On June 15, 2023 LianBio reported that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has granted a breakthrough therapy designation to infigratinib (Febseltiq) for the treatment of patients with gastric cancer (Press release, LianBio, JUN 15, 2023, View Source [SID1234633492]).

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The designation was supported by topline data from a phase 2a trial (NCT05019794), which showed that pretreated patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma harboring FGFR2 gene amplification experienced an overall response rate (ORR) of 25.0% (n = 20). The median duration of response (DOR) was 3.8 months.

"Gastric cancer impacts a disproportionately high number of patients in China," Yizhe Wang, PhD, chief executive officer of LianBio, stated in a news release. "Patients whose disease has progressed on existing treatment options face a poor prognosis today. The topline data from this proof-of-concept trial suggest infigratinib has the potential to provide meaningful clinical benefit in third-line or later gastric cancer. We look forward to further investigating the efficacy and safety of infigratinib in this patient population in a phase 2 study designed to support registration in China that we plan to initiate next year."

Infigratinib is an oral, adenosine triphosphate–competitive, FGFR TKI designed to target the FGFR protein and inhibit downstream activity. In May 2021, the FDA granted accelerated approval to infigratinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.2

However, in October 2022, LianBio reported that its partner, BridgeBio Pharma, informed the company that Helsinn Healthcare SA was permanently discontinuing distribution of the drug and anticipated requesting withdrawal of the new drug application in the United States due to business reasons.3

In December 2022, the European marketing authorization application for infigratinib was withdrawn by Helsinn Birex Pharmaceuticals for the treatment of patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements.4

The multicenter, open-label, single-arm, phase 2a proof-of-concept study enrolled patients with FGFR2-amplified locally advanced or metastatic gastric cancer or GEJ adenocarcinoma, and those with other advanced solid tumors harboring FGFR alterations, who received at least 2 prior lines of treatment. Patients were also required to have measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1.5

Key exclusion criteria included a history of other primary malignancies with 3 years except for adequately treated in situ carcinoma of the cervix, non-melanoma carcinoma, or any other curatively treated malignancy that was not expected to require treatment for recurrence during the study; prior treatment with a mitogen-activated protein kinase or selective FGFR inhibitor; or symptomatic central nervous system metastases.

All patients were treated with 125 mg of oral infigratinib per day on a 3-weeks-on/1-week-off schedule.

ORR served as the trial’s primary end point. Secondary end points included DOR, disease control rate, best overall response, progression-free survival, overall survival, and safety.

In the phase 2a portion of the trial, 57.1% of patients received 2 prior lines of therapy, 33.3% were given 3 prior lines of therapy, and 9.5% had more than 3 prior lines of therapy.1

Regarding safety, the most common any-grade treatment-emergent adverse effects reported in at least 20% of patients included hyperphosphatemia, anemia, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, decreased neutrophil count, diarrhea, constipation, palmar-plantar erythrodysesthesia, increased lipase, increased blood alkaline phosphatase, and increased blood bilirubin.

References
LianBio announces topline results from phase 2a proof of concept trial evaluating infigratinib in patients with gastric cancer & receipt of breakthrough therapy designation in China. News release. LianBio. June 6, 2023. Accessed June 15, 2023. View Source
FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. News release. FDA. May 28, 2021. Accessed June 15, 2023. View Source
United States Securities And Exchange Commission: form 8-K. Securities And Exchange Commission. October 12, 2022. Accessed June 15, 2022. View Source
Withdrawal of application for the EMA marketing authorization of infigratinib. News release. ESMO (Free ESMO Whitepaper). December 1, 2022. Accessed June 15, 2023. View Source
Infigratinib in subjects with GC or GEJ with FGFR2 amplification or other solid tumors with other FGFR alterations (FGFR). ClinicalTrials.gov. Updated June 27, 2022. Accessed June 15, 2023. View Source

On June 15, 2023 Metagen Therapeutics (President & CEO: Taku Nakahara), a company focusing on drug discovery and development based on intestinal microbiome-based therapeutics for various diseases, reported that it has completed its Series A funding in 2 rounds, raising a total of 1.7 billion yen (Press release, Metagen Therapeutics, JUN 15, 2023, View Source [SID1234632772]). Sparx Asset Management, Nippon Venture Capital, Mizuho Capital and SMBC Venture Capital have joined the 1st round investors of JIC Venture Growth Investments, a type of sovereign wealth fund in Japan, JAFCO, Japan’s largest venture capital company, Fast Track Initiative and Keio Innovation Initiative.

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With the closing of the 2nd round, Metagen Therapeutics has raised a total amount of 1.93 billion yen since its inception.

Purpose of Financing
There has been a growing movement to utilize intestinal bacteria in the medical field in recent years. In countries such as Australia and USA, "Fecal Microbiota Transplantation (FMT)" has been implemented as a medical procedure, and in April 2023, U.S. FDA approved the world’s first stool-derived oral formulation for a microbiome drug.

