On May 2, 2018 Refuge Biotechnologies, Inc. ("Refuge"), a company leveraging gene engineering technologies to develop intelligent cell therapeutics programmed to make decisions inside of patients, reported the closing of a $25 million Series B investment round (Press release, refuge biotechnologies, MAY 2, 2018, View Source [SID1234525981]). In addition, the company has appointed immuno-oncology pioneer Francesco Marincola, M.D., as chief scientific officer.

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The Series B financing was led by 3SBio and Sequoia China, with participation from new investors Danhua Capital (DHVC), Sangel Capital and Ocean Pine Healthcare Fund. Refuge’s existing investors, 3E Bioventures, WuXi Healthcare Ventures, and ShangBay Capital, also participated in the round.

The funds from the Series B will support advancement of cell therapies developed with Refuge’s receptor-dCas platform, which utilizes a mutated or dead Cas9 (dCas) as a targeting mechanism to enable precision CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi). The cell therapies are programed to only activate CRISPRa/CRISPRi when they encounter specific sensors found on the surface of cancer cells, which delivers the treatment effect only to target cells. As a result, cell therapies have the potential to bring together multiple anti-cancer approaches in a single cell, such as repression of multiple checkpoint targets, with greater potency and reduced side effects. Refuge’s pipeline is led by RB-1916, a CAR-T cell therapy designed to inhibit the expression of the PD-1 gene, with a potential initial application in diffused large B-cell lymphoma. Refuge has additional CAR cell therapy programs under research that conditionally repress PD-1 and other checkpoint inhibitors for potential treatment of solid tumors.

"We have seen tremendous progress in the development of our technology and science, and believe that our receptor-dCas platform has the potential to create highly targeted cell therapies that bring superior efficacy while overcoming limitations related to toxic side effects," said Bing C. Wang, Ph.D., co-founder and chief executive officer of Refuge Biotech. "This financing will propel our efforts with our growing pipeline as we continue to design these innovative and intelligent cell therapies to fight cancer, and we are encouraged by the support from this top group of global investors."

As part of the investment, the lead investors will have an exclusive right to negotiate with Refuge on the right to the development and commercialization of cell therapies using Refuge’s platform in China. Concurrently, Refuge and 3SBio will also collaborate on research developing programmed cell therapeutics that can produce therapeutic proteins inside a patient’s body using Refuge’s platform technology.

Concurrent with the financing, Zhenping Zhu, M.D., Ph.D., of 3SBio and Trency Gu, Ph.D., of Sequoia China, have joined the Refuge board of directors.

"3SBio’s investment demonstrates our commitment to advancing cutting-edge gene engineering technologies with potential for breakthrough treatments for cancer and other diseases with unmet medical needs," said Jing Lou, M.D., Ph.D., Chairman and CEO of 3SBio Inc. "3SBio looks forward to collaborating with Refuge to accelerate the clinical development of Refuge’s next-generation cell therapies for cancer and to fully realize the potential of the dCas9 platform."

Added Neil Shen, founding and managing partner of Sequoia China, "Sequoia China endeavors to back innovative companies in the life science field such as Refuge Bio, which brings together topnortch scientific and commercial talents in the gene editing and cell therapy space. We are pleased to support Refuge Bio to further develop the dCas9 platform for wide therapeutic applications to improve human health."

The CRISPRa and CRISPRi are made possible by dCas9, which no longer cuts DNA but functions as a carrier to specific areas of the genome for highly targeted delivery a transcriptional activator or repressor to turn on or turn off genes. The novel receptor-dCas platform allows for control of how a cell interacts with its environment. Cells generally communicate and sense their surrounding through membrane receptors. Connecting receptors to dCas creates a therapeutic platform that enables cells to sense its surroundings and activate or repress multiple gene expression based on the receptor-ligand interactions. With receptor-dCas, cells can be now programmed to turn off certain genes, such as PD-1, to generate more potent CAR-T immune cells when it senses the presence of a tumor cell.

