On November 5, 2019 Senti Biosciences, the gene circuit company focused on outsmarting complex diseases with intelligent medicines, reported that Senti scientists will present data at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 6-10, 2019, in National Harbor, Maryland (Press release, Senti Biosciences, NOV 5, 2019, View Source [SID1234550364]).

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Senti’s gene circuit platform enables the programming of any cell and gene therapy modality, including immune cells, stem cells, and viral vectors. The poster presentation highlights preclinical data from one of Senti’s programs, SENTI-101, an allogeneic cell therapy designed to treat patients with ovarian cancer and other solid tumors.

"This SITC (Free SITC Whitepaper) poster presentation is an important milestone for Senti Biosciences because it reveals an exciting translational application of our gene circuit platform, which has the potential to broadly transform cell and gene therapies," said Dr. Timothy Lu, CEO of Senti Biosciences.

The SENTI-101 program uses tumor-homing allogeneic cells as a drug delivery vehicle to achieve localized, combinatorial expression of two cytokines. This pair of cytokines activates a multifactorial immune response against solid tumors, and turns immunologically cold tumors hot. SENTI-101 was developed through Senti’s systematic design-build-test-learn process, wherein more than 250 different gene circuits including individual, two-wise and three-wise combinations of immune effectors were tested for their ability to treat cold tumors and trigger a robust tumor immunity cycle. This approach of programming artificial pharmacology into allogeneic cells enables delivery of high concentrations of multi-factorial immunotherapies locally in the tumor microenvironment, which Senti believes will be critical to transforming therapy for solid tumors.

"There’s a huge unmet need when it comes to developing treatments for patients whose tumors do not respond to checkpoint inhibitors, and we are excited about the potential for SENTI-101 to help these patients," said Gary Lee, Ph.D., Chief Scientific Officer at Senti Biosciences.

SENTI-101 is a novel product candidate comprising allogeneic mesenchymal stromal cells (MSCs) genetically modified to express a combination of immunomodulatory cytokines — Interleukin 12 (IL-12) and Interleukin 21 (IL-21). Together, IL-12 and IL-21 enable highly effective and complementary stimulation of anti-tumor immunity.

Upon administration in preclinical models, SENTI-101:

Innately homes to peritoneal tumors (>10-fold higher vs. normal tissues, p≤0.0001)
Secretes IL-12 and IL-21 in a localized and sustained fashion within tumors of the peritoneal space (~100-fold greater in peritoneal space vs. serum [p≤0.002])
Induces a robust and durable anti-tumor immune response, resulting in more than 200-fold (p≤0.0001) and 10-fold (p≤0.0001) reduction in tumor burden in CT26-fLUC and B16-F10-fLUC models, respectively
Prolongs tumor-free survival compared to controls and checkpoint inhibitor therapy in syngeneic tumor models, including the checkpoint refractory B16-F10 model, and notably, mice treated with the SENTI-101 combination outperformed those treated with MSCs expressing each individual cytokine
Additionally, surviving mice rejected a second round of newly implanted tumor cells, thereby demonstrating anti-tumor immune memory
Mechanistically involves multiple important immune cell subtypes, including CD4 and CD8 T cells, antigen-presenting cells (APCs), B cells and NK cells
The SITC (Free SITC Whitepaper) abstract can be accessed here: http://bit.ly/2Wt2wli

Recent Corporate Update

In addition to its gene circuits and translational biology capabilities, Senti has established in-house process development, regulatory, and clinical expertise to pursue IND-enabling studies, GMP manufacturing, and clinical protocol development for its pipeline. Additional gene circuit cell therapy programs for solid tumors and difficult-to-treat liquid tumors are also underway, with plans to advance candidates for clinical development in the next year.

Senti’s corporate strategy is focused on internal product development, as well as establishing collaborations with other companies. The gene circuit platform can be paired with a variety of complementary technologies to create next-generation cell and gene therapies with improved performance. For example, Senti’s engineered promoters and logic gates enable cell and gene therapies with programmable specificity and high activity in defined cell states or cell types. In addition, Senti’s Pro-Dial platform allows for cell and gene therapies to be titrated up or down in a rheostat fashion with FDA-approved small molecule drugs. These technologies have the potential to make cell and gene therapies controllable, targeted and dynamic, thus increasing the therapeutic window and addressing indications not accessible by current therapies.

