On May 5, 2022 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading 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, 2022 (Press release, Intellia Therapeutics, MAY 5, 2022, View Source [SID1234613618]).

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"Intellia is successfully executing on its 2022 strategic priorities as we advance our proprietary CRISPR-based drug discovery and development platform. We recently shared updated interim data from our landmark study of NTLA-2001, which demonstrated that treatment with NTLA-2001 in people with ATTR amyloidosis with polyneuropathy was generally well-tolerated and delivered rapid, consistent, dose-dependent reductions in serum TTR. In addition to achieving a mean reduction of 93% at the 1.0 mg/kg dose, we were particularly pleased that reductions in serum TTR levels persisted, further bolstering our confidence in NTLA-2001 as a potentially durable, one-time treatment for ATTR amyloidosis. In June, we plan to share additional durability data from the dose-escalation portion of the polyneuropathy arm and data supporting our fixed dose selection for Part 2," said Intellia President and Chief Executive Officer John Leonard, M.D. "Alongside the progress of our lead program, we continued to advance our second in vivo candidate, NTLA-2002, which benefits from the modularity of our platform. We look forward to another important clinical milestone in the second half of this year when we expect to present initial data from the NTLA-2002 first-in-human study. Finally, Intellia remains well-funded to drive forward our robust portfolio and to support continued investment in platform innovation as we build upon our leadership position in genome editing."

First Quarter 2022 and Recent Operational Highlights

In Vivo Program Updates

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit genes inside the human body and has the potential to be the first single-dose treatment for 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, potentially lifelong reduction in transthyretin (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.

In February, Intellia presented updated interim clinical data from 15 patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) treated across four single-ascending dose cohorts of the ongoing Phase 1 study. Treatment with NTLA-2001 led to dose-dependent reductions in serum TTR and achieved maximal reductions by day 28, with mean reductions of 86% (n=3) and 93% (n=6) in the 0.7 mg/kg and 1.0 mg/kg dose group, respectively. The maximum TTR reduction was 98% at 1.0 mg/kg. Mean serum TTR reductions were durable through the observation period, with patient follow-up ranging from two to 12 months following a single dose. NTLA-2001 was generally well-tolerated at all dose levels. The most frequent adverse events included headache, infusion-related reactions, back pain, rash and nausea.
Based on these data, Intellia is evaluating a fixed dose of 80 mg in Part 2 of the Phase 1 study, which is expected to deliver a similar exposure to the 1.0 mg/kg dose. The Company announced today that the first patient has been dosed in Part 2, a single-dose expansion cohort, in the polyneuropathy arm.
The Company plans to present additional interim data from Part 1, the single-ascending dose portion, of the polyneuropathy arm at the European Association for the Study of the Liver (EASL) International Liver Congress 2022, to be held June 22-26.
Intellia also continues to dose patients in the cardiomyopathy arm of its expanded Phase 1 study, which is currently evaluating NTLA-2001 in dose-escalation cohorts of patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). The Company’s goal is to present the first interim data from the cardiomyopathy arm in the second half of 2022. Enrollment across both ATTRv-PN and ATTR-CM patient populations is expected to complete in 2022.
Hereditary Angioedema (HAE)

NTLA-2002: 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 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 and to eliminate the significant treatment burden associated with currently available HAE therapies.

Intellia is progressing the single-ascending dose portion of its Phase 1/2 study evaluating the safety, tolerability and activity of NTLA-2002 in adults with Type I or Type II HAE. The Company has completed dosing in the first dose-escalation cohort (25 mg fixed dose) and has begun enrolling patients in the second dose-escalation cohort (75 mg fixed dose).
The Company anticipates presenting interim data in the second half of 2022 from the first-in-human study, with initial results expected to characterize the emerging safety and activity profile of NTLA-2002, and potentially demonstrate preliminary proof-of-concept.
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 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 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 IV infusions of A1AT augmentation therapy or lung transplant in severe cases.

Intellia is conducting Investigational New Drug (IND)-enabling activities for NTLA-3001, with plans to file an IND or IND-equivalent in 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 initiating IND-enabling activities for NTLA-2003.
Ex Vivo Program Updates

Acute Myeloid Leukemia (AML)

NTLA-5001: NTLA-5001 is an investigational 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 AML.

In March, Intellia announced the first patient was dosed in its Phase 1/2a study evaluating NTLA-5001 for the treatment of AML. The Company continues to enroll patients in the ongoing study.
In March, Intellia announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to NTLA-5001 for the treatment of AML.
CD30+ Lymphomas

NTLA-6001: NTLA-6001 is a wholly owned, allogeneic CAR-T development candidate targeting CD30 for the treatment of CD30-expressing hematologic cancers, including relapsed or refractory classical Hodgkin lymphoma (cHL). NTLA-6001 is the first candidate developed using Intellia’s proprietary allogeneic cell engineering platform, which leverages a novel combination of sequential gene edits to protect T cells from immune rejection by both host T and natural killer (NK) cells.

