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 Mateon Therapeutics Inc. (OTCQB:MATN), reported that it has executed agreements with WideTrial Inc. for an Expanded Access program (EAP) in pancreatic cancer (Press release, Mateon Therapeutics, SEP 9, 2019, View Source [SID1234539377]). Using WideTrial’s novel platform, the investigational therapeutic OT-101 will be made available for elective treatment-use to patients who do not meet the inclusion criteria of OT-101 research trials. The partnership may also support Expanded Access for OT-101 in additional patients with advanced solid tumors, excluding brain cancers (AA, GBM, and other gliomas). Separately, the companies executed data access agreements to support the development of Mateon’s AI/Blockchain technologies with WideTrial’s data assets in cancer and other therapeutic areas.

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OT-101 is a first-in-class RNA therapeutic targeting TGF beta and is the lead immune-oncology drug candidate of Oncotelic, a wholly owned subsidiary of Mateon Therapeutics Inc.. The investigational drug exhibited single-agent activity in relapsed/refractory cancer patients during multiple Phase 2 clinical trials.

Like research trials, cohort Expanded Access programs (EAPs) are centrally monitored trials that enroll patients at designated sites under a single protocol. They differ from research trials in that their primary objective is to provide the option of treatment-use to patients who cannot take part in the product’s research trials.

"This Expanded Access program will allow us to meet the spirit of clinical trial inclusivity, as described in the 2017 FDA Reauthorization Act. We are pleased to have found a viable way to accommodate greater numbers of patients in need and the doctors who seek to treat them," said Dr. Vuong Trieu, Chairman and CEO of Mateon Therapeutics Inc.. "Though the primary objective is treatment, we intend to utilize generated data to improve the power and targeting of future research trials."

"The PointR platform applies cutting edge algorithms to clinical datasets and could be used to quickly and cost-effectively identify the best therapy tailored fit to a single individual. The ability to access EAP data is helpful to the development of this platform" said Saran Saund, CEO of PointR Data, which is becoming a wholly owned subsidiary of Mateon Therapeutics Inc.. "We are thrilled at the opportunity of vertically integrating artificial intelligence and drug development capabilities under one roof to quickly identify promising new therapeutic opportunities for various diseases and to deliver compelling business value."

"We built WideTrial to solve the economic and operational barriers that drug developers face with Expanded Access," said Jess Rabourn, CEO of WideTrial. "The new platform enables larger numbers of gravely ill patients to choose to try investigational medicines under a properly designed protocol. Although treatment is the primary objective, EAP sponsors can learn a lot from patients’ experiences in these programs."

On September 9, 2019 Aptorum Group Limited (Nasdaq: APM) ("Aptorum Group"), a biopharmaceutical company focused on the development of novel therapeutics to address global unmet medical needs, reported the development of two preclinical drug candidates which target obesity and neuroblastoma, respectively (Press release, Aptorum, SEP 9, 2019, View Source [SID1234539378]).

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About CLS-1: Treatment of obesity via modulation of chemical signaling relating to gut microbiota

Under the recently-announced microbiota modulation platform operated by Aptorum Group’s wholly-owned subsidiary Claves Life Sciences Limited, we have commenced the preclinical development of macromolecule candidate CLS-1 targeting the treatment of obesity. CLS-1 is undergoing lead optimization and is expected to progress into the IND enabling stage in 2020.

The prevalence of obesity continues to escalate globally; however, there is no current optimal therapy for this condition1. For the majority of obese patients, conventional medical therapies (i.e., diet, exercise, behavioral counseling) often have a high failure rate for the long term2. We believe current pharmacotherapy has limited efficacy and is associated with substantial safety issues, and this will provide immeasurable market opportunity for CLS-1.

Chemical signaling of gut microbiota is known to be one of the major causes of obesity1. CLS-1 is an orally administered non-absorbable macromolecule that modulates the metabolite excreted by gut microbiota with high affinity and specificity. In this way, we believe the absorption of this particular metabolite, which is linked to obesity, can be inhibited.

Aptorum Group is also pursuing two further indications based on the modulation of microbiota based chemical signaling involving the above large molecule technology, which we believe to be highly scalable and we hope to be making further announcements regarding our efforts in due course.

About SACT-1: Repurposed Drug Candidates for the Treatment of Neuroblastoma

Under the recently announced Smart-ACTTM computational drug discovery platform operated by our wholly-owned subsidiary Smart Pharma Group, Aptorum Group has completed computational screening of approximately 1,615 marketed drugs against 3 therapeutic target proteins to potentially tackle poor prognosis of neuroblastoma, i.e., a rare type of children’s cancer that forms in certain types of nerve tissue and most frequently in the adrenal glands as well as spine, chest, abdomen or neck, especially in children3. For the high-risk group, the 5-year survival rate of this condition is around 40-50% as observed by the American Cancer Society.4 Aptorum Group has identified an array of repurposed candidates and has proceeded to evaluate them in cell-based and animal models in order to validate the candidates’ usage for such new indication and potential efficacies.

Aptorum Group is also pursuing two further indications under the Smart-ACTTM drug discovery platform and hopes to be making further announcements regarding our research in due course.

On September 9, 2019 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported that it has entered into a research agreement with Invectys, a biopharmaceutical company focused on the development of innovative immunotherapy approaches to treat cancers (Press release, Personalis, SEP 9, 2019, View Source [SID1234539379]). Under the terms of the agreement, Personalis will provide comprehensive tumor immunogenomics capabilities to facilitate biomarker discovery in chronic lymphocytic leukemia (CLL) patients enrolled in a Phase II clinical trial assessing the efficacy of INVAC-1, a DNA plasmid encoding a modified human telomerase reverse transcriptase (hTERT) protein, as monotherapy or in combination with ibrutinib.

