What changed in this filing

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Item 2. Management’s Discussion and Analysis

2021-08-05 compared with 2021-05-06 · 166 added, 89 removed, 233 unchanged (52% of the section changed)

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Our business and our forward-looking statements involve substantial known and unknown risks and uncertainties, including the risks and uncertainties inherent in our statements regarding:

our ability to execute our clinical study strategy for NTLA-2001, our program for the treatment of transthyretin amyloidosis;

the anticipated timing of preclinical studies, manufacturing activities, our investigational new drug application (“IND”) or equivalent regulatory filing, and clinical studies for NTLA-5001, our program for the treatment of acute myeloid leukemia;

the anticipated timing of preclinical studies, manufacturing activities, our IND application or equivalent regulatory filing, and clinical studies for NTLA-2002, our program for the treatment of hereditary angioedema;

our ability to use a modular platform capability or other strategy to efficiently discover and develop product candidates, including by applying learnings from one program to other programs;

our ability to research, develop or maintain a pipeline of product candidates;

our ability to manufacture or obtain material for our preclinical and clinical studies, and our product candidates;

our ability to execute our clinical study strategy for NTLA-2001, our program for the treatment of transthyretin amyloidosis, including the ability to successfully complete our Phase 1 study and determine a recommended dose in our ongoing Phase 1 study that can be advanced into later-stage studies, or the success of such program;

the acceptance of our initial clinical trial application filing, the anticipated timing of our clinical trial and initiating patient screening for NTLA-5001, our program for the treatment of acute myeloid leukemia, or the success of such program;

the acceptance of our initial clinical trial application filing, the anticipated timing of our clinical trial and initiating enrollment for NTLA-2002, our program for the treatment of hereditary angioedema, or the success of such program ;

our ability to use a modular platform capability or other strategies to efficiently discover and develop product candidates, including by applying learnings from one program to other programs;

our ability to research, develop or maintain a pipeline of product candidates, including in vivo and ex vivo product candidates;

our ability to manufacture or obtain materials for our preclinical and clinical studies, and our product candidates;

our ability to advance any product candidates into, and successfully complete, clinical studies, including clinical studies necessary for regulatory approval and commercialization, and to demonstrate to the regulators that the product candidates are safe, effective, pure and potent and that their benefits outweigh known and potential risks for the intended patient population;

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estimates of our expenses, future revenues, capital requirements and our needs for additional financing;

the potential benefits of strategic agreements, such as collaborations, co-development and co-commercialization, acquisitions, dispositions, mergers, joint venture and investment agreements, and our ability to establish and maintain strategic arrangements under favorable terms;

the potential benefits of strategic agreements, such as collaborations, co-development and co-commercialization, acquisitions, dispositions, mergers, joint ventures, and investment agreements, and our ability to establish and maintain strategic arrangements under favorable terms;

our ability to acquire and maintain relevant intellectual property licenses and rights, and the scope and terms of such rights;

developments relating to our licensors, licensees, third-parties from which we derive rights, collaborators, competitors and our industry;

the effect of the coronavirus disease 2019 (“COVID-19”) pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations;

developments relating to our licensors, licensees, third-parties and ventures from which we derive or license rights, as well as collaborators, competitors and our industry;

the effect of the COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations;

other risks and uncertainties, including those listed under the caption “Risk Factors.”

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Intellia Therapeutics, Inc.

(“we,” “us,” “our,” “Intellia,” or the “Company”) is a leading clinical-stage genome editing company, focused on developing proprietary, potentially curative CRISPR/Cas9-based therapeutics.

CRISPR/Cas9, an acronym for C lustered, R egularly I nterspaced S hort P alindromic R epeats (“CRISPR”) / C RISPR a ssociated 9 (“Cas9”), is a technology for genome editing, the process of altering selected sequences of genomic deoxyribonucleic acid (“DNA”).

We believe the breakthrough CRISPR/Cas9 technology has the potential to transform medicine by both producing therapeutics that permanently edit and/or correct disease-associated genes in the human body with a single dose of treatment and creating enhanced engineered cell therapies.

Our combination of deep scientific, technical and clinical development experience, and proprietary innovations in genome editing and delivery technologies, along with our intellectual property (“IP”) portfolio, puts us in a position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create new classes of therapeutic products .

(“we,” “us,” “our,” “Intellia,” or the “Company”) is a leading clinical-stage genome editing company, focused on developing novel, potentially curative therapeutics using CRISPR/Cas9 technology.

CRISPR/Cas9, an acronym for C lustered, R egularly I nterspaced S hort P alindromic R epeats (“CRISPR”) /CRISPR associated 9 (“Cas9”), is a technology for genome editing, the process of altering selected sequences of genomic deoxyribonucleic acid (“DNA”).

To fully realize the transformative potential of CRISPR/Cas9, we are pursuing two primary approaches.

Our in vivo programs use intravenously administered CRISPR as the therapy, in which our proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues.

Our ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.

Our deep scientific, technical and clinical development experience, along with our robust intellectual property (“IP”) portfolio, enables us to unlock broad therapeutic applications of CRISPR/Cas9 to create new classes of genetic medicine .