Intellia is initiating IND-enabling activities for NTLA-6001.
At the 2022 Keystone Symposia’s Precision Genome Engineering Conference, Intellia presented preclinical data leading to the development of NTLA-6001. The data demonstrated that Intellia’s proprietary allogeneic solution created T cells that not only avoided immune recognition by host CD4 and CD8 T cells, but also were protected from NK cell-mediated killing in in vitro and in vivo mouse models. Furthermore, allogeneic T cells engineered sequentially with LNPs retained high viability, cell expansion, memory phenotype, cytotoxic and cytokine secretion characteristics.
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.

Intellia plans to advance at least one additional new in vivo development candidate by the end of 2022.
The Company plans to highlight additional advances to its proprietary technology capabilities, including both genome editing and delivery tools, at upcoming scientific conferences in 2022.
Collaboration Updates

In February, Intellia announced a collaboration agreement with ONK Therapeutics Ltd. for the development of allogeneic CRISPR-edited NK cell therapies for the treatment of cancer.
In January, Intellia announced a licensing and collaboration agreement with Kyverna Therapeutics, Inc. for the development of KYV-201, an allogeneic CD19 CAR-T cell investigational candidate for the treatment of select autoimmune diseases.
Corporate Updates

In May, Intellia announced the appointment of Muna Bhanji, R.Ph., to its Board of Directors. Ms. Bhanji brings more than 30 years of strategic and operational experience in the biopharmaceutical industry to Intellia’s board, including a proven track record of driving growth across a broad portfolio of medicines and vaccines.
In February, Intellia completed the acquisition of Rewrite Therapeutics, Inc. (Rewrite), a private biotechnology company focused on advancing novel DNA writing technologies. Rewrite’s DNA writing technology may enable a range of editing strategies, including targeted corrections, insertions, deletions and the full range of single-nucleotide changes.
In February, Intellia announced a lease agreement to develop a 140,000-square-foot manufacturing facility in Waltham, Massachusetts, to support the manufacturing of key components for its CRISPR-based investigational therapies. The new manufacturing facility will be Good Manufacturing Practice compliant and support the preclinical through commercial supply for key components of Intellia’s CRISPR-based therapies.
Upcoming Events

The Company will participate in the following events during the second quarter of 2022:

RBC Capital Markets Global Healthcare Conference, May 17, New York
Jefferies Healthcare Conference, June 9, New York
EASL International Liver Congress 2022, June 22-26, London
Upcoming Milestones

The Company has set forth the following for pipeline progression:

In Vivo

NTLA-2001 for ATTR amyloidosis:

Report additional interim data from ATTRv-PN arm of Phase 1 study in June 2022
Present interim data from ATTR-CM arm of Phase 1 study in 2H 2022
Complete enrollment of Phase 1 study for both ATTRv-PN and ATTR-CM subjects in 2022
NTLA-2002 for HAE: Present interim data from Phase 1/2 study in 2H 2022
NTLA-3001 for AATD: File an IND or IND-equivalent in 2023
Advance at least one additional new in vivo development candidate by the end of 2022
Ex Vivo

NTLA-5001 for AML: Continue to enroll patients in Phase 1/2a study in 2022
Modular Platform

Advance additional novel platform capabilities in 2022
First Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $994.7 million as of March 31, 2022, compared to $1.1 billion as of December 31, 2021. The decrease was driven by cash used to fund operations of approximately $95.7 million as well as the acquisition of Rewrite for $45.0 million. The decrease was offset in part by $38.9 million in net equity proceeds raised from the Company’s "At the Market" (ATM) agreement and $8.4 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue increased by approximately $4.8 million to $11.3 million during the first quarter of 2022, compared to $6.4 million during the first quarter of 2021. The increase was primarily driven by our joint venture with AvenCell.
R&D Expenses: Research and development expenses increased by $93.8 million to $133.1 million during the first quarter of 2022, compared to $39.3 million during the first quarter of 2021. This increase was primarily driven by $56.0 million of expense related to the acquisition of Rewrite, which includes a $45.0 million upfront payment and $10.5 million related to a potential stock-based earnout payment. The remaining $37.8 million was 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 $8.8 million to $22.4 million during the first quarter of 2022, compared to $13.6 million during the first quarter of 2021. This increase was primarily related to employee related expenses, including stock-based compensation of $5.3 million.
Net Loss: The Company’s net loss was $146.9 million for the first quarter of 2022, compared to $46.2 million during the first quarter of 2021.
Conference Call to Discuss First Quarter 2022 Results

The Company will discuss these results on a conference call today, Thursday, May 5, 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 5, at 12 p.m. ET.