On September 10, 2019 Novigenix SA, a leading Immuno-Transcriptomics company that develops and commercializes solutions for early cancer detection and precision medicine, reported the discovery of a new molecular signature in blood that can be used for early colorectal cancer detection using its new LITOseek platform (Press release, Novigenix, SEP 10, 2019, View Source [SID1234539382]). Data explaining the use of next generation sequencing (NGS) and machine learning from the studies leading to this discovery will be presented at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting (27th September -1st October, Barcelona, Spain).

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The company’s currently marketed test, Colox, is the first commercially available Immuno-Transcriptomic blood based RT-PCR test on the market for the screening of colon cancer. The data regarding the discovery and development of a new Immuno-Transcriptomic molecular signature test for early colon cancer screening on the LITOseek platform will be presented at ESMO (Free ESMO Whitepaper).

The data will be presented on September 30, 2019 by our academic partner from The Swiss Institute of Bioinformatics under the title "Discovery of an Immuno-Transcriptomics signature in blood for early colorectal cancer detection" in the Poster Display Session 3 on Biomarkers.

Novigenix has also launched its re-designed website, which reflects the Company’s new business strategy and provides details on the LITOseek technology platform.

"Our new website and branding for the LITOseek technology platform illustrates Novigenix’s aspiration to become a market leader in data-driven medicine and will help our stakeholders to better understand the value proposition of our oncology business," said Dr. Jan Groen, CEO of Novigenix. "Part of the new strategy is the move from RT-PCR to a full immuno-transcriptome sequencing technology. Through the newly developed LITOseek platform, we will be able provide our customers with an NGS-based solution allowing them to implement our proprietary data analysis pipeline on their own instruments. Currently Novigenix is the first liquid biopsy based immuno-transcriptomic NGS company in the molecular diagnostic arena."

Convergence in Oncology Summit

Dr. Jan Groen will lead the discussion of the panel "Advances in Molecular Diagnostics: Early Cancer Detection & Therapy Optimization" at the next Convergence in Oncology Summit. The panel starts at 13:15 on 12 September 2019 in Lausanne, Switzerland.

About LITOseek

Novigenix’s blood Immuno-Transcriptomic sequence platform, LITOseek, analyzes the gene expression modifications (mRNA signatures) induced by the host response to various triggers, such as the onset of cancer. Disease specific algorithms are developed combining the mRNA signature with clinical and medical parameters. The combination of mathematical models with machine learning and collection of new data enables the continuous improvement of the predictive and adaptive algorithms.

On September 9, 2019 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) and BridgeBio Pharma, Inc.’s (NASDAQ:BBIO) subsidiary Eidos Therapeutics, Inc. (NASDAQ:EIDX) reported an agreement that grants Alexion an exclusive license to develop and commercialize AG10 in Japan. AG10 is a small molecule designed to treat the root cause of transthyretin amyloidosis (ATTR) – destabilized and misfolded transthyretin (TTR) protein – by binding and stabilizing TTR in the blood. Eidos is currently evaluating AG10 in a Phase 3 study in the U.S. and Europe for ATTR cardiomyopathy (ATTR-CM) – a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the heart – and plans to begin a Phase 3 study in ATTR polyneuropathy (ATTR-PN) – a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the peripheral nervous system.

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"There is a significant need for new treatments for TTR amyloidosis. We believe AG10 holds promise in its ability to stabilize TTR and halt disease progression," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "We are excited by the potential to grow our amyloidosis portfolio by partnering with Eidos to expand the development of AG10 to Japan. Alexion has more than 10 years of experience operating there, and we look forward to applying our expertise to bring AG10 to Japanese patients."

"The Phase 2 study in ATTR-CM suggested that AG10 has the potential to become an important treatment option for the underserved ATTR-CM population. The trial showed that AG10 was generally well-tolerated and resulted in near-complete stabilization of TTR, which is known to be correlated with disease severity in ATTR-CM. In the study, AG10 also normalized serum TTR levels, a prognostic indicator of survival in ATTR patients," said Jonathan Fox, M.D., Ph.D., President and Chief Medical Officer of Eidos. "We have now begun our Phase 3 program to evaluate the safety and efficacy of AG10 in larger studies. This agreement provides the potential opportunity to help even more patients globally by leveraging Alexion’s significant development and commercial experience to expand the AG10 program into Japan."

