Intellia Therapeutics Announces First Quarter 2019 Financial Results and Company Update
- Remains on track to submit investigational new drug application in 2020 for its first systemically delivered CRISPR/Cas9-based therapy, NTLA-2001, for treatment of transthyretin amyloidosis
- Expects to nominate first engineered cell therapy development candidate for treatment of acute myeloid leukemia by end of 2019
- First demonstration of CRISPR/Cas9-based, targeted insertion of a Factor 9 gene in the liver of non-human primates achieves normal circulating human Factor IX protein levels
- Ends quarter with strong cash position of
“2019 is off to a productive start in support of our mission to advance genome editing to treat a range of severe and life-threatening diseases. We are excited by our achievements in gene knockout and insertion across both our in vivo and engineered cell therapy efforts. In particular, we presented data at the 22nd Annual Meeting of the
First Quarter 2019 and More Recent Operational Highlights
- ATTR Program: Intellia’s lead candidate for the treatment of transthyretin amyloidosis (ATTR), which demonstrated an average of >95% reduction in circulating transthyretin (TTR) protein in non-human primates (NHPs), has been nominated as the Company’s first in vivo development candidate to advance into Investigational New Drug (IND)-enabling toxicology studies. Preliminary results from substantially completed dose-range finding (DRF) studies showed a favorable tolerability profile; and data from multiple studies in NHPs demonstrated durable liver editing with sustained reduction of circulating TTR through 10 months of observation following a single dose.
Today, Intellia announced plans to begin IND-enabling toxicology studies of NTLA-2001 in mid-2019 and that it remains on track to submit an IND application in 2020. NTLA-2001 is being co-developed with
Regeneron Pharmaceuticals, Inc.(Regeneron), with Intellia as the lead development and commercialization party.
- AML Program: Intellia and its research collaborators at IRCCS Ospedale San Raffaele presented new in vitro data at the 22nd Annual Meeting of the
American Society of Gene and Cell Therapy(ASGCT), showing that CRISPR/Cas9 editing resulted in >98% knockout of endogenous T cell receptors (TCRs) followed by insertion of Wilms’ Tumor 1 (WT1)-specific TCRs into >95% of isolated T cells. In addition, the engineered T cells were functional and capable of specifically killing high levels of a panel of leukemic blasts from patients that expressed the WT1 epitope. Based on these results, Intellia has identified multiple lead TCRs restricted to the HLA-A*02:01 allele to move into functional testing in patient-derived xenograft models for an autologous TCR-based therapy targeting WT1 for the treatment of acute myeloid leukemia (AML). These studies are expected to begin in mid-2019 and will inform the nomination of the Company’s first engineered cell therapy development candidate by the end of 2019.
- In Vivo Insertion in NHPs: At the 2019 ASGCT Meeting, Intellia presented data demonstrating the first CRISPR-mediated, targeted transgene insertion in the liver of NHPs, using Factor 9 (F9) as a model gene. F9 is a gene that encodes for Factor IX (FIX) protein, a blood-clotting protein that is missing or defective in hemophilia B patients. In a collaboration between Intellia and Regeneron, researchers combined Intellia’s lipid nanoparticle (LNP) delivery system of CRISPR/Cas9 with an adeno-associated virus (AAV) containing a proprietary bi-directional insertion template. NHP data showed that a single administration achieved ~3-4 μg/mL of circulating human FIX protein at day 14 and was sustained through 28 days (~3-5 μg/mL) of completed observation in an ongoing study. The levels of circulating human FIX protein demonstrated in NHPs correspond with the normal 3-5 μg/mL range of human FIX protein levels (source: Amiral et al, Clin. Chem., 1984). The NHP data shared also incorporates the improved CRISPR/Cas9 LNP identified from the ATTR program and demonstrates the modularity of Intellia’s platform to apply learnings to other programs. This data expands on the clinically relevant human FIX protein levels achieved in mice, first reported in October, which have remained stable through 10 months of observation.
- Modular In Vivo Knockout Update: Today, at the 2019 ASGCT Meeting, Intellia will present new data demonstrating that independent CRISPR-mediated knockout of each of two targets of interest, either lactate dehydrogenase A (Ldha) or hydroxyacid oxidase 1 (Hao1), via the Company’s proprietary LNP delivery technology, results in a durable, therapeutically relevant reduction of oxalate excretion in a disease mouse model of primary hyperoxaluria type 1 (PH1).