About Francesco Marincola, M.D.
As chief scientific officer, Dr. Marincola will lead development of Refuge’s intelligent cell therapy platform and investigation of its lead therapeutic programs. He most recently served as a distinguished research fellow and strategist for immune oncology discovery at AbbVie. Prior to this, he developed and led a genetic research institute at Sidra Medical and Research Center in Qata where he played a pivotal role in the Qatar Genome Project. He also trained in surgical oncology under Steven Rosenberg, M.D., Ph.D., at the National Cancer Institute and subsequently was a tenured investigator and chief of the infectious disease and immunogenetics section at the NIH Clinical Center. Dr. Marincola has spent his career studying tumor immunology and was a pioneer in the development of technologies for studying in real-time the dynamics of the tumor microenvironment adaptations during immune therapy. He described the mechanisms leading to cancer immune rejection describing the immunologic constant of rejection as a conserved process shared responsible for other forms of immune-mediated tissue-specific destruction such as allograft rejection, graft versus host disease, flares of autoimmunity and clearance of pathogen during acute infections. He is currently leading worldwide efforts to understand the mechanism of cancer immune resistance such as the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Task Force on Immune Responsiveness aimed at involving different areas of expertise besides immunology. Dr. Marincola graduated summa cum laude at the University of Milan, Medical School, Italy, and completed a general surgery residency with a focus in immunology at Stanford University. He was president of the Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and is the founding and current editor-in-chief of the Journal of Translational Medicine.

On May 1, 2018 Intellia Therapeutics, Inc. (NASDAQ: NTLA), a leading genome editing company focused on the development of curative therapeutics using CRISPR/Cas9 technology, announced financial results and operational progress for the first quarter of 2018 (Press release, Intellia Therapeutics, MAY 1, 2018, View Source [SID1234525885]).

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John Leonard, M.D., was appointed Intellia’s President and Chief Executive Officer in the first quarter of 2018, and one of his first initiatives was to broaden the Company’s strategy. "We are building the premier CRISPR-based genome editing company with leading in vivo and ex vivo capabilities," said Dr. Leonard. "We are very pleased with the scientific data generated from our in vivo non-human primate (NHP) studies, and the progress with our modular, scalable lipid nanoparticle (LNP) delivery system has allowed us to target a timeframe for our first Investigational New Drug (IND) submission. As we continue to execute on our full spectrum of in vivo and ex vivo genome editing platforms, we will share progress on our differentiated, wholly owned ex vivo approach, starting this month at the American Society of Gene and Cell Therapy Annual Meeting."

The Company announced today that it anticipates submitting an IND application for its lead indication, transthyretin amyloidosis (ATTR), by the end of 2019 and confirms plans to initiate IND-enabling studies in mid-2018. Over the past six months, ongoing NHP studies have demonstrated well-tolerated editing to therapeutically relevant levels of transthyretin (TTR) protein reduction (60 to 80 percent) after a single systemic administration via LNP delivery to NHP hepatocytes. Rates of editing were durable over the six-month period without re-dosing the animals. In support of the proposed IND submission, Intellia has narrowed the field of potential guides to its current development candidate for early human trials. The guide-optimization process used high-throughput screening to evaluate the entire TTR gene for those guides with high levels of activity and undetectable off-target cutting. The Company has completed studies to understand potential dosing regimens and is continuing studies on durability of the effect, both of which may expedite Phase I clinical trials. Intellia has also developed an enhanced LNP formulation through optimization campaigns that is currently being tested for multiple follow-on liver indications, and anticipates that this modular approach may minimize development timelines for each additional and subsequent liver-targeted product candidate.

Intellia has also demonstrated continued progression of its modular liver platform capability to knockout various targets of interest in the livers of mice, including SERPINA1 for alpha-1 antitrypsin deficiency (AATD) and HAO1 for primary hyperoxaluria type 1 (PH1), each of which has resulted in protein expression reductions believed to be therapeutically relevant. This initial knockout edit in AATD lays the groundwork for developing an approach that restores production of the missing protein in AATD, required for the amelioration of the disease.

The table below shows editing rates and corresponding protein reductions in the livers of mice for ATTR, AATD and PH1. ATTR and AATD both produce aberrant proteins hence treatment of these conditions requires reductions in the level of the disease-causing proteins. PH1 results from the low level activity of a particular protein for which treatment requires reducing the levels of substrate for that defective protein to metabolize, achieved by knocking out the gene that encodes HAO1. In each of these three cases, Intellia’s modular LNP delivery system achieved high levels of reduction of the targeted protein. These initial editing rates and corresponding protein reductions are evidence of Intellia’s ability to successfully target monogenic liver diseases by knocking out harmful genetic mutations.

Beyond the liver, the Company continues to advance its application of CRISPR/Cas9 technology to the central nervous system (CNS), including through its collaboration with Beverly Davidson, Ph.D., of the Children’s Hospital of Philadelphia, who will share updated LNP delivery data in a presentation at the American Society of Gene and Cell Therapy Annual Meeting later this month.

In ex vivo applications, Intellia seeks to develop allogeneic cellular therapies, which are cells derived from unmatched tissue donors, which are modified outside of the human body to allow them to be administered to an unrelated patient. This endeavor is supported through multiple efforts, including recently acquired access to intellectual property from researchers at the Karolinska Institutet and Intellia’s collaboration with Ospedale San Raffaele, announced in June of 2017.

