On August 4, 2022 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 second quarter ended June 30, 2022 (Press release, Intellia, AUG 4, 2022, View Source [SID1234617579]).

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"We continue to make excellent progress in both the cardiomyopathy and polyneuropathy arms of the landmark Phase 1 study of NTLA-2001," said Intellia President and Chief Executive Officer John Leonard, M.D. "In June, we presented durability data demonstrating deep reductions in a disease-causing protein were sustained over time following a single-dose treatment. Additionally, we’ve completed the dose-escalation portion of the cardiomyopathy arm and look forward to starting the dose-expansion portion soon."

Dr. Leonard continued, "As the leading full-spectrum genome editing company, our ex vivo capabilities and platform are also advancing. We believe our proprietary, differentiated cell engineering platform can solve many of the known challenges faced by both autologous and current allogeneic approaches. As a result, we plan to focus exclusively on developing allogeneic cell therapies, including an allogeneic version of NTLA-5001. Finally, we expect several important milestones later this year, which will include interim clinical data updates from the NTLA-2001 and NTLA-2002 programs."

Second 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 being evaluated in a Phase 1, two-part, open-label study in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM). NTLA-2001 is subject to a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc.

To date, over 30 patients have been dosed across the polyneuropathy and cardiomyopathy arms. The growing body of data, particularly at therapeutically relevant doses, demonstrated treatment with NTLA-2001 resulted in rapid, deep and consistent reductions of serum TTR.
ATTR-CM arm: Intellia announced today the completion of the dose-escalation portion of the cardiomyopathy arm. The Company is finalizing selection of a fixed dose, at or near the fixed-dose equivalent of the 0.7 mg/kg dose, for evaluation in the dose-expansion portion of the study, subject to regulatory approval. The selection is based on clinical data from patients with ATTR-CM dosed at the 0.7 mg/kg and 1.0 mg/kg doses, which yielded similar TTR reductions. Additionally, both doses were generally well-tolerated. The Company remains on track to present interim data from the cardiomyopathy arm later this year.
ATTRv-PN arm: The Company announced today, subject to regulatory approval, plans to add a second cohort to the dose-expansion portion of the polyneuropathy arm, which will evaluate the same fixed dose selected for the dose-expansion portion of the cardiomyopathy arm. The decision to study a second dose is based on the following: (1) the emerging data from the dose-escalation portion of the cardiomyopathy arm showed similar serum TTR reduction at both the 0.7 mg/kg and 1.0 mg/kg doses, (2) the comparability of performance at the 0.7 mg/kg and 1.0 mg/kg doses in the dose-escalation portion of the polyneuropathy arm, which led to an 86% and 93% mean and 97% and 98% maximum TTR reduction at day 28, respectively, and (3) a significant elevation in liver enzymes, which normalized without medical intervention, observed at day 28 in a patient treated in the dose-expansion portion of the polyneuropathy arm at the 80 mg dose (the fixed dose corresponding to 1.0 mg/kg). While the adverse event is considered possibly related to study drug, this patient was asymptomatic, had no increase in bilirubin and the event was deemed nonserious by the investigator.
Intellia plans to submit a protocol amendment to evaluate a fixed dose corresponding to 0.7 mg/kg in the dose-expansion portion, with enrollment across both arms expected to be completed by the end of 2022, subject to regulatory feedback.
In June, Intellia presented updated interim data from its ongoing Phase 1 study of NTLA-2001 in patients with ATTRv-PN at the European Association for the Study of the Liver International Liver Congress 2022. Extended follow-up data from 15 ATTRv-PN patients, treated across all four single-ascending dose cohorts, showed deep, dose-dependent reductions in serum TTR observed with prior readouts were sustained through the last measured timepoint of follow-up, reaching 12 months in the 0.1 mg/kg and 0.3 mg/kg cohorts and six months in the 0.7 mg/kg and 1.0 mg/kg cohorts. Both 0.7 mg/kg and 1.0 mg/kg doses led to greater than 85% mean TTR reduction at day 28. The durability and persistence of effect continue to support NTLA-2001 as a potential one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein.
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. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE.

Intellia is progressing the single-ascending dose portion of its first-in-human study. The Company anticipates presenting interim data in the second half of 2022, including safety, kallikrein reduction and HAE attack rate data. These initial results are expected to characterize the emerging safety and activity profile of NTLA-2002 and potentially demonstrate the modularity of Intellia’s proprietary CRISPR-based, LNP platform.
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 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 conducting 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 that the first patient was dosed in the Phase 1/2a first-in-human trial of NTLA-5001.

Intellia has decided to concentrate its ex vivo development efforts exclusively on allogeneic cell therapies manufactured from healthy donors. The Company’s proprietary technologies, including its LNP-based cell engineering platform and novel allogeneic solution, offer significant advantages over both autologous and current investigational allogeneic approaches. Preclinical data presented on its differentiated allogeneic engineering platform showed allogeneic T cells were shielded from immune rejection, both host T and natural killer (NK) cell attack.
Intellia announced today plans to discontinue its first-in-human study of NTLA-5001, an investigational autologous TCR-T cell therapy, and is pivoting to an allogeneic version of this program currently in preclinical development. This decision is not due to any safety or efficacy data emerging from the trial. It is instead based on the potential of Intellia’s allogeneic platform to consistently deliver a high-quality, readily available and persistent cell product for treatment of aggressive cancers.
Preclinical data supporting the development of a WT1-directed allogeneic TCR-T cell candidate will be presented at a future scientific conference in 2022.
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.

Intellia is conducting IND-enabling activities for NTLA-6001.
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.
Upcoming Milestones

The Company has set forth the following for pipeline progression:

In Vivo

NTLA-2001 for ATTR amyloidosis:

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 by the end of 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

Present on its proprietary allogeneic cell engineering platform at an upcoming scientific conference in 2022
Modular Platform

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

Cash Position: Cash, cash equivalents and marketable securities were $906.9 million as of June 30, 2022, compared to $1.1 billion as of December 31, 2021. The decrease was driven by cash used to fund operations of approximately $191.2 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 $14.3 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue increased by approximately $7.5 million to $14.0 million during the second quarter of 2022, compared to $6.6 million during the second quarter of 2021. The increase was primarily driven by our collaborations with AvenCell and Kyverna.
R&D Expenses: Research and development expenses increased by $31.3 million to $90.2 million during the second quarter of 2022, compared to $58.9 million during the second quarter of 2021. 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 $5.4 million to $22.1 million during the second quarter of 2022, compared to $16.7 million during the second quarter of 2021. This increase was primarily related to employee-related expenses, including stock-based compensation of $4.5 million.
Net Loss: The Company’s net loss was $100.7 million for the second quarter of 2022, compared to $68.8 million during the second quarter of 2021.
Conference Call to Discuss Second Quarter 2022 Results

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