatric brain cancers DIPG and other DMGs in a study sponsored by the Pacific Pediatric Neuro-Oncology Consortium (PNOC).

The study team at PNOC has been diligently collecting and preparing the data for interim analysis. At this point, Kazia expects that the data will be available in July or August 2023.

LUMOS2 phase II study

On 8 June 2023, Kazia announced that it is supporting the University of Sydney on a molecularly-guided phase II clinical study evaluating paxalisib in adult patients with recurrent/progressive isocitrate dehydrogenase (IDH) mutant grade 2 and 3 gliomas (G2/3 gliomas).

The study, named LUMOS2, will be sponsored by the University of Sydney, and coordinated by NHMRC Clinical Trials Centre, University of Sydney, in collaboration with COGNO (CoOperative Trials Group for Neuro-Oncology). LUMOS2, an umbrella study with multiple arms, is expected to enroll up to 76 patients and will be a multi-centre study at several Australian sites, with the potential to expand internationally. We anticipate enrollment to commence in 4Q23.

MSKCC phase I clinical study

Paxalisib is the subject of an ongoing phase I clinical study in combination with radiotherapy for the treatment of brain metastases, sponsored by Memorial Sloan Kettering Cancer Center in New York, NY.

Kazia is pleased to confirm that the phase I expansion cohort is enrolling. Two world-renowned cancer centres have joined MSKCC in this study: Miami Cancer Institute and Fred Hutch Cancer Center in Seattle, WA. Preliminary data from the expansion cohort is anticipated by 1Q24.

EVT-801

Phase I study

Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data showed EVT801 to be active against a broad range of tumour types and has shown evidence of synergy with immuno-oncology agents. A phase I study commenced recruitment in November 2021.

EVT-801 continues to enroll in the phase I dose finding study. Kazia anticipates stage 1 data in 2H23, which we believe will enable identification of the recommended dose for subsequent phase II trials. Kazia also anticipates reporting preliminary biomarker data focused on high-grade, serous ovarian cancer as part of this data update.

Instil Bio Announces Oral Presentation of ITIL-306 Preclinical Data at British Society for Gene and Cell Therapy Annual Conference

On June 26, 2023 Instil Bio, Inc. ("Instil") (NASDAQ: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported an oral presentation at the British Society for Gene and Cell Therapy Annual Conference, demonstrating that its proprietary CoStimulatory Antigen Receptor (CoStAR) platform enhances activity of TILs against autologous tumor (Press release, Instil Bio, JUN 26, 2023, View Source [SID1234632896]).

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The presentation highlighted CoStAR’s unique mechanism of action which results in greatly enhanced activity of TILs when activation occurs through both the native TCR and engineered CoStAR receptors. Additionally, novel data demonstrated that Instil’s FRα-CoStAR enhances activity of TILs against autologous tumors with varied expression of FRα including ovarian, renal, and non-small cell lung cancer tumors. The robust activity of NSCLC, ovarian, and renal carcinoma CoStAR-TILs against autologous tumor exceeded that of genetically unmodified melanoma TILs, as measured by secretion of IFNγ.

"The finding that CoStAR can enhance the anti-tumor reactivity of TILs in challenging tumor types such as non-small cell lung cancer even beyond that seen with melanoma TILs is compelling," said Robert Hawkins, MBBS PhD, Head of Research and Development at Instil Bio. "These preclinical data continue to support our excitement around the anticipated resumption of the clinical study of ITIL-306 in patients with advanced cancers which express FRα."

First Patient Dosed in Phase 2 MATISSE Trial of IPH5201 in Early Stage Lung Cancer

On June 26, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the first patient was dosed in MATISSE, a Phase 2 multicenter single-arm study (NCT05742607), sponsored by Innate Pharma, evaluating neoadjuvant and adjuvant treatment with IPH5201, an anti-CD39 blocking monoclonal antibody, in combination with durvalumab (anti-PD-L1) and chemotherapy, in treatment-naïve patients with resectable early stage non-small cell lung cancer (NSCLC) (Press release, Innate Pharma, JUN 26, 2023, View Source [SID1234632895]).

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The primary objectives of the study are to assess antitumor activity of neoadjuvant treatment based on pathological complete response (pCR) and safety.

Innate is responsible for conducting the study and shares study costs with AstraZeneca (LSE/STO/Nasdaq: AZN). AstraZeneca supplies clinical trial drugs.

Joyson Karakunnel, MD, MSc, FACP, Chief Medical Officer at Innate Pharma "We are pleased to announce the dosing of a first patient in this Phase 2 study conducted in collaboration with our partner AstraZeneca. The study aims to assess the potential of combining our IPH5201 drug candidate with durvalumab as neoadjuvant treatment with chemotherapy and adjuvant treatment in patients affected by resectable, early stage non-small cell lung cancer. If this combination shows relevant anti-tumor activity while remaining well tolerated, as observed in the previous Phase 1 study, it will be a major step in the development of IPH5201 in this indication."

Fabrice Barlesi, MD, PhD, Professor of medicine at Paris Saclay University, General Manager of Gustave Roussy and principal investigator of the study added "Despite the introduction of novel treatment strategies, including immunotherapy with immune checkpoint inhibitors, many patients with resectable, early stage non-small cell lung cancer relapse following treatment leaving an important medical need in this setting. IPH5201 is a potential approach to reduce immunosuppression and promote antitumor immune responses in the tumor microenvironment. We look forward to continued enrollment and future results from this trial."

More information about the Phase 2 MATISSE trial can be found on clinicaltrials.gov.

Innate received a $5m milestone payment from AstraZeneca when the decision was made to progress IPH5201 to a Phase 2 clinical trial.

About IPH5201:

IPH5201 is a blocking antibody targeting the CD39 immunosuppressive pathway. CD39 is an extracellular enzyme that is expressed in the tumor microenvironment, on both tumor infiltrating cells and stromal cells in several cancer types. CD39 inhibits the immune system by degrading adenosine triphosphate (ATP) into adenosine monophosphate (AMP), which is then further degraded into adenosine by CD73. By promoting the accumulation of immune-stimulating ATP and preventing the production of immune-suppressive adenosine, the blockade of CD39 may stimulate anti-tumor activity.