Our management’s discussion and analysis of our financial condition and results of operations are based upon our unaudited condensed consolidated financial statements included in this Quarterly Report on Form 10-Q, which have been prepared by us in accordance with accounting principles generally accepted in the United States of America (“U.S.

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All of our revenue to date has been collaboration revenue.

Since our inception and through March 31, 2021, we have raised an aggregate of approximately $1,165.3 million to fund our operations, of which $275.0 million was through our collaboration agreements, $170.5 million was from our initial public offering and concurrent private placements, $438.3 million was from follow-on public offerings, $196.5 million was from at-the-market offerings and $85.0 million was from the sale of convertible preferred stock.

Our lead in vivo candidate, NTLA-2001 for the treatment of transthyretin amyloidosis (“ATTR”), is the first-ever systemically delivered CRISPR/Cas9-based therapy to enter clinical evaluation.

Since our inception and through June 30, 2021, we have raised an aggregate of approximately $1,166.1 million to fund our operations, of which $275.9 million was through our collaboration agreements, $170.5 million was from our initial public offering and concurrent private placements, $438.3 million was from follow-on public offerings, $196.5 million was from at-the-market offerings and $85.0 million was from the sale of convertible preferred stock.

Our lead in vivo candidate, NTLA-2001 for the treatment of transthyretin (“ATTR”) amyloidosis, is the first CRISPR/Cas9-based therapy candidate to be administered systemically, via intravenous infusion, for precision editing of a gene in a target tissue in humans.

In parallel, we are developing ex vivo applications to address immuno-oncology and autoimmune diseases, where CRISPR/Cas9 is the tool that creates the engineered cell therapy.

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and for which effective treatments are absent, limited or unduly burdensome.

Our initial in vivo indications target genetic liver diseases, including our ATTR and hereditary angioedema (“HAE”) development programs.

Our initial in vivo indications target genetic liver diseases, including our ATTR amyloidosis and hereditary angioedema (“HAE”) development programs.

Our current efforts on in vivo delivery focus on the use of lipid nanoparticles (“LNPs”) for delivery of the CRISPR/Cas9 complex to the liver.

Transthyretin Amyloidosis (“ATTR”) Program

ATTR is a progressive and fatal disorder resulting from deposition of insoluble amyloid fibrils into multiple organs and tissues leading to systemic failure.

Transthyretin (“ATTR”) Amyloidosis Program

ATTR amyloidosis is a progressive and fatal disorder resulting from deposition of insoluble amyloid fibrils into multiple organs and tissues leading to systemic failure.

Blood-borne transthyretin (“TTR”) protein is produced by hepatocytes and normally circulates as a soluble homotetramer that facilitates transport of vitamin A, via retinol binding protein, as well as the thyroid hormone, thyroxine.

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These tetramers more readily dissociate into the monomeric form, and thence to an aggregative form that results in amyloid deposits in tissues.

These deposits cause damage in those tissues, resulting in a disorder known as hereditary TTR amyloidosis (“hATTR”).

Over 120 different genetic mutations are currently known to cause hATTR.

Deposits of TTR amyloid in the heart, nerves and/or other tissues can lead to diverse disease manifestations, including two main hereditary forms – hATTR with polyneuropathy (“hATTR-PN”), and hATTR with cardiomyopathy (“hATTR-CM”).

These deposits cause damage in those tissues, resulting in a disorder known as hereditary TTR amyloidosis (“ATTRv”).

Over 120 different genetic mutations are currently known to cause ATTRv.

Deposits of TTR amyloid in the heart, nerves and/or other tissues can lead to diverse disease manifestations, including two main hereditary forms – ATTRv with polyneuropathy (“ATTRv-PN”) and ATTRv with cardiomyopathy (“ATTRv-CM”).

Typical onset of disease symptoms is during adulthood and can be fatal within two to 15 years.

Estimates suggest that approximately 50,000 patients suffer from hATTR worldwide.

In addition to the hereditary forms described above, ATTR can also develop spontaneously in the absence of any TTR gene mutation.

This wild-type ATTR (“wtATTR”) is increasingly being recognized as a significant and often undiagnosed cause of heart failure in the elderly and is the subject of active investigation.

Recent estimates suggest that, globally, between 200,000 and 500,000 people may suffer from wtATTR with cardiomyopathy (“wtATTR-CM”).

Estimates suggest that approximately 50,000 patients suffer from ATTRv worldwide.

In addition to the hereditary forms described above, ATTR amyloidosis can also develop spontaneously in the absence of any TTR gene mutation.

This wild-type ATTR (“ATTRwt”) is increasingly being recognized as a significant and often undiagnosed cause of heart failure in the elderly and is the subject of active investigation.

Recent estimates suggest that, globally, between 200,000 and 500,000 people may suffer from ATTRwt with cardiomyopathy (“ATTRwt-CM”).

In non-human primate (“NHP”) studies, we have demonstrated our ability to reduce circulating TTR protein to estimated therapeutically relevant levels after a single systemic administration of LNPs containing our CRISPR/Cas9 complex.

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About the NTLA-2001 Clinical Program

In November 2020, we announced that the first patient had been dosed with NTLA-2001, which we are developing as a single-dose, potentially curative therapy for ATTR, in our global Phase 1 study.