LDHA and HAO1 are enzymes involved in oxalate production. In people with PH1, mutations in a specific liver enzyme cause the production of a surplus of oxalate, which can combine with calcium to form insoluble deposits in the kidney and throughout the body, leading to damage of the kidneys, heart, eyes and skeletal system. An approximate 30% reduction in urinary oxalate in patients with PH1 is considered to be therapeutically relevant (source: Nephrology Dialysis Transplantation 1999; 14:2556-2558). In collaboration with the
University of Alabama at Birmingham, Intellia researchers found that a CRISPR-mediated knockout of the Ldha gene in a PH1 mouse model disrupts LDHA protein production and reduces urinary oxalate levels by 63%. Researchers also observed that a CRISPR-mediated knockout of the Hao1 gene disrupts glycolate-to-glyoxylate conversion, resulting in a urinary oxalate level reduction of 57% in a PH1 mouse model. In each individual knockout approach, these reduced levels of urinary oxalate were sustained for at least 15 weeks.
Today’s presentation, titled “CRISPR/Cas9-Mediated Gene Knockout to Address Primary Hyperoxaluria,” is accessible through the Events and Presentations page of the Investor Relations section of Intellia’s website.
The Company has set forth the following for 2019 pipeline progression:
- Initiate IND-enabling toxicology studies in mid-2019
- Commence manufacturing of NTLA-2001 Phase 1 materials
- Initiate functional testing in patient-derived xenograft models of multiple lead TCRs in mid-2019
- Nominate first engineered cell therapy development candidate by the end of 2019
First Quarter 2019 Financial Results
- Cash Position: Cash, cash equivalents and marketable securities were
$296.6 millionas of March 31, 2019, compared to $314.1 millionas of December 31, 2018. The decrease was driven by cash used to fund operations of approximately $29 million, which was offset in part by $6.0 millionof funding received under the Novartiscollaboration, $3.6 millionof net equity proceeds raised from the Company's "At the Market" (ATM) agreement, $1.5 millionof ATTR cost reimbursements made by Regeneron, and $0.4 millionin proceeds from employee-based stock plans.
- Collaboration Revenue: Collaboration revenue increased by approximately
$3.0 million to $10.4 millionduring the first quarter of 2019, compared to $7.5 millionduring the first quarter of 2018. The increase in collaboration revenue in 2019 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% of the development costs for the ATTR program.
- R&D Expenses: Research and development expenses increased by
$1.2 million to $23.7 millionduring the first quarter of 2019, compared to $22.5 millionduring the first quarter of 2018. 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.
- G&A Expenses: General and administrative expenses increased by
$3.1 million to $10.5 millionduring the first quarter of 2019, compared to $7.4 millionduring the first quarter of 2018. This increase was driven primarily by employee and intellectual property (IP)-related expenses to support Intellia’s growing research and development efforts.
- Net Loss: The Company’s net loss was
$21.9 millionfor the first quarter of 2019, compared to $21.4 millionduring the first quarter of 2018.
Intellia expects that its cash, cash equivalents and marketable securities as of
Conference Call to Discuss First Quarter 2019 Earnings
The Company will discuss these results on a conference call today,
To join the call:
- U.S. callers should dial 800-458-4148 and use conference ID# 7725705, approximately five minutes before the call.
- International callers should click here to access dial-in information and use conference ID# 7725705, approximately five minutes before the call.
A replay of the call will be available on Intellia’s website, beginning on
This press release contains “forward-looking statements” of
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain our intellectual property position; risks related to Intellia’s relationship with third parties, including our licensors; risks related to the ability of our licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for our product candidates; the risk that any one or more of Intellia’s product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies will not be predictive of future results in connection with future studies; and the risk that Intellia’s collaborations with Novartis or Regeneron or its other ex vivo collaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.
|INTELLIA THERAPEUTICS, INC.|
|CONSOLIDATED STATEMENTS OF OPERATIONS (UNAUDITED)|
|(Amounts in thousands, except per share data)|
|Three Months Ended March 31,|
|Research and development||23,709||22,493|
|General and administrative||10,533||7,406|
|Total operating expenses||34,242||29,899|
|Net loss per share, basic and diluted||$||(0.49||)||$||(0.51||)|
|Weighted average shares outstanding, basic and diluted||45,234||42,043|
|INTELLIA THERAPEUTICS, INC.|
|CONSOLIDATED BALANCE SHEET DATA (UNAUDITED)|
|(Amounts in thousands)|
|Cash, cash equivalents and marketable securities||$||296,582||$||314,059|
|Total stockholders' equity||264,338||277,920|
Senior Vice President
External Affairs & Communications
Source: Intellia Therapeutics, Inc.