On June 15, 2023 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported scientific updates in oral and poster presentations selected for international conferences: at the Antibody Engineering & Therapeutics Europe 2023 Conference in Amsterdam, Netherlands (June 7), at the FOCIS 2023 Annual Meeting (June 20-23), the 4th Annual Cytokine-Based Drug Development Summit 2023 (June 27-29) and at the 3rd Annual Tumor Myeloid-directed Therapies Summit 2023 (July 18-20) in Boston, US (Press release, OSE Immunotherapeutics, JUN 15, 2023, View Source [SID1234632769]). The communications feature the latest research on pre-IND programs for BiCKI-IL-7 (bifunctional therapy targeting PD-1 and IL-7), CLEC-1(1) (new myeloid immune checkpoint) in immuno-oncology and for OSE-230 (first pro-resolutive monoclonal antibody) in chronic inflammation.

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Dr Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: "We are very proud to share our latest scientific advances on our innovative pre-IND research programs with the international scientific community. The progress made on our next-generation immunotherapies in immuno-oncology and immuno-inflammation demonstrate our continued commitment to delivering first-in-class treatments for patients in high need for new therapeutic options. We are looking forward to progressing these programs with strategic partners into clinical stage".

Dr Aurore Morello, Head of Research of OSE Immunotherapeutics, said: "The latest data featured in our communications highlight the value and therapeutic potential of our pre-IND assets.

BiCKI-IL-7, our bispecific anti-PD1/IL-7 program, presents an innovative cytokine approach, selectively targeting tumor-specific T-cells to improve the quality and durability of memory T-lymphocyte responses.

CLEC-1, developed in academic collaboration with Dr Elise Chiffoleau’s team at the Center for Translational Research in Transplantation and Immunology (1) in Nantes, acts as a new myeloid immune checkpoint and the CLEC-1/new ligand TRIM21 axis as a new target for cancer immunotherapy. These latest data further support the preclinical evaluation of monoclonal antagonist antibodies targeting CLEC-1.

OSE-230, our most advanced pre-IND program, stands as the first pro-resolutive agonist monoclonal antibody, capable of clearing chronic neutrophil infiltrates and inhibiting the pathogenic NETosis (2) process and fibrosis".

BICKI-IL-7 PROGRAM IN IMMUNO-ONCOLOGY

ANTIBODY ENGINEERING & THERAPEUTICS EUROPE 2023 – JUNE 7, AMSTERDAM
Presenter: Aurore Morello, PhD., Head of Research of OSE Immunotherapeutics

"Anti-PD1/IL7v Cis-activated Stem-like T cells Expressing TCF1"
Human tumor-specific T cells expressed PD1. Stem-like TCF1+ T cells are key for the efficient and durable response of anti-PD1 mAbs in clinic (3). Stem-like TCF1+ co-express PD1 and CD127 and an anti-PD1/IL7v bifunctional molecule preferentially cis-target and expand the proliferation and survival of stem-like TCF1+ T cells without inducing their exhaustion in vitro in human chronic stimulation and exhaustion assays as well as in-vivo in tumor bearing mice.

4TH ANNUAL CYTOKINE-BASED DRUG DEVELOPMENT SUMMIT 2023 – JUNE 27-29, BOSTON
Day: Pre-Conference Workshop Day
Time: 9:00 am
Presenter: Nicolas Poirier, PhD, CEO and CSO of OSE Immunotherapeutics
Seminar:

"Going Beyond IL-2 to Explore Different Possibilities for the Development of Cytokine-Based Drugs"
Although the IL-2s have been the forefront of research within the field of cytokine-based drugs, many interleukins and interferons beyond IL-2 are becoming increasingly relevant. The applications of these cytokines are vast and their different mechanisms of action open up the field to more R&D and an endless number of possibilities to tackle the various diseases affecting the world.