We are conducting our global Phase 1 study to evaluate NTLA-2001 for hATTR-PN patients.

In November 2020, we announced that the first patient had been dosed with NTLA-2001, our lead in vivo genome editing candidate which we are developing as a single-dose treatment for ATTR amyloidosis, in our Phase 1 study.

We are conducting our Phase 1 study to evaluate NTLA-2001 for ATTRv-PN patients.

Our first patient was dosed in the United Kingdom (“U.K.”) pursuant to authorization of our Clinical Trial Application (“CTA”), which was received from the U.K.’s Medicines and Healthcare products Regulatory Agency in October 2020.

In November 2020, as part of our ongoing Phase 1 study for NTLA-2001, we received a second CTA authorization from New Zealand’s Medicines and Medical Device Safety Authority to enroll ATTR patients at a clinical site.

As part of our ongoing global development strategy, we are submitting additional regulatory applications in other countries.

As part of our ongoing development strategy, we are submitting additional regulatory applications in other countries.

In March 2021, we announced that the European Commission (“EC”) granted orphan drug designation to NTLA-2001.

Our global Phase 1 trial is an open-label, multi-center, two-part study of NTLA-2001 in adults with hATTR-PN.

Our global Phase 1 trial is an open-label, multi-center, two-part study of NTLA-2001 in adults with ATTRv-PN.

The trial’s primary objectives are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2001.

Patients receive a single dose of NTLA-2001 via intravenous administration.

The study will enroll up to 38 participants (ages 18-80 years) and consist of a single-ascending dose phase in Part 1 and, following the identification of an optimal dose, an expansion cohort in Part 2.

Following safety assessment and dose optimization, we intend to further evaluate NTLA-2001 in a broader ATTR patient population of both polyneuropathy and cardiomyopathy patients.

We anticipate reporting interim clinical data from the single ascending dose portion of the Phase 1 study evaluating NTLA-2001 in adults with hATTR-PN in mid-2021.

The study will enroll up to 38 participants (ages 18-80 years) and consist of a single-ascending dose phase in Part 1 and, following the identification of a recommended dose, an expansion cohort in Part 2.

On June 26, 2021, at the Peripheral Nerve Society (“PNS”) Annual Meeting and in the New England Journal of Medicine, we publicly disclosed positive interim data from our ongoing Phase 1 clinical study of NTLA-2001.

The interim data cover the first six ATTRv-PN patients across two single-ascending dose cohorts of the Phase 1 study, which is currently being conducted in the U.K.

and New Zealand.

Single doses of either 0.1 mg/kg or 0.3 mg/kg of NTLA-2001 were administered systemically.

Reductions in serum TTR levels were measured from baseline to day 28.

Treatment with NTLA-2001 led to dose-dependent reductions in serum TTR, with mean reductions of 52% among the three patients in the 0.1 mg/kg dose group, and 87% among the three patients in the 0.3 mg/kg dose group, including one patient with a 96% reduction.

At both dose levels, NTLA-2001 was generally well-tolerated by the six patients included in the interim analysis, with no serious adverse events, or abnormal coagulation or liver findings by day 28.

Given the safety and tolerability profile observed to date, NTLA-2001 is continuing to be evaluated in the dose-escalation portion of the study, to determine if a higher dose could result in a deeper reduction in disease-causing protein levels leading to the potential for more meaningful clinical benefit.

For the third cohort in the dose-escalation portion, we will be evaluating NTLA-2001 at the 1 mg/kg dose level.

Following the identification of a recommended dose in the dose-escalation portion of the study, we expect to begin a single-dose expansion cohort in Part 2 of the Phase 1 trial later this year.

After completion of the Phase 1 trial, we plan to move to pivotal studies for both polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis .

We intend to present additional interim data for the dose-escalation portion of the Phase 1 study at a scientific or medical meeting this year.

NTLA-2001 is part of a co-development and co-promotion (“Co/Co”) agreement directed to our first collaboration target with Regeneron Pharmaceuticals, Inc.

(“Regeneron”), ATTR (the “ATTR Co/Co”), for which we are the clinical and commercial lead party and Regeneron is the participating party.

Regeneron shares in approximately 25% of worldwide development costs and commercial profits for the ATTR program.

For more information regarding our collaboration with Regeneron, see the section below entitled “ Collaborations - Regeneron Pharmaceuticals, Inc.

Regeneron shares in approximately 25% of worldwide development costs and commercial profits for the ATTR amyloidosis program.

For more information regarding our collaboration with Regeneron, see the section below entitled “ Collaborations - Regeneron ”

Hereditary Angioedema (“HAE”) Program

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These results affirm NTLA-2002’s therapeutic hypothesis of preventing HAE attacks.

We plan to submit an IND or IND-equivalent for NTLA-2002 in the second half of 2021.

In June 2021, we submitted a CTA for NTLA-2002 to the New Zealand Medicines and Medical Devises Safety Authority to initiate our Phase 1 study.

We plan to enroll our first patient in the Phase 1 study by year-end and we are also submitting additional regulatory applications to enable enrollment in other countries.

