Intellia Therapeutics, Inc.

Good morning and welcome to the Intelia Therapeutics fourth quarter and full year 2021 financial results conference call. My name is Andrew and I will be your conference operator today. Following formal remarks, we will open the call up for a question and answer session. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star then zero on your telephone keypad. I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and Corporate Communications at Intelia. Please proceed.

Thank you, operator. Good morning, everyone. Welcome to Intellia Therapeutics' fourth quarter and full year 2021 earnings call. Earlier this morning, Intellia issued a press release outlining the company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investors and Media section of Intellia's website at intelliatx.com. This call is being broadcast live, and a replay will be archived on the company's website. At this time... I would like to take a minute to remind listeners that during the call, Intelia management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intelia undertakes no duty to update this information unless required by law. Joining me from Intelia are Dr. John Leonard, Chief Executive Officer, and Glenn Goddard, Chief Financial Officer, Dr. David Ledwall, Chief Medical Officer, and Dr. Laura Sepp-Lorenzino, Chief Scientific Officer, will also be available for the Q&A portion of today's call. John will begin with an overview of recent business highlights, followed by Glenn, who will review Intellia's financial results for the fourth quarter and full year 2021. John will provide concluding remarks, and then we'll open up the call for Q&A. With that, I'll turn the call over to John.