In February of 2018, Cell Reports published Intellia’s first peer-reviewed paper entitled "A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing." This landmark paper documented Intellia’s delivery of Cas9 mRNA and single guide RNA using its proprietary LNPs to achieve a 97 percent reduction in mouse TTR protein levels in the liver, which was sustained for at least 12 months.

During the course of 2018, Intellia plans to share additional pre-clinical data on its TTR genome editing program, including the achievement of a near ten-fold reduction in the required dose, derived via improvements in potency, as well as other knockout targets and data on delivery via LNPs to the CNS of NHPs. Additionally, Intellia plans to share pre-clinical data on both immuno-oncology and autoimmune disease targets in 2018.

First Quarter 2018 Financial Results

Collaboration Revenue

Collaboration revenue was $7.5 million for the first quarter of 2018, compared to $6.2 million during the first quarter of 2017. The increase in collaboration revenue in 2018 was primarily driven by amounts recognized under Intellia’s collaboration agreement with Regeneron.

Since inception through March 31, 2018, the Company has received $112.1 million in funding from the collaborations with Novartis and Regeneron, excluding amounts received for equity investments, and had an accounts receivable balance of $7.5 million at March 31, 2018.

Operating Expenses

Research and development expenses increased by $9.1 million to $22.5 million during the first quarter of 2018, compared to $13.4 million during the first quarter of 2017. This increase was driven primarily by the advancement of Intellia’s research programs, research personnel growth to support these programs, as well as the expansion of the development organization, and includes laboratory supplies and research materials such as reagents.

General and administrative expenses increased by $1.7 million to $7.4 million during the first quarter of 2018, compared to $5.7 million during the first quarter of 2017. This increase was driven primarily by increased salary and related headcount-based expenses to support Intellia’s larger research and development organization, public company compliance, and administrative obligations.

The Company’s net loss was $21.4 million for the first quarter of 2018, compared to $12.6 million during the first quarter of 2017.

Balance Sheet

Cash and cash equivalents at March 31, 2018, were $327.8 million, compared to $340.7 million at December 31, 2017.

Financial Guidance

The Company’s primary uses of capital will continue to be for research and development programs, laboratory and related supplies, compensation costs for current and future employees, consulting, legal and other regulatory expenses, patent prosecution filing and maintenance costs for Intellia’s licensed intellectual property, and general overhead costs.

As of March 31, 2018, the Company had an accumulated deficit of $137.0 million. The Company expects losses to increase as it continues to incur significant research and development expenses related to the advancement of Intellia’s therapeutic programs and ongoing operations. Based on Intellia’s research and development plans and expectations related to the progress of the Company’s programs, the Company expects that the cash and cash equivalents as of March 31, 2018, as well as technology access and research funding from Novartis and Regeneron, will enable Intellia to fund operating expenses and capital expenditures through mid-2020, excluding any potential milestone payments or extension fees that could be earned and distributed under the collaboration agreements with Novartis and Regeneron or any strategic use of capital not currently in the base-case planning assumptions.

On May 1, 2018 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a clinical-stage biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported its first quarter 2018 financial results on Wednesday, May 9, 2018, after the NASDAQ market close (Press release, CytomX Therapeutics, MAY 1, 2018, View Source;p=RssLanding&cat=news&id=2346043 [SID1234525909]).

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The company will not be conducting a conference call in connection with this financial results press release.

On May 1, 2018 Sangamo Therapeutics, Inc. (Nasdaq: SGMO) reported that the company will release its first quarter 2018 financial results before the market opens on Tuesday, May 8, 2018 (Press release, Sangamo Therapeutics, MAY 1, 2018, View Source [SID1234525926]). The press release will be followed by a conference call at 8:00 a.m. ET, which will be open to the public via telephone and webcast. During the conference call, the company will review its financial results and provide a business update.

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The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 1194369. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 1194369.

On May 1, 2018 Jounce Therapeutics, Inc. (NASDAQ:JNCE), a clinical stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers for patient enrichment, reported that Richard Murray, Ph.D., chief executive officer and president of Jounce, will present at the Deutsche Bank 43rd Annual Health Care Conference on Tuesday, May 8, 2018 at 1:30 PM ET in Boston, MA (Press release, Jounce Therapeutics, MAY 1, 2018, View Source;p=RssLanding&cat=news&id=2345890 [SID1234525886]).

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A live webcast of the presentation will be available by visiting "Events and Presentations" in the Investors and Media section of Jounce’s website at www.jouncetx.com. A replay of the webcast will be archived for 30 days following the presentation.