In Vivo Research Programs

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These results extend our modular in vivo capabilities to treat inherited blood disorders such as sickle cell disease.

Ex Vivo Programs

Ex Vivo P rograms

We are independently researching and developing proprietary engineered cell therapies to treat various oncological and other disease indications, for example TCR-engineered T cells and chimeric antigen receptor T (“CAR-T”) cells for immuno-oncology applications and engineered regulatory T cells for autoimmune disorders.

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While these treatments have led to improvements in response rates and in some cases increased overall survival, the outcomes demonstrated thus far have been incremental in nature and long-term outcomes in AML continue to be extremely poor.

NTLA-5001 is our engineered T cell therapy development candidate for the treatment of AML, utilizing our TCR-directed approach to target the WT1 intracellular antigen.

NTLA-5001 is our engineered T cell therapy development candidate for the treatment of AML, utilizing our TCR-directed approach to target the WT1 intracellular antigen and restricted to the HLA-A*02:01 allele .

As WT1 is overexpressed in >90% of AML blasts, we are developing NTLA-5001 as a broadly applicable treatment for AML, regardless of mutational subtypes of a patient’s leukemia.

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In December 2020, we presented data on NTLA-5001 highlighting the high anti-tumor activity observed in proof-of-concept mouse models of acute leukemias and the faster expansion and superior function of T cells manufactured by our proprietary approach, compared to T cells engineered with a standard genome editing process.

We expect to submit an IND or IND-equivalent for NTLA-5001 in mid-2021.

We recently submitted our first CTA to the U.K.

Medicines and Healthcare products Regulatory Agency for NTLA-5001 to initiate a Phase 1 study.

This first-in-human trial intends to evaluate safety and activity in patients with persistent or recurrent AML who have previously received first-line therapies.

Additional research efforts are underway to evaluate the potential use of NTLA-5001 to treat WT1-positive solid tumors.

Ex Vivo Research Programs

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We continue to advance efforts to move from autologous to allogeneic therapies and from liquid to solid tumors.

Our researchers are developing and improving cell-engineering manufacturing and delivery processes that, we believe, may allow us to deliver T cell therapies with high levels of editing, robust levels of cell expansion, desirable memory phenotypes, improved function and no translocations above background levels.

Our proprietary T cell engineering process enables multiple, sequential gene edits and is a significant improvement over standard engineering processes commonly used to introduce proteins and nucleic acids into cells.

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Novartis is developing several other product candidates arising from the 2014 Novartis Agreement.

For more information regarding our collaboration with Novartis, see the section below entitled “ Collaborations - Novartis Institutes for BioMedical Research, Inc.”

For more information regarding our collaboration with Novartis, see the section below entitled “ Collaborations - Novartis”

Collaborations

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The collaboration was extended until April 2024, at which point Regeneron has an option to renew for an additional two years.

The 2020 Regeneron Amendment also grants Regeneron rights to develop products for five additional in vivo CRISPR/Cas-based therapeutic liver targets and non-exclusive rights to independently develop and commercialize up to 10 ex vivo gene edited products made using certain defined cell types.

Through March 31, 2021, excluding the amounts allocated to Regeneron’s purchase of our common stock, we have recorded $145.0 million in upfront payments under the 2016 Regeneron Agreement and the 2020 Regeneron Amendment (the “Amended Agreements”) and $35.6 million primarily for research and development services under the ATTR Co/Co agreement, as described in Note 7 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q.

Through March 31, 2021, we have recognized $129.7 million of collaboration revenue under all arrangements, including $6.4 million and $7.9 million during the three months ended March 31, 2021 and 2020, respectively, in the condensed consolidated statements of operations and comprehensive loss.

This includes $0.9 million and $4.8 million during the three months ended March 31, 2021 and 2020, respectively, primarily representing payments due from Regeneron pursuant to the ATTR Co/Co agreement, which is accounted for under Accounting Standards Codification 808, Collaborative Arrangements .

As of March 31, 2021, and December 31, 2020, we had accounts receivable of $1.0 million and $2.1 million, respectively, and deferred revenue of $68.4 million and $73.9 million, respectively, related to these arrangements.

The 2020 Regeneron Amendment also grants Regeneron exclusive rights to develop products for five additional in vivo CRISPR/Cas-based therapeutic liver targets and non-exclusive rights to independently develop and commercialize up to 10 ex vivo gene edited products made using certain defined cell types.

Through June 30, 2021, excluding the amounts allocated to Regeneron’s purchase of our common stock, we have recorded $145.0 million in upfront payments under the 2016 Regeneron Agreement and the 2020 Regeneron Amendment (the “Amended Agreements”) and $35.6 million for research and development services, primarily under the ATTR Co/Co agreement, as described in Note 7 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q.

Through June 30, 2021, we have recognized $135.2 million of collaboration revenue under all arrangements, including $5.5 million and $12.0 million during the three and six months ended June 30, 2021, respectively, and $16.3 million and $24.2 million during the three and six months ended June 30, 2020, respectively, in the condensed consolidated statements of operations and comprehensive loss.

