On November 4, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported financial results for the third quarter ended September 30, 2021, and recent operational highlights (Press release, Intellia Therapeutics, NOV 4, 2021, View Source [SID1234594565]).
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"Intellia continues to make important progress toward advancing its full-spectrum genome editing pipeline. Today, we are pleased to share that we remain highly encouraged by the safety profile, consistency of TTR reduction and ongoing effect of NTLA-2001 in the Phase 1 study. We believe we are closing in on identifying the recommended therapeutic dose for NTLA-2001 in patients with ATTR amyloidosis with polyneuropathy for further evaluation in Part 2, a single-dose expansion cohort. Additionally, while it has long been our plan to develop NTLA-2001 for all forms of ATTR amyloidosis, we have decided to accelerate the evaluation of NTLA-2001 in patients with ATTR amyloidosis whose primary clinical manifestation is cardiomyopathy. Based on the strength of our interim dataset, we are now seeking regulatory feedback for inclusion of the ATTR-CM patient population in our current Phase 1 study. We look forward to sharing updates from this program in Q1 2022," said Intellia President and Chief Executive Officer John Leonard, M.D. "Beyond our lead program, we remain focused on advancing NTLA-2002 for HAE and NTLA-5001 for AML. We received regulatory clearance for both programs to initiate first-in-human studies and we expect those studies to begin later this year. Finally, we nominated two gene insertion development candidates – NTLA-3001, our wholly owned AATD program, and a Factor 9 gene insertion candidate for Hem B in collaboration with Regeneron. Our rapidly expanding pipeline is yet one more example of the benefits of our modular platform in generating novel and potentially curative treatment options for the patients we aim to serve."
Third Quarter 2021 and Recent Operational Highlights
In Vivo Program Updates
NTLA-2001 for ATTR amyloidosis: NTLA-2001 is the first systemically delivered CRISPR-based therapy to be dosed in a patient and has the potential to be a curative treatment for transthyretin (ATTR) amyloidosis. Delivered with the Company’s in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc. (Regeneron).
NTLA-2001 is completing the dose-escalation portion of the Phase 1 study to determine the recommended dose for evaluation in Part 2 of the study, a single-dose expansion cohort. During the third quarter, to more fully elucidate the dose-response relationship, Intellia began dosing of subjects in Cohort 4, evaluating NTLA-2001 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) at the 0.7 mg/kg dose level.
Intellia accelerated the evaluation of NTLA-2001 for the treatment of patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). The Company is in discussions with regulatory authorities on a protocol amendment to expand the Phase 1 trial population to include patients with ATTR-CM.
Intellia now plans to present interim data from Part 1, the single-ascending dose portion, and to initiate Part 2, a single-cohort expansion, in the first quarter of 2022. Data to be presented at a company-sponsored event will be from all four cohorts in Part 1 and include safety and serum TTR knockdown for Cohorts 3 and 4, as well as an early look at durability across all cohorts.
In October, Intellia announced that NTLA-2001 received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of ATTR amyloidosis.
NTLA-2002 for HAE: NTLA-2002 leverages Intellia’s proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of hereditary angioedema (HAE). This approach aims to prevent attacks for people living with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and to eliminate the significant treatment burden associated with currently available HAE therapies.
In October, Intellia announced the authorization of its Clinical Trial Application (CTA) by the New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE) to initiate a Phase 1/2 study evaluating NTLA-2002. Additionally, a CTA has been subsequently authorized by the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) for the first-in-human study of NTLA-2002.
Intellia intends to enroll the first patient in the first-in-human study by year-end. The Phase 1/2 study will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II HAE, and will leverage insights gained from the development of NTLA-2001 enabling this study to begin evaluating NTLA-2002 at a higher initial dose.
NTLA-3001 for AATD-associated lung disease: NTLA-3001 is Intellia’s first and wholly owned CRISPR/Cas9-mediated in vivo targeted gene insertion development candidate. It is designed with the aim to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to permanently restore expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to address alpha-1 antitrypsin deficiency (AATD)-associated lung disease and eliminate the need for sub-optimal weekly IV infusions of A1AT augmentation therapy or transplant in severe cases.
Today, Intellia announced the nomination of a new development candidate, NTLA-3001 for treatment of AATD. At the 29th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), Intellia presented data showing that insertion of a healthy form of the SERPINA1 gene led to normal human A1AT levels in non-human primates (NHPs) which were durable through 52 weeks in an ongoing study. The Company is advancing towards Investigational New Drug (IND)-enabling activities for this program and continues to explore additional editing strategies for AATD.
Ex Vivo Program Updates
NTLA-5001 for AML: NTLA-5001 is an autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms’ Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of acute myeloid leukemia (AML).
In September, Intellia announced that the U.S. FDA accepted its IND application for NTLA-5001.
Intellia intends to initiate patient screening by year-end for a Phase 1/2a study evaluating NTLA-5001 in adults with persistent or recurrent AML who have previously received first-line therapy.
Research and Corporate Updates
Modular Platform and Pipeline Expansion: Intellia is advancing its modular platform technologies to broaden the in vivo and ex vivo applications of genome editing. This includes progressing capabilities for innovative CRISPR/Cas9-mediated targeted transgene insertion, in vivo editing in multiple tissue types and an allogeneic approach for the development of "off-the-shelf" T cell therapies. These efforts support new therapeutic candidates and strategic business development partnerships for advancing treatments for genetic diseases, cancers and autoimmune diseases.