On November 5, 2019 IONpath, Inc., a company revolutionizing multiplexed tissue imaging, reported that launched the MIBIscope System, the first commercially available Multiplexed Ion Beam Imaging (MIBI) system (Press release, IONpath, NOV 5, 2019, View Source [SID1234550363]). The MIBIscope enables researchers to image over 40 biomarkers simultaneously at higher sensitivity, resolution, and throughput than existing methods. IONpath is showcasing the platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Maryland from November 6-10.

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To help scientists see deeper into the tissue microenvironment and study the relationships between proteins, cells and their environment in intact tissue samples, IONpath has leveraged secondary ion mass spectrometry and elementally labeled antibodies to create MIBI technology. This method enables higher throughput than existing multiplexed imaging technologies, such as mass cytometry, and is far more sensitive, permitting single-molecule detection. The MIBIscope can image cellular structures as small as 280 nm and visualize over 40 biomarkers simultaneously with a dynamic range of five orders of magnitude.

"Scientists in oncology and translational research will benefit from the unprecedented insights into spatial relationships within the tissue microenvironment by imaging and characterizing tissue samples at subcellular resolution," said Harris Fienberg, chief executive officer and co-founder, IONpath. "After successfully piloting the MIBIscope in leading research and biopharma institutions, we are excited to bring the platform to market."

The MIBIscope System removes only a thin layer of sample during imaging, thus permitting scientists to perform multiple scans on a single sample. Further, by scanning at different levels of depth, researchers can study tissue architecture in three dimensions. The MIBIscope System can be automated to image tissue samples continuously for multiple days, allowing researchers to process hundreds of samples a week and conduct broad cohort studies.

The simple staining process employs a standard immunohistochemistry workflow and is compatible with both FFPE and fresh/frozen tissue. Furthermore, samples are stable for months following staining.

To learn about the MIBIscope, visit IONpath at SITC (Free SITC Whitepaper) booth #326, or attend the company’s symposium on Saturday, November 9 at 12:35 pm in Riverview Ballroom A3, where leading researchers from the Dana-Farber Cancer Institute, Stanford University, and University of Colorado, Denver, will be presenting their research using the MIBIscope to characterize the tumor microenvironment. More information about IONpath’s activities at SITC (Free SITC Whitepaper) can be found at View Source Information about the MIBIscope System can be found at View Source

On November 5, 2019 PureTech Health plc (LSE: PRTC) ("PureTech"), a clinical-stage biotechnology company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the presentation of new preclinical data from its wholly-owned immuno-oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Md (Press release, PureTech Health, NOV 5, 2019, View Source [SID1234550362]).

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The two scientific posters detail the Company’s continued progress in advancing two fully human monoclonal antibodies (mAbs) developed to inhibit two foundational immunosuppressive orchestrators, galectin-9 (LYT-200) and pathogenic gamma delta-1 (γδ1) T cells (LYT-210).

"These data further show the unique position and importance of galectin-9 and γδ1 as immunosuppressors in cancer biology. Both have been observed to have powerful properties to disable immune-mediated cancer attack, which may explain some of the fundamental efficacy limitations of other immuno-oncology therapies," said Joseph Bolen, PhD, chief scientific officer at PureTech. "Our novel antibodies targeting galectin-9 and γδ1 have produced compelling single-agent preclinical data against a number of difficult-to-treat cancers in models where approved immunotherapies haven’t worked. We are excited to share our continued progress with the scientific community at premier conferences such as SITC (Free SITC Whitepaper)."

The new data presented at SITC (Free SITC Whitepaper) indicate that galectin-9 is not only a potent therapeutic target, but also a potentially relevant biomarker. Across multiple cohorts, galectin-9 was significantly increased in blood samples of individuals with primary and metastatic pancreatic cancer, lung tumors, and colorectal carcinoma, compared to healthy individuals.