Join this workshop to:

Discuss the progress of novel technologies on IL-7, IL-12, IL-18, IL-15 and more.
Understand the different mechanisms and mode of action employed by these cytokines.
Explore the TNF super family and interferons.
Understand clinical evaluation of non-alpha IL-2 and IL-15 cytokine therapies and implications for future drug development.
Discover how anti-PD1/IL7v bispecific selectively expand and maintain stemness of TCF1+ stem-like T cells.
CLEC-1 PROGRAM IN IMMUNO-ONCOLOGY

3RD ANNUAL TUMOR MYELOID-DIRECTED THERAPIES SUMMIT 2023 – 18-20 JULY, BOSTON
Day: Day Two
Time: 9:30 am
Presenter: Nicolas Poirier, PhD, CEO and CSO of OSE Immunotherapeutics

"CLEC-1 is a Novel Inhibitory Myeloid Receptor Sensing Cell Death & Limiting Tumor Antigen Cross-Presentation"

Details:

The orphan receptor CLEC-1 interacts with Trim21 over-expressed during cell death.
CLEC-1 inhibitory function limits T-cell cross-priming.
Positive preclinical efficacy with antagonist anti-CLEC1 mAb.
OSE-230 PROGRAM IN INFLAMMATION DISEASE

FOCIS 2023 ANNUAL MEETING – 20-23 JUNE, BOSTON
Date: June 20
Presenter: Vanessa Gauttier, Researcher, OSE Immunotherapeutics

Tu 220 – "Agonist anti-ChemR23 mAb inhibits NETosis and neutrophil-mediated inflammation"

(1) Collaborative academic program between OSE Immunotherapeutics and Dr Elise Chiffoleau’s research teams (Center for Research in Transplantation and Translational Immunology (CR2TI), UMR1064, INSERM, Nantes University at Nantes University Hospital, View Source).

(2) NETosis is a program for formation of neutrophil extracellular traps (NETs), which consists of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Recent research has highlighted that neutrophils, and in particular NETs that can be released upon activation, have central roles in the initiation and perpetuation of systemic autoimmune disorders and trigger complex and chronic inflammatory responses that lead to organ damage and fibrosis.

(3) Connolly K A et al. Sci Immunol. 2021, A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response

On June 15, 2023 GE HealthCare has reported the first patient scanned in a Phase I clinical trial2 of a first-of-its kind fluorine-18 PET radiopharmaceutical ([18F]GEH200521) specific for CD8, which is expressed on CD8+ T cells – a subpopulation of white blood cells which fight cancer (Press release, GE Healthcare, JUN 15, 2023, View Source [SID1234632768]).

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There are around 5000 immunotherapies in development today1, almost all of which work by activating CD8+ T cells both within and outside a tumor. The clinical trial will use this investigational radiopharmaceutical to help understand if patients have CD8+ T cells in their tumors and will, therefore, be more likely to respond to immune checkpoint inhibitors, the main class of immunotherapies currently approved for use. The study will also then help identify early response to immunotherapies, using sequential whole-body imaging to monitor CD8 changes over time, enabling physicians to switch patients who are not responding to alternative treatment options sooner.

The clinical trial, initiated in the Netherlands, is studying the safety and tolerability of the 18F-labeled radiopharmaceutical in patients with solid tumor malignancies. It will also determine the optimal timing for a patient scan following the administration of 18F-CD8 PET, which would be within the same day and, potentially, as soon as one hour, reducing the need for separate or multiple visits – providing more convenience for patients. 18F-CD8 PET may enable sequential imaging which could increase the likelihood of capturing even modest spatial and temporal changes in CD8+ T cells as soon as two to four days after an initial dose of immunotherapy or combinations of agents, compared to months with the standard RECIST (response evaluation criteria in solid tumors) approaches.

Only 20-40 percent3 of patients typically respond to immune checkpoint inhibitors. If successful, this tracer could help select patients more likely to respond to the appropriate immunotherapy. This could also avoid unnecessary treatment for those less likely to respond, or those not responding, who could be offered alternative treatment options earlier. For pharmaceutical companies and researchers, using this tracer to better understand the mechanism of action – i.e. the effect of immunotherapies on a patient’s immune response to their cancer – could, potentially, enable them to better select patients to participate in clinical trials and bring new immunotherapies to market.

Dr. Ken Herrmann, Section Editor of the Journal of Nuclear Medicine, said: "The clinical translation of a fluorine-18 PET tracer that targets CD8 would be a significant breakthrough in the field, not just for patients but also in the world of drug development."

Dr. Paul Evans, Head of Global Research & Development with GE HealthCare’s Pharmaceutical Diagnostics segment, said: "Immunotherapies can transform patients’ lives but low response rates, the potential of serious adverse effects, and high costs present challenges. That’s why research in this area is so important, to help individualize diagnosis and treatment for each patient. We will continue to innovate in this space, working alongside pharmaceutical companies and the oncology research community to develop a new class of complementary and companion imaging diagnostics."