With the latest financing, Metagen Therapeutics aims to achieve 3 goals.

The construction and operation of an intestinal microbiota bank, research and development of Microbiota Drug Discovery Programs, and the social implementation of FMT.

By establishing an intestinal microbiota bank in Japan we will be able to connect patients and donors, which in turn will support and promote the social implementation of FMT, and from there help develop internationally competitive microbiome drugs that originates from Japan.

Use of Funds
1. Development and operation of the intestinal microbiota bank

Development of registration system for intestinal microbiota donor candidates
Operation of intestinal microbiota bank (in accordance with institutional guidelines) – Donor recruitment/online interview, donor eligibility evaluation, intake of stool donations, manufacturing/assessment/storage of intestinal microbiota solution
Establishing process regarding preparation and quality control for intestinal microbiota solution
2. Promotion of basic and clinical research for clinical application of FMT (such as joint research related to immune checkpoint inhibitors)

3. Research and development of intestinal microbiota drug discovery program (including probiotics)

Message from investors
Sparks Asset Management Co., Ltd.
Mr. Mitsuhiro Ito, Next Generation Growth Investment Division
FMT therapy has recently been studied mainly overseas, and its social implementation is awaited in Japan as a new treatment method for various diseases including ulcerative colitis. We hope that Metagen Therapeutics, with its abundant intestinal microbiota data accumulated through years of clinical research and advanced bioinformatics technology, will lead the promotion of microbiome medicine and drug discovery and serve as gospel for many patients.

Nippon Venture Capital Co.
Ms. Yuko Kitaoka and Ms. Sayuri Okamoto, Investment Division
It is with great pleasure to be here with Metagen Therapeutics, which is engaged in the research and development of innovative medical and pharmaceutical products such as the social implementation of FMT and microbiome drug discovery, as well as with its many investors. We are very much looking forward to seeing the excellent team led by Mr. Nakahara make a significant contribution to further develop microbiome science and the practical application of new medical and pharmaceutical products.

Mizuho Capital Co.,Ltd.
Mr. Keisuke Omori, Investment Manager
Metagen Therapeutics is a bio-venture company with Japan’s leading research and development capabilities in intestinal microbiota transplantation and microbiome drug discovery. With the increasing number of regulatory approvals for microbiome drugs overseas, we expect to see the creation of innovative medicine and pharmaceutical products based on microbiome science originating from Japan. We, together with our excellent management team led by President Nakahara, CMO Ishikawa, and CSO Terauchi, will continue to support this company with all our resources.

SMBC Venture Capital.
Mr. Masakazu Komahashi, Investment Sales Dept.
Microbiomes are believed to be involved in various diseases other than inflammatory bowel disease, and the development of therapies is attracting worldwide attention. It is a new modality, and we expect to face many challenges in its implementation in society, but with the science and enthusiasm of the Metagen Therapeutics team, I believe we will be able to overcome these challenges. As a leading company in microbiome therapy development, we look forward to bringing therapies to patients as soon as possible.

Message from Taku Nakahara, President and CEO, Metagen Therapeutics
June 15th marks the final close of our Series A funding round, raising a total of 1.7 billion yen. We are very grateful for the deep trust and support of our top-tier investors, including FTI, JAFCO, and KII, who have supported us since the Seed and Pre-A rounds, JIC-VGI, who participated in the Series A First Close in April, and SPARX, NVCC, Mizuho Capital, and SMBC Venture Capital, who joined us at this final close.

This funding will provide a powerful boost to expand the impact of microbiome medicine and drug discovery from Japan to the rest of the world, working to fulfill our mission of "Living up to the hopes of patients through microbiome science". Intestinal microbiome therapy is entering a new phase globally, with the approval of stool-derived oral formulations in the United States. We are determined not to miss this trend and renew our strong determination to bring advanced treatments to patients in Japan as soon as possible.

What is a microbiome?
A microbiome refers to the community of bacteria present throughout the human body including the intestines, skin and mouth. There are known to be approximately 40 trillion* bacterial cells in the human intestine, and in recent years, it has become evident to have significant impact on human health.

* Sender, R., Fuchs, S. & Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 14, e1002533 (2016)

What is FMT?

FMT refers to the transplantation of intestinal microbiota from the stool of healthy individuals into the intestines of patients using a colonoscope. This is a medical technology and procedure that improves the imbalance of the microbiota, or dysbiosis. Clinical research began in 2014, and Juntendo University has accumulated a track record of FMT in more than 200 patients** with ulcerative colitis, publishing research papers and case studies internationally in a number of top journals.

**View Source

What is the Intestinal Microbiota Bank?

The intestinal microbiota bank is a system that recruits and screens potential intestinal microbiota donors, prepares intestinal microflora solution to be transplanted into patients when performing FMT, and delivers solutions to medical institutions. The intestinal microbiota bank also serves as a foundation for research and development of pharmaceuticals using intestinal bacteria.

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.