"These findings validate the importance of galectin-9 in cancer biology and its potency as a target," said George Miller, MD, Director of S. Arthur Localio Laboratories and Director of the Cancer Immunology Program at NYU School of Medicine and a PureTech collaborator. "Our research indicates that galectin-9 is a master immunosuppressor; it induces a highly favorable microenvironment for tumor growth. LYT-200 has potential both as a single agent and in combination with checkpoint inhibitors to have therapeutic potential by reversing the immunosuppression which can be present in the tumor microenvironment."

PureTech expects to file an Investigational New Drug application (IND) for LYT-200 in the first half of 2020 and to initiate a Phase 1a/1b clinical trial in solid tumors in 2020. The mAb has been tested as a single agent as well as in combination with anti-PD1 checkpoint inhibitors in preclinical murine and human-derived ex vivo models, showing robust and reproducible activity, immune activation potential as well as excellent drug properties.

PureTech also presented data on its monoclonal antibody LYT-210 that targets γδ1 T cells whose immunosuppressive features leads to a tumor permissive microenvironment. The research presented at SITC (Free SITC Whitepaper) showed that γδ1 T cells were the most abundant T cell within the studied tumors, which included pancreatic, colorectal, cholangiocarcinoma, and liver cancer, and represented up to 50% of all infiltrating T cells. PureTech also presented data showing that LYT-210 depletes immunosuppressive γδ1 T cells through cytotoxicity and phagocytosis. Together, these findings further support the ability of LYT-210 to potentially restore the immune system’s ability to fight difficult-to-treat cancers. PureTech expects to file an IND for LYT-210 in 2021 for solid tumors.

"These data show that γδ1 cells play a key role in suppressing the immune system’s ability to attack tumors. LYT-210 is designed to remove and destroy pathogenic γδ1 T cells enabling immune mediated cancer attack. We therefore believe LYT-210 holds significant promise as a potential immunotherapy," said Dr. Miller.

On November 5, 2019 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket"), a leading U.S.-based multi-platform clinical-stage gene therapy company, reported that Gaurav Shah, M.D., Chief Executive Officer and President of Rocket is scheduled to present on Wednesday, November 13, 2019, at 2:15 p.m. Eastern Time at the Barclays Gene Editing & Gene Therapy Summit, New York, N.Y (Press release, Rocket Pharmaceuticals, NOV 5, 2019, View Source [SID1234550361]).

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On November 5, 2019 Seres Therapeutics, Inc. (Nasdaq: MCRB) reported financial results for the three months ended September 30, 2019 and provided a business update (Press release, Seres Therapeutics, NOV 5, 2019, View Source [SID1234550360]).

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"Seres continues to advance our microbiome programs, and the Company is well resourced to reach important corporate milestones in 2020, including two late-stage clinical readouts: SER-287 Phase 2b study in mild-to-moderate ulcerative colitis and SER-109 Phase 3 study in recurrent C. difficile infection," said Eric D. Shaff, President and Chief Executive Officer at Seres. "We are very pleased that our SER-109 ECOSPOR III study is now approaching target enrollment. SER-109 could provide patients with a meaningful new treatment option and also provide definitive clinical validation for our microbiome therapeutic approach. We are eagerly looking forward to top-line results from both of these important programs."