GE HealthCare’s Pharmaceutical Diagnostics segment is a global leader in imaging agents used to support around 100 million procedures per year globally, equivalent to three patient procedures every second. Its Molecular Imaging portfolio combines established proprietary products across cardiology, neurology, and oncology, with an innovative pipeline, all aimed at enabling better-informed diagnosis and monitoring for improved therapy decision-making and clinical outcomes.

On June 15, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the US Food and Drug Administration (FDA), after reviewing the comprehensive submission, has approved the company’s Investigational New Drug (IND) application to evaluate the company’s lead asset NOX-A12 in a Phase 2 study in pancreatic cancer (OPTIMUS) in the United States (Press release, TME Pharma, JUN 15, 2023, View Source [SID1234632767]).

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OPTIMUS is an open-label Phase 2 study designed to evaluate the safety and efficacy of NOX-A12 combined with anti-PD-1 pembrolizumab (Keytruda from Merck) and two different chemotherapy regimens (nanoliposomal irinotecan/5-FU/Leucovorin or gemcitabine/nab-paclitaxel) in second-line pancreatic cancer. The study is expected to enroll approximately 70 patients in clinical sites in the US, as well as France and Spain, where the study has been previously approved.

"The US Food and Drug Administration’s approval of our IND application is an important milestone for TME Pharma, as it represents the first review and approval of NOX-A12 – and more broadly the first review of our class of compounds – by the FDA. Now we will be able to test NOX-A12 in clinical trials in the US, and this is a very positive piece of news for the future development of NOX-A12. We have thus delivered on our promise to the market to bring the OPTIMUS IND application with the FDA to successful completion, allowing rapid resumption of the pancreatic cancer program once financing is available," said Aram Mangasarian, CEO of TME Pharma.

As announced in June 2022, TME Pharma is currently focusing its capabilities on the development of NOX-A12 in glioblastoma. Therefore, the OPTIMUS Phase 2 trial in second-line pancreatic cancer will be initiated once appropriate funding becomes available.

NOX-A12 is currently being developed in GLORIA, a Phase 1/2 study evaluating NOX-A12 in combination with radiotherapy and with or without bevacizumab in first-line glioblastoma brain cancer (glioblastoma) patients with tumors resistant to standard chemotherapy (with unmethylated MGMT promoter). Interim data reported to date from GLORIA demonstrate that NOX-A12 has an excellent safety profile with extremely encouraging signs of efficacy showing an 83% rate of survival at 14 months in patients with detectable chemotherapy refractory tumor remaining after surgery.

On June 15, 2023 bioAffinity Technologies, Inc. (Nasdaq: BIAF; BIAFW), a biotechnology company addressing the need for early-stage cancer detection and broad-spectrum cancer therapeutics, reported the poster "Vitamin B12 deprivation does not phenocopy selective cytotoxicity of CD320 and LRP2 silencing" at the University of Massachusetts (UMass) T.H. Chan Medical School’s fifth annual RNA Therapeutics Symposium June 21-23, 2023, in Worcester, MA (Press release, BioAffinity Technologies, JUN 15, 2023, View Source [SID1234632766]).

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The RNA Therapeutics Institute at UMass leverages RNA biology and clinical research to develop new therapeutics for multiple diseases based on the fundamental mechanisms of cellular RNAs.

David Elzi, Ph.D., Vice President of Research, and William Bauta, Ph.D., Senior Vice President of Therapeutics, will discuss the Company’s recent work that demonstrated that deprivation of vitamin B12 does not play a role in the selective cytotoxicity of cancer cells observed after silencing the expression of two specific genes, CD320 and LRP2. The vitamin B12 research follows the Company’s discovery that using small interfering RNA (siRNA) to knock down CD320 and LRP2 killed cancer cells in vitro without harming healthy cells.

One of the functions of CD320 and LRP2 is to bind to and transport vitamin B12 into cells. Since they have that in common, Drs. Elzi and Bauta tested the hypothesis that eliminating vitamin B12 could be the mechanism behind the death of cancer cells when CD320 and LRP2 are silenced. Experiments proved otherwise.

"Our research on targeted gene silencing began in order to better understand the mechanism behind our proprietary porphyrin TCPP’s ability to selectively stain cancer cells. In the process, we learned that treatment with siRNAs targeting specific cell surface receptors, CD320 and LRP2, both of which transport vitamin B12, adversely affects cancer cell survival but not normal cells," Dr. Elzi said. "However, when the cell culture medium did not contain measurable amounts of vitamin B12, we found no difference in cell growth compared to the culture medium supplemented with vitamin B12."