Under the terms of the agreement, Alexion will acquire an exclusive license for the clinical development and commercialization of AG10 in Japan. Eidos will receive an upfront payment of $25 million and an equity investment of $25 million at a premium to the market price upon deal execution, with the potential for additional Japanese-based milestone- and royalty-dependent payments.

About AG10

AG10 is an investigational, orally-administered small molecule designed to potently stabilize tetrameric transthyretin, or TTR, thereby halting at its outset the series of molecular events that give rise to TTR amyloidosis, or ATTR. In a Phase 2 clinical trial in patients with symptomatic ATTR-CM, AG10 was generally well tolerated, demonstrated greater than 90 percent average TTR stabilization at Day 28, and increased serum TTR concentrations, a prognostic indicator of survival in a retrospective study of ATTR-CM patients, in a dose-dependent manner.

AG10 was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a rescue mutation because co-inheritance has been shown to prevent or ameliorate ATTR in individuals also inheriting a pathogenic, or disease-causing, mutation in the TTR gene. To our knowledge, AG10 is the only TTR stabilizer in development that has been observed to mimic the stabilizing structure of this rescue mutation.

The Phase 3 ATTRibute-CM study of AG10 in patients with ATTR-CM is underway in the United States and Europe. Part A of the study will assess the change from baseline in 6-minute walk distance (6MWD) at 12 months. Part B of the study will evaluate reduction in all-cause mortality and frequency of cardiovascular-related hospitalizations will be evaluated at 30 months. In addition, Eidos plans to initiate a Phase 3 study of AG10 in ATTR polyneuropathy (ATTR-PN) in the second half of 2019.

About Transthyretin Amyloidosis (ATTR)

There is significant medical need in transthyretin amyloidosis (ATTR) given the large patient population and an inadequate current standard of care. ATTR is caused by the destabilization of TTR due to inherited mutations or aging and is commonly divided into three distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN). The worldwide prevalence of each disease is approximately 400,000 patients, 40,000 patients and 10,000 patients, respectively.

All three forms of ATTR are progressive and fatal. For patients with untreated ATTRwt-CM and ATTRm-CM, symptoms usually manifest later in life (age 50+), with median survival of three to five years from diagnosis. ATTR-PN either presents in a patient’s early 30s or later (age 50+), and results in a median life expectancy of five to ten years from diagnosis for untreated patients. Progression of all forms of ATTR causes significant morbidity, impacts productivity and quality of life, and creates a significant economic burden due to the costs associated with progressively greater patient needs for supportive care. (Press release, BridgeBio, SEP 9, 2019, View Source [SID1234576264])

On September 9, 2019 Kaleido Biosciences, Inc. (Nasdaq: KLDO), a clinical-stage healthcare company with a chemistry-driven approach to leveraging the microbiome organ to treat disease and improve human health, reported plans to develop Microbiome Metabolic Therapies (MMT) to enhance the effects of cancer immunotherapies under a new research collaboration with Gustave Roussy, the largest cancer treatment center in Europe (Press release, Kaleido Biosciences, SEP 9, 2019, View Source [SID1234540069]). Gustave Roussy is a pioneer in cancer immunotherapy and research into the relationship between the microbiome and cancer.

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Kaleido’s MMTs are designed to modulate the metabolic output and profile of the microbiome by driving the function and distribution of the organ’s existing microbes. Working closely with world-leading scientists at Gustave Roussy – Professors Laurence Zitvogel, M.D., Ph.D., and Guido Kroemer, M.D., Ph.D. – Kaleido aims to identify and characterize MMT candidates with the potential to improve cancer immunotherapy efficacy by increasing the number of patients who respond to inhibitors of immune checkpoints such as CTLA-4 and PD-1/PD-L1. While checkpoint inhibitors have been effective in treating certain cancers, studies have shown that overall, the majority of cancer patients do not respond to checkpoint therapy.