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"Personalis is known for their innovative and expansive cancer immunogenomics expertise, and we’re delighted to partner with them on this project to evaluate biomarker signatures in responders and non-responders to our leading cancer vaccine candidate, INVAC-1," said Pierre Langlade Demoyen, CEO of Invectys. "INVAC-1 has the potential to become a key component of combination therapy approaches for the treatment of various solid and hematologic cancer types. Our work with Personalis will help us to determine which patients are most likely to respond favorably to these novel treatment regimens."

Invectys is now enrolling CLL patients in this Phase II, open-label, single-arm trial consisting of two patient groups: 45 patients receiving INVAC-1 as monotherapy and an additional 45 patients receiving INVAC-1 in combination with ibrutinib, a Bruton’s Tyrosine Kinase inhibitor. The primary goal of the study is to achieve minimal residual disease negativity in both groups. The trial is being conducted at the MD Anderson Cancer Center in Houston, Texas. For more information, please visit clinicaltrials.gov identifier NCT03265717.

"Invectys has built an exciting pipeline of novel, next-generation immunotherapies, and we’re thrilled to help drive their lead program forward," said John West, CEO of Personalis. "Having already established ourselves as a leader in comprehensive tumor immunogenomic profiling and biomarker discovery for solid tumor indications, we’ve seen increasing use of our capabilities for biomarker evaluation in hematologic cancer types. This bodes well as we continue to rollout and onboard customers for our newly-launched, universal cancer immunogenomics platform, ImmunoID NeXT."

On September 9, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported the submission of a New Drug Application (NDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the use of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), for the treatment of patients with HER2 positive metastatic breast cancer (Press release, Daiichi Sankyo, SEP 9, 2019, View Source [SID1234539362]).

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The Japan NDA is primarily based on the positive results from the pivotal phase 2 DESTINY-Breast01 trial of [fam-] trastuzumab deruxtecan, an open-label, global, multicenter trial, which evaluated dosing, efficacy and safety in patients with HER2 positive metastatic breast cancer. The submission also includes data from the phase 1 trial published in The Lancet Oncology.[1] The response rate observed in DESTINY-Breast01, as assessed by an independent review committee, confirmed the clinical activity observed in the phase 1 trial. Data from DESTINY-Breast01 will be presented at an upcoming medical meeting.

"We are proud to initiate this critical next step in the regulatory process in Japan and look forward to the presentation of the phase 2 DESTINY-Breast01 study of [fam-] trastuzumab deruxtecan to the scientific community," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "We look forward to working closely with the Japan Health Authority on our application for [fam-] trastuzumab deruxtecan in order to bring this important potential new treatment to patients in Japan."

[Fam-] trastuzumab deruxtecan is currently in development for the treatment of patients with a variety of HER2 expressing or HER2 mutant cancers, including gastric, colorectal and lung cancer, as well as in breast cancer with HER2 low expression.

The safety and tolerability profile of [fam-] trastuzumab deruxtecan in DESTINY-Breast01 was consistent with the phase 1 trial data published in The Lancet Oncology, in which the most common adverse events (≥30 percent, any grade) included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea and constipation. Cases of drug-related pneumonitis, including grade 5 events, have also been reported in the clinical development program.

About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis in breast cancer patients.[2] To be considered HER2 positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.[2] A finding of IHC 3+ and/or FISH amplification is considered positive.[2] There are currently no approved HER2 targeted therapies for HER2 FISH negative, IHC 2+ or IHC 1+ tumors.

Unmet Need in HER2 Positive Breast Cancer
Approximately one in five breast cancers are HER2 positive.[3],[4] Despite recent improvements and approvals of new therapies, there remains significant unmet clinical needs for patients with advanced HER2 positive metastatic breast cancer.[5],[6] This disease remains incurable with these patients eventually progressing after available therapies.[5],[6]

About DESTINY-Breast01
DESTINY-Breast01 is a pivotal phase 2, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1). The primary endpoint of the trial is objective response rate. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival.

The first part of the trial includes a pharmacokinetic stage and a dose-finding stage to identify the recommended dose of [fam-] trastuzumab deruxtecan to be evaluated in the second part of the trial. The second part enrolled patients into one of two cohorts: patients resistant or refractory to T-DM1 (part 2a) and patients who discontinued treatment with T-DM1 for reasons other than resistant or refractory disease (part 2b). Enrollment into DESTINY-Breast01 was completed in September 2018 with 253 patients at more than 100 sites across North America, Europe, Japan and other countries in Asia.

About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; fam-trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced program in AstraZeneca’s ADC Scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia, including five pivotal trials in HER2 expressing breast and gastric cancers, including in breast cancer patients with HER2 low expression. [Fam-] trastuzumab deruxtecan is also in phase 2 development for HER2 expressing advanced colorectal cancer and metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC, and phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancers.

[Fam-] trastuzumab deruxtecan was granted Breakthrough Therapy Designation in 2017 by the U.S. FDA for the treatment of patients with HER2 positive, locally-advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1. Fast Track Designation was also granted in the U.S. for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted medicines, including T-DM1. Trastuzumab deruxtecan has received SAKIGAKE designation for the treatment of advanced HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare.

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication

in any country. Safety and efficacy have not been established.

About the Collaboration Between Daiichi Sankyo and AstraZeneca
In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize [fam-] trastuzumab deruxtecan as a medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.