This includes $1.0 million and $1.8 million during the three and six months ended June 30, 2021, respectively, and $3.8 million and $8.6 million during the three and six months ended June 30, 2020, respectively, primarily representing payments due from Regeneron pursuant to the ATTR Co/Co agreement,

which is accounted for under Accounting Standards Codification 808 , Collaborative Arrangements .

These revenues are offset in part by contra-revenue related to the Hemophilia Co/Co agreements amounting to $1.0 million during the three and six months ended June 30, 2021, respectively.

As of June 3 0 , 2021 and December 31, 2020 , we had accounts receivable of $ 1.

0 million and $2.1 million , respectively, related to these arrangements.

We had deferred revenue of $ 6 2.

8 million and $ 73.9 million as of June 30, 2021 and December 31, 2020 , respectively, related to th ese a r range ment s .

As described in Note 7, “Collaborations—Novartis Institutes for BioMedical Research, Inc.,” to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, i n December 2014, we entered into a strategic collaboration agreement with Novartis (the “2014 Novartis Agreement”), primarily focused on the development of new ex vivo CRISPR/Cas9-edited therapies using CAR-T cells and HSCs.

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In December 2019, per the terms of the 2014 Novartis Agreement, the research term ended, although the 2014 Novartis Agreement remains in effect, for which we will be eligible to receive milestone and royalty payments in the future.

Since December 31, 2020, there have been no material changes to the key terms of the 2014 Novartis Agreement and the Novartis Amendment.

In June 2021, we entered into Amendment No.

3 (the “Amendment”) to the 2014 Novartis Agreement.

The Amendment amends Novartis’ rights with respect to all the CAR-T Therapeutic Targets (as defined in the 2014 Novartis Agreement) that Novartis selected under the 2014 Novartis Agreement, including (a) making Novartis’ license non-exclusive for such CAR-T Therapeutic Targets, (b) removing Novartis’ diligence and related reporting obligations for such CAR-T Therapeutic Targets, and (c) refining the scope of Novartis’ sublicense rights for such CAR-T Therapeutic Targets.

We made a one-time payment to Novartis of $10.0 million within 30 days after the effective date of the Amendment, which was recorded as research and development expense in the condensed consolidated statements of operations and comprehensive loss for the three and six months ended June 30, 2021.

Since December 31, 2020, there have been no other material changes to the key terms of the 2014 Novartis Agreement and the Novartis Amendment.

For further information on the terms and conditions of these agreements, please see the notes to the consolidated financial statements included in our Annual Report for the year ended December 31, 2020.

Revenue Recognition – Milestone .

During the three months ended March 31, 2020, the U.S.

Food and Drug Administration (“FDA”) accepted the IND application submitted by Novartis for a CRISPR/Cas9-based engineered cell therapy for the treatment of sickle cell disease.

In March 2020, the U.S.

Food and Drug Administration (“FDA”) accepted the investigational new drug (“IND”) application submitted by Novartis for a CRISPR/Cas9-based engineered cell therapy for the treatment of sickle cell disease.

As a result of meeting this milestone, we recognized $5.0 million as collaboration revenue within the condensed consolidated statement of operations and comprehensive loss.

No other milestones under the 2014 Novartis Agreement and the Novartis Amendment were achieved during the three months ended March 31, 2021 or 2020.

No other milestones under the 2014 Novartis Agreement and the Novartis Amendment were achieved during the six months ended June 30, 2021 or 2020.

We are eligible to receive additional downstream success-based milestones and royalties.

As of March 31, 2021 and December 31, 2020, we had no accounts receivable or deferred revenue related to the 2014 Novartis Agreement and the Novartis Amendment.

As of June 30, 2021 and December 31, 2020, we had no accounts receivable or deferred revenue related to the 2014 Novartis Agreement and related amendments.

New CAR T-Cell Therapy Company

On June 22, 2021, we announced that we have entered into an agreement with Cellex Cell Professionals GmbH (“Cellex”) and funds managed by Blackstone Life Sciences Advisors L.L.C.

(“BXLS”) to establish a new CAR-T cell therapy company (“NewCo”) that will be focused on the development of allogeneic universal CAR-T cell therapies for immuno-oncology and autoimmune diseases.

The new company will be headquartered in Cambridge, Massachusetts and will acquire Cellex’s subsidiary GEMoaB GmbH (“GEMoaB”), with established offices and labs in Dresden, Germany.

The new company will have an exclusive license to Intellia’s CRISPR/Cas9 allogeneic cell engineering platform limited to its use with GEMoaB’s switchable, universal CAR-T cell platforms (UniCAR and RevCAR).

As a subsidiary of the new company, GEMoaB will continue to advance its clinical stage, autologous CAR-T cell therapy programs.

Funds managed by BXLS have committed up to $250 million to the transaction and with us and Cellex (and certain related entities) have equal ownership of the new company at the time of the initial closing.

The transaction closed in the third quarter of 2021.

In July 2021, we entered into a license and collaboration agreement with NewCo, under which we will collaborate to develop allogeneic universal CAR-T cell therapies, as well as a co-development and co-funding (“Co/Co”) agreement to co-develop an allogeneic universal CAR-T cell product for an immuno-oncology indication, which the parties will co-commercialize in the U.S.

and key European countries.

