On May 4, 2023 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, reported operational highlights and financial results for the first quarter ended March 31, 2023 (Press release, Intellia, MAY 4, 2023, View Source [SID1234631032]).

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"We’ve had a productive start to the year with the successful clearance of our first IND application for an investigational in vivo CRISPR-based therapy alongside broad pipeline and platform progress," said Intellia President and Chief Executive Officer John Leonard, M.D. "Today, we are pleased to announce dosing has begun in the Phase 2 study of NTLA-2002, and based on strong interest from investigators and patients, we expect to complete enrollment in the second half of this year. Our rapid progression of the clinical development of NTLA-2002 supports our goal to bring forth a potential functional cure for the treatment of hereditary angioedema. Simultaneously, we are working toward submitting our second in vivo IND application and initiating a global pivotal trial for NTLA-2001. We look forward to sharing new interim data from both the NTLA-2001 and NTLA-2002 first-in-human studies in the months to come."

First Quarter 2023 and Recent Operational Highlights

In Vivo Program Updates

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is an in vivo, systemically delivered, investigational CRISPR-based therapy designed to inactivate the TTR gene in liver cells and thereby prevent the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. NTLA-2001 is subject to a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc.
ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
Intellia plans to submit a U.S. Investigational New Drug (IND) application in mid-2023. Subject to regulatory feedback, the Company anticipates initiating a global pivotal trial for ATTR-CM by year-end 2023.
The Company expects to present additional data from the ATTR-CM arm of the Phase 1 study in 2023, including longer-term safety and durability data, as well as emerging clinical endpoints.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
As previously announced, during the first quarter of 2023, the planned enrollment of the dose-expansion portion of the ATTRv-PN arm in the Phase 1 study was completed to inform a pivotal study. The Company is actively preparing for a global pivotal study, which includes discussions with regulatory authorities.
Intellia recently began redosing patients in the 0.1 mg/kg cohort (n=3), the initial cohort and lowest dose tested in the dose-escalation portion of the Phase 1 study, with the 55 mg dose selected for the dose-expansion cohort.
The Company plans to present additional clinical data from the ATTRv-PN arm of the Phase 1 study in 2023.
Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 is a wholly owned, in vivo, systemically delivered investigational CRISPR-based therapy. NTLA-2002 is designed 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 HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous reduction of plasma kallikrein activity, following a single dose. It also aims to eliminate the significant treatment burden associated with currently available HAE therapies. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE.
Intellia announced today that the first patient has been dosed in the global Phase 2 portion of its Phase 1/2 clinical trial of NTLA-2002. Based on encouraging study interest from both investigators and patients, the Company expects to complete enrollment (n=25) in 2H 2023.
The Company announced in March that the U.S. Food and Drug Administration (FDA) cleared the NTLA-2002 Phase 2 IND application. Additionally, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to NTLA-2002 for the treatment of HAE.
In January 2023, Intellia was awarded the Innovation Passport for NTLA-2002 by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA). The Innovation Passport is the point of entry into the U.K.’s Innovative Licensing and Access Pathway (ILAP), which is designed to accelerate time to market and facilitate patient access to innovative medicines.
The Company plans to present additional clinical data from the Phase 1 portion of the first-in-human study in 2023. Data expected to be presented include updated safety, durability of pharmacodynamic effect and attack-rate measures from all three patient cohorts.
Alpha-1 Antitrypsin Deficiency (AATD)

NTLA-3001 for Associated Lung Disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to improve patient outcomes, including eliminating the need for weekly intravenous infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia is conducting IND-enabling activities for NTLA-3001 and plans to submit an IND or IND-equivalent filing in 2H 2023.
NTLA-2003 for Associated Liver Disease: NTLA-2003 is a wholly owned, in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.
Intellia is conducting IND-enabling activities for NTLA-2003, with the expectation of completing these activities by year-end 2023.
Ex Vivo Program Updates

Immuno-oncology and Autoimmune Diseases

Intellia is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.
Board of Directors Update: In April, Intellia announced the appointment of Bill Chase to its board of directors. Mr. Chase will be a member of the audit committee and will succeed Caroline Dorsa as chair of the audit committee upon her retirement from the board on June 15, 2023.
Corporate Responsibility Report: In May, Intellia published its 2023 Corporate Responsibility Report. The report highlights the Company’s Environmental, Social and Governance (ESG) principles and practices as part of its objective to build a sustainable company while delivering on its commitments to patients, employees and shareholders.
Upcoming Events

The Company will participate in the following events during the second quarter of 2023:

Bank of America Securities 2023 Health Care Conference, May 9, Las Vegas
2023 RBC Capital Markets Global Healthcare Conference, May 16, New York City
Barclays Gene Editing & Therapy Summit, May 24, New York City
Stifel Genetic Medicines Day, May 30, virtual
Upcoming Milestones

The Company has set forth the following expected milestones for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Submit an IND application in mid-2023 to enable inclusion of U.S. sites in a pivotal study of NTLA-2001 for patients with ATTR-CM.
Present additional clinical data from the ongoing Phase 1 study of NTLA-2001 in 2023.
Initiate a global pivotal NTLA-2001 trial for ATTR-CM by year-end 2023, subject to regulatory feedback.
Prepare for a Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN, including discussions with regulatory authorities.
NTLA-2002 for HAE:
Present additional clinical data from the ongoing first-in-human study of NTLA-2002 in 2023.
Complete enrollment in the Phase 2 portion of the Phase 1/2 study in 2H 2023.
AATD Franchise:
Submit an IND or IND-equivalent application for NTLA-3001 for AATD-associated lung disease in 2H 2023.
Complete IND-enabling activities for NTLA-2003 for AATD-associated liver disease by year-end 2023.
Platform Innovation:
Advance novel gene editing technologies, including DNA writing and delivery to other tissues outside of the liver.
First Quarter 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.2 billion as of March 31, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of approximately $120.9 million. The decrease was offset in part by $12.0 million of interest income, $3.4 million of reimbursement from its collaborators, $1.5 million of net equity proceeds from the Company’s "At the Market" (ATM) program and $0.8 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue increased by $1.3 million to $12.6 million during the first quarter of 2023, compared to $11.3 million during the first quarter of 2022.
R&D Expenses: Research and development expenses decreased by approximately $36.0 million to $97.1 million during the first quarter of 2023, compared to $133.1 million during the first quarter of 2022. This decrease was primarily driven by $56.0 million of expense related to the acquisition of Rewrite Therapeutics, Inc. during the first quarter of 2022. The decrease related to the acquisition of Rewrite Therapeutics, Inc. was offset by an increase in expenses of $20.0 million primarily driven by the advancement of its lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $16.9 million for the first quarter of 2023.
G&A Expenses: General and administrative expenses increased by $5.0 million to $27.4 million during the first quarter of 2023, compared to $22.4 million during the first quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $2.1 million. Stock-based compensation expense included in general and administrative expenses was $10.3 million for the first quarter of 2023.
Net Loss: The Company’s net loss was $103.1 million for the first quarter of 2023, compared to $146.9 million during the first quarter of 2022.
Conference Call to Discuss First Quarter 2023 Results

The Company will discuss these results on a conference call today, Thursday, May 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 intelliatx.com, beginning on May 4, at 12 p.m. ET.