Professor Zitvogel, scientific director of the Gustave Roussy immunotherapy program and director of the INSERM Tumour Immunology and Immunotherapy Laboratory said, "In our work at Gustave Roussy, we will soon be able to predict with a high degree of accuracy which patients with certain cancers may respond to immunotherapies, such as checkpoint inhibitors, based on specific features of their intestinal microbiota. We are excited by Kaleido’s unique approach to the microbiome and believe it has the potential to provide cancer patients with new options to optimize and personalize treatment."

"Researchers at Gustave Roussy have been at the forefront of global efforts to understand the links between cancer, immunity, and the gut microbiome. We are exceptionally pleased to be collaborating with Professors Zitvogel and Kroemer on the development of MMTs aimed at improving patients’ response to treatment," said Johan van Hylckama Vlieg, Ph.D., Chief Scientific Officer of Kaleido. "This is also an exciting milestone for Kaleido as it marks our entry into immuno-oncology, an area with significant opportunity to help advance the treatment and care of patients with cancer."

The collaboration is aimed at improving outcomes in patients who don’t respond to checkpoint inhibitor treatment by changing their microbiome composition and metabolic output. Kaleido will employ its proprietary screening platform to analyze intestinal microbiome samples from checkpoint inhibitor non-responder patients and identify MMTs that induce changes in the microbial communities associated with favorable response to treatment. Gustave Roussy researchers will then use their advanced preclinical models to identify those compounds that stimulate the targeted therapeutic responses. Initial data obtained with these models (Routy et al, Science, 2018) indicate translational potential and suggest that they may serve as a critical step prior to clinical testing as well as serve as powerful tools for delineating underlying mechanisms of action.

Based in Paris, France, Gustave Roussy is the leading center in immunotherapy in Europe. In 2015, Gustave Roussy launched an institutional program dedicated to immunotherapy: the GRIP (Gustave Roussy Immunotherapy Program). This program aims to strengthen Translational Research on these new treatments, and accelerate the clinical development of immunotherapy, in order to facilitate access to these treatments to a larger number of patients. Between 2013 and 2018, nearly 250 immunotherapy-based clinical trials were implemented at the Institute and more than 3,300 patients have been treated with immunotherapy. Gustave Roussy is also a leading coordinator of the RHU LUMIERE, a French multi-institutional microbiome network in lung cancers supported by the Health Ministry as well as of the Oncobiome consortium, a five-year project with 16 international partners supported by the European Commission.

About Microbiome Metabolic Therapies (MMT)
Kaleido’s Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiome organ’s existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Company’s initial MMT candidates are targeted glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome. Kaleido utilizes its human-centric discovery and development platform to study MMTs in microbiome samples in an ex vivo setting, followed by advancing MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.

On September 9, 2019 Medigene AG (FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that Dr. Slavoljub Milosevic, Vice President of Technology and Innovation at Medigene AG, will be presenting "iM-TCR (inducible Medigene TCR): Controlled cytotoxicity of tumor-specific TCR-modified T cells with improved avidity through control of TCR surface expression" at the CAR-TCR Summit 2019 in Boston, USA on 13 September at 11:30 am.

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T cells are effector cells of the human immune system which, via their T cell receptors (TCRs), can recognize and kill cancer cells. While genetically engineering patient T cells to carry TCRs specific for tumor antigens has been shown to enable elimination of tumor cells, potential off-tumor cross-reactivity can occasionally lead to unwanted toxicity against normal cells and healthy tissues causing serious and/or life-threatening adverse events.

