On February 27, 2019 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology in both in vivo and ex vivo applications, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2018 (Press release, Intellia Therapeutics, FEB 27, 2019, View Source [SID1234533778]). In addition, Intellia highlighted select corporate milestones for 2019 and upcoming events for the first quarter of 2019.
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"We are delivering on our full-spectrum strategy, and we expect to have two candidates in development in 2019. Our in vivo transthyretin amyloidosis program is on track for IND filing in 2020, and by the end of this year we anticipate having our first engineered cell therapy development candidate targeting acute myeloid leukemia," said Intellia President and Chief Executive Officer John Leonard, M.D. "We have shown that a single lipid nanoparticle administration can produce very substantial transthyretin protein reduction in non-human primates, reaching levels that we believe hold great therapeutic promise for patients. We also look forward to sharing additional data on our acute myeloid leukemia program this year. We believe our TCR-based, CRISPR-engineered cell therapy will provide a much-needed option for patients."
Recent Operational Highlights
ATTR Program: During the fourth quarter, Intellia completed confirmatory non-human primate (NHP) studies, previewed in October, using its lead candidate for the treatment of transthyretin amyloidosis (ATTR). Fifty-one days post infusion, these NHP studies verified a favorable tolerability profile across various dose levels, and a near-complete (average of >95 percent) reduction in
circulating transthyretin (TTR) protein in the liver. The improvements in TTR protein reduction were the result of certain modifications made to the lipid nanoparticle (LNP) cargo components of the therapy, and these modifications have been incorporated into the ongoing, dose-range finding studies and scale-up activities. These modifications will also have application in subsequent programs. The ATTR program is being co-developed with Regeneron Pharmaceuticals, Inc. (Regeneron) with Intellia being the lead party. Intellia confirmed that it is on track for submitting an Investigational New Drug (IND) application in 2020 for ATTR.
In Vivo Insertion: In October, Intellia demonstrated in vivo CRISPR-mediated, targeted transgene insertion in mouse liver. Data shared at the Annual Congress of the European Society of Gene and Cell Therapy highlighted the use of Intellia’s bi-directional DNA template, delivered in a proprietary hybrid LNP/adeno-associated viral (AAV) template delivery system. Insertion of the human F9 gene, the gene encoding the protein deficient in hemophilia B, yielded Factor IX protein levels in mice at or above therapeutic targets in patients. This work was done in collaboration with Regeneron. Additionally, the Company demonstrated the versatility of the hybrid LNP/AAV approach by successfully inserting a functional human SERPINA1 gene (encoding alpha-1 antitrypsin) into the same locus. These experiments in mice yielded human protein expression levels consistent with those of normal individuals without alpha-1 antitrypsin deficiency.
Engineered Cell Therapies: As part of the broad engineered cell therapy platform that the Company is developing, Intellia and its partner, Ospedale San Raffaele, isolated novel active T cell receptors (TCRs) recognizing an epitope of the Wilms’ Tumor 1 (WT1) protein. This protein is overexpressed in many blood cancers, as well as in solid tumors. T cells modified with these TCRs successfully killed acute myeloid leukemia (AML) blasts in an in vitro model. This work will be the foundation for the Company’s first wholly owned ex vivo development candidate for the treatment of AML.
Novartis: In December, Intellia announced an expansion of the existing cell therapy collaboration with Novartis Institutes for Biomedical Research, Inc. (Novartis) to include ocular stem cells. The Company received a $10 million payment from Novartis in relation to the inclusion of this cell type. Regarding its proprietary LNP delivery system and improvements, Intellia also obtained expanded access to Novartis’ LNP library, including the rights to use these lipids for in vivo or ex vivo applications in any genome editing technology.
Board of Directors: In January of 2019, Intellia appointed Fred Cohen, M.D., D.Phil, F.A.C.P., to its board of directors, adding both biotechnology drug development experience and extensive medical expertise to the current knowledge base of the Company’s board.
The Company has set forth the following for 2019 pipeline progression:
ATTR: Complete dose-range finding studies, initiate IND-enabling toxicology studies and commence manufacturing of lipid and CRISPR/Cas9 cargo
Engineered Cell Therapy: Nominate first engineered cell therapy development candidate for acute myeloid leukemia by the end of 2019
Present additional in vivo NHP insertion data and ATTR formulation improvement data at upcoming scientific conferences
Upcoming Events
The Company will participate in the following investor events:
Leerink Healthcare Conference, February 28, New York City
Barclays Global Healthcare Conference, March 12, Miami
Fourth Quarter and Full Year 2018 Financial Results
Cash Position: Cash, cash equivalents and marketable securities were $314.1 million as of December 31, 2018, compared to $340.7 million as of December 31, 2017. The decrease was driven by cash used to fund operations of approximately $96 million, which was offset in part by $28.5 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $11.7 million in proceeds from employee-based stock plans, $10.4 million of ATTR cost reimbursements made by Regeneron, and $19.0 million of funding received under the Novartis collaboration. The Novartis funding received included a $10.0 million upfront payment related to the expansion of the existing collaboration in the fourth quarter of 2018.
Collaboration Revenue: Collaboration revenue increased by $1.2 million to $7.9 million during the fourth quarter of 2018, compared to $6.7 million during the fourth quarter of 2017. The increase in collaboration revenue in 2018 was primarily driven by amounts recognized from the expansion of the existing collaboration with Novartis, as well as by amounts recognized under the Company’s ATTR Co/Co agreement with Regeneron. As previously disclosed, Regeneron is obligated to fund approximately 50 percent of the development costs for the ATTR program.
R&D Expenses: Research and development expenses decreased by $1.3 million to $19.9 million during the fourth quarter of 2018, compared to $21.2 million during the fourth quarter of 2017. This decrease was driven primarily by lower consumable costs, as well as the timing of general R&D expenses.
G&A Expenses: General and administrative expenses decreased by $1.5 million to $8.7 million during the fourth quarter of 2018, compared to $10.2 million during the fourth quarter of 2017. This decrease was driven primarily by a decrease in stock-based compensation.
Net Loss: The Company’s net loss was $19.1 million for the fourth quarter of 2018, compared to $24.0 million during the fourth quarter of 2017.
Intellia expects that its cash, cash equivalents and marketable securities as of December 31, 2018, as well as technology access and funding from Novartis and Regeneron, will enable Intellia to fund its anticipated operating expenses and capital expenditure requirements into the first half of 2021. This expectation excludes 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.