"We are continuing our investigation into how and why the simultaneous knockdown of CD320 and LRP2 inhibits cancer cell growth with no apparent effect on healthy cells. Our ultimate objective is to use this discovery to develop targeted therapeutics for multiple cancers," Dr. Bauta added.

bioAffinity Technologies’ noninvasive test for early-stage lung cancer, CyPath Lung, incorporates TCPP to identify cell populations in sputum that indicate cancer is present in the lung. CyPath Lung uses flow cytometry and AI-driven automated analysis to detect signals indicative of lung cancer.

On June 15, 2023 The Jerome Canady Research Institute for Advanced and Biological Technological Sciences (JCRI-ABTS) and US Medical Innovations, LLC (USMI) reported significant positive results from the first FDA Phase I IDE (#G190165) clinical trial for cancer using Canady Helios TM Cold Plasma (CHCP) combined with standard surgical resections at the 2023 American Society of Clinical Oncologists (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (May 31-June 4, 2023) (Press release, JCRI-ABTS, JUN 15, 2023, View Source [SID1234632765]). Safety was the primary endpoint; secondary endpoints were the effect on local regional recurrence (LRR), cancer cell death, preservation of surrounding healthy tissue, and patient survival. (ClinicalTrials.gov identifier: NCT04267575)

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Cancer remains a significant global health challenge, with over 1.9 million new cases and 608,570 cancer-related fatalities in the United States in 2021. Advances in chemotherapy, radiation, surgery, immunotherapy, and molecular targeted therapy regimes have improved survival, but solid tumor resections still have a risk of LRR and a poor five-year survival rate. Surgery is the primary treatment for most solid tumors, but complete removal of cancerous tissue (R0), microscopic tumor cells (R1) or visible tumor (R2) is challenging which can lead to LRR in 5% to 65% of cases.

USMI’s Canady Helios Cold Plasma (CHCP) system, a non-thermal (26-30°C) and non-contact Cold Atmospheric Plasma (CAP) jet, offers a promising solution. The three-dimensional bioelectric Plasma Treated Electromagnetic Field (PTEF) created by CHCP causes a biophysical phenomenon known as Irreversible Electroporation (IRE), that increases cancer cell membrane permeability to CAP species such as Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). This process results in cancer cell death while sparing the noncancerous tissue. The JCRI-ABTS research laboratory discovered and patented the process by which CHCP-treated cancer cells undergo histone mRNA oxidation and degradation, leading to the activation of DNA damage response genes and cell death (link)1. Standard CHCP treatment dosages for 32 cancer cell lines including breast, sarcoma, glioblastoma, melanoma, ovarian, prostate, colorectal, and lung cancers. have been developed in the JCRI-ABTS laboratory.

The Clinical Trial was a multi-center, open-label, prospective, and controlled study conducted between March 2020 – April 2021 at Rush University Medical Center (RUMC) in Chicago, IL, USA, and Sheba Medical Center (SMC) in Tel HaShomer, Israel. Molecular biological studies were performed at JCRI-ABTS. Twenty patients ranging from 26-85 years of age undergoing surgery for advanced stage 4 or recurrent solid tumors were enrolled. Patients with preoperative treatments such as neoadjuvant chemotherapy, immunotherapy, radiation, and previous surgery were eligible.

Characteristics of Patients

Characteristic

No.

%

No. of Patients

20

Sheba Medical Center

5

25

Rush Medical Center

15

75

Age

Median

59.5

Range

26-85

Female

10

50

Male

10

50

Ethnicity

White

18

90

African American

1

5

Other

1

5

ECOG1 Performance Status

<2

20

100

Cancer types (all metastatic)

Adenoid Cystic Carcinoma

1

5

Anal

1

5

Angiosarcoma

1

5

Breast

1

5

Cholangiocarcinoma

1

5

Chordoma

1

5

Colon

2

10

Melanoma

1

5

Mesothelioma

1

5

Non-Small Cell Lung*

3

15

Ovarian

1

5

Renal

1

5

Sarcoma**

4

20

Squamous Cell Carcinoma

1

5

1 ECOG – Eastern Cooperative Oncology Group
* Two Carcinomas and 1 Adenocarcinoma
** Desmoplastic small round cell sarcoma, myxofibrosarcoma, pleomorphic sarcoma, and pleomorphic spindle cell sarcoma

Overall response rates (ORR) at 26 months for R0 and R0 with Microscopic Positive Margins (R0-MPM) patients were 69% (95% CI, 19-40%) and 100% (95% CI, 100 – 100.0%), respectively. ORR was defined as no recurrence from the time of CHCP treatment to LRR in R0 resected patients. ORR was evaluated by postoperative T2 weighted MRI, PET or CT scans.