Medigene’s new inducible ‘iM-TCRs’ offer an approach that enables exquisite dose-dependent and rapid control of TCR surface expression and thereby also TCR-T (TCR-modified) T cell functional activity. Engineering TCR-Ts using iM-TCRs is also shown to generate T cells with higher avidity for target antigens without inducing changes in the TCR complementarity determining regions (CDRs) that bind to the target antigens. iM-TCRs permit the function of TCR-T therapies to be finely tuned by conditionally turning TCR expression "on and off" as needed in patients. Importantly, by tightly up- or down-regulating iM-TCR expression at the T cell surface, any off-tumor activity of TCR-T cells can be closely controlled without resorting to killing these therapeutically valuable cells by other more drastic measures. Thus, iM-TCR-T cells which remain viable when the iM-TCR is down-regulated, could subsequently be reactivated at a potentially more appropriate time and level of activity. For clinicians, the ability to manage therapeutic activity by dialing iM-TCR levels up or down, would provide treatment options to potentially tune safety and efficacy according to clinical needs.

Dr. Slavoljub Milosevic commented: "Our high avidity inducible iM-TCRs represent a way to precisely affect and control the responsiveness of genetically modified T cell receptors, thereby potentially reducing the risk of side effects. The ability to finely control the activity of these iM-TCRs could enable an even broader scope of antigens to be effectively targeted more safely."
In addition, Prof. Dolores J. Schendel, CEO of Medigene AG, is participating at the summit as member of the CAR-TCR Scientific Advisory Board.

On September 9, 2019 Thermo Fisher Scientific reported an agreement with Eli Lilly and Company for development of a companion diagnostic that will use the U.S Food and Drug Administration-approved, next-generation sequencing-based Oncomine Dx Target Test to identify certain non-small cell lung cancer (NSCLC) and thyroid cancer patients who may be treated with Lilly’s investigational therapy, LOXO-292 (Press release, Thermo Fisher Scientific, SEP 9, 2019, View Source [SID1234539392]). Specifically, the test would be used with patients whose tumors harbor a rearranged during transfection (RET) alteration. RET variants are found in about two percent of NSCLC, about 60 percent of medullary thyroid cancer (MTC) and up to approximately 20 percent of other thyroid cancers.

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LOXO-292 is a highly selective and potent oral RET inhibitor being studied by Lilly in a Phase 1/2 clinical trial for the treatment of advanced cancers that harbor activating alterations of the RET kinase. Changes in the RET kinase, including fusions and mutations, can cause uncontrolled cell growth leading to tumor development. Cancers driven by such alterations are mostly dependent on this singularly activated pathway, making them highly susceptible to small molecule inhibitors.

"One of the biggest barriers to realizing the full power of precision medicine in oncology is having access to high-quality testing, such as next-generation sequencing-based tests, that identify a broad range of clinically actionable alterations, can be performed locally and allow treating institutions to participate in this important step in the evolving treatment paradigm," said Anne White, president of Lilly Oncology. "With this agreement, we believe that more patients will gain access to high-quality tumor profiling, identifying those with RET alterations potentially suitable for LOXO-292 therapy, in addition to other alterations suitable for treatment with other therapies."

Mark Stevenson, executive vice president and chief operating officer of Thermo Fisher Scientific said: "We are pleased to enter into this agreement with Lilly and leverage our Oncomine platform as a means to quickly identify cancer patients who may benefit from this breakthrough therapy, even in cases of limited sample availability. We are committed to working with our global pharmaceutical partners to help bring forth next-generation sequencing-based companion diagnostics and best-in-class therapies that can have a profound impact on treating cancer patients."

Under the terms of the agreement, Thermo Fisher will retain the rights to commercialize the test in all markets, including the United States, Europe and Japan. Once validation is complete, Thermo Fisher will submit a supplemental premarket approval (sPMA) application to the U.S. Food and Drug Administration (FDA) to broaden the clinical claims of its Oncomine Dx Target Test.

The NGS test, which received FDA approval in 2017, simultaneously screens tumor samples for multiple gene variants associated with NSCLC, a subset of which are utilized to identify patients who may be eligible for several approved targeted therapies. It is covered in the United States by the Centers for Medicare & Medicaid Services and a majority of the largest commercial U.S. health plans. Oncomine Dx Target Test is also approved for reimbursement by the Japan Ministry of Health, Labor and Welfare (MHLW).