We will have one additional option to enter into a second Co/Co agreement from selected allogeneic universal CAR-T cell therapy products that the parties will develop under the collaboration.

Financial Overview

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The following discussion of the financial condition and results of operations should be read in conjunction with the accompanying condensed consolidated financial statements and the related footnotes thereto.

Comparison of Three Months Ended March 31 , 2021 and 2020

The following table summarizes our results of operations for the three months ended March 31, 2021 and 2020:

Three Months Ended March 31,

Comparison of Three Months Ended June 30 , 2021 and 2020

The following table summarizes our results of operations for the three months ended June 30, 2021 and 2020:

Three Months Ended June 30,

Period Change

(In thousands)

Collaboration revenue

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Collaboration Revenue

Collaboration revenue decreased by $6.5 million to $6.4 million during the three months ended March 31, 2021, as compared to $12.9 million during the three months ended March 31, 2020.

The decrease in collaboration revenue during the three months ended March 31, 2021 is primarily driven by the $5.0 million milestone payment earned from Novartis for the IND submission of OTQ923 in 2020.

Collaboration revenue decreased by $9.7 million to $6.6 million during the three months ended June 30, 2021, as compared to $16.3 million during the three months ended June 30, 2020.

The decrease in collaboration revenue during the three months ended June 30, 2021 is primarily caused by an $8.4 million one-time cumulative catch-up adjustment related to the modification of the 2016 Regeneron Agreement recorded in 2020.

Refer to Note 7 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q for further details.

Research and Development

Research and development expenses increased by $4.6 million to $39.3 million during the three months ended March 31, 2021, as compared to $34.7 million during the three months ended March 31, 2020.

The following table summarizes our research and development expenses for the three months ended March 3 1 , 202 1 and 20 20 , together with the changes in those items in dollars (in thousands) and the respective percentages of change:

Three Months Ended March 31,

Research and development expenses increased by $21.1 million to $58.9 million during the three months ended June 30, 2021, as compared to $37.8 million during the three months ended June 30, 2020.

The following table summarizes our research and development expenses for the three months ended June 3 0 , 202 1 and 20 20 , together with the changes in those items in dollars (in thousands) and the respective percentages of change:

Three Months Ended June 30,

Period Change

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Total research and development expenses

The increase in research and development expenses for the three months ended March 31, 2021 compared to the three months ended March 31, 2020 was primarily attributable to:

The increase in research and development expenses for the three months ended June 30, 2021 compared to the three months ended June 30, 2020 was primarily attributable to :

a $1.0 million decrease in external costs related to the development of NTLA-2001, our lead product candidate, primarily due to a decrease in contracted services and manufactured components incurred as compared to the prior period;

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a $1.3 million increase in external costs related to the development of NTLA-5001, primarily due to an increase in contracted services as we prepare to enter into the clinic;

a $3.0 million increase in employee-related expenses driven by an increase in the size of our workforce due to the advancement of our programs;

a $1.1 million increase in research materials and contracted services primarily due to an increase in purchased materials;

a $5.3 million increase in employee-related expenses driven by the expansion of our development organization;

a $9.2 million increase in research materials and contracted services primarily related to a $10.0 million one-time payment related to the amendment of the 2014 Novartis Agreement;

a $1.9 million increase in facility-related expenses primarily related to rent, depreciation and technology expense allocated to research and development;

a $3.7 million increase in stock-based compensation driven by our larger workforce and stock valuation.

Through 2021, we expect research and development expenses to increase as we continue to grow our development team, execute clinical trials for ATTR and progress our AML and HAE programs into the clinic.

General and Administrative

General and administrative expenses increased by $2.3 million to $13.6 million during the three months ended March 31, 2021, compared to $11.3 million during the three months ended March 31, 2020.

General and administrative expenses increased by $5.2 million to $16.7 million during the three months ended June 30, 2021, compared to $11.5 million during the three months ended June 30, 2020.

This increase was primarily related to employee-related expenses, including stock-based compensation of $2.1 million.

Interest Income

Interest income decreased by $1.0 million to $0.2 million during the three months ended March 31, 2021 as compared to $1.2 million during the three months ended March 31, 2020.

This decrease was due to a decline in investment income due to market conditions.

Interest income decreased by $0.4 million to $0.2 million during the three months ended June 30, 2021 as compared to $0.6 million during the three months ended June 30, 2020.

This decrease was due to a decline in investment income due to overall market conditions.

Comparison of Six Months Ended June 3 0 , 20 2 1 and 20 20

The following table summarizes our results of operations for the six months ended June 30, 2021 and 2020:

Six Months Ended June 30,

Period Change

(In thousands)

Collaboration revenue

Operating expenses:

Research and development

General and administrative

Total operating expenses

Operating loss

Interest income

Collaboration Revenue

Collaboration revenue decreased by $16.2 million to $13.0 million during the six months ended June 30, 2021, as compared to $29.2 million during the six months ended June 30, 2020.

The decrease in collaboration revenue during the six months ended June 30, 2021 is primarily caused by an $8.4 million one-time cumulative catch-up adjustment related to the modification of the 2016 Regeneron Agreement and a $5.0 million milestone payment earned from Novartis for the IND submission of OTQ923, both of which were recorded in the first six months of 2020.