Program Updates and Corporate Highlights

SER-287 Phase 2b ECO-RESET study in ulcerative colitis: SER-287 is an orally-administered, biologically-derived, live microbiome therapeutic candidate designed to modulate the gastrointestinal microbiome of individuals with ulcerative colitis. Seres continues to enroll the SER-287 Phase 2b ECO-RESET induction study in patients with active mild-to-moderate ulcerative colitis. The SER-287 Phase 2b ECO-RESET study is expected to enroll approximately 201 patients. Based on U.S. Food and Drug Administration feedback, Seres expects that with positive Phase 2b study results, the study could serve as one of two pivotal trials to enable a SER-287 Biologics License Application submission. Seres expects Phase 2b ECO-RESET study top-line results in the second half of 2020.
SER-109 Phase 3 ECOSPOR III study in recurrent C. difficile infection: SER-109 is an orally-administered, biologically-derived, live microbiome therapeutic candidate designed to restore the depleted, or dysbiotic, gastrointestinal microbiome of patients with recurrent C. difficile infection. The Company continues to enroll the ECOSPOR III trial, which is evaluating efficacy and safety in 188 patients with recurrent C. difficile infection. All patients enrolled in ECOSPOR III are required to test positive for C. difficile cytotoxin to ensure enrollment of only patients with an active C. difficile infection. As of October 31, ECOSPOR III was more than 85% enrolled, and top-line study results are expected in mid-2020.
SER-301 preclinical candidate for ulcerative colitis: The Company has nominated the lead candidate for SER-301, a rationally-designed, live microbiome therapeutic for ulcerative colitis. Next-generation, rationally-designed microbiome therapeutics may provide important benefits that include the optimization of pharmacological properties for target diseases and streamlined manufacturing. The consortia of bacteria in SER-301 are designed to modify the microbiome and microbe-associated metabolites in the gastrointestinal tract to modulate ulcerative colitis-relevant anti-inflammatory and immune pathways and to improve epithelial barrier integrity. SER-301 incorporates species associated with clinical efficacy in prior Seres human studies. Further, bacterial species selected for inclusion in SER-301 have been confirmed to engraft across human subjects. The consortia has demonstrated the capacity to modulate disease-relevant cellular mechanisms in human cell-based screening assays and in vivo models. Seres is entitled to a $10 million milestone payment associated with the SER-301 Phase 1 clinical study from its ongoing collaboration with Nestlé Health Science. Seres expects to initiate clinical development in early 2020.
SER-401 Phase 1b in metastatic melanoma: SER-401 is an orally-administered, biologically-derived, live microbiome therapeutic candidate comprising bacteria that reflect the bacterial signature in the gastrointestinal microbiome associated with response to checkpoint inhibitor immunotherapy. The ongoing Phase 1b study, supported by the Parker Institute for Cancer Immunotherapy and The University of Texas MD Anderson Cancer Center, will evaluate the potential for SER-401 to improve clinical response to nivolumab, an approved anti-PD-1 checkpoint inhibitor therapy, and will evaluate tumor biopsies and various biomarkers. Seres expects to obtain SER-401 Phase 1b preliminary study results in the second half of 2020.
New debt financing: Seres entered into a debt financing agreement with Hercules Capital in October 2019 that provides the Company with up to $50 million in additional capital. The Company received a first tranche of approximately $25 million following the agreement closing. Two subsequent tranches of $12.5 million each would become available to the Company upon the achievement of certain milestones.
Financial Results
Seres reported a net loss of $16.4 million for the third quarter of 2019, as compared to a net loss of $21.9 million for the same period in 2018. The third quarter net loss was driven primarily by clinical and development expenses, personnel expenses and ongoing development of the Company’s microbiome therapeutics platform. The third quarter net loss figure was inclusive of $7.0 million in recognized revenue associated primarily with the Company’s collaborations with Nestlé Health Science and AstraZeneca.

Research and development expenses for the third quarter of 2019 were $18.3 million, as compared to $23.7 million for the same period in 2018. The research and development expense was primarily related to Seres’ late stage SER-109 and SER-287 clinical development programs.

General and administrative expenses for the third quarter of 2019 were $5.9 million, as compared to $7.6 million for the same period in 2018. General and administrative expenses were primarily due to headcount, professional fees and facility costs.

Seres ended the third quarter with approximately $83.8 million in cash, cash equivalents and investments. This amount does not include the $25 million in debt capital obtained in October 2019.

Cash resources are expected to fund operating expenses and capital expenditure requirements, excluding net cash flows from future business development activities or potential incoming milestone payments, into the second quarter of 2021.

Conference Call Information
Seres’ management will host a conference call today, Nov. 5, 2019 at 8:30 a.m. ET. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 3577505. To join the live webcast, please visit the "Investors and Media" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.