Thank you, Ian. And thank you all for joining us this morning. At Intelia, we're building a full-spectrum genome editing company with the industry's broadest and deepest toolbox to fully realize the promise of CRISPR-based medicines for both in vivo and ex vivo applications. 2021 was a landmark year for Intelia, during which we shared the first clinical data offering proof of concept for our platform and showing it is possible to precisely edit a disease-causing gene within the body through a systemically delivered CRISPR-based therapy. We initiated two additional clinical programs, dosing the first patient with NTLA-2002 and screening AML patients for NTLA-5001's first in-human study. We nominated two new development candidates, leveraging our targeted insertion platform, NTLA-3001 for alpha-1 antitrypsin deficiency, and a program for hemophilia B led by our partner Regeneron. We also presented several noteworthy platform advancements, including preclinical proof of concept for in vivo editing of bone marrow, a novel allogeneic technology to engineer cells capable of evading immune attack, and a proprietary base editor. And finally, we launched a new company called Avancell in partnership with Cellix and Blackstone to develop allogeneic universal CAR-T cell therapies. This collaboration is another example of our strategy to maximize the value of our platform and gain future product rights to innovative therapies. While we accomplished a tremendous amount in 2021, we are already building upon these achievements in 2022. More specifically, this year, we're focused on three core priorities. First, accelerating the clinical validation of our in vivo pipeline. On this front, we're looking forward to presenting additional clinical data from our lead candidate, NTLA-2001, for ATTR amyloidosis next week. And later this year, we plan to present initial clinical data from NTLA-2002 for the HAE program. Next, we are actively expanding our pipeline by advancing NTLA-5001, our first wholly-owned ex vivo candidate, into the clinic. along with the nomination of multiple new development candidates in both the in vivo and ex vivo settings, as well as through strategic business development opportunities. And finally, we're building on our scientific leadership by driving forward key platform innovation through expansion of our genome editing, delivery, and cell engineering capabilities. With robust execution against these objectives so far in 2022, Intelia is firing on all cylinders. Our Phase 1 study of NTLA-2001, recently expanded to include an additional arm with cardiomyopathy patients, continues to progress. We look forward to hosting a company-sponsored event next week, during which we plan to present additional interim data from patients with hereditary ATTR amyloidosis with polyneuropathy. The event will feature data from all four dose cohorts in Part 1, the single ascending dose portion. It will include safety and serum TTR reduction data, as well as an early look at durability across all cohorts. We expect these results to inform the dose selection for Part 2, and we remain on track to initiate the single-dose expansion cohort in the first quarter of this year. For NTLA-2002, we continue to dose patients in the dose escalation portion of the Phase 1-2 study. Based on the insights gained from NTLA-2001, which are directly applicable to NTLA-2002, we believe we've increased the likelihood of success as we advance this program. Looking ahead, we anticipate presenting the first cut of interim data from this trial for the second half of this year. In addition to NTLA-2002, we are now advancing two wholly-owned development candidates for the treatment of Alpha-1 antitrypsin deficiency, or AATD. This includes NTLA-3001, a gene insertion candidate for AATD-associated lung disease, for which we expect to file an IND or equivalent application next year. And today, we're pleased to announce the nomination of NTLA-2003, a knockout candidate for the liver manifestation of AATD. NTLA-2003 is designed to inactivate the serpent A1 gene responsible for the production of abnormal alpha-1 protein in the liver. with the aim of halting the progression of liver disease and eliminating the need for liver transplant. For AATD, our modular platform provides us the optionality for patient-tailored treatments relevant to the particular disease manifestation. Moving on to our ex vivo pipeline, for NTLA 50-on-1, we've begun enrolling patients in the Phase 1-2A study and expect to dose the first AML patient with our autologous TCR T-cell therapy in the coming weeks. Today, we are also excited to announce the nomination of our first allogeneic development candidate, NTLA-6001. NTLA-6001 is an allocard T designed for the treatment of CD30 positive expressing hematologic cancers, such as relapsed or refractory classical Hodgkin's lymphoma. It was developed using our proprietary allogeneic cell engineering platform. In preclinical studies, our allogeneic T-cells were shielded from immune rejection by both host T-cell and, critically important, host NK cell attack. This approach is distinct from others and is designed to ensure long-term persistence of the engineered cells. We are currently advancing this program towards IMD-enabling activities and plan to present preclinical data leading to the development of MTLA-6001 at an upcoming scientific conference this year. In parallel, we continue to drive forward our platform innovation, maintaining our leadership position at the forefront of the genome editing revolution. Reflective of this strategy, we announced in February the acquisition of Rewrite Therapeutics, a private biotechnology company whose DNA writing technology may enable a range of additional editing strategies. The acquisition of Rewrite further expands our leading genome editing toolbox, by adding complementary technologies to our existing CRISPR-Cas9 and base editing capabilities, thereby allowing us to employ the best tool for each therapeutic application. With the strength and breadth of our CRISPR-based platform, we recognize that our proprietary technologies can have expanded application when we strategically partner with others who possess complementary capabilities. This year, we've already completed two strategic collaborations. both of which extend the reach of our platform beyond our core areas of focus and provide us with valuable commercial product rights to future programs. In January, we announced a collaboration agreement with Kiberna Therapeutics to leverage our allogeneic platform to develop KYV201, an LLCD19 CAR T cell investigational candidate for the treatment of select autoimmune diseases. This is a novel approach aimed at targeting CD19 for inflammatory diseases as compared to traditional oncology indications, importantly, with an option to lead U.S. commercialization for this candidate under a co-development and co-commercialization agreement. In just this month, we announced a collaboration agreement with ONK Therapeutics to develop CRISPR-edited NK cell therapies for the treatment of cancer. NK cells are specialized, naturally occurring immune cells that play a critical role in immune activation against abnormal cells, including cancer cells. The agreement grants ONK a non-exclusive license to our proprietary ex vivo genome editing platform for up to five NK cell therapies, similar to the Kiberna transaction we hold rights to global co-development and co-commercialization options, including lead U.S. commercialization rights for up to two engineered cell therapies derived from the collaboration. Finally, earlier this week, we announced a lease agreement to develop a 140,000-square-foot facility in Walden, Massachusetts to support the manufacturing of key components for our CRISPR-based medicines. This new facility will be GMP-compliant and offer capacity and capabilities to deliver preclinical through commercial supply for our rapidly expanding pipeline. The ability to efficiently and reliably manufacture our products is crucial to ensuring commercial readiness and ultimately for our mission to bring transformational medicines to patients. Altogether, with these recent announcements, we've carried forward the strong momentum of the past year. positioning Intelia to advance the next wave of clinical candidates while ensuring we stay at the cutting edge for years to come. With that, I'll now hand over the call to Glenn, our CFO, who will provide an overview of our fourth quarter and full year 2021 financial results. Thank you, John, and good morning, everyone. Intelia is in a strong financial position as we aggressively advance and expand our pipelines. Our cash, cash equivalents and marketable securities were $1.1 billion as of December 31, 2021, compared to $597.4 million as of December 31, 2020. The increase was mainly driven by net proceeds of $648.3 million from our July follow-on offering, $45.3 million of net proceeds from the company's ATM agreement, $43.1 million in proceeds from employee-based stock plans and $6.3 million from regenerating cost sharing. These increases were offset in part by cash used to fund operations of $254.7 million. Our collaboration revenue increased by $6.3 million to $12.9 million during the fourth quarter of 2021. compared to $6.6 million during the fourth quarter of 2020. This increase was driven by $5.8 million in revenue recorded in 2021 from our joint venture with Avancell. Our R&D expenses increased by $32.9 million to $71.2 million during the fourth quarter of 2021, compared to $38.2 million during the fourth quarter of 2020. This increase was mainly driven by the advancement of our lead programs and the expansion of the R&D organization to support these programs. Our G&A expenses increased by $11.3 million to $22.1 million during the fourth quarter of 2021, compared to $10.8 million during the fourth quarter of 2020. This increase was mainly related to employee-related expenses, including stock-based compensation of $3.8 million. Finally, we expect our current cash balance to fund our operating plans beyond the next 24 months, as Intelia is well positioned to drive long-term growth. With that, I will now turn the call back over to John for closing remarks. Thank you, Glenn. We are already well on our way towards executing against our strategic priorities across all facets of the business. We are advancing a robust pipeline, including both wholly owned and partnered programs, now with eight development candidates, four of which are in the clinic. We're delivering against our corporate objectives and rapidly expanding the reach of our platform to accelerate the impact on patients. We're expanding our manufacturing network by adding in-house GMP manufacturing capacity to support our continued growth. And we've continued to propel our own scientific leadership and innovation to support the next wave of clinical candidates. Despite all this progress, we still have much to accomplish later in the year. Before we open the call to questions, we understand many of you are interested in the upcoming NTLA 2001 investor event. Given our proximity to the data readout, we will not be addressing any questions regarding our progress with NTLA 2001 or the planned interim data on this call. We look forward to sharing additional data with you next week and kindly request that you refrain from using today's call to ask questions on this topic. With that, we'd be happy to answer any questions about the rest of our pipeline and platform. Operator?