Overall Survival (OS) for R0 (n=7), R0-MPM (n=5), R1 (n=6), and R2 (n=2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative OS rate was 24% at 31 months (n=20, 95% CI, 5.3 – 100.0). OS was defined as the duration from the intraoperative CHCP treatment to death.

CHCP treatment did not affect intraoperative physiological vital signs (blood pressure, pulse, O2 saturation, end tidal CO2, and temperature, p > 0.05). No systemic toxicities or device-related adverse events were observed. Overall, CHCP treatment combined with surgery is safe, selective towards microscopic tumor cells at the margin, and demonstrates exceptionally low LRR in R0 and R0-MPM patients.

Time
(Months)

Number at
Risk

Deaths

Survival Rate

Standard
Error

Lower 95% CI

Upper 95% CI

0

20

0

100%

0.00

1.00

1.00

5

18

2

90%

0.07

0.78

1.00

10

16

3

75%

0.10

0.58

0.97

15

15

0

75%

0.10

0.58

0.97

20

15

1

70%

0.10

0.53

0.93

25

8

0

70%

0.10

0.53

0.93

30

3

2

48%

0.15

0.26

0.88

31

2

1

24%

0.19

0.05

1.00

OS analysis for CAP-treated patients (n=20). P=0.0058.

Jerome Canady, MD., FACS., Surgical Oncologist, and CEO stated, "One inherent problem of excising any solid tumor tissue is ensuring complete surgical removal of the tumor and the microscopic tumor cells at the margins, which reduces the chance of local regional recurrence. To date, there are no treatments on the market that ensure the complete eradication of microscopic tumor cells at the surgical margin without damaging the surrounding healthy tissue. CHCP treatment with surgery shows immense promise in controlling local recurrence and improving survival in patients with advanced solid tumors. The treatment selectively kills microscopic tumor cells at the surgical margin. CHCP treatment is non-invasive, administered for 5 – 7 minutes intraoperatively, and has no side effects. It seamlessly integrates into existing treatment protocols without disruption."

Professor of Surgery Giacomo Basadonna MD., Ph.D., FACS Department of Surgery University of Massachusetts School of Medicine Worcester and co-author of the study stated, "The results of this clinical investigation are truly remarkable and offer renewed hope to cancer patients with advanced disease. The data from the trial combined with the amount of mechanistic information collected over many years, clearly show that Canady Helios Cold Plasma treatment causes cancer cells to die within a brief period leaving normal tissue untouched. The current trial shows that treating the surrounding tissue following tumorectomy prevents local recurrence and increases overall survival. Although this trial was conducted in patients with severe disease for regulatory reasons, the results open the door to treating the tumor bed and the adjacent tissue following removal of primary malignancies and truly guarantee cancer-free surgical margins."

These groundbreaking results highlight the safety, selectivity, and significant reduction of local regional recurrence achieved through the combination of CHCP treatment and surgery. USMI’s Canady Helios Cold Plasma system opens a new and promising avenue for addressing the challenges of eradicating microscopic residual cancer cells following surgical tumor resection without damaging surrounding healthy tissue.

JCRI-ABTS and USMI thank the participating patients and their families, prior compassionate use patients, surgical teams performing these advanced surgical procedures, and allowance by SMC and RUMC.

USMI’s FDA Phase 2 Multi-Center Clinical Trial is expected to take place in Q/4 2023.

The accompanying report for this Phase 1 Clinical Trial has been submitted to a peer review journal. The Abstract can be viewed on the ASCO (Free ASCO Whitepaper) website at View Source

Reference data1 JCRI Discovers the Mechanism using Canady Helios Cold Plasma to Induce Cell Death in Breast Cancer

For more information about the CHCP clinical trial and USMI’s innovative medical technologies, please visit ClinicalTrials.gov identifier: NCT04267575.