Refer to Note 7 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q for further details.

Research and Development

Research and development expenses increased by $25.7 million to $98.2 million during the six months ended June 30, 2021, as compared to $72.4 million during the six months ended June 30, 2020.

The following table summarizes our research and development expenses for the six months ended June 30, 2021 and 2020, together with the changes in those items in dollars (in thousands) and the respective percentages of change:

Six Months Ended June 30,

Period Change

External development expenses by program:

Unallocated research and development

Employee-related expenses

Research materials and contracted services

Facility-related expenses

Stock-based compensation

Total research and development expenses

The increase in research and development expenses for the six months ended June 30, 2021 compared to the six months ended June 30, 2020 was primarily attributable to:

a $5.8 million decrease in external costs related to the development of NTLA-2001, our lead product candidate, primarily due to a decrease in contracted services and manufactured components incurred as compared to the prior period;

4 million increase in external costs related to the development of NTLA-2002, primarily due to an increase in component cost s as we prepare to enter into the clinic;

a $4.2 million increase in external costs related to the development of NTLA-5001, primarily due to an increase in contracted services as we prepare to enter into the clinic;

an $8.3 million increase in employee-related expenses driven by the expansion of our development organization;

a $9.5 million increase in research materials and contracted services primarily due to a $10.0 million one-time payment related to the amendment of the 2014 Novartis Agreement;

a $2.1 million increase in facility-related expenses primarily related to rent, depreciation and technology expense allocated to research and development;

a $5.1 million increase in stock-based compensation driven by our larger workforce and stock valuation.

Through 2021, we expect research and development expenses to increase as we continue to grow our development team, execute clinical trials for ATTR amyloidosis and progress our HAE and AML programs into the clinic.

General and Administrative

General and administrative expenses increased by $7.4 million to $30.3 million during the six months ended June 30, 2021, compared to $22.8 million during the six months ended June 30, 2020.

This increase was primarily related to an increase in employee related expenses, including stock-based compensation of $3.0 million.

Interest Income

Interest income decreased by $1.5 million to $0.4 million during the six months ended June 30, 2021 as compared to $1.9 million during the six months ended June 30, 2020.

This decrease was due to a decline in investment income due to overall market conditions.

Liquidity and Capital Resources

Since our inception through March 31, 2021, we have raised an aggregate of $1,165.3 million to fund our operations, of which $275.0 million was through our collaboration agreements, $170.5 million was from our initial public offering and concurrent private placements, $438.3 million was from follow-on public offerings, $196.5 million was from at-the-market offerings and $85.0 million was from the sale of convertible preferred stock.

As of March 31, 2021, we had $600.8 million in cash, cash equivalents and marketable securities.

Since our inception through June 30, 2021, we have raised an aggregate of approximately $1,166.1 million to fund our operations, of which $275.9 million was through our collaboration agreements, $170.5 million was from our initial public offering and concurrent private placements, $438.3 million was from follow-on public offerings, $196.5 million was from at-the-market offerings and $85.0 million was from the sale of convertible preferred stock.

As of June 30, 2021, we had $551.3 million in cash, cash equivalents and marketable securities.

In July 2021, we closed an underwritten public offering of 4,758,620 shares of common stock, including the exercise in full of the underwriters’ option to purchase an additional 620,689 shares of common stock, at the public offering price of $145.00 per share, for aggregate estimated net proceeds of $648.1 million, after deducting approximately $41.9 million in underwriting discounts and estimated offering costs.

We are entitled to receive research payments under our collaboration with Novartis and are also eligible to earn a significant amount of milestone payments and royalties, in each case, on a per-product basis under our collaboration with Novartis and on a per-target basis under our collaboration with Regeneron.

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We agreed to pay to Jefferies cash commissions of 3.0% of the gross proceeds of sales of common stock under the 2019 Sales Agreement.

During the three months ended March 31, 2021, we issued 641,709 shares of our common stock in a series of sales at an average price of $72.79 per share in accordance with the 2019 Sales Agreement, for aggregate net proceeds of $45.3 million after payment of cash commissions to Jefferies and approximately $0.1 million related to legal, accounting and other fees in connection with the sales.

As of March 31, 2021, $47.4 million in shares of common stock remain eligible for sale under the 2019 Sales Agreement.

During the six months ended June 3 0 , 202 1 , we issued 641,709 shares of our common stock in a series of sales at an average price of $ 72.79 per share in accordance with the 2019 Sales Agreement, for aggregate net proceeds of $ 45.3 million after payment of cash commissions to Jefferies and approximately $0.

1 million related to legal, accounting and other fees in connection with the sales .

As of June 30, 2021, $47.4 million in shares of our common stock remain eligible for sale under the 2019 Sales Agreement.

Funding Requirements

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Until such time as we can generate substantial product revenues, if ever, we expect to finance our ongoing cash needs through equity financings and collaboration arrangements.

We receive cost reimbursements from Regeneron for the ATTR and hemophilia programs.

We receive cost reimbursements from Regeneron for the ATTR amyloidosis and hemophilia programs.

