On September 9, 2019 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported that it has entered into a research collaboration with Carisma Therapeutics to evaluate the potential of Phio’s self-delivering RNAi compounds to synergistically modify Carisma’s chimeric antigen receptor macrophages (CAR-M) (Press release, Phio Pharmaceuticals, SEP 9, 2019, View Source [SID1234539376]). Silencing of key genes using sd-rxRNA compounds may enhance the immune function of these cells as a novel adoptive cell therapy for use in cancer treatment.

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"Overcoming local tumor immunosuppression remains a significant challenge in the treatment of cancer," said Dr. John A. Barrett, Chief Development Officer of Phio Pharmaceuticals. "We have established collaborations with several companies and academic institutions to validate our technology’s ability to improve the activity of T cells, TILS, NK cells and dendritic cells towards tumors. Macrophages are sentinel cells of the innate immune system that robustly accumulate in most solid tumors. Combining Phio’s gene silencing technology with Carisma’s CAR-M technology has the potential to enhance aspects of macrophage anti-tumor activity and may further tip the scale in favor of an immunostimulatory phenotype and enhance tumor cell killing. We believe we can leverage both technologies to turn cold tumors hot and ultimately improve outcomes for patients."

Dr. Gerrit Dispersyn, Phio Pharmaceuticals’ President and CEO stated "We are very excited to work with the Carisma Therapeutics team, which represents our first collaboration addressing macrophages utility as an immunotherapeutic. By combining Carisma’s unique approach to adoptive cell therapy using CAR macrophages with our self-delivering RNAi technology, we expect to demonstrate potential synergies between our platforms that could enable us to bring new and improved forms of adoptive cell therapy to patients in the future. Our overall strategy in this setting is to generate robust data that validate our platform for the weaponization of a broad range of immune cells against tumors in order to generate future partnerships and build shareholder value."

"Metastatic solid tumors have been an intractable challenge for engineered cell therapies. Our platform technology, based on the genetically engineered macrophage, has a unique opportunity to provide benefit in this disease state," said Dr. Michael Klichinsky, co-Founder and Vice President of Discovery at Carisma. "We are excited to work with Phio to evaluate sd-rxRNA mediated silencing of genes that have the potential to enhance macrophage immunotherapy."

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).

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.