ESGCT Annual Congress: In October, Intellia presented new preclinical data demonstrating key platform capabilities.
Intellia shared the first data highlighting its proprietary allogeneic cell engineering platform, demonstrating it can prevent immune rejection of allogeneic T cells for application in TCR-T and CAR-T cell therapy. Intellia’s proprietary approach leverages a novel combination of sequential gene edits to shield the engineered cell therapy from host T and NK cell attack. It does not rely on long-term, aggressive immune suppression of patients or the knockout of a protein required for HLA class I expression, which are approaches currently employed by others to address the challenge of immune rejection of the allogeneic cell product. Intellia intends to nominate its first allogeneic cell therapy development candidate by the first half of 2022.
Intellia shared new data on its proprietary cell engineering process, demonstrating LNP-based delivery of CRISPR/Cas9 ex vivo allows for sequential editing of T cells with high efficiency, faster expansion and minimal translocations as compared to electroporation. The data support the ability of this platform to be used for a variety of targeting modalities, including CAR and TCRs, and to support both autologous and allogeneic T cell candidates. This LNP-based approach is being used for NTLA-5001.
Collaboration Updates:
In the third quarter, Intellia and Regeneron nominated a Factor 9 (F9) gene insertion development candidate for its Hemophilia B (Hem B) program, leveraging their jointly developed targeted transgene insertion capabilities to insert F9. This candidate is part of a co-development/co-funding agreement between Intellia and Regeneron, the lead party for this program. F9 is a gene that encodes for Factor IX (FIX), a blood-clotting protein that is missing or defective in Hem B patients. In preclinical studies, the companies demonstrated the first CRISPR/Cas9-mediated targeted transgene insertion in the liver of NHPs, which resulted in circulating FIX levels at or above those found in normal human plasma.
In October, the Company announced a strategic collaboration with SparingVision to develop novel genomic medicines utilizing Intellia’s proprietary CRISPR/Cas9 technology for the treatment of ocular diseases. As part of the collaboration, Intellia will receive an equity stake in SparingVision, option for exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets, and eligibility for development and commercial milestone payments as well as royalties on potential future sales of products arising from the collaboration. The companies will additionally research and develop novel self-inactivating AAV vectors and LNP-based approaches to address delivery of CRISPR/Cas9 genome reagents to the retina.
In July, the Company completed the formation of a new universal CAR-T cell therapy company, which Intellia launched in collaboration with Blackstone Life Sciences and Cellex Cell Professionals GmbH. The new company will combine clinical-stage universal CAR-T platforms with Intellia’s differentiated allogeneic cell engineering platform to develop therapies for immuno-oncology and autoimmune diseases.
Upcoming Events
The Company will participate in the following events during the fourth quarter of 2021:
Barclays Gene Editing & Gene Therapy Summit, November 15, Virtual
Evercore ISI 4th Annual HealthCONx Conference, December 1, Virtual
63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition, December 11-14, Atlanta, GA and Virtual
Upcoming Milestones
The Company has set forth the following for pipeline progression:
ATTR:
Report additional interim clinical data from Phase 1 study of NTLA-2001 in Q1 2022
Initiate Part 2, a single-dose expansion cohort, of Phase 1 study of NTLA-2001 in Q1 2022
HAE: Initiate enrollment in the first-in-human study of NTLA-2002 by year-end
AML: Initiate patient screening in the first-in-human study of NTLA-5001 by year-end
Pipeline Expansion: Nominate the Company’s first allogeneic development candidate by 1H 2022
Third Quarter 2021 Financial Results
Cash Position: Cash, cash equivalents and marketable securities were $1,148.7 million as of September 30, 2021, compared to $597.4 million as of December 31, 2020. The increase was driven by net proceeds of $648.3 million from a follow-on offering in Q3 2021, $45.3 million of net proceeds from the Company’s "At the Market" (ATM) agreement, $40.8 million in proceeds from employee-based stock plans, and $4.2 million of funding for a cost-sharing agreement received from Regeneron. These increases were offset in part by cash used to fund operations of approximately $187.3 million.
Collaboration Revenue: Collaboration revenue decreased by $15.0 million to $7.2 million during the third quarter of 2021, compared to $22.2 million during the third quarter of 2020. The decrease in collaboration revenue in 2021 was primarily driven by $15.3 million related to the transfer of control of the license to develop the Factor VIII target for hemophilia A that was recorded during Q3 2020.
R&D Expenses: Research and development expenses increased by $20.7 million to $60.5 million during the third quarter of 2021, compared to $39.8 million during the third quarter of 2020. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs, and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $8.1 million to $18.7 million during the third quarter of 2021, compared to $10.6 million during the third quarter of 2020. This increase was primarily related to employee related expenses, including stock-based compensation of $3.8 million.
Net Loss: The Company’s net loss was $71.6 million for the third quarter of 2021, compared to $27.8 million during the third quarter of 2020.
Conference Call to Discuss Third Quarter Earnings
The Company will discuss these results on a conference call today, Thursday, November 4, at 8 a.m. ET.
To join the call:
U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at www.intelliatx.com, beginning on November 4 at 12 p.m. ET.