Additionally, we are eligible to earn milestone payments and royalties, in each case, on a per-product basis under our collaboration with Novartis and on a per-target basis under our collaboration with Regeneron, subject to the provisions of our agreements with each of them.

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If we are unable to raise additional funds through equity financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of March 31, 2021, as well as research and cost reimbursement funding from Regeneron, will enable us to fund our ongoing operating expenses and capital expenditure requirements at least through the next twenty-four months, excluding any potential mile stone payments or extension fees that could be earned and distributed under the collaboration agreements with Regeneron and Novartis or any strategic use of capital not currently in the base case planning assumptions.

Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of June 30, 2021, along with the proceeds from the July 2021 public offering of common stock, will enable us to fund our ongoing operating expenses and capital expenditure requirements beyond the next twenty-four months, excluding any potential mile stone payments or extension fees that could be earned and distributed under the collaboration agreements with Regeneron and Novartis or any strategic use of capital not currently in the base case planning assumptions.

We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.

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and attracting, hiring, and retaining qualified personnel .

The following is a summary of cash flows for the three months ended March 31, 2021 and 2020:

Three Months Ended March 31,

The following is a summary of cash flows for the six months ended June 30, 2021 and 2020:

Six Months Ended June 30,

(In millions)

Net cash used in operating activities

Net cash (used in) provided by investing activities

Net cash (used in) provided by operating activities

Net cash provided by investing activities

Net cash provided by financing activities

Net cash used in operating activities

Net cash used in operating activities of $52.4 million during the three months ended March 31, 2021 primarily reflects the increased spend in our research and development activities, offset in part by the receipt of $2.4 million in payments from our collaboration partners during those periods.

Net cash used in operating activities of $38.5 million during the three months ended March 31, 2020 primarily reflects increased spend in our research and development activities, offset in part by the receipt of $1.0 million in payments from our collaboration partners during those periods.

Net cash (used in) provided by investing activities

During the three months ended March 31, 2021, our investing activities used net cash of $25.5 million.

The decrease in the three months ended March 31, 2021 is primarily due to a decrease in marketable securities activity during the period, as $148.3 million in marketable securities were purchased and $125.2 million in marketable securities matured.

The decrease in cash is also due to $2.4 million for the purchase of property and equipment during the period.

The increase in the three months ended March 31, 2020 is primarily due to an increase of $58.3 million in marketable securities activity during the period, as $89.5 million in marketable securities matured and $31.2 million in marketable securities were purchased.

This increase in cash was offset in part by the use of $0.8 million in cash for the purchase of property and equipment during the period.

Net cash (used in) provided by operating activities

Net cash used in operating activities of $105.4 million during the six months ended June 30, 2021 primarily reflects the increased spend in our research and development activities, offset in part by the receipt of $3.2 million in payments from our collaboration partners during those periods.

Net cash provided by operating activities of $18.9 million during the six months ended June 30, 2020 primarily reflects the receipt of a $70.0 million up-front payment and $8.4 million in additional payments under our collaboration with Regeneron and $6.0 million in payments from Novartis, offset in part by increased spend in our research and development activities.

Net cash provided by investing activities

During the six months ended June 30, 2021 and 2020, our investing activities provided net cash of $7.7 million and $150.4 million, respectively.

The increase in the six months ended June 30, 2021 is primarily due to an increase in marketable securities activity during the period, as $185.4 million in marketable securities were purchased and $198.5 million in marketable securities matured.

The increase in the six months ended June 30, 2020 is primarily due to an increase of $152.3 million from marketable securities activity during the period, as $183.5 million in marketable securities matured and $31.2 million in marketable securities were purchased.

These increases in cash provided by investing activity were offset in part by the use of $5.4 million and $1.9 million related to purchases of property and equipment in the six months ended June 30, 2021 and 2020, respectively.

Net cash provided by financing activities

Net cash provided by financing activities of $58.6 million during the three months ended March 31, 2021 includes $45.3 million in net proceeds from at-the-market offerings and $13.3 million in cash received from the exercise of stock options.

Net cash provided by financing activities of $4.9 million during the three months ended March 31, 2020 includes $4.5 million in net proceeds from at-the-market offerings and $0.3 million in cash received from the exercise of stock options.

Net cash provided by financing activities of $65.7 million during the six months ended June 30, 2021 includes $45.3 million in net proceeds from at-the-market offerings, $19.5 million in cash received from the exercise of stock options and $1.0 million in cash received from the issuance of shares through our employee stock purchase plan.

Net cash provided by financing activities of $137.1 million during the six months ended June 30, 2020 includes $107.7 million in net proceeds from a follow-on offering, $14.7 million in net proceeds from at-the-market offerings, $12.6 million in proceeds from the issuance of common stock to Regeneron in a private placement, $1.4 million in cash received from the exercise of stock options and $0.7 million in cash received from the issuance of shares through our employee stock purchase plan.

Critical Accounting Policies

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Contractual Obligations

There were no material changes to our contractual obligations during the three months ended March 31, 2021.

There were no material changes to our contractual obligations during the six months ended June 30, 2021.

For a complete discussion of our contractual obligations, please refer to our Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report for the year ended December 31, 2020.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis