On August 3, 2021 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company leveraging the microbiome to develop therapeutics designed to prevent and treat gastrointestinal ("GI") diseases in areas of high unmet need, reported an amendment to the Company’s option for an exclusive license with Massachusetts General Hospital ("MGH") to include intellectual property ("IP") and technology related to the use of SYN-020 intestinal alkaline phosphatase ("IAP"), the Company’s proprietary recombinant version of bovine IAP, to inhibit liver fibrosis in select diseases, including nonalcoholic fatty liver disease ("NAFLD") (Press release, Synthetic Biologics, AUG 3, 2021, View Source [SID1234585629]).

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Synthetic Biologics, Inc. www.syntheticbiologics.com (PRNewsFoto/Synthetic Biologics, Inc.)

Synthetic Biologics previously announced an option agreement with MGH to negotiate an exclusive license to IP and technology for the use of SYN-020 to prevent and treat metabolic and inflammatory diseases associated with aging. The option agreement has now been expanded to include technology developed by MGH to use SYN-020 to inhibit liver fibrosis in select diseases, including NAFLD. If executed, the license agreement would further strengthen the SYN-020 portfolio and build upon the Company’s intention to pursue SYN-020 for the treatment of NAFLD, and, in particular, to slow the course of fibrosis associated with progressive disease.

"We are pleased to announce the expansion of our collaboration with Massachusetts’s General Hospital and share their enthusiasm for SYN-020’s potential to address diseases associated with liver fibrosis such as nonalcoholic fatty liver disease," said Steven A. Shallcross, Chief Executive Officer of Synthetic Biologics. "We continue to view SYN-020 as a potential platform therapeutic that has a remarkable opportunity to address a considerable unmet need for innovative new therapies targeting GI disorders stemming from immune and inflammatory responses."

Under the terms of the amended agreement, Synthetic Biologics is granted an option to negotiate an exclusive worldwide license with MGH to commercially develop SYN-020 to treat and prevent metabolic and inflammatory diseases associated with aging and fibrosis of the liver.

About SYN-020 Phase 1 SAD & MAD Clinical Trials

Synthetic Biologics recently announced the completion of patient dosing and observation of its Phase 1 single-ascending dose ("SAD") clinical trial of SYN-020 in 24 healthy adult volunteers. Results from this trial demonstrated that SYN-020 maintained a favorable safety profile, was well tolerated at all dose levels, and no adverse events were attributed to SYN-020. No serious adverse events were reported. A second Phase 1 multiple-ascending dose ("MAD") clinical trial of SYN-020 in healthy adult volunteers is expected to commence during the third quarter of 2021 with topline results anticipated during the second quarter of 2022. Both Phase 1 SAD and MAD studies are intended to support the development of SYN-020 in multiple potential clinical indications, including celiac disease, radiation enteropathy, metabolic and inflammatory disorders associated with aging, and to inhibit fibrosis in select diseases, including NAFLD.

About SYN-020 Intestinal Alkaline Phosphatase (IAP)

SYN-020 is a recombinant bovine Intestinal Alkaline Phosphatase (IAP) formulated for oral delivery to the small intestine. The published literature indicates that IAP functions to diminish intestinal inflammation, tighten the gut barrier to diminish "leaky gut," and promote a healthy microbiome. Despite its broad therapeutic potential, a key hurdle to commercialization has been the high cost of IAP manufacture. Synthetic Biologics has overcome this hurdle and has the ability to produce SYN-020 at a scale and cost viable for clinical and commercial development. Synthetic Biologics is currently developing SYN-020 in multiple potential clinical indications, including celiac disease, nonalcoholic fatty liver disease (NAFLD), radiation enteritis, and indications to treat and prevent metabolic and inflammatory disorders associated with aging.

On August 3, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported that Michel Detheux, PhD, President and Chief Executive Officer, will present at the upcoming Wedbush PacGrow Healthcare Conference 2021 on Tuesday, August 10, 2021 at 2:20 p.m. ET (Press release, iTeos Therapeutics, AUG 3, 2021, View Source [SID1234585628]).

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A live webcast of the presentation will be available on the Investors section of the company’s website at View Source An archived replay will be available for approximately 30 days following the presentation.

On August 3, 2021 Orion Corporation ("Orion") reported that it has signed a European wide marketing and distribution agreement with Marinus Pharmaceuticals, Inc. ("Marinus") for ganaxolone, a GABAA receptor modulator being investigated in multiple rare seizure disorders (Press release, Orion , AUG 3, 2021, View Source [SID1234585627]).

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Under the terms of the agreement, Orion will have the right to sell and market ganaxolone in Europe. Orion has made an upfront payment of EUR 25 million to Marinus as a signing fee. Marinus is also eligible to receive tiered royalty ranging from low double-digits to low twenties on Orion’s future sales. In addition, Marinus is eligible to receive milestone payments upon achievement of certain development and commercialisation milestones.

Marinus will be the marketing authorisation holder and responsible for current and future clinical trials of ganaxolone. Orion will be responsible for market access in all 30 countries comprising the European Economic Area (EEA) as well as in the United Kingdom and Switzerland.

In September 2020, Marinus reported positive phase III data from a study that evaluated orally administered ganaxolone for the treatment of seizures in children and young adults with Cyclin-dependent Kinase-like 5 (CDKL5) deficiency disorder (CDD). Based on the study results, Marinus submitted a new drug application (NDA) to the United States Food and Drug Administration (FDA) for ganaxolone in CDD and expects to file a marketing authorisation application (MAA) with the European Medicines Agency (EMA) later this year. Both agencies have granted orphan drug designation to ganaxolone for the treatment of CDD.

In addition to CDD, orally administered ganaxolone is being investigated for the treatment of seizures associated with tuberous sclerosis complex (TSC) and intravenously administered ganaxolone is being investigated for the treatment of seizures associated with refractory status epilepticus (RSE). Marinus is also looking into additional indications and patient populations that could benefit from ganaxolone.

Satu Ahomäki, SVP Commercial Operations of Orion Corporation said: "We are pleased to be the partner of choice for Marinus in Europe. What we have seen so far with ganaxolone is encouraging and signifies an ongoing commitment to the rare epilepsy communities. I look forward to these efforts to advance effective medicines for these disorders. Ganaxolone could be a promising treatment option for patients suffering from rare epilepsies."

"Orion has a strong presence across Europe in rare neurological disorders, brings an extensive commercial infrastructure and is an ideal partner to introduce ganaxolone in Europe," said Scott Braunstein, M.D., Chief Executive Officer of Marinus. "This collaboration not only serves as an important step in our global development strategy for ganaxolone, it also represents the confidence Orion has in its potential. I believe that the collaboration allows both parties to share in the long term success of ganaxolone."

On August 3, 2021 4SC AG (4SC, FSE Prime Standard: VSC) reported that it will publish its half-year report 2021 on 10 August 2021 (Press release, 4SC, AUG 3, 2021, View Source [SID1234585626]). On this day, the Management of 4SC AG will host a conference call at 2 pm CEDT (8 am EDT) to inform about important developments in the reporting period and beyond.

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Investors, financial analysts, and journalists interested in participating in the conference call can access via the telephone numbers stated below. Please join the event conference 5-10 minutes prior to the start time. You will be asked to provide the confirmation code.

On August 3, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies (Press release, Fate Therapeutics, AUG 3, 2021, View Source [SID1234585625]). FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

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"Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement."

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

Use of a clonal master engineered iPSC line as the starting cell source, which enables CAR T cells to be mass produced and delivered off-the-shelf for broad patient access;
Incorporation of a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion as described in the journal Nature Medicine (View Source);
Insertion of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency as described in the journal Nature (View Source); and
Complete bi-allelic disruption of T-cell receptor (TCR) expression for the prevention of graft-versus-host disease (GvHD), a potentially life-threatening complication associated with allogeneic T-cell therapy.
The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).